Dermpath Board Review: 100 Classic Cases

Dermpath Board Review: 100 Classic Cases

So I’m going to start with case one so with
case one you so like I keep whenever like we are talking with the residents we always
tell them that you should always have a format of approaching a digit of a slide a pathology
slide so just don’t jump to a diagnosis try to always develop some sort of a form
some sort of plan in your mind that this is how I’m going to approach a skin pathology
slide. So you always start from the top and then you go to the bottom actually so like
do I see any changes in the stratum corneum? Do I see any changes in the epidermis? Then
you go to the dermal-epidermal junction. Then you go to the dermis. Then you go to the subcutis.
If you follow that format every time it will make your it will make coming to a diagnosis
much, much easier rather than jumping to what is the diagnosis actually. So following that
format here if you start from the top. Zoom in and start from the top it is almost like
a Basket weave-type hyperkeratosis. But the epidermis is showing all this spongiotic changes.
So by spongiosis … the word spongiosis means dema of the epidermis, actually. So edema
is collection of fluid. So what we see is collection of fluid in between the keratinocytes
so that is we see these keratinocytes they are separated out and then the edema becomes
intense you start forming these vesicles actually. So there’s quite a bit of spongiosis of
the epidermis with vesiculation if you look at the dermis you have a superficial perivascular
lymphocytic infiltrate. You might have some eosinophils or the eosinophils are not always
present but if they’re present it’s good. So basically the differential the the reaction
pattern that you are seeing here is eczematous process or a spongiotic dermatitis and because
of the acute reaction and acute spongiotic process and the prototypical lesion for an
acute spongiotic process is allergic contact dermatitis and allergic contact dermatitis
when the patient has been exposed to something and they are going to develop these spongiotic
changes in the epidermis with the vesiculations. But you have to always remember many times
the reporter is going to get a spongiotic dermatitis as a report basically and it can
be related to a lot of different things so there’s a paper about spongiosis and the
way it goes is spongiosis can be caused by eight hundred things actually. So this pattern
can be seen in discoid eczema. This pattern can be seen in nummular eczema. So a clinical
pathological correlation is very important when you are talking about any eczematous
processes actually if this was an acral site then more likely it would be more likely discotic
eczema. If the clinician says that these are nummular lesions, then most likely that these
are coin-shaped lesions then it is most likely going to be nummular eczema. the irritant
contact dermatitis is going to be show more it is based on the pathophysiology of contact
dermatitis because something is irritating the epidermis. So based on that what is the
changes you are going to see in the skin going to be some changes that will tell you something
is irritating the epidermis on the top you will see some dyskeratotic cells and also
some neutrophils so if you see those then you think of irritant contact dermatitis actually.
So you have to link to clinical pathological correlation to come to a definitive diagnosis
in an eczematous process. Otherwise most of the times the report that you’re going to
get is spongiotic dermatitis because it could be acute, it could be subacute or it could
be chronic. When it becomes chronic the patient has been scratching a lot and so the center
because of the scratching the epidermis is going to react in a certain way so it is going
to become acanthotic, the dermis is going to show you some fibrosis so if you start
seeing those changes along with mild spongiosis also then you think of a chronic eczematous
process actually so this was a type of allergic contact dermatitis. Moving on to case two.
So what do we see here? So again, follow the same pattern. Dyskeratotic cells the
most important thing thing that you are going to see is is a lot of eosinophils in the epidermis
so when you’re thinking of … actually. So coming on to slide two so again when we
start from the top what do we see? We see a lot of confluent parakeratosis you can see
that the … is quite confluent. And then if you zoom in high power you are also going
to see some neutrophils abscesses in the stratum corneum the epidermis the epidermis is less
likely acanthotic and shows this psoriasiform hyperplasia and by psoriasiform hyperplasia
what do you mean is that you see the elongated bulbous where it resides. So you see that
if you look at the parakeratosis just below the parakeratosis you see loss of granular
layer. there is thinning of the suprapapillary plates so suprapapillary means that this is
the dermal papillae and the part of the epidermis above the dermal papillae is the suprapapillary.
So the thinning of the supra papillary plates and when you look the dermal papillae you’re
going to see increased capillaries actually so all these features are pointing towards
psoriasis actually. So this is a very prototypical slide for psoriasis so if you go back and
what are the changes that you want to see in psoriasis then? What is the one change
that is always present in psoriasis is the presence of neutrophils in the stratum corneum.
If you don’t have that then we can just call it psoriasis from dermatitis. You cannot
like say this is compatible with psoriasis because if you look at lesions of guttate
psoriasis you might not see any of the changes that we talked about – the parakeratosis,
the psoriasiform from hyperplasia, the thinning of the suprapapillary plate because all that
takes a little time to develop actually. So in guttate psoriasis which is a very acute
process the only thing you are going to see that points to this is psoriasis is the presence
of the neutrophils in the stratum corneum so that is a very important feature to look
for whenever you are thinking of psoriasis, psoriasiform or psoriasis from reaction pattern.
So the confluent parakeratosis, the other thing to remember is psoriasis will only be
biopsied if the patient is not responding to some of the treatment actually. Otherwise,
for a dermatologist to make the diagnosis of psoriasis is very easy actually. So he’s
not going to biopsy he or she is not going to biopsy that lesion. So whenever you are
going to get a biopsy in real life those are … that are already being treated for psoriasis
so you might not see all of the changes that have been described in a classic lesion of
psoriasis. So when we talk about classic changes we talk about confluent parakeratosis but
that might not always be present because the patient has been treated or he’s not responding
to the treatment so the parakeratosis is not confluent enough actually so you are going
to see stop and go sort of of the parakeratosis. A very important feature to look for is where
do I see the loss of the granular layer. The loss of the granular layer is always below
the parakeratosis so if you have stop and go parakeratosis you are going to see the
loss of granular layer just below wherever you see the parakeratosis and beyond that
again you are going to see normal granular layer, so you might see normal granular layer,
loss of granular layer based on if the patient has been treated prior to taking the biopsy
actually. So in a very classic case confluent parakeratosis very important the presence
of neutrophils in the stratum corneum, the loss of the granular layer, the psoriasiform
hyperplasia of the epidermis, thinning of the suprapapillary plates increased capillaries
in the dermal papillae and a superficial perivascular lymphocytic infiltrate. Those are all the
features you want to look for when you’re thinking of psoriasis actually. You might
also see some neutrophilic abscesses in the epidermis that is not uncommon but that is
not always present but yes you’ll always see the neutrophilic abscesses in the stratum
corneum. And another thing to remember in psoriasis is the pathophysiology that the
skin is that the is multiplying, the epidermis is multiplying much faster than normal actually
so you might see increase mitosis in in the epidermis that doesn’t equate to actinic
keratosis because whenever you see increased mitosis you might think maybe I’m dealing
with actinic keratosis or seeing the parakeratosis on the top but again remember the pathophysiology
of psoriasis because of increased proliferation you might see some mitosis that doesn’t
that might bring up the differential diagnosis of AK, but it can be present in psoriasis
actually. So psoriasis or case number three. So following the same pattern we start from
the top. So what do we see? We see some normal stratum corneum. And then you see this? Very
nice parakeratosis that appears like a mound actually. Okay so these are like small hills
of parakeratosis that you see a very, very important word that you are going to see in
this differential whenever you are thinking of diagnosis is mounds of parakeratosis. So
you see these mounds of parakeratosis one mound here and another mound here. The epidermis
shows mild spongiotic changes so you can see there are increase spaces between the keratinocytes
so there is mild spongiosis in the epidermis and in the dermis you see a superficial perivascular
lymphocytic infiltrate you might see some eosinophils but they are not always present,
you don’t have to have them for this diagnosis but if you see them it is good it is okay
like if you don’t need them for the diagnosis. But the other feature that most of the books
are going to describe is the presence of red cell extravasation in the dermis. So mounds
of parakeratosis, mild spongiotic changes in the epidermis, superficial perivascular
lymphocytic infiltrate plus or minus eosinophils and red cell extravasation so if you see all
these features then you are going to think of PR actually. So this is very classic pityriasis
rosea is going to show you all these features actually. if you see eosinophils another thing
to think of is a psoriasiform drug eruption. Sometimes a drug eruption can look very much
like PR. In that one you are going to see more eosinophils than you would normally want
to see in PR. If you see that the thought should go through your mind that maybe this
is a PR-like drug eruption actually. Otherwise, very classic PR. So mild spongiosis, the parakeratotic
mounds, the superficial perivascular lymphocytic infiltrate, the extravasated erythrocytes
and sometimes admixed eosinophils. Moving on to the next case. So even on low power
we know we are dealing with something that is very lichenoid-like. So you see this very
so what do you mean by lichenoid-like? Lichenoid infiltrate is an infiltrate of lymphocytes
that is hugging the dermal-epidermal junction. You have to make sure that you don’t mix
up lichenoid with the superficial perivascular lymphocytic infiltrate. I’ve seen that happen
quite often actually. Because if the infiltrate is quite dense people then consider that as
a lichenoid infiltrate. The lichenoid infiltrate the basic definition is the infiltrate is
hugging the dermal-epidermal junction so it has to almost like obscure the dermal-epidermal.
If you see that then you are thinking of a lichenoid infiltrate. Now when you’re looking
at a lichenoid infiltrate your differential diagnosis narrows down quite a bit, actually.
Either I’m dealing with lichen planus or I’m dealing with lichen planus-like keratosis,
or I’m dealing with a lichenoid drug eruption. Those are the only three things to think of
so how do you differentiate between the two? The most important thing is going to be history,
but many times you are not given the history. So in the history like if they tell you it’s
a single lesion then almost likely it’s a lichenoid keratosis. They say it’s a rash,
then it could be lichenoid drug eruption or it could be lichen planus. So in lichen planus
like if you listen to all the big people like Elston then they say that lichen planus is
like a restrictive parent, actually. And what do they mean by that is you do not have any
parakeratosis in lichen planus and you do not have any eosinophils in lichen planus.
But in pathology what we have learned is you never say never because the moment you say
never then the next case is going to show it, actually. But that is what is being described
– no parakeratosis in lichen planus and no eosinophils in lichen planus. so here we don’t
see any parakeratosis and but if I go high power and start looking in the infiltrate
there is the eosinophil, actually. I already like highlighted the eosinophils so there
is the eosinophil actually. So if I see the eosinophil then most likely this is going
to be a lichenoid drug eruption. If I didn’t see that then it would be a lesion of lichen
planus. So here’s one eosinophil and here’s the other eosinophil actually. So I can like
if I could so whenever you get a slide out like this to look at the most important thing
is to go high power and then scan the dermal-epidermal junction very carefully to look for any eosinophils.
If you see that then you pick lichenoid drug and if you don’t see that then you pick
lichen planus. So lichenoid drug eruption everything that looks like LP plus eosinophils.
So moving on the next case. So what do we see here? You see a big pustule that is composed
of neutrophils. So you see a- so the pattern of the reaction pattern that this would fall
under would be a sub-corneal neutrophilic pustulosis. So you’re going to say it’s
a whenever you see a sub-corneal neutrophilic abscess there should be a list of differential
diagnoses that goes through your mind, actually. So what am I dealing with? Am I dealing with
pustular psoriasis? Am I dealing with acute generalized exanthematous pustulosis? Am I
dealing with, uh, … syndrome? Or am I dealing with …? Those are the four main differential
diagnoses whenever you see something like this where you see a big neutrophilic abscess
in the stratum corneum. So many people consider pustular psoriasis and … as a spectrum of
the same disease, actually. so like if you talk to any of the older people that have
been practicing dermatopathology for quite some time like Dr. Phelps who’s my boss
who’s been practicing dermpath for 25-30 years then he considers AGEP and the pustular
psoriasis as one disease, actually, and they are just a spectrum of the same part. But
for the newer generation I think they think of them as separate entities, actually. So
that you might find people who say that they are the same disease and you might find people
that so how do you differentiate between AGEP and pustular psoriasis? So again, you have
to think about what would you see in psoriasis. Normally you are going to see loss of granular
layer under the neutrophilic under the parakeratosis. So do I see any loss of granular layer actually?
do I see any, uh, thinning of the supra papillary plates? If I see all those features then if
I go high power then I don’t see any granular layer, but below the neutrophilic abscess
and if I go and look in the dermis I’m going to find the eosinophils. If I see the eosinophils
and I see the neutrophilic, sub-corneal neutrophilic abscess my most likely diagnosis that I need
to pick is AGEP, actually. So acute generalized exanthematous pustulosis is going to be sub-corneal,
pustular, neutrophilic abscess plus eosinophils in the dermis, but remember some people might
still call that pustular psoriasis. Pustular psoriasis is the only variant of psoriasis
that … describes can have eosinophils, actually. So if you can go and read that pustular psoriasis
he says that, uh, they can have some eosinophils. So there is a lot of overlap between pustular
psoriasis and AGEP but if this was on the board exam then the thing to pick would be
AGEP actually if you see the eosinophils. So then we’ll continue need more history
to make the diagnosis but again you may not see the eosinophils and for … because you
need immunofluorescence to make the diagnosis. Otherwise, all of them are going to show you
very similar histology, actually. So AGEP. Moving on to the next case. If you have any
questions please don’t hesitate to stop me and because the main thing that you should
take from this three hours what are my differential diagnoses whenever I see some slide, not what
is the diagnosis. Because on the board exam you are not always going – on the exam you
are not going to get a similar slide. So the thought process is what is more important
to take out of this room and when I see this what should be my thought process of approaching
a slide. So again, what do we see here if we start from the top – we see a very normal
looking stratum corneum, but when we look at the epidermis what do we see here basically?
We see a lot of dyskeratotic cells actually. Because you see dyskeratotic cells in the
epidermis and at the dermal-epidermal junction there is some sort of vacuole interface changes.
So we are seeing a – so again the reaction pattern is now vacuolar interface dermatitis
with dyskeratosis. So again once you have thought of that your differential diagnosis
narrows down quite a bit, actually. So now I am dealing with something that is a vacuolar
interface change and that is dyskeratosis so my list of differential diagnosis is either
I’m dealing with erythema multiforme-like reaction or I’m dealing with acute graft
versus host disease or I’m dealing with a fixed drug eruption. Those are the only
three differential that you need to think of. Sometimes a photo allergic or phototoxic
might show similar changes but then you won’t see the vacuolar interface changes. You are
going to see the dyskeratosis, but you won’t see the vacuolar interface changes. So if
you see vacuolar interface changes with dyskeratosis in the epidermis uh, am I dealing with erythema
multiforme, acute graft versus host disease or a fixed drug eruption? So what will you
see in erythema multiforme? Like if you start from the top because it is an acute process
you are going to see the basket weave hyperkeratosis. I’m going to see some dyskeratosis in the
epidermal layer or it could be in all layers of the epidermis and then at the junction
I’m going to see vacuolar interface changes and in the dermis I’m going to see a superficial
perivascular lymphocytic infiltrate. If it is related to some drug I might see some eosinophils
maybe. So those are the features I’m going to see and if I see that then most likely
I’m either dealing with most likely erythema multiforme. Uh, if it was fixed drug eruption
what would you see, actually? How would you differentiate this from fixed drug eruption?
We have a slide, I think, coming up with fixed drug so we can talk about that when we talk
about fixed drug but what would you see in acute graft versus host disease? How would
this be different from most likely there might not be much difference actually. But whatever
cases we are seeing mostly don’t show the amount of dyskeratosis in graft versus host
disease that you would see in erythema multiforme. So one is the degree of dyskeratosis but you
can’t use that in the board exam. In real life that might help because most of the time
the degree of dyskeratosis you see in erythema multiforme is not is quite high compared to
what you would see in graft versus host disease. Uh, if you look at … and McGee they talk
about hypergranulosis in graft versus host disease, so sometimes people use that like
if you see some hypergranulosis that is more likely and then the most important feature
that Dr. … my mentor taught me was dyskeratosis involving the follicle, so if I say dyskeratosis
involving the follicle then more likely I’m thinking of graft versus host disease rather
than erythema multiforme so if you – if they give you a follicle that is showing some
dyskeratosis than most likely that is graft versus host disease rather than erythema multiforme.
So many times their distinction is not that easy people struggle a lot in clinical – in
real life it’s very easy to pick up the phone, talk to the clinician how is the patient
presenting? Is there any … transplant and then the diagnosis becomes much easier, but
if you get this on the board exam then you start thinking how would I differentiate?
So start looking for hypergranulosis and look for any dyskeratosis involving the hair follicle.
What does the degree of dyskeratosis and hopefully that will help you differentiate between the
two actually. The satellite cell necrosis is always associated with this like whenever
you see dyskeratosis you’re going to see some lymphocytes and that- some people call
that satellite cell necrosis. Any of them would have showed that. So preserved basket-weave
because it is a very acute process you’re going to see dyskeratotic keratinocytes at
all levels, these vacuolar interface changes, the superficial perivascular lymphocytic infiltrate
plus or minus eosinophils, actually. So next case here. So again, what do we see? We see
a normal-looking stratum corneum and then again in the- there’s a lot of these are
you can see the dyskeratotic keratinocytes so this pink keratinocytes that you see- this
pink cytoplasm the pyknotic nucleus is what is called a dyskeratotic keratinocyte. So
you see those so again now I’m in the same differential diagnosis, but here what is different
here? What do you see in the dermis here? You see a lot of pigment incontinence so you
see a lot of pigment incontinence and there is some loss of dermal fibrosis actually.
So I heard Dr. … talk about acute on acute and acute on chronic, so when you see acute
changes in the stratum corneum and acute changes in the dermis that is acute on acute that
favors erythema multiforme. When you talk about acute on chronic means acute changes
in the stratum corneum and chronic changes in the dermis because how does fixed drug
present actually? So it is a reaction that is occurring at the same place every time
the patient takes the drug actually. So the reaction will happen, the patient discontinues
the drug and the reaction goes away so the epidermis will again show when it again happens
the epidermis is going to show you the acute changes, but the dermis still has some remnants
of the previous type basically so you are still going to see some dermal fibrosis and
the pigment incontinence that is telling you that is the reaction had happened before.
So that is called acute on chronic. So if you see the pigment incontinence and you see
the dermal fibrosis, if you see some eosinophils, you are going to favor a fixed drug eruption
rather erythema multiforme. So acute on acute and acute on chronic and by chronic I mean
the chronic changes in the dermis, which is some mild dermal fibrosis and the pigment
incontinence and some and usually the other things that most books describe is the infiltrate
in fixed drug eruption goes a little bit deeper than with erythema multiforme. Sometimes that
might help, actually. If you see the infiltrate going a little bit deeper that is also in
favor of – so remember like there is not one feature to use as a cookie cutter basically
we’re going to look at the entire thing and what will I see in the stratum corneum?
What do I see in the epidermis? What do I see in the dermis? And try to put the whole
picture together to come up with a with a diagnosis, actually. So this is an example
of a fixed drug eruption. So acute stratum corneum and then necrotic dyskeratotic keratinocytes,
the vacuolar changes, pigment incontinence then, uh, the papillary dermal fibrosis and
then you might see the eosinophils and then that makes it easy that this is a fixed drug
eruption. So here again we start from the top. The stratum corneum looks pretty normal.
The epidermis looks a little bit atrophic, actually. It looks a little bit atrophic epidermis,
but what do you see at the dermal-epidermal junction? You see a lot of vacuolar interface
changes, so you are again in that same chapter or reaction pattern of vacuolar interface
dermatitis. So the first question do I see any dyskeratosis? There is no dyskeratosis
here, so the other differential diagnoses that we talked about are gone basically. So
what is the other feature that is very striking on low power? There’s a very dense infiltrate.
So you see the dense infiltrate which is around the follicles, actually. So you see a vacuolar
interface change with a dense infiltrate that is perivascular and perifollicular, actually.
So if you go high power so whenever you see an infiltrate in the dermis you fly in and
look at the player like if you are … that is what he says fly in and look at the players,
actually. So if you look at the players this is mostly lymphocytes I don’t see any eosinophils,
actually. So it’s a perivascular and perifollicular infiltrate of lymphocytes with a little bit
of atrophic epidermis and vacuolar interface changes at the dermal-epidermal junction.
So what is your differential diagnosis here now? Lupus or connective tissue disease, so
you are going to think of connective tissue. So what are the features that you want to
look for? You might see other very characteristic features that you see are follicular plugging
actually. So you see follicular plugging you see the vacuolar interface changes, you see
the perifollicular lymphocytic infiltrate and the perivascular. If it appears they may
show me thickened basement membrane at the dermal-epidermal junction and if I did a mucin
stain either with prussian blue or … I’m going to see increased mucin in the dermis
actually with all these features this is describes lupus. So lupus- vacuolar interface changes,
the perivascular and the periadenexal lymphocytic infiltrate the intradermal mucin and then
basement membrane thickening. Moving on to the next one. So again we start from the top.
So pretty normal stratum corneum. The epidermis also looks quite normal. If you look at the
dermal-epidermal junction I don’t see any vacuolar interface change or lichenoid infiltrate,
but in the dermis what do I see in the dermis? You see a perivascular infiltrate, actually.
So we see all of this perivascular infiltrate which is quite so whenever I see all this
infiltrate we again go in and look at the layers basically so what do I see actually?
There’s predominantly lymphocytes but we see a lot of eosinophils, so then your diagnosis
becomes very easy. So this is a predominantly perivascular infiltration in the dermis with
a lot of eosinophils, so our list of differential diagnoses narrows down quite a bit actually.
So am I dealing with drug, I’m dealing with bug, or I’m dealing with urticarial phase
of BP. Those are the main three differential diagnoses to think of whenever you see perivascular
dermatitis with eosinophils. So drug, bug or urticarial phase of BP. Uh, yes, Wells
can show you a similar picture, Churg-Strauss might sometimes show you a similar picture
but those are not very common diagnoses actually. Should like whenever we are thinking of in
dermatopathology don’t go to the zebras first, actually, always think common things
first. Yes, the zebras should always be in the back of your mind but you shouldn’t
be jumping to those diagnoses immediately. Like am I dealing with Wells am I dealing
with Churg-Strauss because those are not very common diagnoses and even for an extremely
experienced dermatopathologist many times that needs a lot of clinical-pathological
correlation to make the diagnosis, actually. So common things would be drug, a bug bite
which could be just even scabies or it could be like and urticarial case of BP. And for
the urticarial case of BP you need immunofluorescence to make the diagnosis. But one very characteristic
feature that has been described if you’re thinking of urticarial phase or predominant
phase of BP is the presence of eosinophils going into the epidermis or lining the dermal-epidermal
junction. So if you see eosinophils that are lining up at the junction or going into the
epidermis you are most likely dealing with some sort of a vesicular bullous disorder.
In … bug bite the other thing that we are seeing that is not being described in books
is the infiltrate tends to go into the subcutis. So many times I will see the eosinophils in
the subcutis. If I see that then most of the time I’m dealing with an … bug bite. These
are like features that help you come to like to pick some if there are two very close diagnoses
if one of these are present then you might favor one. Remember this can happen in all
three of them, but just to favor one you might use some of these features. So this is a nice
prototypical example of a drug eruption. So moving on to the next case. So here the important
thing at low power when you’re looking at this slide is to understand where the location
is because with that you are going to be able to make the diagnosis here. So what is the
location of this biopsy? Acral site basically because and why do we say acral site? Because
of the presence of this hyperkeratosis that you see on the top. So this is an acral site
biopsy because of the presence of this thick hyperkeratosis on the top and then if I look
at the changes like do I see any changes in the epidermis? There’s mild acanthosis,
but not much actually. And this might be normal for an acral site. So do I see any vacuolar
interface changes at the dermal-epidermal junction? Not much because it looks pretty
normal dermal-epidermal, but what do I see in the dermis? You see a little bit of edema
in the papillary dermis and then you see a perivascular lymphocytic infiltrate so you
can see this is composed predominantly of lymphocytes. There are not many eosinophils
here. You might sometimes see them, but usually they are not present so there is not much
so it is predominantly a lymphocytic perivascular infiltrate and if you look at the inflammation
that is going quite deep actually. And very characteristically if you look at this eccrine
structures in the base of the biopsy the lymphocytes are also going to involves these eccrine structures,
actually. So you see this lymphocytes involving the eccrine? So it’s paraeccrine, it’s
perivascular, acral site. So first of all like if you see a perivasicular and periadenexal
infiltrate always the first common thing to think of would be lupus, actually so again
you’re going to think of connective tissue diseases but now this is an acral site and
if I did a mucin stain most likely it’s going to be not increased mucin so what would
be your differential diagnosis? Perniosis. And remember that acral site is going to help
you conquer the diagnosis, so if you have to think of perniosis think of acral site,
papillary dermal edema, superficial and deep perivascular infiltrate and then characteristically
also involving the eccrine structures at the base actually. Sometimes even going into the
subcutis. If you see all these features then most likely you’re dealing with perniosis
actually. Again, there is quite an overlap with lupus so if this was on the exam they
are not going to give you both of these differential diagnosis on the list either perniosis or
connective tissue because you need a little bit of history, you need to do the stains
to differentiate between the two actually. But this is predominantly perivascular it
is not around the follicles. I see it more around the eccrine structures but not around
the hair follicles. The papillary dermal edema what else raises the differential diagnosis?
What is the condition that can show you papillary dermal edema? Polymorphous like – it’s
very characteristic of polymorphous light eruption, so perniosis and polymorphous light
eruption are the two very characteristic features that … So three things they always talk
about papillary dermal edema perniosis, Sweet’s syndrome and then polymorphous light reaction.
The polymorphous like eruption is the reaction to the sun, basically. So it is going to show
you some changes in the epidermis more, basically. Some dyskeratosis and all that. We don’t
see that here. This is an acral site so that is that is like you can rule that out but
you have to remember whenever you see papillary dermal edema three things to think of are
polymorphous light eruption, Sweet’s syndrome and perniosis. So moderate to dense superficial
infiltrate and sometimes around the acrosyringium, the papillary dermal edema and then sometimes
they also describe fibrin thrombi within vessels in some cases of perniosis, actually. So moving
on to the next case. That’s what they describe actually so remember like vascular like I
tried to avoid that word because vasculitis has been described and if you look at some
of the posts there are talk about lymphocytic vasculitis in perniosis, actually. But for
me like whenever I think of vasculitis I don’t want to give you that impression because vasculitis
always involves fibrinoid degeneration of the vessel walls. So, yes, if you read in
the books they talk about lymphocytic and what do they mean by lymphocytic vasculitis
is there is some edema of the vascular wall with lymphocytes but they are around the vessels,
actually. That is the definition of lymphocytic vasculitis, but whenever we are teaching like
we always cover, emphasize the fibrinoid degenerations whenever you are talking about vasculitis
or it can get confusing actually so better not to use the word lymphocytic vasculitis
but if you read in the books they definitely talk about lymphocytic vasculitis in perniosis
and what would they mean by that? It’s edema of the vessel wall with lymphocytes almost
traversing the vessels wall. Uh, so I’m moving on to the next case. If you look at
the top what do we see here? Some parakeratosis, hyperkeratosis, the epidermis is showing a
lot of spongiosis, a lot of lymphocytic exocytosis. So whenever we are talking about lymphocytes
going into the epidermis it is called lymphocytic exocytosis. So when lymphocytes go into the
epidermis either it could be related to some sort of inflammatory process that is attracting
the lymphocytes into the epidermis or it could be MF. So when you’re talking about MF you
don’t use the word exocytosis you use the word epidermal tropism. So when you’re talking
about an inflammatory process and lymphocytes going into the epidermis it’s called lymphocytic
exocytosis. And when you’re talking about mycosis fungoides or something atypical T-cell
infiltrate that is going into the epidermis then you say lymphocytic epidermal tropism.
