Table 11.
Differential diagnoses of SEF.
| Diagnosis | Morphology | IHC | Common Genetic Alterations |
|---|---|---|---|
| Ossifying fibromyxoid tumor | 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) |
| Carcinoma (lobular, signet ring cell) | Files-small nests; round-oval cells with variable cytoplasm and nuclear atypia; and intracytoplasmic mucin vacuole | Pankeratins, lineage specific markers (depending on site of origine) | Diverse (depending on site of origin) |
| Sclerosing lymphoma | Variably sized hyperchromatic-blastoid cells with variable atypia; scant cytoplasm; and sclerotic stroma | CD45, B/T-cell markers | Diverse |
| Synovial sarcoma | Sheets-fascicles; cellular, monomorphic spindle cells; high N/C ratio, variable epithelial differentiation; staghorn vessels; variable amount of collagen; mast cells; and calcification/ossification; poorly differentiated areas may show round-epithelioid cells | CD99, BCL2, CD56, TLE1, S100 (focal), EMA, and keratins (variable) | SS18-SSX1/2/4 |
| 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) |
| Osteosarcoma | Highly diverse; infiltrative growth; severely anaplastic and pleiomorphic cells; monomorphic small cell appearance is rare; and atypical neoplastic bone formation (essential) | SATB2, osteocalcin (BGLAP), osteonectin (SPARC), osteoprotegerin (TNFRSF11B), RUNX2, S100, actins, CD99, keratin, and EMA | Highly complex chromosomal aneuploidy |
| Myoepithelioma | Divers spectrum; reticular/trabecular pattern; variable spindle/epithelioid/clear/plasmocytoid/rhabdoid cells; rarely ductal component (mixed tumors); fibromyxoid stroma; and hyalinization | Pankeratins, S100, EMA, GFAP, SOX10, P63, SMA, calponin, and desmin (focal) | EWSR1 rearrangements (various fusion partners); PLAG1 rearrangements (mixed tumors) |