Plasma Cell Leukemia with atypical CCND1/IGH fusion and Monocytoid morphology; A Rare Case Finding

Abstract Introduction/Objective Plasma cell leukemia (PCL) is a rare and aggressive form of plasma cell dyscrasia, often presenting as a variant of multiple myeloma (MM). It is characterized by the presence of ≥5% circulating plasma cells in peripheral blood, either as a primary or secondary manifestation of MM. Methods/Case Report Our case is of a 77-year-old male who presented with epigastric tenderness and bi-basilar crackles. Laboratory results showed severe hypercalcemia, elevated creatinine, leukocytosis, and elevated absolute neutrophil and lymphocyte counts. Imaging revealed widespread lytic lesions in the ribs, scapulae, thoracolumbar spine, and bony pelvis. Peripheral blood smear showed significant macrocytic anemia with rare polychromatophilic cells, numerous immature plasmacytoid cells (>20% of total cell count) and monocytoid morphology. Flow cytometry confirmed a population of monotypic plasma cells (28% of total cells). Bone marrow biopsy revealed a hypercellular plasma cell infiltrate with complex clonal karyotypic abnormalities, including the t(11;14)(q13;q32), rearrangements of 1p, and gain of 1q. FISH analysis showed an atypical CCND1/IGH fusion in 57% of cells, with one fusion, two orange (CCND1), and two green (IGH) signals. The case presented demonstrates a rare instance of an atypical CCND1/IGH fusion in plasma cell leukemia with monocytoid morphology, which poses diagnostic challenges. Prompt and accurate diagnosis is essential for managing the condition, given its consistently poor prognosis despite advancements in therapy over the past decade. Results (if a Case Study enter NA) NA Conclusion Our case highlights the importance of recognizing rare molecular abnormalities in PCL and suggests that further research into the molecular pathways involved in the disease is needed to improve diagnosis, treatment options and clinical outcomes.