So in this one its mostly lymphocytic exocytosis because there’s a lot of spongiotic changes
also what else do we see here? We just gathered dyskeratosis, so hyperkeratosis, parakeratosis,
mild spongiotic changes in the epidermis, a lot of lymphocytic exocytosis dyskeratotic
cells in the epidermis and then if you go to low power there is inflammation in the
dermis actually. And the inflammation is also going deep. But how is there like what is
like the shape of the infiltrate- it’s almost like a wedge shape actually. So you see a
wedge-shaped infiltrate in the dermis and if I go high power and look at the infiltrate
it is only lymphocytes. There is no eosinophil in this one actually. And there are papers
that have described that this diagnosis will not show any eosinophils in the dermis. So
I would normally not want to see any eosinophils if I’m thinking of PLEVA, actually. So this
diagnosis is going to be PLEVA. So what are the features in PLEVA you want to look for?
Hyperkeratosis, parakeratosis on the top, sometimes neutrophils, uh, epidermal spongiosis,
lymphocytic exocytosis in the epidermis, presence of dyskeratotic cells in the epidermis and
then this wedge-shaped lymphocytic infiltrate in the dermis with no eosinophils. many times
I will hear never say never but I think this is the condition when you don’t want to
see eosinophils. If you see eosinophils then most likely you’re dealing with some sort
of drug eruption. Uh, so PLEVA is the one condition that I’ve seen the papers that
have looked at 500 cases of PLEVA and they haven’t found eosinophils, actually. So
there is some sort of at least the literature goes and correlates that actually. So if you
see all these features then the clinical history will also help you. It’s usually young kids
or teenagers which are developing this pustular-like reaction to the body actually. So PLEVA compact
hyperkeratosis, focal parakeratoiss often with neutrophils, dyskeratotic cells in the
epidermis, vacuolar interface changes, dense wedge-shaped infiltrate, erythrocyte extravasation
and neutrophils within dermal vessels. These are all the features and when you go back
we share a copy of this presentation again with the slides and the presentation so you
can go back and again review that whole thing once over again actually. So moving on to
the next case. So what do we see here? What is a striking feature here? Something is happening
in the stratum corneum. So something is happening, but if you look at the epidermis what is the
pattern here? Regular psoriasiform so you see psoriasiform reaction pattern so that
is the bigger picture. So this is in the psoriasis chapter, actually. So you are seeing something
that has a psoriasiform reaction pattern and you see this bulbous ridges but now when you
think of psoriasiform reaction pattern the first thing do I see any neutrophils in the
stratum corneum? So I go high power but instead of neutrophils what do we see here? we see
this clearing or ballooning like degeneration of the stratum corneum actually. So you see
this balloon degeneration or very clear looking stratum corneum. So if we see that with the
psoriasis hyperplasia what is your main differential diagnosis? Acrodermatitis you’re going to
start thinking of zinc deficiency. If you see this very clear changes in the stratum
corneum or you see this very ballooning degeneration of the stratum corneum- there’s another
word that’s not coming to me its not ballooning degeneration- ballooning degeneration is not
the right word actually. Alright it is called sorry but if you go and read about this there’s
a specific description of this change that you see here. You see this clear, the clear
cytoplasm, the cytoplasm looks very, very clear actually. It’s not ballooning. Ballooning
degeneration is more commonly described with … or something. like some poxvirus and that
one is ballooning degeneration. This is herpes or something. This is more like the stratum
corneum looks quite like clear actually. Maybe I described it here. So psoriasiform pallor-
so it is called pallor, actually. Sorry. So the right word to use for that is pallor of
the stratum corneum, actually. What do you see here is? So by pallor I mean that there
is a little bit discolored. So you see here discoloration or pallor of the stratum corneum,
very regular psoriasiform hyperplasia and then in the dermis I see a superficial perivascular
infiltrate, actually. So if I that the pallor is the thing that is going to push you into
acrodermatitis enteropathy and that is caused by zinc deficiency. But what you also have
to remember is that there are other conditions like pellagra or necrolytic migratory erythema
that are going to look exactly the same histology. So when you see this histology – you see
the pallor of the stratum corneum, psoriasiform hyperplasia, yes the most common thing to
think of would be zinc deficiency which can occur in a child or can occur in an older
patient, but also the similar histology is going to be seen on either in pellagra or
you’re going to see it in necrolytic migratory erythema so if this was on the board exam
they’re not going to give you all three in the differential diagnosis. It has to be
one of them because histologically it is impossible to make the differential diagnosis unless
I get more clinical history that is what I’m dealing with actually. But very characteristic
pallor should point you to acrodermatitis eneteropathica. So psoriasiform dermatitis
on pallor and ballooning degeneration, loss of granular layer and superficial perivascular
lymphocytic infiltrate. Moving on to the next slide. So again if you start from the top
it’s very normal looking stratum corneum. The epidermis also looks pretty normal, but
in the dermis what do we see in the dermis? There’s some, there’s some action going
on in the dermis so if you go high power there’s an infiltrate in the dermis that is composed
of neutrophils and lymphocytes. So whenever you see neutrophils in the dermis the next
question that should come to your mind is do I see any vasculitis? So if you’re thinking
if it is a neutrophilic dermatosis or any neutrophils in the dermis the first question
to always ask yourself is do I see any vasculitis? So we are going to go high power and then
start looking around the vessels actually. So if I go to the vessels so here’s a vessel
here what do I see around the vessel here? I see the fibrinoid pinkish I see the pinkish
dot, pinkish color and that is what is fibrinoid degeneration of the vessel wall. So I want
to see this neutrophils traversing through the vessel wall to call it vasculitis. Just
presence of neutrophils in the vessel wall doesn’t equate to vasculitis like in tonsils
if you see neutrophils in the tonsils it’s tonsillitis or if you see anywhere else it
is like gastritis you’re going to see neutrophils in the in the stomach biopsy, but in the skin
just presence of neutrophils doesn’t equate to vasculitis. You have to see fibrinoid degeneration
of the vessel wall to call it vasculitis so you want to see fibrinoid degeneration plus
neutrophils traversing the vessel wall. If you see that then your diagnosis is going
to be really easy. This is leukocytoclastic vasculitis. So in leukocytoclastic vasculitis
as the word says leukocytic leukocyte is the neutrophil and the clastic means the breaking
of the neutrophilic nuclei. So breaking of the neutrophilic nuclei or will show up as
dust basically. That is what we call neutrophilic dust so if I go high power I’m going to
see this blue dots scattered throughout the epidermis. This is the leukocytoclasia that
is in the leukocytoclastic vasculitis. So when this nuclei break down you see this blue
dots in the dermis so these are all scattered, broken down neutrophilic nuclei. Plus the
presence of this fibrinoid degeneration the diagnosis becomes very easy that this is leukocytoclastic
vasculitis. Leukocytoclastic vasculitis can be caused by many things so you don’t have
to go into the etiology. If I see some eosinophils, yes, I say this might be related to drug but
most of the time we do not go into the etiology based on the histology. It is more of a clinical-pathological
correlation like why is the patient on some drugs, is does the patient have connective
tissue disease and that will tell you why is the patient developing leukocytoclastic
vasculitis. But based on histology it is almost impossible to go to more definitive diagnosis
so you just say … and move on basically. So perivascular mixed infiltrate with neutrophils,
nuclear dust and the fibrinoid degeneration of the vessel wall is what you want to see
for leukocytoclastic vasculitis. Moving on to the next case. So on low power what is
the striking feature here? There’s a lot of hemorrhage happening so if the hemorrhage
is happening then something is happening to the vessels actually. So when you see this
low power image and if you see a lot of hemorrhage in the dermis what is the first thing that
is going through your mind is that something is wrong with the vessels actually. So what
could be wrong with the vessels? Either it is a vasculitis or it is a vasculopathy. Those
are the only two things that can happen within a vessel. So for a vasculitis what do I need
to see? I need to see the fibrinoid degeneration that we talked about. And for vasculopathy
what would you see? Occlusion of the vessels. So those are the two things to think of basically.
So now we are going to go high power and see what we are going to see here basically. So
do I see any neutrophils or do I see any fibrinoid degeneration of the vessel walls? No basically.
So on first look, what is the striking feature here? There is a lot of hemorrhage happening.
So if the hemorrhage is happening, something is happening to the vessels. So when you see
this low power image, we see a lot of dermis, the first thing that should go through your
mind is that something is wrong with the vessels. So what could be wrong with the vessels? Either
it is a vasculitis or it is a vasculopathy. Those are the only 2 things that can happen
with a vessel. So if it is a vasculitis, what do I need to see? I need to see the fibrinoid
lesion that we talked about. And if it is a vasculopathy, what will you see? Occlusion
of the vessels. And those are the 2 things to think of. So now we are going to go high
power and see what we see. So do I see any neutrophils, or do I see any fibrinoid lesions
on the vessel wall? No. So do we see any occlusion of the vessels? All these are vessels actually.
And you see this pink, homogenized material that is filling up the vessel wall, and this
can sometimes be very nicely highlighted with EASR stains. So whenever I see this, I know
I’m dealing with some sort of vasculopathy. And this can be caused by a bunch of different
things. But the most common thing that you are going to see on an exam would be cryoglobulinemia.
In that we see this pink hyalinized material within the vessel wall. So if it is type 1,
I don’t see any vasculitis, but if I see something like this I know it is associated
with cryoglobulinemia. But remember this can also happen with some sort of coagulopathic
disorders. So in real life we can’t just call this cryoglobulinemia, we have to get
more history, but on board exams this is most likely cryoglobulinemia. It can be highlighted
with PAS stain if you need to. So PAS positive glassy material in the dermal vessels. Little
or no inflammation in type 1. And then vasculitis in type 2. So next case, what do we see here?
There some sort of sub-corneal pustule. And what else is happening here? If we look at
this here, acantholysis. What do I mean by acantholysis? Acantholysis is when the keratinocytes
start breaking off. But there is still. So this keratosis is, when I see this pink cytoplasm
within the keratinocytes and those are like necrotic or apoptotic keratinocytes. When
you are talking about dyskeratotic keratinocytes, those are more single cell apoptosis that
is happening of the keratinocytes. Keratinocytes have started to die and then the cytoplasm
becomes very pink and the nucleus becomes very pyknotic. When you talk about acantholysis,
you talk about keratinocytes and the intracellular bridges are breaking off and the keratinocytes
become more rounded when they are separating off, but there is no necrosis or apoptosis.
So here I see the keratinocytes breaking off, and so this is acantholysis. So what I see
is a subcorneal split with some neutrophils and then acantholysis of the keratinocytes.
So whenever you see a subcorneal split, your list of differential diagnoses will again
narrow quite a bit. So again, when you are talking about vesicular bullous disorder,
first thing to always think of is “where is the split?” Within the epidermis, or
is it subepidermal? If it is within the epidermis, where is it? Is it subcorneal or is it suprabasal?
So if you think always like this then your differential diagnosis will narrow. So this
one is intraepidermal, subcorneal split. So when I am thinking about intraepidermal, subcorneal
splits, my list of differential diagnoses narrows quite a bit. Am I thinking about pemphigus
foliaceus? Am I dealing with Staphylococcal Scalded Skin Syndrome? Or am I dealing with
Bullous Impetigo? Those are my 3 big picture differential diagnoses. So if I see the presence
of these neutrophils, what does it point towards? Of the 3 differential diagnoses, which one?
Bullous impetigo. So in staphylococcal scalded skin syndrome, the main feature would be a
very clean split. So all you see in staphylococcal scalded skin syndrome is a subcorneal split
between the epidermis and the stratum corneum and nothing else. There are not going to be
any neutrophils. And usually even the dermis is pretty clean. So if you don’t see too
much inflammation, and you don’t see subcorneal split, then you are going to favor staphylococcal
scalded skin syndrome. If you see some neutrophils, within the bulla, with the acantholysis and
then some gram positive organisms within the stratum corneum. If you see all that, you
are going to favor bullous impetigo. If you don’t see the neutrophils, you see the split,
you see acantholysis, you see the superficial perivascular infiltrate with some eosinophils,
that is from pemphigus foliaceus. But at least get the differential diagnosis narrowed down
quite a bit. And then you are going to look for more features to make your diagnosis.
All of these are attacking desmoglein 1, and that is the reason you see the split happening
at the stratum corneum. Why is the split happening at the stratum corneum? In bullous impetigo,
the causative organism is staph, which is releasing an exotoxin that is attacking desmoglein
1. Actually even in staphylococcus scalded skin syndrome, that is the same thing that
is happening. It is the desmoglein 1 that is being targeted actually. Desmoglein 1 is
supposed to be more interval in the epidermis. So that is the reason you see the subcorneal
split. It is mostly a split with acantholysis and mainly down in the dermis you are going
to see superficial infiltrate actually, which is not seen in staphylococcal scalded skin
syndrome. So if you see the split with acantholysis, and then you see the superficial more likely
from the pemphigus foliaceus. But in real life I need to make a list and I need immunofluorescence
to make the diagnosis. So I’m always going to do immunofluorescence to see the intracellular
pattern of immunofluorescence within the epidermis to make my diagnosis of pemphigus foliaceus.
But yes, on the exam if they start picking, what are the features that can help me? First,
what is my differential diagnosis? That is what you should take out of this room. Like,
what is my differential diagnosis by every entity. And then, once you have a differential
diagnosis, what are the subtle features that I want to look for to come to a specific diagnosis.
That is more important than jumping to diagnosis from pemphigus foliaceus to bullous impetigo.
The thinking process is very important to take out of this room. Inaudibile. So Bullous
Impetigo is subcorneal bulla with few neutrophils. So now we move on to the next case. So again
we are dealing with the. What are we dealing with? So we are dealing with a vesicular bullous
disorder because most of the epidermis is gone. What are we left with basically? We
are left with just the lower part of the epidermis. Some places you see more layers of the epidermis.
Some places only the basal layer is still stuck to the dermis. So this is known as…
So again, this is a vesicular bullous disorder, so the split is intraepidermal, not suprabasal.
So intraepidermal, not supra basal split. What is our differential diagnosis? I am either
dealing with pemphigus vulgaris but also sometimes can cause ciliary action pattern. But most
likely it is pemphigus vulgaris. So how do you differentiate between the two? So 1 characteristic
feature of Hailey Hailey is the dilated brick wall. So you will see acantholysis completely
through the epidermis from end to end. So that is a characteristic feature of Hailey
Hailey. The most important feature that every book describes is the absence of follicular
involvement in Hailey Hailey. So you can see the follicular and you see the nice involvement
by the acantholysis, so once you see that, Hailey Hailey is out. Involvement of the hair
follicle is very characteristically seen in pemphigus vulgaris and not in Hailey Hailey.
So if you see that, the tombstoning is also very characteristic in pemphigus, but there
are cases of Hailey Hailey that can cause the tombstoning. But on the board exam these
are more going to be in the mid spinous layer. So if you see a split in the mid spinous layer,
like a dilated brick wall with acantholysis, you are going to favor Hailey Hailey. You
see the tombstoning in the suprabasilar split. And then if you see the follicles involved,
everything is out, this is pemphigus vulgaris. And then if they try to do the immunofluorescence,
you are going to see the intracellular IgG and C3 in the epidermis. So pemphigus vulgaris,
the intraepidermal split and the tombstoning is very characteristic. The follicular extension
is very important to look for. And then the perivascular infiltrate you might see or you
might not. They are not needed for the diagnosis. If they are there, well and good. Then in
the immunofluorescence you are going to see the IgG and C3.
So what do you see here? Look at this split. Where is the split even at low power? It’s
in the spinous layer actually. So now you are
dealing with something that is intraepidermal but more in the spinous layer. So yes, there
may be some tombstoning like seen here, but most of the split is in the spinous layer
and you can see the cells throughout the split. So a lot of acantholytic cells almost going
from end to end. So it is involving the entire epidermis. The split is almost involving the
entire epidermis from end to end. And it is more in the spinous layer. So what is your
differential diagnosis? Hailey Hailey. So this is a biopsy of Hailey Hailey. So what
we see is a split that is end to end in the spinous layer that is all dilated brick wall.
And what is the mutation involved here? 2c1. 2c1 is the one with Hailey Hailey. In real
life, the diagnosis is much easier because I’m going to pick up the phone and ask where
are the lesions, how is the patient presenting? Then I get the indigenous areas and all that
in my diagnosis because that is much easier. But on the board exam you have to start thinking
about what are the features that are going to help me differentiate this from pemphigus
vulgaris. “I want 2 see (c ) Hailey’s comet 1 day” So now we are moving to the
next case. What is the reaction back in here? So again you are dealing with something causing
a split of the… The split is subepidermal. So whenever you see a split of the subepidermis,
think of. So I keep stressing this to my residents. Now I am in a subepidermal split, the next
question I ask is “is there any inflammation or not?” So is it cell poor, or is it cell
rich. If it is cell poor, then my differential diagnosis will be different. If it is cell
rich, then I ask myself what is the kind of infiltrate that I see. Do I see eosinophils?
Do I see neutrophils? Or do I see predominantly lymphocytes? So based on that, again, my differential
diagnosis will change. So what do we see here? We see a lot of inflammation, and what is
the kind of inflammation that we see here? For eosinophils, we want to see that orange
color. We don’t see that orange color. We see mostly multilobulated cells. So if you
see the multilobulated cells, more likely these are neutrophils. Because these slides
are 20X, these are not well seen, but on a glass slide these are very easy to differentiate
between neutrophils and eosinophils. So if I see a lot of neutrophils, what is your list
of differential diagnosis? Linear IgA, what else? Bullous lupus. So those are the two.
If I see a subepidermal split? Next question, do I see infiltrate? Yes, so what is the kind
of infiltrate? I see a lot of neutrophils. So if I see a lot of neutrophils, my list
of differential diagnosis. Again, remember, in real life BP is still going to be in the
differential. Because 95% of cases we see are always Bullous Pemphigoid. So if it is
cell poor, if it is neutrophilic rich, whatever it is, in real life BP is always on my diagnosis
list. On the board exam, yes, if I see a cell poor, I’m not going to think of BP because
you cannot make the diagnosis without the immunofluorescence. If I see a lot of neutrophils
on the board exam, it is most likely going to be BP. In real life, I am always going
to think of BP. So if this was a slide on the exam, this would be either Bullous Lupus
or IgA vesicular lupus disorder. Yes, BP is still going to be in the differential. It
is difficult. That is all I can go to based on the histology. Yes, if there is an infiltrate
in the dermis, then yes I might favor connective tissue disease. But acute Bullous lupus doesn’t
show all that. It is only going to show that subepidermal split with neutrophils. DH would
also be in the differential, but the characteristic feature will show you papillary based micro-abscesses
of neutrophils. If you see that you are thinking Dermatitis Herpetiformis. If I see a very
linear split and the neutrophils lining the dermal-epidermal junction, then I am going
to think of linear IgA and bullous lupus. And then the immunofluorescence is the only
way to go. If I see the linear IgA, then it is favoring linear IgA, If I see a full house
then I favor Bullous lupus. But without the immunofluorescence, I cannot go beyond these
2 diagnoses. There is no specific feature that is going to point me toward either of
them. Inaudible. That would favor more Bullous lupus actually. So subepidermal blister with
linear neutrophils along the dermal-epidermal junction, DH is a thing to always think of,
but in DH it is always going to be in the papillary dermis. If there is on the board
exam the neutrophilic abscesses are going to be limited to the papillary microabscesses.
So again, what is the reaction pattern here? Subepidermal split. So again, when you see
a subepidermal split, next question is do I see any inflammation? Is there any inflammation?
Yes, there is some inflammation. So what is the kind of inflammation? Eosinophils. You
see a lot of eosinophils. Both within the bulla and also in the dermis. So if I see
a subepidermal split with bulla, then my list of differential diagnoses 95% of the time
it is going to be BP, but what about a bullous arthropod bite, it can present like this also.
Those should be in your differential, but 95% of the time it is going to be BP. So BP
subepidermal bulla and then the immunofluorescence is what is going to help you make your diagnosis.
If I see the IgG and C3 at the dermal-epidermal junction, then I am going to say it is BP.
So again, what is the split here? It is a subepidermal split. Next question, is there
any inflammation? No, not really. It is cell poor infiltrate. So now, what is your differential
diagnosis? PCT or Epidermolysis Bullosa. In real life BP would still be on the diagnosis,
but on boards this is PCT or Epidermolysis Bullosa. So those are the two that are cell
poor. So now, how do we make the diagnosis of PCT? What are the features you want to
see to make PCT diagnosis? So what is this called here? Festooning. So you see festooning
because the dermis is very sclerotic in PCT, the patient has a very sclerotic dermis. Similar
thing is going to be seen on histology. The dermis is going to be sclerotic because of
the sclerosis. The dermal papilla retain their structure. When they don’t collapse, you
are going to see the festooning. The papillary are maintaining their structure because of
the dermis. That is known as festooning. So when you see this basement membrane material
hanging from the roof, that is known as caterpillar body. So when you see this basement membrane
hanging from the blister, that is caterpillar bodies. The presence of festooning. Look around
the vessels, this duplication of the basement membrane material around the vessels. So you
see some sort of thickening of the vessel wall. It can be very nicely highlighted with
PAS. If you do a PAS, it is going to highlight the thickening of the vessel wall. So you
see all these features favor porphyria cutanea tarda. So if you see festooning and caterpillar
body, thickening of the vessel walls in the dermis, this is more likely to favor PCT than
epidermolysis bulla. So PCT. So now, what are we dealing with here? The biopsy is telling
you what you are dealing with. Look at the size of the biopsy. If you are going to do
that biopsy, you are going to do it for what? If you do such a big punch biopsy, you are
thinking of something happening in the fat. That biopsy should tell you to look at the
fat very carefully. If you have a punch biopsy that is going into the subcutaneous fat, no
dermatologist is going to do that unless they are thinking deep. What is happening deep
in the dermis? You see some sort of septal thickening. So these are the septa and these
are the lobules. So you see the septa are quite thickened, so you see a very thickened
septa. And lobules. So what is the main prototypical lesion you are thinking of? Erythema Nodosum.
So once you start thinking, then you are going to look for what are the other features I
want to see if I want to call it erythema nodosum? Granulomatous inflammation. You are
going to see some eosinophils, neutrophils, lymphocytes. All in the septa. And then some
of this inflammation is going to go into the lobules. That is going to describe an infiltration
into the lobule. The central part of the lobule is preserved. It is not a lobular panniculitis.
So this is a prototypical lesion of a septal panniculitis. You see the thickened septa
and then the inflammation which is mostly chronic in the septa with the presence of
these giant cells in the micelles: Granulomas. You don’t have to go into all this, but
some of these granulomas are giant round cells and some of these macrophages around cleft
like spaces are called granulomas. But very characteristically even at low power, you
are dealing with something that is in the fat, thickened septa, and the presence of
the chronic inflammation should make the diagnosis very easy that you are dealing with erythema
nodosum. So again these biopsies are to the deep part of the fat. So again, you know you
have done a very deep biopsy. So the deep biopsy must have been done for something deep
in the dermis or fat. Even the epidermis looks pretty normal. So focus on the lower part
of the biopsy. What do we see in the lower part of the biopsy? So if you look at the
fat, what is happening to this fat here? There is a lot of necrosis actually. There is almost
like this purple degeneration of the fat wall. What is this purple material? This is saponification.
So calciphylaxis is going to be in these small dots. You can see all this purple like deposition
with a lot of neutrophils. You see lobular panniculitis with this purple degenerative
material. You can see this very nicely here. This is all fat. Saponification because of
release of the pancreatic enzymes within the fat actually. When you see this purple color
within the fat with neutrophils. When you see this you know you are dealing with pancreatic
panniculitis. This is because of the enzyme lipase that is being released and causing
a lot of necrosis of the fat and that is known as saponification and that points to the diagnosis
of pancreatic panniculitis. So again, a deep biopsy here, look at the biopsy. But here
what is also happening. What is a feature that is different from the other biopsies
here? There are inflammation changes in the dermis. There is something that is wrong in
this dermis. What is wrong in this dermis? It looks very sclerotic or fibrotic actually.
So if you go high power and start from the top, what is happening here? Look at these
vessels. These are not normal vessels. So the vessels are proliferating. When do the
vessels proliferate? Stasis dermatitis. So when you see the vessels proliferating in
the papillary dermis, you know you are dealing with some sort of stasis dermatitis. And the
stasis dermatitis becomes very exaggerated, and what happens? Start thinking of the deep
biopsy with the fibrosis and then what is happening to the fat here? See this is a big
fat lobule. Normally when you look at the subcutaneous fat, it is very regular shape.
But what is happening to the fat lobules here. Some are fat, some are big, some are …, quite
a bit actually. There is destruction that has happened in the lobules of the subcutaneous
fat. Because of the destruction this is all coiled into one big lobule. You see this fibrosis.
This is known as fat necrosis. So when you see the fibrosis, the macrophages, the combination
of the fat lobules into 1 big lobule, that is known as fat necrosis. So you see fat necrosis,
you see the dermal fibrosis, and you see the stasis dermatitis, so you diagnosis is going
to be: lipodermatosclerosis. So in lipodermatosclerosis you are going to see the dermal changes of
stasis dermatitis. The lobular proliferation of thick walled vessels in the wall vessels.
And then in the subcutaneous fat, you are going to see fat necrosis with the lipomembranous
changes. So when the membrane of the fat are being destroyed so that they coil into 1 big
lobule. So again, big biopsy so you know we are dealing with something in the fat. So
is it septal or lobular? Lobular. You see a lot of inflammation in the lobules, so you
know you are dealing with a lobular panniculitis. Are there any features that can help you make
the diagnosis? What is the kind of inflammation that we can see here? This is something that
is very characteristic. What is this? It is needle shaped cleft. This is another great
example of a needle shaped cleft. These are needle shaped clefts in the lipopolysaccharides.
What is your differential diagnosis? Subcutaneous fat necrosis. It can also be seen in steroid
panniculitis. So the history is very important on the board exam. The most likely diagnosis
is going to be subcutaneous fat necrosis of the newborn. That is the more common thing
seen with the needle shaped clefts within the lipocytes. And then I think this is the
final panniculitis slide. So is this septal or lobular. More lobular. And then when we
go high power. What is the first thing you are going to ask yourself. Do I see neutrophils?
If I see neutrophils then I am dealing with pancreatic panniculitis or dealing with alpha
1 antitrypsin deficiency or some sort of infection or trauma. If I see lymphocytes, I am going
to be thinking of something else. If I see eosinophils, it is called eosinophilic panniculitis.
So what is the kind of infiltrate that we see here? It is mostly lymphocytes. It is
mostly clear lymphocytic panniculitis. What is the other characteristic that we see here?
Rimming. So you see lymphocytes that are rimming around the lipoceles. When you see this rimming
around the fat cells, you can see it nicely around this fat cell. You are going to think
subcutaneous panniculitis of T cell lymphoma. I am not going to jump to the diagnosis. I
am going to do a lot of staining, a lot of history before I even put that diagnosis on
paper. But on the test, if you have to make the diagnosis, what is the characteristic
feature that you want? Rimming of the atypical lymphocytes around the adipocyte. You can
see that without the stains and you can pick that it is most likely subcutaneous panniculitis
like T cell lymphoma. If this was a biopsy, we would do all the CD4, CD3 7,8,56, granzyme,
TIA, alpha-beta 1. So there’s a lot of stains that would go before we make any diagnosis
of a lymphoma. But the subcutaneous panniculitis of T cell lymphoma is predominantly CD8 positive.
Cd56 positive. Those are the two most common stains that are positive in a subcutaneous
panniculitis like T cell lymphoma. CD8 and Cd 56. Cd3 and 4 are mostly negative and many
times the granzyme endotoxic enzymes are positive in subcutaneous panniculitis like T cell lymphoma.
