Gonadotropin-Dependent Krukenberg Tumor Causing Virilization During Pregnancy

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Abstract
A 38-yr-old woman developed progressive virilization beginning in the 6th month of pregnancy. Extreme elevations of urinary 17-ketosteroids and dehydroepiandrosterone (DHA) were observed at term. Following delivery these urinary steroids gradually decreased, reaching normal values by the 10th day post partum, though plasma and urinary testosterone were found elevated at that time. During 5 days of human chorionic gonadotropin (HCG) administration in the 4th week after delivery, a sharp rise in plasma testosterone, androstenedione and DHA was observed, together with an impressive increase in urinary production of testosterone and 17-ketosteroids. Simultaneously an ovarian mass appeared and this was surgically removed a few days later. Histologic examination of the tumor revealed typical characteristics of a signet-cell adenocarcinoma (Krukenberg), associated with luteinization of the stromal cells. Re-examination of an ovarian tumor removed from this patient 14 months before delivery revealed identical histologic changes except for the absence of luteinization of the stroma. These findings led to a search for a primary gastric carcinoma, which was found by radiographic examination and later excised. The patient remains asymptomatic and free of disease 36 months after gastric surgery. These clinical and biochemical studies demonstrated conclusively the dependence of androgen overproduction by an ovarian tumor upon chorionic gonadotropin stimulation. Evidence is also presented which suggests that some malignant tumors metastasizing to the ovary may modify the ovary's functional state, resulting in an overproduction of steroid hormones, particularly under the stimulus of pregnancy. It seems likely that the stromal compartment rather than the malignant tumor cell is the site of the abnormal steroid production in these situations.