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

ABSTRACT

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.