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C‐C chemokine receptor 4 expression in CD8+ cutaneous T‐cell lymphomas and lymphoproliferative disorders, and its implications for diagnosis and treatment
Author(s) -
Geller Shamir,
Hollmann Travis J,
Horwitz Steven M,
Myskowski Patricia L,
Pulitzer Melissa
Publication year - 2020
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13960
Subject(s) - ccr4 , mycosis fungoides , medicine , lymphoma , lymphoproliferative disorders , cd8 , cd30 , immunohistochemistry , pathology , chemokine receptor , immunology , chemokine , receptor , immune system
Aims Patients with aggressive CD8+ cutaneous T‐cell lymphomas (CTCLs) progress rapidly and respond poorly to therapy. Confounding treatment planning, there is clinicopathological overlap between aggressive CD8+ CTCLs and other lymphoproliferative disorders (LPDs). Hence, improved diagnostic methods and therapeutic options are needed. The aim of this study was to examine C‐C chemokine receptor 4 (CCR4) expression as a diagnostic and therapeutic biomarker in CD8+ CTCLs/LPDs. Methods and results Forty‐nine cases (41 patients) with CD8+ CTCLs/LPDs were examined, including CD8+ mycosis fungoides (MF) ( n = 14), aggressive epidermotropic CD8+ cytotoxic T‐cell lymphoma (AETCL) ( n = 8), subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) ( n = 7), CD30+ LPDs ( n = 6), primary cutaneous γδ T‐cell lymphoma (GDTCL) ( n = 6), and others ( n = 8). Immunohistochemical tissue staining was performed with a CCR4 monoclonal antibody on formalin‐fixed paraffin‐embedded tissue sections. CCR4 immunostaining was graded as percentage infiltrate, i.e. high (>25%) and low (≤25%), and the results were correlated with clinicopathological diagnoses. CCR4 expression was seen in 69% of the studied cases. Any CCR4 positivity was seen in all CD8+ MF cases, in 83% of CD30+ LPD cases, in 75% of AETCL cases, in 33% of GDTCL cases, and in none of the SPTCL cases. High CCR4 expression was seen in 79% of CD8+ MF cases versus 33% of CD30+ LPD cases, in 17% of GDTCL cases, and in 12.5% of AETCL cases. Patients with more advanced MF stage had higher CCR4 expression. Conclusions CCR4 immunohistochemistry may be an adjunct in distinguishing advanced CD8+ MF from other CD8+ CTCLs/LPDs. Although CCR4 expression may justify therapeutic targeting of this receptor in CD8+ MF, the role of such therapies in other CD8+ CTCLs/LPDs is not yet clear.