Primary Cutaneous Small/Medium CD4+ T-CELL Lymphoproliferative Disorder Occurring in a Patient With Metastatic Melanoma

Abstract

Therapeutic agents designed to stimulate the immune system are now cornerstones in the treatment of metastatic melanoma. These drugs promote lymphocyte growth and survival, which could plausibly result in clinical lymphoproliferative disorders. We report the case of a 62-year-old female with metastatic melanoma who developed primary cutaneous small/medium CD4 T-cell lymphoproliferative disorder (PC-SMTCL) after treatment with vemurafenib and recombinant high-dose interleukin-2 (IL-2). The patient developed a painless red papule behind the ear. A biopsy showed a dense population of CD4 lymphocytes with a T-follicular helper cell phenotype. Molecular studies confirmed the presence of a clonal population of T cells, and the process was classified as PC-SMTCL. The patient was diagnosed with metastatic melanoma approximately 3 years before the development of the cutaneous lymphoma and had been treated with vemurafenib followed by 2 courses of IL-2. The patient's last course of IL-2 was completed in April of 2013. She developed the cutaneous lymphoma behind her ear in December of 2015. An association between PC-SMTCL and vemurafenib treatment for advanced melanoma has been reported previously in one patient; however, an association between PC-SMTCL and IL-2 treatment has not been documented. The immunostimulatory properties of IL-2 or vemurafenib may be responsible for the development of PC-SMTCL in our patient. Additionally, antigenic stimulation of the immune system by melanoma itself could contribute to clonal selection of lymphocytes.

Primary cutaneous CD4+ small/medium pleomorphic T‐cell lymphoproliferative disorder: Where do we stand? A systematic review

“…However, Davick et al. recently detected focal germinal centers with CD10+ and BCL‐6+ cells in one patient; this deserves larger studies.…”

“…A few unusual clinical presentations have been reported such as acneiform , alopecia and leprosy‐like disease . Drug‐induced PCSMP‐TLPD has also been reported for the methotrexate‐etanercept combination , vemurafenib , interleukin (IL)‐2 therapy for metastatic melanoma and standard triple‐agent immunosuppressive therapy (cyclosporine, prednisolone, and azathioprine) following heart transplantation surgery , although this is an extremely rare presentation. This drug‐induced variant should be carefully differentiated from drug‐induced nodular T‐cell pseudolymphoma.…”

“…Furthermore, a child with a unique association of PCSMP‐TLPD and erythema chronicum migrans showed complete remission with oral amoxicillin . Finally, PCSMP‐TLPD has also been associated with advanced melanoma (n = 2) , superinfection of an ulcerative lesion with zygomycosis (n = 1) and rheumatoid arthritis (n = 1) .…”

Primär kutane CD4+ klein‐ bis mittelgroßzellige pleomorphe T‐Zell‐Lymphoproliferation: Wo stehen wir? Eine systematische Übersicht

“…Es wurde auch über einige wenige atypische klinische Manifestationen berichtet, wie Akne‐ oder Lepra‐ähnliche Veränderungen und Alopezie [–]. Des Weiteren wurde nach Behandlung mit der Kombination Methotrexat‐Etanercept , mit Vemurafenib , Interleukin (IL)‐2 bei metastasiertem Melanom und immunsuppressiver Dreifachstandardtherapie (Cyclosporin, Prednisolon und Azathioprin) nach Herztransplantation über arzneimittelinduzierte PCSMP‐TLPD berichtet, wobei dies jedoch äußerst selten ist. Die arzneimittelinduzierte Variante sollte sorgfältig vom arzneimittelinduzierten nodulären T‐Zell‐Pseudolymphom unterschieden werden.…”

“…In diesem Fall wurde durch orale Behandlung mit Amoxicillin eine komplette Remission erzielt . Schließlich gab es auch Fälle, bei denen die PCSMP‐TLPD auch mit fortgeschrittenem Melanom (n = 2) , Superinfektion einer ulzerierenden Läsion mit Zygomyzeten (n = 1) und rheumatoider Arthritis (n = 1) assoziiert war.…”