Soft Tissue Tumors of the Head & Neck: What’s New?

November 24, 2021

Information

November 18, 2021

Yale Pathology Grand Rounds

Jason L. Hornick, MD, PhD

ID7207

To CiteDCA Citation Guide

00:04To see you again. So.
00:08There are already 52 participants,
00:12so I'm going to go ahead
00:15and start introducing you.
00:17Uhm? So welcome everyone for
00:22the pathology grand rounds.
00:24Today's speaker is doctor Jason Hornick.
00:28He's a professor of pathology at
00:31Brigham and Women's Hospital in Boston,
00:35or Doctor Hornick grew up in
00:38California and then came up north to
00:43do his college at Amherst College.
00:47He went back to do MD PhD.
00:50In California,
00:51and then he must have missed the
00:54seasons because he came right
00:56back to Boston where he did his
01:00residency and stayed on and his.
01:05He completed his entire residency at Brigham.
01:09He knew exactly what he wanted.
01:11He did,
01:12and AP only residency and a fellowship,
01:16which was three months each in soft tissue.
01:20Him path,
01:21jiwan pathology and general
01:24pathology and this might seem mad.
01:27But all of this exposure shaped
01:30his academic career anyway.
01:32He rounded it off with one.
01:35Year of GI pathology.
01:39I'm not sure how that helped his career.
01:43His doctor Hartnick made his name
01:46as a soft tissue pathologist.
01:49He is an outstanding educator and
01:52a frequent speaker at national and
01:55international meetings and courses.
01:58He is codirector of surgical pathology
02:02update course at Brigham and Women's
02:07and of the diagnostic pathology
02:10update course for the US CAP.
02:13Doctor Hornik is very generous of his time.
02:16He wears many hats,
02:18director of Surg Path,
02:20medical director of Histology and
02:24the immunohistochemistry lab.
02:26His cheer of the QA committee and his
02:30also on several cancer focused committees
02:33at the Brigham and Women's Hospital.
02:38He nationally,
02:39he served on the education and committee.
02:43All of us cap and is currently
02:46on the Board of Directors.
02:48He's been a panelist and moderator on
02:52several of the educational sessions.
02:56His written guidelines, his chair,
02:59dicey committee for CAP,
03:01and he developed the proficiency
03:04testing for thousands of IFC
03:07labs around the country,
03:09our lab being one of those.
03:12He is involved with the agencies
03:16sarcoma staging and the cancer genome.
03:20Atlas is a sarcoma analysis working group.
03:25He also finds time to write board questions
03:28for the American Board of Pathology.
03:32Uhm?
03:32Doctor Hornick has developed and
03:35described many IHC markers that
03:39diagnose genetic abnormalities,
03:41and many of these are actually
03:45have affected our practice,
03:47so these are significant practice changers.
03:51Some of a short list would be I and
03:54I won that detects smart B1 genetic
03:58aberrations start six that detects the
04:03translocation in solitary fibrous tumors.
04:07Back story for sinonasal sarcomas.
04:10Panther Gabino history chemistry,
04:12which we use on head and neck tumors.
04:17This 18 it says X fusion specific
04:21antibody for synovial sarcomas
04:23that he talked about and showed
04:27in this morning's conference,
04:29and many, many, many others.
04:32The list is long,
04:34he's he's the editor in chief
04:37of the fifth series of if IPS,
04:40atlases of tumor, and non tumor pathology.
04:45He is an associate editor.
04:47For Sternberg's diagnostic
04:49surgical pathology,
04:51he is on the editorial board
04:54of a JSP and
04:56modern pathology.
04:58He is he has a senior leadership position
05:02on the editorial boards of histopathology
05:06advances in anatomic pathology,
05:10surgical pathology, clinics,
05:12archives of pathology and lab medicine, and.
05:18Not surprisingly,
05:19he has more than 400 original articles,
05:24reviews and chapters,
05:26and harking back to his first fellowship
05:30were his spent three months in
05:33various subspecialities his not only
05:36on the editorial board of these soft
05:39tissue and bone blue book by WHO,
05:43but also on the blue books.
05:46He's contributed to breast.
05:48Do you want him to rasik
05:51and pediatric Bluebirds?
05:53So in conclusion, Dr.
05:57Hornig still has a lot of time on his hands,
06:01and I'll show what else he does
06:04by sharing my screen here.
06:07Recently this year,
06:09Doctor Hornick with his here on the
06:12keyboard has cut an album for his
06:15band with his band up there teardowns.
06:19And this is available on Spotify.
06:22If anyone cares if anyone is
06:26tired of learning pathology,
06:28we can all go back and listen
06:31to his band instead.
06:32So with that short introduction I will.
06:36See the floor to Doctor Hornick.
06:41Thank you very much Montreux
06:43for that Nice introduction.
06:45Let me make sure this works.
06:48I always have a little bit of trouble.
06:52Can you let me know if you
06:54can see my full screen?
06:55Yep. We can. Is it in the
07:01presentation mode or full screen?
07:03Yes, it's in the presentation mode. No notes.
07:10Oops was that good?
07:12Yeah, that's the full screen mode.
07:14OK, perfect. So as you heard,
07:18I have very diverse interests.
07:20My main area of.
07:21Interest where I do most of my research
07:24is in soft tissue tumor pathology
07:27and Doctor Prasad has invited me
07:30today to give a lecture focusing on
07:32soft tissue tumors of the head neck.
07:34This is a a complicated area obviously
07:37not only for soft tissue tumors,
07:40but this is a an area with lots
07:42of vital structures and a diverse
07:44array of different tumor types
07:46that can arise in these structures.
07:49And I'm going to talk about some really
07:52dramatic changes that have come to
07:55head neck pathology for mesenchymal
07:57neoplasia in the last ten years or so.
08:01I have the following disclosures.
08:04I'm a consultant to Addie Biosciences
08:07and Trey Con Pharmaceuticals,
08:08which is not relevant to
08:10the discussion for today.
08:13I'm going to be framing my
08:15presentation in terms of cases.
08:17I think it's nice to bring them
08:20home to practical applications,
08:22and many of the findings that I'm
08:24going to be discussing are nicely
08:27illustrated by by these cases.
08:29I'm going to start off with a
08:31with a tumor type that we've known
08:33about for a long time, but it's a.
08:35It's a nice framing for the
08:36rest of the discussion,
08:38because this is a tumor that is often
08:40overlooked and is prone to misdiagnosis.
08:43At this anatomic site.
08:44So we're starting off with a 43 year
08:47old man with a left sinus mass.
08:50As is often the case,
08:51these specimens,
08:52these two readings often look kind of messy.
08:55There's a lot of hemorrhage,
08:57and lots of separate fragments of tissue,
08:59and on the low power,
09:00it's kind of hard to see what's going on,
09:02although there are some sailor foci
09:04in the scanning image and let's
09:07focus on a few of these areas.
09:09So now we see those one fragmente
09:11with some blue cells.
09:13Hard to know what's going on.
09:15Higher power another area.
09:17We also have these streams of blue cells,
09:20but certainly to make anything more
09:22of this will have to go closer.
