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This is a group of rare tumors of the testis derived from the interstitial cells. Sertoli cells, together with the Leydig cells comprise the majority of these cells. These tumors may present with hormonal manifestations.


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Stromal testis tumors in children: a report from the prepubertal testis tumor registry.

Thomas JC, Ross JH, Kay R.

Urological Institute, Section of Pediatric Urology, Cleveland Clinic Foundation, Cleveland, Ohio.

J Urol 2001 Dec;166(6):2338-40 Abstract quote

PURPOSE: Stromal testis tumors are rare and generally exhibit a benign behavior in prepubertal patients. We reviewed the Prepubertal Testis Tumor Registry to elucidate further the behavior of these tumors.

MATERIALS AND METHODS: Epidemiological and clinical information on stromal testis tumors was compiled and reviewed from the Prepubertal Testis Tumor Registry. In addition, original pathology reports were requested for all patients registered as having undifferentiated stromal tumors.

RESULTS: There were 43 patients registered with stromal tumors. Of the 21 patients with unspecified stromal tumors pathology reports were obtained on 11. Eight patients had truly mixed or undifferentiated stromal tumors. Mean patient age at presentation was 38 months (Leydig cell 70, Sertoli cell 52.5, juvenile granulosa cell 1.5 and mixed/undifferentiated 41.2). No patient with a Leydig cell, Sertoli cell or juvenile granulosa cell tumor had metastases at presentation or metastatic disease during an average 24.6 months of followup. One undifferentiated tumor demonstrated malignant behavior by presenting with metastatic disease. Pathological examination revealed a poorly differentiated tumor with extension into the adjacent tunica and frequent mitotic figures. While other stromal tumors displayed mitotic figures, none showed local invasion.

CONCLUSIONS: Stromal testis tumors are rare. Data from the Prepubertal Testis Tumor Registry confirms the benign behavior of most of these tumors. However, undifferentiated stromal tumors may exhibit metastatic behavior. A high index of suspicion is appropriate when there are a large number of mitotic figures, the tumor is poorly differentiated or when local invasion is present in the primary tumor. Metastatic evaluation and close followup are warranted for this select group of patients.



Overexpression of aromatase leads to development of testicular leydig cell tumors : an in vivo model for hormone-mediated TesticularCancer.

Fowler KA, Gill K, Kirma N, Dillehay DL, Tekmal RR.

Department of Gynecology and Obstetrics , Division of Animal Resources, Departments of Pathology and Laboratory Animal Medicine, Emory University School of Medicine, Atlanta, Georgia 30322-4710, USA.

Am J Pathol 2000 Jan;156(1):347-53 ABSTRACT QUOTE

Despite recent advances in diagnosis and treatment of testicular cancer, its causes remain unknown. The most common conditions known to be associated with testicular cancer are cryptorchidism, infertility, and overexposure to pesticides or radiation. Recent studies also indicate hormones may play a crucial role in testicular tumorigenesis.

Our studies show that about half of the male transgenic mice overexpressing aromatase in testis were infertile and/or had larger than normal testicles. Gross pathology and histological analysis showed the mice to have Leydig cell tumors, unilaterally or bilaterally. Serum estradiol levels for transgenic mice were at least twice as high as those for nontransgenic mice. Expression of aromatase and estrogen receptor were also very high in testicular tissue of transgenic mice compared to nontransgenic mice. Consistent with increased estrogenic activity in the testicular tissue, we also saw an increase in the levels of genes involved in cell cycle that are regulated by the estrogen. To obtain a better understanding of the biological significance of testicular tumorigenesis, a reliable animal model is necessary to clarify the mechanisms and correlations associated with human cancers.

Here we describe such a model, which shows that overexpression of aromatase results in increased estrogen production and a changed hormone milieu, leading to the induction of testicular cancer (Leydig cell tumors). This predictable and useful model is a potential tool for the study of testicular tumorigenesis, hormonal carcinogenesis, synergistic action of other carcinogens on hormone-induced tumors, and tumor dependency on endocrine factors.



Leydig cell tumor and metachronous Leydig cell hyperplasia: a case associated with gynecomastia and elevated urinary estrogens.

Castle WN, Richardson JR Jr.

J Urol 1986 Dec;136(6):1307-8 Abstract quote

We report a case of unilateral Leydig cell tumor associated with gynecomastia and elevated urinary estrogens. Nine years after orchiectomy urinary estrogens became elevated and Leydig cell hyperplasia but no distinct tumor was identified in the remaining contralateral testicle.

