title: Gonadoblastoma arising in undifferentiated gonadal tissue within dysgenetic gonads.
abstract: OBJECTIVE
  The purpose of the study was to define the histological origin of gonadoblastomas, allowing the identification of high-risk patients.
  
  
  METHODS
  Sixty paraffin-embedded gonadectomy or gonadal biopsy samples of 43 patients with gonadal dysgenesis were selected from our archives. We studied the morphology and immunohistochemical properties of the germ cells in 40 samples without neoplastic transformation and compared these findings with the morphological and immunohistochemical characteristics of 20 samples containing gonadoblastoma/dysgerminoma.
  
  
  RESULTS
  The overall incidence of germ cell tumors in our patient series was 35%. In dysgenetic gonads without germ cell neoplasia, besides the presence of areas with testicular and/or ovarian differentiation, areas of undifferentiated gonadal tissue were identified in 13 of 40 samples (32.5%). A subpopulation of germ cells within these undifferentiated areas stained positive for octamer binding transcription factor (OCT)3/4, the stem cell factor receptor, placental-like alkaline phosphatase, and testis-specific protein-Y encoded. Gonadoblastoma germ cells display identical staining results. Moreover, in gonads containing gonadoblastoma, adjacent to this lesion, areas of undifferentiated gonadal tissue with identical immunohistochemical characteristics were identified in 10 of 20 samples (50%). No adjacent tissue was available in five cases, whereas in the five remaining cases, it consisted of streak tissue. In three cases, an accumulation of OCT3/4-positive germ cells in the proximity of the malignant lesions was found, suggesting clonal expansion and final organization into gonadoblastoma nests.
  
  
  CONCLUSIONS
  Based on these observations, we hypothesize that gonadoblastomas originate from surviving OCT3/4-positive germ cells in areas of undifferentiated gonadal tissue within the dysgenetic gonad. Supportive evidence was obtained that carcinoma in situ arises in regions with testicular differentiation.
authors.affiliation: Department of Pathology, Erasmus Medical Center, University Medical Center Rotterdam, Josephine Nefkens Institute, Room 430b, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
authors.forename: Martine
authors.initials: M
authors.lastname: Cools
authors.forename: Hans
authors.initials: H
authors.lastname: Stoop
authors.forename: Anne-Marie F
authors.initials: AM
authors.lastname: Kersemaekers
authors.forename: Stenvert L S
authors.initials: SL
authors.lastname: Drop
authors.forename: Katja P
authors.initials: KP
authors.lastname: Wolffenbuttel
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bourguignon
authors.forename: Jolanta
authors.initials: J
authors.lastname: Slowikowska-Hilczer
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kula
authors.forename: Sultana M H
authors.initials: SM
authors.lastname: Faradz
authors.forename: J Wolter
authors.initials: JW
authors.lastname: Oosterhuis
authors.forename: Leendert H J
authors.initials: LH
authors.lastname: Looijenga
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000032:analysis; D002278:Carcinoma in Situ / Q000473:pathology; D018797:Cell Cycle Proteins / Q000032:analysis; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D004407:Dysgerminoma / Q000473:pathology; D005260:Female; D006059:Gonadal Dysgenesis / Q000378:metabolism / Q000473:pathology*; D018238:Gonadoblastoma / Q000737:chemistry / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D050814:Octamer Transcription Factor-3 / Q000032:analysis; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000473:pathology*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D013736:Testicular Neoplasms / Q000737:chemistry / Q000473:pathology*
chemical_list: D018797:Cell Cycle Proteins; D007527:Isoenzymes; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C497749:TSPY1 protein, human; C055791:germ-cell AP isoenzyme; D019009:Proto-Oncogene Proteins c-kit; D000469:Alkaline Phosphatase