09:25So now you begin to see that there
09:27are these very large, rounded,
09:29slightly angulated cells embedded
09:32in this dense fibrous stroma.
09:35Even a higher power we can see this
09:37as a somewhat nested proliferation,
09:39infiltrating through the submucosal.
09:41We have some normal,
09:44normal glandular structures here.
09:47Higher power,
09:47this is a tumor that has significant
09:51crush artifact.
09:53Just the last few hypower images
09:55and you can see this is a small
09:57round blue cell tumor.
09:58Although the cells aren't so small,
10:00they're actually quite large.
10:01Then we come to really high power and
10:04you can see the primitive chromatin.
10:06Very large nuclei,
10:08very limited cytoplasm.
10:10So I think on morphologic grounds
10:13the differential diagnosis
10:14would certainly be broad.
10:16This is a young,
10:17not quite middle aged adults,
10:19so we have to think of sarcomas,
10:22lymphoma,
10:22Melanoma,
10:23sometimes sinonasal melanomas have
10:26round some morphology or given
10:29the the high nucleocytoplasmic
10:30ratio and the print
10:32of primitive appearance.
10:34We certainly could also
10:36consider endocrine carcinoma,
10:38a very wide panel of screening markers.
10:41Was done in this case and the first
10:43pass only revealed a single finding
10:46and that is very strong intense
10:48standing for Desmond in every cell.
10:52You can see on high power the limited
10:55silo plasm is nicely highlighted by the
10:58Desmond Stainless intermediate filament.
11:00Then additional confirmatory
11:02marker was performed.
11:03Actually, 2 markers MYLDE 1,
11:06which is positive in every nucleus,
11:09as is myogenin in a very strong,
11:12intense fashion.
11:12And I'm sure by now many of you in
11:16surgical pathology have made the diagnosis.
11:18This summarizes the immunity chemistry,
11:21all the markers that were negative,
11:22excluding your endocrine carcinoma,
11:25Melanoma, and lymphoma.
11:27This is alveolar Rhabdomyosarcoma.
11:32I don't expect you to
11:33follow this entire table.
11:35This table was included in a review
11:37article that I I recently wrote for
11:40seminars and diagnostic pathology with a
11:43junior colleague of mine, Michael Kaelin,
11:45who's a bone and soft tissue pathologist
11:47at the University of Maryland,
11:49where we focused on these new emerging
11:52categories of round soul sarcomas.
11:54But we also included this table that really
11:58highlights some of the conventional lineages,
12:00markers keratin Desmond.
12:01Myogenin Myo D1 that we've already mentioned,
12:05as well as some more,
12:07much more recently developed markers that
12:10correlate with molecular genetic alterations,
12:13which in some cases are really
12:16sufficient to make the diagnosis of
12:18some of these round cell sarcoma types.
12:22So let's talk about Rhabdomyosarcoma
12:24in general.
12:25There are four different classes of
12:27tumors that we consider Rhabdomyosarcoma,
12:29as these are all sarcomas that shows
12:33skeletal muscle differentiation.
12:35The classic embryonal and alveolar
12:37Rhabdomyosarcoma is typically
12:39affect children, adolescents,
12:41and young adults,
12:42and they do have particular anatomic
12:45sites where these tumors arise,
12:47and if you're familiar with the
12:49epidemiology of these classes of tumors,
12:52it is often possible to suggest the diagnosis
12:55even before you look down the microscope,
12:57and I always emphasize the
13:00demographics is critical and
13:02understanding some basic epidemiology.
13:05Of sarcomas can really help you
13:08dramatically toward a specific diagnosis.
13:10We're not going to talk about 3
13:13amorphic Rhabdomyosarcoma spindle
13:15cells sclerostin Rhabdomyosarcoma.
13:16We're going to come back to a little bit
13:19later in the session this afternoon.
13:22Another example of alveolar Rhabdomyosarcoma.
13:25This is really one of the classic
13:28round cell sarcomas that has
13:30fairly uniform nuclear morphology.
13:32The nuclear,
13:32often much larger than the nuclei
13:35of Ewing sarcoma,
13:36and if you're lucky you'll find an
13:38occasional reflight giant cell as you
13:40see in the middle of the field here.
13:42That's a very correct characteristic.
13:44Giant cell type of alveolar Rhabdomyosarcoma.
13:49In contrast to embryonal Rhabdomyosarcoma,
13:52alveolar Rhabdomyosarcoma
13:53typically shows very strong,
13:56intense diffuse staining for myogenin.
14:00The skeletal muscle transcription factor.
14:02And Brian or Rhabdomyosarcoma usually shows
14:06much more heterogeneity of the nuclei.
14:08Some small rounded cells,
14:10some short spindle cells,
14:12often embedded within a lucid
14:14demonised for myxoid stroma.
14:16And here you can see the striking
14:18difference in Myogenin immunoreactivity.
14:21And Brian or Rhabdomyosarcoma
14:22will show quite variable.
14:24My agenda and expression.
14:26It's often between maybe 20
14:28and 60 or 70% of nuclei,
14:30but quite different from the strong diffuse
14:33standing we see in alveolar Rhabdomyosarcoma,
14:36and in fact,
14:37in a limited biopsy sample,
14:39the extent of myogenin is very
14:42helpful to support the diagnosis
14:44of alveolar Rhabdomyosarcoma.
14:47These classes of sarcoma
14:49have distinct genetics.
14:50Again,
14:50I'm going to come back to spindle cells
14:53sclerostin Rhabdomyosarcoma little bit later.
14:55The really important thing to remember
14:58is alveolar Rhabdomyosarcoma's Harbor
15:00FOXO 1 gene fusions and this is really
15:03different from Brian or Rhabdomyosarcoma
15:06which does harbor wrasse mutations,
15:08but only in a small subset of cases.
15:12So now let's talk a little bit more
15:15detail about alveolar Rhabdomyosarcoma.
15:17Another good clinical clue to the
15:20diagnosis is the fact that alveolar
15:24Rhabdomyosarcoma often presents with
15:26metastasis to cervical lymph notes,
15:28so the presentation can be quite similar to.
15:33Oropharyngeal or nasopharyngeal
15:35carcinomas that often present with
15:38cervical lymph node metastases.
15:40The same thing goes for
15:43alveolar Rhabdomyosarcoma,
15:43so this is always important to have in
15:46mind in your differential diagnosis when
15:48you're dealing with a primitive round cell,
15:51malignant neoplasm.
15:52Alveolar Rhabdomyosarcoma has the worst
15:55prognosis of all of the Rhabdomyosarcoma
15:58types and in terms of differential
16:00diagnosis and one of the reasons that this.
16:03Class of sarcoma is often misdiagnosed
16:06when it arises in the sinus.
16:08Is is the fact that it's quite
16:11common for these tumors to express
16:15keratins and or synaptophysin,
16:16and there was a very nice
16:18paper published by Andrew.
16:20Folks will come back to in a minute
16:22that indicated the really high rate
16:24of standing for these markers.
16:26This is an example of metastatic alveolar
16:29Rhabdomyosarcoma in the cervical lymph node.
