Paraneoplastic humorally mediated hypercalcemia induced by parathyroid hormone-related protein in gynecologic malignancies: a systematic review

Abstract

Humoral hypercalcemia of malignancy (HHM) is a metabolic phenomenon that is mediated by the paraneoplastic secretion of parathyroid hormone-related peptide (PTH-rP). Gynecologic malignant neoplasms complicated by HHM have been reported for organs such as the uterus, cervix, ovary, vulva and the vagina. The purpose of our study was to perform a review of the published cases in the literature and, further, to identify parameters with effect on outcome. Among 34 women with gynecologic neoplasms, 22 suffered from ovarian and 6 from uterine malignancies, while 3 had vulvar and another 3 cervical cancer. Furthermore, clear cell carcinoma was the predominant histology associated with PTH-rP expression. A significant correlation was found between serum calcium and PTH-rP levels. Treatment of hypercalcemia was successful in all cases; pamidronate was utilized in 8 patients. Ovarian cancer patients with severe hypercalcemia and high PTH-rP serum levels had shorter survival compared to their counterparts with mild hypercalcemia or moderately elevated PTH-rP serum levels, but the differences were not statistically significant