eMedicine Specialties > Urology > Cancer, Testicle

Leydig Cell Tumors

Author: Edmund S Sabanegh Jr, MD, Director, Center for Male Fertility, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation
Coauthor(s): Anil A Thomas, MD, Urology Resident, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation; Scott Rutchik, MD, Assistant Professor, Department of Surgery, Division of Urology, University of Connecticut School of Medicine
Contributor Information and Disclosures

Updated: Jun 11, 2008

Introduction

Background

Leydig cell tumors are rare testicular tumors of the male gonadal interstitium. They are frequently hormonally active, leading to feminizing or virilizing syndromes.

Although uncommon, Leydig cell tumors comprise 1-3% of all testicular neoplasms. These tumors can be pure or can be mixed with other sex cord-stromal or germ cell tumors. Leydig cell tumors are usually benign, but malignant variants also occur.

Leydig cell tumors were once managed primarily with radical orchiectomy. However, the experience with conservative approaches has been growing, and enucleation has been used increasingly in both the adult and pediatric populations.1

Pathophysiology

A German anatomist, Franz Leydig, first described Leydig cells in 1870. 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. 

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.

Frequency

United States

Leydig cell testicular neoplasms are the most common sex cord-stromal tumors and comprise 1-3% of all testicular neoplasms. The tumors are most common in prepubertal boys aged 5-10 years and in adults aged 30-60 years. Approximately 10% of Leydig cell tumors are bilateral and 10% are malignant. However, Leydig cell tumors are always benign in children, as malignant variants have been reported only after puberty.

Mortality/Morbidity

Leydig cell tumors are usually benign, but approximately 10% are malignant. The malignant variants occur only in adults.

Sex

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.

Age

Leydig cell tumors may occur in prepubertal boys but are most common in men aged 30-60 years.

Clinical

History

  • In most cases, patients present with an incidental finding of a testicular mass on scrotal ultrasonography during evaluation of hydroceles or varicoceles or during workup of other conditions (eg, infertility).
  • A nontender palpable testicular mass or nodule may be noted.
  • Prepubertal boys with androgen-secreting tumors may present with precocious puberty; features may include prominent external genitalia, pubic hair growth, accelerated skeletal and muscle development, and mature masculine voice.
  • Boys with estrogen-secreting tumors may present with feminizing symptoms such as gynecomastia, breast tenderness, and gonadogenital underdevelopment.
  • Adults with androgen-secreting tumors are generally asymptomatic.
  • In adults with estrogen-secreting tumors, symptoms such as loss of libido, erectile dysfunction, and infertility have be reported.

Physical

  • An intratesticular mass may be palpated.
  • In children, early pubertal and musculoskeletal development may be appreciated.
  • In adults, gynecomastia, feminine hair distribution, and/or gonadogenital atrophy may be observed.

More on Leydig Cell Tumors

Overview: Leydig Cell Tumors
Differential Diagnoses & Workup: Leydig Cell Tumors
Treatment & Medication: Leydig Cell Tumors
Follow-up: Leydig Cell Tumors
Multimedia: Leydig Cell Tumors
References
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References

  1. Henderson CG, Ahmed AA, Sesterhenn I, Belman AB, Rushton HG. Enucleation for prepubertal leydig cell tumor. J Urol. Aug 2006;176(2):703-5. [Medline].

  2. Iczkowski KA, Bostwick DG, Roche PC, Cheville JC. Inhibin A is a sensitive and specific marker for testicular sex cord-stromal tumors. Mod Pathol. Aug 1998;11(8):774-9. [Medline].

  3. Augusto D, Leteurtre E, De La Taille A, Gosselin B, Leroy X. Calretinin: a valuable marker of normal and neoplastic Leydig cells of the testis. Appl Immunohistochem Mol Morphol. Jun 2002;10(2):159-62. [Medline].

  4. Basciani S, Brama M, Mariani S, De Luca G, Arizzi M, Vesci L, et al. Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity. Cancer Res. Mar 1 2005;65(5):1897-903. [Medline].

  5. Froehner M, Beuthien-Baumann B, Dittert DD, Schuler U, Wirth MP. Lack of efficacy of imatinib in a patient with metastatic Leydig cell tumor. Cancer Chemother Pharmacol. Nov 2006;58(5):716-8. [Medline].

  6. Al-Agha OM, Axiotis CA. An in-depth look at Leydig cell tumor of the testis. Arch Pathol Lab Med. Feb 2007;131(2):311-7. [Medline].

  7. Bertram KA, Bratloff B, Hodges GF, Davidson H. Treatment of malignant Leydig cell tumor. Cancer. Nov 15 1991;68(10):2324-9. [Medline].

  8. Brunner HG, Otten BJ. Precocious puberty in boys. N Engl J Med. Dec 2 1999;341(23):1763-5. [Medline].

  9. Carmignani L, Colombo R, Gadda F, Galasso G, Lania A, Palou J, et al. Conservative surgical therapy for leydig cell tumor. J Urol. Aug 2007;178(2):507-11; discussion 511. [Medline].