16:32You can see this is a nested tumor.
16:34Where the differential diagnosis would
16:37certainly be with a Melanoma and a
16:40primitive poorly differentiated carcinoma.
16:43Obviously it's easy to confirm the
16:46diagnosis with Desmond or myogenic.
16:48And this is the paper I alluded to.
16:50Andrew fopen.
16:51Colleagues from some different
16:54institutions many years ago
16:56highlighted this potentially serious
16:58diagnostic pitfall of expression of
17:01keratins and your endocrine markers
17:03and alveolar Rhabdomyosarcoma.
17:05And in fact,
17:06I would estimate that maybe once
17:08every three or four years coming to
17:11our head and neck on koleji clinic,
17:13there will be a patient who was
17:15thought to have a poorly differentiated
17:17and render carcinoma.
17:18Of the sinonasal tract that turned out in,
17:21in retrospect,
17:22on RE review to be alveolar Rhabdomyosarcoma.
17:28OK, so that's it for alveolar rabdo.
17:30Now we're going to go to the second case.
17:33This is from a 70 year old man who
17:35had a lesion in the sphenoid sinus
17:38were starting with some sinus lesions.
17:41Another curettage specimen,
17:44not a lot going on here.
17:45Most of these fragments of
17:47tissue look pretty normal,
17:49but I think you'll probably notice there's
17:51just a few fragments that look very cellular.
17:54Here is one of those fragments.
17:56This is a spindle cell neoplasm.
18:00It's a pretty cellular process.
18:03Fascicle sheets of spindle cells
18:05that look fairly uniformly spaced,
18:08even if this intermediate magnification.
18:11And other fragments involved by the tumor.
18:13And now you could appreciate those thin,
18:15walled, dilated and branching blood
18:18vessels which we refer to as staghorn
18:22vessels or hemangiopericytoma like vessels,
18:25alluding to the tumors that we used to call
18:29hemangiopericytoma that now do not exist.
18:32Except for this tumor.
18:33Little higher powerview and again
18:35we see those thin walled dilated.
18:38Somewhat branching blood vessels,
18:40and you can begin to appreciate
18:43better than cytology.
18:44This is a uniform tumor.
18:46Oval to short spindle cells that are fairly
18:50evenly distributed and evenly spaced.
18:52Another nice field of that,
18:53the higher power with those
18:56classic blood vessels.
18:57Some areas are devoid of vessels
18:59and you could see some somewhat
19:02sharply defined cell borders,
19:04and then we come to very high
19:05power and we can see that the
19:08nuclear morphology is uniform.
19:09The chromatin is actually fairly even.
19:11It's not so course there's limited,
19:14if any mitotic activity,
19:16and really not any significant
19:19nuclear atypia.
19:22One more high power view again,
19:24you could see the even spacing
19:26of these uniform nuclei.
19:28So what's our differential
19:30diagnosis for this case?
19:32Given the anatomic sites
19:33and given the prior case,
19:35we could also think about Melanoma carcinoma,
19:38which would obviously be much more
19:40common than the tumors were talking
19:42about in the session this afternoon.
19:44Maybe monophasic synovial sarcoma?
19:46This is a very uniform spindle cell neoplasm.
19:50Although,
19:50as the residents discussed this
19:52morning in the slide seminar,
19:53so noville sarcoma usually has
19:56somewhat overlapping nuclei because
19:58they have such limited cytoplasm.
20:01In this case, the nuclear,
20:03the nuclear, fairly evenly spaced,
20:05which would argue against synovial sarcoma.
20:08And then finally. Possibly a gloom angio.
20:12Perry cytoma, whatever that is.
20:14This is a tumor that's also called
20:17sinonasal hemangiopericytoma.
20:21Smooth muscle actin and some areas.
20:23It's not so impressive,
20:24but on other areas there was
20:26quite strong staining for SMAD.
20:29One other stand I'm going to
20:30show you is beta catenin.
20:32This is normal tissue.
20:33You can see the the upper respiratory
20:35epithelium has beautiful membranous
20:38staining for beta catenin,
20:40whereas in the tumor we have
20:43this incredibly intense nuclear
20:45and cytoplasmic staining was in,
20:47which is an aberrant pattern for
20:50nuclear Vatican for forbidding catenin.
20:52The other markers that were investigated
20:55in this case were negative,
20:57and I'm sure you've already guessed
21:00this is William Angio Perry Cytoma.
21:03This is a tumor that for many
21:05years was called
21:06sinonasal hemangiopericytoma.
21:08This terminology has evolved a bit
21:10over the years, in part because the
21:14hemangiopericytoma term has sort of
21:16been abandoned and most organ systems.
21:17So in the head neck there's trying
21:19to get away from it as well.
21:21This is a lesion that arises most
21:24commonly in the ethmoid sinus.
21:26It's benign, although it can recur
21:28locally in about 1/3 of cases.
21:31Most patients present with a nasal
21:34or sinus polyp fairly small in size,
21:37although occasionally they can be large.
21:39They often have some expression
21:42of actin filaments.
21:43These are thought to be perivascular cells.
21:46The cells that have contractile properties,
21:49which is why they express
21:52the actin filaments.
21:53Are there negative for Desmond Keratins?
21:56But we learned in 2015 by these Nice
22:00papers published by two different groups,
22:03one of them by Florian Haller
22:05and Abasa Gammy, and colleagues,
22:07the other by Jersey Losada,
22:09Mark home yet,
22:10and and a few other colleagues
22:12in and head and neck pathology
22:14that Glow Manju Perry.
22:16Cytoma harbors consistent
22:19activating mutations in C, TNN B1,
22:24the genes that encodes beta catenin.
22:26Which leads to this incredibly
22:29intense nuclear and cytoplasmic
22:31staining for beta catenin,
22:33which has become a very easy
22:35to apply diagnostic marker.
22:37The only problem with beta catenin in
22:40head and neck spindle cell neoplasms is
22:43the fact that it's not entirely specific.
22:46My colleagues,
22:47Vicki Jo and Chris Fletcher,
22:49published this follow up paper and head
22:52neck pathology soon after investigating
22:56immunohistochemistry for beta catenin.
22:57In a range of different
23:00spindle cell neoplasms,
23:01and they confirmed the beautiful staining
23:03we find in Glen Angio Perry Cytoma.
23:06But at least you should be aware that
23:09the majority of solitary fibrous
23:11tumors and synovial sarcomas also
23:13shown aberrant nuclear beta catenin,
23:16but it really doesn't show
23:18that incredibly diffuse,
23:19intense staining that you see
23:20in Gorman Joe Perry cytoma.
23:25Now we go on to case three or
23:27still in the Sinonasal region.
23:29This is from a 36 year old
23:31man with a nasal cavity mass
23:33extending into the ethmoid sinus.
23:37This is a much larger tumor than the
23:40previous samples I've shown you.
23:42This is a really purple looking
23:44tumor from scanning magnification.
23:46Little bit higher power.
23:47You could also you can already
23:49begin to appreciate that this tumor
23:52has a fascicular architecture.
23:54Again, it has that somewhat
23:56purple appearance.