The two variants are the alpha beta type and gamma type. The alpha beta type tends to involve
mostly the subcutis. It does not involve the dermis and the epidermis. The gamma is the
worst prognosis. It tends to involve the dermis and epidermis. So if I have a subcutaneous
panniculitis that involves the dermis as well as the epidermis, I am going to think of gamma
delta type of subcutaneous panniculitis T cell lymphoma which has a very bad prognosis
compared to the alpha beta type. So alpha beta type is mostly linked to the subcutis.
But that would all be a long list of stains to any of those diagnosis. On the board exam,
the only thing you are going to get to make the diagnosis is subcutaneous panniculitis
like t cell lymphoma. So what is happening here? Some sort of inflammation limited to
the papillary dermis that is forming a lobule. But what is the other feature here that is
used to describe? The presence of a grenz zone. The grenz zone is an onion ring part
of the papillary dermis. Just below the dermal epidermal junction if you have a dermis that
is not involved. That is known as the grenz zone. The grenz zone has been described in
3 conditions. One is granuloma faciale, lepromatous leprosy, and b cell lymphoma. Those are the
three places where you are going to read about grenz zone. So either in the papillary dermis,
very clearly uninvolved just below the dermal-epidermal junction. Because in most of the other inflammations
you are going to see the inflammation almost going to the dermis. It won’t spare the
papillary dermis, but if it spares the papillary dermis, it is known as the grenz zone, very
characteristic of granuloma faciale. So if you start thinking about granuloma faciale,
what are other features that you want to see. Mixed, and most of the time I see this lobular
pattern in the papillary dermis around vessels. So you always see a central vessel here and
you see this big lobular inflammation in the vessel. And when I go high power, what is
the kind of inflammation? I am going to see a lot of eosinophils. I am going to see some
lymphocytes and neutrophils, but characteristically it tends to have a lot of eosinophils. So
if I see a lot of inflammation that is forming lobules in the papillary dermis with a mixed
infiltrate and a lot of eosinophils with the grenz zone, then my diagnosis is most likely
going to be granuloma faciale. You get nodular dense mixed infiltrate. The infiltrate is
often in a perivascular pattern grenz zone is present. Sometimes you see LCVR. Next slide.
What is happening here. So the dermis is pretty normal, but the action is in the dermis. What
is happening in the dermis? There is some sort of infiltrate in the dermis that is composed
of . What are these cells here? If you look at these cells, look at the cytoplasm. Is
it a little bit of cytoplasm or a lot of cytoplasm? It is a lot of cytoplasm. If I see a lot of
cytoplasm, this is most likely histiocytes. Macrophages. So if I see a lot of cytoplasm,
this is most likely macrophages. This is a histiocytic infiltrate in the skin. This is
granular dermatitis. What is the pattern here? Palisading granulomas. In the skin if you
think of granular dermatitis, is it a palisading granuloma, is it a sarcoidal granuloma, or
a foreign body granuloma? If it is associated with a lot of neutrophils, it is known as
suppurative dermatitis. And then you are going to think of some sort of infectious process.
So if I see a granulomatous inflammation, with a lot of neutrophils, I am going to think
maybe I am dealing with a fungal infection, maybe an atypical mycobacteria, and I’m
going to go in that direction. If I see palisading granuloma. Palisading comes from fence. So
it is forming like a fence around something. So if you think of a palisading granuloma,
you either are dealing with granuloma annulare, rheumatoid nodule, or necrobiotic xanthogranuloma.
Those are the 3 main thing sto think of. These are the three common ones, Granuloma annulare,
rheumatoid nodules, necrobiotic xanthogranuloma. Those are the 4. There are zebras, but for
you if you can remember these 4, then that is more than enough. So how do you differentiate?
So what are the features that you want to see to make a diagnosis of granuloma annulare?
See mucin or if they don’t give you a mucin stain, what do you see this palisading granuloma
around? It is mostly necrobiotic collagen basically. In rheumatoid nodule, it is mostly
fibrinoid necrosis. If I see a very pink material in the palisade, that is the fibrinoid degeneration,
then I am going to think fibrinoid nodule. In GA, mostly around necrobiotic collagen
so mostly what I see is all collagen within the palisades. If I see collagen within the
palisades, I am most likely going to think of granuloma annulare. What if I see layers?
If I see palisaded granulomas in layers, I am going to think (didn’t understand). And
the last one is necrobiotic xanthogranuloma. The word itself is telling you what to look
for. Necrobiotic. So I am going to look for a bunch of necrosis basically. If a see a
lot of necrobiosis, I am going to think of necrobiotic xanthogranuloma. If I see very
pink material within the palisades, I am going to think of rheumatoid nodule. If I see very
altered collagen, I am going to think Granuloma annulare. And if I see the (not understandable).
So what one is this? GA actually, because you see the palisaded granuloma around altered
collagen bundles. Yes, if I do a mucin stain, I am going to see increased mucin within the
palisade. So if I see increased mucin within the palisade, that tells me the diagnosis
is granuloma annulare. But remember when you start seeing macrophages, the first thing
is I am dealing with a granulomatous process. Next, what is the kind of granuloma. Is it
sarcoidal? Is it palisading? Is it suppurative? This is a palisaded granuloma, so my list
of differential diagnosis is 4. Then you just go through your list of differential diagnoses
and make your diagnosis. So perivascular lymphocytes with interstitial macrophages. Palisaded granulomas
around areas of necrobiosis. So now what are we dealing with. First it’s very busy. So
what is making the dermis very busy? Some sort of infiltrate. Again, you can see the
same type of cells like with granuloma annulare with a lot of cytoplasm. So yes, they are
macrophages, but what is the other cell type you see here? We see a lot of neutrophils.
You see multilobulation of the nuclei, so you can see all these cells there. If it was
a lymphocyte, you would see a very nice round cell. But if you start seeing this multilobulation,
then you know you are dealing with a lot of neutrophils. If I see this lobulation with
a bunch of orangish background, then I’m dealing with eosinophils. So here I don’t
see the orange background. I am seeing multilobulation, so I’m dealing with a lot of neutrophils.
This is some sort of neutrophilic dermatosis. So if I’m dealing with neutrophilic dermatosis,
your list of differential diagnoses narrows down. So what is your list of differential
diagnoses for neutrophilic dermatosis? Sweets is one. EED. So all those things that can
look like Sweets. (Not understandable). The neutrophilic dermatosis of the dorsal hands
can look very much like Sweets, and then the one that is associated with inflammatory bowel
disease can also look like Sweets. So that is your list of differential diagnoses. So
if it was Sweets, what are the other characteristics you want to look for? You want to look for
papillary dermal edema, and then. Like I said, whenever you see neutrophils, first question
is do I see any vasculitis. I go and look for the vessels and I try to see if I see
any vasculitis. I don’t see any vasculitis. At least that part is out now. Now, how do
you differentiate between Sweets and erythema elevatum diutinum? Think clinically. Nodules.
If it is something that is presenting as nodules, what is forming that? Fibrosis. Think clinically
and go to histology. If it is a nodule, it going to fibrosis. This shows a lot of thickened
fibrous septa. So when you start seeing this thickened fibrosis, think clinically. This
is going to present as a nodule around the joints. That is how it presents. It is a neutrophilic
dermatosis with a lot of fibrosis. That is what is going to cause the nodule to form
and if I see the (not understandable). Sweet s and EED can look very similar. The clinical
presentation helps you differentiate between the two. So if I see vascular symptoms, it
is not always present. So if you see vascular symptoms it could be EED, but fibrosis is
very characteristic when you go and look back at the clinical picture. So the presence of
a neutrophilic dermatosis with fibrosis favors EED rather than Sweets. And the other thing
described in Sweets is the presence of the papillary dermal edema that is not seen in
EED. The other condition that we talked about, the pustulosis of the dorsal hands, or the
inflammatory bowel disease associated neutrophilic dermatosis will show exactly the same picture
as Sweets. You cannot differentiate just based on histology. You need clinical history. So
what are we dealing with here? Something with the deep part of the dermis. So what are these
cells here? Histiocytes again,. They are forming a palisade. Around the pink homogenous material.
What is your diagnosis here? This is Rheumatoid nodules. So in the deep part of the dermis
you see this palisading material. What is your main differential diagnosis here? Deep
granuloma annulare (GA). But you are not going to see this pink hyalinized material. Books
also describe the presence of eosinophils in Deep GA. The other thing is, if this was
real life, I would pick up the phone and talk. This is usually a young child less than around
8-10 that has Deep GA not rheumatoid disease. The history makes it very easy. But you might
not get the history, so following that algorithm is very important. So start building that.
So again, now we are dealing with the? So what is happening here in the dermis? These
cells are histiocytes. There are some giant cells. There is an infiltrate of giant cells,
so again you are dealing with granulomatous dermatitis. It is a little bit of palisading.
If you go low power, what is the other characteristic feature that can help you? Layering basically.
Same pattern follows every time. Is it macrophages, giant cells, so it is a granuloma. Most likely
here it is palisading. This layering makes it very easy. So if I see this layering, what
is the layer composed of? The layer is composed of these palisading cells of histiocytes and
macrophages and some sort of giant cells. Then you have the sclerotic dermis. Again,
you have the layer of inflammation. This is characteristically seen in NLDR. And then
if you go into much more detail, you are going to see some plasma cells. You will see some
plasma cells in NLDR. You are always going to see some plasma cells. But you don’t
have to go into that much detail. The low power view and that algorithm in your brain
should make that diagnosis much more simple to come to the diagnosis of Necrobiosis lipoidica.
So what is happening here? What are these cells here? Very similar pattern, so you see
a lot of histiocytes, lymphocytes, and giant cells. But what are they forming? They are
forming these palisades actually. What is the other feature that was not presenting
in the other biopsies? Palisades are forming around what basically? There is a lot of necrosis
actually. So I see a lot of necrosis of the skin here, of the dermis. Look at the detail
is gone basically, in necrosis the detail is quite lost actually. So when I see a lot
of necrosis, I see the palisades, I see the granulomas, your diagnosis is much easier.
What is your diagnosis? Necrobiotic Xanthogranuloma (NXG). So what are the features you want to
look for in NXG, what are the other things the books describe? Cholesterol clefts within
the necrosis and the presence of Touton giant cells actually. So this is the cholesterol
clefts. If I go high power and look for these cholesterol clefts I go to these areas of
necrosis and I find the cholesterol clefts. If I want to look for a Touton giant cell
I go high power and just look around and I am going to find the Touton giant cell. If
I see all of these features, then I am pretty sure I am dealing with Necrobiotic Xanthogranuloma.
So again this is a…? What are these cells here? Histiocytes, again you are dealing with
a granulomatous dermatitis. So what is the pattern here basically? It is not the palisades
so what is this pattern called? Sarcoidal granulomatosis. So what is a sarcoid granuloma?
Sarcoidal granuloma is a granuloma composed of these macrophages. They are also called
naked granulomas. The word naked comes from the absence of lymphocytes. Normally granulomas
are always associated with a lot of lymphocytes. If the lymphocytes are not present, then they
are called naked granulomas. The lymphocytes are supposed to be the clothes of the granuloma.
So if you do not see any lymphocytes or there are only scant lymphocytes, then that is a
naked granuloma. So if we see a naked granuloma that is most likely going to be a sarcoidal
granuloma. And sarcoidal granuloma the diagnosis is going to be sarcoidosis, but again you
will first do all the stains. I would do an AFB… a DMS and make sure I am not dealing
with an infectious process. Once I have ruled all that out I am going to call this sarcoidal
granulomatosis compatible with sarcoidosis. The other thing to always remember is sarcoidal
granulomas can occur with foreign bodies. Zirconium and beryllium are the two foreign
body materials that can look exactly like this. So the two foreign body materials that
can cause sarcoid granulomas are zirconium and beryllium. So if there is a worker that
is working in any of the industries that deal with zirconium or beryllium they can have
a very similar reaction pattern with naked granulomas and sarcoidal granulomas. Most
of the time this is sarcoidosis after I have ruled out any infectious etiologies. So I
get a big punch biopsy. So what is happening here? There is a big punch biopsy but is there
any inflammation here? No, so if you look at the epidermis it is pretty normal, the
dermis also looks pretty normal. But the size of the biopsy is telling you what basically?
Where is the biopsy from? The back basically because no one is going to take that big of
a biopsy from anywhere else. So if we see a big punch biopsy it is usually from the
back. So the epidermis looks pretty normal, even the dermis looks pretty normal. There
is normal collagen bundles. There is not much inflammation. But when you go low power there
is something not right about the lower part of the dermis. What is happening here? You
see a lot of mucin here. So there is a lot of mucin collected here that is very easily
seen with H&E I don’t need a stain. So if I see a lot of mucin on back biopsy what is
my diagnosis? Scleredema. What does scleredema clinically present with? Thickened skin of
the heads, the skin just below the neck, and the skin of the back. This is a thickened
dermis, that is telling you that the skin is thickened. But what is causing the thickness
is the presence of all this mucin that is causing separation of the collagen bundles
which causes thickening of the skin. Then the only thing to think of is scleredema.
How is this different from scleroderma? This could be a punch biopsy of scleroderma, so
why is it not scleroderma? There is no sclerosis actually. In scleroderma you will see a bunch
of pink sclerotic material. And what is all this here? You see the adnexa basically. In
morphea scleroderma the adnexa is mostly gone. Do I see any eccrine structures? There are
some eccrine structures here. In scleredema I am not going to see the loss of the perieccrine
fat. The loss of the perieccrine fat is characteristically described in morphea scleroderma. What is
my main differential? Because of the thickened skin on the back and the big punch biopsy?
Morphea scleroderma. So what are the features that help me figure it out? The presence of
the adnexa and no loss of perieccrine fat. So again you see the same, very similar changes,
but what is different about this one? Look at the color basically, how is it different
from the previous one? Very pink and sclerotic. So you know this is different form the scleredema.
And there is no adnexa, the adnexa are gone. It is very sclerotic and it has that same
rectangular pattern. So on low power I know I am most likely dealing with morphea scleroderma.
So what are the changes you will see in morphea scleroderma? Very sclerotic looking dermis,
loss of adnexa, loss of fat surrounding eccrine ducts. You can see the eccrine ducts here.
All the fat around the eccrine ducts is gone basically. In normal skin, there is always
some fat around the eccrine ducts. In morphea you lose that perieccrine fat. So rectangular
biopsy, loss of adnexa, very sclerotic looking dermis, and loss of perieccrine fat the diagnosis
is scleroderma morphea. If I go high power in a standard field I am going to find one
or two plasma cells. So again a similar looking biopsy but what is
different here now? There is some pallor in the superficial part of the epidermis. So
if I go high power, what is causing that pallor actually? It mostly edema but what is the
thing that we see that is different? What are these here? Stellate fibroblasts. When
I see these stellate fibroblasts they have this atypical appearance. They have very hyperchromatic
nuclei and variations in the size and the shape. So I am seeing some fibroblasts that
are pleomorphic looking. So if I see something that looks like morphea with a sclerotic dermis
but then I go high power and I see these fibroblasts what do I need to think of? Radiation, that
the patient has had some sort of radiation. And very characteristically I will find these
atypical fibroblasts scattered throughout papillary dermis. If I go high power anywhere
I will see these atypical stellate nuclear fibroblasts. If I see that then my diagnosis
will be radiation dermatitis. Okay so next one. What is happening here? There is something
happening in the dermis. What do we see here in the dermis? A very feathery degeneration
material that is deposited in the dermis. So when I see this what do I think of? Gout.
And what is the other differential diagnosis? Triamcinolone. So any pinkish material deposition
in the dermis that has this feathery degeneration material I am going to think this is gout
or this is triamcinolone. How do you differentiate between the two? Triamcinolone does not cause
a foreign body reaction. Remember gout causes a foreign body reaction and triamcinolone
does not. So what do I mean by that? When I go the periphery of this pinkish material
I will see these macrophages and lymphocytes lining and trying to form a foreign body reaction
and enclose the material basically. If I see that foreign body reaction around this feathery
material deposition in the dermis then this is most likely gout. And if I do not see that
and it is just pink globules, then it is just triamcinolone. So what is happening here?
The stratum corneum looks normal the epidermis normal, the dermal-epidermal junction looks
normal and even the dermis does not have much to talk about. So it is a normal looking skin
biopsy. So when you get a normal looking skin biopsy you have to think about what are the
findings that I am missing that will help me make a diagnosis? So you look at the stratum
corneum very carefully. Do I see any fungal infection? Do I see and bacteria? Do I see
any findings that make me think of some sort of xerotic disorder basically? And do I see
see any deposition in the papillary dermis when I go high power? See these pink globules
within the papillary dermis? This pink pigmented content should point you towards what? Amyloidosis.
Whenever I see pink contents and I see pink globules I am going to think of amyloidosis.
I could do the Congo Red stain, I could do a keratin marker, I could do a PAS to highlight
it, but whenever I see this pigmented content and go high power on the papillary dermis
and see this deposition then I know that my diagnosis
is amyloidosis. So again what is happening here? This one is very classic. Again I see
a lot of material that is deposited in the papillary dermis. You see this pinkish homogenous
material that is deposited in the papillary dermis. Let’s list our differential diagnosis
when we see pink homogenous deposition in the papillary dermis what are the things to
think of? Colloid milium, amyloidosis, erythropoetic protoporphyria, and lipoid proteinosis. In
colloid milium what is the feature I look for? It is the fracturing within the pinkish
homogenous material coming from degenerative elastic fibers. This is mostly where? In sun
exposed area of the skin where I will see a lot of elastic degeneration. At low power
I will see some solar damage. If I see solar damage, I see this pink deposition, and I
see the clefting then I know I dealing with colloid milium. For erythropoetic protoporphyria
the deposition is mostly around the vessels. I will see the deposition mostly on the vessels.
Then I know I am dealing with erythropoetic protoporphyria. In lipoid proteinosis where
are the depositions? So again go back to the clinical findings. How does lipoid proteinosis
present? It presents with very tight skin. The tight skin is being causes by the sclerosis
of the dermis. Where do we see this deposition in the dermis? It is perieccrine so I will
see it around the adnexal structures. So If I see pink amorphous deposition around the
adnexal and in the papillary dermis, think lipoid proteinosis. So what is happening here?
You see some neutrophilic infiltrate that is almost forming a path through the epidermis.
So this is some sort of a perforating disorder. So when you are dealing with a perforating
disorder there are three or four things to think of. I am either dealing with elastosis
perforans serpiginosa (EPS), reactive perforating collagenosis, perforating folliculitis, or
a patient with renal disease who has acquired a perforating dermatosis. For EPS what do
I need to see? When I go high power I am going to see pink elastic fibers forming a path
through the epidermis. If I see a lot of degenerating collagen bundles then I am going to think
of reactive perforating collagenosis. If it is associated with a follicle then it is perforating
folliculitis. If the patient has renal disease then I am dealing with an acquired perforating
dermatosis. The board may ask you what is the drug associated with EPS. What is the
drug? Penicillamine drug class. So what is happening here? What do you see in the dermis?
You see a lot of fibroblastic proliferation. What is the background? There is some sort
of a mucinous background with a fibroblastic proliferation that is limited to the papillary
dermis. So what are the things you need to think of? Scleromyxedema or lichen myxedematosus.
So if you see a fibroblastic proliferation in the papillary dermis with a lot of mucin
in the background you should think of lichen myxedematosus or scleromyxedema. Which are
essentially the same thing. One is localized and one is generalized. Both present with
this mucin background in the papillary dermis with a lot of fibrosis in the papillary dermis.
The fibrosis is what is causing the tight skin in scleromyxedema. Lichen myxedematosus
is a localized lesion of scleromyxedema. Where is the action here? In the fat. What is happening
in the fat? There is a vessel that has a lot of inflammation in the wall that is destroying
the vessel. Something that is inflammation involving the larger vessels in the deep part
of the dermis, what is something to think of here? Polyarteritis Nodosa (PAN) . So if
you see a medium vessel vasculitis that is involving the deep part of the dermis you
are going to think of PAN. A very characteristic feature of PAN is that you will see vessels
in different stages of inflammation. So lesions will be in late stages of vasculitis, the
fibrosis will already have started to form. So if you see a medium vessel vasculitis in
different phases think of PAS. What is happening here? So again this is a big punch biopsy.
This is a biopsy for alopecia to rule out some sort of alopecia. So when we see alopecia
you are either dealing with scarring or non-scarring alopecia. What type of alopecia are we dealing
with here? Do we see much scarring of the dermis? No, so we are dealing with a non-scarring
alopecia. The main two differential diagnoses are: alopecia areata or androgenic alopecia.
So what are the features you want to see to diagnose alopecia areata? You will look for
inflammation around the follicles. Do we see any inflammation around the follicles here?
There is some sort of lymphocytic infiltrate at the dermal papillae so that is a very nice
feature. What is the kind of hair this: androgen of catagen? This is a catagen hair. What would
I see in adrogenic alopecia? You are going to see miniaturization of the hair follicles.
What do I mean by miniature? Smaller hair follicles and see more hair in androgen phase,
fibrous streamers, and increased sebaceous glands. If I see more hair in catagen phase
then we are dealing with alopecia areata. Okay, keep moving. What is happening here
now? Where is the action here mainly? In the epidermis. So what is happening in the epidermis?
What are these cells here? Lymphocytes. Is there anything wrong with these lymphocytes?
They are much bigger than normal. If you look at the hyperchromasia and they are much bigger
than normal. So I see a lot of lymphocytic exocytosis and epidermal tropism in the epidermis.
And some of these lymphocytes are quite bigger and hyperchromatic. If you look at this lymphocyte,
what is happening here? It is like a lump of coal. You see a lot of lymphocytes that
appear a little bit bigger, hyperchromatic, and going into the epidermis. So what is the
main differential diagnosis here now? Mycosis Fungoides. When I see a lot of lymphocytic
exocytosis into the epidermis, this is called lymphocytic exocytosis that is out of sync
basically. Normally in spongiosis you will also see lymphocytic exocytosis, but it is
in sync with the amount of spongiosis. Here there is not much spongiosis, but there is
a lot of lymphocytes going into the epidermis. When I look at high power these lymphocytes
are quite hyperchromatic. Some of them have this convolution, and very characteristically
they are lining up the dermal-epidermal junction. And then if you look at the dermis you see
these wiry collagen bundles, they can this wiry pattern. These are all features in favor
of… mycosis fungoides. In real life I am going to do the CD3, 4, 7, 8, 20, and even
a CD30 before I even go in that direction. I want to see increased CD4 compared to CD8.
I want to see some loss of CD7. If I see all these features and the clinical history is
concerning for mycosis fungoides, I would say compatible with the clinical impression
of mycosis fungoides. But on the board exam they are not going to give you the CD4, 7,
and 8. So what you want to look for is hyperchromatic lymphocytes going to the epidermis out of
proportion to the spongiosis, and some lining of the dermal-epidermal junction. If you see
all those features with the wiry collagen then you are going to think of mycosis fungoides.
So again this is very normal looking skin. Normal stratum corneum. Nothing in the epidermis.
Nothing at the dermal-epidermal junction. The dermis also looks pretty bland actually.
You have to start thinking what are the features that I need to look for to make a diagnosis?
So I go high power and I look at the stratum corneum. Do I see any fungal elements or bacteria?
I don’t see anything. Do I see changes in the dermal-epidermal junction? No. Do I see
and deposition in the papillary dermis? No basically. Do I see any reticular reaction
in the dermis? Even the reticular looks pretty normal. So now what is left basically? So
this one, the history is that the patient has presented with slate-colored lesions on
the skin. The patient has some slate-like discoloration of the skin. If I give you that
history what is the other thing you need to think of? You should start thinking of some
kind of deposition. So for argyria what do you want to see? You can see this black deposition
around the eccrine vessel walls. And that is characterized by the history. Otherwise
I wouldn’t even think about the diagnosis, even after 20 years of pathology. But when
I get the history of slate-like discoloration, and the patient is on some sort of silver
drugs or something, then yes I would think about the diagnosis. If you see something
that looks pretty normal then you have to think of argyria especially on the board exam.
So just go to the eccrine ducts and look for the deposition and when you see that you know
you are dealing with argyria. So what is happening here? Scabies. You can see the nice organisms
within the stratum corneum. And they are all over the all over basically. This is very
classic scabies. If you see something that looks like an arthropod bite on the board
exam so that you see a superficial and deep perivascular with a lot of eosinophils you
have to think of scabies and look at the stratum. Again if you don’t think about it, you are
going to miss the diagnosis. So just make sure you look at the stratum corneum very
carefully to look for these organisms. If you see them that is scabies and the diagnosis
becomes much easier. The pattern is always going to be the superficial and deep with
eosinophils. If you see that you have to think of scabies. This one is much easier because
you can see the organisms all over but one the exam you may get just a single organism.
So on this next slide there is something that is affecting the hair follicle. What is affecting
the hair follicle? What is happening to the follicle that is causing some sort of degeneration
actually? So what is causing the degeneration? Herpes. So what are the features you want
to see for herpes? Multinucleations. Multinucleation, molding, and margination are the three things.
By multinucleation I mean that the nucleus starts becoming like a multinucleated giant
cell. By molding I mean the nuclei are molding on top of each other. And then by margination
I mean you see the clearing of the nucleus with the chromatin way in the periphery. So
there is a dark rim at the periphery of the nucleus, that is the margination of the chromatin
that is going to the periphery. The nucleus becomes clear. Multinucleation, margination,
and molding are the three features you want to see for Herpes actually. So what is the
site here? Acral site actually. You see this organism. This usually comes in order to rule
out a melanoma. They mostly come because they presented with pigmented lesions. But the
history is the patient has gone to South America and walked on the beach and got this infectious
process on the acral site. So what is this organism? Tungiasis. Once you see this you
won’t forget. This is a gravid female actually. So you see the all these eggs. So it is a
gravid female, it is always a gravid female and you see this in the stratum corneum and
it usually presents as a pigmented lesion. Once you see this you always remember it;
acral site tungiasis. The organism is Tunga penetrans. What is happening here? There is
a lot of inflammation in the dermis. What is causing the inflammation here? So there
is some sort of organism here. You can see all of these round organisms here. Whenever
you see these organisms you should start thinking about Cryptococcus, lobomycosis, blastomycosis,
or coccidioidomycosis. So there is Cryptococcus. One thing that I think is helpful about Cryptococcus
is that you have pleomorphic yeast, right? You have small ones, medium, and big ones.
They all look different sizes and shapes and I think that is really helpful. Plus the capsule
around them. Here is a piece of tissue that is kind of fragmented. And if you look here
you can see there is a lot of scale and keratin debris on top and ulceration. The dermis is
completely filled with infiltrate. And if we look closer at that it is a whole mixture
of cells: neutrophils, histiocytes, all sorts. And I can’t get any closer on this one but
you can see these round structures here; these are large round uniform yeast. Here are some
more. See the little circles. You can see them because they have thick cell walls. Here
is another place over here that is a little bit better. You can see them kind of floating
in the background and what you will see is a large yeast here and here is another large
yeast right here. They are budding, you have these broad-based budding. They are big round
balls of yeast that look relatively uniform in size and then they have buds coming off.
