What is the most probable diagnosis?

Diagnosis: Leydig Cell Tumour

Discussion:

Leydig cell tumour accounts for about 3% of testicular neoplasms. It has two age peaks, with about 20% of cases occurring in children and 80% occurring in adults. Adults most commonly present with a testicular mass, with about 30% of patients developing gynecomastia. Bilateral involvement occurs in about 3% of cases. This tumour shares some of the epidemiological features of testicular germ cell tumours, occurring more commonly in patients with cryptorchidism, testicular atrophy, and infertility, and almost exclusively in white patients.

Grossly, most Leydig cell tumours appear as yellow, brown, or tan, solid, sometimes lobulated, instratesticular nodules, infrequently with areas of necrosis or hemorrhage. The majority are 2-5cm in diameter, but some exceed 10cm.

Microscopically, a number of patterns may be seen; the solid, sheet-like pattern is most common, but pseudoglandular, cord-like (trabecular, and compact nested patterns may also be present, often in the same neoplasm. It is common for nodular aggregates of tumour cells to be separated by edematous or fibrous stroma. The cells are polygonal, with abundant eosinophilic cytoplasm, round, variably sized nuclei, and prominent, central nucleoli. Rod-shaped, intracytoplasmic crystals of Reinke are identified in up to 40% of cases. Mitotic figures are usually infrequent, and a rate of 3 or more per 10 high-power fields is a features that suggests malignancy.

Immunohistochemistry can assist with the diagnosis of Leydig cell tumour. Inhibin is positive in almost all Leydig cell tumours, as are stains for MelanA (MART-1), and calretinin. CD99 is detected in about 2/3 of cases. P53 is detected in some malignant cases. Vimentin is the dominant cytoplasmic intermediate filament, although cytokeratin reactivity may also be seen.

About 10% of Leydig cell tumours are clinically malignant. Some clinical features correlate with the natural history of Leydig cell tumour, including that older patients are more likely to have malignant tumours, malignant behaviour has not been reported before puberty, and that gynecomastia is more common with benign cases. Malignant behaviour also correlates with a number of pathologic features, including larger tumours (>5cm), high mitotic rate (>3-5 mitotic figures per 10 hpf), atypical mitotic figures, vascular space invasion, significant nuclear atypia, necrosis, infiltrative borders, invasion of the rete testis or beyond, DNA aneuploidy, high proliferative activity (>5%) as assessed by staining the the MIB-1 antibody, and increased expression of p53 protein by the tumour cells. None of these features, however, is pathognomonic of malignancy, and some non-metastasizing tumours may have a limited number of them.

Radiation and chemotherapy are not effective in the treatment of malignant Leydig cell tumour. Tetroperitoneal lymphadenectomy may be performed in patients with testicular sex cord-stromal tumours with malignant features, but the therapeutic role of this intervention remains unclear. Mean survival of patients with malignant Leydig cell tumour is about 4 years, but some may develop metastases I more than 10 years after orchiectomy.