Primary Bone Lymphoma Masquerading as Multiple Myeloma: Challenges in the Diagnostic Workup of Severe Hypercalcemia

In this case, we explore the diagnostic workup of a patient presenting with symptomatic hypercalcemia. Initially suspected to have multiple myeloma, the diagnostic evaluation instead unveiled non-germinal center (non-GC) diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common histologic subtype of non-Hodgkin lymphoma and is heterogeneous in terms of presentation, genetic drivers, and morphology. As primary bone DLBCL is exceedingly rare, the case presented proved to be a diagnostic challenge. The patient presented with one week of weakness, one to two days of nausea, and leg pain. On admission, hypercalcemia, renal failure, anemia, and lytic bone lesions were present and suggestive of multiple myeloma. However, serum protein electrophoresis and immunoglobulin levels did not fit the 2016 World Health Organization (WHO) diagnostic criteria for multiple myeloma. A negative bone marrow biopsy also argued against a diffuse plasma cell neoplasm. Finally, a biopsy from another bone lesion was diagnostic of DLBCL. This case discusses an unusual presentation of DLBCL.