So instead of a tiny little narrow-based buds they have these big buds. So that is classic
for what? Yeah, Blastomycosis. Again they are much larger than a lot of the other yeasts
and they are very uniform in size. And you do tend to get a mixture of neutrophils and
histiocytes, so anytime you see granulomatous dermatitis with neutrophils, always think
of infection until proven otherwise. Or if you see granulomatous dermatitis with plasma
cells you often have infectious etiology. Until you have ruled that out always keep
that in mind. Plasma cells are a nice clue. This piece is upside down. I have moved over
here. The presence of epidermal hyperplasia that pseudoepitheliomatous hyperplasia pattern
with neutrophils with granulomas also really strongly makes you think of deep fungal infections
over other types of infectious things. So that is Blastomycosis. And obviously to be
sure about a fungal infection, cultures are important or other modalities. Yeast a lot
of times can be classified pretty precisely in most cases by the H&E or PAS and GMS by
their morphology. Hyphal fungal infections are totally different though. All of the rules
that we use to diagnose Aspergillus or Fusarium or Mucor are not reliable on tissue sections.
I had been taught that rule and I tried to break that rule before and was proven wrong
by culture. So anyway I always have to talk the clinicians down from it and say: “well
we can’t tell you for sure. We can tell you whether it is septate or not but sometimes
treatment alters the way those hyphae look.” We will talk about that in a second. Here
is a nice shave and again you can see a dermal infiltrate. When you look at an infiltrate
from low power, if it is really blue and diffuse it is probably lymphocytes, right? If it is
really pink or gray, it is probably histiocytes. It is not always true, but that is a useful
thing because histiocytes have a lot of cytoplasm. That is why they look more pale because the
nuclei are spread out from each other by extra pale cytoplasm. So that is a useful low power
way to start thinking about histiocytes. And I was wrong, this is not actually histiocyes.
It is actually collagen. So see I told you it doesn’t always work, haha. But these
areas are histiocyte aggregates. So by definition these are granulomas. You don’t have to
look around very long on this case to find the organisms. These big round cystic structures
are classic for Coccidioidomycosis. And they are filled with, they are too small to see,
but they are tiny little endospores or sporangia are inside the cysts. So sometimes the cysts
are filled and you have lots of little tiny dots in them. Sometimes cysts break open and
spill their sporangia out into the dermis and then leave open empty cystic structures.
Sometimes they won’t always look perfect like that, sometimes they look broken down.
And of course with a lot of these fungal infections, where you are geographically matters a great
deal, right? If you are in the American southwest Coccidioidomycosis is really common. You never
see it where I live in Arkansas. We see Histoplasmosis all the time. You can see Blastomycosis sometimes.
So there are certain things that are very different geographically depending on your
environment and whether the fungus likes to live there. So that is Coccidioidomycosis.
And there is some information about that. Alright, I think we will go that way. Again
a biopsy. We have a little bit of reactive epidermal hyperplasia. Not real dramatic.
And then the dermis has completely filled with an infiltrate and kind of cystic breakdown
even. Looking closer we can start to see multinucleated giant cells even from this power. And then
hopefully you can pick them up from here, you see these little guys here? These little
round structures, and what color are they? They are brown like kind of a golden brown
color. Even with H&E you can see there are numerous, numerous little round, oh they are
actually showing up really nicely on the screen I didn’t realize. Heck I will just move
my podium a little bit so I can see the big screen. Alright now we are in style. Okay
so what are these called? There are lots of names because we can never have one name for
anything in dermpath, right? We have to have like 5 names. So what are some of the names
for these? Sclerotic bodies, medlar bodies, copper pennies, all the things. You guys can
go publish papers and make up new names and then we can teach them to people and just
make it more complicated. But they are round pigmented fungal structures, okay. And I think
there is actually some debate over whether they are actually yeast forms or spore forms.
I am not a mycologist. I think fungus is cool but I am certainly not an expert on the mycology
aspect. But what they do is they are round pigmented fungal structures. You don’t even
need to do any stains here but obviously they stain with PAS and GMS. They also stain with
Fontana-Masson because what this is, is basically a form of melanin being produced by the fungi.
And when you have these round structures only in the dermis, and look at all the giant cells
and histiocytes, we call this what? What is the diagnosis here? Yeah, chromoblastomycosis.
It is important to know that that is a descriptive term. That is not actually the name of a fungus.
Most other fungal infections are named after the name of a fungus, but this is not named
after chromoblastomycosis, that’s not actually a fungal genus name. There is a bunch of different
genii and species and a handful of different fungal species that are pigmented or dematiaceous
fungi that are soil dwelling saprophytic fungi. They are basically mildew. They are similar
fungi to what we see in black molds and mildew. So they are often from traumatic implantation.
People will step on a stick or cut their hand when they are gardening and get a little piece
of wood implanted. Where I live in Arkansas almost every time I see a wood splinter, which
is not really a splinter, it is usually a stick or thorn from a garden. Almost always
you can see little pigmented fungi as little passengers on the wood because it is a relatively
humid climate where we live and it is warm. They often just stay on the wood and the host
immune response keeps them from overgrowing but in people that don’t have as good immunity
or get a high load of fungus they can develop these. They can be ulcerated nodules or kind
of draining plaques or nodules on the lower extremity. And if you see pigmented hyphal
structures we use a different name. This is purely descriptive, but what is that called?
Yeah phaeohyphomycosis. So chromoblasto and phaeohypho to me are on a spectrum it is just
a matter of terminology that we use. And again the actual species you can culture out and
find out. Some of the species do behave a little bit more aggressively than others so
it is actually sometimes helpful for clinicians and infectious disease doctors sometimes want
to know that information. Chromoblastomycosis. Always a delight to see it because is kind
of cool to be able to see the fungi so darkly colored.
Alright. For low power it doesn’t look like much. Can I use the up arrow to go back or
will it not do that? Okay, just zoom out? Okay. Look from low power it might not look
very exciting here. Here is the epidermis down here. There is not much inflammation
or anything. The only thing you see are these dilated vessels here that are either filled
with blood or thrombus. It is hard to tell with low power. When you go closer, look what
is happening. There is blood. There is fibrin, there is clot here. But look at all of these
things, what are those? Yeah, bad news is what those are. Those are fungal hyphae growing
out of the blood vessel. The dilated congested vessel that is filled with thrombus mixed
with fungal hyphae and the hyphae are growing through the vessel wall. So this is angioinvasive
fungus. This is basically metastatic fungus if you like to think of it that way. Probably
they have a nodule on the lung or somewhere else. One of my early autopsies I did was
a transplant patient that had just tons of Aspergillus, which is what this is in this
case, in the lung. And then had some of it go into the vessel in the lung, spread to
the GI tract and then eroded its way in and the patient died from bleeding out into GI
tract. It was really a terrible case for that poor patient but a really good example of
exactly how these fungi operate. Once your immune system is broken down and you get a
nidus of this growing inside your body and it gets into the bloodstream it can spread
all over the place. So this will show up as purple of black areas of ischemic necrosis
and the skin will eventually ulcerate and turn into eschars. And then when you biopsy
what you are going to look for is the vessel. So anytime you have one of those things where
the vessel is blocked off by clot or thrombus always think about could it be angioinvasive
fungus that is causing the clot, okay? It is important to learn to recognize ischemic
changes in the skin and then looking at what is wrong with the vessel. Is it because there
is cryoglobulin, are there thrombi from DIC or HUS, is it because there are fungal hyphae
invading the vessels, is it calciphylaxis? Those are always important things once you
recognize ischemic changes in the skin you have to figure out why that is there because
a lot of those things are really urgent acute things that are basically derm emergencies.
So a lot of times if you are lucky you will see the hyphae on the H&E even without doing
a stain but if I have any suspicion I will do the stain. These tend to be in immunocompromised
patients. If this were in any of us we would have a lot of inflammatory response here.
But in these patients they are wiped out and they have no immune response, so it is often
very pink or red appearance on low power because you will see blood and hemorrhage and fibrin
and no inflammatory response. And also once this thing gets ischemic it gets even more
pink even less purple. So it often has a very pink wiped out appearance to me and very little
inflammatory response. And there are multiple vessels in here with that same finding. Again
don’t call this Aspergillosis unless there is a culture. You can say angioinvasive fungus
and that there is septation and acute angle branching. There is a paper from the American
Journal of Clinical Pathology I think from 2010 that has a real nice evidence that you
cannot reliably speciate fungi. Sometimes you are going to be right. But you are going
to be wrong sometimes too. We actually cite that in our report so when clinicians call
and say: “come on what do you think it is?” and we tell them it looks like it is probably
Mucor actually. No it was Aspergillus when they actually cultured it. The patient had
been treated with amphotericin which can cause the fungal morphology to change. All those
classic descriptions are based on cultured microbiology dishes and not on tissue basically.
So you have to be really careful with that and don’t get bullied into trying to be
a culture dish. Tell them to do PCR, we do that sometimes too. So in this case it was
Aspergillosis but remember that Fusarium and other species can have identical morphological
appearance. This is a great case. Geronimo Jr Lapac (in
audience) may have seen this before. I have never seen a case in the United States but
I am always looking for it. This is a bit of an older slide, it is a little washed out
you can see this is muscle and fat down here and a really thick epidermis up here. And
then a nodule here of histiocytes and foreign body giant cells. If we look closely… look
at those. You see those little white circles? And they are all perfectly uniform in size,
much like Blastomycosis, right? But in some areas if I can find some good areas they are
kind of making chains. Blasto is kind of haphazard, but these are kind of linked to their neighbor
and the often line up and make rows or chains. So they look like a string of pearls or some
people say they are like “pop beads” like those little toys that babies have that you
can snap together. I don’t know. I didn’t know that is what they were called until I
saw that on Twitter like a year or two ago and I was like oh so those are pop beads.
We had them when I was a little kid but anyway I didn’t know what they were called. Or
brass knuckles if you are from like a tough inner city place I guess you can call them
that, I don’t know. We try to be a little bit more pacifistic so we will say pearls
around here. This is what? Lobomycosis or as one of my friends from the
Amazon region of Brazil likes to call it lacaziosis because its Lacazia loboi and usually we named
fungi by their genus and I thought, “oh okay”. It is actually named after a guy
named Lobo who discovered this fungus. And if you want to impress your friends at cocktail
parties, there is a cool bit of trivia: what kind of animal gets lobomycosis? Dolphins,
pink Amazon river dolphins. Woah, drop that at your next party and your friends will be
super impressed. This might explain a lot about my social life. I think it is cool though
and like the way it looks, but of course I never see it in real life because I live in
the United States. And it tends to make a real keloidal nodule and a lot of times you
tend to a have a keloidal, dense fibrosis and scar in the background in addition to
the fungal organisms and granulomatous infiltrates, and that can be a useful clue as well. It
is like we are on a theme here again a dense, dermal infiltrates. Look at that, look at
all those tine white circles. So, we got to go way in and see what is in those circles.
Circles usually mean something; something is usually making the circle. It’s artifact,
mucus, capsule, or something. When you see little white holes in tissue you have to stop
and wonder why it is there. Can you see what’s there? It is hard to see because we can’t
go any higher power on here, but I still think it is enough. Do you see those little dots?
Ya, well that’s the buzzword, right. I think kinetoplasts are imaginary things that are
not real; no, I am just joking, they are real but they are just so tiny that unless you
have oil immersion I do not think you can reliably see them. When I am a board certified
dermatopathologist and I am confessing I cannot see them—it is like the emperor’s new
clothes, right? Like everyone is like “they are great clothes” or “look at those kinetoplasts”,
well, no it is fake news, man. I’m just joking, they do have them, they are protozoa
kinetoplasts; the diagnosis is leishmania. But in real life, they look almost identical
to histoplasmosis. They are the same size, uniform, super tiny. They are intracellular
usually within histiocytes. They tend to make they vacuoles—the one thing that is supposed
to be helpful though is that in leishmania they tend to line up around the outside of
vessels like a ferris wheel or marquis sign, I don’t know what that is but that’s what
people say. But like a ferris wheel, right? They have all the little cars lined up around
the circle and in the circle, there are no people in the middle. And people tend to say
that’s good for leishmania, whereas histo doesn’t do that. I think what tends to help
me in real life is that I live in Arkansas—the diagnosis is histoplasmosis because everyone
who lives in Arkansas has been exposed to histo. I have lived there 6 years, I probably
have it now too. It’s really common, it’s everywhere in our environment. So, if someone
has never been outside our state, I am sure they do not have leishmania, unless they keep
pet sandflies at home or something, which they probably do not. If, however, they are
in the military and have been to the Middle East, then you really need to think about
that. Travel history is super important. You can also do urine histoplasmosis urine antigen.
You can do PCR. Or, by the way, for infectious things, the CDC in Atlanta offers free consultation
and they have every immunostain and molecular test known to man. It takes a few weeks, but
it is free and I feel like in difficult infectious cases or cases where I feel like there is
a real concern for infection but we cannot find organisms, I will often send samples
over to the CDC. No conflict of interest obviously. It’s a free service and it is one of the
few things that I am like glad I pay my taxes because it goes to that which helps to provide
such a high level of care to patients with such a complex infectious disease. So anyway,
histo I think is the real differential here with leish, which both can cause an epidermal
hyperplasia, which can cause carcinoma. Pretty much what is true of any angioinvasive fungus,
is true of leish. It can make the epidermis really get revved up and look like squam,
but it is just benign and reactive. So, telling reactive and squamous stuff apart from neoplastic,
even with experience, I think is still challenging. I struggle with is almost on a daily basis.
So, anyways, that is leish. Supposedly, you can see little kinetoplasts. Also, if you
do GMS or PAS to highlight the fungi in histo, I feel like a lot of times they look the same
until the stain. In GMS, I feel like you can really see little budding yeast spores in
histo. So, obviously leish won’t look like that. I think sometimes leish will pick up
some of those fungal stains, I don’t know if it is supposed to, but I feel like it does.
Giemsa is supposed to be positive in these, but I don’t have a great deal of experience
with using that stain here. I also think that recently didn’t someone describe Cd1a, there
is like one clone of Cd1a that a Langerhans marker for some reason has a cross reactivity
with leish. I have not tried that yet but it is a thing, you can look it up. I am sure
it is a thing. But I think it is only some clones and a weird cross reactivity. I think of the marquis sign similar to the
ferris wheel, like the round circle. And although it is hard to see here, on this big screen
because they are pale. I think that this is about as good as I’ve seen it, because every
single circle has organisms just around the outside. You see, they are all around the
outside; just a few have them in the middle. But most of them are empty circles with little
dots around the periphery. See there are dot, dot, dot, dot and in the middle, is nothing
with dots around the outside. See that is leish, that’s classic. Alright, so there
is leishmania. Alright, so here is a solid cellular sort
of thing. I like infections, but I like tumors too though. We can’t tell for sure but we
might be on acral skin or we might be on skin that has been picked or scratched. Sometimes
it is hard to tell. We have a dense dermal, kind of multi-nodular proliferation. We look
closer and what shape are these cells? Ya, some of them are spindle, you could argue
some are epithelioid, they are kind of rounded. That’s the thing about spindle cells, especially
when they grow together in fascicles. You cut the fascicle long ways and it looks like
they are spindles. But if there are plump spindle cells in the fascicle, when you cut
a cross section, it is going to look round. Think of a hot dog, if you cut in long ways
vs a cross section it looks totally different, right? So, I think that is a nice way to think
of it. So, here, depending of which way you section through the fascicle, you are going
to get a difference in appearance. So, here are spindle cells and fascicles that I know
are not as perfectly well-formed maybe as a smooth muscle neoplasm. Though that could
cross your mind here. You could think of a leiomyoma or a leiomyosarcoma. But they are
all kind of in fascicles together and what else do we have? What is all the red stuff?
Blood, right. So, we got little dots of scattered red blood cells that are outside of vessels,
in between all these spindle cells. So, what is this probably? Kaposi sarcoma, ya, you
guys already said it. So, this is described as slit-like spaces with blood and you might
say “where are the slit like spaces?”. That’s the problem. The vessels are not
well formed in Kaposi and what you have is that all of these are endothelial cells, but
instead of making well-formed vascular channels, like endothelial cells are supposed to do,
they start spindling and growing out of the dermis. In the early phases of Kaposi, it
can be very subtle and you just have these trickling of endothelial cells and some dilated
channels in the dermis. And those can be quite challenging to diagnose. The late tumor stage
of Kaposi can also be challenging when the blood is not present. When the blood is here,
everyone is like “oh, that’s easy, no problem.” Take the blood away and all of
a sudden you are like “what the heck is this” and I have definitely had cases before
that didn’t have much blood, and I really scratched my head for a little bit. So, on
your test you’ll probably have the blood. If the slit like spaces with the extravasated
red cells are good and if the fascicular pattern is really good like in tumor stage Kaposi,
and the other thing one of my mentors Mark Edgar taught me, and he taught me so many
little pearls that are visual clues is, look, here we are not getting the spindle cells
because they are round because we are cutting the fascicles in cross section, so it doesn’t
look like slit like spaces any more, it looks like a bunch of little holes, like a colander
or a sieve, like a spaghetti strainer. So, you’ll never think of pasta the same again,
but truly not a food analogy. It’s just a kitchen utensil analogy, so I think it’s
legit. Food analogies are out but kitchen utensils are in. So, anyways, little holes
(it’s a tough crowd today, okay) filled with blood when you cut the fascicles in cross
section, I think is a helpful clue also. And what kind of inflammatory cell is almost always
present in Kaposi? Plasma cells, such a useful clue. If you think it is Kaposi, go look for
plasma cells, they are almost always there. And obviously the traditional setting is older
Mediterranean men or Ashkenazi Jewish men or any older person can get Kaposi; it’s
usually on the feet or lower extremity because your immune system goes down and your HHV8
levels go up and drives the proliferation of these endothelial cells and cause the tumor.
You can’t cure Kaposi but you can treat it palliatively and most times it usually
does not kill people. People die with it, not from it. With the exception of uncontrolled
HIV. With AIDS, Kaposi can be more aggressive. One thing that can help you know Kaposi from
angiosarcoma, it that in Kaposi the cells are kind of atypical but they are not wildly
pleomorphic. Telling Kaposi from angiosarcoma, you might say they are both vascular and both
sarcomas, but it is as different as nevus and melanoma. It is that much difference.
You can’t cure this and you don’t need to do some big surgical excision because there
is no point to try because it will pop back up because the virus is everywhere, right.
These people get multifocal disease not because it is metastases, but because the virus is
all over there body running amuck. Angiosarcoma on the other hand gets aggressively treated
and has a poor prognosis and is a totally different disease. We now know that the use
of HHV8 or LANA1 immunostain to prove that it is Kaposi sarcoma; it is almost always
positive. I would never make a definitive Kaposi diagnosis without it. I may make a
diagnosis on H&E sometimes if it is very definitive, but it just doesn’t hurt to do the stain.
Angiosarcoma arises in different settings, right? Most of the times I see angiosarcoma,
it’s the head and neck of old, sun damaged folks and also in radiation sites. So, if
it’s an old person on the head or neck, do not call it Kaposi sarcoma unless they
have like AIDS or are positive for HHV8. I don’t care how much it looks like Kaposi
sarcoma, it is probably angiosarcoma. And I’ve definitely seen a couple examples of
angiosarcoma that were very spindled and looked very much like Kaposi. Also, if there is dramatic,
wild atypia it is more likely to be angiosarcoma than Kaposi sarcoma. Sorry, I get a little
excited about these sarcomas. Alright here is all the stuff I already told you. Ya, that’s
nice too, I get excited about this also. Alright I just like dermpath.
Alright, just look at this. So, like Raj was saying earlier, there is a Grenz zone here.
I personally don’t find the Grenz zone to be helpful for most things. They work nice
for granuloma faciale, but I feel like in general the rule gets violated so much that
I have just given up on it. But look at this, we have some sort of infiltrate that is in
the dermis and subcutis. It is very striking that it is organized into structures somehow.
How would you describe these? Ya, they are kind of like nodules. Look at this one, it
is kind of serpiginous, like a snake or S shape or long, linear kind of shape, okay.
So, let’s go closer and see what this infiltrate is. Well, it is kind of hard to tell. It is
cells with a bunch of cytoplasm. Usually that should be a thought of histiocytes. Or whenever
I see cells and am like “I don’t know what kind of cell that is”, the answer is
histiocyte. That’s how I learned it honestly. I asked my mentor who had little triads to
remember everything; his name was Dr. Ro and I’d ask him “What’s the triad for histiocyte?”
And he would go “Well, you’ll have to make that one up yourself, Jerad.” So, what
I learned was that once I learned all the cells and there was something left over, it
was a histiocyte. Because they are kind of vague and just blend into their surroundings.
And so anyways, that’s the way I do things. So, if you look there are bluish, kind of
fuzzy, frothy, bubbly stuff—I mean honestly if you looked at this on high power you could
think of metastatic signet ring carcinoma, a real subtle example of that could certainly
look that way. Pathologists are really paranoid about that always. But also, when you see
histiocytes with little bluish stuff in them, always think or organisms, okay. Particularly
here, when you see histiocytes that are aggregated in this linear way, this isn’t a well formed
sarcoidal granuloma, it’s kind of loose granulomatous processes with sheets of histiocytes
and I guarantee there will be plasma cells in there if we hunt around for a while and
they are kind of growing around the dermal structures. They are around the eccrine coils.
They are around the nerves. They are around the vessels. Once I tell you nerves, then
you are like “oh, yeah”, but they grow around all the other structures in the dermis
too because nerves and vessels tend to tract together and often they are near eccrine coils.
So, I feel like often in this disease often I see eccrine coils surrounded like this and
vessels. See, there is a nerve right here though. That’s a nerve right there though.
So, what stain do we do and what is the diagnosis? Yes, this is leprosy. This is lepromatous
leprosy and you can do the Fite stain which is a different form of acid fast stain. And
there will be a “bajillion” maybe even a few “bajillion” organisms in this. Each
of these places, these little holes, are called globi and they are filled with like thousands
and thousands of organisms. So, you usually on H&E can actually see them. It is hard on
scan because they are so small, but you can actually see this fuzzy little material in
these spaces. And you can learn to pick up leprosy and you can obviously see leprosy
is endemic in many parts of the world still, like in India and the Middle East. But also,
we see in Arkansas; a few times a year we diagnose this, usually for people that have
had something to do with armadillos. Usually the vast majority of them in the wild populations
in the southern and southeastern United States which can carry leprosy and have a huge load,
like 200 times that of what humans normally have. I don’t know why they are cool with
it but it’s fine. I mean like every time I drive by and pass a dead armadillo on the
road—and I know you guys are like “oh my gosh, where does this guy live”; well,
I live in Arkansas and we have armadillos. So, I am always like I got to stop and get
some tissue and we are going to make some controls and so in my mind I keep thinking
about getting armadillo road kill to make some controls. Control tissue is hard to come
by unless you live in India and you got leprosy all the time, it is like hard to find good
Fite controls. And that’s good news because it means we are wiping out mycobacteria, but
it means it is hard to find good control tissue. We can do this stain all the time, but rarely
do we find organisms, except in a certain subset, but we stain all the time because
you don’t want to miss it, right? So, lepromatous leprosy and there are all these borderline
forms and all that stuff to me is clinical and the most important thing to me about classifying
leprosy is that on the lepromatous end you have sheets of these frothy histiocytes. You
have numerous organisms, okay. And on the other hand, you have these sarcoidal, tight
granulomas with big epithelioid cells that will also track along nerves and they will
also have very few organisms. Sometimes they will stain and look like “I’m sure this
has got to be leprosy but I don’t see any organisms.” So, in those cases we will usually
send it off for PCR to make sure because usually the differential there is sarcoidosis, which
also can sometimes track along nerves. And can cause anesthesia and nerve tingling and
stuff like that, the same kind of things leprosy does. And if the PCR fails, then what we usually
tell our clinical team is to treat with steroids and then watch the patient closely. If the
patient gets better, its sarcoid. If it gets worse, biopsy again and it is probably leprosy.
And there is actually a Hansen’s Disease Center; Hansen’s Disease is actually a pseudonym
for leprosy. There is a Hansen’s Disease research center in Baton Rouge, LA and they
used to have a leper colony in rural Louisiana but they do not have that anymore as more
have moved to Baton Rouge. They are actually excellent experts and they know so much about
leprosy and will actually coordinate with local doctors to send drugs, for free I think
actually, because patients have to stay on meds for like a year. So, really good to know
about that. If you ever get a patient with leprosy, the CDC or Hansen’s Research Center
are great resources that can help your patients. So, this is lepromatous leprosy. We are actually
writing a paper about leprosy in Arkansas because we think that people don’t actually
know that it is out there. Armadillos are dangerous. They are kind of cute though, just
don’t pet them Well, there is something pink or red there,
huh. What are the players…What’s wrong with this skin? It’s dead skin, right? The
epidermis is pink, not purple, right? All the nuclei die with ischemia and the first
thing to go are the nucleic acids, the first things to stain purple. So, whenever the nuclei,
which dissolve quickly, go, the proteins in the cytoplasm, which are structural and big,
linked chains, take a long time for your body to break down after coagulative necrosis occurs.
So, when you see pink, think how there is no nuclei left, so ischemic necrosis is a
good thing to think about. And once the tissue dies, it bleeds into itself. So, we got an
ulcer that’s ischemic and it looks like a purple, black ulcerative lesion on the patient.
This is one I don’t think I have ever seen on a patient actually in real life. It is
actually a little hard to show here, but around some of these dead vessels are little smudgy,
bluish-purple, hazy areas. And these will have little, tiny gram-negative organisms
in them. And culture would show pseudomonas aeruginosa usually. So, what is this disease?
Ya, ecthyma gangrenosum. Again, I don’t think I have ever seen this in real life.
The important thing though, is that when you see these ischemic zones and that clinical
setting, rule out calciphylaxis, rule out invasive fungus, rule out coagulative neuropathy,
and make a phone call to the physician right away. This is not something to leave from
a Friday to a Monday for the patient. For any of those ischemic things, it is really
urgent. It is more urgent than a diagnosis for melanoma, that can wait awhile, like a
week or something, and this can’t. So, anytime you have that setting, recognizing ischemia
is so important and I have actually seen a general pathologist that did not recognize
the signs of calciphylaxis that had been going on the whole time; because it doesn’t look
like cancer, it is important to know those non-cancerous things that are still really
important for those of you in the room that are pathologists. That’s an important thing
for you to remember for patient care. Doesn’t always have to be malignancy to be deadly
to the patient. So, ecthyma gangrenosum. And here we have an infiltrate in the dermis.
The epidermis looks normal. Ignore the orange, that is just ink, for those of you who are
new residents here. We got these big, frothy looking cells here that have these big nuclei
and a bunch of foamy cytoplasm. Sometimes it can be hard to tell foamy and granular
apart. When you look closely, you can see tiny little bubbles that are clear with lipid.
