Tre-P-28 - Primary cutaneous B-cell lymphoma leg-type related to an anti-TNF-alpha therapy

Abstract

<h3>Introduction:</h3> Drug-induced primary cutaneous B-cell lymphomas are rare. <h3>Observation:</h3> A 63 year old woman was referred for a lumbar cutaneous lesion which had been rapidly growing for 1 month. Her past medical history included multiple allergies and a rheumatoid arthritis which was treated with oral methotrexate 10 mg per week and adalimumab. Methotrexate had been taken for 8 years, while adalimumab had been initiated 6 months earlier. Physical examination revealed a solitary thick, violaceous plaque of 6 X 4 cm in diameters, without enlarged lymph nodes. No fatigue, fever or pruritus were present. The first clinical hypothesis was a cutaneous B-cell lymphoma. The histological examination of a skin biopsy specimen showed a monomorphous dermal proliferation of large centroblast-like cells with large round, sometimes irregular, nuclei. Only rare reactive small cells were present. The infiltrate spared the epidermis, with a Grenz zone. The tumor cells were positive for CD45, CD20, bcl2, bcl6, MUM1, highly proliferating (Ki67 95%), and negative for CD3, CD30, CD10 and EBV/EBER. No CD21 or CD23 positive follicular dendritic cell network was identified. Fluorescence in situ hybridization showed no BCL2, BCL6 or CMYC rearrangement, while high resolution melting identified the MYD88 L265P mutation. A B-cell rearrangement was detected in the lesion. Whole body FDG-PET/CT showed a single hypermetabolic activity corresponding to the cutaneous lombar lesion, without distant tumours. Although the Borrelia burgdorferi serology was negative, a 15 days course of doxycyline 200 mg daily was given. Once the diagnosis of primary cutaneous large B-cell lymphoma, leg type (PCLBCL-LT) was made, adamimumab (but not methotrexate) was discontinued. The tumor completely disappeared within 4 months. No other TNF inhibitors were later given. No recurrence was observed after a follow-up time of 4 years. <h3>Discussion:</h3> PCDLBCL-LT are aggressive B-cell lymphomas mainly (but not exclusively) located on the leg, characterized by a monomorphous proliferation of large CD20+, Bcl2+, Mum1+, CD10 - B cells, frequently exhibiting the MYD88 L265P mutation, as observed in our patient. In contrast with indolent subtypes of primary cutaneous B-cell lymphomas, spontaneous regressions in PCLBCL-LT are exceptional, and constantly followed by recurrences. Progression of undiagnosed cutaneous lymphomas after anti-TNF-alpha therapy (mainly cutaneous T-cell lymphomas misdiagnosed as psoriasis or eczema) have been reported [1]. However, the role of anti-TNF-alpha in the occurrence of new lymphoproliferative disorders remains controversial [2,3]. To our knowledge, no PCLBCL-LT related to TNF-alpha inhibitors has been reported to date. Although methotrexate may play a role as a cofactor for the development of this B-cell malignancy, the negative EBV staining and the long-term complete remission after adalimumab withdrawal while methotrexate was continued, strongly argue for a predominant role of the anti-TNF-alpha in the occurrence of this lymphoma.