Metastatic mature
teratoma is often present in postchemotherapy surgical specimens of lymph nodes from patients with pathological stage II or III testicular
germ cell tumors. The stromal cells in these lesions have generally been considered "
fibrosis" secondary to the
chemotherapy and the
necrosis it causes, although the frequent cytological atypia of the stromal cells suggests that they may be neoplastic. We studied 25 patients with pathological stage II or III
testicular cancer who were treated with
platinum-based
chemotherapy followed by surgical resection of retroperitoneal lymph nodes that contained metastatic mature
teratoma with "
fibrosis" to determine the reactive or neoplastic nature of the stromal cells. We compared the pattern of allelic loss using nine microsatellite
DNA markers (D9S177, D9S303, D9S778, D9S171, D12S1015, D1S508, D2S156, D18S46, and D11S903) between the epithelial cells of the
teratoma and the cells in the adjacent stroma. A
laser capture microdissection technique facilitated preparation of genomic
DNA from the epithelial components of
teratoma, adjacent stromal cells, and normal lymph node tissue from each patient. Of the 25 patients, loss of heterozygosity was seen at a minimum of one focus in 22 (92%) of the
teratoma specimens and 16 (64%) of the adjacent stroma. Of the 16 cases for which the stroma showed loss of heterozygosity, 8 cases showed the identical pattern of allelic loss in the epithelial cells of the adjacent
teratoma at all nine
DNA loci studied. The remaining eight cases showed similar allelic loss in at least one of the nine
DNA loci analyzed. Interestingly, three cases showed loss of heterozygosity in the stroma that was not seen in the matching
teratoma specimens. Our results indicate that the stromal cells adjacent to metastatic mature
teratoma in postchemotherapy lymph node specimens frequently have genetic abnormalities similar to the metastatic
teratoma. Concordant genetic alterations observed in
teratoma and stroma suggest that both are derived from the same
element of the original
germ cell tumor or the same progenitor cell.