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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.