Hypercalcemia associated with renal cell carcinoma: probable role of neoplastic stromal cells

Sarcomatous proliferation of the fibroblast-like stromal cells in renal cell carcinoma was found in three patients who had apparently tumor-associated hypercalcemia but no evidence of bone metastases. The proliferation of stromal cells was not found in 20 patients who also had renal cell carcinoma without hypercalcemia. Immunoreactive parathormone-like substance was detected in two of the three patients with hypercalcemia, despite high levels of serum calcium. The parathormone assay was not conducted on the third hypercalcemic patient, however. Buffer extract from one of the tumors associated with hypercalcemia was able to elicit an increase of the serum calcium in rats, whereas buffer extract from a tumor not associated with hypercalcemia failed to induce hypercalcemia in rats. Findings suggest that the stromal cells of renal cell carcinoma may play a role in the tumor-associated hypercalcemia. The exact nature of the hypercalcemic agent is uncertain. However, in the case studied it appears that a parathormone-like substance was responsible.