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 ex tragonadal germ cell tumors. Previous studies show ovarian mature tera tomas to be karyotypically normal; those with increasing immaturity sh ow increasing cytogenetic abnormalities. Adult testicular teratomas, r egardless of maturity, most often show the isochromosome 12p, a consis tent 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 an d fluorescence in situ hybridization. EXPERIMENTAL DESIGN: Karyotypic analysis was performed on two tumors. Four additional tumors were anal yzed by dual-labeled fluorescence in situ hybridization. Paraffin bloc ks were disaggregated, and nuclei were hybridized with both biotin- an d digoxigenin-labeled probes to the centromeric domains of the X and Y chromosomes, respectively. Tumor cells were scored for X and Y copy n umber. Tumor ploidy was determined by image analysis of the disaggrega ted specimens. RESULTS: The patients (five male, one female) ranged fr om 2 to 25 years of age. All presented with a solitary mass in the sup rasellar region. A mature teratoma was 48, XXYY; an immature teratoma was 47, XXY, dir dup 11 (q12-22). Lymphocyte analysis of the second pa tient showed a normal constitutional karyotype. Fluorescence in situ h ybridization analysis of four additional patients showed both one matu re 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 s howed 2X and 2Y signals. The above three tumors were diploid by static image analysis. An immature teratoma from a female host showed multip le (four to six) X signals in more than 70% of the cells. Ploidy analy sis was unavailable for this case. CONCLUSIONS: Although patients with Klinefelter syndrome (47, XXY) and patients with 46, XY gonadal dysge nesis show an increased incidence of germ cell tumors, numerical sex c hromosomal abnormalities have not been described in extragonadal terat omas. Our results support a role for sex chromosomes in the developmen t of central nervous system teratomas.