Table 3.

Differential diagnoses of DSRCT (except small blue round-cell sarcoma; see Ewing).

Diagnosis	Morphology	IHC	Common Genetic Alterations
Neuroblastoma	Primitive cells; rosettes; neuropil; and ganglion cells	CD56, synaptophysin, and chromogranin	nMYC amplification; ATRK, ALK mutations; and chromosomal aberrations (1p, 17q, and 11q)
Lymphoma	Variably sized hyperchromatic-blastoid cells with variable atypia; minimal cytoplasm	CD45, B/T-cell markers	Diverse
Blastemic Wilms	Primitive, undifferentiated round-to-spindled cells	WT1 (N-terminus), CD56	WT1, TP53 mutations; 11p15.5 deletion
Small cell/neuroendocrine carcinoma	Small-medium round-oval cells; salt and pepper chromatin; indistinct nucleoli; molding; and apoptosis	Keratins CD56, synaptophysin, chromogranin, and TTF1	Diverse; TP53, PTEN mutations; RB1, 3p loss; and MYC amplification
Metastatic Merkel cell carcinoma	Round-oval nuclei; high N/C-ratio; salt and pepper chromatin; indistinct nucleoli; molding; and apoptosis	Broad spectrum keratins; CK20 (dot-like), CD56, chromogranin, and synaptophysin	Diverse; depends on polyomavirus (PyV) status; PyV- tumors: Rb1, TP53 mutations
Small cell mesothelioma	Solid nests; high N/C-ratio; well defined membrane; fine chromatin; and indistinct nucleoli	Calretinin, CK5/6, WT1 (N-terminus), and D2-40	Diverse; P16 loss; BAP1 mutation; NF2 deletion; and ALK/EWSR1/FUS rearrangments