[Diagnosis and treatment of Leydig cell tumors]. / Diagnose und Therapie des Leydig-Zell-Tumors.

BACKGROUND: Tumors of the testes not originating from germinal epithelium are a rare entity and represent a diagnostic and therapeutic challenge. Leydig cell tumors (LCT) are rare stromal tumors of the testis. OBJECTIVES: To present current approaches in diagnostic and treatment of LCT. METHODS: A literature search in PubMed was performed and the currently available guidelines concerning LCT were evaluated. Articles and book chapters were selected based on relevance to daily practice. RESULTS: The low incidence of Leydig cell tumors not originating from the germinal epithelium, but from the stroma of the testis requires a standardized approach to determine relevant differential diagnosis and to optimize diagnosis and treatment depending on the current standard of knowledge and to determine whether it is benign or malignant. While more than 90% of LCT are benign and treatment is only restricted to the testis, malignant subtypes require radical surgical resection of the testicular and metastatic sites. CONCLUSION: A standardized diagnostic and therapeutic approach as well as a prospective registry of rare LCT could facilitate further detailed analysis to improve the understanding of tumor biology resulting in optimized therapeutic guidelines including follow-up strategies.

Evaluation of cytotoxic T lymphocyte-mediated anticancer response against tumor interstitium-simulating physical barriers.

Tumor antigen-specific cytotoxic T lymphocyte (CTL) is a promising agent for cancer therapy. Most solid tumors are characterized by increased interstitial fluid pressure (IFP) and dense collagen capsule, which form physical barriers to impede cancer treatment. However, it remains unclear how CTL-mediated anticancer response is affected at the presence of these obstacles. Using a microfluidic-based platform mimicking these obstacles, we investigated the migration characteristics and performance of anticancer response of CTLs targeting hepatic cancer cells via antigen-specific and allogeneic recognition. The device consisted of slit channels mimicking the narrow interstitial paths constrained by the fibrous capsule and increased IFP was simulated by applying hydrostatic pressure to the tumor center. We found that antigen-specificity of CTLs against the targeted cancer cells determined the cytotoxic efficacy of the CTLs but did not significantly affect the success rate in CTLs that attempted to infiltrate into the tumor center. When increased IFP was present in the tumor center, CTL recruitment to tumor peripheries was promoted but success of infiltration was hindered. Our results highlight the importance of incorporating the physical characteristics of tumor interstitum into the development of CTL-based cancer immunotherapy.

Risk Factors and Treatment Outcomes of 1,375 Patients with Testicular Leydig Cell Tumors: Analysis of Published Case Series Data.

PURPOSE: Leydig cell tumors are rare but they are the most common nongerm cell testicular tumors. Only limited evidence exists for reliably differentiating between benign and malignant Leydig cell tumors and for optimally managing the different types and stages of this rare disease. In this review we synthesize the available evidence on the clinical presentation and clinicopathological characteristics associated with Leydig cell tumor malignancy and management. MATERIALS AND METHODS: We analyzed published case series data on Leydig cell tumors. The association between clinicopathological variables and the presence of metastatic disease was assessed using regression analyses. RESULTS: We included 357 reports, reviewing available data from 1,375 patients (median age 34 years). Testis sparing surgery was performed in 463 patients. Local recurrence after testis sparing surgery occurred in 8 of 121 (7%) patients with available followup information. Metastases were found in 101 patients and were most often located in the retroperitoneal lymph nodes (60%), lungs (38%) and/or liver (29%). The multivariable models with or without multiple imputation predicting metastatic disease included older age, larger tumor size, presence of any adverse factor (larger tumor diameter, necrosis, angiolymphatic invasion, pleomorphism, high mitotic index, atypia) and any protective factor (Reinke crystals, lipofuscin pigments, gynecomastia) with model AUCs of 0.93. Durable remission after resection of metastases or use of platinum based chemotherapy was rarely seen. CONCLUSIONS: Our risk tables using clinicopathological parameters can help identify patients with malignant tumors. These patients should undergo disease staging and be followed or receive further treatment. In some patients with metastatic disease surgical and systemic treatment might result in disease control.

Testicular tumors of adrenogenital syndrome: From physiopathology to therapy.

Testicular tumor of adrenogenital syndrome is a rare and benign anomaly usually presenting as bilateral testicular masses. It is the most important cause of infertility in adult male congenital adrenal hyperplasia. Distinction between testicular tumors of adrenogenital syndrome and Leydig cell tumors can be problematic; it is based on clinical, histopathologic, immunohistochemical and endocrine features. Biopsy is advised in cases of longstanding tumors in infertile patients and when surgery is indicated. Fertility preservation is a key management goal in testicular tumor of adrenogenital syndrome. In stages 2 and 3, intensified glucocorticoid treatment is recommended as a first step treatment. Sparing surgical approach is preferred for tumors of stage 4 and steroid unresponsive masses. Magnetic resonance imaging is recommended before surgery. The only indication of surgery in stage 5 is testicular pain.

