Malignant Gonadal Germ Cell Tumors (Other Than Pure Germinoma) in Patients With Disorders of Sex Development: A Report of 21 Cases Based Largely on the Collection of Dr Robert E. Scully, Illustrating a High Frequency of Yolk Sac Tumor With Prominent Hepatoid and Glandular Features.

Abstract

We describe 21 nonpure germinomatous gonadal germ cell tumors (9 with a germinoma component), all but 1 associated with gonadoblastoma, in patients with disorders of sex development who ranged from 7 to 36 years old (average, 20 y). Twenty patients were clinically described as phenotypic females with ambiguous genitalia/virilization and primary amenorrhea. The most common documented peripheral karyotype was 46,XY (10/12; 83%). Fifteen of 16 tumors with available clinicopathologic data were unilateral. They ranged from 7 to 30 cm (mean, 15.5 cm) and were solid and cystic with frequent necrosis and hemorrhage. Gonadoblastoma, in its classic (70%), dissecting (5%), or combined (25%) forms, was identified in all but 1. The malignant germ cell tumors were typically mixed except for 5 pure yolk sac tumors and 1 expansile gonadoblastoma with syncytiotrophoblast cells. When admixed, the most common component was yolk sac tumor (n=10), followed by germinoma (n=9), embryonal carcinoma (n=5), choriocarcinoma (n=4), immature teratoma (n=3), and teratoma (n=2). Typical morphologic patterns of yolk sac neoplasia, including reticular/microcystic, solid (including blastema-like), and endodermal sinus (Schiller-Duval bodies), were seen, as well as glandular (n=10) and hepatoid (n=6) differentiation, with cystically dilated glands and diffuse hepatoid morphology in 3 and 2 tumors, respectively. Two yolk sac tumors showed a sarcomatoid pattern. Somatic-type malignancies (alveolar rhabdomyosarcoma and low-grade spindle cell sarcoma, not otherwise specified) were identified in 1 case each. This is the first large series of germ cell tumors other than typical pure germinoma associated with gonadoblastoma. The high frequency of yolk sac tumor with glandular (especially cystic glandular) and hepatoid morphologies is noteworthy, and their presence should prompt further evaluation for an associated gonadoblastoma and possible disorder of sex development.