Malignant Leydig cell tumor of the testis associated with Klinefelter's syndrome.

Soria JC, Durdux C, Chretien Y, Sibony M, Damotte D, Housset M.

Oncology-Radiotherapy Department, Tenon Hospital, Paris, France.

Anticancer Res 1999 Sep-Oct;19(5C):4491-4 ABSTRACT QUOTE

We reported the case of a 35-year-old man with Klinefelter's syndrome and a malignant Leydig cell tumor of the testis.

Bilateral gynecomastia and right testicular enlargement led the patient to seek medical assistance. Despite initial orchidectomy two years later the patient developed lung and iliac lymph node metastases. The tumor appeared to be refractory to chemotherapy and to hormonal treatments including op'DDD. Finally, the patient died within 20 months of developing metastases. Leydig cell tumor is an exceedingly rare tumor, especially when associated with Klinefelter's syndrome.

This association as well as presentation, pathologic features, hormonal abnormalities, clinical course and response to therapy of malignant Leydig cell tumors are discussed.



Leydig cell tumor in a patient with gynecomastia.

Anderson MS, Brogi E, Biller BM.

Neuroendocrine Unit and Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Endocr Pract 2001 Jul-Aug;7(4):267-71 Abstract quote

OBJECTIVE: To report a case of a clinically occult testicular tumor causing gynecomastia and to alert physicians to the importance of use of testicular ultrasonography in patients with progressive gynecomastia despite normal findings on testicular examination.

METHODS: We present a detailed case, including results of clinical, laboratory, and radiologic assessment, of a man with hyperprolactinemia and gynecomastia.

RESULTS: A 36-year-old man with progressive gynecomastia was referred to our clinic because of an increased serum prolactin level. Subsequent clinical investigation revealed no evidence of hypogonadism and several possible causes of the gynecomastia. Because of the patient's age and progressive symptoms, testicular ultrasonography was performed despite normal findings on testicular examination. This ultrasound study showed a right testicular mass, which proved to be a Leydig cell tumor. The patient was referred for definitive therapy with orchiectomy. Follow-up studies showed resolution of the gynecomastia and substantial decreases in prolactin and estradiol levels.

CONCLUSION: Although gynecomastia is a relatively common disorder with a benign cause in most cases, physicians should be aware that normal findings on testicular examination do not completely rule out the possibility of a testicular tumor as the cause. Because of the potentially high morbidity of testicular tumors and their known association with gynecomastia, early performance of testicular ultrasonography in a patient with gynecomastia of unknown cause is advised.


An in-depth look at Leydig cell tumor of the testis.

Department of Pathology, State University of New York Downstate Medical Center, 450 Clarkson Ave, Box 25, Brooklyn, NY 11203, USA.

Arch Pathol Lab Med. 2007 Feb;131(2):311-7. Abstract quote

Leydig cell tumor (LCT) is a rare tumor of the male testicular interstitium. This article provides an overview of the major pathologic manifestations of LCT of the testis; patient characteristics; clinical, radiologic, and laboratory features; prognosis; and management. LCTs of the testis are frequently hormonally active, leading to either feminizing or virilizing syndromes.

The tumor is usually benign, but malignant variants can occur. The pathologic diagnosis of LCT is usually made based on morphologic characteristics of the tumor cells. The significance of Reinke crystals in the diagnosis of LCT both cytologically and histologically is underscored.

Pathologists have to be familiar with the diagnostic histopathologic features, immunohistochemical panel of this tumor, and its principal differential diagnoses to prevent tumor misdiagnosis.

Leydig cell tumors of the testis. A clinicopathological analysis of 40 cases and review of the literature.

Kim I, Young RH, Scully RE.

Am J Surg Pathol 1985 Mar;9(3):177-92 Abstract quote

The clinical and pathological features of 40 Leydig cell tumors of the testis were analyzed.

The patients ranged from 2 to 90 (average 46.5) years of age. The most common initial manifestation was testicular swelling, which was sometimes associated with gynecomastia; 15% of the patients presented because of gynecomastia and were found to have palpable testicular tumors. All three children were brought to the physician because of isosexual pseudoprecocity.

The tumors, one of which was asynchronously bilateral, ranged from 0.5 to 10.0 (average 3) cm in greatest diameter. They were usually well circumscribed, but in seven of them the margin with the adjacent testis was ill-defined.