23:57You can see some finwall dilated
23:59blood vessels at the top.
24:01We have entrapment of these these glands.
24:04The glands of the sinus,
24:06which sometimes look a little
24:08bit hyperplastic.
24:09They look very prominent in this
24:12embedded within this tumor.
24:15Higher Power area and we can now
24:17appreciate the nuclear morphology.
24:19Very bland, fairly uniform nuclei,
24:23somewhat overlapping.
24:24Coming back to our previous comment.
24:27Areas are much more purple,
24:30uniformly fascicular we see those
24:33fascicles nicely at high power.
24:36This tumor comes all the way up to
24:39the surface of the sinonasal mucosa.
24:41And then we come again to high power
24:44and you can see the uniform nuclear
24:46morphology and we even can see some
24:48areas with these wiry collagen
24:51bundles between the tumor cells.
24:54So most of what I've described
24:56now would fit very well with
24:59monophasic synovial sarcoma.
25:00But I think given the rarity of
25:02that tumor in this anatomic site,
25:05we have to think of some of the other
25:07tumors we discussed this morning like
25:09malignant peripheral nerve sheath tumor.
25:11Perhaps leiomyosarcoma,
25:12although this tumor is not so eosinophilic,
25:15it's a bit more purple.
25:17And then biphenotypic sinonasal sarcoma.
25:21As I go through each of these examples,
25:24I'm sure even if you don't
25:25know what you're looking at,
25:27you could probably guess the diagnosis by
25:30how I'm framing the differential diagnosis.
25:33Let's look at administer chemistry.
25:35Smooth muscle actin was positive
25:37in this case.
25:38A fairly kind of variable.
25:40Not so impressive.
25:42Overall positive in these areas.
25:44There was some limited staining for Desmond,
25:47and there was also some limited
25:49staining for S100 protein,
25:51but this is the characteristic nuclear
25:54and cytoplasmic staining pattern you
25:56should look for to feel confident that
25:59you're dealing with true staining for S 100.
26:03TLE One was also positive.
26:04We didn't talk about Tilly one this morning.
26:07Tillie one has been developed as
26:09a marker for synovial sarcoma.
26:12It was identified by gene expression
26:14profiling about 15 years ago,
26:16but we now know that T one is
26:18really not so specific.
26:20It's only has kind of moderate specificity,
26:22although the sensitivity for
26:24synovial sarcoma is very high.
26:27So to summarize the immuno.
26:29SM Afocal Desmond S 100 TL E1.
26:33Whereas epithelial markers
26:35and socks 10 were negative.
26:37This is in fact,
26:40Biphenotypic sinonasal sarcoma.
26:42So what is this tumor that goes
26:45by this unusual descriptive name?
26:47Well,
26:47lucky for us,
26:48the name that we now use is a little
26:51bit easier to remember than the
26:54first descriptor of this tumor type.
26:56Lewis and colleagues published this
26:58paper almost ten years ago now where they
27:02first to find this interesting tumor
27:04that they called low grade sinonasal
27:07sarcoma with neural and myogenic features,
27:10which is a perfect description
27:13for this tumor type.
27:15This is a low grade sarcoma that seems
27:18to be unique to the sinonasal tract.
27:21It occurs in adults over a wide age range,
27:24slightly more common in female patients.
27:27It's most common in the nasal
27:30cavity and ethmoid sinus.
27:31Despite the fact that we call this a sarcoma,
27:34it doesn't appear to have metastatic
27:37potential, at least thus far.
27:39No metastatic cases have been
27:41published with molecular confirmation
27:42as I'll come back to in a minute.
27:46There have been several tumor related deaths.
27:49This seems to be a very rare event,
27:52primarily due to intracranial extension.
27:55Given the anatomic site,
27:56so these tumors can be locally aggressive,
27:59they seem to recur in about
28:0230 to 40% of cases.
28:05Sometimes patients experience
28:07multiple local recurrences.
28:10As we saw in our case,
28:11these tumors look strikingly
28:14similar to monophasic.
28:16Synovial sarcoma, including cytologic,
28:20uniformity, fascicular growth.
28:24Often somewhat WAVY nuclei and
28:26indistinct cytoplasm that have delicate
28:29stromal collagen similar to synovial
28:32sarcoma and solitary fibrous tumor.
28:35It's common to see occasional
28:38staghorn vessels confusingly,
28:40these tumors sometimes have rare rhabdom.
28:44I'll blast,
28:45which can be highlighted
28:46by Desmin myogenin Myo D1,
28:48which might lead you to consider the
28:51possibility of a malignant peripheral.
28:54Nerve sheath tumor with
28:56heterologous elements.
28:57But those tumors are almost invariably
28:59hygrade with a very high mitotic rates.
29:02Striking nuclear atypia necrosis
29:05or as biphenotypic sinonasal
29:07sarcoma is remarkably uniform.
29:10Rarely shows necrosis and
29:12has a low mitotic rate.
29:14The defining immunophenotypic
29:16features of this tumor type.
29:19ARCO expression of S 100 and muscle
29:23markers most often smooth muscle
29:25actin and muscle specific actin,
29:27but you can sometimes see Desmond
29:29as well and as I mentioned the small
29:33subset of cases with rabdo myoblasts
29:36have myogenin Myo D1 expression
29:38only in the skeletal muscle cells.
29:41As we saw in our case,
29:42TLE one can be positive which
29:44could lead to confusion with
29:46monophasic synovial sarcoma,
29:48and finally, socks tennis negative.
29:50So these are not true.
29:52Peripheral nerve sheath tumors.
29:54These are not MPNST's.
29:56They do not show true nerve
29:59sheath differentiation.
30:01In fact,
30:01we don't really know what the lineages
30:04of these unusual tumors but coexpression
30:07of S 100 and actin filaments is a
30:10very helpful diagnostic feature.
30:12Andre Oliveira and colleagues published
30:15this beautiful paper in Nature
30:17Genetics in 2014 from the Mayo Clinic,
30:21identifying a recurrent pack 3 mammal
30:243 gene fusion in biphenotypic,
30:28sidell nasal sarcoma and over the next
30:31few years several different groups
30:33of published cases of biphenotypic
30:35sinonasal sarcoma with other packs,
30:383 Fusion partners including FOXO One and two.
30:43But it seems that PAX three is
30:46almost always involved in the
30:48pathogenesis of these tumors.
30:50A couple of nice large series published
30:53since the initial descriptions.
30:55This was a nice paper published
30:58by a diverse group
30:59of colleagues in Virchows archives in 2018.
31:03A fairly large series where you
31:05can see the anatomic distribution,
31:07ethmoid cavity and nasal sinus,
31:09or most common,
31:10as we saw in the initial description.
31:13And in this paper, mammal three was was
31:16still the most common fusion partner by far.
31:19A small subset of cases had
31:22foxo one and NCO A1 fusions.
31:25We haven't identified
31:27all the fusion partners.
31:29A small subset of cases have as of
31:33yet undefined PAX 3 fusion partners.
31:37And then finally,
31:38most recently another large series
31:40by the French sarcoma group with a
31:42few other collaborators from the US.
