Table 9.
Differential diagnoses of myoepithelial tumors.
| Diagnosis | Morphology | IHC | Common Genetic Alterations |
|---|---|---|---|
| Extraskeletal myxoid chondrosarcoma | Multinodular; lace-like/reticular pattern; round-spindle monomorphic cells with eosinophilic cytoplasm; and myxoid stroma | Non-specific; S100 (focal) | NR4A3-EWSR1/TAF15/TCF12/TFG |
| Chordoma | Lobulated; fibrous septa; cords/nests of large epithelioid/polygonal cells, physaliphorous cells (bubbly cytoplasm); and variable myxoid stroma | Cytokeratin, EMA, S100, Brachyury | Germline tandem duplication of TBXT (rare); germline loss-of-function mutations of TSC1/2 (rare) |
| Sclerosing epitheloid fibrosarcoma | Infiltrative; cords/nests of monomorphic epithelioid cells; and hyalinized/sclerotic/collagenous stroma; | MUC4, SMA, and EMA | EWSR1/FUS/PAX5-CREB3L1/CREB3L2/CREB3L3/CREM |
| (Adeno)carcinoma | Sheets/nests/trabeculae, glands; round-oval-epithelioid cells with nuclear atypia and variable cytoplasm; and ductular structures (adenocarcinoma) | Pankeratins, lineage specific markers (depending on site of origin) | Diverse (depending on site of origin) |
| Small, blue, round cell tumors | Cells with small round-oval-spindle cells with little cytoplasm | Diverse (depending on entity) | See Table 1, Table 2 and Table 3 |
| Epitheloid sarcoma | Nodules of uniform epithelioid-spindled cells with eosinophilic cytoplasm; central geographic necrosis (classic type); multinodular/sheet-like growth; large-slightly pleomorphic epithelioid cells with eosinophilic cytoplasm (proximal type) | CD34, keratins, EMA, and loss of INI1 | Loss of SMARCB1 |
| Melanoma | Diverse growth patterns; large, atypical spindle-epithelioid-bizarre cells with vesicular nuclei and prominent, eosinophilic nucleoli; nuclear pseudo-inclusions; abundant eosinophilic-clear cytoplasm; and melanin pigment | S100, SOX10, Melan-A, HMB45, and MITF | Diverse: ARID2, BAP1, BRAF, GNAQ, HRAS, KIT, NF1, NRAS, PTEN mutations; and chromosomal gains/losses |
| Epithelioid schwannoma | Multilobulated growth; capsule; nests or singly cells; variable epithelioid cells; and myxoid-hyalinized stroma | S100, SOX10, and loss of INI1 (~40%) | Loss of SMARCB1 (~40%) |
| Epitheloid malignant peripheral nerve sheath tumor | Lobulated growth; atypical epithelioid cells with enlarged nuclei; and prominent nucleoli and eosinophilic cytoplasm | S100, SOX10 (strong and diffuse), and loss in INI1 (~75%) | Loss of SMARCB1 (~75%) |
| Ossifying fibromyxoid tumor (mostly benign, rarely malignant) |
Multilobulated; nests/cords of uniform round-spindle cells; indistinct cytoplasm; no atypia (rarely high nuclear grade in malignant lesions); fibromyxoid stroma; partial rim of mature bone; and atypical osteoid in malignant tumors | S100, desmin, GFAP (focal), and pankeratin (rare) | PHF1 rearrangements (diverse fusion partners) |
| Clear-cell sarcoma | Nested-fascicular pattern; epithelioid-plump spindle cells with vesicular nuclei and macronucleoli; fibrous septa; and scattered wreath-like multinucleated giant cells | Melanocytic markers (S100, SOX10, Melan-A, HMB45, and MITF) | EWSR1-ATF1/CREB (most often); EWSR1-CREM (rare) |
| Malignant rhabdoid tumors | Solid pattern; uniform rounded-polygonal cells with vesicular nuclei and prominent nucleoli; and eosinophilic hyaline-like cytoplasmic inclusions | Diverse; keratins, EMA, CD99, synaptophysin, SALL4, glypican-3, and INI1 loss | SMARCB1 biallelic loss |
| Epithelioid hemangio-endothelioma | Infiltrative, sometimes angiocentric growth; cords/nests of bland looking epithelioid and spindle cells; glassy cytoplasm; intracytoplasmic vacuoles (blister cells); and myxohyaline stroma | CD34, CD31, ERG, D2-40, keratins (subset), SMA, CAMTA1, and TFE3 |
WWTR1-CAMTA1 (>90%); YAP1-TFE3 |
| Pseudomyogenic (epitheloid sarcoma-like) hemangio-endothelioma | Multiple discontinuous nodules; possibly involvement of different tissue planes; sheets/fascicles of plump-spindle-epithelioid cells with abundant, brightly eosinophilic cytoplasm; vesicular nuclei with small nucleoli; mild nuclear atypia; not obvious vascular; and prominent stromal neutrophils (50%) | Keratins (AE1/AE3 but not MNF116), FLI, ERG, CD31 (50%), SMA (focal), and FOSB | SERPINE1/ACTB-FOSB |