GLI1 Coamplification in Well-Differentiated/Dedifferentiated Liposarcomas: Clinicopathologic and Molecular Analysis of 92 Cases - PubMed GLI1(12q13.3) amplification is identified in a subset of mesenchymal neoplasms with a distinct nested round cell/epithelioid phenotype. MDM2 and CDK4 genes are situated along the oncogenic 12q13-15 se...

pubmed.ncbi.nlm.nih.gov/38621503/

This is classic morphology for a GLI1 coamplified differentiated liposarcoma with perineurial-like whorls. So now the MDM2 amplification makes sense. The current tumor is showing essentially classical features of a GLI1 amplified soft tissue sarcoma. So the morphology/molecular explain each other.

Last 2

Well, it turned out he had a tumor in the same laryngeal location a few years ago, diagnosed as a “fibroinflammatory lesion with some features of IgG4 disease”.

A big panel of IHC was negative. For somewhat unclear reasons, MDM2 FISH was ordered and was amplified. Does this make any sense?

It’s also got some bland spindle cell areas.

#PathSky Laryngeal mass, older adult male. Primitive, highly vascular round cell neoplasm for the most part.

Epithelioid angiosarcoma with extensive intravascular growth. Obviously there must be a right sided primary. There’s supposed to be a liver mass.

CD20

CD31

CD34

Just because the ddx includes intravascular lymphoma (at one time known as “intravascular angioendothelioma”), the first pic is CD20. The others of course are CD31 and CD34.

#PathSky 53F with shortness of breath and “ground glass” pulmonary opacity. Not a hard dx, but a spectacular (if very unfortunate) case.

Desmoid Fibromatosis With TP53 Mutation and Striking Nuclear Pleomorphism - PubMed Desmoid fibromatosis is a myofibroblastic neoplasm of intermediate biologic potential, which has a strong predilection for local recurrence but does not metastasize. Arranged in long, sweeping fascicl...

So- desmoid fibromatosis with bizarre cells and p53 mutant pattern- r/o Li-Fraumeni syndrome.

Happy Friday!

pubmed.ncbi.nlm.nih.gov/36908221/

P53

P53

There is a single case report of a desmoid occurring in a Li-Fraumeni patient, with identical morphology. p53 IHC done on this case shows a null/mutated pattern.

Fear not. It’s also got these really bizarre cells, all over the place. Those don’t belong in a desmoid! Not a desmoid? Or is there another explanation?

Beta-catenin

#PathSky Abdominal wall mass, middle aged woman. Women basically only get 3 abdominal wall tumors, so it’s got to be a desmoid, DFSP or endometriosis. Classic desmoid morphology, aberrant nuclear beta-catenin. I can hear the cries of “boring..”

#PathSky Someone shared a chest wall Ewing sarcoma with me today, and I queried them about exactly what they were Askin. I should probably retire today.

I wrote a complaint.

SS18-SSX

SSX c-terminus

Pics would be nice, right?

A Novel SS18-SSX Fusion-specific Antibody for the Diagnosis of Synovial Sarcoma - PubMed Synovial sarcoma (SS), an aggressive soft tissue sarcoma with a predilection for the extremities of young adults, harbors the pathognomonic t(X;18)(p11;q11) translocation, resulting in SS18-SSX rearra...

It’s diffusely positive for SS18-SSX fusion protein and SSX c-terminus antibody. Monophasic synovial sarcoma, with nuclear palisading. Yes, I’ve seen this before. No, not anywhere near this much. pubmed.ncbi.nlm.nih.gov/32141887/

#PathSky Middle aged woman, leg mass. It all looks like this. More nuclear palisading/ Verocay bodies than you’ve seen in your entire career. Nerve sheath? S100/Sox10 negative. LMS? Negative for all the muscle markers. Any other ideas?

Oh, ok. Thx.

?

MDM2

Oops, I forgot the MDM2 photo.

Dedifferentiated Liposarcoma With Epithelioid/Epithelial Features - PubMed Dedifferentiated liposarcoma (DDLPS) demonstrates a variety of growth patterns, and their histologic resemblance to other spindle cell mesenchymal tumors has been widely recognized. However, epithelio...

This is actually a rather spectacular example of dedifferentiated liposarcoma with epithelioid/ epithelial features, a rather rare but reported phenomenon. pubmed.ncbi.nlm.nih.gov/28719466/

Now, it turns out that she has a clinical history of retroperitoneal dedifferentiated liposarcoma, with multiple local recurrences over a decade. Here’s the MDM2 IHC, diffusely and strongly positive. FISH was also done and 100% of cells showed high level gene amplification.

Metastatic carcinoma, obviously. A big clinical work up didn’t identify a primary tumor, and a very broad panel of site-directed markers, including neuroendocrine markers, was negative. So, yet another carcinoma of unknown primary, right?

AE1/AE3

#PathSky Right femur lesion in an older woman. Diffusely keratin-positive with 3 different antibodies.

Took me a while…

So this truly is a superficial MPNST arising in a neurofibroma (an almost always wrong dx!) If you’re wondering, absent EED/SUZ12 mutations explain normal H3K27me3.

Well, although I usually try to emphasize morphology, this is one where the molecular bails us out. It showed very low TMB (unlike melanoma), had two different NF1 mutations, lacked melanoma-associated mutations (other than NF1), and had loss of CDKN2A and B.

SOX10

H3K27me3

SOX10- higher power

PRAME

So we’re done, right? “Spindle cell melanoma- next case”. Oddly, SOX10, however was absent in about 50% of cells, as seen in MPNST. H3K27me3 expression was retained, which doesn’t help. PRAME was negative.