[Malignant Leydig Cell Tumor of the Testis : A Case Report].

A 69-year-old Japanese man was referred to our hospital for a left inguinal testicular tumor and paraaortic lymph node swelling and pleural dissemination. A left orchiectomy was performed in October 2013. Histologically, this testicular tumor was a malignant Leydig cell tumor. The antineoplastic agent mitotan was administered after the orchiectomy. Two months later, although his plasma level of testosterone had de-escalated, the para-aortic lymph node did not decrease in size. A retroperitoneal lymph node dissection was performed in January 2014. Unfortunately, three days after the surgery, the patient died due to disseminated intravascular coagulation and gastrointestinal hemorrhage of unknown cause.

Metastasized Leydig cell tumor in a dog.

We present the clinical findings, diagnosis and treatment of an 11-year old intact male Fox Terrier with a malignant Leydig cell tumor of the right testicle, which metastasized to the skeletal musculature of the left hind limb. The primary tumor and the metastasis were resected with narrow margins. The dog was treated with metronomic chemotherapy using thalidomid and dyclophosphamide. Local recurrence at the site of the metastasis and a pulmonary metastasis were present 30 months after surgery. The dog was euthanized.

Testicular and testicular adnexa tumors in the elderly.

Neoplasms in the testis and in the testicular adnexa of elderly patients are completely different from those observed in younger patients. Indeed, although conventional seminomas and nonseminomas are mainly observed in the age range of 20-45 years, spermatocytic seminoma, malignant Leydig tumors, and lymphomas in the testis and sarcomas in the paratesticular region are encountered in individuals older than 60 years of age. Here, we discuss the testis and paratesticular region neoplasm more commonly diagnosed in elderly men.

Clinical analysis of management of pediatric testicular germ cell tumors.

OBJECTIVE: To analyze our experiences of pediatric testicular tumors and investigate the management of pediatric testicular germ cell tumors. Pediatric testicular tumors are rare and the treatment of them has not been well defined. METHODS: Children treated for primary testicular tumors between January 1998 and July 2010 were retrospectively analyzed. For yolk sac tumor, the difference of survival rates between patients with and without retroperitoneal lymph node dissection (RPLND) was calculated. RESULTS: Eighty-seven cases met our criteria and 78 were germ cell tumors, including 40 cases with yolk sac tumor. Patients were 3-128 months old (median 19), and 53 patients were diagnosed at younger than 2 years of age. For germ cell tumors, serum α-fetoprotein and ß-human chorionic gonadotropin were elevated in 48 and 7 patients, respectively, including 38 and 2 in those with yolk sac tumor. RPLND and chemotherapy were performed in 13 and 19 patients, respectively, and surveillance was performed in 50 patients. With median follow-up of 50 months, 6 patients had recurrence, 4 patients died, and the others achieved complete remission. For stage I yolk sac tumor, the difference of survival rates between patients with and without RPLND was not significant (P = .808). CONCLUSION: Yolk sac tumor is the most common type of pediatric testicular tumor. For stage I yolk sac tumor, radical inguinal orchiectomy is effective, salvage chemotherapy is promising, and RPLND may not be necessary.

Leydig cell tumor in two brothers with congenital adrenal hyperplasia due to 11-ß hydroxylase deficiency: a case report.

Congenital adrenal 11-ß hydroxylase deficiency is a rare autosomal recessive syndrome characterized by deficient cortisol synthesis and testicular masses. It is extremely difficult to distinguish testicular tumors caused by this syndrome from Leydig cell tumors. As management for each differs, it is important to differentiate the syndromes from each other. Hereby, we present the case of two brothers affected by 11-ß hydroxylase deficiency and presenting with bilateral testicular masses. Two differential diagnoses were noticed for both patients: testicular adrenal rest tumors (TART) and Leydig cell tumor (LCT). In this study the tumors were yellow, firm, and non-tender with intra-testicular location. Histological studies showed cells in a cluster arrangement with low lipochrome pigment concentration. Tumors were unresponsive to ACTH suppression therapy, but a drop in levels of plasma testosterone and urinary 17-ketosteroids occurred after surgical treatment. Considering all above, they were finally diagnosed as having Leydig cell tumors. Both cases were managed by testis-sparing surgery.