Sometimes they will just kind of gently scallop the nucleus, kind of like you would see in
a sebocyte. And that is kind of a good sign that you have a foamy cell, a foamy histiocyte
probably. And if this is a little yellowish, like a little yellowish flat lesion near the
eye, what would that be called? Ya, xanthelasma. And other forms of xanthoma will have a similar
appearance. I feel that you don’t see xanthoma or xanthelasma biopsied very often, so I actually
don’t have as good of a handle on the difference histologically between the different forms
of xanthoma. Okay, so xanthelasma is near the eye. If you see free-floating, gooey,
lipid material, you can think of eruptive xanthomas, which do have correlations with
different lipid abnormalities. And obviously, looking at the histology, once you think it
is a xanthomatous type process, finding out what the clinical scenario is obviously can
be helpful in deciding if they need to go in and do more work up for the patient to
rule out lipid abnormality. If you don’t get excited about this, I don’t
know what will make you happy. What’s that? Ya, we don’t even have to come closer, but
we will because it is awesome. It is the mother of all hair is a big dilated
central follicle and it has got little, tiny baby hair follicles around the outside that
are draining into and emptying into the big cystic follicle. Classically, these are described
as a big crater opening up onto the skin’s surface. But, like anything that is a crateriform
lesion, if you cut anything down the middle, think in 3D, it will look like it opens to
the surface. I guarantee this opens to the surface, but we have to section deep under
the block or else we have already sectioned too far. And so, what happens is, and this
is true for molluscum or any of these sort of crater-shaped things like some of the keratocanthoma
type squams, is if you cut just a little away from the center they can look like cysts in
the dermis. So, it is real important to recognize that cysts in the dermis and umbilicated crater-like
lesions—same thing, just sectioned differently. And the central cyst will look very similar
to a follicular infundibular cyst and what some pathologists will call an epidermal inclusion
cyst. And it will have a granular layer and flaky loose keratin. Looking on the outside,
you can see the little follicles and you have metrical basaloid cells. You’ve got the
inner root sheath with those beautiful tricohyaline granules and they empty into the center. You
can even see that there are little hair shafts in there too. You can see they are making
hair shafts. It is actually a relatively well-functioning hair follicle. Here is more of the hair follicle
here. You’ll see little papillary mesenchymal bodies or a little mesenchymal stuff around
the roots. A lot of times, if you look from lower power, you can see that the whole lesion
tends to be—it is a little harder to appreciate here—wrapped in a fibrous stroma that is
analogous to the adventitia that winds around normal follicles. Many follicular tumors have
that fibrous cellular stroma, as opposed to the basal cells that get that more myxoid
loose stroma, right. So, I think that’s a nice clue for follicular neoplasia; when
you see that sort of thick, pink stroma separating the tumor—see, here there is the rest of
the dermis here and if you go over here and way back you can kind of almost imagine that
this is the border of the lesion. Out here is where the stroma is; it is like a big circle
around the whole thing. And I feel like it is a little harder to appreciate unless you
have seen it up close, but I think that is a really useful clue that helps me with follicular
neoplasms. So, this is a trichofolliculoma. And here is skin from where?… How do you
know? …Ya, hair follicles and what else? Skeletal muscle is usually below the fascia
which is below the subcutis which is below the dermis. So, anywhere else in the body
you will have to go a mile deep to get skeletal muscle. If you see skeletal muscle getting
up into the dermis, you are almost always near or on the face, the platysma, the neck,
the scalp, somewhere up in that region. So, it is good to learn those little clues to
help you. Where do you see a bunch of smooth muscle in the dermis? Like more than usual
for the arrector pili; you know you usually see a couple strands, but what if you see
a bunch in the dermis? Where are you? Genital skin, right, or nipple, areolar skin. Nipple,
areolar, labia majora, scrotum. Those are the areas. This can be especially helpful,
especially if on exam they are not giving you general history. You can kind of cheat
in a way by saying, “oh, look I know this has got to be from the nipple.” Or if it
is squamous mucosa with a bunch of skeletal muscle you are on the tongue. So, you can
really narrow down your differential by knowing that, “oh, I know that this, this, this,
and this won’t occur in this site.” In real life, too it can help you if something
gets swapped and you accidentally get something cut and they say it is from the forearm and
you are like “I don’t think so” and don’t ignore that. I have sometimes tried
to blow that off like and then come back to realize later that this was a swapped slide
and had to go back and amend my report. So, you know, trust your gut. So, after that little
walk down memory lane, here we have something. This is an abnormal something. And how would
you kind of describe these? Tadpoles, awh that’s the best, right? Little cords or
strands of epithelioid cells in the dermis and tadpole-shaped or sperm-shaped (if you
like that analogy better, you got to find the visual analogy that works for you, no
judgement)—my derm residents would say “sperm in the derm”, which is the way they would
remember tadpole-pattern or, I guess if you are a little classier, you can say paisley-tie
pattern if you are old school. I don’t know what a paisley is, but I know what it looks
like, but I don’t know why it is called that, so anyways there are these little cords
in the dermis. So, what is the differential for this pattern? There are usually like four
things people talk about. Ya, like MAC (microcystic adnexal carcinoma), desmoplastic trichoepithelioma,
morpheaform or infiltrative pattern basal cell, and syringoma. So, it is really useful
to recognize this pattern and know those things are on your radar. The problem is that we
do not usually have this huge excision going all the way down to fascia. Usually we get
like this, a little shave and I get like three of these guys and that is really challenging.
So, what helps me is that if I see really obvious ducts up here and they look tadpole-shaped,
it is almost always syringoma, okay? MAC (microcystic adnexal carcinoma) has ducts also and it is
a locally aggressive form of carcinoma and it is important not to miss this. It is rare,
but it is important not to miss and it does not look atypical; it looks bland, so it is
really hard to diagnose. It has ducts too, but they are usually down deep, though there
are some exceptions. So, the main this I want to rule out is MAC. Then basal cell I find
that most of the time you are going to find some kind of islands of traditional, classic
basal cell. If you get a big enough biopsy it is usually there. Or there will be a little
mucin or a little cleft or something. So, I feel like that is usually the one that is
easiest to rule out. So, what I usually get down to, is that I am between desmoplastic
trichoepithelioma and MAC. And on a shave a usually have a difficult time reliably telling
them apart. So, if I have a transected desmoplastic trichoepithelioma I tell them “basal neoplasm
of the dermis; I favor DTE but I can’t exclusively rule out MAC. I recommend excision.” And
this happens like once or twice a year; it is not a common thing and I would rather have
a few patients get more surgery than they need for DTE but not miss a MAC. That’s
what I would want if it was my face or my wife’s or kids’ face. So, that is the
way I handle those cases. But what you see here both in MAC and desmoplastic trichoepithelioma,
you see the tadpole-shaped cords and the stroma tends to be a little fibrotic in the background
and you see these cysts; and these cysts are keratinaceous cysts that are tiny keratin
or follicular microcysts. Again, with MAC you will usually, eventually see tubules.
In real life, I think it is a quite hard to appreciate; it is also hard because sweat
ducts can get entrapped in the middle and they do have ducts and they look like tubules.
So, I think it’s hard. People have described all sorts of stains to try to sort this out,
like cytokeratin 20, which I have occasionally found useful. It will stain scattered Merkel
cells in the background of desmoplastic trichoepithelioma and other follicular tumors. And those cells
are usually not present in the background of MAC or basal cell. So, I have found that
useful occasionally, but most the time of a small biopsy, I am still going to hesitate
and tell them to excise so I usually just don’t mess with it and say, “here is the
differential and reexcise.” I feel as if a big enough sample and an H&E is what I need
more than a bunch of stains. So that is my personal, practical approach, but you can
read the literature. The fact that there are so many stains described to work this out
tells you that none of them work perfectly well and that it is hard…you got a bunch
of different treatments for something, it is because none of them work perfectly well
and I think the same is true for stains. When we have to keep investigating new stains,
it is because they are all suboptimal in some way or another. This is a good example of
desmoplastic trichoepithelioma because we can see the tumor is limited to the dermis.
If I see perineural invasion, even though that has been described in some desmoplastic
trichoepitheliomas by dermpaths that I like and trust, it still doesn’t sit well with
me in my soul. I just don’t like that idea of seeing perineural invasion in desmoplastic
trichoepithelioma; usually that is a feature that makes me strongly consider MAC. So, here
is desmoplastic trichoepithelioma, a challenging diagnosis.
And what is that one? Another beauty. Trichoadenoma, ya. And they are basically a bunch of keratinaceous,
tiny little cysts that are all relatively even-ish in size and are all packed together
in the dermis. And look at that stroma, look at how you can see that is where the lesion
ends. Out around the outside of the whole thing it is encased in this fibrotic stroma
that is again analogous to the adventitia, that outer fibrous layer around normal hair
follicles. Go look at normal hair follicles sometime if you have never seen that before.
There is this little band of fibrous stuff around normal follicles and that is what’s
getting recapitulated here. Follicular tumors are what I think are the hardest subset of
adnexal tumors because there are so many of them; and Dr. Rapini who had a huge impact
on my career also and I got to spend a couple months with him in residency in Houston and
I love what he says which is that each one is like a snowflake, a little bit different.
This is so true, there is no two that are quite exactly alike. They all have slight
difference to them each time, which makes them more challenging to classify. Fortunately,
most of them are benign. One thing you can see in anything with keratin microcysts is
this granulomatous reaction to keratin debris. You can see that in any keratinaceous, keratin-producing
thing—if that keratin breaks out, gets into the dermis, and keratin is find as long as
it is outside the body. Once gets down past that basement membrane and into the dermis,
the body is really unhappy about it. So, some people compare these to donuts, but my program
director, Doug Parker, likes to say that if you go to Home Depot (a hardware store) and
you look at the aisle that they have PVC pipe, you know those plastic pipes, and look at
a stack of PVC pipes, this looks like a bunch of PVC pipes stacked up. And I thought that
was a pretty cool analogy. So, if you are into like building and stuff, maybe you like
that better. I like donuts too. Sometimes you can get cysts like this in trichoepitheliomas;
the difference there to me is if I start seeing basaloid aggregates, either little strands
of them or more nodular forms that look almost like a basal cell, then I start think of it
more towards being a trichoepithelioma. Guess what, it matters 0% for clinical care. If
a person has a solitary trichoadenoma or a solitary trichoepithelioma, it doesn’t matter
what you call it. Splitting is fun, but don’t lose sleep over splitting benign things that
are treated the same and have the same prognosis. Save your worry for things like spitzoid melanoma
vs spitz nevus; that’s the time to hedge. Don’t waste it on “well, it could be a
verruca or it could be a seb.” …then you can save up those hedging points for when
you really need them for patient care. So, I think that’s a good take home point. Practical
pearls. Cause in the real world, when the tests are done, those are things where you
are like, “gosh, what should I say, how sure am I, and how do I write a report”,
and then you’ll wish you asked your attending a lot more questions. I sure do; I am like,
“gosh, why didn’t I think about that and ask more and beg to look at every slide in
a recut set”? Look at this, we got kind of a funky weird
looking lesion here. It is kind of papillomatous on the surface. It is ulcerated a little bit.
It’s got these kind of clefting spaces pushing down that have these little islands floating
in them. So, what’s this? Ya, this is SCAP—syringocystadenoma papilliferum. So, that’s why we call it
SCAP because it is too long to say all the time. So, on the low power you have papillomatous
and/or ulcerated surface. These kind of branching, dilated duct spaces get pushed down into the
dermis. And then papillae in the duct spaces, and for those of you who are more junior residents,
papillae mean finger-shaped structures. See, this thing is kind of finger-shaped; it goes
up and down. These are also finger-shaped, just cut in cross section and you can’t
see where they connect. So, floating islands that are aligned on the outside of the epithelium
sitting in a space are papillary. If you are a senior resident you already know this, but
junior residents this is an important take home. And if you look at the lining, the lining
is made of a double layer of cuboidal, columnar lining. The inner apical cell layer tends
to be more columnar and tends to have more apical snouts on the top, those little nubs
of pink cytoplasm. The basal layer tends to be like a myoepithelial layer and more small,
round, and cuboidal. But this I analogous to sweat ducts. The only place you ever really
see double cuboidal to columnar epithelium is salivary ducts and sweat ducts. So, when
you see this, it is a strong indication you are dealing with some sort of a sweat gland
tumor. And look at all this inflammation packed in the middle here. What are these cells mostly?
Plasma cells, oh yes, loads of plasma cells in this lesion. And if you find this on the
scalp, what is a good chance you’ll find if you look around in the periphery? Nevus
sebaceus of Jadassohn, that’s right. Nevus sebaceus is like a fertile ground to give
rise to all these weird adnexal tumors, SCAP being one of the most common ones. I’ve
got a YouTube video about this entity and if you are real bored you can check that out.
I put videos of pathology stuff on YouTube for any of you guys that don’t know. So,
eventually I will cover all of the entities and then I will retire, but until then I probably
better keep working. Occasionally they can occur off the scalp, but the vast majority
of them are on the scalp. Here is a lesion that is a nodule down in
the deep dermis, relatively circumscribed. It has got cystic spaces and lots of papillary
structures folding into the middle of the cystic spaces. And if you look closer at the
lining cells, you’ll again see that kind of same thing we saw in SCAP. I think there
is a lot of overlap in this lesion and syringocystadenoma papilliferum. There is a columnar layer with
little apical tufts or snouts and you’ll have an outer basaloid layer that usually
as myoepithelial differentiation. So, what is this lesion probably? Ya, hidradenoma papilliferum—the
“happy pappy” because my derm residents teach me all the awesome and sometimes inappropriate
ways to remember things. So, anyways, I give them credit and blame for all the things I
am teaching you. I’m only kidding, and not only future, so no one is incriminated, but
future and/ or past residents have taught me these things. Hidradenoma papilliferum
is almost always in the vulva. A couple other things can look kind of like this; if you
are on the nipple and you see papillomatous stuff that is growing in cystic think about
nipple adenoma. Depending whether that is in small localized skin or deeper in ductal
structures of the breast, intraductal papillomas can have very similar features too. If you
see something on the hands or fingers or toes, that looks like this or looks like SCAP, what
is it until proven otherwise? Ya, digital papillary adenocarcinoma, which used to be
called aggressive digital, but people have suggested we drop the aggressive name. I mean
it is a carcinoma so it metastasizes in like 20% to 30%, but it’s not like it kills 90%
of people, so it is not like it is much more aggressive than other kinds of carcinomas,
I guess. So, if you see papillary structures in an epithelial lesion on the hand or feet,
you got to excluded digital papillary adenocarcinoma. They don’t always have cytological atypia
and I feel like more often they don’t have it than do. And they really otherwise would
look benign and yet they can still metastasize. Real important not to miss that. I was giving
a talk a couple years ago and right before I gave the talk a day before, some lawyer
called me wanting me to testify on a lawsuit for a patient with a misdiagnosis… and I
was like, “No, I am not real into that, but thank you for the offer.” But it was
great to scare the crap out of the people I was just about to give my lecture to because
I was like, “Oh ya, just yesterday someone called me about a misdiagnosis of this and
they are suing someone.” So, this is really important to know because it does not necessarily
look malignant. Just keep that in mind. Any adnexal tumor on the hands and feet, just
think about that, especially if you see papillae. Real important. But this is okay, this is
hidradenoma papilliferum, so we are fine. Alright, so what kind of little nub thing
are we dealing with here? It is like a bump on the face. You can tell anytime it is kind
of a dome, it is either a bump on the face or on the nose and they thought it was a basal
cell, like every time. Ya, it is something sebaceous. So, then we got to decide where.
There are not many options in the sebaceous family. Unfortunately, sometimes sorting out
which option can be challenging even though there are not a lot of options. The main options
are sebaceous hyperplasia, right, basically big, huge very mature looking sebaceous glands
with a very white appearance, okay. And then there is sebaceous adenoma and sebaceoma,
which to me are on a spectrum and it is just splitting of not hairs, but sebaceous glands
I guess. If you have more than 50% of blue basaloid cells then and less than 50% of the
mature white bubbly cells, you can call it sebaceoma. If you have a predominance of the
bubbly cells and fewer of the basaloid cells, you can say sebaceous adenoma; it really doesn’t
matter. And then there is sebaceous carcinoma of course. This is a small lesion; it looks
like they got most of it with the shave. I think arguably there are more than 50% bubbly
cells here. And you can’t really see the bubble here really well, but they are little
vacuoles and they are clear because they are filled with lipid and they dent into the nucleus.
So, same kind of rule as I used for sebocytes as a use for lipoblasts. In the soft tissue,
an atypical cell that is…mesenchymal tumor… that has clear bubbles and indents the nucleus,
those are lipid droplets and it is probably a lipoblast. In an epithelial tumor, those
bubbles that indent the nucleus are usually going to be sebaceous. I do see squams that
are vacuolated that seem to just be squam and not sebaceous that do actually have true
bubbles though. So, I have come to doubt myself over time with that. So, anyways, this I think
is a sebaceous adenoma and we usually in our practice include a comment in the report that
sebaceous adenomas are sometimes associated with Muir-Torre Syndrome. What is Muir-Torre
Syndrome? Ya, it is a mismatch repair. It is basically hereditary nonpolyposis colorectal
cancer syndrome with the addition of sebaceous tumors of the skin. So, sebaceous adenoma,
sebaceoma, and some sebaceous carcinomas when they are off the head and neck usually can
be associated with that. Sebaceous hyperplasia has no association. We don’t usually perform
the stains for the mismatch genes but we will do it upon request. Different people have
different ways they handle that. So, we usually just put that comment in the report and let
the treating physician decide how they want to address it depending on the patient’s
clinical situation. I find that you should not have marked atypia. You should not have
atypical mitosis and you should not have infiltrative growth. Those are worrisome signs for sebaceous
carcinoma. The problem is that mitoses are often found. I was giving a lecture one time
and I couldn’t find a single sebaceous adenoma in my entire collection, which is pretty extensive,
that didn’t have a mitosis. And to me that either means I misdiagnosed a ton of sebaceous
carcinomas, which I think is probably not the case because no one has come and said
that, or that the mitoses are just there. So, don’t get freaked out by a few mitoses
in these. And the basaloid cells, they look blue and basaloid and that is normal, right?
That’s what normal sebaceous glands have. But it can be hard to tell how much is atypia
enough. And if I have one that is a little funny looking and is shaved across the bottom
and transected. Sometimes I will say that I think it is a sebaceous adenoma but I has
got some atypia, so please do an excision so I can see the whole thing. Because I did
have one once that I thought was a sebaceous adenoma and it recurred and it was a carcinoma,
but on a superficial shave it did not look atypical at all. So, I don’t routinely recommend
that these be excised but if I have something concerning and it is broadly transected, well
it is just one of those things that though it doesn’t happen that often I’d rather
see the whole thing than miss something serious. Alright, here is a tumor that is bulging down
off the epidermis. It is very blue and basaloid. I would argue those are quite atypical, very
large, hyperchromatic cells. And look at all the bubbles denting the nuclei. Not nearly
as well-formed bubbles as a normal, mature sebocyte, but this is probably sebaceous differentiation
here. And I would say this is probably sebaceous carcinoma. Telling sebaceous carcinomas apart
from squams and other adnexal carcinomas can be challenging sometimes. There are a bunch
of different stains we use, like Factor XIIIa sometimes, the AC-1A1 clone for some weird
reason stains the nuclei of sebocytes very strongly in most cases; it’s not perfect
because it will stain some squamous cells and other things and it only works with that
clone. But I published that and it is like my one contribution to medicine, so I am waiting
for the Nobel Prize committee to call me up one of these days. Anyways, it is not true
Factor XIIIa expression, it is just one of those weird cross-reactivity but it seems
to be relatively sensitive and specific. EMA will also stain them, but EMA stains a lot
of things. The key for EMA is that it should highlight the individual vacuoles. Some people
use adipophilin to do the same thing. Again, the fact that we have so many stains means
none of them are perfect. The clinical is important. Anytime you have a weird carcinoma
anywhere near the eye or eyebrow region, always think of sebaceous carcinoma, particularly
if it is not a straightforward squam, if it is a real ugly looking squamous or basaloid
thing, you have to exclude sebaceous carcinoma. And they are going to treat that differently.
Sebaceous carcinoma tends to grow up into the epidermis, particularly when it is near
the eye and can grow way back in the conjunctiva in a pagetoid fashion. So the ophthalmologists
or surgeons will go and do like scouting biopsies to decide because they will treat it differently
than a squam. Off the head and neck, well, they are just going to do a wide excision
as they can be a little more aggressive than other tumors. But near the eye is where it
is a particular issue to be aware of. And the ones near the eye are not usually associated
with Muir-Torre Syndrome. The ones away from the eye, particularly if they are on the trunk
or extremities, many of those are Muir-Torre associated.
You guys hanging in there? You guys surviving? It is hardcore. Alright, it is very busy.
Let’s see if we can find out where we are. We got some smooth muscle here and, somewhere
in here, and now I won’t find it of course. Well, there are apocrine glands here somewhere
I promise. Okay, maybe there’s not, I thought there were. Anyway, we are in the groin. I
don’t know which gender of the groin we are talking about but the epidermis is acanthotic;
it is expanded here. It is very busy because it has all these large cells with vacuolated
pale cytoplasm. So, what is this? Well, that is your differential because clearly we have
big cells that are atypical trickling up and spreading up into the epidermis. So, it is
something with pagetoid growth. So, the differential here is Paget’s Disease, either Paget’s
of the nipple or extramammary Paget’s, they look the same. Or Bowen’s or squamous carcinoma
in situ, which is actually the most common thing I see because squams are so common.
And then also melanoma. The site is a big thing. If you were in the vulva or anywhere
in the anogenital area, it’s Paget’s until you prove to me with a good immunostain that
it’s not. In other sun exposed sites, I have seen Paget’s or Paget-like things like
one or two times in the extremity of an old sun damaged arm, really rare, okay? Certainly
not common. Near the nipple, you got to rule out internal malignancy in Paget’s. In the
anogenital area, many of the times there are primary extramammary Paget’s, meaning they
are arising in the skin, but not involving the internal organs. The biggest thing I think
is important is if you have Paget’s around one of the openings, be it right around or
going up to the anal opening or the urinary meatus or the urethral meatus or the vagina,
you’ve got to make sure there is nothing internally. If it is on the scrotum but does
not come near any of the orifices, then the chance that it has spread from an internal
source out is unlikely. But it is important to know. These will usually stain with what?
What kind of markers will usually stain Paget’s Disease? Ya, I like CK7, it’s my favorite.
What else? CK20 will sometimes stain only usually near the anus. That is probably because
embryologically the glands around the anus are derived from that same endoderm, that
posterior cloaca or something like that. It is the same area that gives rise to the rectum.
And so just like rectal mucosa stains with CK20, sometimes extramammary Paget’s can
be CK20 positive but not be from a rectal carcinoma. So, don’t make that mistake of
saying, “Oh, CK20 is positive so it has got to have spread from the inside.” If
there is any doubt, have them scoped. But CK7 is the best, CAM 5.2, low molecular weight
keratin, some people like CEA, all those things, okay? And usually, well that is not a real
good example of eyeliner sign, usually there is a little layer of normal keratinocytes
underneath and the epidermis is getting filled up with pagetoid cells above. Sometimes you
can see little mucin droplets in them so you can do mucin.. or mucin stain to see the mucin.
Sometimes they actually form little glands. Um, sometimes they actually form little glands
and occasionally they can invade out of the epidermis, down into the dermis. And when
there’s a focal invasion, it seems like the behavior long term is probably the same. It’s
probably not like a high risk of getting mets or anything, I’ve seen , We’ve seen that a
handful of times in those patients who are still alive and well 20 years later still
struggling with their disease. Local control is a big problem for umm pagets. They either
radiate or do a huge surgery. It’s not an ideal thing to have in ano-gential area, but
it doesn’t usually kill you. What’s that? It’s Low Power Silhouette? What’s that?
(background) Yeah, that’s a poroma, right? We’ve got a nodule. This one’s even got like
the little, the little, um, the little gutter or what’s the word you guys use? (background)
Yeah, it’s got a collarette and it’s got like a little, like a little channel, a furrow
around the outside, a little grove that it’s dipped down in and the lesion is bulging up.
It’s often ulcerated or inflamed or crusted on the top. Okay. And um, you have this really
marked acanthosis, proliferation of the epidermis of these small little rounds keratinocytes
that are pushing way down and sometimes it’ll be thick like this and those, their actual
finger like extensions that are pushing down from the epidermis into the dermis. And when
you look closer, these cells are, yes, there’ll be ducts. These cells are very round nuclei.
They have a little bit of cytoplasm and they can have some clear cell change.
The, the bits of Stroma in between the bits of papillary dermis there and trap tend to
be edematous. See how white and clear that is. Very edematous and also very sclerotic
or dilated vessels. They’ll have sclerotic collagen or basement membrane material, real
dense pink stuff. And they’ll have edema that dense pink stuff goes along well with many
different, um, sweat gland tumors. And even other adnexal tumors, some right here is basically
like basement membrane material laid down in here, big dilated vessels, edema, inflammation.
Those are common findings. And then finding the ducts can sometimes be hard, but it’s
like in this case, it’s worth looking around. So you look for tiny little holes. The big
spaces end up usually being vessels actually. So don’t say, oh, look at there’s q duct.
That’s actually the vessel because it’s in. It’s surrounded by dermis. See, it’s a little
space and then it’s got to say there too. It’s a vessel, it’s got serum, blood cells,
and then it’s got its own little bit of collagen around it. A duct is not going to have collagen
around it because it’s being formed by the epithelial cells. That’s probably a duct,
the little tiny hole. And sometimes you can see a little pink layer we call cuticle that
lines the inside of that. If you really want to prove that you can do like a cea or an
ema to highlight those little duct spaces. Some people have shown that ck expression
is seen in poromas and porocarcinomas. Um, a lot of times I just diagnosed it on H&E
and again, the differential would be like, is this a funny, seb, inflamed sebs or inverted
follicular Keratosis. Those can look quite a bit like poroma and the differences. There
are all benign things, right? Poromas are cooler and so we like to diagnose those when
we can. I believe poromas are etiologically on a spectrum with hidradenomas. I think they’re
like in the same family because you can see areas that look very much like hidradenomas
in poromas. You can see hidradenomas that connect up to the surface and on the top with
like a poroma and on the bottom with like a hidradenoma. So I believe they kind of all
belonged to the acrospiroma family. And again, dermpaths love to split and resplit and then
argue and fight with each other about who’s splitting is, right. It doesn’t matter if
it’s a benign sweat gland tumor, it’s okay. Just like, just breathe and let it go. It’ll
be fine. Okay. Poroma. here, we’ve got nodule and big cystic spaces. So what’s that make
you think of? Yeah. (background) Hidradenomas tends to have nodules. Cyst spaces. The cells
tend to be either pink and sqaumoid in appearance or clear, clear cell changes common. Hidradenomas
have a wide range of appearance. If you see something that you think is the sweat gland
tumor and you’re not sure what to classify as your best guess should be hidradenoma or
mixed tumor because they have a wide wide range of features and when you’re like, I’m
pretty sure this isn’t a sweat gland tumor, then that’s. Those are the two things you
should go towards because they really can have a wide range. So here’s that dense sclerotic
stuff. This is basement membrane. Here the cells have a little bit more of a squamous
appearance with a pink cytoplasm. Sometimes the pink can be real abundant and then here
you’re getting more of that clear cell change and in the middle you could sit with that
looks kind of infiltrative in the middle of sweat gland and follicular areas, Sometimes
you can get real busy areas that look infiltrative and so if you get a fragment or partial biopsy,
that can be challenging, so looking at low power on full extension, you can see actually
this is quite well even though it’s big, it’s pretty well circumscribed, so that’s reassuring.
Alright, and here’s the cystic area and the cysts are actually ducts. This is actually
the… Whereas you get tiny little ducts in poromas and spiradenomas and cylindromas.
The ducts spaces in hidradenomas tend to get massively dilated and turn into these cysts.
Cysts are there. You’ll often have this double layer of Kinda cuboidal or columnar epithelium
on the outside. Again, it will look at that basement membrane, so collagen type IV. Okay,
so that is a hidradenoma or acrospiroma. If you like that name better and again, I feel
like no one teaches this, but I’d say 10 or 15 percent of cases I see maybe more, probably
a little bit more because we see a referral bias. People send them in consultation when
they connect to the surface, they connect to the surface and hidradenoma also does.
I know people say it doesn’t, but I see a do it on occasion. Maybe I should be calling
those hidradenoma-like SCAP? and then write a paper about it, but I’m not going to do
that to you guys because that’s cruel. No laughs. Okay. Too real to get a couple of
years older, that was funny. Or hidradenoma. Tough crowd. All right. Here we’ve got blue
balls in the dermis. Right? So the answer you already know is big blue nodules down
in the dermis. Spiradenoma. Yeah. Spiradenoma is like blood brothers with what other tumor?
