Diffuse Large B-cell Lymphoma with Hypercalcemia as the Initial Presentation

Introduction / Background / Significance: Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma (NHL), accounting for approximately 25% of all NHLs. The typical presentations of DLBCL include a rapidly enlarging symptomatic mass and systemic “B” symptoms of fever, weight loss, and night sweats. Hypercalcemia, while being a known complication of DLBCL, has rarely been reported as the its first sign.

Materials and Methods / Case Presentation / Objective: An 82-year-old woman came to the emergency room because of weakness and frequent falls for 3 days. She also had constipation and polyuria for about 6 weeks. In the hospital she was found to have elevated calcium level of 16.1, along with worsening anemia and evidence of acute kidney injury. A diagnosis of severe hypercalcemia was made and she was started on treatment with bisphosphonates, intravenous fluids, and calcitonin. An underlying malignancy was highly suspected given the magnitude of her hypercalcemia, and multiple myeloma (MM) was considered very likely due to her clinical presentations and her known history of osteoporosis. However, further workups including serum protein electrophoresis and immunofixation tests did not show any monoclonal proteins. She then underwent full-body CT scan, which revealed extensive intra-abdominal masses and a 4-cm left posterior neck mass. At the same time, additional workups showed that she had abnormally high levels of both parathyroid hormone-related protein (PTHrP) and 1,25-dihydroxyvitamin D (calcitriol), while ACE and IL-6 levels were negative. She then underwent biopsy of left posterior neck mass, which turned out to be diffuse large B-cell lymphoma. Her hypercalcemia eventually stabilized with continued treatment and she was later started on chemotherapy with R-CHOP for DLBCL.

Results / Description / Main Outcome Measure(s): Cancer-related hypercalcemia is frequently seen in both hematologic malignancies and solid tumors, and is most commonly reported in breast, renal, and lung cancer and multiple myeloma. In some studies, the prevalence of hypercalcemia in DLBCL patients can reach up to 23%, yet it has rarely been reported as the initial presentation. Also, while the most common mechanisms of hypercalcemia in DLBCL are either through secretion of PTHrP or extrarenal production of calcitriol, interestingly in our case, patient was found to have both elevated PTHrP and calcitriol. Lastly, despite exhibiting classic signs of multiple myeloma, this patient turned out to have diffuse large B-cell lymphoma. This underscores the importance of keeping other possible differentials under consideration even in face of a seemingly clear diagnosis.

Conclusion(s): Hypercalcemia can be an unusual first sign of diffuse large B-cell lymphoma. Patients who are found to have hypercalcemia and classic symptoms of multiple myeloma should also be screened for other malignancies that have been known to cause disorders in calcium metabolism.

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