Not All Neutrophilia Is Leukemia: Leukemoid Reaction Associated with MGUS Mimicking Chronic Neutrophilic Leukemia – A Case Report

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic plasma cell disorder with potential for malignant transformation, but it rarely presents with marked leukocytosis. We report a unique case of MGUS presenting as a persistent neutrophilic leukemoid reaction (LR), initially raising concern for a myeloproliferative neoplasm. A 48-year-old man was found to have sustained neutrophilic leukocytosis exceeding 30 × 10³/µL, with peripheral smear and bone marrow findings suggestive of granulocytic hyperplasia. Extensive evaluation excluded infectious, inflammatory, autoimmune, and common myeloproliferative causes, including BCR-ABL1, JAK2, and CALR mutations. Serum protein electrophoresis and immunofixation revealed an IgA lambda monoclonal gammopathy, and bone marrow biopsy demonstrated 5% lambda-restricted plasma cells, consistent with MGUS. Next-generation sequencing showed no pathogenic myeloid mutations, including CSF3R, effectively ruling out chronic neutrophilic leukemia. The neutrophilia was attributed to a paraneoplastic leukemoid reaction, likely mediated by cytokine production from clonal plasma cells. Over three years of follow-up, the patient demonstrated stable neutrophilia and gradual increases in IgA and free light chain levels without progression to myeloid malignancy. This case highlights the importance of considering plasma cell disorders in the differential diagnosis of unexplained neutrophilia and underscores the critical role of CSF3R mutational analysis in distinguishing reactive leukemoid reactions from true chronic neutrophilic leukemia.