Cylindrinoma. They’re like twinsies. They can. They can occur right next door to each
other and merge into one. They are like the same. The same, two expressions of the same
thing. Okay. And they’re both. Even though the name spiradenoma can sound kind of like
hidradenoma, or acrospiroma. They look totally different. They’re much more blue usually.
Whereas hidradenomas are usually pink or clear, Pale looking. Spiradenoma are very blue because
they have round nuclei and very little cytoplasm. Right, and people like to say that there’s
two cell types and I think it’s true, but I feel like it’s kind of subtle and actually
even though we teach it, I feel like it actually causes maybe a little more confusion for,
for trainees, but since everyone else teaches that I probably better to, the you can kind
of see vague nests in here, see how that’s kind of a nest and then this is one of these
nests or trabeculae that are all packed together and around the outside of the nest you have
these little round dark nuclei and in the inside of the nuclei get a little bigger and
more pale. I think it’s sometimes it’s obvious, most of the time it’s subtle and I feel like
is probably, um, something that you can appreciate after doing this for awhile, but people you’re,
getting ready to take the boards. It’s not nearly as helpful as it blue it’s a spiradenoma
does it look blue and puzzle pieces? It’s a cylindroma. Okay. Does it have cysts and
clear cell change? It’s a hidradenoma and in real life. It’s a benign-oma, and it doesn’t
matter. I’m not trying to be like diagnostically nihilistic. I’m just saying that when they’re
all benign, it’s fun to like talk about like all the things, but in the end don’t lose
sleep over that or concern your clinicians over that with you know saying, well, there’s
really overlapping features here between cylindroma and spiradenoma. I got a video about that
too. This is like my sixth lecture this week, I think, or something. I lost count. Um, all
right. Here we got a nodule down the subcutaneous problem with face, right, big, huge sweat
and sebaceous glands and follicles. And This tumor has a very unusual appearance, right?
It’s got cystic spaces kind of some Nest or Islands here is bluish, weird looking colors
and purple stuff. Um, you’re unusual. Look closer. Those cystic spaces really are true
cysts lined by a layer of epithelial cells, right? If you see a white space in tissue,
it’s got to be one of three things. It’s either got to be an epithelium lined space, which
means it’s a gland or a cyst or it’s got to be a lymphovascular space, meaning it’s
lined by Endothelium, it’s a lymphatic or vessel, or it’s an artifact, whether because
there was lipid there that washed out, the tissue ripped or tore during processing, there
was foreign body and it fell out, so that’s something. Dr Jae Ro, one of my great mentors
that made me decide to go into academics and he’s a general surg path, but he taught so
many great pearls and so he said it’s one of three things if there is clear white space.
It’s one of those three things and so far I’ve found that to be pretty true. So anyway,
here we’ve got spaces line by columnar epithelial cell, so true epithelial differentiation.
So again, you see spaces like that and the dirt. You’ll probably dealing with sweat gland
tumor. Always do keep metastases in mind, especially if you start seeing Atypia. Metastatic
Adenocarcinoma in the skin can mimic sweat gland tumors. What, if you have only one stain
to use to tell apart a primary sweat gland tumor from a metastatic Adenocarcinoma from
one of your internal organs. What would you choose? (inaudible) CK will stain all of them,
CEA will… I don’t even know because I don’t use CEA that much. It will stain many things.
Yes, p63 or p40. P63 which has been published, but also p40 which is an isoform of p63. The
vast majority of primary adnexal tumors, both benign and malignant, will stain strongly
in the nucleus with p63 or p40, just like basal cells and swings do adenocarcinomas
from visceral organs tend to be negative. A small subset of lung adenos can stain with
p63 and even p40 rarely, but it has been reported, but so it’s real helpful. You got strong nuclear
staining for one of those, then that strongly argues against a met from someone’s colon
or stomach or, or anywhere else internally because again, a primary tumor of the skin
even if you think it’s malignant they are going to do an excision with a negative margin,
a met from the lung that’s stage four cancer, huge difference in prognosis. Huge difference
in everything for the patient. Okay? Cystic spaces lined by epithelial cells, nests of
epithelial cells. And then what the heck’s going on here? What’s that? (inaudible) Yeah,
it’s cartilage, right? You can see little chondrocytes in lacunae. There’s actual true
cartilage right there, but the rest of it, and what I tend to see more often is this,
this Chondro-myxoid. It’s kind of Myxoid, mucin cartilage-y mixture. It’s kind of a
mélange of all those things together. Okay. So when you see obvious cartilage or even
bone formation, that’s awesome. But I feel like that’s only in a minority of cases. More
often I see myxoid stroma or myxoid kind of chondroid-Stroma or adipocytes scattered in
the background of a myxoid stroma. And then you tend to see these cells here, these kind
of funny looking polygonal or epithelioid cells that are sitting there in the spaces
out here in the contract, myxoid stuff. Sometimes they get clear, sometimes they get spindled,
sometimes they make little clusters or nests. Like you can see kind of rights. Here’s the.
There’s kind of an ill-defined cluster. It’s not making a gland. So what kind of cells
are these? (Inaudible) Very good. What would they stain with? They do kind of stain with
p63 and they classically in myoepithelial tumors and mixed tumors, which is what this
is, is this is a, um, a mixed tumor or also known as a chondroid syringoma. I don’t like
this. This does not look like syringoma at all. Okay. So that name, should be right out,
but people still use it. Um, it doesn’t look like tadpoles to me, but it’s chondroid only
part of the time. So anyway, mixed tumor/chondroid syringoma, which is basically like the cutaneous
analog of pleomorphic adenoma of the salivary glands, um, is the epithelial-myoepithelial
part tends to differentiate into, to soft tissue stuff like bone and cartilage and mixology
backgrounds. Okay. Um, if you see marked atypia, be careful for malignancy. You can have malignant
myoepithelium is or might feel carcinoma arise out of these. And so if you see a lot of Atypia,
be aware of that. And also do know that myoepithelial cells stain, with s100 strongly and it can
stain with SOX-10. Also, I’ve seen something got misdiagnosed as a melanoma. That was actually
myoepithelioma of soft tissue and they just did S100 and the guy got a sentinel node.
It was long time ago, but it can happen. So keratin and s100 co-expression is seen in
almost always in myoepithelial cells and tumors and the tumors to act in the other. Myoepithelial
markers are less likely to be positive, so if actin is negative. Doesn’t matter. It’s
still. Those are still myoepis. Okay, so just know that myoepithelial tumors is kind of
a hot topic because they can occur in soft tissue. It can be malignant. Chris Fletcher,
Jason Hornick have published a lot about the soft tissue, wasn’t Christina Antonescu And
some of them had Ewing’s gene rearrangements. Actually, if you’re ever in doubt about a
gene rearrangement in anything soft tissue-ey, EWS is the answer. Okay? It’s Promiscuous
it partners with everything is it translocates with all sorts of different genes. Alright,
so there you go. Mixed Tumor. So Here’s a big nodule and inflammation underneath. Let’s
Look at the topFirst. You got keratin cysts, and then we’ve got tadpoles. So we’re back
in that same differential. DTE, microcystic Adnexal Carcinoma, Basal cell or syringoma.
Well, probably too big to be syringoma and also the keratin cyst doesn’t go with that.
Then really look like basal cell anywhere else here. So probably not that. And again,
like I said, that one I feel is like kind of the. They just added him to the list because
they felt bad, like it doesn’t really look as much like the other tumors usually. and
here their cords. You can’t tell if they have ducts or not right?. I don’t know. Is there
a duct in there? Maybe. So as you go down that those are ducts, but guess what? That’s
an eccrine tubule that entrapped.. It’s in you. Usually when you go way down deep, the
tubules will start to open up and show some duct spaces, but it can. You have to hunt
around for awhile and it can be quite challenging to see. And this is why it’s really hard to
diagnose these on superficial biopsy. See, those are like the little duct spaces here.
Probably very hard. Sometimes the immunostains can help highlight it, but here you’re invading
weight onto the fat. No Way doesn’t possibly. This is microcystic adnexal carcinoma. This
one’s almost like too good to be true. Like it’s almost never this robust is usually much
more subtle and much more tricky. Like that desmoplastic trichoepi only it’ll be. That
trickles all the way down to like the nasal septum. It’ll be all the way down in muscle
and around nerves and cartilage. It’s out of control, but usually not this cellular.
Um, so don’t expect them to all look like this. So that’s microcystic adnexal carcinoma.
locally aggressive usually occur on the face, middle aged women oftentimes, and they don’t
usually have a tibia if it looks infiltrated like that. And marked atypical cells. It’s
almost certainly not a microcystic on next was probably an infiltrative screen or maybe
a basal would be my best bet. Okay. Pink thing. Looks kind of busy? Lots of stuff going on.
So the key here is this. So what’s this? Pilar cyst or trichilemmal cyst or follicular cyst
the isthmus catagen type. There can never be one name, never. it how? Oh yeah. So how
do we know that we’ve got what looks like a stratified squamous, right? It looks like
kind of like the Epidermis, like there was no granular layer and it transitions immediately
into dense sheet of pack dense pink orthokeratin. Okay. Unlike the flaky Keratin and the nice
granular layer you get in the follicular infundibular cysts or eics in pilar cyst or trichilemmal
cyst you don’t use that much greater layer and you get the pink stuff in the middle.
Okay, so once you’ve identified that, then let’s look over here and Whoa, what’s going
on? We’ve got all sorts of sqaumoid looking islands. Looks almost like a squamous carcinoma
you. These, it looks kinda like a sqaumous and then find areas that look like pilar cyst.
You’re probably dealing with a what proliferating Pilar tumor proliferating trichilemmal tumor
and even though this looks invasive, usually on a complete excision, you’ll see all this
busy stuff is in the midst of the cystic spaces, not actually invading into the soft tissue,
but again on a fragment and partial biopsy because these clinically look like cysts so
they often get just kind of chunked out and then you, you can’t see the edge. So I do
think it’s probably good to excise these. I believe Ackerman, at least at one point,
thought of these should all be regarded as Carcinomas, but I’ve seen ones that are really
big and in young people and no connection to the epidermis and to me it doesn’t make
sense for them to be squames in the traditional sense. So I think they’re benign and indolent,
but probably good to have them excise the whole thing. Um, in any case though, that
all the busy stuff that was usually in the middle of the cystic areas, but finding those
areas like this with that nice trichilemmal pattern of keratinization is really the key
proliferating trichilemmal tumor proliferating pilar tumor whichever name you Like. Do we
have to? Yes we do. Alright. Look. Nests? So melanocytic, right? I’m writing a basic
dermpath survival guidebook and I foolishly decided to write the melanocyte chapter first
and I about gave up, um, because it’s just so much and so much controversy in Omg. How
can you simplify all that? So the, [laughs] but I did it. I got it done it’s 45 pages
long, so well, it’s like half the book. So anyway, there’s the nests. Okay. The nests
are down the tips. There’s bridging between rete to rete. There’s pink fibrosis wrapping
around the nest and we will call that concentric fibrosis or lamellar fibroplasia because it’s
lamellar. It’s like little layer after layer, like phyllo dough, right. Okay. Maybe it got
more interesting and then lymphocytes and uhh pigment. Oftentimes underneath this is
the body’s way of responding against the melanocytic lesion as it grows. Okay. And I don’t think
there is much. Maybe there’s a little epidermal component. Here’s a little bit of intradermal
melanocytes in the middle and then the junctional stuff goes out to the side. We call that shoulder.
And when you have several rete of junctional stuff that go out to that, if you hold your
arms out, you do this at home, in front of the mirror, if you don’t want to hear, if
the intradermal stuff’s your chest and the shoulders and upper arms are the junk, the
shoulder, okay. Of the lesion. So all of these things I just described are the features of
people say our go for what? Dysplastic nevus or Clark nevus, nevus with architectural disorder
or whatever the heck you want to call these things. Okay? The basic thing is some people
get a bunch of Atypical nevi clinically and they look like this microscopically. And those
people seem to have a higher risk of melanoma. That’s like the dysplastic Nevi Syndrome.
What this means when you have occasional lines in regular people is mmm… hotly debated
and probably not nearly as significant. And um, they’re supposed to have some cytologic
Atypia, which different sources have defined as being various numbers of times the size
of the basal or the mid-spinous keratinocytes. And you can read all that stuff in the literature
and decide for yourself. The most important thing is making sure it’s a dysplastic nevus
and not a melanoma and once you’re sure it’s a nevus and not a melanoma that it’s uneven.
It’s probably okay. And some people bread the Atypia I do because our, our terms like
it, I’m not convinced that it is meaningful or that it’s even reliable, but that’s how
I was trained and that’s how most people around me umm.. practice. And I would rather be pragmatic
in the name of patient care than be semantically pure. But a lot of you argue that these are
not probably true dysplasia in the sense that they’ll evolve into cancer. Most of them probably
will not evolve in the melanoma. I see melanomas grow out of regular nevi more often actually
than dysplastic nevi. So in my experience, but I still do use the term dysplastic nevus.
And I do provide a grade, but you can. I think the advice I give to my fellows is when you
go into practice, don’t be all dogmatic and say, well Dr Gardner said, who cares? Just
find out what your derms like and what your group does and unless it’s totally abhorrent
to you on a moral level, try to adapt to the language that’s spoken by the people taking
care of the patients and if you can speak the language that they speak and get good
patient care across, I would. I think that’s more important than being super meticulously
accurate about what exact name you want for scientific purposes. That’s just my approach.
You can take it or leave it. I don’t mind. I don’t want you to be dogmatic, but anyways,
this is a dysplastic nevus and I think this is a really, to me, this is a real classic
good example of dysplastic nevus. In my chapter I start with sigh… in the dysplastic nevus
section. Seriously, we’ll see if the publisher let me get away with it, but it just sums
up all the ways I feel. All the feels. Okay. What? Oh, that’s it. There’s your 2x diagnosis
on the boards. You’re like done and you move on and real life take a little more time.
But um, but what’s that? [inaudible] Oh, it’s so cellular blue nevus. Exactly. It’s like
a, it’s the Dumbbell, right? The bulging nodule against cellular need, a sales pushing down
into the cutest pigment sometimes there’s abundant, but actually I feel more often.
I see ones that are Hypo pigmented when I see cellular blues. Okay. The thing is is
some books will show a picture like this and they’ll call it deep penetrating nevus and
it’s exactly what I would call a cellular blue. And they’ll like call things cellular
blue that I would call deep penetrating. And I used to say, it’s so easy to tell them apart.
And then we did a study which was recently got published and I realized when we did them
back to back, it actually is a little more hard to tell apart than I thought. So uhh
arrogance is quickly cured um, with experience and um, one way or the other. But to me, I
think this bulging dumbbell shape is really good for cellular blue nevus. And one of the
things I find most helpful is look, before we look at the cellular stuff, go up to the
top and out the sides and the dermis. And almost always cellular blue nevus will have
stuff like this, and if I show you a picture of that, that’s slam dunk regular old blue
nevus. This almost always you can find a conventional blue nevus component at the upper periphery
of the lesion as an interface with the dermis, spindle cells, bland, sclerotic backgrounds,
pigmented melanophages in the background, and a little bit dusty pigment variable amounts
in the spindled melanocytes. Okay? So find blue nevus and then in the middle it gets
cellular and dives down deep and makes a nodule awesome cellular blue. This is one of those
nearby that breaks the rules of maturation. Levi are supposed to be more cellular at the
top and get less cellular and smaller cells as you go down it this does precisely the
opposite of that. Okay? But don’t worry about it. Okay? And as you get down here, they’re
they’re oval or round cells, but they tend to be real uniform in size. You might get
occasional mitosis even down deep. That’s okay. You don’t want to see atypical mits.
You don’t want to see severe pleomorphism. You start seeing real big nucleoli, you gotta
think about clear Cell Sarcoma of soft tissue and a weird melanomas. There are rare melanomas
that mimic blue, so there are some other things. The buttocks of a kid is the best place to
see these, but I see them also in the extremities and other sites too. And umm our clinicians
tend to usually like to excise them because a lot of times they’ll broadly transect it
and they go back and excise it and I don’t think I’ve ever seen a case that was actually
something more nefarious. But uh, the most important thing is whatever name you use,
deep, penetrating, cellular blue, they probably are different molecularly actually these are
actually mutations, GNAQ which goes along with blue nevi…and deep penetrating some
of them at least have, um, have HRAS mutations, which is what you see in spitz and probably
related to Spitz nevi. So at least that’s my general understanding that the most important
thing is weird benign nevus and not melanoma. That’s the important take home, don’t call
it melanoma. Okay. Whatever name you use, doesn’t matter. Just don’t call it melanoma
because it looks so weird and if you’re not familiar with it, you’re going to see that
and see some lights and you’re freak out. Don’t freak out, keep calm, put the case on
your desk can come back tomorrow and if you’re still worried, send it for a consult. Okay?
Just not to me, if it’s something real easy to diagnose, you can send it to me. Otherwise,
send it to Raj. So it will believe this and they strongly stay with HMB-45. So that’s
the other thing is to have you guys heard of that. HMB-45 is supposed to highlight maturation
in nevi, I feel like it works really great and perfect in classic nevi where I don’t
need it at all. And the more atypical and weird and diagnostically challenging it gets,
the less easy it is to interpret of course. Right. Thank you body for making it hard for
us. Um, but the, the, the big epithelioid cells at the top of a nevus are strong HMB
45 positive and the junction component. And as you go deeper in the Dermis, you lose expression
of, of HMB 45, Blue Nevi, break that rule that they tend to be diffuse, strong, HMB,
45 all the way down. And what is the HMB 45, it is human melanoma black. That’s what it
stands for. Try that out at a cocktail party. See what happens. I don’t know where the 45
comes from. Probably some molecular weight or something stupid. Um, but what’s the antigen
that it targets because it’s always good to know both names, the antibody and the antigen
name because you never know which one to boards will ask and you can know everything in the
world, but not knowing the alternate name. You missed the question which is not cool.
Right? I don’t write the questions. What’s the, what’s the what antigen is being stained
by HMB 45? GP 100. It’s a molecule in the melanosome complex. So again, these things
are nearby that make a bunch of pigment. They got a bunch of melanosomes. They stain strongly
with HMB 45. That’s like panorama mode. Look at that. It’s like a picture of Yosemite Valley
that I took that’s pretty cool. All right. Here, we got to think. You don’t. Let me stop
looking at this from a low power. Even before we see anything else isn’t melanocytic lesion.
I’ll just tell you that’s a little pale, but their nest sites here do you think is benign
or malignant? Okay. Does anyone think it’s malignant? I think is really good because
I looked at it last time on high power, but also. Yo, what? What about it? [inaudible]
It’s broad. Yeah. That’s one good clues. He gets that it’s cheating, but I do all the
time. If my derm, that is not like somebody who’s a first year resident, they might go
down to the fat with their shave and it might just be a nothing. Right. But if an experienced
derm gives me a broad shave, I’ll look again if I don’t think it’s. I’m like, why are they
so worried about this? You know? And so yeah, when I see a big excision or a wide shave,
I usually know that they’re freaked out about it. It’s asymmetric. This area looks very
different than this and that is not always proof of melanoma, but it is, you gotta really
worry if you see asymmetry site. That saved me several times where at first glance I didn’t
think about it and I was like, oh, it looks really different over here than there and
I cut deeper and that’s cause there was a melanoma growing out of nevus or something,
so do some deeper. So if you can’t sell here, thankfully we don’t have to do that. We just
got a high power and see the marked atypia the top of the lesion and the bottom leg and
you can’t tell which side is up or down. There’s no maturation there. The melanocytes in the
epidermis are nested here, but with pagetoid cells. Okay, and over here, look to more pagetoid.
Now, how do I know? Let’s see if I can pull this off. Probably not. Every time I try,
there’s only one of the artifacts that I need in any given section. [inaudible] That’s a
fair thing. And the reason that you’re thinking that is because there’s a lot of cytoplasm
in cells. They’re kind of big and epithelioid and they’re making big nest with cliffs around
them. Okay, but I don’t like all that pagetoid and you can have some pagetoid right in the
middle of the Spitz, but especially be nice and circumscribed because you could argue
a circumscribed there. To me, this is too asymmetric. We got a ton of host response
and there’s some almost regression like change lots of inflammation. Again, it’s patchy and
spread out spits should be usually real symmetric, very sharply circumscribed, but it’s. I think
that’s actually a good, uhh, take home. I often will look at them and think, am I sure
it’s not a spitz? Because it’s one of those things that you don’t think about a spitz.
You will go straight to melanoma. That’s what Sophie Spitz called it back in
the 40s. She looked at these things in kids and so these are melanomas of childhood because
until you know, spitzoid is a thing, nothing about that lesion looks benign. There’s cells
like wild and then only later he found, well these these kids do well and actually most
of them seem to be fine and that’s where I think it’s an important point of history to
remember that it looked atypical enough that it was published by a good pathologists as
melanoma of childhood, or something like that, and later proven to be benign with followup.
So I think it’s always good to think is there any way that I can get out of a molecular
diagnosis here? Is there any benign thing because that way you don’t overdiagnose people
with cancer and I definitely think that spitzoid things can look a lot like melanoma.
I’m so that’s actually a really good take home and there’s plenty of times I think about
it and then I’m like, oh, they’re 80 and their sun damaged is probably not. It’s okay, but
it’s good to think about because if you don’t think you’ll just. You’ll just blow right
past that idea and you’ll go straight to melanoma. Okay. Same with Reed nevi by which people
think are probably spitz. You’ll go right to like moderate or severe dysplastic and
you’ll get worried because are big cells and there’s bridging and then once you’re like,
oh, it’s a young woman and it’s a dark spot and It’s circumscribed and you’re like, oh,
I guess it’s a reed nevus isn’t it? So we don’t have a reed nevus today, but you can
go look them up later. All right. So anyway, the one thing I was going to tell you before
I got off on that tangent is vacuolated cells in the epidermis. It can be hard to tell apart
keratinocytes from melanocytes. Right. And I think the one nice trick that I like is
a little hard because this is faded a bit. The cytoplasm of melanocytes sticks to the
nucleus when the cells shrink during tissue processing, the cytoplasm all bulges up to
the nucleus. Maybe a couple of little strands of it’ll touch the neighboring cells, but
there’s. Because there’s no desmosomes to hold it onto its neighbor. Okay. Keratinocytes,
their cytoplasm is full of what kind of filaments? What do they stand for? [inaudible background]
Keratin. Big. Huge rope. Like filaments of intermediate filaments. Keratin. It’s like
reinforced concrete, rebar, right? It’s like all of these huge strands of keratin going
back and forth. It’s not just there to make it easier for us to do immunostains. That’d
be convenient. It’s actually there for a functional purpose and that purpose is it goes across
the cytoplasm and it hooks onto desmosome, the desmosome hooks onto the neighbor cell
death zone, and that has Keratin filaments that go across to the next cell and that crisscross
that times 10,000 and that’s why you’re at, but there was some fall apart when you have
it. Okay. It’s not just because it’s got a basement membrane and hemidesmosomes holding
it down. The whole network has to be strong and the reason that’s important is that when
the cell shrinks that cytoplasm it ain’t going anywhere, it’s stuck to all of its neighbors
and what you get is a naked, sad little nucleus sitting here in a little hole by itself. It’s
a little halo of nothingness around the nucleus and all the cytoplasm stuck to the outside.
It’s a little hard on this because it’s a faded, but I have a basic skin histology video
and right around like seven minutes or nine minutes into the video, I talk about this,
but I think either Jon Reed or Victor Prieto one of my mentors. This is not my idea. I
stole this blatantly from someone else. I just can’t remember which; someone else taught
me, but it’s so useful and so at first I think a lot of trainees or like how do you tell
it’s a melanoctye? Say you see a blob of cytoplasm stuff to nucleus. It’s melanocyte,
usually naked nucleus is Keratinocyte, superficial spreading melanoma. The classic example that
you think of as melanoma, superficial spreading and in reality I still use the subtypes because
our clinicians like it, but it’s pretty historical and doesn’t really pretend much for patient
care. Most of the time. Umm with some exceptions like desmoplastic melanoma and other things.
And so here we got an excision. What’s wrong with that? Can anyone tell me the diagnosis
from here? I’ll give you a hint. It’s a 80 year old on the scalp, your one diagnosis?
Maybe in real life there’s other things, but [inaudible background] I love you for thinking
of that because I’m really interested in angiosarc, but no. Okay. Maybe there’s a couple of possible
diagnoses, but until, the first and second and third thing you have to rule out when
you see this pattern is pink stuff and look, look up here. This is solar elastosis. This
is this guy’s normal dermis at 80. Okay. In Arkansas, half the people have this. They’re
old white folks that been working out on the farm or fishing their whole life and they’re
really sun damaged and their whole dermis is blazed it’s layer after layer of elastosis
like the polar ice caps 100 years ago when they were really thick. Right? And then when
you see the elastosis. Just look, it’s going along. It’s all blue. Blue, blue, blue gone.
Now it’s pink. No, that’s a good thought too. But you’re right to notice the lymphocytes.
When there’s pink collagen replacing elastosis. Something has put new collagen down since
the person got old, since they got damaged. It doesn’t work in young people or non sun
damage people, but in blaze Sun damaged skin. When you see pink fibrosis or placing Dermis,
it’s either scar or it’s regression around a melanoma or it’s a biopsy site or it’s they’ve
picked it and it’s healed. Something did that. And you’ve got to figure out what. And in
this case, yes, this is desmoplastic melanoma. Pink going all the way down through the Dermis,
replacing elastosis, replacing much of the collagen, I mean the fat in the subcutis and
all the way down to the freaking periosteum, the galea aponeurotic. This is classic. This
is what almost every case on the scalp looks like, it goes all the way down to the skull
just like this. And they almost always have lymphocytic aggregates. So when you see scar
like stuff on an old sun damaged scalp and lymphocyte aggregates that’s desmoplastic
melanoma, until you prove it’s not through a SOX-10 or S100 they will stain almost always.
And Mart-1 and HMB45 will never stain in pure desmoplastic melanoma. Some desmos, um, have
mixed areas of cellular spindle component or epithelioid, regular melanoma component,
but when they’re purely desmoplastic, they will not stain with regular melanocytic markers
and what you’ll see as you got the, the background is pink and fibrotic and usually it’s a little
faded out here, but usually they have a little myxoid, Blueish, blueish mucin and collagen
in between the spindle cells and the spindles, those don’t really even stand out, so you’ve
got a high power and see, look at that. The big hyperchromatic scattered guys a little
bit hard to appreciate the cytology here, but you start seeing large cells scattered
about, but many of the cells will be bland, spindled, and definitely kind of areas. It
looks just like scar, just like neurofibroma. Beware of the scar on the old Sun damaged.
beware a neurofibroma with inflammation on an old sun damage head and neck. beware any
spindle thing like that in an old sun damage person, just do S 100 or the SOX so that you
don’t miss a desmo. Okay. It can be real subtle. Only about half the cases had in situ over
top of that, so that complicates matters further. Okay. Um, if you ask a soft tissue pathology
because of referral bias, even fewer cases will have the in situ. You’re okay. But if
you find that that’s helpful, the lymphocytic aggregates are so incredibly helpful. Dr Rapini
said lymphocytes are like smart bombs, they can see like the antigens on the cells that
we can’t see and they go in to attack. So it’s a useful thing and see, look at the hyperchromasia.
