Table 2.

Differential diagnosis of ALK- ALCL and non-hematopoietic tumors (lymph node metastasis or extranodal mass).

Entity	Morphologic Features	CD43/ CD45	CD30	T-Cell Markers	ALK	CKs	p63	EMA	Melanoma Markers: S100, MART1, HBM-45, SOX10	OCT3/4, SALL4	INI1/SMARCB1	Desmin	Vascular Markers, Other
ALK- ALCL	Hallmark cells PleomorphismSinusoidal pattern May show starry-sky pattern DUSP22-rearranged: >Doughnut cells <Pleomorphism	Usually + Few -	+	Variable, usually CD4+ All may be –(null phenotype)	-	- Very rarely +	Variable, + in TP63-rearranged cases	Variable + EMA (40%)	-	-	Retained	-	-
Carcinoma	May show hallmark-like cells Variable pleomorphism Sinusoidal pattern	-	-	-	-	+	+ if squamous cell carcinoma	+	-	-	Retained	-	- Other markers may be + depending on subtype: TTF1, PAX8
Embryonal carcinoma	May show hallmark-like cells Variable pleomorphism Pseudoglandular, alveolar, solid patterns	-	+	-	-	+	-	+	-	+	Retained	-	-
Melanoma	May show hallmark-like cells Variable pleomorphism Sinusoidal pattern	-	- Very rarely +	-	-	-	-	-	+	-	Retained	-	-
Epithelioid sarcoma, other rhabdoid tumors	May show hallmark-like cells Variable pleomorphism Nodular and solid growth, central necrosis Subcutaneous, soft tissue mass	-	-	-	-	+	-	+	-	-	Loss	-	+ ERG
Alveolar soft part sarcoma	May show hallmark-like cells Variable pleomorphism Nodular and alveolar growthSoft tissue mass	-	-	-	-	-	-	-	-	-	Retained	-	- + TFE3 and cathepsin K
Epithelioid myofibroblastic sarcoma	Variable pleomorphism Intraabdominal mass Very rare	-	+	-	+ nuclear membrane or perinucleolar	-	-	-	-	-	N/A	+	- - caldesmon variable + SMA

Abbreviations: ALK: anaplastic lymphoma kinase; ALCL: anaplastic large cell lymphoma; CKs: cytokeratins; EMA: epithelial membrane antigen; SMA: smooth muscle actin.