Discussion:

Testicular cancer, overall, is a relatively rare tumor comprising only 1 to 2% of worldwide male cancer diagnoses. Of testicular cancer, Leydig cell tumors have historically been considered a rare subtype, comprising only 1% to 3% of total testicular masses removed annually. Some recent publications, however, have called into question the historicity of Leydig cell tumors as a rare diagnosis citing rates as high as 14% to 22% of all surgically removed testicular cancer

Leydig cell tumors have a bimodal distribution, with an initial peak in the prepubertal age group, 4 to 10, and then a second peak between the ages of 30 and 60.

Testicular cancer, overall, is a relatively rare tumor comprising only 1 to 2% of worldwide male cancer diagnoses. Of testicular cancer, Leydig cell tumors have historically been considered a rare subtype, comprising only 1% to 3% of total testicular masses removed annually. Some recent publications, however, have called into question the historicity of Leydig cell tumors as a rare diagnosis citing rates as high as 14% to 22% of all surgically removed testicular cancer

Leydig cell tumors, like other testicular tumors, most commonly present as a painless testicular mass or swelling.

Unique to the hormonally active nature of Leydig cell tumors, patients may present with symptoms of gynecomastia, breast tenderness, precocious puberty, infertility, hypogonadism, or erectile dysfunction. The most common of these in adult patients is gynecomastia due to the conversion of excess (unregulated) testosterone to estradiol by aromatase.

The mass usually reveals a well-circumscribed lesion in the testis. The cut surface of the mass shows a distinct golden brown or homogeneous yellow to light brown appearance. Microscopically, the tumor cells are large to polygonal with a round to oval nucleus and deeply acidophilic with granular cytoplasm. The cytoplasm also shows rod-shaped crystals referred to as "crystalloids of Reinke," which appear in 35% of tumors, and lipofuscin pigment in a smaller percent (10% to 15%).

Positive stains: Inhibin, Melan A(granular, cytoplasmic), vimentin, WT1, Androgen, chromogranin (>90%), synaptophysin(70%)

Negative stains: EMA, SALL4

Radical orchiectomy alone is generally curative for clinically benign Leydig cell tumors.

Testis-sparing surgery can be a consideration if the clinical suspicion of Leydig cell tumor is high, pre-operative testicular tumor marker levels are within normal limits, and the tumor size is less than 2.5 cm. An intra-operative frozen section should always be obtained, and a radical orchiectomy performed if malignant.

Leydig cell tumors demonstrate malignancy by metastasizing. Approximately 10% of Leydig cell tumors in adults exhibit malignant behavior.

The only treatment for malignant Leydig cell tumors is retroperitoneal lymph node dissection, as they are resistant to chemotherapy and radiation.