Diagnostic challenges in a case of CD5-negative leukemic non-nodal mantle cell lymphoma with monoclonal IgM that initially presented as gastrointestinal polyposis and misdiagnosed as low-grade intraepithelial neoplasia

Mantle cell lymphoma (MCL) is conventionally characterized by CD5 positivity and nodal involvement. Leukemic non-nodal MCL (nnMCL) constitutes a well-recognized distinct subtype of MCL with indolent clinical behavior. Although CD5 negativity, leukemic non-nodal phenotype, gastrointestinal lymphomatous polyposis, and monoclonal IgM paraproteinemia have each been reported as isolated atypical features of MCL, their concurrent presentation in a single patient is rare and easily leads to clinical misdiagnosis. A 65-year-old male patient was admitted to our department on June 11, 2025, due to splenomegaly, elevated lymphocyte level, and decreased platelet count for over 2 months. The patient was asymptomatic but presented with splenomegaly when multiple gastrointestinal polyps were incidentally detected on gastroscopy and colonoscopy on April 3, 2025. Postoperative pathology revealed low-grade intraepithelial neoplasia of the gastric and colonic glands. However, no further diagnosis was made for the splenomegaly at that time. Bone marrow (BM) aspiration and biopsy revealed CD5-negative nnMCL. Immunofixation electrophoresis showed the presence of IgM. A retrospective analysis of gastric polyp pathology showed the presence of CD5-negative MCL. Finally, the patient was diagnosed with CD5-negative nnMCL with gastrointestinal lymphomatous polyposis and with an elevated monoclonal IgM. Subsequently, the patient was treated by two courses of bendamustine and rituximab, and partial remission of lymphoma was achieved. However, the patient refused to continue chemotherapy and chose orelabrutinib. Currently, the patient has been followed up for over 6 months and remains in a stable condition. This paper presents a retrospective review of a patient who was initially misdiagnosed with low-grade intraepithelial neoplasia on routine workup for gastrointestinal polyps and was ultimately diagnosed with CD5-negative nnMCL complicated by monoclonal IgM. The confluence of these atypical features creates substantial diagnostic challenges, as overreliance on any single diagnostic modality may result in misdiagnosis. It also emphasizes the necessity of a multidisciplinary diagnostic strategy, integrating clinical suspicion, advanced immunophenotyping, and molecular genetics, particularly when faced with atypical presentations or discordant initial findings. Heightened awareness of this entity among endoscopists, pathologists, and hematologists is crucial to avoid diagnostic delay.