MON-315 - Diffuse Large B-Cell Lymphoma Presenting with Critical Hypercalcemia: A Rare Initial Presentation - A Case Report

Hypercalcemia is a common paraneoplastic complication in malignancies, particularly in solid tumors (e.g., lung and breast), but is relatively rare in hematologic malignancies such as diffuse large B-cell lymphoma (DLBCL). In lymphoma, hypercalcemia typically results from tumor production of parathyroid hormone–related peptide (PTHrP), although ectopic 1,25-dihydroxyvitamin D (calcitriol) production is a less frequent mechanism.
We describe an 82-year-old woman with a history of follicular lymphoma in remission who presented with progressive lethargy, cognitive decline, and recurrent falls over one month. She was found to have severe hypercalcemia (serum calcium 13.8 mg/dL) with suppressed intact PTH ( < 2 pg/mL) and low-normal 25-hydroxyvitamin D. There was no evidence of primary hyperparathyroidism or osteolytic disease. Computed tomography revealed a large (13.1 cm) anterior pelvic mass, and a biopsy confirmed recurrent lymphoma, now transformed into DLBCL. Further workup demonstrated an elevated 1,25-dihydroxyvitamin D level with undetectable PTHrP, consistent with calcitriol-mediated hypercalcemia. The patient was treated with intensive hydration and calcitonin, resulting in normalization of calcium levels.
This case illustrates an uncommon presentation of aggressive B-cell lymphoma manifesting as hypercalcemia. Although malignancy accounts for most cases of non-parathyroid hypercalcemia, only ~10–20% of non-Hodgkin lymphomas present with hypercalcemia. When present, lymphoma-associated hypercalcemia correlates with high tumor burden and adverse prognostic features, including advanced stage and shorter survival. Recognizing this paraneoplastic syndrome is crucial, as prompt management of hypercalcemia and the underlying lymphoma can improve patient outcomes. This report underscores the importance of considering occult lymphoma (or disease transformation) in patients with unexplained hypercalcemia, as well as evaluating for uncommon causes such as calcitriol overproduction in malignancy.

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