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Leydig cell tumor (LCT) should be distinguished from hyperplastic/hamartomatous nodules that may be seen in the following conditions: elevated gonadotropin levels, elevated hCG levels, Klinefelter syndrome, adrenogenital syndrome, and Nelson syndrome.
These hyperplastic/hamartomatous nodules are usually bilateral, multifocal and show prominent fibrous bands, more abundant cytoplasm, prominent lipofuscin, adipose metaplasia, and lymphocytic infiltrate. Reinke's crystalloids are absent. In contrast to LCT, the testicular tumor of adrenogenital syndrome is more strongly positive for synaptophysin and CD56 and is negative for androgen receptor.
Other entities in the differential diagnosis of LCT include large cell calcifying Sertoli cell tumor (often bilateral and multifocal; no Reinke's crystalloids; prominent calcification/ossification; intratubular growth; myxoid stroma), metastatic prostatic adenocarcinoma (positive for PSA, PSAP, NKX3.1; clinical history of prostate cancer), seminoma (positive for OCT3/4, PLAP; GCNIS; characteristic lymphocytic infiltrate along fibrous septa), and malakoplakia (eosinophilic histiocytes; Michaelis-Gutmann bodies).
These hyperplastic/hamartomatous nodules are usually bilateral, multifocal and show prominent fibrous bands, more abundant cytoplasm, prominent lipofuscin, adipose metaplasia, and lymphocytic infiltrate. Reinke's crystalloids are absent. In contrast to LCT, the testicular tumor of adrenogenital syndrome is more strongly positive for synaptophysin and CD56 and is negative for androgen receptor.
Other entities in the differential diagnosis of LCT include large cell calcifying Sertoli cell tumor (often bilateral and multifocal; no Reinke's crystalloids; prominent calcification/ossification; intratubular growth; myxoid stroma), metastatic prostatic adenocarcinoma (positive for PSA, PSAP, NKX3.1; clinical history of prostate cancer), seminoma (positive for OCT3/4, PLAP; GCNIS; characteristic lymphocytic infiltrate along fibrous septa), and malakoplakia (eosinophilic histiocytes; Michaelis-Gutmann bodies).