mart-1-antigen and Puberty--Precocious

Testis enlargement in McCune-Albright syndrome (MAS) is generally bilateral and associated with clinical and biochemical manifestations of sexual precocity.. We describe for the first time an unreported clinical expression of MAS in a 4.6-year-old boy presenting with monolateral testis enlargement and no signs of sexual precocity or other clinical manifestations of MAS at the time of presenting with macroorchidism. Both testosterone and LHRH-stimulated gonadotropin levels were in the prepubertal range. Serum inhibin B was increased to a pubertal level indicating Sertoli cell activation. The histological and immunocytochemical evaluation of the enlarged testis revealed Sertoli cell hyperplasia with no mature Leydig cells. Mutation R201C of GNAS1 gene, classically responsible for MAS, was identified in DNA samples from the right testis biopsy and leukocytes.. (a) MAS should be taken into consideration in the clinicopathological approach to a boy with monolateral macroorchidism; (b) testicular enlargement may be only the presenting clinical manifestation of MAS and is not necessarily linked to manifestations of peripheral precocious puberty; (c) testicular autonomous hyperfunction in MAS may be restricted to Sertoli cells, as also demonstrated previously by others.

Topics: Antigens, Neoplasm; Child, Preschool; Chromogranins; Diagnosis, Differential; Fibrous Dysplasia, Polyostotic; Gonadotropins; GTP-Binding Protein alpha Subunits, Gs; Humans; Hyperplasia; Immunohistochemistry; Inhibins; Male; MART-1 Antigen; Mutation; Neoplasm Proteins; Puberty, Precocious; Sertoli Cells; Testis; Testosterone

The article reports the clinical, histopathological, and immunohistochemical findings of a 1-year-old boy presenting with isosexual pseudoprecocity attributable to a functioning Leydig cell tumor of the testis. The case appears to represent the youngest patient ever recognized with this well-known syndrome. Malignancy features were also for the first time initially assessed using criteria, retrospectively developed from the literature, for metastasizing Leydig cell tumor. All the following were found: infiltrative borders, cellular pleomorphism, high mitotic index (12-14/high-power field), high MIB-1 index (40%), P53 positivity in 50% of the cells, and bcl-2 positivity in 15% of the cells. Immunohistochemistry proved the cells of the tumor to be positive for inhibin, Melan-A, synaptophysin, cytokeratin, and calretinin and negative for S-100 and chromogranin A. Notably, lipochrome and crystals of Reinke were not found in the tumor cells. Although the neoplasm fulfilled the criteria for a potentially metastasizing Leydig cell tumor, there was no evidence of that event having occurred, perhaps as a result of early treatment or as indication that criteria developed for Leydig cell tumor of adults may not apply to children.

Topics: Antigens, Neoplasm; Calbindin 2; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Infant; Inhibins; Keratins; Leydig Cell Tumor; Male; MART-1 Antigen; Neoplasm Proteins; Puberty, Precocious; S100 Calcium Binding Protein G; Synaptophysin; Testicular Neoplasms