Squamous cell carcinoma of the mandible associated with humoral hypercalcemia of malignancy (HHM) and an establishment of experimental animal model in nude mice

A 39-year-old man with squamous cancer of the left mandible, who previously had received irradiation, chemotherapy and surgery in another hospital, was seen in January 1985 complaining of severe pain due to recurrence of the cancer. He was given chemotherapy with VEMF (Vincristine, Endoxan, Methotrexate, 5-FU) and consecutively with cisplatin in our clinic. Unfortunately, they were ineffective, which resulted in marked growth and extension of the tumor. In parallel with this, he manifested the hypercalcemia (8meq/l) with no evidence of metastases to bones. Serum level of parathyroid hormone and active metabolite of vitamin D3 were both lower, though within normal range, but nephrogenous cyclic AMP was significantly elevated. These clinical and laboratory data clearly suggested the hypercalcemia seen in this patient is so-called humoral hypercalcemia of malignancy (HHM).We then implanted the patient's tumor into nude mice and succeeded in an establishment of tumor-bearing animals. They demonstrated the hypercalcemia similar to that of the patient in parallel with tumor growth. Endosteal surface of femurs of tumor-bearing nude mice showed an increased osteoclastic bone resorption.These findings suggest humoral stimulator of osteoclastic bone resorption is released from the tumor. We believe these animals are a useful model for the study of HHM.