The mantle’s deception: a diagnostic challenge in a case of mantle cell lymphoma

Introduction: Mantle cell lymphoma (MCL) is a neoplasm derived from mature B-lymphocytes, with heterogeneous clinical course. The defining genetic feature of MCL is the t(11;14)(q13;q32) translocation, which results in IGH:CCND1 fusion. However, not all MCL carry this translocation. Case Report: Our patient is a 69-year-old woman with a prolonged history of chronic cough, accompanied by appetite and weight loss. Physical examination was unremarkable except for a right palatine tonsil enlargement and multiple cervical lymphadenopathies. A CT scan performed revealed right palatine tonsil enlargement. She had no cytopenias, and no abnormal lymphoid cells were detected on the peripheral smear. The bone marrow aspirate examination revealed 2.6% abnormal small- to medium-sized lymphoid cells with scanty cytoplasm; some cells have clefted nuclei. Immunophenotyping showed 0.8% abnormal lymphoid cells gated at low SSC/ bright CD45 area that expressed CD19, CD20, CD5, and CD79b, with lambda light chain restriction. They were negative for FMC7, CD200 and CD10. The bone marrow trephine biopsy was hypercellular, with altered topography. Marrow infiltration was focal, with abnormal cells exhibiting dense chromatin pattern and irregular nuclear outline. They were immunoreactive to CD20, CD5, CD23 (weak), BCL2, and Cyclin D1 and negative for CD10 and CD3. This reactivity pattern was replicated in the tru-cut biopsy of the left cervical lymph node. However, interestingly Fluorescence in-situ hybridization (FISH) using CCND and IGH fusion probes showed negative for CCND1/IGH translocation. Based on the typical morphology and immunohistochemistry, a mantle cell lymphoma diagnosis was made. The patient was initiated on a combination of chemotherapy and targeted therapy and is currently well. Discussion: While the t(11;14) translocation and IGH:CCND1 fusion are defining features of MCL, a small subset presents with atypical mechanisms of cyclin D1 overexpression. Cyclin D1 overexpression, rarely, can occur through cryptic rearrangements or IG:CCND2 fusion, which might the case for our patient.