Leydig Cell Tumors

Updated: Sep 18, 2023
  • Author: Thomas Calvert, MD, MPH; Chief Editor: Edward David Kim, MD, FACS  more...
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Practice Essentials

Leydig cell tumors (see the image below) are rare testicular tumors of the gonadal interstitium that may be hormonally active and lead to feminizing or virilizing syndromes. Leydig cell tumors comprise approximately 4% of adult testicular neoplasms [1] and 3% of testicular tumors in infants and children. These tumors can be pure or can be mixed with other sex cord–stromal or germ cell tumors. Leydig cell tumors usually have a local presentation; metastases occur in about 2.5% of cases. [1] The most common sites for metastases are lymph nodes, lung, liver, and bones. [2]

Leydig cell tumor. Leydig cell tumor.

As with germ cell tumors, the route of spread is hematogenous and lymphatic to the retroperitoneal lymph nodes. Unlike germ cell tumors, however, Leydig cell tumors show relative lack of sensitivity to radiotherapy and chemotherapy agents. [3]

Signs and symptoms

Clinical manifestations include the following:

  • A nontender palpable testicular mass or nodule
  • Precocious puberty in prepubertal boys with androgen-secreting tumors
  • Feminizing symptoms in boys with estrogen-secreting tumors

Adults with androgen-secreting tumors are generally asymptomatic. Manifestations in adults with estrogen-secreting tumors include the following:

  • Loss of libido
  • Erectile dysfunction
  • Infertility
  • Gynecomastia
  • Feminine hair distribution
  • Gonadogenital atrophy

Leydig cell tumors may be an incidental finding of a testicular mass on scrotal ultrasonography performed for other conditions.

See Presentation for more detail.


Serum testosterone levels are usually elevated; however, serum estradiol levels may also be increased, especially when feminization is evident. Results of the following laboratory studies are normal in patients with pure Leydig cell tumors:

  • Serum alpha-fetoprotein
  • Beta human chorionic gonadotropin
  • Lactate dehydrogenase
  • Urine ketosteroids
  • Plasma cortisol
  • Adrenocorticotropic hormone stimulation test
  • Dexamethasone suppression test

Imaging studies

  • Scrotal ultrasonography: Confirms the diagnosis, especially when physical examination findings are equivocal [4, 5]
  • Magnetic resonance imaging: Can reveal small nonpalpable Leydig cell tumors that are not visible on ultrasound.
  • CT scanning of the abdomen and chest radiography: Indicated if malignancy is suspected

See Workup for more detail.


Radical orchiectomy was once the primary treatment for Leydig cell tumors, and it remains in use for malignant cases. However, prognosis is poor for metastatic disease and there are no standard treatment recommendations.  Although complete or partial remission following chemotherapy has been reported, it has been found ineffective in the majority of cases. [2]

Testis-sparing surgery with enucleation of the mass is increasingly being reported for benign cases, in both the adult and pediatric populations. [6, 7, 8] When Leydig cell tumors are diagnosed and treated early, testicle-sparing surgery has proved to be feasible and safe and could be regarded as first-line therapy.

See Treatment for more detail.



The German anatomist Franz Leydig first described Leydig cells in 1870. [9] Leydig cells are located within the interstitium of the testis, between the seminiferous tubules, and produce testosterone in response to luteinizing hormone. Through their hormonal balance, these cells play an important role in the development of secondary male characteristics and spermatogenesis.

The etiology of Leydig cell tumors remains unknown. Unlike germ cell testicular tumors, Leydig cell neoplasms are not associated with cryptorchidism. It is thought that an endocrine role may contribute to the development of these tumors. For example, an excessive stimulation of Leydig cells with luteinizing hormone due to a disorder of the hypothalamic-pituitary axis may induce their oncogenesis. Animal models have also demonstrated Leydig cell tumorigenesis following long-term estrogen administration. [10]

Although these tumors usually secrete testosterone, the production of estrogen, progesterone, and corticosteroids has also been described. Estrogen excess and feminizing syndromes may occur from the peripheral aromatization of testosterone or from the direct production of estradiol by the tumor itself.




In the United States, Leydig cell testicular neoplasms are the most common sex cord–stromal tumors and comprise 1-3% of all testicular neoplasms. [10] However, a study in Austria demonstrated of all patients that are undergoing surgery for testicular tumor between 1999 and 2008, Leydig cell tumors accounted for 14.7% of all testicular tumors removed. [11] The tumors are most common in prepubertal boys aged 5-10 years and in adults aged 30-60 years. Approximately 2.5% of Leydig cell tumors are metastatic. [1] However, Leydig cell tumors are always benign in children, as malignant variants have been reported only after puberty.

Sex-, race-, and age-related demographics

Leydig cell tumors are most commonly found in males. Nonetheless, these tumors have been well-described in the ovarian stroma of females, who may present with signs and symptoms of virilization. Ovarian Leydig cell tumors are usually malignant, unlike Leydig cell tumors found in males.

African-American race is more common in Sertoli and Leydig cell tumors (23 and 24% respectively), than germ cell tumors (3%). [10]

The incidence of Leydig cell tumors peaks in children 3 to 9 years and in adults 30 to 60 years. [12]



Patients with benign Leydig cell tumors have an excellent prognosis. In contrast, the mean survival in patients with a malignant variant is 2-3 years. Advanced patient age is associated with a poorer prognosis. Pathologic risk factors for occult metastatic disease include the following [13] :

  • Tumor diameter >5 cm
  • Positive margins or rete testis invasion
  • Lymphovascular invasion
  • Cellular atypia
  • Necrosis
  • Increased mitotic rate (≥5 mitoses per high-power field [HPF])

A systematic review of pathologic risk factors found that the risk of occult metastatic disease (OMD) increased with each additional risk factor. Five-year OMD-free survival was 98.1% for patients with fewer than two risk factors vs 44.9% for those with two or more risk factors (P < 0.001). [14]


Patient Education

Patients should be taught to examine their remaining testicle monthly.

For patient education information, see Testicular Cancer and Testicle Self-Exam.