31:45This was another large series where
31:48packs 3 mammal free fusions were found
31:51in 37 out of 41 molecularly confirmed cases.
31:56They identified another fusion
31:57partner in the form of WW T R1 and
32:01we have those same fusion partners
32:03we saw in the previous case.
32:07And again, my colleague Vicki Jo,
32:09with some other collaborators
32:11in my department,
32:12published a study with us a few years
32:14ago where we we looked at using packs
32:173 administer chemistry as a surrogate
32:20for biphenotypic sinonasal sarcoma.
32:22This worked very well.
32:24We had a uniform staining in all 15 cases.
32:28We investigated many of these cases.
32:30We confirm by fish as you
32:32see in the lower left image,
32:34we have the break apart using.
32:37Pax three directed probes and the
32:39tumors we might consider in the
32:41differential diagnosis are almost
32:43always negative for PAX three.
32:45This is a very easy to apply marker.
32:48We have a very nice nuclear staining in
32:51a characteristic case of biphenotypic
32:54sinonasal sarcoma and one other
32:56example where you see it just
32:58underneath the surface epithelium.
33:02All right, we have a few
33:03more cases to go through.
33:04A few more different topics.
33:06Case four is from a 56 year old
33:10woman who presented with dyspnea,
33:12and she was found to have a large,
33:14soft palate tumor.
33:15So we're now moving away from the
33:18sinus is down into the palace.
33:20This was from the resection.
33:22It was actually kind of a debulking because
33:25this patient was having breathing difficulty.
33:27They recognized his tumor and they did
33:30surgery urgently so that she could.
33:32They could make sure they
33:33could maintain an airway.
33:35We have this very large,
33:37highly cellular purple tumor.
33:39Which had higher power.
33:40We can now begin to appreciate
33:43the Fascicular architecture.
33:45The primitive nuclear
33:47morphology and other areas.
33:49We have a slightly nested or cordlike
33:51architecture with this somewhat
33:54prominent collagenous stroma.
33:56In other areas we have much more
34:00uniformly fascicular architecture.
34:01Primitive nuclear morphology.
34:03This somewhat coarse chromatin.
34:06Higher power in the first
34:07area as I showed you,
34:08we have the nests and cords of
34:11primitive cells within this very dense.
34:14Collagen rich stroma.
34:17In some areas in the stroma,
34:19rich foci.
34:20These nests almost look like they're
34:24forming these cleft like or pseudo
34:27vascular spaces a little bit LV.
34:29Older in.
34:30In cytology this is another classic
34:33appearance to this type of sarcoma.
34:37And finally we look at high power
34:39and we see the primitive chromatin.
34:41Course very limited cytoplasm in these
34:45nests within this collagenous matrix.
34:48So what about differential diagnosis?
34:50If you notice the vascular appearance
34:52or you the pseudo vascular parents,
34:55perhaps you might consider angiosarcoma.
34:58If you thought the funny stroma
34:59looked a bit like bone matrix,
35:02osteoid that hadn't quite calcified.
35:05You might consider extra stone lost,
35:07you Sir coma.
35:08This morning we saw an example of
35:11sclerosing epithelioid fibrosarcoma,
35:13so you might consider that
35:15as a possible diagnosis,
35:17given the very dense expression.
35:21Excuse me at deposition of collagen.
35:25Sclerosing Rhabdomyosarcoma, perhaps?
35:27Synovial sarcoma,
35:29given the uniformity of
35:31the nucleo morphology?
35:34So let's look at a minister
35:35chemistry on this case.
35:36Desman is very strongly positive
35:39and pretty much every cell.
35:41And mild D1 is also strongly
35:43positive even in the scanning image.
35:45You can appreciate that every nucleus
35:48has strong expression of my OG.
35:50One high power.
35:51We confirm that impression from low power.
35:54In contrast, if you look at myogenin,
35:57it's only a very small subset
36:00of nuclei that are positive.
36:03So in summary,
36:04we have skeletal muscle marker expression.
36:06We have negative staining for EMA.
36:09The vascular transcription factor ERG
36:13and the sclerosing epithelioid fibrous
36:15sarcoma marker mark for all negative.
36:18And you've guessed it,
36:21this is sclerostin Rhabdomyosarcoma.
36:24So at the beginning of the session this
36:26afternoon I mentioned I was going to
36:28come back to this topic of spindle cell,
36:30sclerosing revenue mile sarcoma.
36:32This is the most recent addition
36:35to these sarcomas that shows
36:38skeletal muscle differentiation.
36:40Spindle cell sclerostin Rhabdomyosarcoma
36:41is occur most often in the head and neck,
36:45although you can see them in the extremities
36:48and trunk or in parrot testicular locations.
36:51Paratesticular tumors are almost
36:54only seen in infants,
36:57male infants,
36:58and young boys as they'll
37:00come back to in a minute.
37:01These tumors often have my old
37:05one trans activating mutations.
37:07There is a slight female
37:09predominant for that.
37:10Group of tumors.
37:12These tumors,
37:12as we saw in our clinical case,
37:14often present as a rapidly growing mass.
37:18And symptoms are related to local
37:21compression because of their very
37:23characteristic anatomic sites of
37:26presentation in the head neck.
37:28There are another group of spindle
37:32cells thrusting rhabdomyosarcoma's
37:33that do not have mild you.
37:35One mutations that instead have gene
37:38fusions as they'll come back to in a minute.
37:40Those tumors have a very good prognosis.
37:42Those are almost only seen
37:44in very young infants,
37:46sometimes with congenital presentation.
37:49In contrast,
37:50the miod one mutant spindle cell
37:54speros in rhabdomyosarcoma's really
37:56have a dismal prognosis with a
37:58less than 20% five year survival.
38:03At one end of the spectrum,
38:04these tumors look very similar to
38:08leiomyosarcoma's with intersecting
38:10fascicles of elongated spindle cells
38:13with abundant bright pink seidel plasm.
38:16Some cases you'll appreciate us
38:19true skeletal muscle differentiation
38:21at the HD level.
38:23We have these occasional polygonal
38:25or strap like cells that have really
38:28intense somewhat orange or red or cytoplasm.
38:32Other examples have a much more
38:35primitive fibrosarcoma like
38:37appearance with coarse chromatin,
38:39a high mitotic rate and limited
38:42set up plastic differentiation at
38:45the other end of the spectrum.
38:46We have these incredibly densely
38:49hyalinized sclerosing tumors where
38:52we have this osteoid matrix like
38:56deposition of hyalinized collagen.
39:00And other cases kind of sit somewhere
39:02in the middle as we saw in our case,
39:04in our clinical case for this discussion.
39:07I think this this example has
39:09some fascicular architecture,
39:11but you could still appreciate in the
39:14background the dense collagenous stroma.
39:17Desmond is diffusely positive,
39:19similar to many rhabdomyosarcoma's
39:21the best skeletal muscle
39:23transcription factor to used for
39:26this tumor is miod want.
39:27Some cases are entirely
39:29negative for myogenic,
39:31so if you only run myogenin,
39:33you may get confused and think
39:36you're not dealing with this
39:38distinctive form of Rhabdomyosarcoma.
