Abstract:

This video features soft tissue pathologist Dr. Jared Gardner and resident Dr. Terence Lin reviewing 10 challenging "unknown" soft tissue pathology cases in an educational format. The session systematically covers rare and complex neoplasms and benign entities, including translocation sarcomas, benign mimics of malignancy, and vascular tumors. Key cases discussed include Alveolar Soft Part Sarcoma and Alveolar Rhabdomyosarcoma (differentiating the "pink" versus "blue" tumors), the characteristic features and molecular profiles of pleomorphic lipoma (RB1 loss) and perineurioma, and the subtle morphology of Epithelioid Hemangioendothelioma (EHE) and Chondroid Lipoma. The presentation concludes with a dramatic example of Malignant Triton Tumor (MPNST with rhabdomyosarcomatous differentiation). Dr. Gardner emphasizes key low-power patterns, specific cellular features (like "floret cells" and "blister cells"), appropriate immunohistochemical panels, and recent molecular updates pertinent to each diagnosis.

Soft Tissue Pathology Unknown Cases (Educational Review)

• 0:28 | Case 1: Alveolar Soft Part Sarcoma (ASPS)
  • Details: 15yo female, anterior thigh mass. Features include thick fibrous septa, an alveolar/pseudo-alveolar pattern, and prominent large, pink/plasmacytoid cells with primary nucleoli, often exhibiting "Pacman" or "bitten apple" notched nuclei.
  • Molecular/IHC: Translocation X;17 involving the TFE3 gene (nuclear TFE3 positivity is a marker).
  • Key Takeaway: A distinct neoplasm, cytologically different from alveolar rhabdomyosarcoma, with a main differential being metastatic renal cell carcinoma.
• 7:37 | Case 2: Alveolar Rhabdomyosarcoma (ARMS)
  • Details: 15yo female, deep soft tissue mass. A round blue cell tumor with prominent fibrovascular septa separating discohesive nests of cells. Key features include multi-nucleated "wreath cells."
  • Molecular/IHC: Translocation 1;13 or 2;13, involving PAX3 or PAX7 and FOXO1. Shows strong, diffuse nuclear positivity for Myogenin/MyoD1 and Desmin.
  • Key Takeaway: Must be distinguished from ASPS (a "big pink cell" tumor). ARMS tends to be more aggressive than Embryonal Rhabdomyosarcoma.
• 13:31 | Case 3: Perineurioma
  • Details: 45yo male, slow-growing soft tissue mass. Well-circumscribed lesion characterized by thin, elongated spindle cells arranged in whirling or spiraling, storiform patterns.
  • IHC: Positive for EMA, Claudin-1, and GLUT1; negative for S100.
  • Key Takeaway: A benign tumor. Differential includes DFSP (infiltrative, CD34+) and Low-Grade Fibromyxoid Sarcoma (MUC4+).
• 20:34 | Case 4: Pleomorphic Lipoma
  • Details: 55yo male, posterior neck/upper back mass (classic site). Features include mature adipocytes, dense ropey collagen bundles, and large, atypical, hyperchromatic cells often arranged in a "floret" or "wreath" pattern (Touton-like).
  • Molecular: Loss or deletion of the RB1 gene (13q).
  • Key Takeaway: Benign, despite atypical appearance. Ropey collagen and the presence of small uniform spindle cells help distinguish it from Atypical Lipomatous Tumor (ALT)/Well-Differentiated Liposarcoma, which usually has hyalinized collagen.
• 30:03 | Case 5: Embryonal Rhabdomyosarcoma, Botryoid Type
  • Details: 5yo female, polypoid mass protruding from the uterine cervix (classic presentation). The tumor is hypocellular, featuring loose myxoid tissue with a subepithelial layer of increased cellularity (the "cambium layer").
  • IHC: Desmin and Myogenin positive.
  • Key Takeaway: Good prognosis; diagnosis relies heavily on the classic history and low-power pattern, as the cellularity is misleadingly low.
• 35:38 | Case 6: Cellular Neurothekeoma
  • Details: 25yo female, dermal nodule. Micro-nodular growth pattern separated by fibrous septa; cells are oval/round with pale chromatin, mimicking melanocytes.
  • IHC: Negative for standard melanocytic markers (S100, Sox10). May be positive for S100A6, PGP 9.5, NKIC3.
  • Key Takeaway: Not a neural tumor (negative for S100/Sox10) but likely a fibrohistiocytic precursor. Benign, even if cytologically atypical.
• 41:59 | Case 7: Chondroid Lipoma
  • Details: 35yo female, proximal leg mass. Nodular lesion containing mature fat, chondromyxoid matrix, and definitive lipoblasts (multivacuolated cells indenting the nucleus).
  • Key Takeaway: A rare, benign tumor. The presence of true lipoblasts historically causes misdiagnosis as liposarcoma.
• 46:24 | Case 8: Epithelioid Hemangioendothelioma (EHE)
  • Details: 40yo female, liver lesion (often multifocal). Characterized by dense, homogeneous pinkish-blue/periwinkle chondromyxoid stroma. Epithelioid cells form cords and nests, often filling vessels.
  • Diagnostic Feature: "Blister cells" (cytoplasmic vacuoles containing fragments of broken-down red blood cells).
  • Molecular: WWTR1/CAMTA1 fusion (majority) or YAP1/TFE3 fusion.
  • Key Takeaway: Vascular neoplasm of intermediate malignant potential; prognosis is often problematic when occurring in the liver or lungs.
• 56:05 | Case 9: Nerve Sheath Myxoma
  • Details: 34yo female, finger lesion. Multi-nodular, lobulated lesion with a swirling pattern of spindle cells in a loose mixoid background. May show nuclear palisading (Verocay body-like).
  • IHC: S100 and Sox10 positive (true neural tumor).
  • Key Takeaway: Benign. Represents the conventional/mixoid form of neurothekeoma and is unrelated to the cellular form (Case 6).
• 1:00:18 | Case 10: Malignant Triton Tumor (Malignant Peripheral Nerve Sheath Tumor - MPNST with Rhabdomyosarcomatous Differentiation)
  • Details: 35yo female with NF1, rapidly growing deep soft tissue mass. Features include malignant spindle cells in fascicles (vague herringbone pattern) and prominent heterologous muscle differentiation (abundant desmin/myogenin-positive rhabdomyoblasts).
  • Molecular/IHC: Neural sarcoma associated with NF1 or occurring sporadically. Characterized by loss of H3K27me3 (sporadic cases).
  • Key Takeaway: An extremely aggressive form of MPNST. The heterologous differentiation is named after the regenerating tail of the Triton salamander.