Final Diagnosis -- Leydig cell tumor



Leydig cell tumors are rare tumors that comprise 1-3% of all testicular neoplasms (1). These tumors are most commonly observed in adults aged 30-60 years but may occur in infants and prepubertal children (approximately 20% of cases). Adults with Leydig cell tumors typically present with testicular swelling, but decreased libido (20%) and gynecomastia (15-30%) are also common symptoms (1-3). Pseudoprecocity is usually seen in children. Most Leydig cell tumors are unilateral and only 3% are bilateral (2). The tumor is well-circumscribed, occasionally encapsulated and usually 3-5 cm in diameter. The cut surface is homogeneously yellow to light brown. Foci of hemorrhage or necrosis are present in 25% of the cases, and extraparenchymal extension can be seen in 10-15 % of cases (2, 4). The most common histologic pattern of growth is sheets of tumor cells without appreciable stroma. Other growth patterns include small clusters, trabeculae, tubular, and pseudofollicular with variable amount of fibrous or occasionally myxoid stroma. The tumor cells are large and polygonal with abundant, eosinophilic cytoplasm and distinct cell borders. The nuclei are round or oval with a prominent nucleolus. Mitoses are generally rare. Crystalloids of Reinke were identified in 35% of the tumors, and lipofuscin pigment in 10-15%.

The majority of Leydig cell tumors are benign, but approximately 10 % of cases are malignant and can metastasize. Metastatic disease frequently involves the lymph nodes (70%), especially the retroperitoneal and inguinal nodes. Other metastatic sites are liver (45%), lungs (40%), and bone (25%) (5). Although there is no single histologic criterion to define malignant Leydig cell tumors, malignant tumors are usually larger than benign tumors (>5cm) and show nuclear atypia, increased mitotic figures, infiltrative margin, angiolymphatic invasion, necrosis, DNA aneuploidy, and increased MIB-1 proliferative activity (4,6).

Immnohistochemically, the tumor cells are positive for inhibin, calretinin, vimentin in more than 90 % of the cases (7-9). The stains for Melan A and synaptophysin are also positive in 70-90 % of cases (10). AFP is negative and cytokeratins are negative or weak. The differential diagnosis includes Leydig cell hyperplasia (multifocal, not expansile growth pattern), testicular "tumors" of adrenogenital syndrome (clinical history, bilaterality, decrease in size after corticosteroid therapy), and malakoplakia (1, 2, 11). The differential diagnosis would also include malignant melanoma, malignant lymphoma, and metastatic carcinoma.

Radical orchiectomy is the treatment of choice for all solid testicular masses. A retroperitoneal lymph node dissection is recommended if the tumor is malignant. Survival from the initial diagnosis of malignant Leydig cell tumor ranges from 2 months to 17 years (median 2 years) (5).

The case presented here represents a 0.8 cm testicular Leydig cell tumor in a 71 year old man. The tumor is limited to the left testis and had no histologic features suggestive of malignancy. The tumor cells are morphologically and immunohistochemically typical for a Leydig cell tumor.


  1. Sesterhenn et al: Sex cord / gonadal stroma tumours. In: Eble JN, Sauter G, Epstein J, Sesterhenn I eds.: Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon, France: IARC Press, 2004. World Health Organization Classification of Tumours, pp 250-1.
  2. Ulbright TM, Amin MB, Young RH. Atlas of tumor pathology. Tumors of the testis, adnexa, spermatic cord, and scrotum, 3rd series, Fascicle 25. Washington, DC: AFIP, 1999; pp 211-9.
  3. Mellor SG, McCutchan JD. Gynaecomastia and occult Leydig cell tumour of the testis. Br J Urol. 634:420-2, 1989.
  4. 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. 9:177-92, 1985.
  5. Bertram KA, Bratloff B, Hodges GF, Davidson H. Treatment of malignant Leydig cell tumor. Cancer. 68:2324-9, 1991.
  6. Cheville JC, Sebo TJ, Lager DJ, Bostwick DG, Farrow GM. Leydig cell tumor of the testis: a clinicopathologic, DNA content, and MIB-1 comparison of nonmetastasizing and metastasizing tumors. Am J Surg Pathol. 22:1361-7, 1998.
  7. McCluggage WG, Shanks JH, Whiteside C, Maxwell P, Banerjee SS, Biggart JD. Immunohistochemical study of testicular sex cord-stromal tumors, including staining with anti-inhibin antibody. Am J Surg Pathol. 22:615-9, 1998.
  8. 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. 10:159-62, 2002.
  9. Gordon MD, Corless C, Renshaw AA, Beckstead J. CD99, keratin, and vimentin staining of sex cord-stromal tumors, normal ovary, and testis. Mod Pathol. 11:769-73, 1998.
  10. Ramos-Vara JA, Beissenherz ME, Miller MA, Johnson GC, Kreeger JM, Pace LW, Turk JR, Turnquist SE, Watson GL, Yamini B. Immunoreactivity of A103, an antibody to Melan A, in canine steroid-producing tissues and their tumors. J Vet Diagn Invest. 13:328-32, 2001.
  11. Mangini J, Olson PR. Pathologic quiz case: a testicular mass in a 19-year-old man. Arch Pathol Lab Med. 124:785-6, 2000.

Contributed by Eizaburo Sasatomi MD, PhD and Rafael Medina-Flores MD

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