Humoral hypercalcemia in seminomas

Abstract

Seminomas are germ cell tumors that are rarely associated with hypercalcemia. In this report, four cases of seminoma with concomitant hypercalcemia are presented and another three from the literature are reviewed. All seven patients exhibited hypercalcemia with a normal serum concentration of inorganic phosphorus and no evidence of skeletal metastases. The peripheral venous level of parathyroid hormone (PTH) was normal in four of the five patients in whom it was measured. The serum concentration of calcitriol was elevated in the two patients in whom it was measured. After systemic chemotherapy, the serum "corrected" total calcium concentration returned to normal and remained normal; the decrease in the levels temporally paralleled the decrease in tumor volume. Both patients with elevated calcitriol levels remained eucalcemic after treatment of the malignancy, suggesting that the increased serum calcitriol level was linked to the development of hypercalcemia as this humoral agent was inappropriately elevated by patients with this syndrome. In contrast to many forms of malignancy, the development of hypercalcemia did not adversely affect the prognosis of the patients with seminoma, since all seven patients entered complete remission. Hypercalcemia appears to be heretofore unrecognized paraneoplastic syndrome associated with seminoma.

Calcitriol-Mediated Hypercalcemia: Causes and Course in 101 Patients

“…However, given the overlap of chronic lymphocytic leukemia with small-cell leukemia and the well-known association of calcitriol-mediated hypercalcemia with non-Hodgkin's lymphoma (7), this is not a surprising association. Hypercalcemia related to elevated calcitriol concentration with seminoma has been reported in only two previous cases (26,27). All these cases were well documented, with no suggestion of other underlying pathology, and all cases were pathologically verified.…”

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

“…85 These include androgenic ones from secondary hyperplasia of Leydig cells in the testis or stimulation of the ovarian stroma; estrogenic ones, either because of direct stimulation of ovarian stroma and/or nonneoplastic follicles or peripheral conversion of androgen to estrogen, thereby resulting in abnormal uterine bleeding or, in men, gynecomastia; and hyperthyroidism because of the thyroid-stimulating hormone-like activity of hCG. 86,87 A number of other interesting, paraneoplastic manifestations may be seen in association with germ cell tumors, especially germinomas, including hypercalcemia, 86,88 hypoglycemia, 89 exophthalmos, 90,91 autoimmune hemolytic anemia (usually ovarian dermoids), ataxia telangiectasia, 86 and limbic encephalopathy. 92,93 Spermatocytic seminoma Spermatocytic seminoma may be confused with usual seminoma, a very important distinction from the clinical standpoint since spermatocytic seminomas virtually never metastasize (except for those with a rare complication mentioned below) and do not merit treatment apart from orchiectomy.…”

Morphological approach to tumours of the testis and paratestis

“…7 Hypercalcaemia, probably due to production of a parathyroid hormone-like substance, has been reported in association with seminoma. 9 Endocrinologically active tumours are more likely to be sex cord-stromal tumours than germ cell tumours. In boys, approximately 10% of cases of precocious pseudopuberty may result from steroid hormone production by Leydig cell tumours.…”