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 [1] [2] [3]. 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 [1] [3] [4]. The tumor is diagnosed in two age groups - in prepubertal boys, and more commonly, in adults between 30-60 years of age [1] [3] [5] [6]. In children, excess testosterone results in the development of precocious puberty - the early growth of pubic hair, the penis and the musculoskeletal system [1] [4]. On the other hand, increased estrogen production will induce feminization (gynecomastia and tenderness of the breasts, as well as feminine hair distribution) [1]. 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 [1] [4]. 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 [1] [2] [4]. 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 [1] [5] [6]. Thus, signs and symptoms that indicate a disbalance in androgen hormones should alert the physician to conduct a meticulous workup.

• Precocious Puberty

  We report two boys who developed true precocious puberty after surgical treatment of a Leydig cell tumor of the testis that presented peripheral precocious puberty. [journal.frontiersin.org]

  In children, excess testosterone results in the development of precocious puberty - the early growth of pubic hair, the penis and the musculoskeletal system. [symptoma.com]

  Clinical presentation is testicular mass, pain and hormone alteration such as precocious puberty and gynecomastia. We present one case of LCT and his conservative management after an incidental finding. Literature is reviewed. [ncbi.nlm.nih.gov]

• Weight Loss

  Therefore has been indicated to the patient the weight loss in the hope that he will return to normal levels of estradiol and gynecomastia will disappear. [bmcresnotes.biomedcentral.com]

• Abdominal Pain

  CASE PRESENTATION: A 12 year old girl referred acute abdominal pain with no other clinical manifestations. An abdominal ultrasound showed a semisolid mass suggestive of ovarian tumor. The diagnosis was confirmed by a computed tomography. [ncbi.nlm.nih.gov]

  Other symptoms that a patient may experience are abdominal pain and swelling. Diagnosis and Staging Ovarian tumors are diagnosed by a physician during a pelvic exam or other physical examination. [knowcancer.com]

  Clinical description Malignant SCST of ovary may occur at any age but usually occurs in child bearing or post menopausal age groups, presenting with manifestations of mass effect (abdominal pain or distention, gastrointestinal symptoms, or abdominal mass [orpha.net]

• Pelvic Mass

  Abdomino-pelvic computed tomography revealed a hypodense pelvic mass without enhancement, suggesting a leiomyoma of intraligamentary type or sex cord tumor of right ovary with submucosal myoma of uterus. [ncbi.nlm.nih.gov]

  SLCTs are rare hormone producing tumors that must be considered when a young woman presents with virilizing manifestations and a pelvic mass. [ccij-online.org]

  Case report A 13-year-old female presented to the Shandong Provincial Hospital affiliated to Shandong University (Jinan, Shandong, China) with a 7-day history of abdominal distension, a 3-day history of abdominal pain and a pelvic mass. [spandidos-publications.com]

• Hirsutism

  While rare and difficult to diagnose, androgen secreting tumors should be suspected in women with hyperandrogenism and hirsutism, especially in the postmenopausal population. [ncbi.nlm.nih.gov]

• Alopecia

  A 60-year-old woman, presented with increased hair growth and androgenic alopecia and the hormonal laboratory examination showed that she had elevated serum testosterone level and normal dehydroepiandrosterone sulfate (DHEAS), androstenedione, 17- hydroxyprogesterone [ncbi.nlm.nih.gov]

  Her family referred to the rapid onset of virilization, with hirsutism, androgenetic alopecia, and deep voice, starting one year before. [scielo.br]

  […] primates), 012150, human, 女性, ｼﾞｮｾｲ(ｵﾝﾅ), woman, 017049, ｼﾞｮｾｲ, 成人, ｾｲｼﾞﾝ, adult(person), 017082, adult, 症例報告, ｼｮｳﾚｲﾎｳｺｸ, case report, 054676, NMRイメージング, NMRｲﾒｰｼﾞﾝｸﾞ, NMR imaging, 047139, 腹腔鏡下手術, ﾌｸｸｳｷｮｳｶｼｭｼﾞｭﾂ, laparoscopic surgery, 060806, 脱毛症, ﾀﾞﾂﾓｳｼｮｳ, alopecia [togodb.biosciencedbc.jp]

• Confusion

  Misinterpretation of symptoms, conflicting medical information and advice from previous doctors had confused the patient. [ncbi.nlm.nih.gov]

  Interstitial cell tumour should not be confused with renomedullary interstitial cell tumour. General Arises from the interstitial cell. May be associated with increased testosterone. [librepathology.org]

  It was also emphasized by Young and Scully that presence of retiform pattern often poses difficult diagnostic problems in about 10% of SLCTs and they are confused for endodermal sinus tumor or serous cystadeno carcinomas on histological grounds. [5] The [indianjcancer.com]

