Table 3.

Differential diagnoses of primary cutaneous ALCL.

Entity	Main Clinical and Histopathologic Features
Systemic ALK+ ALCL with cutaneous involvement	Cutaneous involvement occurs in up to 60% of cases Peripheral lymph nodes and extranodal sites also affected CD30+, ALK+, EMA+ (strong) ALK gene rearrangement
Systemic ALK- ALCL with cutaneous involvement	Peripheral lymph nodes and/or extranodal sites affected Morphologically and immunophenotypically indistinguishable from pc-ALCL
MF with large cell transformation	Clinical history of MF with patches, plaques, and tumors Histological characteristics of MF may be present pan T-cell antigens +, may be CD7- and/or CD5- CD30 may be variable +, GATA3+
Classic Hodgkin lymphoma with cutaneous involvement	Peripheral lymphadenopathy, very rarely presents with skin involvement PAX5+ (weak), often CD15+, lack of CD45 Often Epstein-Barr virus + (EBER ISH, LMP-1) T-cell markers usually -
Lymphomatoid papulosis (LyP) type C	Multiple papular and papulonecrotic eruptions < 10 mm History of spontaneous regression favors LyP Morphologically and immunophenotypically indistinguishable from pc-ALCL
PTCL, NOS, with cutaneous involvement	B symptoms and evidence of disseminated lymphadenopathy Very rarely presents with skin involvement CD30- or weakly +
Subcutaneous panniculitis-like TCL	Median age: 35 years, F > M Infiltrate confined to subcutaneous tissue with fat necrosis; dermis and epidermis typically uninvolved CD30-, CD8+, cytotoxic proteins +
Primary cutaneous gamma-delta TCL	Common hemophagocytic syndrome Three histologic patterns: epidermotropic, dermal, and subcutaneous Apoptosis, necrosis, and angioinvasion present TCRγ/δ+, CD2+, CD5-, CD7+/-, CD56+, cytotoxic proteins +, CD30 variable
Primary cutaneous CD8+ aggressive epidermotropic cytotoxic TCL	Extensive ulcerated cutaneous nodules with an aggressive clinical course Epidermotropic proliferation with pagetoid pattern Ulceration, necrosis, and angioinvasion CD3+, CD8+, cytotoxic proteins +, TCRαβ+, CD2-, CD30-, high Ki-67
Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder	Solitary plaque or nodule in face, neck, or upper trunk <30% of large cells CD3+, CD4+, cytotoxic proteins -, CD30- TFH phenotype: PDL-1 (CD279)+, bcl6+, CXCL13+

Abbreviations: ALK: anaplastic lymphoma kinase; ALCL: anaplastic large cell lymphoma; TCL: T-cell lymphoma; PTCL, NOS: peripheral TCL, not otherwise specified; MF: mycoses fungoides; EBER ISH: Epstein-Barr virus encoded RNA in situ hybridization; LMP-1: latent membrane protein-1 of EBV; THF: T follicular helper; pc: primary cutaneous; F: females; M: males.