title: Clonal evidence for the progression of a testicular germ cell tumor to angiosarcoma.
abstract: Testicular germ cell tumors may have multiple histologic subtypes. Teratoma components are capable of transformation into somatic malignancies. An alternative hypothesis for the development of angiosarcoma in a patient with germ cell tumors is secondary to radiation or chemotherapy. We report a patient with a mixed testicular germ cell tumor who presented with retroperitoneal, mediastinal, and pulmonary metastases after chemotherapy. Forty months after his original diagnosis, a mediastinal angiosarcoma was diagnosed. Using tissue microdissection-loss of heterozygosity analysis and fluorescence in situ hybridization, we analyzed the clonality of the primary germ cell tumor, angiosarcoma, and metastatic teratoma. Six microsatellite polymorphic markers from 3 different chromosomes were used to examine the pattern of allelic loss; chromosome 12p alterations, including isochromosome 12p and 12p overrepresentation, were investigated. Loss of heterozygosity was demonstrated for microsatellite loci of all 3 chromosomes, and completely concordant loss of heterozygosity patterns were observed among primary germ cell tumor components, metastatic teratoma, and angiosarcoma. Isochromosome 12p and 12p overrepresentations were consistently found in the primary germ cell tumor components, metastatic teratoma, and angiosarcoma. The results indicated a clonal origin of the tumors, which supports that angiosarcoma, as well as the teratomas, arose from the testicular germ cell tumors.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Idrees
authors.forename: Matthew
authors.initials: M
authors.lastname: Kuhar
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Ulbright
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
authors.forename: Narsimhan
authors.initials: N
authors.lastname: Agaram
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Wang
authors.forename: David J
authors.initials: DJ
authors.lastname: Grignon
authors.forename: John N
authors.initials: JN
authors.lastname: Eble
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D002999:Clone Cells; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D006394:Hemangiosarcoma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008297:Male; D008479:Mediastinal Neoplasms / Q000235:genetics / Q000473:pathology*; D042282:Microdissection; D018895:Microsatellite Repeats / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000473:pathology*; D013724:Teratoma / Q000188:drug therapy / Q000235:genetics / Q000556:secondary*; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*
chemical_list: D004273:DNA, Neoplasm