Gonadoblastoma Arising in Undifferentiated Gonadal Tissue within Dysgenetic Gonads

Cools, Martine and Stoop, Hans and Kersemaekers, Anne-Marie F. and Drop, Stenvert L. S and Wolffenbuttel, Katja P and Bourguignon, Jean-Pierre and Slowikowska-Hilczer, Jolanta and Kula, Krzysztof and Faradz, Sultana M.H. and Oosterhuis, J. Wolter and Looijenga, Leendert H. J (2006) Gonadoblastoma Arising in Undifferentiated Gonadal Tissue within Dysgenetic Gonads. The Journal of Clinical Endocrinology & Metabolism, 91 (6). pp. 2404-2413. ISSN 0021-972X

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Official URL: http://jcem.endojournals.org/


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.

Item Type:Article
Subjects:R Medicine > R Medicine (General)
Divisions:Faculty of Medicine > Department of Medicine
Faculty of Medicine > Department of Medicine
ID Code:542
Deposited By:Mr. Sugeng Priyanto
Deposited On:09 Sep 2009 11:26
Last Modified:09 Sep 2009 11:26

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