Leydig Cell Tumors Workup

  • Author: Edmund S Sabanegh Jr, MD; Chief Editor: Edward David Kim, MD, FACS   more...
 
Updated: Nov 28, 2011
 

Laboratory Studies

  • Laboratory studies in Leydig cell tumors are usually nonspecific.
  • Levels of testicular tumor markers such as serum alpha-fetoprotein (AFP), beta human chorionic gonadotropin (beta-HCG), and lactate dehydrogenase (LDH) should be within the reference range in pure Leydig cell tumors.
  • The steroid secretion of Leydig cell tumors varies. Serum testosterone levels are usually elevated; however, serum estradiol levels may also be increased, especially when feminization is evident.
  • Urine and serum endocrinological tests such as urine ketosteroids, plasma cortisol, or the dexamethasone suppression test may help differentiate Leydig cell tumors from other adrenocortical disorders.
  • Leydig cell tumor endocrine function is independent of the hypothalamus-pituitary-gonadal hormonal axis and should not demonstrate a response to adrenocorticotropic hormone stimulation or dexamethasone suppression.
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Imaging Studies

  • Scrotal ultrasonography is typically performed to confirm the diagnosis, especially in patients in whom the physical examination findings are equivocal.[2, 3]
  • MRI can reveal small nonpalpable Leydig cell tumors not otherwise visible on sonograms.
  • CT scanning of the abdomen and chest radiography are indicated if malignancy is suspected.
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Histologic Findings

Macroscopically, Leydig cell tumors present as well-circumscribed, yellow to brown masses within the testicle.

Microscopically, these tumors are composed of large, closely packed cells with eosinophilic cytoplasm, bland nuclei, and small nucleoli (see image below). Reinke crystals are pale-staining, cylindrical, rectangular, or rhomboid inclusions that are pathognomonic for Leydig cell tumors and are found in up to 30% of patients with such tumors. Microscopic features such as necrosis, marked pleomorphism, lymphovascular invasion, increased mitotic activity, and DNA aneuploidy are more consistent with a malignant variant.[4]

Leydig cell tumors. Leydig cell tumors.

Immunohistochemical markers such as alpha-inhibin,[5] calretinin,[6] and melan-A have also been shown to be valuable in the identification of Leydig cell and other sex cord-stromal testicular tumors.

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Contributor Information and Disclosures
Author

Edmund S Sabanegh Jr, MD  Chairman, Department of Urology, 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.

Specialty Editor Board

Erik T Goluboff, MD  Professor, Department of Urology, College of Physicians and Surgeons, Columbia University College of Physicians and Surgeons; 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.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Dan Theodorescu, MD, PhD  Paul A Bunn Professor of Cancer Research, Professor of Surgery and Pharmacology, Director, University of Colorado Comprehensive Cancer 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: Key Genomics Ownership interest Co-Founder-50% Stock Ownership; KromaTiD, Inc Stock Options Board membership

J Stuart Wolf Jr, MD, FACS  The David A Bloom Professor of Urology, Director, Division of Endourology and Stone Disease, Department of Urology, University of Michigan Medical School

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: Nothing to disclose.

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, Sexual Medicine Society of North America, and Tennessee Medical Association

Disclosure: Lilly Consulting fee Advisor; Astellas Consulting fee Speaking and teaching; Watson Consulting fee Speaking and teaching; Allergan Consulting fee Speaking and teaching

References

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  2. Leonhartsberger N, Ramoner R, Aigner F, Stoehr B, Pichler R, Zangerl F, et al. Increased incidence of Leydig cell tumours of the testis in the era of improved imaging techniques. BJU Int. Nov 2011;108(10):1603-7. [Medline].

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  5. 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].

  6. 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].

  7. 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].

  8. 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].

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  16. 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].

  17. 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].

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  20. 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].

  21. 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].

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