Abstract
Marginal zone lymphoma (MZL) rarely presents with skeletal involvement or hypercalcemia, making diagnosis and management particularly challenging. We report a rare case of a 44-year-old woman with extensive lytic bone lesions, hypercalcemia, and no lymphadenopathy, initially suspected to have multiple myeloma. Imaging revealed widespread osteolytic involvement, and a bone marrow biopsy confirmed MZL. She was successfully treated with rituximab-bendamustine and bisphosphonates. To contextualize this presentation, we conducted a systematic review of case reports and series describing non-Hodgkin lymphoma with skeletal disease and hypercalcemia. Across 16 studies, diffuse large B-cell lymphoma was the most common subtype, but mechanisms of hypercalcemia, including cytokine-driven osteoclast activation, parathyroid hormone-related protein (PTHrP) secretion, and vitamin D dysregulation, were consistent across subtypes. Our case illustrates the importance of considering lymphoma in patients with unexplained lytic lesions and hypercalcemia. Early biopsy, positron emission tomography-computed tomography (PET-CT) imaging, and appropriate therapy can significantly improve outcomes. This case highlights the diagnostic complexity of bone-involved lymphoma and is supported by findings from a systematic review, emphasizing the need for increased recognition of this underreported presentation.