Ectopic production of 1,25-dihydroxyvitamin D by B-cell lymphoma as a cause of hypercalcemia

A patient with long-standing rheumatoid arthritis developed hypercalcemia (3.13 mmol/l) and was subsequently found to have a B-cell lymphoma (centroblastic type). The hypercalcemia was associated with high circulating concentrations of 1,25-dihydroxyvitamin D (235 pmol/l) and both abnormalities were corrected with treatment. A lymph node was excised before treatment and was incubated in vitro with either labeled or unlabeled 25-hydroxyvitamin D3. After purification of the extract and chromatography on three different HPLC systems, material comigrating with authentic 1,25-dihydroxyvitamin D3 was identified. This was shown to bind to a specific chick intestinal cytosol receptor and to dilute in parallel with synthetic 1,25-dihydroxyvitamin D3 in the receptor binding assay. In conclusion, hypercalcemia in malignant B-cell lymphoma can be due to extrarenal production of 1,25-dihydroxyvitamin D by lymphomatous tissue.