Hypercalcemia in non-Hodgkin's lymphoma due to cosecretion of PTHrP and 1,25-dihydroxyvitamin D

Hypercalcemia occurs in up to 30% of patients with malignancies and can be due to osteolysis by metastases, parathyroid hormone-related protein (PTHrP), excess 1,25-dihydroxyvitamin D (1,25(OH)₂D) production or, rarely, ectopic parathyroid hormone (PTH) secretion. Hypercalcemia in non-Hodgkin's lymphoma has been described with elevations in PTHrP or, more commonly, excess 1,25(OH)₂D production. We present the first case of a patient with new diagnosis of non-Hodgkin's lymphoma and severe hypercalcemia who was found to have concurrently elevated PTHrP and 1,25(OH)₂D. In human studies, PTHrP has shown limited ability to stimulate 1,25(OH)₂D production. To demonstrate that both PTHrP and 1,25(OH)₂D were of tumor origin in our patient, tissue from her tumor underwent histochemical staining, demonstrating expression of both PTHrP and CYP27B1, indicating the presence of 1,25(OH)₂D production in the tumor tissue. Our case illustrates the complexity of hypercalcemia in patients with underlying malignancy and highlights the importance of a thorough diagnostic workup for achievement of a successful therapeutic approach. In our patient, definitive chemotherapeutic treatment resulted in achievement and maintenance of normal calcium, PTHrP and 1,25(OH)₂D levels 18 months after initial diagnosis. Hypercalcemia occurs in up to 30% of malignancies and can be due to several mechanisms. We present the first case of cosecretion of parathyroid hormone related peptide (PTHrP) and 1,25-dihydroxyvitamin D (1,25(OH)₂D) in a patient with non-Hodgkin's lymphoma and demonstrate that both PTHrP and 1,25(OH)₂D were of tumor origin by immunohistochemical staining.