So scattered hyperchromatic cells are really helpful if you start looking around, usually
if you have a big enough sample, you’ll find some mitosis. Okay. So scattered Mites, scattered
hyperchromasia, it was usually perineural invasion if you get a big deep sample, but
on a shave you won’t usually see that. But the lymphocytic aggregates are helpful. And
umm, telling apart a neurofibromas kind of scattered Atypia telling a neurofibroma with
atypia apart from a desmo is one of the hardest differentials. There’s different stains. None
of them are, in my opinion, are totally reliable. We’ve occasionally had to tell people to reexcise
we’re not sure if it’s a neurofibroma or desmo, but that’s a huge differential. Totally benign,
totally malignant. These are usually 15 or 20 millimeters deep when you take them out,
but when they’re pure desmo, the behavior is much better on a depth per depth basis
than other melanomas. Local recurrence is a huge problem. I’ve seen them grow through
the skull, into the dura outside the brain. Patients still alive, no mets. That’s totally
a weird different thing than regular melanoma. It’s like it’s gone back to its neural crest
origin, which is why it only expresses sox and S100 neural markers and not melanocytic
differentiation markers like mart-1 and Hmb45 in pure desmos. They don’t clinically look
bad either. They look like scar clinically so they don’t get. The patient doesn’t come
in. I had one that we published a couple of years ago that was a punch biopsy for Alopecia.
Alopecia Protocol. They actually even bisected it horizontally and it was scarring alopecia,
due to desmoplastic melanoma. Clinically a dermatologist thought it looked like alopecia
areata or something. That’s scary, right? This isn’t like someone who doesn’t know what
they’re doing, someone who actually knows that doesn’t, didn’t even look like a tumor
to them, so that’s why it’s problematic. So they’ll think it’s a scar or something. You’ll
think it’s a scar. So it’s a false clinical path correlation. You feel like, oh, it all
fits, but it all fits wrong. Okay. Be Very afraid of Desmo. See, I wrote a lot about
it because I’m real passionate about it. Klaus Busam has published some really great papers
for Memorial Sloan Kettering about desmoplastic melanoma, which to me are essential reading
for dermpath. 2004 American journal of Surg Path is the classic one. All right, here we’ve
got a nub, a nodule, a polyploid nodule on the finger or toe, and it’s acral skin and
it’s dense, dense collagen in the dermis and dilated vessels. Nothing else. Very little
cellularity. So what’s this? Yeah, acquired digital fibrokeratoma, very good. And these
to me look almost identical to Angiofibromas periungal fibromas, which are to me like the
Angiofibromas that we see in tuberous sclerosis. So the biggest thing that helps there, I think,
because I don’t know how to reliably make that diagnosis. If you’d tell me a person’s
got multiple little nodules around their fingernail, that’s probably periungual fibromas. The other
thing is that this sequelae of tuberous sclerosis, the latest thing to develop is the periungual
fibromas. Usually the patient already is known to have tuberous sclerosis by the time they
start developing those. So. But I used to worry about that, oh, what if I missing this?
And then I someone published a paper about that and I thought that was helpful. Acquired
digital fibrokeratoma. And if you start seeing more spindle cells and myxoid stuff, you can
think of other weird acral spindle things like superficial acral (digital) fibromyxoma
just send it to a soft tissue pathologist at that point. If you don’t want to mess with
it, we’re almost done I think, alright, what’s this? I don’t remember what this one is. Hopefully
I will in a minute. Oh, now I do. Any thoughts? One piece. [inaudible] Beautiful. You don’t
go straight to high power for DF on your tests. Look at 2X. Okay. Or whatever they have for
4x for the boards, they don’t have 2x. The epidermis has hyperplasia acanthosis and flattening
blunting of the rete, it’s like an invisible force-field that the DF is throwing up, trying
to go down to it and then hitting that forcefield. Somehow at the edge you’ll see collagen that
gets entrapped. The stain is a little faded on this one, but normally you can see that
big collagen bundles entrapped at the edge. There’s your dermal Collagen and see how the
little bright pink bundles of collagen and are getting wrapped by the cells. Okay, that’s
helpful. Go around also and look for areas of hemorrhage. If you see areas of blood or
hemosiderin deposition, strong point in favor of dermatofibroma. The last thing you should
look at is this cytologic features. Do not go to high power. You’re gonna freak out.
You can get big, ugly scattered cells in dermatofibromas. Totally benign. You can have mitoses in dermatofibroma
totally benign. You can have some fat entrapment at the bottom even. Totally. Okay. It looks
like there’s some fat there, so I get these sent to me when they trap the fat, but that’s
okay. You do have to think about DFSP, okay. Dermatofibrosarcoma protuberans, but most
of the time you can tell DF and DFSP apart on H&E, not with immunostains. I do occasionally
do immunostains to tell it apart, particularly if I have a partial biopsy and I can’t see
the bottom or the sides, so I lose a lot of those clues that I have about the interface
with the Collagen and the fat, okay, but fat entrapment is sometimes seen in DF, particularly
big cellular ones like this. This is cellular DF, giant cells, foamy histiocytes,
Touton cells, hemosiderin blood, all favor, dermatofibroma over DFSP. Epidermal hyperplasia
occasionally it can be seen in the DFSP, usually not, but I’ve seen a few cases that had real
good epidermal hyperplasia and yet were still Dfsp. the other thing is if you see Atypia,
it’s almost certainly NOT dfsp. Very, very rare to have pleomorphism in dfsp because
dfsp is a translocation associated Sarcoma and translocation Sarcomas have monotonous
uniform cells. They all have the same DNA problem. They don’t have pleomorphism. Pleomorphism
is not a feature usually of translocation sarcomas. These do have some tendency to grow
back, not necessarily because they’re aggressive, but because they’re usually superficially
biopsies, so you’re just taking the top of the iceberg and the rest is left down there
and it just keeps growing. Okay. Very, very rare cases have been reported to metastasize.
Do not put that in your report. Okay. Do you, do you tell your patients that get basal cell,
oh, well this could metastasize? No, you don’t do that because it’s one in like 500,000 cases
or less. Right. Same thing here. Dr Weiss, my mentor in soft tissue said, don’t go telling
people, they’re going to freak out and do big excisions and, and the vast majority of
them are, are benign, totally benign. I do tell people that if a lot of it’s left in
there, it could recur and they could decide if they want to either follow it or, or take
it out. I personally think it’s fine to just follow these. Alright, cellular dermatofibroma.
Also, these are known as benign fibrous histiocytoma (cellular fibrous Histiocytoma) is the same
thing and they can even have necrosis. Okay. This is DFSP. It looks so different. Okay.
There’s a little fat trapping in that last one, but this thing is this all used to be
pristine subcutaneous landscape real estate and it’s been just totally overrun by the
DFSP entrapping making that honeycomb pattern of fat entrapment here. Okay. Classic Islands
of stranded adipocytes being squeezed in the middle of the process of the tumor. The tumor
has some fine collagen in the background. Myxoid change is pretty common in these. It
can be extensive sometimes and those are diagnostically challenging. Usually it’s pretty subtle. If
you’re having a bad day this looks like a dermatofibroma, I mean, a neurofibroma.
They’re bland spindle cells. They’re long and thin. It can be a little wavy. They can
have myxoid background, diffuse neurofibromas can have entrapped fat like this. If You’re
having a bad day. You can make a big mistake there. So what do you do? Which thing would
you do to tell apart diffuse neurofibroma from dfsp? Okay, factor 13a, patchy here.
I don’t like factor 13a. I honestly, I just don’t feel like it helps that much. It does
usually stain in scattered dendritic cells in DFs and those tend to be absent and the
DFSP. CD34 is good because it’s strong, difuse staining in the majority of the DFSP, unless
you have a high grade fibrosarcomatous version, but the problem is so do neurofibromas. Seventy
percent of neurofibromas are going to be cd34 positive. So you make a big mistake if you
do 34, do S100 with your 34, that’s going to always be negative in DFSP. See this case
actually did have a little hyperplasia of the epidermis and basal pigmentation, so that’s
a useful clue and on a test I would say you see that, call it dermatofibroma, but in real
life I’ve definitely had a few that I thought, well, it really has a lot of features that
df, but when I looked close, the cells were so bland and so thin and stretched out and
spindly; almost neural looking and that makes me really think that my really think is this
a dermatofibroma not a dfsp. And in those times you can do 34, you can
do FISH for. What’s the translocation? t(17;22). And the genes? [inaudible background]
Yeah, Collagen 1a1. And PDGF Beta, platelet derived growth factor Beta. And that’s a tyrosine
kinase. And like other tyrosine kinase, tyrosine kinase inhibitors sometimes have response
and can be used to treat really large dfsp or those rare cases that metastasize doesn’t
usually cure it, but it can hold it at bay. Okay. And then classically we describe it
as having a storiform pattern. Uh, in real life I feel it doesn’t always help as much,
but storiform is kind of this swirled pattern. This is probably not the best example of it.
It is one of the things you have to see a bunch of times and then you’re like, oh, that
storiform. But I can describe it 100 ways and it won’t make sense until you’ve seen
a few of them back that you’re like, oh, that storiform pattern. But it doesn’t always have
it. Okay. And DF can also be storiform. So I feel like it’s not terribly helpful. The
fat entrapment like that, that honeycomb pattern really helpful in the very bland, thin, stretched
out spindle cells are helpful. DFSP. Don’t often metastasis, but recurrence is a big
problem in these patients get huge surgeries. I work with a DFSP Facebook patient support
group and these, the scars these patients get are enormous. So it’s not a great cancer
to have even though it doesn’t kill people. Usually lots of morbidity. Okay.
I’ve got a video about that on my youtube channel too about working with the Facebook
support groups. If you’re curious about how I do that, you can go watch that. So here’s
a nodule and the sun damage scalp of an old guy or a woman. Let’s not be. Let’s not
be sexist here. Okay. Women can get these too. But um, but what this will be as a Red
Scaly nodule clinically there you’re going to think it’s a sqaum. They’re going to shave
it and transect it across the bottom. And then you go look in high power and it’s going
to be like atypia outta control. Big pleomorphic, ugly cells, huge mitoses tri polar, mitoses.
Figure 8 mitoses. These all the Atypia you could want, right? It’s going to be real ugly.
So what do you do with the real ugly spindled cell tumor filling the dermis in an old sun
damaged person? What’s your differential? AFX. Atypical fibroxanthoma? Everyone’s favorite.
Okay. What else? Spindle cell squamous cell carcinoma? Yeah.
Poorly differentiated squam. That’s spindled. And what else? Melanoma that is spindled.
and occasionally angiosarcoma can be solid and spindled not, usually you’ll see vascular
channels, but I’ve seen a few that looked a lot like an AFX. So I always actually now
include a marketer at melanoma sox, or S100. I include, I’m a p63 or p40 to rule out spindled
squam. I usually I’ll do a keratin too, but you don’t have to do that. Um, and then I
include ERG or CD 31 for vascular. I don’t like 34 as a vascular marker they are negative
in some angiosarcs and it’s also dirty and nonspecific. And then also I usually will
include desmin because I’ve seen rare examples of rhabdomyosarcoma in skin. Quite rare but
quite aggressive. So I’m paranoid the more stuff I see the more paranoid I get, so I’m
going to be a real problem in 10 years, but I’m married to a psychiatrist so that will
help. I think, true story. I really am. Um, and
she’s given me permission to use her as a joke in every talk. So there’s no hipaa violations
here or anything. So anyway, you do all your stains and they’re negative. Okay. I don’t
like any of the other things like cd 10, pro collagen and I just feel like they’re all
so nonspecific. If you want it to turn Brown do vimentin it turns everything brown and
if you want to know my views on vimentin I got a youtube video about that too. And I’ll
tell you a spoiler alert… they’re not positive views. I do not like vimentin. I
don’t think it ever, ever helps. I’ve never seen it change a diagnosis in any case
ever. In, in all of fellowship and practice. So I don’t ever use it where I practice
the first order of business in my lab was to have them cancel using vimentin. So..but
I know some people who do and that’s ok. If you do want something to turn brown that’s
your antibody. Pick vimentin it’ll turn it brown ok. In any case um… I’m getting
old I’ve got to have some curmudgeonly pet peeves. So instead of yelling at kids on my
yard I yell about vimentin on youtube. know we’ve all got our thing. How do you
tell apart AFX from an undifferentiated sarcoma. An entity formerly known as MFH. We don’t
use that term any more. It’s ancient. We call them undifferentiated pleomorphic sarcoma.
They look the same they stain the same they have no specific positive markers. But the
difference is real important because behavior is different. Ok. It’s all about the size
and depth. If it’s a big lesion going down in the sub cutis it is not AFX. It is sarcoma
ok. And the term that people have recently used although it’s confusing is pleomorphic
dermal sarcoma. The weird thing about that is you only call it that once it invades the
subcutis so…I don’t know but I’m not I don’t write these rules I’m just telling
so what I do in my report is I say “pleomorphic spindle cell neoplasm, atypical fibroxanthoma
vs pleomorphic dermal sarcoma” right in the line which I’m sure you’re like “versus”?!
– how can you do that? But that makes them read the comments and so what that what’s
this guy talking about and I say you’ve got to re-excise this and see how deep it
goes. If it’s down in the fat on the head neck or … about 30% of those metastasize.
Behave much more aggressively. AFX, even when they’re ugly as sin, if they’re confined
to the dermis it’s very very rare to get metastasis or aggressive behavior. Either
way you need a wide excision with Mohs with negative margins, but when they go down in
the fat they should be regarded as a fully malignant sarcoma ok? And some people think
that some AFX are actually spindled squams that have dedifferentiated and lost all markers.
We have no real good way to prove that. But I think of them as like pleomorphic sarcomas
that are just arising in the skin. And when they get big and grow down in the dermis we
call them sarcoma. But the I think this is a big problem, I see practicing pathologists
and derm paths make is they’ll say AFX and its braodly transected and I think its important
to let the dermatologists and the treating physicians know, hey this could be a little
bit more um of a problem than your regular old AFX. Which a lot of like old school people
think oh that’s a benign atypical but benign, you know. So it’s important for them to
know you gotta have the whole thing out. And they’re almost always transected just like
this I think we’re down to the last couple of
cases. If you guys have to leave you can. I won’t be offended don’t worry. That’s
something filling the dermis huh? Yeah, malignancy I like that. Malignancy identified. They say
rule out melanoma, I say no melanoma identified sign out. Boy my day would go a lot faster.
But you’re right, and then on low power this… Im just teasing you. And I think you’re
right. To be able to look on low power and say that is bad until I prove its not is an
absolutely essential skill for a derm path. You’ve gotta be able to look at low power
and think I need to be worried here. This is a worrisome thing. Know when to worry.
And then go spend more time at high power on those cases. You don’t have to spend
long on this case cause look at that. Whew you got it! Yeah its Merkel it’s got that
powdery fine salt and pepper whatever that is chromatin see I don’t like any of the
old names cause they just don’t work. Maybe my eyes are wrong but yeah kind of fine powdery
chromatin and the nuclei are all smashed together there’s no cytoplasm and the growth pattern
is really classic here. Its filling up the space between the collagen. The nests are
all squished and leaving some of the collagen. What other tumor in the skin will do that?
Blue atypical cells from low power with reticular dermal collagen kind of left intact and filling
up the space. A few other things can do it but heres one other thing I always think of.
Leukemia cutis grows just like that from low power my first guess on that would be leukemia
cutis. Merkels are bad news, they occur on the sun damaged head and neck of old folks.
If you don’t find lymphovascular invasion in a Merkel biopsy go back and look again.
Cause its almost always there. You may not have it on the biopsy but on the excision
it’ll be there. I had one just the other day that was an excision of an ear, and there
was a bunch of lymphovasc… I went and checked the margin again which at first glance I thought
was negative and in the background it looked like little hair buds but it wasn’t. It
was little lymphovascular invasion foci all over the margin. I mean, before I signed it
out I saw that but its terrifying. Learn from the fear and the mistakes of your attendings.
And then when you’re an attending share those mistakes so that your trainees can learn
too. You know if that saves someone someday from making a mistake everyone wins there.
Ego should never get in the way of patient care. CK20 dot like positivity real helpful,
neurofilament also stain these and I find that to be kind of helpful too. It works pretty
well neurofilament and CK20 dot like staining. Other keratins will stain with dot like pattern
to like pan keratin ok. And you can do neuroendocrine markers and all that stuff but I feel like
If I think it’s Merkel like this and 20s positive done. I sign it out as Merkel cell. Could
I be wrong maybe 1 in like 10000 times? Maybe. There are other CK20 positive neuroendocrine
carcinomas but the idea of one of those showing up as a skin met or a lung. A small cell lung
showing up as a skin met and CK20 positive it is exceptionally rare. We’ve seen only
three cases of metastatic small cell to the skin. One patient had a known stage 4 small
cell. And the other two actually were primary diagnosis, which is kinda shocking cause it’s
pretty rare, but we’ve seen that twice. But they didn’t stain with CK20, and so
that is why once the 20s negative then you expand your panel and include melanoma markers
for small cell melanoma. Include CK7, TTF-1 for lung cancer, you can do neuroendocrine
markers. I don’t usually use neuroendocrine as first line because some basals and other
things will stain with synapto and then what do you do? 20s negative but synapto is positive,
and it’s kinda blue. And then you’re gonna put in your report well it might be a basal
and I can’t exclude Merkel and. Just don’t open that box you’ll regret it. You’ll
ignore me and you’ll do it a couple years in to practice and then you’’ll be like
ahh I shouldn’t have opened that box. Stained yourself into a hole that’s what
happens alright, it’s a nodule in the dermis… it happens you’ll see. Just trust me. Nodule
in the dermis reactive someone’s been scratching it. They’ve got LSC change over top lichen
simplex chronicus. Dermis is filled with what, what is it? BOOM! Nailed it! Yeah. These huge
massive cells, big nuclei, big nucleoli. A bunch of pink cytoplasm, varied amounts of
information. One of the most helpful features I like, is well…you kind…there’s some
areas on here that had it really good. Let me look at this, color here is a little different.
They have two toned cytoplasm most of the time. Where you’ll get like a central zone
of kind of a dark purple cytoplasm near the nucleus. And then as you go out to the side
it gets more light pink. That two toned cytoplasm there, you can see purple, vs kind of the
other cells are a little pink. That’s really helpful I think for reticulohistiocytoma if
they have multiple lesions it its called reticulohistiocytosis and sometimes its associated with gammopathies
and debilitating arthritis. and then also I think that even though these are probably
etiologically different, they awfully look a lot like juvenile xanthogranuloma histologically.
To me they are histologically on a spectrum, and what I use is if it’s a lot more eos
and a lot of foamy touton cells then I tend to call it juvenile xanthogranuloma. If it
doesn’t have the stains and it looks with that touton cytoplasm then I favor reticulohistiocytoma.
If it’s a solitary lesion ether way it benign. That’s ok.
Ok. A nodule in the dermis, kind of ill-defined right? Its pink and it kinda just merges into
the surrounding dermis. Again a little epidermal hyperplasia over top. What kinda cells are
these? …Yes and yes, both true. True and true. They are spindle cells, and because
they are spindle cells that have abundant pink filaments in their cytoplasm, they are
probably smooth muscle cells. Smooth muscle and fibroblasts both can run in fascicles
and they’re both pink. And so that confuses a lot of people. But if you see the pink is
it actually stringy filament in the actual cell itself. That’s the muscle. Um fibroblasts
lay down collagen in between and if you kinda move your finger under the scope or flip your
condenser you can see the wavy collagen fibers in between cells. If that what you’re seeing
you’re probably dealing with a fibroblastic or myofibroblastic process. Or nerve sheath
tumors also lay down collagen whereas smooth muscle you can see a tiny bit of background
dermal collagen that the pink is all in the cell. Ok. And if you stain them, what’s
the best stain for a smooth muscle tumor? What? So ah bless you, yes desmin, you’re
right. No smooth muscle actin, its stains a bunch of stuff. It’ll stain dermatofibroma,
myofibroblastic things but it sounds like it should be the right answer cause it says
smooth muscle. No I’ve seen lots of people misdiagnose things case they’re like its
actin positive so its gotta be a leiomyoma and I was like no it does not. I didn’t
really say that, in my head I said it. Maybe in a little bit more aggressive terms even.
But, but my fellows will never tell. So in any case you looked around and over all the
cells have a pretty uniform nuclei and you can see the nice fascicles and some of them
are cut long ways and some of them are coming out at us as as 90 degree orientation of fascicles
is classic for smooth muscle. And look it infiltrates the dermis. Cause these are erector
pili muscle differentiation. Most of the leiomyomas in the dermis are pilar type leiomyomas. And
just like rector pili they just kind of trickle out of the edges into the skin. If you see
marked atypia or mitotic activity, it could be a leiomyosarcoma. Chris Fletcher has made
papers saying that if it’s in the dermis, even like a really high grade looking leiomyosarcoma
almost never metastasies or does anything bad. So he’s suggesting calling them atypical
epidermal smooth muscle neoplasm. It’s probably not going to catch on as much cause it’s
not quite catchy enough but his points well taken. I actually I still call them leiomyosarcoma
when they’re atypical, but I put a comment that because it’s totally confined to the
dermis the change of aggressive behavior is close to 0. And I cite that publication and
say some people think we shouldn’t even call them sarcoma. Cause if the patient goes
home and googles leiomyosarcoma. So any of you derms in the room make sure you tell your
patients it is not the leiomyosarcoma they will find on the internet which is all about
uterine leiomyosarcoma which is a totally different story. And deep soft tissue leiomyosarcoma
in the subcutis or deeper can metastasize and behave aggressively. Dermal ones do not.
But anyway if you see a lot of times people are like well but there a little atypia, don’t
worry. Cause even if there’s a…, even if it’s a leiomyosarc its still gonna be
ok as long as it’s in the dermis. So I, theres not good criteria published so far
like how many mitosis are ok. I see things all the time that are leiomyoma that have
a couple mitosis. I don’t know. And people text me like my co residents are like hey
how many can you have. I was like I don’t know, no one knows. Like Don’t worry about
it. But they’re like but, but there’s gotta be a rule. And I was like I know but
I don’t know what it is. And I’ve published on this topic. So maybe maybe I should just
make up a rule and publish it right? And then. Just kidding, just kidding alright. Leiomyoma
pilar type. Any in the dermis, I mean in the subcutis what kind of leiomyoma do you get?
They look quite different in the subcutis. They’re angio, and basically every other
place in the body when you get a smooth muscle tumor, unless it’s in a visceral organ,
its smooth muscle or in the dermis, it has to come from vessels right? Cause you’ve
got vessels everywhere and they’re made of smooth muscle, and so vessels are arise
out of, the vessel is what gives rise to the leiomyoma. And they’re usually in the subcutis
and the lower legs. More common in women. Painful. And they’re like a little donut
you know in the middle or a little vessel in the side and then a big smooth nodule like
a marble ok. …smooth muscle, leiomyoma. What’s that one? Beautiful! It’s a little
cup shaped, it pushes down. It’s got acantholysis, dyskeratosis, warty D, part of a nutritious,
I don’t know something… there’s some joke there. Warty D. Alright warty dyskeratoma.
And if you have solitary lesions that are not cup shaped other places on the body sometimes
people call those acantholytic acanthomas, or acantholyic dyskeratotic acanthomas. And
you see those in the genital region. Just have one of those a couple weeks ago actually.
So it’s good to learn all the things that can cause acantholysis and dyskeratosis. .., grovers
disease, warty dyskeratoma, acantholytic acanthoma. You guys can do this. I know it. It’s a
blue nodule. Could think of spiradenoma, blue ball in the dermis right? But someone already
is on it right? Look at all the blood vessels. When you go to high power there are round
blue little cells and very uniform. And they form little layers in rows that are wrapping
around the vessels. See that vessel is wrapped. This vessel is wrapped. So this is a glomus
tumor. Glomus tumors can mimic adnexal tumors though. So do keep that in mind as a differential.
A lot of people don’t think of that. Spiradenoma or even occasionally hidradenoma. I’ve seen
glomus that have pink a pink a um a oncocytic change sor clear cell change that look a lot
like a sweat gland tumor. And its easily solved cause they’re gonna be keratin negative
P63 negative, and positive for what? What do these stain with? What kind of cells are
glomus cells? They’re, they’re basically modified perivascular smooth muscle. What
we call pericytes. So they are a true pericytic tumors. That old school tumor called hemangiopericytoma
is not pericytic which is why we renamed it. And also because we like to rename stuff in
soft tissue pathology. Its job security and we have to get published so. So any way, but
I think the points well taken that hemangiopericytomas are not pericytic. Glomus tumors actually
are and they stain with smooth muscle actin. But they’re negative for desmin, and they’re
negative for all the endothelial markers like CD34 and CD31. And of course negative for
keratins. And if you’ve got a solid nodule with not that many vessels you call glomus
tumor. If there’s lots of vascular spaces that are dilated and it looks more like dilated
spaces with just a little glomus. You can call it a glomangioma also known as a glomulovenous
malformation. And some people get multiple examples of those as a familial thing. They
inherit it and get multiple glomangiomas. One useful clue about glomus on H&E. I think
you can see it on this one. Is if you look at the periphery of the tumor and find a vessel
that’s leading away from the tumor. You’ll see the glomus cells follow along the vessel,
follow along the ves…see they’re still out here. They follow and track along vessels
away from the tumor. Really really useful clue ok? And theres a spindled kind of variant
of glomus that people called myopericytoma at least that what I, my … myopericytoma
it’s like spindly form of glomus. Ok, so if you hear myopericytoma that’s what that
is. Uh, ok. I think I’ve got to give another
lecture this afternoon too. Alright. We’re gonna need some pizza before then. Alright.
We’ve got a nodule on the like acral skin. But its, it’s probably down in the…deeper.
Like you can see it’s like they’ve taken of the top of the skin and then popped out
this nodule. And on acral skin if you see a nodule like this, if you see a nodule of
tumor taken off, not taken off by a surgeon from like the abdomen or something, but taken
off by a derm…a nodule of tumor with nothing around it it’s almost always centered in the
subcutis. Cause if it’s in the dermis, they’re gonna take epidermis and they’ll be attached.
If it’s in the muscle they’re not gonna go down underneath the fascia and pop a little
thing out and not bring muscle with it. You’ll see muscle attached. In the subcutis sometimes
fats attached sometimes the fat strips away. But that’s a useful clue on tests, nodule
of something that you can see looks like a whole thing shelled out, and there’s nothing
attached to it, almost always that’s a subcutaneous nodule. And if you see little ratty strands
of pink dense collagen around it that’s almost always a subcutaneous nodule from the
hand or the foot. Cause the hand surgeons going in and they just try to pluck that out
without damaging anything else. And so things that are on the tendon sheath can push up
into the subcutis on acral surfaces and they’ll just they’ll pluck it out, ok? So here we’ve
got a nodule we’ve got dense collagen in the back ground, real dense pink. And we’ve
got osteoclastic giant cells very good. And we have another area here that has the cell
I want to show let me see if I can find it. These cell you kinda can appreciate…um…let’s
see they’re better on my screen but I don’t know why I can’t see it up here. The actual
cells of the tumor are these. They’re histiocytoid cells and they usually have abundant pink
cytoplasm. And an eccentric nucleus, oh wait, there, this guy. See that? It almost looks
like a plasmacytoid or even rhabdoid cell where it’s got a pink blob of cytoplasm
pushing the nucleus out to the side. This is really characteristic of giant cell tumor
tendon sheath. Don’t go hunting for the giant cells right away. That’s fine in real,
….it is a good way to learn them. But there are examples that don’t have any giant cells
or very few. And if you don’t learn how to diagnose these with all of the other features,
you’ll be in real big trouble when you have a frozen section and there’s no giant cells.
And they tell you well the patient has a history of cancer, they’ve got a nodule that’s
hot on PET. And you see mitosis and rhabdoid cells and you say probably metastatic carcinoma,
you’ll go down the tubes. Cause … they are often mitotically active and they are
hot on PET so they show up sometimes occasionally in weird sites. Like I’ve seen one in the
shoulder other places, in a patient with breast cancer that they were doing PET scans on.