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

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 tumor. Case report and review of the literature]. / Tumor de células de Leydig. A propósito de un nuevo caso y revisión de la literatura.

OBJECTIVE: To report a new case of the rare Leydig cell tumor, and to perform bibliographic review. METHODS: We report the case of a 38-year-old male with the clinical and ultrasound diagnosis of testicular tumor, and normal hormonal and extension studies. He underwent inguinal radical orchyectomy and the pathology report of the specimen showed a Leydig cell tumor. It was staged as T1N0M0, not receiving any further treatment with chemotherapy or radiotherapy. Five years after surgery there is no evidence of disease on follow-up. RESULTS: The patient does not show evidence of recurrence after chest x-rays, abdominal-pelvic CT scan, ultrasound of the contralateral testis, and tumor markers. CONCLUSIONS: We recommend a long-term follow-up with contralateral testicle ultrasound, CT scan, chest x-ray, and tumor markers.

Tumor de células de Leydig. A propósito de un nuevo caso y revisión de la literatura / Leydig cell tumor. Case report and bibliographic review

OBJETIVO: Presentar un nuevo caso del infrecuente tumor de células de Leydig, junto a na revisión de la literatura. MÉTODOS: Presentamos el caso de un varón de 38 años de edad con u diagnostico clínico y ecográfico de tumoración testicular, con estudio hormonal y de extensión normal. Se interviene practicándose orquiectomía radical vía inguinal y la pieza fue informada como un tumor de células de Leydig. Estudiado como T1N0M0 no recibió tratamiento posterior con quimioterapia ni radioterapia. Tras 5 años de seguimiento no se ha evidenciado recidiva. RESULTADOS: El enfermo no presenta recidiva de la enfermedad, habiéndose realizado estudios radiológicos de Radiografía de Tórax, T.C. abdominopélvico, Ecografía del teste contralateral, así como estudio de marcadores tumorales. CONCLUSIONES: Como conclusión, se aconseja el seguimiento a largo plazo con la práctica de ecografia del teste contralateral, otros estudios radiológicos como T.A.C y radiografía de tórax, así como marcadores tumorales

OBJECTIVE: To report a new case of the rare Leydig cell tumor, and to perform bibliographic review. METHODS: We report the case of a 38-year-old male with the clinical and ultrasound diagnosis of testicular tumor, and normal hormonal and extension studies. He underwent inguinal radical orchyectomy and the pathology report of the specimen showed a Leydig cell tumor. It was staged as T1N0M0, not receiving any further treatment with chemotherapy or radiotherapy. Five years after surgery there is no evidence of disease on follow-up. RESULTS: The patient does not show evidence of recurrence after chest x-rays, abdominal-pelvic CT scan, ultrasound of the contralateral testis, and tumor markers. CONCLUSIONS: We recommend a long-term follow-up with contralateral testicle ultrasound, CT scan, chest x-ray, and tumor markers

A novel targeted therapy of Leydig and granulosa cell tumors through the luteinizing hormone receptor using a hecate-chorionic gonadotropin beta conjugate in transgenic mice.

We investigated the antitumoral efficacy, endocrine consequences, and molecular mechanisms underlying cell death induced by the Hecate-chorionic gonadotropin (CG)beta conjugate, a fusion protein of a 23-amino acid lytic peptide Hecate with a 15-amino acid (81-95) fragment of the human CGbeta chain. Transgenic (TG) mice expressing the inhibin alpha-subunit promoter (inhalpha)/Simian Virus 40 T-antigen (Tag) transgene, developing luteinizing hormone (LH) receptor (R) expressing Leydig and granulosa cell tumors, and wild-type control littermates were treated either with vehicle, Hecate, or Hecate-CGbeta conjugate for 3 weeks. Hecate-CGbeta conjugate treatment reduced the testicular and ovarian tumor burden (P < .05), whereas a concomitant increase (testis; P < .05) or no change (ovary) in tumor volumes occured with Hectate treatment. A drop in serum progesterone, produced by the tumors, and an increase in LH levels occured in Hecate-CGbeta treated mice, in comparison with vehicle and Hecate groups, providing further support for the positive treatment response. Hecate-CGbeta conjugate induced a rapid and cell-specific membrane permeabilization of LHR-expressing cells in vitro, suggesting a necrotic mode of cell death without activation of apoptosis. These results prove the principle that the Hecate-CGbeta conjugate provides a novel specific lead into gonadal somatic cell cancer therapy by targeted destruction of LHR-expressing tumor cells.

Leydig cell tumor of the testis. New cases and review of the current literature.

