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Leydig Cell Tumor of the Testis
Pathology Page
Leydig Cell Tumor of the Testis GERM cell tumors and sex cord stromal tumors constitute the 2 predominant groups of primary testicular neoplasms. Leydig cell tumors are sex cord stromal tumors that arise from Leydig cells, which occupy the testicular interstitium between the seminiferous tubules and produce testosterone in response to stimulation by luteinizing hormone. Leydig cell tumors comprise 1% to 3% of all testicular neoplasms.1–3 Although rare, they are the most common interstitial neoplasm of the testis. Leydig cell tumors may occur at any age but demonstrate a bimodal distribution, affecting prepubertal boys between 5 and 10 and men between 30 and 60 years old.1–3 These tumors are frequently hormonally active and produce androgen (mainly testosterone) or, less frequently, estrogen directly or by peripheral conversion of testosterone.2 Hormone production often results in striking clinical manifestations. In boys with Leydig cell tumor isosexual precocious puberty is more common than feminization, and it is manifested by penile and pubic hair growth, advanced musculoskeletal growth, skin changes and increased 17-ketosteroid levels. Androgen secretion by Leydig cell tumors in adult males generally is unnoticeable. Gynecomastia is the most common presentation of estrogen secreting tumors, and it is accompanied by feminine hair distribution and gonadogenital underdevelopment in boys, and by reduced libido, erectile dysfunction and infertility in men. A painless intratesticular
Figure 1. Leydig cells form sharply circumscribed yellow-brown tumor.
0022-5347/09/1815-2299/0 THE JOURNAL OF UROLOGY® Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION
Figure 2. Sheets of eosinophilic tumor cells with uniform nuclei and indistinct cell borders. Inset, Reinke’s crystals.
mass is typically palpable, although ultrasound identification is sometimes necessary. Leydig cell tumors are usually unilateral and rarely bilateral, solid, 3 to 5 cm in diameter and generally confined to the testis.2,3 The tumors are sharply circumscribed and are most often yellow or yellow-tan but may be white, gray, golden brown or green-brown (fig. 1). Features that raise concern for malignancy include large size (diameter greater than 5 cm), complete testicular ablation by tumor, hemorrhage, necrosis and tumor extension into the lymphovascular spaces or adjacent soft tissues. Histologically most Leydig cell tumors are composed of cells resembling normal Leydig cells with abundant slightly granular eosinophilic cytoplasm, indistinct cell borders and uniform round or oval nuclei with prominent nucleoli (fig. 2).2,3 Tumor cells may also exhibit distinct cell borders, smaller size with scant dense cytoplasm and grooved nuclei or spindled (sarcomatoid) morphology. Leydig cell tumors typically grow in diffuse sheets. Less often the tumor cells form large nodules and are arranged to form small nests, trabeculae, pseudotubules or ribbon-like structures. The background stroma may be hyalinized, edematous or myxoid. Vol. 181, 2299-2300, May 2009 Printed in U.S.A. DOI:10.1016/j.juro.2009.02.051
www.jurology.com
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PATHOLOGY PAGE
Tumor cells may contain lipid and quite often exhibit an abundant golden yellow to brown lipofuscin pigment. Reinke’s crystals are distinctive for Leydig cell tumors and are demonstrable in approximately a third of cases (fig. 2, inset). These crystals may be cylindrical, rectangular or rhomboid, and may be intranuclear or intracytoplasmic. Their significance is unknown. Immunohistochemical stains that help establish a diagnosis of Leydig cell tumor include ␣-inhibin, calretinin and Melan-A. Leydig cell tumors in children do not metastasize and are adequately treated with radical orchiectomy or testis sparing surgery. 1 Approximately 10% of Leydig cell tumors in adults exhibit malignant behavior, metastasizing to retroperitoneal lymph nodes, liver, lungs and bone. Malig-
nant Leydig cell tumors respond poorly to chemotherapy or radiation. Survival of patients with metastases ranges from 2 months to 17 years (median 2 years).2 Paul Jou and Gregory T. MacLennan Department of Pathology Case Western Reserve University University Hospitals of Cleveland Cleveland, Ohio 1. Agarwal PK and Palmer JS: Testicular and paratesticular neoplasms in prepubertal males. J Urol 2006; 176: 875. 2. Al-Agha OM and Axiotis CA: An in-depth look at Leydig cell tumor of the testis. Arch Pathol Lab Med 2007; 131: 311. 3. Young RH: Testicular tumors—some new and a few perennial problems. Arch Pathol Lab Med 2008; 132: 548.
