1992 年 7 巻 3 号 p. 276-280
We reported a case of humoral hypercalcemia of malignancy (HHM) in association with squamous cell carcinoma of the skin. The term HHM describes the condition in which the hypercalcemia is due to the production by the cancer of some substance which acts generally upon the skelton to increase bone resorption.
The patient was a 51-year-old man. He became aware of asymptomatic tumor, on his lower back, measured about 2×2cm in 1971. From June, 1992, the lesion enlareged rapidly and ulcerlated. At the same time, both inguinal lymph nodes metastases were found. When he was addmitted our hospital on September, 1992, the size of the lesion on the lower back was 18×10cm. Histopathological examination of the lower back and inguinal lymph nodes revealed an infiltrating, well differentiated squamous cell carcinoma of the skin with involvement of the lymph nodes. The cell masses showed keratinization, horn pearls were present.
Laboratory studies on admission showed as following: the WBC count was 8, 600/ mm3, with a normal differential cell count. The hemoglobin level was 15.6g/dl, and the hematocrit reading was 45.7%. The liver function tests, urinalysis were normal. The total protein level was 7.3g/dl and an albumin level was 4.0mg/dl. The serum calcium level was 13.4mg/dl, the phosphate value was 2.1mg/dl. The serum parathyroid hormone (PTH) level was lower than 100 pg/ml (normal: 180-560pg/ml) . The serum calcitonin level was 5lpg/ml (normal: 0-100pg/dl) . Bone scintigram, computed tomography (CT), and X-ray examination showed no evidence of metastatic bone lesion. Culture from his wound revealed Staphylococcus aureus.
We treated him for hypercalcemia with sodium chloride infusion and calcitonin. However, the serum calcium level was not significantly decreased. Then, we treated with aminohydroxyprolidene diphosphonate (APD) 30mg. Two days after this treatment, the serum calcium level fell to normal (10mg/dl) . APD is a kind of bisphosphonates which are analogues of pyrophosphate. They have high affinity for bone. The precise effects of bisphosphonates on bone and bone cells are not known in detail, however, they are thought to be taken up by osteoclasts and appear to inhibit the action of these cells.
The tumor of lower back and inguinal lymph nodes were excised and skin graft wasapplied. And we administered doxorubicin hydrochloride and cisplatin. However, because of recurence, the serum calcium level rose again and his condition deteriorated. He died on Jan. 23, 1992.
Parathyroid hormone related protein (PTH-rP) is one of the substance which cause HHM. Recently, cDNAs coding for a PTH-rP has been cloned. PTH-rP shares 80% homology with the first 13 amino acids of PTH in the resion responsible for binding to the PTH receptor. Whether PTH-rP has a physiological role is uncertain, but the compound seems to be primary associated with epithelium. Very high concentrations have been found in breast milk, and immunocytochemical studies have demonstrated high concentrations of PTH-rP in mammary epithelium. It is also abundant in skin, and most squamous cell carcinomas contain PTH-rP. During his hospitalization, we studied his serum level of PTH-rP. The normal level was from 13.8 to 55.3pmol/l. The patient's was 728.4pmol/l. So, we thought the secretion of PTH-rP from SCC was responsible for his hypercalcemia.