39:41So as I mentioned, these tumors
39:43most often have my O D1 mutations.
39:46There were three proper papers published
39:49the same year by Marc Ladanyi,
39:52Pockrus Hogendoorn and Christina Senescu.
39:55These really nice papers in nature Genetics,
39:58Journal of pathology and genes
40:00chromosomes and cancer identifying this
40:03very common recurrent trans activating
40:05mutation in my O D1 which leads to
40:08very strong expression of the mild D1.
40:11Protein, as I showed you in
40:14the last few slides.
40:15But we've learned over time that these tumors
40:19do not always show my OG one mutations.
40:22Some of these tumors have gene fusions
40:25with a variety of fusion partners and
40:28this nice paper published two years
40:30ago by the Group of Memorial Narse.
40:33Agaram was the first author.
40:35He's one of the bone and soft
40:37tissue pathologists at memorial in
40:39New York with Cristina Antonescu.
40:41And they're suggesting that you really
40:44should think of these as different
40:47risk groups depending on what the
40:51underlying molecular pathogenesis is.
40:53The mild you want mutant tumors,
40:55which are pretty much
40:56all the tumors in adults,
40:58have mild you one mutations.
41:00I have a really poor prognosis,
41:03whereas the tumors that present in
41:06very young infants have various gene
41:09fusions and have a very good prognosis.
41:12If you don't find miodowa mutations,
41:14those tumors also have a fairly
41:17good prognosis.
41:18There are some second hits that have been
41:21identified as you see from this study,
41:23but really the thing to remember
41:25is the my OG one mutations.
41:29All right, we are back to the nasal cavity.
41:31The last case I'm going to discuss
41:34this afternoon is from a young woman
41:36who was found to have a right nasal
41:39cavity mass when she presented to
41:41her primary care physician with
41:43a unremitting nasal congestion.
41:46Another very cellular tumor.
41:49This is the excision specimen,
41:51another tumor with a purple
41:53appearance from low power.
41:54But when you begin to look
41:56at a little bit higher power,
41:57you begin to see that these tumor
42:00cells have abundant eosinophilic
42:02granular cytoplasm.
42:05And in the background you see this
42:07very delicate capillary vascular
42:09network that compartmentalizes the
42:12tumor into these delicate bundles,
42:15or nests higher power.
42:17You can see the central nucleoli quite
42:21uniform appearance to the nuclei,
42:23although there are some very slight
42:26nuclear contour irregularities.
42:28Some of the cells have a little
42:30bit more optically clear cytoplasm,
42:32but most of the cells have this granular.
42:35Eosinophilic appearance and now
42:36in this image these images you
42:39can nicely see that delicate.
42:41Capillary vascular network.
42:43Looking very similar to the vascular
42:47pattern of clear cell renal cell carcinoma.
42:51High power you can nicely see those nucleoli.
42:54Occasional cells are multinucleated
42:56with slightly more nuclear atypia.
43:00Finally,
43:01high power we now begin to
43:03appreciate the mitotic activity.
43:05We found some scattered mitotic figures.
43:07I think it was up to maybe two or three
43:11and 10 high power fields in this case.
43:14So what is our differential diagnosis?
43:16I mentioned metastatic renal cell carcinoma,
43:19but we have to think about the
43:21other tumor types that also present
43:24with a similar nested architecture
43:26and a similar vascular pattern.
43:28So obviously today's session
43:30is on soft tissue tumors,
43:32so it can't be renal cell carcinoma.
43:34This is a this is a good testing strategy.
43:37Alveolar soft part sarcoma perhaps
43:40clear cell sarcoma malignant pecoma.
43:43Maybe we should consider a
43:45these tumors possibly.
43:46So let's look at a minister.
43:49Chemistry TFE 3 is very strongly
43:52and intensely positive,
43:54so that could suggest several of
43:57the possibilities I mentioned.
43:59The only other marker that
44:01was positive was HMB 45.
44:03That marker of melanocytic differentiation
44:05and it was not so impressive,
44:08but it did show that really
44:10distinctive granular subtle plasmic
44:12pattern of staining which we look
44:15for for tumors that have melanosomes.
44:18So to summarize, the immunophenotype.
44:21Muscle markers were negative.
44:23As well as Melanie.
44:25If you're thinking of Melanoma S
44:28100 stocks tender negative,
44:29those are also uniformly positive
44:32and clear cell sarcoma.
44:34And finally,
44:35thinking about renal cell carcinoma
44:37characins were also negative.
44:39This is a malignant pecoma.
44:43So Pecoma is this very mysterious tumor.
44:46That has a very unusual definition.
44:49Tacomas are said to be composed of
44:54perivascular epithelioid cells which
44:57are distinctive epithelioid cells
44:59that are often closely associated
45:01with blood vessel walls and that
45:04often Co Express Millen, acidic,
45:06and smooth muscle markers.
45:09We think of Petco misses being
45:11a family of tumors that include
45:14the much more common and better
45:16known family member,
45:17Angiomyolipoma,
45:18which usually presents in the kidney.
45:21But this morning we talked about tumors
45:23in the liver that are also often
45:27called angiomyolipomas that are in
45:29fact just pecoma's of the of the liver.
45:32We have a rare rare disorder called Lam
45:36Lymphangioleiomyomatosis that mostly
45:37occurs in the lungs and lymph nodes.
45:40And the tumor we're talking about today.
45:43A group of distinctive tumors that have
45:45been called pecoma not otherwise specified,
45:48or simply pecoma All these tumors share
45:52this distinctive magical cell type that we
45:55call the perivascular epithelioid cell,
45:58which has no known normal
46:01cellular counterpart,
46:02so this isn't really a known cell type,
46:05but it's a concept that was invented
46:07by a group from Italy from Verona
46:09more than 20 years ago now,
46:11and this concept has stuck and
46:14we use it to describe pecoma.
46:18The first large series of soft tissue,
46:20Petco Miss,
46:21was published by Andrew Phillip Thomas,
46:23Mensal Sharon Weiss and colleagues and
46:262005 when they first proposed criteria
46:29for malignancy based on the small series.
46:33We now know that Petco massacre at a
46:35very broad range of anatomic sites.
46:37You can see them primarily presenting
46:40is very small skin tumors.
46:42They are relatively common in
46:44the gastrointestinal tract.
46:46I promised the GI pathology faculty earlier
46:48today that I would allude to the GI tract,
46:52even though today I'm talking about
46:54soft tissue tumors of the head neck.
46:56Because I am also a GI pathologist.
46:59So pack owners are much more
47:02common in women than men.
47:04They usually present in adults and unlike
47:09angiomyolipoma and lymphangioleiomyomatosis,
47:12pecoma unspecified the tumors
47:14in the soft tissue.
47:16GI Tracting uterus are rarely associated
47:19with the cancer predisposition syndrome,
47:22TSC, the tubers sclerosis complex.
47:26You can find them in the extremities,
47:28trunk wall and skin,
47:30but those are a small minority
47:31of all pecoma's.