Leydig Cell Tumor of the Testis GERM cell tumors and sex cord stromal tumors constitute the 2 predominant groups of primary testicular neoplasms. Leydig cell tumors are sex cord stromal tumors that arise from Leydig cells, which occupy the testicular interstitium between the seminiferous tubules and produce testosterone in response to stimulation by luteinizing hormone. Leydig cell tumors comprise 1% to 3% of all testicular neoplasms.1–3 Although rare, they are the most common interstitial neoplasm of the testis. Leydig cell tumors may occur at any age but demonstrate a bimodal distribution, affecting prepubertal boys between 5 and 10 and men between 30 and 60 years old.1–3 These tumors are frequently hormonally active and produce androgen (mainly testosterone) or, less frequently, estrogen directly or by peripheral conversion of testosterone.2 Hormone production often results in striking clinical manifestations. In boys with Leydig cell tumor isosexual precocious puberty is more common than feminization, and it is manifested by penile and pubic hair growth, advanced musculoskeletal growth, skin changes and increased 17-ketosteroid levels. Androgen secretion by Leydig cell tumors in adult males generally is unnoticeable. Gynecomastia is the most common presentation of estrogen secreting tumors, and it is accompanied by feminine hair distribution and gonadogenital underdevelopment in boys, and by reduced libido, erectile dysfunction and infertility in men. A painless intratesticular
Figure 1. Leydig cells form sharply circumscribed yellow-brown tumor.
0022-5347/09/1815-2299/0 THE JOURNAL OF UROLOGY® Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION
Figure 2. Sheets of eosinophilic tumor cells with uniform nuclei and indistinct cell borders. Inset, Reinke’s crystals.
mass is typically palpable, although ultrasound identification is sometimes necessary. Leydig cell tumors are usually unilateral and rarely bilateral, solid, 3 to 5 cm in diameter and generally confined to the testis.2,3 The tumors are sharply circumscribed and are most often yellow or yellow-tan but may be white, gray, golden brown or green-brown (fig. 1). Features that raise concern for malignancy include large size (diameter greater than 5 cm), complete testicular ablation by tumor, hemorrhage, necrosis and tumor extension into the lymphovascular spaces or adjacent soft tissues. Histologically most Leydig cell tumors are composed of cells resembling normal Leydig cells with abundant slightly granular eosinophilic cytoplasm, indistinct cell borders and uniform round or oval nuclei with prominent nucleoli (fig. 2).2,3 Tumor cells may also exhibit distinct cell borders, smaller size with scant dense cytoplasm and grooved nuclei or spindled (sarcomatoid) morphology. Leydig cell tumors typically grow in diffuse sheets. Less often the tumor cells form large nodules and are arranged to form small nests, trabeculae, pseudotubules or ribbon-like structures. The background stroma may be hyalinized, edematous or myxoid. Vol. 181, 2299-2300, May 2009 Printed in U.S.A. DOI:10.1016/j.juro.2009.02.051
www.jurology.com
2299
2300
PATHOLOGY PAGE
Tumor cells may contain lipid and quite often exhibit an abundant golden yellow to brown lipofuscin pigment. Reinke’s crystals are distinctive for Leydig cell tumors and are demonstrable in approximately a third of cases (fig. 2, inset). These crystals may be cylindrical, rectangular or rhomboid, and may be intranuclear or intracytoplasmic. Their significance is unknown. Immunohistochemical stains that help establish a diagnosis of Leydig cell tumor include ␣-inhibin, calretinin and Melan-A. Leydig cell tumors in children do not metastasize and are adequately treated with radical orchiectomy or testis sparing surgery. 1 Approximately 10% of Leydig cell tumors in adults exhibit malignant behavior, metastasizing to retroperitoneal lymph nodes, liver, lungs and bone. Malig-
nant Leydig cell tumors respond poorly to chemotherapy or radiation. Survival of patients with metastases ranges from 2 months to 17 years (median 2 years).2 Paul Jou and Gregory T. MacLennan Department of Pathology Case Western Reserve University University Hospitals of Cleveland Cleveland, Ohio 1. Agarwal PK and Palmer JS: Testicular and paratesticular neoplasms in prepubertal males. J Urol 2006; 176: 875. 2. Al-Agha OM and Axiotis CA: An in-depth look at Leydig cell tumor of the testis. Arch Pathol Lab Med 2007; 131: 311. 3. Young RH: Testicular tumors—some new and a few perennial problems. Arch Pathol Lab Med 2008; 132: 548.