  10. Cheville JC. Classification and pathology of testicular germ cell and sex cord-stromal tumors. Urol Clin North Am. Aug 1999;26(3):595-609. [Medline].

  11. Dilworth JP, Farrow GM, Oesterling JE. Non-germ cell tumors of testis. Urology. May 1991;37(5):399-417. [Medline].

  12. Grem JL, Robins HI, Wilson KS, Gilchrist K, Trump DL. Metastatic Leydig cell tumor of the testis. Report of three cases and review of the literature. Cancer. Nov 1 1986;58(9):2116-9. [Medline].

  13. Holm M, Rajpert-De Meyts E, Andersson AM, Skakkebaek NE. Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio. J Pathol. Mar 2003;199(3):378-86. [Medline].

  14. Kaufman E, Akiya F, Foucar E, Grambort F, Cartwright KC. Viralization due to Leydig cell tumor diagnosis by magnetic resonance imaging. Case management report. Clin Pediatr (Phila). Jul 1990;29(7):414-7. [Medline].

  15. Kim I, Young RH, Scully RE. Leydig cell tumors of the testis. A clinicopathological analysis of 40 cases and review of the literature. Am J Surg Pathol. Mar 1985;9(3):177-92. [Medline].

  16. Konrad D, Schoenle EJ. Ten-year follow-up in a boy with Leydig cell tumor after selective surgery. Horm Res. 1999;51(2):96-100. [Medline].

  17. Maeda T, Itoh N, Kobayashi K, et al. Elevated serum estradiol suggesting recurrence of Leydig cell tumor nine years after radical orchiectomy. Int J Urol. Nov 2002;9(11):659-61. [Medline].

  18. Mineur P, De Cooman S, Hustin J, Verhoeven G, De Hertogh R. Feminizing testicular Leydig cell tumor: hormonal profile before and after unilateral orchidectomy. J Clin Endocrinol Metab. Apr 1987;64(4):686-91. [Medline].

  19. Ober WB, Sciagura C. Leydig, Sertoli, and Reinke: three anatomists who were on the ball. Pathol Annu. 1981;16 Pt 1:1-13. [Medline].

  20. Testis-sparing surgery for benign testicular tumors in children. J Urol. Jun 2001;165(6 Pt 2):2280-3. [Medline].

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Further Reading

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Keywords

Leydig cell tumor, stromal testis tumor, interstitial testis tumor, interstitial testicular tumor, precocious puberty, androgenizing tumors, feminizing syndrome, virilizing syndrome, testicular neoplasms

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Contributor Information and Disclosures

Author

Edmund S Sabanegh Jr, MD, Director, Center for Male Fertility, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation
Edmund S Sabanegh Jr, MD is a member of the following medical societies: American Medical Association, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association, Society for the Study of Male Reproduction, Society of Reproductive Surgeons, and Southwest Oncology Group
Disclosure: Nothing to disclose.

Coauthor(s)

Anil A Thomas, MD, Urology Resident, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation
Anil A Thomas, MD is a member of the following medical societies: American Urological Association and Endourological Society
Disclosure: Nothing to disclose.

Scott Rutchik, MD, Assistant Professor, Department of Surgery, Division of Urology, University of Connecticut School of Medicine
Scott Rutchik, MD is a member of the following medical societies: American Urological Association
Disclosure: Nothing to disclose.

Medical Editor

Erik T Goluboff, MD, Professor, Department of Urology, College of Physicians and Surgeons, Columbia University; Director of Urology, Allen Pavilion, New York Presbyterian Hospital
Erik T Goluboff, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Urological Association, Medical Society of the State of New York, New York Academy of Medicine, Phi Beta Kappa, and Society for Basic Urologic Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Dan Theodorescu, MD, PhD, Paul Mellon Professor of Urologic Oncology, Department of Urology, University of Virginia Health Sciences Center
Dan Theodorescu, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Urological Association, Medical Society of Virginia, Society for Basic Urologic Research, and Society of Urologic Oncology
Disclosure: Nothing to disclose.

CME Editor

J Stuart Wolf Jr, MD, FACS, David A Bloom Professor of Urology, Director of Division of Minimally Invasive Urology, Department of Urology, University of Michigan
J Stuart Wolf Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, Society of University Urologists, and Society of Urologic Oncology
Disclosure: Terumo Corporation Consulting fee Consulting; Gyrus-ACMI Honoraria Speaking and teaching

Chief Editor

Edward David Kim, MD, FACS, Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center
Edward David Kim, MD, FACS is a member of the following medical societies: American College of Surgeons, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association, and Tennessee Medical Association
Disclosure: Lilly Consulting fee Consulting; Astellas Consulting fee Speaking and teaching; Indevus Consulting fee Speaking and teaching

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