Table 7.

Differential diagnoses of CCS.

Diagnosis	Morphology	IHC	Common Genetic Alterations
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; encapsulated; nests or single cells; variableschwannoma epithelioid cells; and myxoid-hyalinized stroma	S100, SOX10, Loss of INI1 (~40%)	Loss of SMARCB1 (~40%)
Myoepithelial tumors	Divers spectrum; reticular/trabecular pattern; variable spindle/epithelioid/clear/plasmocytoid/rhabdoid cells; rarely ductal component (mixed tumors); fibromyxoid stroma; and hyalinization	Pankeratins, S100, SOX10, EMA, GFAP, P63, SMA, calponin, and desmin (focal)	EWSR1 rearrangements (various fusion partners); PLAG1 rearrangements (mixed tumors)