DNA CONTENT OF OVARIAN IMMATURE TERATOMAS AND MALIGNANT GERM-CELL TUMORS

Objective. Ovarian germ cell tumors (GCT) show greater histologic and biologic heterogeneity than their testicular counterparts and remain p oorly understood. Ploidy analysis was performed on ovarian GCT registe red on Pediatric Oncology Group germ cell tumor protocols 9048 and 904 9 to distinguish biologically distinct subsets of immature teratomas a nd malignant ovarian germ cell tumors. Methods. Tumors from 22 patient s (mean age 12 years) were analyzed and classified according to the su bmitting diagnosis; when pure samples of different histologic subtypes within a single tumor were possible, these were analyzed separately. Archival tissue was disaggregated and Feulgen stained; DNA index (DI) was determined by static image analysis utilizing internal normal cell s as diploid controls. Results. 26 histologic subtypes from 22 patient s were analyzed. The tumors of 18 patients were composed of a single h istologic subtype according to the submitting institution, including 6 dysgerminomas, 8 immature teratomas (IT), and 4 endodermal sinus tumo rs (EST). Two tumors contained both IT and EST components that were se parately analyzed. Two tumors were classified as mixed germ cell tumor s; 1 showed multiple intermingling subtypes unable to be separately an alyzed and the second showed three histologic subtypes separately anal yzed (IT EST, embryonal carcinoma). From a total of 15 malignant histo logic GCT subtypes in 14 patients, all but 2 demonstrated a DI of 1.4- 2.4 (mean 1.85). Two diploid malignant GCT (1 EST, 1 dysgerminoma) wer e both associated with gonadoblastoma. Overall, 11 IT subtypes were an alyzed and 9 were diploid (2 grade 1, 5 grade 2, and 2 grade 3). Two t umors originally submitted and classified as pure IT (grades 2 and 3) were aneuploid with a dominant diploid and a secondary aneuploid peak (both DI 1.7). On central review, both of these tumors demonstrated th e presence of subtle patterns of EST that were unrecognized by the sub mitting institution and were much too small for separate analysis. Ana lysis of the 3 patients containing sufficient IT and EST to be separat ely analyzed all showed a diploid IT component and an aneuploid EST co mponent. Conclusions. Analysis of ploidy data suggests that polyploidi zation is a consistent finding in malignant ovarian GCT arising in nor mal patients, similar to the data for adult testicular GCT, Immature t eratomas in this pediatric population, however, are most commonly dipl oid, regardless of grade. The development of EST within an IT is assoc iated with the development of an aneuploid clone. Therefore, the findi ng of such a clone in an IT may be of diagnostic utility, as EST may b e difficult to recognize. Last, the development of a malignant GCT in patients with gonadal dysgenesis may be pathogenetically different fro m those arising in normal patients, in that polyploidization is not re quired. (C) 1998 Academic Press.