Phenotypic variability in primary cutaneous anaplastic large T-cell lymphoma: a study on 35 patients

Primary cutaneous anaplastic large T-cell lymphoma (pcALCL) is a well-defined entity characterized by neoplastic cells expressing CD30, CD2, CD3, CD4, and CD5. Cases with different phenotype have been reported, including variable loss of CD2, CD3, and CD5, and expression of cytotoxic phenotype (CD8⁺) and/or of cytotoxic proteins. Aberrant phenotypes represent a diagnostic pitfall and may be the cause of misdiagnoses. We reviewed 35 cases of pcALCL (M:F = 19:16; mean age, 50.8 years; range, 14-92 years), to better characterize the immunophenotypic spectrum of the disease. Twelve cases (34%) had a T-helper phenotype (CD4⁺/CD8⁻), and TIA-1 was positive in 5 of 8 stained cases. Six cases (18%) had a T-cytotoxic phenotype (CD4⁻/CD8⁺) and were also positive for TIA-1. Positivity for both CD4 and CD8 was observed in 7 cases (20%), 4 of which were stained for TIA-1 and found to be positive, whereas both CD4 and CD8 were negative in 9 cases (26%, only 1/8 tested cases being TIA-1 positive). CD2 was positive in 21 of 27 tested cases (78%), CD3 in 21 of 34 cases (62%), and CD5 in 15 of 31 cases (48%). Interestingly, 11 cases (31%) showed a profoundly aberrant phenotype lacking simultaneously several T-cell markers. Our data allow a better characterization of pcALCL with aberrant phenotypes, showing the remarkable variability in expression of different markers.