Morphological and immunohistochemical differences between gonadal maturation delay and early germ cell neoplasia in patients with undervirilization syndromes.
CONTEXT: Maturation delay of germ cells and their progression into carcinoma in situ (CIS) frequently occurs in intersex patients. A developmentally delayed germ cell resembles a CIS cell and displays prolonged expression of immunohistochemical markers used for the diagnosis of CIS. This questions their applicability in young children. OBJECTIVE: The objective of the study was the elaboration of tools to distinguish germ cells with maturation delay and CIS. DESIGN: The design was a qualitative and quantitative analysis of the expression of diagnostic markers for CIS in gonads of young patients with undervirilization syndromes. Setting: The study was conducted in the pathology department of a university center, specializing in germ cell tumor pathogenesis. PATIENTS: Fifty-eight formalin-fixed, paraffin-embedded testicular tissue samples of 30 undervirilized patients (1 month to 23 yr of age) were analyzed. Interventions: Interventions included hematoxylin-eosin staining, immunohistochemistry for octamer binding transcription factor (OCT)3/4, gene encoding the stem cell factor receptor that has tyrosine kinase activity c-KIT, placental/germ alkaline phosphatase (PLAP), testis-specific protein Y encoded (TSPY), and VASA, double staining for OCT3/4 and VASA, with ploidy determination by fluorescent in situ hybridization. MAIN OUTCOME MEASURE: Maturation delay and CIS are characterized by the staining patterns of the immunohistochemical markers. RESULTS: CIS was diagnosed in three of 30 patients (10%) and four of 58 gonads (6.9%). Patient age, distribution of OCT3/4-positive cells throughout the gonad, and their position within the seminiferous tubule differ between maturation delay and CIS. Abnormal OCT3/4 and testis-specific protein Y encoded expression appear to be of pathogenetic relevance in the development of these lesions. CONCLUSION: The dimorphic expression of OCT3/4 allows distinction between maturation delay and CIS. Studies in larger patient series are essential before a biopsy to evaluate the neoplastic risk can eventually be proposed as an alternative for gonadectomy.
|Keywords||Adolescent, Adult, Carcinoma/*metabolism/*pathology, Case-Control Studies, Child, Child, Preschool, Diagnosis, Differential, Germinoma/*metabolism/*pathology, Gonadal Dysgenesis, 46,XY/genetics/*metabolism/*pathology, Humans, Immunohistochemistry/methods, Infant, Male, Ploidies, Spermatozoa/pathology, Staining and Labeling, Testis/pathology|
|Persistent URL||dx.doi.org/10.1210/jc.2005-0139, hdl.handle.net/1765/13866|
Cools, M.B.C.M., van Aerde, K., Kersemaekers, A.M., Boter, M., Drop, S.L.S., Wolffenbuttel, K.P., … Looijenga, L.H.J.. (2005). Morphological and immunohistochemical differences between gonadal maturation delay and early germ cell neoplasia in patients with undervirilization syndromes.. Journal of Clinical Endocrinology and Metabolism, 90(9), 5295–5303. doi:10.1210/jc.2005-0139