On microscopic examination the most common pattern was that of diffuse sheets of neoplastic cells, but insular, trabecular, pseudotubular, and ribbon-like patterns were also encountered. The neoplastic cells were most often large and polygonal with abundant eosinophilic, slightly granular cytoplasm; occasionally the cytoplasm was abundantly vacuolated. In eight tumors some of the cells were spindle-shaped, and in six some had scanty cytoplasm. Crystalloids of Reinke were identified in 35% of the tumors. Conspicuous nuclear atypicality was present in 12 tumors and the mitotic rate ranged from less than 1 to 32/10 high-power fields. Blood vessel invasion, lymphatic invasion, or both were identified in four tumors.

Follow-up of 2 months to 22 years (average 4 years) was available for 30 patients. Five of them died as a result of spread of their tumor. A comparison of the clinically malignant tumors with those associated with survival for 2 or more years postoperatively revealed that the former occurred in older patients and were accompanied by symptoms of shorter duration and an absence of endocrine manifestations.

The malignant tumors were larger, often had an infiltrative margin and had spread beyond the testis, frequently exhibited blood vessel or lymphatic invasion, and had a greater degree of cellular atypia and necrosis and a higher mitotic rate than the benign tumors.

Intracytoplasmic and intranuclear Reinke's crystals in a testicular Leydig-cell tumor diagnosed by fine-needle aspiration cytology: a case report with review of the literature.

Jain M, Aiyer HM, Bajaj P, Dhar S.

Department of Pathology, Lady Hardinge Medical College and S.K. Hospital, New Delhi, India.

Diagn Cytopathol 2001 Sep;25(3):162-4 Abstract quote

We report on the cytopathologic findings of a Leydig-cell tumor of the testis in a young adult male with no evidence of endocrine dysfunction.

The preoperative diagnosis was based on fine-needle aspiration cytology (FNAC) alone, which was subsequently confirmed on histopathology. The present case was of interest on account of the paucity of literature regarding the cytodiagnosis of this lesion. In addition, the finding of intracytoplasmic lipofuscin pigment and several intracytoplasmic as well as intranuclear Reinke's crystals served to clinch the diagnosis on FNA.

Therefore, the use of FNAC, especially in the presence of diagnostic Reinke's crystals, may vitiate the need for more invasive biopsy procedures in the preoperative diagnosis of testicular Leydig-cell tumors


Leydig Cell Tumors of the Testis With Unusual Features: Adipose Differentiation, Calcification With Ossification, and Spindle-Shaped Tumor Cells

Thomas M. Ulbright, M.D.; John R. Srigley, M.D.; Dimitris K. Hatzianastassiou, M.D.; Robert H. Young, M.D.

Am J Surg Pathol 2002; 26(11):1424-1433 Abstract quote

We report 19 Leydig cell tumors (LCTs) of the testis with adipose differentiation (n = 12) and/or spindle cell growth (n = 8) in patients 28-70 years of age; three tumors with adipose differentiation showed psammomatous calcifications, two of which also had foci of ossification.

In eight tumors fat-like cells apparently derived from lipid accumulation within neoplastic Leydig cells and appeared as focal to prominent clusters in a background of vacuolated, neoplastic Leydig cells. The fat-like cells were usually immunoreactive for Leydig cell markers (inhibin-a, calretinin, and melan-A) but were typically strongly positive for the adipose tissue marker, S-100 protein, supporting a hybrid cell phenotype. Four tumors had fat of stromal derivation. In two of these there were intermixed mature adipocytes, but in two others only lipoblastic cells were present.

These four tumors lacked vacuolated, neoplastic Leydig cells, and the fat cells in the single case studied were negative for inhibin-a and melan-A but positive for S-100. Three of the 12 LCTs with adipose differentiation were clinically malignant, and each had several of the established malignant features. Eight tumors with spindle cells occurred in men 34-70 years of age. Two tumors had ill-defined fascicles of spindle cells, and three showed prominent edematous to myxoid areas with spindle-shaped tumor cells. Two additional tumors had a fibroma-like spindled component that blended with islands of more plump, polygonal to spindle-shaped Leydig cells. Finally, one tumor had foci resembling an unclassified sarcoma that merged with conventional LCT; the spindle cell component in this case did not react for Leydig cell markers in contrast to the spindle cells in five of the six other cases in which immunostains were performed. Spindle cell differentiation, by itself, did not appear to have prognostic significance.