Cause they’re hot, they show up and then they biopsy it. So it’s important to be
careful about that ok. So anyway because they do look kinda epithelioid and they do often
have quite a few mitosis totally benign still. The giant cells are great when you find them
but learn that the rhabdoid or plasmacytoid histocytes the very dense sclerotic collagen
in the background. Usually hemosiderin is present and sometimes it’ll make like a
little ring or a halo. I couldn’t find it in this example, but a little ring or a halo
around the outside of those histiocytoid cells. And you’ll also get little areas that make
like little pools that fall, the cells fall apart and the little histiocytes go, go for
a little swim in these little cystic spaces. And if you’re real lucky you’ll find foamy
xanthomatous histiocytes around the periphery. And that’s a really good clue when you find
those. So spend some time the next time you see a giant cell tumor tendon sheath and,
there’s a foamy cell, and look around and learn those other features, cause that really,
see another one look at that rhabdoid eccentric plasmacytoid nucleus there. Really useful
clues. These are common, and when they don’t have giant cells you can be in big trouble
if you don’t recognize those features. Most of the time you do not get any skin with these.
This surgeon was nice and included that top of the skin cause they’re rarely ever in
the dermis almost always below. Subcutis or tendon sheath ok. I mean they do always attach
to the tendon sheath but that can present as a subcutaneous nodule. So giant cell tumor
tendon sheath. The other name for this is tenosynovial giant cell tumor comma, localized
type. And there’s a diffuse form of this, which is large usually in the knee and sometimes
villous. And that called pigmented villonodular synovitis, which derms you don’t need to
worry about, paths you definitely do. At a high power it looks identical to giant cell
tumor tendon sheath. They are just two endos of the same spectrum. But those are problematic
cause they invade the knee and cause contractures and scaring and even though they’re not
malignant they’re problematic. Ok. Look where we are, we got skeletal muscle.
We’ve got squamous mucosa. So were on the…tongue, good. In the middle it looks like skin because
it’s got reactive change and you’ve got little nests of atypical looking squamous
stuff growing down. So when you’re having a bad day you’ll call that invasive carcinoma
and get a hemiglossectomy specimen. And then you’ll see that there’s granular cells
filling the dermis or the whatever submucosa. And that’s a bad day when that happens.
So you want to avoid that and always if you end up doing any oral path, if you think it’s
a squam on the tongue check in the whatever the equivalent of the dermal papillae are.
I don’t know. But those little spaces in between the rete, and make sure that there’s
not granular cells there because granular cell tumor can induce a really brisk overlying
reactive epidermal hyperplasia. Pseudoepitheliomatous hyperplasias can mimic carcinoma. I feel like
more often I see them not do that in real life, but when they do it’s a problem. And
uh, so just know that and cells have abundant granular cytoplasm round nuclei. And they
tend to kinda make a syncytia. They merge their neighbor it’s hard to see where one
cell ends and another begins. Another early helpful thing is this. The way they grow,
they grow out into like, and they kind of ooze into the spaces between the dermal collagen.
See the collagen bundles are left. And kinda just like that leukemia cutis pattern, although
they’re not anywhere near as atypical. But they just kind of merge in between the spaces.
And they can infiltrate way down even into muscle. They can recur some time but in general
most of the mare benign. There are very rare malignant examples you don’t probably need
to know that for boards purposes. They’re really really rare. And guess what peri-neural,
I won’t say invasion, but involvement. I don’t know if we can see it here, yeah there,
there seethe cells and here’s your nerve. Like 90% of cases have it, do not be afraid.
You see it in congenital nevi because they’re related to the neruoectodermal stuff. We see
that schwannomas, and palisading encapsulated neuromas and granular cell tumors are nerve
sheath tumors. They just have a very funny appearance. So don’t be worried when you
see perineural involvement by granular cell tumors. They are very common and totally benign
finding. Marked atypia, um mitotic activity, big huge nucleoli, then you start to get worried
ok? And scattered random atypia just like for a schwannoma total benign and ok don’t
worry. And what will these stain with? S100, Sox 10, neural markers, they also will stain…what
is the granularity of the cytoplasm? Why are they granular? Yeah lysosomes. And what’s
the marker for lysosomes? You know it you just don’t realize that you know it. Cause
then people don’t teach it this way but they should. CD68. People teach it as a histiocyte
marker but it’s not, it’s a lysosome marker. Histiocytes have lysosomes and they stain,
but it stains a bunch of other stuff. It’s not a specific histiocyte marker. If its negative
for 68 it’s probably not a histiocyte but if its positive doesn’t mean anything it
could be a lot of things and these are loaded with lysosomes so they’re blazing with 68.
I mean usually you don’t need much you can, uh, just uh, s100 is enough to confirm. And
I have one time seen an angiosarcoma that looked essentially identical although it had
a lot of mitosis. From a colleague in brazil that I think … We haven’t written it up
yet but we’re going to. We presented at a meeting that the residents … still thinking,
thinking about the paper. Granular cell tumor. Always a beauty. Alright these are great.
They’re great when you can make the diagnosis. See here’s a problem. You get a biopsy like
this, and you’re like what is this psoriasis? Is it a weird seb, is it and ak, well, not
really any atypia, is it wart? I don’t know its funny squamous something. Sometimes they’ll
be fibrosis and inflammation here and you’ll scratch your head and they want a single lesion
and I’ll think I know it’s a thing, but I don’t know what kind of a thing it is.
Some weird keratinocytic thing but it doesn’t fit into any of the categories. And then you
go to the side and then you find that. What is it? Yeah cornoid lamellae. A stack of parakeratosis
with some little vacuoles underneath and a little divot in the epidermis. So once you
find that then your diagnosis is done. But in real life what happens all the time is
ill, I, if you don’t see the coronoid lamellae on the section you’ll really scratch your
head thinking like there’s got to be a name for this but it doesn’t’ quite add up
to anything. And then if you find a coronoid lamella and if you get a good biopsy you’ll
see a coronoid lamella this side, and you’ll see another one over here. Which this case
is behaving beautifully, there’s a coronoid lamella. It’s like if a an old timey train
like from back to the future 3 was going this way and the smoke was billowing out behind
it. That’s what the coronoid lamella looks like to me, so if you’re into that kind
of thing you can do that. And what my fellow Nathan Lee said, and I’ll make him famous
for this, he said what happens between the coronoid lamellae stays between the coronoid
lamellae. And I think … that you get all this wild weird crazy changes, inflammation,
acanthosis, atrophy. And it’s all between the lamellae. So it will explain a multitude
of things once you find that coronoid lamellae. So porokeratosis. Alright and there are some
weird forms of it you can read about in your spare time.
Boy it seems like more than 50 cases. Did you add some more like in..he’s in the background
like plugging more cases in. I can tell it. I’m just joking alright. I think we’re
were I kept saying we’re almost done but that was like 30 slides ago. Alright we’ve
got a nodule pushing up here, it’s kind of it bulges down but its relatively flat
across the bottom. Doesn’t infiltrate. And then we’ve got these. …Squamous eddies.
These beautiful swirls and whorls of bright pink keratin. And they’re not invading down
into the derms. So I think there’s two different considerations when you see this pattern.
It could just be. Well what’re you…what would you think? Could be a squam, but in
a squam usually what I want to see is that stuff invading out into the dermis. In real
Iife I do struggle on a regular basis. Is it squam or is it one of these other things.
Yeah, irritated seborrheic keratosis will make squamous eddies. and one other thing
in the follicular family will do it too. Which some people think is related to seb….IFK.
So if you see it bulging donward into a hair follicle and has squamous eddies you can call
it inverted follicular keratosis. If you think it looks more like a seb. You can call it
irritated seb. They I think they’re really a lot of overlap there. In real life I do
see on a regular basis some that have glassy kind of atypical stuff. And especially if
its transected ill sometimes include a comment well there’s atypia that I think is reactive
but I can’t see the base lesion if it grows back or you’re worried you can do another
biopsy. That way I’m not obligating the derms to do anything. But I am letting them
know, you know there’s some stuff there I can’t see. When see the whole lesion like
this and I can see its nice smooth bottom, I just sign this out as either and IFK or
irritated seb. Whichever direction you would want to go with it. Again I feel there’s
a close relationship probably between those two.
But the swirling squamous eddies are the the sign that irritating in the seb and there
common feature also in um in um uhh IFK inverted follicular keratosis. Alrighty here we got
a a thing. Its so beautiful. I know isn’t it pretty. Epidermodysplasia verruciformis.
That’s why we call it EDV. Cause who can say that. And you get big nuclei with cleared
out kind of funny chromatin it’s a wierd HPV change. So this is basically a form of
flat wart. And there’s a like a growing list of many many different viral types that
can be seen in EDV. And what you tend to get is some para on type sometimes. You get hypergranulosis
that’s a common feature of verruca of warts. And you get this gray blue abundant cytoplasm.
Its um really vivid when you get on a freshly stained section. But its real expanded cytoplasm
in the keratinocytes it’s a distinct gray blue color. If you go google EDV or go search
on twitter I’ve tweeted about it many times because I like it so much. I have to restrain
myself from taking more pictures because I have like a hundred pictures of it. I don’t
need more. But its really cool. So anyway it’s a form of flat wart. We see it incidentally
all the time. if it’s the only thing they biopsy they call it EDV. And if its in the
back ground of like a nevus or squam its nothing. But some people do have a germ line mutation
that predisposes them to get this. And they get many many flat warts all over that all
look like this. And those patients have a higher risk of squamous cell carcinoma particularly
if there’s sun damage. And we’ve seen a few syndromic familial patients where both
the mom and the daughter had it and already in their 20s they’re getting squames and
stuff. So it’s a, and I think any time you have a flat wart its harder to tell, it they
have more atypia. They have bigger nuclei because the HPV. So especially if they’re
real sun damaged to me it becomes real hard to tell is this just a funny flat wart? Or
is this squam in situ? I feel it’s a lot harder to judge atypia once you have viral
change. And I see squames in sun damaged skin away from the genital sites that have a viral
change like all the time in my practice. Some other people tell me they never see that but
I feel like I see it on a like a weekly basis. So, but this is classic when you’ve got
that gray stuff. Epidermodysplasia verruciformis EDV.
And here we’ve got a crater shaped lesion right? It cups down into the dermis. It’s
got a volcano of keratin in the middle. OK. It invades just a little bit at the edges.
So what do you like to call these things? Yeah this can be considered a keratoacanthoma
particularly if it grew quickly and you can see the whole thing. I was trained to call
these squamous cell carcinoma keratoacathoma type. Other people vehemently disagree with
that and are sure these are benign. Cause many times they regress. The big problem I
have is: A if I can’t see the bottom, And B If I don’t know the whole history. Which
is almost always the case. So I feel in all of my derms that I work with treat these like
squames. But I have heard I think Elston and some other people have talked about where
it was like on the finger and they decided to wait and it regressed on its own instead
of you know amputated part of the finger doing something real aggressive. So I do keep that
in mind and bring up keratoacanthoma as a type when it’s in a sensitive site or something
where they may handle it differently. But most of the time my dermatologists will treat
them like squames ok. They have glassy atypia and they’re crater shaped and they’re
full of keratin. They don’t usually have acantholytic pattern and they don’t really
infiltrate much. … if you see it really infiltrating out I don’t like to call that,
or real marked atypia I don’t like to call those a keratoacanthoma. Other things people
find useful is the presence of little cluster oh I thought I saw some clusters of neutrophils
that get entrapped . And also sometimes elastic fibers from the dermis will get entrapped
up into the peripheral edges of these lesions. So whether you call it a keratoacanthoma or
squamous cell keratoacanthoma type or whatever, that’s what it is.
But the classic examples go away on their own. But I’m not totally sure that I can
always predict which ones will. Alright here you’ve got a little infiltrative thing its
little basaloid islands, tad poles in the dermis right? So what would you do with this?
Good see even on this one which is actually pretty darn morpheaform but there’s still
some island that begin to look more like regular basal. You tend to get more of that myxoid
change in the stroma. Um I feel like these usually are pretty easy to diagnose most of
the time. So this is a real good example of morpheaform um or sclerosing or ….I just
call them all infiltrative pattern basal cell to encompass all the infiltrative pattern.
But morpheaform is another term that’s used by many people. Real thin little cords of
basal cell invading the dermis. When you see these look for perineural invasion. Its often
they I mean its I find it on a regular basis. A couple times a month. I feel like people
it’s not on people’s radar. Um they probably don’t need like radiation or anything but
they do have to usually get wider margins on it when it takes them longer to clear when
they do Mohs. So I usually like to at least comment on it if I find it. Alright.
That’s a big ulcerated nodule, lots of inflammation. Atypical spindle cells. Really atypical. They’re
kind of making fascicles. What do you think? Nodular melanoma is a great that. Spindle
cell melanomas that are nodular often make fascicles. So do leiomyosarcomas that’s
another thought. I definitely had had times where I thought some of them looked like muscle
and it ended up being melanoma. Cause it’ll make fascicles and they’re kinda plump cells.
Spindled squam. AFX. All that stuff right? So this one would stain with keratin and P40
or P63. So this is a spindled squam. They can be essentially impossible to distinguish
unless you have some area that’s more differentiated. I can’t as a sarcoma pathologist. I did
a whole sarcoma fellowship. I cannot tell you what kind of sarcoma that is by that field.
I can’t tell you if it’s a spindled squam or a melanoma or an AFX or a undifferentiated
pleomorphic sarcoma or leiomy… I can’t reliable tell you, you just have to use stains
on things like this. And it really does make a difference in behavior. If that’s a spindled
squam, well its not great but they’re gonna get around, they you know be probably fine.
If that’s a spindled melanoma that patients gonna have a problem. So it’s a big difference.
If you’re not sure be sure. Do stains. A lot rides on that.
What’s that? You guys nailed it! How’d you know? Hypercellular antoni A, hypocellular
antoni B, well circumscribed got a thin capsule or a lot of times thick capsule around the
outside which is expanded perineurium. And then you get these beautiful palisades which
we call Verocay bodies. All the cells are lining up. People say they look like a picket
fence or something like that. But my co-fellow Toby Foster who is from rural north Georgia,
and he had all these really cute little southern wisdom sayings. And he’s like well it looks
like if you had a pile of leaves and you took a broom and swept em in to two piles. That’s…And
I was like Toby! That’s the best example of what a Verocay body is. He is like one
of the smartest dudes I’ve ever known. He sounds like he’s from the rural south cause
he is…but he’s the best example of not judging a book by its cover that guy is wicked
smart. So he also come up with all these really cool clues. So I learned a lot from having
a fellow who’s way smarter than me as my co-fellow. And he had also been in practice
five years in the military so. I was nervous but he’s like the nicest guy ever so I still
tell that story about Toby because I love the pile of leaves and I’ve never heard
anyone else say that. and when you look at the antoni B areas. They can look an awful
lot like neurofibroma. Real loose bland schwann cells that are kinda mixed around. Um and
a scattered pleomorphism and atypia that are totally fine in nerve sheath tumors. Neurofibromas
can have it, schwannomas can have it. That ok. Mitosis are usually infrequent. If you
start seeing a lot of mitosis still could be a schwannoma but you might want to think
a little more about it or get a consult just to be sure. Um I still I’ve definitely seen
plenty that have had that but it makes me still a little nervous if I’m not sure.
Oh and the vascular change there it is. The vessels tend to get this really dense collagen
hyalinization and fibrin around the edges. You often get abundant hemorrhage you often
get hemosiderin. I’ve seen people mistake these for weird vascular tumors. Because they
were so bloody and had dilated vessels and they hadn’t done an S100. If you’ve got…there’s
the hemosiderin right there. If you’ve done five stains or more on a spindle cell tumor
and you haven’t done and S100 or a SOX-10 you better go back and do an S100 ok. In heme
path you don’t have to but in spindle cell land S100 should be like on your first tier.
Or you’re gonna miss a melanoma or something bad …
Ok. A nodule, dermal, hypercellular. Bland spindle cells. Haphazard. Yeah, neurofibroma.
Mast cells will be present too. Usually you can find little nerve twigs. Neurofibroma.
What do you do with this? Can they solve it? Ok. Well what type? Good. This is the worst
possible thing that we’ve done in the derm path literature after dysplastic nevus. This
is the worst. Is we named something that totally unrelated just like something else. I like
to call these nerve sheath myxoma. Ok. That’s the newer name and I think it’s less confusing.
They’re a myxoid proliferation of the nerve sheath and they make multiple nodules that
are hypocellular and myxoid and have bland spindled or stellate cells that are kinda
swirling around in that myxoid background. And they usually have collagen in between
the nodules are separated from each other. Sometimes they go down in the subcutis. Multinodular.
hand is a good site for them. And if you do S100 or SOX-10 they will always be positive,
ok? They are true nerve sheath tumors they’re probably are like weird plexiform myxoid variants
of schwannoma. I’ve seen a few that have nice palisading like verrucae bodies ok? So
this is called a dermal nerve sheath myxoma. In the olden days this was called conventional
or myxoid neurothekeoma. Ok? I know it’s confusing. But then later people found things
that looked kinda like this but had nodules that were cellular histiocytoid cells. and
so they said well these are cellular neurothekeoma. But once we got immunostains we found out
that all of these cellular ones are dead negative for S100 and Sox. They are not neural we don’t
really know what they are but they’re something totally different. I do have video on YouTube
that explains this in detail so you can check that out if you really want that is all the
time I have to explain this and I got tired of typing on Facebook. So I just made a YouTube
video and now I keep that link saved on my phone and I just share it when everyone’s
like what about the dif… and I’m like link. Watch the video there you go. So anyway.
To save you from the boredom it will explain in detail. If its S100 positive, it’s a
nerve sheath myxoma or what used to be called conventional neurothekeoma. S100 negative
is cellular neurothekeoma which despite the name is not at all neural. I don’t blame
you for being angry about this. It’s a deep deep hurt that we caused to the world in the
future by naming all these things so similarly. Ok so that’s a nerve sheath myxoma.
Benign. Oh I remember now I was like what is this. It’s a nodule. Lymphocytic aggregates
with germinal centers. What are these? They’re vessels. They’re vessels in which the endothelial
cells are so big and plump that they’ve squished the lumen. You can barely even see
that there’s a lumen in there anymore. If you do stains, you can see there’s a little
tiny lumen. But the vessels have such epithelioid plump endothelial cells that they’ve packed
the lumens of these little vessels. And in the background there’s a bajillion eos.
And there’s brisk lymphocytic infiltrate with some germinal centers even. So what’s
this? Angiolymphoid Hyperplasia with Eosinophilia also known as epithelioid hemangioma. Because
sometimes they don’t have much inflammation and they have these real epithelioid vessels.
A classic site is the temple. Often arises off of a damaged vessel like the temporal
artery. If you like bang your head and then sometimes you’ll see like a damaged vessel
wall in the middle and its growing out of it. So there’s been debate over whether
it’s a neoplasm or reactive thing. I’m not sure if that’s fully satisfied yet.
In any case good to know about because it’s got really plump endothelial cells. A couple
things that I think that no one told me in training, but in practice I think this and
LYP and bug bite are … on the differential together. Robust bug bites sometimes have
prominent vessels and eos and can have CD 30 positive cells. LYP can have all of those
things and so can ALHE. So I never thought of those things as being on a differential.
But in real life I actually consider those three: Robust bug bite, ALHE, and lymphomatoid
papulosis um together and try to parse it out with clinical info. It can be challenging
and CD 30 positive cells have been described in bug bite and I think also in ALHE reactive
um immunoblasts are 30 positive. So it’s a nice example of ALHE.
Another malignant thing filling the dermis probably. The question again is what kind
of malignant is it? I mean you could go a lot of directions with this huh? Epithelioid
cells round nuclei. I mean is it a carcinoma? Is it a melanoma? What about now? What is
it? Angiosarcoma very good. This is an epitheloid angiosarc actually I think. And they can be
quite cellular and very much mimic carcinomas and melanomas ok? This is a great example
though. These are collagen bundles and the individual collagen is being completely wrapped
and invaded. Every space being a lined by malignant endothelial cells. And what happens
is you get these floating little collagen bundles that are totally wrapped by endothelial
cells. And this is like the form of infiltrating the channels are so … just made one huge
space. Sometimes the epidermis can lift away. You can have the rest of the dermis move away
from sweat ducts and sweat glands because its such abundant infiltration. Um, so this
is what you want to look for, this and infiltrating vascular channels. It can be very challenging
in some cases to see. Usually when you look to the periphery of an angiosarc you can find
these areas. And that’ll help you make the diagnosis. This is part of why I always include
a vascular marker in poorly differentiated um spindle or epithelioid things in the skin.
Particularly in old sun damaged people. These are aggressive a lot of these patients die.
They need rapid treatment and they need to be handled differently than regular sarcomas.
If you get an angiosarcoma patient send them either to Dr. Ravi at MD Anderson or Dr. Van
Tyne at Wash U. Those are two medical oncologist that have extensive experience with angiosarc.
And it’s so different from other sarcomas. I actually put that on my report now. People
can argue or complain if they want but I care more about the patient getting the right care
right away and getting some chance at doing ok. Um and no one’s complained yet so. I’m
in a Facebook group for angiosarc patients too. That’s been a very life changing experience.
Very sobering experience. It’s a bad, bad tumor. But I’ve met some people who’ve
done well and lived a long time and been essentially cured so there’s hope. Right angiosarc.
What’s the gene in radiation induced angiosarcs? Not on the head…Ahhh you guys are savvy.
Good job. I that’s been out long enough that I think it’s hot enough to end up on
the boards at some point. C-MYC amplification in either chronic lymphedema or radiation
induced angiosarcs. Not usually in the radiated…I mean I’m sorry the UV exposed ah old people
with angiosarc which is actually the most common ones that I see. Are on the old, old
people on the head and neck. How about that? What? Yeah metastatic renal cell. Nests of
clear cells in the dermis. Vessels in between. Real pale cytoplasm. Big nucleoli. Always
keep renal cell in your differential for clear cell tumors in the skin. One other thing that
can kind of make nests of clear cells and be in the dermis…What if I told you keratins
negative, and HMB and actin, and desmin are positive. Blue cell nevus, blue cell melanoma
you can think of those. Yeah, yes very rare in the skin but yes. Hyalinizing clear cell
carcinomas. And also um, PEComas could look potentially like this. And PEComas stain with
CD10. I don’t personally love CD 10 very much as a marker because it stains a lot of
things. Its very nonspecific. And it stains PEComas too. So for renal cell the markers
I like is like pan keratin, keratin 7, stains mostly renal cells, um pax 8 is a great stain
for renal cells. And the most important thing, also if you’re thinking about primary clear
cell tumors of adnexal origin. Doing a P63 or P40 will help you cause its, its essentially
always negative in renal. And almost always positive in clear cell. …I’ve seen it
in clear cell hidradenoma that was called metastatic renal cell it was the clearest
clear cell hidradenoma I’ve ever seen. But then they scanned the patient and their kidneys
were negative. So then they send it in for consult and I was like oh yeah, it’s actually
a hidradenoma P63 was positive. And it had focal duct differentiation. So it all worked
out well in the end but that probably was not a great experience for anyone involved
at the time. So, clear cell this is renal cell that met to the skin.
Alright, dermal infiltrative something. How did you get to that so quickly. Very well
done? How’d you know? Fried eggs boy! You have good eyes! There are two types of dermal
infiltrate that tend to fill the papillary derms. Mastocytosis and what? Yeah Langerhans
histiocytosis. And what’s the easy way even without cytology? I know fired eggs, grooves,
coffee beans. But what on low power can tell you the difference between those two? Usually?
Yes, kind of yes. But there’s a reason for that. These cells are totally in the dermis.
They are completely respecting, and Langerhans normally live in the epidermis its their home.
They’re just like hey guys what’s up and they can go right through that basement membrane
somehow and get up in to the epidermis cause that’s where they live. Like in happy Gilmore
like the ball goes to its home. Ok this is really dating this video now, everyone’s
gonna be like what movies is he talking about cause clearly none of you guys have ever seen
it so um wow. Yeah you guys were like three probably. But anyway the the papillary dermis
is filled with cells and no violation of basement membrane. These are mast cells you can see
that they’re fried eggs and at higher power they have blue little granules. And what stains
will stain mast cells? CD117 or CKIT. Leder stain, giemsa stain. Good! All those things.
Toluidine blue which is more or less like a variation of giemsa on some of those things
ok. And um you can do all of those and mast cell tryptase also will stain these ok. So
what if I did a kit and all this stuff is positive but I see scattered kit positive
cells right along the basal layer? So does that mean it’s you know infiltrating the
epidermis? What would that mean? What would positive kit cells be … melanocytes! See
you guys are too good. Yeah melanocytes normally stain with KIT. And guess what metastatic
melanoma will stain with KIT. Including metastatic melanoma to the GI tract. So don’t use kit by itself
for GIST ok? If you’re a general surgical pathologist use S100 plus kit. OR use DOG1
which is much more specific. But someone much better than me once told me they once called
something a malignant GIST and it was metastatic melanoma. …So use that S100 ok? Its important
to know those pitfalls. This is mastocytosis. And then clinical I let them sort out whether
it team effort urticaria pigmentosa. When they’re real cellular like this it usually
means they’re a younger patient it’s probably urticaria pigmentosa. Or a solitary mastocytoma
but the clinical I just say mastocytosis and let
the clinical sort it out ok? And if you have cells involving epidermis think of Langerhans.
At high power Langerhans looks quite different
from mastocytosis. But ahh. We did it!! Thank you all for attending and hopefully that was
helpful. Raj, thank big round for Raj put this whole thing together. …

30 Replies to “Dermpath Board Review: 100 Classic Cases”

  1. See video description above (click "show more") to see a list of all 100 entities discussed. I'll add timestamps soon so you can click the time and go directly to the part of the video discussing that entity. There's also a link to view the WSI digital slides of all 100 cases in case you want a closer look. Raj and I hope you enjoy this dermpath marathon!

  2. Bravo!!! Excellent and gigantic attempt by the duo-Dr. Singh and Dr. Gardner…. Very useful indeed!!!


  3. Thank you very much. But I can't turn on subtitle on youtube. I will try to understand your guide. Thanks a lot again

  4. this is a huge took me 4 days to find the time in tidbits to finally finish the video but it was an awesome ride

  5. Thank you for all your work Drs. Gardner and Singh. This is an invaluable resource for pathology residents.

  6. slightly unrelated to this, but I just started my residency (so super junior resident), and will be starting my first dermatopathology rotation and was wondering what book I should buy/ use as a reference. I've heard variable opinions: Rapini, Elston, Barnhill, McKee…I would love your opinion/suggestions!

  7. Thank you for this video. It is super helpful and practical!! Great for residents and practicing pathologists!

  8. Thank you so much for all your efforts Dr. Rajendra Singh and Dr.Jerad Gardner …This is the most complete study material in skin pathology….this video is a priceless treasure….Sir can we have a similar kind of video for soft tissue? Please accept my regards

  9. Thank you both for the amazing review, can i ask what else would cause a cornoid lamella other than porokeratosis ?

  10. Need closed captions? Download text transcript of entire video here: HUGE thanks to my awesome UAMS medical students who typed the transcript for this ENTIRE 4+ hour video (nearly 50,000 words!) to make closed captions available. Unfortunately, I talk so fast that it seems that YouTube cannot sync the timing of the closed captions with what I'm saying during my portion of the video (sorry!). If you need closed captions and are having trouble with timing of them, just download the document at the link above and search for the entity name to see what I'm saying.

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