TY - JOUR
T1 - Gonadoblastoma arising in undifferentiated gonadal tissue within dysgenetic gonads
AU - Cools, Martine
AU - Stoop, Hans
AU - Kersemaekers, Anne-Marie F
AU - Drop, Stenvert L S
AU - Wolffenbuttel, Katja P
AU - Bourguignon, Jean-Pierre
AU - Slowikowska-Hilczer, Jolanta
AU - Kula, Krzysztof
AU - Faradz, Sultana M H
AU - Oosterhuis, J Wolter
AU - Looijenga, Leendert H J
PY - 2006/6
Y1 - 2006/6
N2 - PURPOSE: The purpose of the study was to define the histological origin of gonadoblastomas, allowing the identification of high-risk patients.EXPERIMENTAL DESIGN: 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.
AB - PURPOSE: The purpose of the study was to define the histological origin of gonadoblastomas, allowing the identification of high-risk patients.EXPERIMENTAL DESIGN: 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.
KW - Adolescent
KW - Adult
KW - Alkaline Phosphatase/analysis
KW - Carcinoma in Situ/pathology
KW - Cell Cycle Proteins/analysis
KW - Cell Differentiation
KW - Child
KW - Child, Preschool
KW - Dysgerminoma/pathology
KW - Female
KW - Gonadal Dysgenesis/metabolism
KW - Gonadoblastoma/chemistry
KW - Humans
KW - Immunohistochemistry
KW - Infant
KW - Isoenzymes/analysis
KW - Male
KW - Octamer Transcription Factor-3/analysis
KW - Ovarian Neoplasms/chemistry
KW - Proto-Oncogene Proteins c-kit/analysis
KW - Testicular Neoplasms/chemistry
UR - http://www.scopus.com/inward/record.url?scp=33744962247&partnerID=8YFLogxK
U2 - 10.1210/jc.2005-2554
DO - 10.1210/jc.2005-2554
M3 - Article
C2 - 16608895
SN - 0021-972X
VL - 91
SP - 2404
EP - 2413
JO - The Journal of clinical endocrinology and metabolism
JF - The Journal of clinical endocrinology and metabolism
IS - 6
ER -