47:32Most of the time you'll find them in
47:36central body cavity or visceral locations.
47:38This is a nice resection that was
47:42performed in our hospital of a
47:44primary pecoma of the pancreas.
47:47This was such a nice gross photograph
47:49that I included in The Who the last
47:51two times the 4th and 5th series.
47:54It looks kind of similar to
47:56the pancreatic parenchyma.
47:57It's very sharply demarcated
47:58from the pancreas,
48:00but this is a pecoma that looks really
48:03similar to the angiomyolipoma of the liver.
48:06They were reviewed in the
48:08slide seminar this morning.
48:10And here you can see a very
48:12interesting accentuation around
48:14the blood vessel in the middle.
48:16We have these blood vessels that
48:18seem to have the tumor cells just
48:22underneath the endothelial lining.
48:25Sometimes these tumors have very striking,
48:28clear cell morphology and a
48:30beautiful nested appearance,
48:32making them almost indistinguishable
48:34from clear cell renal cell carcinoma.
48:37Some of them have trabeculae
48:39are architecture.
48:40This example also arose in the nasal cavity
48:44and then also had a TFE 3 gene fusion.
48:48Other examples look much more
48:51similar to leiomyosarcoma's with
48:54fascicular spindle cell morphology,
48:56but in contrast to true smooth muscle tumors,
48:59which typically show very
49:01dense core cytoplasm.
49:03The cytoplasmic quality of pecoma,
49:05as is almost always this delicate
49:08granular eosinophilic to clear cytoplasm.
49:13There is a distinctive sclerosing variant
49:16of pecoma that has a marked predilection
49:20for the pararenal retroperitoneum.
49:23As you see in these two images on this slide,
49:27we again have that orientation under
49:29the endothelium of the blood vessel,
49:32and these cords of somewhat
49:34clear cells within a very dense
49:37hyalinized collagenous stroma.
49:39As I mentioned, we define these
49:41tumors as showing a mixed Milan,
49:44acidic and myogenic phenotype.
49:46They're nearly always positive for HMB 45.
49:50That's the best marker for pecoma.
49:52Smooth muscle actin is the most
49:54sensitive of the muscle markers.
49:56However,
49:57it's important to be aware of the
50:00fact that in particular the clear cell
50:03examples that harbor TFE 3 fusions
50:06are sometimes entirely negative.
50:09For smooth muscle actin and desmin.
50:13You can find focal S 100 in
50:15a subset of cases,
50:16but it's usually unimpressive
50:19and predominantly cytoplasmic,
50:21which helps distinguish them
50:23in a phenotype from Melanoma.
50:26In addition,
50:26socks 10 that marker we think of as
50:29being very strongly expressed in close
50:31to 100% of melanomas is negative and pecoma.
50:36And in correlating with the presence
50:39of the gene fusions TFE 3 protein
50:42is expressed at high levels in
50:45about 10 to 15% of cases.
50:47And that's a good surrogate by
50:49administer chemistry for the
50:51presence of the gene rearrangement.
50:54This is a,
50:55uh,
50:55some examples of smooth muscle
50:57actin and desmin staining.
50:59This was actually from the case
51:00in the pancreas.
51:01I showed you a few minutes ago
51:03and these were are nice examples
51:06of the variability of staining
51:08for HMB 5:45 and Melanie.
51:10And in fact,
51:12in order to support the diagnosis,
51:14I usually run all four markers
51:17SMAD and Desmond.
51:18HMB 45 MLN A and if you do that,
51:21usually you'll get a hit,
51:22at least with one of the muscle markers,
51:24and one of them will anesthetic markers.
51:27We don't really have very good
51:29criteria for malignancy in pecoma.
51:31As I mentioned Andrew folks first
51:35suggested criteria but we don't
51:36have a lot of cases to go on.
51:38We know that features associated with
51:41malignant behavior include large tumor size,
51:43mitotic activity and atypia pleomorphism.
51:47So in my practice I really use
51:50the combination of essentially
51:51any mitotic activity with atypia
51:54pleomorphism the support the diagnosis.
51:57Of malignancy this is a malignant
51:59pecoma of the colon,
52:01a large fleshy sarcoma like lesion.
52:05These tumors can look very similar
52:08to metastatic Melanoma.
52:09With macro nucleoli striking pleomorphism
52:13and eosinophilic or amphiphilic cytoplasm,
52:16whereas in other cases they have much
52:18more of a clear cell appearance,
52:20looking very similar to metastatic
52:23clear cell renal cell carcinoma,
52:25this is obviously a metastasis to the liver.
52:29We again see those macronuclei,
52:32plia, morphic,
52:33and multinucleated tumor cells.
52:36Pete Argani from Hopkins with
52:38Sharon Weiss first presented
52:40this series of tumors with TFE 3
52:43gene fusions about 10 years ago.
52:46This was the case.
52:47I mentioned that I had just
52:48a couple of years ago from the sinus that
52:51trabeculae are tumor with fairly clear
52:55cytoplasm that had a TFE 3 gene fusion.
52:58A and RC Agram and Christina TSQ published
53:01this beautiful paper six years ago in the
53:04American Journal of Surgical Pathology,
53:06highlighting what we understand about
53:09the molecular genetics of Pecoma TSC.
53:112 mutations are found in the majority of
53:15cases and we also have trends locations in
53:18a range of of pecoma TFE 3 being the most
53:23common gene involved in translocations.
53:28Because of the alterations of TSC 2 in the
53:32majority of Tacomas and visceral locations,
53:34including in tumors that
53:36pursue an aggressive course.
53:38The malignant examples we can use
53:42mtor inhibitors to effectively treat
53:45patients with this tumor type.
53:48These are some sort of case reports
53:50and small series published almost
53:52ten years ago now showing that M
53:54Tor inhibitors such as Sorolla,
53:56Miss or quite effective in treating
53:59patients with malignant pecoma's.
54:01This is an example of a patient treated
54:04in our hospital at the Dana Farber Cancer
54:06Institute by my colleague Andy Wagner,
54:08who's he's really the world expert in
54:11treating patients with malignant pecoma.
54:13He's treated on the order of about
54:1570 patients with this sarcoma type.
54:17Over the last ten years or so,
54:19and you can see this very dramatic
54:22clinical benefit to serralles therapy
54:24with a marked decrease in size of
54:27these multiple metastatic lesions
54:29in the abdominal cavity and pelvis.
54:32Very recently,
54:32this is a paper that was just
54:34published online a few weeks ago.
54:36There is now a modified albumin
54:39conjugated version of sirolimus
54:41that is also really effective in
54:44patients with malignant pecoma,
54:46especially patients that have TSC 2
54:50mutations thus far in this series,
54:52all the patients whose tumors
54:54were confirmed to harbor TSC.
54:562 alterations were are alive either
54:59without disease or with disease.
55:02And you can see from that plot
55:04in the lower left,
55:05the striking clinical benefit in the
55:08majority of patients with malignant pecoma
55:11treated with this seromas conjugate.
55:16So for my final slide of
55:18summary of practice points,
55:20don't forget that head and neck location
55:22is very common for both alveolar
55:25Rhabdomyosarcoma and spindle cells.
