This presentation, likely from a dermatopathology meeting, focuses on Case Number 12: a deep intramuscular nodule in a 20-year-old male, diagnosed as an Epithelioid Malignant Peripheral Nerve Sheath Tumor (Epithelioid MPNST). The presenter emphasizes the importance of recognizing this tumor due to its challenging differential diagnosis, particularly with metastatic melanoma. Key features highlighted include the tumor's deep location within a central nerve bundle, the presence of ugly, atypical epithelioid cells forming nests and sheets, and the tumor wrapping around or invading the nerve (perineural invasion). Cytologically, it strongly mimics melanoma, staining positive for S100 and SOX10 while being negative for Melan-A and HMB-45. Crucially, the presenter contrasts Epithelioid MPNST with the conventional spindle-form MPNST: the epithelioid variant strongly expresses S100/SOX10 and typically shows loss of INI1/SMARCB1 (present in 75% of cases), whereas the spindle form is usually S100/SOX10 negative/patchy, associated with NF1, and often lacks H3K27me3. The speaker advises dermatopathologists to consider Epithelioid MPNST when encountering a deep lesion that resembles melanoma immunohistochemically but occurs in a young patient around a large nerve.
Case Review: Epithelioid Malignant Peripheral Nerve Sheath Tumor (Epithelioid MPNST)
00:00:08 Introduction and Apology: Speaker begins Case 12, apologizing for exceeding time limits, a recurring issue.
00:00:42 Case Presentation: The case involves a deep intramuscular nodule in a 20-year-old male. The tumor is noted to occur rarely in the skin but can be found in the subcutis.
00:01:00 Deep Nerve Bundle Location: A critical feature is the tumor's location deep within a central nerve bundle, containing large nerves with obvious axons and thick perineurium, distinguishing it from typical superficial dermatopathology findings.
00:01:49 Histopathology: The tumor consists of ugly, atypical epithelioid cells forming nests, cords, and sheets.
00:02:27 Perineural Invasion: The tumor is seen surrounding and expanding outward from the nerve, showing tumor cells "wrapped around by tumor" inside the perineurium, characteristic of nerve origin.
00:03:03 Cytological Mimicry: The cells are highly atypical and can cytologically resemble epithelioid angiosarcoma, epithelial sarcoma, and most notably, metastatic melanoma due to abundant cytoplasm and nest-like structures.
00:04:21 Immunohistochemistry (IHC) Overlap with Melanoma: This tumor is strongly and diffusely positive for S100 and SOX10, but negative for Melan-A (MART-1) and HMB-45, confusing the picture compared to typical melanoma.
00:04:45 Key Diagnostic Clue: The combination of melanoma-like staining (S100/SOX10 positive) in a young patient with a solitary deep lesion wrapped around a large nerve strongly suggests Epithelioid MPNST over metastatic melanoma.
00:05:03 Epithelioid vs. Spindle MPNST: The speaker distinguishes Epithelioid MPNST from the conventional spindle form, considering them distinct entities despite grouping:
Epithelioid MPNST (Case shown): Strong diffuse S100/SOX10 positive; usually lacks H3K27me3 loss; no association with NF1.
Spindle MPNST (Conventional): Usually S100/SOX10 weak/patchy or negative; often associated with NF1; frequently shows H3K27me3 loss.
00:06:34 Sorting Differential Diagnosis: A helpful distinguishing stain for Epithelioid MPNST is testing for INI1/SMARCB1 loss, which is seen in about 75% of cases (also seen in epithelial sarcoma).
00:07:31 Relevance to Dermatopathology: This tumor is presented because it can occur superficially (subcutis) and non-Derm Pathologists often consult Derm Path on S100+ lesions they suspect are melanoma, regardless of location.
00:08:15 Warning on Spindle MPNST: Conventional spindle MPNST rarely occurs in the skin and almost never presents as a strongly S100/SOX10 positive spindle cell lesion in the skin (which should default to spindle cell melanoma).
00:08:39 Conclusion: Speaker concludes the session, apologizing again for the length, and thanking the organizers.