ELSEVIER Isochromosome 12p and Maternal Loss of lp36 in a Pediatric Testicular Germ Cell Tumor Cornelia Stock, Sabine Strehl, Franz-Martin Fink, Silvia Bauer, Thomas Lion, Alfons Kreczy, Helmut Gadner, and Peter F. Ambros ABSTRACT: Analysis of a pediatric germ cell tumor by conventional cytogenetic investigation and flu- orescence in situ hybridization showed consistently the presence of two isochromosomes 12p, loss of the maternal bar.rd lp36, and other numerical and structural chromosome changes. The rearrangements observed resulted mainly from breaks occurring at paracentromeric regions. This report represents the first description of i(12)(p10) in a pediatric testicular embryonal carcinoma. © Elsevier Science Inc., 1996 INTRODUCTION Testicular germ cell tumors (GCT) in adults are character- ized by the presence of i(12)(p10) or multiple copies of 12p [1-7]. In malignant F ediatric GCT, however, the cyto- genetic data available arc; scarce. The benign mature ter- atomas (TD) have a normal diploid karyotype [8], whereas teratomas containing immature elements (IT) display a normal karyotype [8-10] c r may have structural and numer- ical chromosomal abnormalities [10-12]. Neither i(12)(p10) nor an excess of 12p seqnences were reported from a pri- mary intracranial germinoma (GE) showing a large homo- geneous region [13]. In the hypotetraploid cells from a yolk sac tumor (YST) and from an IT with focal GE and embryonal carcinoma (EC) components, however, at least four copies of chromosome 12 were present [14, 15]. To date, only three isochromosome 12p-positive cases have been karyotyped: one ovarian YST [16], one ovarian resid- ual TD [17], and a pineal GE [18]. Recently, the study of paraffin-embedded pedia':ric GCT by means of interphase cytogenetics reported the presence of an excess of chromo- some 12 copies and frequent loss of lp36.3 in malignant GCT [19]. This case not only underlines our previous find- ings, but also represents the first description of an i(12)(p10)- positive pediatric testicular EC. CASE REPORT The patient, a 14-year-old boy, was admitted to the Pediat- ric University Hospital Innsbruck/Austria because of micro- hematuria, flank pain, loss of appetite, and fatigue. A tumor 3 cm in diameter was detected in the left testis. Ultra- sound and computed tomography scan confirmed the pres- ence of a tumor in the testis, and showed a metastatic tumor mass in the retroperitoneum measuring about 5.5 × 5 × 8.5 cm. Serum alpha fetoprotein (183.8 ng/mL) and beta human chorionic gonadotropin (756.4 mU/mL) were ele- vated. Hemiorchidectomy was performed. The histologic diagnosis revealed a combined GCT with seminoma (SE) and EC components (WHO classification). Postoperative chemotherapy was started according to the protocol of the German Society of Pediatric Oncology (MAHO 1992) for stage IIc, which included vinblastin, bleomycin, and cis- platinum. After induction chemotherapy, the serum tumor marker levels normalized within 7 weeks after tumor resec- tion. The residual retroperitoneal tumor was removed 7 weeks after the first surgery. In the histologic sections from the retroperitoneal lymph nodes, the only vital cells detected displayed features of mature teratoma. Finally, two courses of vinblastin, etoposide, cisplatinum were administered, and the patient has been in complete remission for 2 years. From Children's Cancer Research Institute (C. S., S. S., S. B., T. L., H. G., P F. A.), St. Anna Kinderspital (H. G.), Vienna; Pediatric University Hospital Innsbruck, (F-M. F.), Innsbruck; and Institute of Pathologie/University of hmsbruck (A. K.), Innsbruck, Austria. Address reprint requests to: Cornelia Stock, Ph.D., CCRL St. Anna Kinderspital, Kinderspitalgasse 6, A-1090 Vienna, Austria. Received February 21, 1995; accepted June 29, 1995. Cancer Genet Cytogenet 91:95-1G0 (1996) © Elsevier Science Inc., 1996 655 Avenue of the Americas, New York, NY 10010 MATERIALS AND METHODS Cytogenetic Analysis The primary untreated tumor sample was finely minced and the cells were resuspended in RPMI 1640 plus antibi- otics and 10% fetal calf serum for culturing. The direct and short-term culture chromosome preparations failed. Due to the slow growth of the tumor cells, the first meta- phase spreads of good quality could be assessed 8 months 0165-4608/96/$15.00 SSDI 0165-4608(95)00190-Z