DP11: Methotrexate-induced cutaneous lymphoproliferative disorders presenting as Epstein–Barr virus-positive mucocutaneous ulcer mimicking high-grade lymphoma

Posters

Philip Macklin,¹ Rachel Fisher,² Rubeta Matin³ and Eleni Ieremia¹

¹Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; ²Department of Dermatology, Royal Berkshire Hospital NHS Foundation Trust, Reading, UK; ³Department of Dermatology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

Methotrexate-associated B-cell lymphoproliferative disorders (LPD) involving the skin are rare, and can present with nodules, plaques or ulcers. Predominantly, they develop in the context of autoimmune conditions treated with methotrexate (e.g. rheumatoid arthritis, dermatomyositis and Sjögren syndrome) and their histology may mimic high-grade lymphoma. One such entity, Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU), typically presents as an ulcerated lesion in the oropharynx, gastrointestinal tract or skin of immunosuppressed individuals. Skin-limited EBVMCU is rare and has only recently been included as a provisional entity in the latest edition of the World Health Organization (WHO) Classification of Skin Tumours. We present four cases of methotrexate-associated EBV⁺/CD30⁺ B-cell LPD, all of which showed histological findings similar to EBVMCU, and clinicopathological correlation determined this to be the final diagnosis. Clinicopathological data were collected through review of case notes and pathology records between 2015 and 2021. Mean age was 75 years (range 66–85 years) with a female predominance (three females and one male). Three patients were treated with methotrexate for rheumatoid arthritis and one patient for polymyositis. All patients had been receiving long-term methotrexate prior to developing EBVMCU (range 6–16 years). Mean follow-up was 4·7 years (range 2·5–6). Presentation included cutaneous nodules and ulcers on the forehead, upper limb (axilla, arm, elbow and hand) and lower limb (buttock/thigh and leg). Systemic disease was excluded through imaging. Histological findings included well-demarcated ulcers with an associated dense inflammatory infiltrate that included large, Hodgkin/Reed-Sternberg (HRS)-like cells within a mixed inflammatory background. Immunohistochemical staining revealed that the HRS-like cells expressed B-cell markers (CD20, CD79a and/or PAX5) and CD30 with EBV-encoded small RNA (EBER) detected by chromogenic in situ hybridization. Abundant T cells were identified in the mixed inflammatory background comprising both CD4⁺ and CD8⁺ subtypes. In all cases, clinicopathological correlation identified the correct diagnosis and withdrawal of methotrexate resulted in healing of ulcers at a mean time of 2 months (range 1–3). Methotrexate-induced cutaneous B-cell LPD presenting as skin-limited EBVMCU is a rare but distinctive entity. Close clinicopathological correlation is essential given its excellent prognosis and that management involves a conservative approach of withdrawal of methotrexate without the need for high-grade lymphoma treatment.