Laboratory Studies

Laboratory study results in patients with 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.

Imaging Studies

Scrotal ultrasonography is typically performed to confirm the diagnosis, especially in patients in whom the physical examination findings are equivocal.^{[4, 5]}On color Doppler ultrasonography (CDUS), a typical Leydig cell tumor appears as a round, infracentimeter hyperechoic mass with a clear delineation from the surroundings; lobulated margins are seen in up to 50% of cases.^[16]

MRI can reveal small nonpalpable Leydig cell tumors not otherwise visible on sonograms. On T1-weighed imaging, the tumors are not visible before administration of contrast agents, since they have similar signal intensity as normal testicular parenchyma. They appear with marked enhancement after intravenous injection of contrast material. Other testicular tumors do not show a similar pattern of enhancement.^[17]

CT scanning of the abdomen and chest radiography are indicated if malignancy is suspected.

Contrast-enhanced ultrasound (CEUS) is a possible future imaging technique for Leydig cell tumors. CEUS demonstrates hypervascularization in these cases. In CEUS, Leydig cell tumor is suggested by findings of a short filling time or by a circumferential vessel with rapid centripetal filling.^[18]

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.^[2]Microscopic features such as necrosis, marked pleomorphism, lymphovascular invasion, increased mitotic activity, and DNA aneuploidy are more consistent with a malignant variant.^[19]

Leydig cell tumor.

Immunohistochemical markers such as alpha-inhibin,^[20]calretinin,^[11]and melan-A have also been shown to be valuable in the identification of Leydig cell and other sex cord–stromal testicular tumors. Alpha-inhibin is expressed in all Leydig cell tumors and calretinin is useful in distinguishing Leydig cell tumors from Sertoli cell tumors.^[15]

Treatment & Management

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Lock G, Schmidt C, Helmich F, Stolle E, Dieckmann KP. Early experience with contrast-enhanced ultrasound in the diagnosis of testicular masses: a feasibility study. Urology. 2011 May. 77(5):1049-53. [QxMD MEDLINE Link].
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Carmignani L, Colombo R, Gadda F, Galasso G, Lania A, Palou J, et al. Conservative surgical therapy for leydig cell tumor. J Urol. 2007 Aug. 178(2):507-11; discussion 511. [QxMD MEDLINE Link].
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Stoop H, Kirkels W, Dohle GR, Gillis AJ, den Bakker MA, Biermann K, et al. Diagnosis of testicular carcinoma in situ '(intratubular and microinvasive)' seminoma and embryonal carcinoma using direct enzymatic alkaline phosphatase reactivity on frozen histological sections. Histopathology. 2011 Feb. 58 (3):440-6. [QxMD MEDLINE Link].
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Media Gallery

Leydig cell tumor.

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Author

Thomas Calvert, MD, MPH Resident Physician, Department of Urology, UMass Memorial Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Pamela I Ellsworth, MD Chief, Division of Pediatric Urology, Nemours Children's Hospital; Professor of Urology, University of Central Florida College of Medicine

Pamela I Ellsworth, MD is a member of the following medical societies: American Urological Association, Massachusetts Medical Society, Society for Fetal Urology, Society of Women in Urology

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Edward David Kim, MD, FACS Professor of Urology, Department 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 Society for Reproductive Medicine, American Urological Association, Sexual Medicine Society of North America, Society for Male Reproduction and Urology, Society for the Study of Male Reproduction, Tennessee Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

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 of Andrology, Society of Reproductive Surgeons, Society for the Study of Male Reproduction, American Society for Reproductive Medicine, American Urological Association, SWOG

Disclosure: Nothing to disclose.

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, Society for Basic Urologic Research

Disclosure: Nothing to disclose.

Anil A Thomas, MD Urologist, Department of Urology, Sunnybrook Medical Office,Kaiser Permanente

Anil A Thomas, MD is a member of the following medical societies: American Urological Association, Endourological Society, Society of Robotic Surgery

Disclosure: Nothing to disclose.

Acknowledgements

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.

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

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