55:27Grossing revenue miles sarcomas.
55:29Beware of keratin and
55:32neuroendocrine marker expression,
55:33so you don't go down the tubes and make a
55:37misdiagnosis of alveolar Rhabdomyosarcoma.
55:39I've now shown you lots of examples
55:42of biphenotypic sinonasal sarcoma.
55:44This distinctive pack three
55:46translocation associated low
55:48grade sarcoma that Co expresses.
55:51Muscle markers and neural markers
55:53and finally Pecoma Harbor either TSC,
55:572 deletions, or TFE 3 fusions.
56:02So I'm going to close there and I
56:04want to thank you very much to the
56:06department into Manju Prasad for
56:08inviting me to visit your department today.
56:10I'm sorry that it had to be
56:12converted to a virtual visit,
56:15but I always have to now advertise
56:17for my rock band the teardowns.
56:19As you heard,
56:20we released our first album that's
56:22available on all streaming services
56:24and after a very long delay we're
56:25beginning to play some shows
56:27around town where we're playing in
56:29Summerville coming up next month and
56:31then in Jamaica Plain in Boston.
56:33In January,
56:34I doubt that we're ever going to
56:36travel outside of the Boston area.
56:38Since this is a hobby for all of
56:40us who have different careers,
56:42and honestly,
56:43we're not good enough to make
56:45this our our our full time job.
56:48And I'm happy to answer any questions,
56:50thank you.
56:57That was wonderful, Jason.
57:00I'm sure you're good enough to.
57:03Play for us at one of
57:07our departmental events.
57:08Uhm, there was a comment.
57:11My computer crashed.
57:15All the way through your presentation.
57:18So I lost all the comments in chat and
57:22I know that singing Pan had a comment,
57:25so singing can you unmute yourself and?
57:30And say your comments.
57:35I think it was about alveolar
57:39Rhabdomyosarcoma metastatic to lymph nodes.
57:42Can you hear me yes?
57:44Hi, so thank you for the
57:46wonderful presentation. So
57:47I just want to make a quick comment
57:50so I haven't seen. Like if you cases
57:52of metastatic tremors. Psycho Martin.
57:56If notes showing us purely sinusoidal
57:59pattern with polymer cells.
58:02And the tumor cells
58:04he feels in a positive for CD56 and
58:07AWK. So one case was misdiagnosed
58:10as a hog positive and approximately
58:1470 former by our third pathologists.
58:17So just beware.
58:19Both types of randomized sarcoma
58:22may have expression that thank you.
58:26No thank you. That's that's a great point.
58:28I think alveolar Rhabdomyosarcoma is a
58:30very good mimicker of many different
58:32tumor types because of these very
58:34strange appearances of expression
58:36and alk is quite commonly positive,
58:39and that's a very interesting.
58:41Interesting problem,
58:42thank you and all 56 as well. So yes.
58:47Oh, I always wondered why we had both
58:52my D1 and myogenin so clearly it has.
58:56Prove to be useful both these stains
59:00and why both might should be or might
59:04be ordered and can be useful. Yeah,
59:07I think that's a very good point,
59:08and in fact, before we recognize
59:11spindle cell and sclerostin rabdo,
59:13I don't think we really needed
59:14my OD one and for many years the
59:17antibodies available were pretty bad.
59:19They often showed a lot of
59:21subtle plasmic staining.
59:21The new clones are much better.
59:23They actually worked beautifully and
59:25they're really helpful for this class of.
59:27Of Rhabdomyosarcoma.
59:30Yeah, and I brought my my journey into our
59:34lab and I stopped using my D1 altogether,
59:38but clearly we'll have to look at our clones.
59:43The other thing I wanted to ask
59:45Jason is many of these antibodies.
59:48This newer antibodies that affusion
59:51specific or gene aberration specific.
59:55Do you offer them as test only
59:59like like the other labs?
01:00:01Yeah, unfortunately we don't
01:00:03because we just don't have the
01:00:04staffing to be a reference lab.
01:00:06At this point we can barely keep
01:00:09up with our volume in House.
01:00:10We we have about.
01:00:13650 to 700 a day not counting him path,
01:00:17so it's just it's it's impossible,
01:00:19so we for now we're only doing it
01:00:22as part of diagnostic consults.
01:00:23I think in a couple of years
01:00:26some of you might have heard our
01:00:29institutions are probably going to
01:00:30be forming a central lab for all of
01:00:32the mass General Brigham Hospital.
01:00:34So at that point, maybe will do.
01:00:37Reference lab work,
01:00:37but at this point we can't.
01:00:41Thank you. Any other
01:00:44questions from anyone else?
01:00:46I see that I see Don Pot had a
01:00:48comment that I'm a very good cook.
01:00:50If I want to thank you for that.
01:00:51I I only really started cooking
01:00:53full force after we had started the
01:00:55lock down with the pandemic and
01:00:57now I'm really obsessed with it and
01:00:59I love taking photographs during
01:01:00the process as dog pot as seen.
01:01:02So it's a it's a new hobby and I I love
01:01:06cooking very different ethnic groups.
01:01:08I love like Thai and and and
01:01:11various other types of food.
01:01:13And dump, as other question had to do with.
01:01:16Fusion detection we haven't.
01:01:18We haven't brought on one of the the RNA
01:01:22based NGS fusion panels yet in our lab.
01:01:26We have really only been reserving
01:01:30molecular confirmation for the
01:01:31cases that we struggle with,
01:01:33which because we have so many antibodies
01:01:35that I bring on and I enjoy doing as my
01:01:38kind of translational research effort,
01:01:40we don't do a lot of genetics,
01:01:41but we've mostly been using
01:01:43fish at this point.
01:01:44Really old school conventional fish.
01:01:46On occasion we'll do Archer,
01:01:49one of the fusion panels,
01:01:51but it's at MGH or Children's Hospital.
01:01:54We don't.
01:01:55We don't do it right now in our lab.
01:01:57I think that.
01:01:59Especially for round cell sarcomas,
01:02:01it's really valuable to
01:02:03have that method because.
01:02:05If it isn't Ewing sarcoma, it is very hard.
01:02:10To confirm the diagnosis of the
01:02:14other so-called undifferentiated
01:02:16round soul circles.
01:02:19Thank you.
01:02:20Yeah,
01:02:20in the head and neck area,
01:02:22this sarcoma is extremely baffling
01:02:24because that's not the first
01:02:27thing that comes to our mind.
01:02:30Fortunately for me, I also sign out
01:02:33on the bone and soft tissue service,
01:02:36so sometimes it strikes me
01:02:38it's not a head and neck tumor,
01:02:40but a soft tissue tumor.
01:02:43But they can be very challenging and we
01:02:46are trying to validate the orchard fusion,
01:02:49Plex version three,
01:02:50and we can't wait to get it started.
01:02:58If there are no other questions then.
01:03:02I'd like to thank Doctor Hornick profusely.
01:03:06For his generous time and for these
01:03:10very lucid discussions. Thank you, thank
01:03:14you again thanks everyone. Have a great day.