Cutaneous Marginal Zone Lymphoproliferation Arising from Circumorificial Plasmacytosis During Nivolumab Therapy for Urothelial Carcinoma
Year: 2025
Type: article
Study design: Case Report
Abstract: Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 antibodies, have significantly improved outcomes in a variety of solid tumors, including urothelial carcinoma. However, their use is frequently associated with immune-related adverse events (irAEs) which frequently affect the skin and mucous membranes. Among these, plasma-cell-rich infiltrates are exceptionally rare. Circumorificial plasmacytosis (COP) is a rare, predominantly reactive condition typically involving mucosal transition zones, with histologic features characterized by dense, polyclonal plasma cell infiltrates and a benign clinical course. Only two case reports have described COP in association with ICI therapy and, to date, transformation or overlap with lymphoproliferative disorders such as marginal zone lymphoma has not been documented. We report the case of an 86-year-old male with urothelial carcinoma who developed a progressive, ulcerated, bleeding lesion of the lower lip during adjuvant nivolumab therapy. Histologic examination revealed a dense subepithelial infiltrate of mature plasma cells and lymphocytes. Direct and indirect immunofluorescence studies were negative, excluding autoimmune blistering disorders. Immunohistochemistry showed a predominance of CD138-positive plasma cells with a moderate kappa light-chain shift, CD19 expression, and absence of CD56, Cyclin-D1, and CD117, arguing against a plasma cell neoplasm. Molecular analysis via multiplex PCR revealed a clonal B-cell population with distinct IgH rearrangements, and some EBV-positive cells were also identified by EBER in situ hybridization. The histopathologic and molecular findings suggested a marginal zone lymphoma-like, plasmacytic proliferation arising in the setting of COP. This case illustrates a rare and diagnostically challenging constellation at the intersection of reactive and clonal B-cell proliferations in the context of ICI therapy. Although the lesion demonstrated features of clonality, the overall low B-cell content, indolent clinical course, and lack of systemic involvement support a reactive, immunodeficiency-associated lymphoproliferation rather than overt lymphoma. This case expands the known spectrum of mucocutaneous irAEs and highlights the need for careful clinicopathologic correlation, including immunophenotyping and molecular diagnostics. Awareness of such rare presentations is essential to avoid overdiagnosis and unnecessary systemic treatment in patients with otherwise indolent lesions.
Source: Dermato
Authors: Thilo Gambichler, Heinz-Wolfram Bernd, Sera Weyer-Fahlbusch, Anke Lücke, Johann Lorenzen, Laura Susok
Institutions: Witten/Herdecke University, Ruhr University Bochum
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,207
OpenAlex ID: W4416940468