  […] crystals; patchy staining for MelanA and CD10, more diffuse S100 beta; unlike Leydig cell tumor ( Pathol Int 2005;55:366 ) Malakoplakia : Michaelis Guttman bodies, prominent intratubular involvement Nelson syndrome ( Urol Int 1996;56:200 ) Seminoma : confused [pathologyoutlines.com]

  Conclusion Poorly differentiated SLCT can be confused with many other tumors of the ovary. The diagnosis is especially important from therapeutic point of view. References 1. Young RH. [ccij-online.org]

• Testicular Mass

  Hereby, we present the case of two brothers affected by 11-β hydroxylase deficiency and presenting with bilateral testicular masses. [ncbi.nlm.nih.gov]

  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. [symptoma.com]

• Clitoromegaly

  These tumors usually present virilizing symptoms such as oligomenorrhea or amenorrhea, hirsutism, voice raucity, laryngeal protuberance and clitoromegaly. [ncbi.nlm.nih.gov]

  Signs and Symptoms (Pathophysiology) Symptoms can include infrequent or no menstrual periods, the development of facial hair, a hoarse voice, increased muscle mass, acne, and clitoromegaly. [knowcancer.com]

  Her serum AFP levels returned to normal and hirsutism and clitoromegaly regressed. [indianjcancer.com]

  In a woman with signs of virilization, it is essential to perform a careful gynecological examination, to evaluate the presence of adnexal masses or clitoromegaly. [scielo.br]

• Testicular Pain

  In the other patients diagnosis was made by ultrasound performed for testicular pain (4 patients, 16.6%) or the appearance of gynecomastia (3 patients, 12.5%). Frozen section examination was done in 20 of 24 patients (83%). [ncbi.nlm.nih.gov]

  Indications for Leydig Cell Tumor of the Testis include: Loss of libido Overdevelopment of breasts in males (gynecomastia) Breast pain, especially if accompanied by enlargement Trouble breathing Headache Low blood pressure Anemia Testicular pain, lump [dovemed.com]

• Testicular Disease

  Schweyer, Tumoren des Gonadenstromas, Der Pathologe, 2014, 35, 3, 245 CrossRef 11 Giorgio Bozzini, Stefano Picozzi, Dario Ratti, Stefano Casellato, Luca Carmignani, Long-term follow up with sparing surgery for testicular diseases: A safe choice in benign [onlinelibrary.wiley.com]

• Scrotal Mass

  The malignant forms are generally discovered in elder men presenting a scrotal mass with no hormonal changes [1-7]. We describe a small and rare benign Leydig cell tumor found incidentally in an old man. [smirg.org]

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 [6]. 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 [1] [6]. 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 [1] [6]. 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 [1] [3] [4] [6]. In addition to clinical and laboratory studies, imaging procedures, such as ultrasonography (US) of the testes, is the next step in confirming the diagnosis [2] [3] [6]. 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 [1] [2] [3] [4] [6]. A definite diagnosis is made after a biopsy and subsequent histopathological examination with immunohistochemistry [1]. 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 [1].

• Ovarian Mass

  She is disease free two years after the last treatment and 7 years after initial onset of disease. » Discussion This young woman had right ovarian mass followed by mesenteric cyst in ileocecal region and left sided ovarian mass consecutively with associated [indianjcancer.com]

  The diagnosis is suspected on the basis of an ovarian mass on examination and further investigation and should be proven by biopsy. [ncbi.nlm.nih.gov]

  At abdominal examination, huge ovarian mass of variegated consistency was palpable occupying right iliac fossa, hypogastrium and upto umbilicus. It was approximately 20X15 cm. There was free fluid in the abdomen. Mass was tender on deep palpation. [npplweb.com]

  Pelvic ultrasonographic findings were normal in first patient and there was 1×1 right ovarian mass in USG in second patient. Magnetic resonance (MR) imaging of the abdomen and pelvis were performed, which demonstrated normal adrenal glands in both. [endocrine-abstracts.org]

  Management of ovarian masses. AAGL 1990 survey. J. Reprod. Med. 37, 599–602 (1992). 27. Fanfani, F. et al. A prospective randomized study of laparoscopy and minilaparotomy in the management of benign adnexal masses. Hum. [nature.com]

We report on the--to our knowledge--first treatment experiment with imatinib in a patient with metastatic Leydig cell tumor. Unfortunately, the tumor progressed during treatment. [ncbi.nlm.nih.gov]

Treatment Surgical removal of the affected ovary is the most common treatment -- and usually all the treatment that is necessary. That's because more than 75% of these tumors are found early (grade I) and in only one ovary. [ovariancancer.about.com]

Abstract Malignant Testicular Leydig Cell tumors (leydigomas) are extremely rare to occur and mostly carry a bad prognosis. [ncbi.nlm.nih.gov]

Typically, in a vast majority of cases, the prognosis is excellent, since it is usually a benign tumor In rare case of a malignancy, the prognosis may depend upon several factors including the stage of the tumor and health status of the individual Generally [dovemed.com]