Of the six patients with available follow-up, two developed metastases, but their tumors had malignant features apart from spindle cells; the remaining four patients were disease free at a mean of 3.6 years.

Awareness of these unusual patterns in LCTs may prevent misinterpretation of fat admixed with neoplastic Leydig cells as evidence of extratesticular growth (a criterion for malignant LCT) may help avoid misdiagnosis of a LCT as a testicular "tumor" of the adrenogenital syndrome (which may contain fat) and may prevent misdiagnosis of a LCT with spindle cells as a sarcoma or unclassified sex cord-stromal tumor.



Malignant Melanoma Metastatic to the Testis: A Report of Three Cases with Clinically Significant Manifestations.

Datta MW, Young RH.

Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Int J Surg Pathol 2000 Jan;8(1):49-57 Abstract quote

Three cases of malignant melanoma metastatic to the testis, each of which was a challenge in pathologic interpretation, are reported.

The patients were 43, 55, and 80 years of age, respectively. A history of malignant melanoma was not known to the initial examining pathologist in two of the cases. The testicular tumors were all unilateral. One took the form of multiple nodules, but the others were discrete solitary masses. On microscopic examination diffuse, nested, follicular, and fascicular patterns, usually in combination, were seen. The tumor cells had moderate to abundant eosinophilic cytoplasm in two cases, but scanty cytoplasm in a third. In one case there was also a component of cells with copious foamy cytoplasm. Rare areas of melanin pigment were identified in two tumors. Immunohistochemistry for S-100 and HMB-45 was positive in the two cases in which it was performed. In the third case electron microscopy revealed aberrant melanosomes within the tumor cells.

The differential diagnosis in these and rare other cases of malignant melanoma involving the testis during life is broad and includes seminoma, malignant lymphoma, and Leydig cell tumor. When the diagnosis is entertained, a search for melanin pigment, immunohistochemical stains for S-100 protein and HMB 45, and further inquiry into the clinical history are often crucial.



Deoxyribonucleic acid flow cytometry of testicular Leydig cell tumors.

Palazzo JP, Petersen RO, Young RH, Scully RE.

Department of Pathology, Jefferson Medical College, Philadelphia, Pennsylvania.

J Urol 1994 Aug;152(2 Pt 1):415-7 Abstract quote

We analyzed by flow cytometry the deoxyribonucleic acid content of 13 paraffin embedded, formalin-fixed Leydig cell tumors of the testis. Of the tumors 10 were clinically benign (9 diploid and 1 aneuploid) and 3 were malignant (aneuploid). The benign aneuploid tumor showed moderate cellular atypia and a low mitotic count (less than 2 per 10 high power fields).

Our study suggests that the majority of Leydig cell tumors are diploid and the less common malignant tumors are typically aneuploid, and that deoxyribonucleic acid flow cytometric findings can be useful as a prognostic indicator in these tumors.


Ten-year follow-up in a boy with Leydig cell tumor after selective surgery.

Konrad D, Schoenle EJ.

Division of Endocrinology and Diabetology, University Children's Hospital, Zurich, Switzerland.

Horm Res 1999;51(2):96-100 Abstract quote

In a 4(8)/12-year-old boy with precocious puberty and an enlarged right testis, a Leydig cell tumor was diagnosed.

Surgical exploration revealed an encapsulated tumor which was selectively removed without orchiectomy. Within 1 year the signs of precocious puberty disappeared. Ten years later, the patient remained free of disease and had developed normal spontaneous puberty. Despite of highly advanced bone age at the time of diagnosis (13 years according to Greulich and Pyle), his height at age 15 was in the upper normal range and within the familial target height. Most of these prepubertal patients affected by this tumor underwent orchiectomy, although no malignant course of Leydig cell tumors before puberty has been reported.

This work provides the first example of long-term follow-up of a prepubertal boy after testis-sparing surgery for a Leydic cell tumor. We conclude that selective removal of the tumor may be the procedure of choice in this entity.

Organ-sparing surgery for bilateral leydig cell tumor of the testis.

Masoudi JF, Van Arsdalen K, Rovner ES.

Division of Urology, Hospital of the University of Pennsylvania, Philadelphia, USA.

Urology 1999 Oct;54(4):744 Abstract quote

Leydig cell tumors of the testis are uncommon, and bilateral lesions are extremely rare.

We report a case of bilateral Leydig cell tumor of the testis treated with radical orchiectomy and contralateral subtotal orchiectomy with the intent of preservation of hormonal function and fertility.

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Last Updated February 19, 2007

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