Table 13.
Differential diagnoses of epithelioid and spindle cell rhabdomyosarcoma.
| Entity | Morphology | IHC | Common Genetic Alterations |
|---|---|---|---|
| Inflammatory myofibroblastic tumor | Fascicular pattern (variable); plump-spindle cells with vesicular nuclei and small nucleoli and amphophilic cytoplasm; oedematous-myxoid-fibrous stroma; and mixed inflammatory infiltrate | SMA, calponin, desmin, keratin (focal), ALK, and ROS1 | ALK rearrangements (various fusion partners); ROS1, NTRK3, RET, or PDGFRB rearrangements |
| Carcinoma | Sheets/nests/trabecules; round-oval-epithelioid cells with variable cytoplasm and nuclear atypia | Pankeratins, lineage-specific markers (depending on site of origine) | Diverse (depending on site of origin) |
| Myoepithelial carcinoma | Solid sheets/nests of variable myoepithelial cells (epitheloid, spindled, plasmocytoid, rhabdoid, and clear) with high nuclear grade or undifferentiated round-cell morphology; necrosis; and high mitotic count | Pankeratins, EMA, S100, SOX10, GFAP, P63, SMA, calponin, desmin (focal); and INI1 loss (subset) | EWSR1 rearrangements (various fusion partners); PLAG1 rearrangements (mixed tumors) |
| EWSR1-PATZ1 sarcoma | Diverse morphology: round-spindle cells; fibrous stroma | Co-expression of myogenic markers (desmin/myogenin/MyoD1) and neurogenic markers (S100/SOX10/MITF/GFAP) | EWSR1-PATZ1 |
| Dedifferentiated chondrosarcoma | Conventional chondrosarcoma with abrupt transition to a high-grade non-cartilaginous sarcoma (undifferentiated sarcoma, osteosarcoma, angiosarcoma, leiomyosarcoma, and rhabdomyosarcoma) | Diverse (according to line of differentiation); loss of H3K27me3, MDM2 overexpression, p53 overexpression, and PDL1 | Complex karyotype; IDH1/2, TP53 mutations |
| Pseudomyogenic (epitheloid sarcoma-like) hemangioendothelioma | 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 |
| Rhabdomyosarcoma (spindle cell) | Cellular fascicles with intersecting/herringbone pattern; atypical uniform spindle cells with pale eosinophilic cytoplasm; primitive round cells may be present; and tadpole/strap cells (sometimes) | Desmin, MyoD1 (focal or diffuse), myogenin (focal) | SRF/VGLL2/TEAD1-NCOA2, VGLL2-CITED2 (congenital spindle cell RMS); and MYOD1 mutation |
| Leiomyosarcoma | Intersecting fascicles of smooth muscle cells; blunt-ended, cigar-shaped nuclei; variable atypia and pleomorphism (depending on grade); eosinophilic cytoplasm; mitoses; necrosis | SMA, desmin, and caldesmon | Extensive genomic instability (leiomyosarcoma); diverse gene involvement with p53 mutations; deleterious ATRX alterations; ALK rearrangement (small subset); and NF1 mutations (subset of inflammatory leiomyosarcoma); |
| 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, and PTEN mutations; chromosomal gains/losses |
| Malignant peripheral nerve sheath tumor | Fascicles of spindle cells with perivascular accentuation and alternating cellularity; staghorn vessels; necrosis; and heterologous differentiation | S100, SOX10 (focal), and loss of H3K27me3 | Inactivating mutations of NF1, CDKN2A/B, EED, and SUZ2 |