Leydig Cell Tumor of the Testis With Histological and Immunohistochemical Features of Malignancy in a 1-Year-Old Boy With Isosexual Pseudoprecocity

Abstract

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.

Histopathological and immunophenotypic features of testicular tumour of the adrenogenital syndrome

“…Approximately 10% of LCT are malignant, which is almost always observed in older patients 14–17 . Pre‐adolescent LCT is always benign, except for one reported case of morphologically malignant LCT in a 1‐year‐old boy, but no evidence of malignant behaviour occurred in this case 18 …”

Testicular and paratesticular tumors and tumor-like lesions in the first 2 decades

“…In a series of 40 cases of Leydig cell tumor, only three (8%) occurred in patients under 25 years old, at 2, 3.8, and 5.6 years, 158 and the youngest patient in a series of 29 tumors was 16 years old. 159 Drut et al, 160 however, reported a histologically malignant Leydig cell tumor in a 13-month old with isosexual pseudoprecocity, although there was no evidence of metastasis on short-term follow-up after orchiectomy.…”

Gonadotropin-Dependent Precocious Puberty in an 8-Year-Old Boy with Leydig Cell Testicular Tumor

“…In fact, when prepubertal children are exposed to testosterone, this can trigger the development of central precocious puberty, either from the priming effect of the sex steroid on the hypothalamus or from sudden lowering of sex steroid levels following improvement in the control of gonadotropin-independent precocious puberty [7,18,19]. There are few reported cases of central precocious puberty after treatment of testicular Leydig cell tumors [5,20,21,22,23]. …”

“…Molecular abnormalities such as activity mutations of the gene encoding the LH receptor and G proteins that transduce the effect of this receptor can lead to autonomous hyperplasia and hyperfunction of Leydig cells [5,9,10,11,12]. Leydig cell tumors do not typically produce markers such as AFP and β-hCG [4].…”

“…They account for 1-3% of all testicular tumors [3] and are more commonly found in adults with a median age between 40 and 50 years [4]. Although Leydig cell tumors are believed to be universally benign during childhood, they may seldom exhibit histopathological and immunohistochemical criteria for malignancy [5]. …”