Leydig cell tumor is a rare neoplasm arising from the Leydig cells of the testicular interstitium that produce testosterone. It can develop in children as a benign lesion, or in adults when 10% of cases undergo malignant transformation, in which case prompt recognition is necessary. A testicular mass is almost always present, and further imaging and histopathological findings are used to identify the exact tumor type.
Leydig cell tumors belong to the group of sex cord-stromal tumors of the testes and constitute only 1-3% of all testicular neoplasms, making them a rare occurrence in clinical practice   . Leydig cells are located in the interstitium, and are responsible for the production of testosterone, but also estrogen to a lesser extent, which is why signs and symptoms are often related to the excess effects of androgen hormones caused by abnormal cellular proliferation   . The tumor is diagnosed in two age groups - in prepubertal boys, and more commonly, in adults between 30-60 years of age    . In children, excess testosterone results in the development of precocious puberty - the early growth of pubic hair, the penis and the musculoskeletal system  . On the other hand, increased estrogen production will induce feminization (gynecomastia and tenderness of the breasts, as well as feminine hair distribution) . This clinical presentation is also seen in adults, but they are accompanied by loss of libido, impotence, erectile dysfunction, infertility, and most importantly, an enlarged testicle  . Studies have confirmed the rare appearance of a bilateral testicular mass, but in the vast majority of patients, a unilateral and sometimes painful intratesticular mass is typical for Leydig cell tumors   . It is exclusively benign in infants, but the potential for malignant transformation in adults, seen in 10% of cases, implies that early recognition of the tumor is vital, as dissemination through the retroperitoneal lymph nodes into the liver, the lungs, and the skeletal system has been observed   . Thus, signs and symptoms that indicate a disbalance in androgen hormones should alert the physician to conduct a meticulous workup.
The initial diagnosis of a testicular tumor can be rather easily made with a proper physical examination that will palpate a mass and a detailed patient history that will assess the course and progression of symptoms . However, a mass may not always be present, especially in the beginning of tumorigenesis. For this reason, a detailed laboratory workup is necessary. In all patients in whom signs of excess androgen production are present, serum values of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen, estradiol, progesterone, adrenocorticotropin hormone (ACTH) and cortisol should be evaluated  . Testosterone levels will almost always be raised in the setting of precocious puberty, whereas increased estrogen and estradiol are seen in patients who suffer from feminization and gynecomastia  . It should be noted that tumor markers for testicular tumors, including alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β- hCG), lactate dehydrogenase (LDH) and placental alkaline phosphatase (PALP) are negative, as they are only useful for germ cell testicular tumors    . In addition to clinical and laboratory studies, imaging procedures, such as ultrasonography (US) of the testes, is the next step in confirming the diagnosis   . A homogeneous hypoechoic appearance on US is the hallmark of a benign Leydig cell tumor, but if the lesion is heterogeneous, malignant transformation should be suspected, in which case computed tomography (CT) and magnetic resonance imaging (MRI) of the pelvis and abdomen are recommended to exclude metastatic spread     . A definite diagnosis is made after a biopsy and subsequent histopathological examination with immunohistochemistry . α-Inhibin, but also calretinin and Melan-A are reliable markers for differentiation between sex cord stromal tumors and germ cell tumors of the testes .