Leydig cell tumors are the most frequent non-germ cell tumors of the testis, accounting for 1-3% of all testicular tumors. They present most commonly as a testicular mass or with endocrine symptoms. We report three new cases of Leydig cell tumors that presented in different forms. The relevant literature is reviewed and the management of these tumors is discussed.

Tumor de células de Leydig: reporte de nueve casos / Leydig cell tumor: report of nine cases

Objetivo: El objetivo de este trabajo es referir retrospectivamente la incidencia de tumores de celulas de Leydig en pacientes con tumores testiculares atendidos en el servicio de Urología del Hospital Italiano de Buenos Aires, así como los aspectos diagnósticos y terapéuticos emplesdos. Asimismo se evalua la evolución de los casos tratados. Materia y Métodos: Entre los meses de enero de 1990 y diciembrte de2003 inclusive fueron realizados 152 cirugías por tumores de testículo. Los pacientes con diagnóstico de masa testicular fueros explorados quirúrgicamente por vía inguinal con realización de biopsia intraoperatoria por congelación. A aquellos con diagnóstico de tumor de células de Leydig se les realizó orquiectomía radicalo tumerectomía. Se efctuo seguimiento clínico y ecográfico. Valoramos la edad del paciente en el momento diagnóstico, la forma de presentación, los antecedentes de patología testicular, el método de diagnóstico,el estudio hormonal, el patrón histológico, el tratamiento realizado y la evolución posterior, con un seguimiento mínimo de 6 meses. Resultados: Se diagnosticaron 9 (5,9 por ciento) tumores de células de Leydig del total de neoplasias testículares. La edad promedio fue de 30 años (14 a 57). El 67 por ciento se presentó como masa testicular, el 22 por ciento en forma incidental y el 11 por ciento con dolor. Uno se asoció con criptorquidia y no hubo sindromes de feminización. Todos los casos presentaron hitología con caracteres de benignidad. Se realizaron 5 orquiectomías y 4 tumorectomías. Ningún paciente presentó metástasis a distancia o progresión local. Conclusiones: El tumor de células de Leydig representó un porcentaje menor en el total de lod tumores testiculares. La presentación más frecuente fue como masa testicular. Se diagnosticó en la adolescencia y edad adulta, en todos los casos con caracteres histopatológicos de benignidad, hecho confirmado solo por el estudio diferido de la biopsia. No hemos hallado diferencias en el seguimiento de pacientes tratados con orquiectomía radical o con tumorectomía

Tumor de células de Leydig: reporte de nueve casos / Leydig cell tumor: report of nine cases

Objetivo: El objetivo de este trabajo es referir retrospectivamente la incidencia de tumores de celulas de Leydig en pacientes con tumores testiculares atendidos en el servicio de Urología del Hospital Italiano de Buenos Aires, así como los aspectos diagnósticos y terapéuticos emplesdos. Asimismo se evalua la evolución de los casos tratados. Materia y Métodos: Entre los meses de enero de 1990 y diciembrte de2003 inclusive fueron realizados 152 cirugías por tumores de testículo. Los pacientes con diagnóstico de masa testicular fueros explorados quirúrgicamente por vía inguinal con realización de biopsia intraoperatoria por congelación. A aquellos con diagnóstico de tumor de células de Leydig se les realizó orquiectomía radicalo tumerectomía. Se efctuo seguimiento clínico y ecográfico. Valoramos la edad del paciente en el momento diagnóstico, la forma de presentación, los antecedentes de patología testicular, el método de diagnóstico,el estudio hormonal, el patrón histológico, el tratamiento realizado y la evolución posterior, con un seguimiento mínimo de 6 meses. Resultados: Se diagnosticaron 9 (5,9 por ciento) tumores de células de Leydig del total de neoplasias testículares. La edad promedio fue de 30 años (14 a 57). El 67 por ciento se presentó como masa testicular, el 22 por ciento en forma incidental y el 11 por ciento con dolor. Uno se asoció con criptorquidia y no hubo sindromes de feminización. Todos los casos presentaron hitología con caracteres de benignidad. Se realizaron 5 orquiectomías y 4 tumorectomías. Ningún paciente presentó metástasis a distancia o progresión local. Conclusiones: El tumor de células de Leydig representó un porcentaje menor en el total de lod tumores testiculares. La presentación más frecuente fue como masa testicular. Se diagnosticó en la adolescencia y edad adulta, en todos los casos con caracteres histopatológicos de benignidad, hecho confirmado solo por el estudio diferido de la biopsia. No hemos hallado diferencias en el seguimiento de pacientes tratados con orquiectomía radical o con tumorectomía(AU)