Numerical sex chromosomal abnormalities in pineal teratomas by cytogenetic analysis and fluorescence in situ hybridization

BACKGROUND: Central nervous system teratomas are a rare subgroup of extragonadal germ cell tumors. Previous studies show ovarian mature teratomas to be karyotypically normal; those with increasing immaturity show increasing cytogenetic abnormalities. Adult testicular teratomas, regardless of maturity, most often show the isochromosome 12p, a consistent chromosomal abnormality seen in adult testicular germ cell tumors. This study investigates the cytogenetic abnormalities of six central nervous system teratomas by the use of routine karyotypic analysis and fluorescence in situ hybridization. EXPERIMENTAL DESIGN: Karyotypic analysis was performed on two tumors. Four additional tumors were analyzed by dual-labeled fluorescence in situ hybridization. Paraffin blocks were disaggregated, and nuclei were hybridized with both biotin- and digoxigenin-labeled probes to the centromeric domains of the X and Y chromosomes, respectively. Tumor cells were scored for X and Y copy number. Tumor ploidy was determined by image analysis of the disaggregated specimens. RESULTS: The patients (five male, one female) ranged from 2 to 25 years of age. All presented with a solitary mass in the suprasellar region. A mature teratoma was 48, XXYY; an immature teratoma was 47, XXY, dir dup 11 (q12-22). Lymphocyte analysis of the second patient showed a normal constitutional karyotype. Fluorescence in situ hybridization analysis of four additional patients showed both one mature and one immature teratoma from male hosts to have 2X and 1Y signals in the majority of the cells. An immature teratoma from a male host showed 2X and 2Y signals. The above three tumors were diploid by static image analysis. An immature teratoma from a female host showed multiple (four to six) X signals in more than 70% of the cells. Ploidy analysis was unavailable for this case. CONCLUSIONS: Although patients with Klinefelter syndrome (47, XXY) and patients with 46, XY gonadal dysgenesis show an increased incidence of germ cell tumors, numerical sex chromosomal abnormalities have not been described in extragonadal teratomas. Our results support a role for sex chromosomes in the development of central nervous system teratomas.