Outlook (Prognosis) Prognosis of SLCT depends on the stage and degree of differentiation of the tumor. Since these tumors are typically benign and their growth is slow, outlook is generally very positive. [knowcancer.com]

It is recommended that all endocrine, nutritional, neoplastic, chromosomal, and drug etiologies of gynecomastia be investigated before surgical resection of the enlarged breasts. [popline.org]

Etiology Mutations in the DICER1 (14q32.13) gene have been found to be a susceptibility factor for SCST, particularly in malignant Sertoli-Leydig cell tumor of ovary. [orpha.net]

(Etiology) The cause of Leydig Cell Tumor of the Testis is unknown. [dovemed.com]

[…] are malignant Sites Origin from testis is demonstrable in most cases Rarely originates from epididymis ( Andrologia 2013;45:430 ) Pathophysiology Produce testosterone, dehydroepiandrosterone and androstenedione, which cause symptoms described below Etiology [pathologyoutlines.com]

Leydig Cell Tumors Epidemiology & Pathology Leydig cell tumors are the most common non-germ cell tumors of the testis and account for 1-3% of all testicular tumors. [health.am]

Epidemiology 1–3% of all testicular tumors. Most common in boys (5–10 years old) and in adults aged 30–60 years. Pathology of the Leydig cell tumor Small yellow-brown tumors, sharply circumscribed in the testicular tissue. [urology-textbook.com]

Summary Epidemiology Age related incidence rate was found to be 1 per 500,000 women. Sex cord stromal tumors constitute about 5% of ovarian malignancies. [orpha.net]

Epidemiology Leydig cell tumours constitute 1-3% of all testicular tumours. Clinical features In children, they may present with isosexual pseudoprecocity. In adults, they present with a mass and/or gynaecomastia. [e-immunohistochemistry.info]

Definition / general Most common sex cord stromal tumor; recapitulates normal development and evolution of Leydig cells Epidemiology 1 - 3% of testicular tumors No predilection based on ethnicity or race ~10% are malignant Sites Origin from testis is [pathologyoutlines.com]

Signs and Symptoms (Pathophysiology) Symptoms can include infrequent or no menstrual periods, the development of facial hair, a hoarse voice, increased muscle mass, acne, and clitoromegaly. [knowcancer.com]

[…] and evolution of Leydig cells Epidemiology 1 - 3% of testicular tumors No predilection based on ethnicity or race ~10% are malignant Sites Origin from testis is demonstrable in most cases Rarely originates from epididymis ( Andrologia 2013;45:430 ) Pathophysiology [pathologyoutlines.com]

^ a b "Leydig Cell Tumors: Practice Essentials, Background, Pathophysiology". 2016-10-27. ^ Biegel, L. B.; Liu, R. C.; Hurtt, M. E.; Cook, J. C. (1995). [en.wikipedia.org]

Background Pathophysiology A 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 [emedicine.medscape.com]

Pathologists have to be familiar with the diagnostic histopathologic features, immunohistochemical panel of this tumor, and its principal differential diagnoses to prevent tumor misdiagnosis. [ncbi.nlm.nih.gov]

[…] the adrenogenital syndrome (which may contain fat) and may prevent misdiagnosis of a LCT with spindle cells as a sarcoma or unclassified sex cord-stromal tumor. [journals.lww.com]

A long term follow-up is needed to prevent possible late relapse. © 2008 Sociedad Española de Andrología. [mendeley.com]

Removal of the testis Debulking surgery to reduce tumor size, followed by chemotherapy Clotting the vessels in the tumor (embolization) Chemotherapy Radiotherapy Undertaking treatment of underlying conditions How can Leydig Cell Tumor of the Testis be Prevented [dovemed.com]

1. Al-Agha OM, Axiotis CA. An in-depth look at Leydig cell tumor of the testis. Arch Pathol Lab Med. 2007;131(2):311-317.
2. Gheorghisan-Galateanu AA. Leydig cell tumors of the testis: a case report. BMC Res Notes. 2014;7:656.
3. Suardi N, Strada E, Colombo R, et al. Leydig cell tumor of the testis: presentation, therapy, long-term follow-up and the role of organ-sparing surgery in a single-institution experience. BJU Int. 2009;103(2):197-200.
4. Albers P, Albrecht W, Algaba F, et al. Guidelines on Testicular Cancer: 2015 Update. Eur Urol. 2015;68(6):1054-1068.
5. Thambi R, Pothen L, Emmanuel KM, Vijayalakhmi A. Leydig cell tumor of testis with indeterminate features. Indian J Cancer. 2015;52(4):529-530.
6. Sönmez N, Ton Ö, Arısan S, Kılınç F, Eken K, Güney S. Bilateral Leydig cell tumor of the testis: a case report. Contemp Oncol (Pozn). 2012;16(4):356-359.