Diffuse Large B-Cell Lymphoma Presenting With Hypercalcemia

Hypercalcemia is a common metabolic complication associated with malignancies, particularly in solid tumors, such as lung and breast cancers. However, its occurrence in hematologic malignancies, including diffuse large B-cell lymphoma (DLBCL), is rare. The pathophysiology of hypercalcemia in lymphomas is often related to the secretion of parathyroid hormone (PTH)-related peptide (PTHrP). However, an alternative and less common mechanism involves the ectopic overproduction of 1,25-dihydroxyvitamin D (1,25(OH)2D), which has been reported in some cases of lymphoma-associated hypercalcemia. In this case report, we present a 60-year-old female who was incidentally found to have hypercalcemia during the evaluation of nonspecific symptoms, ultimately leading to the diagnosis of DLBCL with liver and splenic involvement. The patient presented to the emergency department with symptoms of shortness of breath, palpitations, insomnia, polydipsia, and polyuria. Laboratory evaluation revealed a critical calcium level of 12.5 mg/dL, along with suppressed PTH levels and elevated 1,25(OH)2D levels, suggesting an ectopic source of 1-alpha-hydroxylase activity. Imaging revealed hepatic and splenic masses, and a liver biopsy confirmed the diagnosis of DLBCL. Further evaluation ruled out more common causes of hypercalcemia, such as osteolytic metastases and PTHrP-related mechanisms, reinforcing the likelihood that the patient's hypercalcemia was due to ectopic 1,25(OH)2D production. This case underscores the complexity of hypercalcemia in patients with DLBCL, particularly when uncommon mechanisms such as ectopic 1,25(OH)2D synthesis are involved. While the exact etiology of hypercalcemia in DLBCL remains incompletely understood, it is emerging as a potential biomarker for poor prognosis. Studies suggest that hypercalcemia in DLBCL may correlate with aggressive disease features, shorter diagnosis-to-treatment intervals, and worse overall outcomes. In this case, the patient's hypercalcemia may reflect the biological aggressiveness of her disease, with a relatively short interval to treatment after diagnosis. Further research is necessary to better understand the prognostic significance of hypercalcemia in DLBCL and its underlying mechanisms.