Histological and immunohistochemical characterization of 17 gonadal tumours in koi carp (Cyprinus carpio koi).

Reports on abdominal tumours in koi carp are scarce and most are from the gonads. Their histological diagnosis is challenging due to the occurrence of mixed populations of neoplastic cells and the few availability of cross-reactive antibodies in fish tissues. The present study aims to provide a histopathological characterization of seventeen gonadal tumours, enriched by a wide antibody panel (vimentin, CD117, placental alkaline phosphatase-PLAP, AE1/AE3 cytokeratin, E-cadherin, proliferating cell nuclear antigen-PCNA, müllerian-inhibiting substance-MIS, GATA4 and Inhibin-α) applied on whole and tissue microarray (TMA) sections. Abdominal enlargement was associated with tumours filling 30%-80% of the abdominal cavity; frequently, the gonads had been completely replaced by neoplastic tissue. Twelve cases were characterized as sex cord-stromal tumours (SCSTs), three as germ cell tumours (GCTs), one as mixed germ cell sex cord-stromal tumour (MGCSCST) and one as carcinoma. By immunohistochemistry, PLAP enabled confirmation of GCTs, ovarian carcinoma and the objective identification of a further cell component in 8 out of the 12 SCSTs that were reclassified as mixed tumours. The use of an immunohistochemical panel can help in refining the histological diagnosis, but the morphological diagnosis still represents the main tool for the characterization of these tumours in koi carp.

Variation of Gonadal Dysgenesis and Tumor Risk in Patients With 45,X/46,XY Mosaicism.

OBJECTIVE: To describe the gonadal features of patients with 45,X/46,XY mosaicism, and to evaluate the prevalence of gonadal tumor in different phenotypes. MATERIALS AND METHODS: The medical records of consecutive patients with 45,X/46,XY karyotype or its variants who had undergone gonadal biopsy or gonadectomy at a single institute between 1996 and 2017 were retrospectively reviewed. RESULTS: Of 34 patients with 45,X/46,XY mosaicism, a unilateral dysgenetic testis and a contralateral streak gonad was detected in 20 patients (59%), bilateral streak gonads in 9 (26%), and bilateral dysgenetic testes in 5 (15%). A gonad composed of both streak and dysgenetic testicular portions was observed in 7 gonads of 6 patients. All streak gonads were removed, and bilateral gonadectomy was performed in 15 patients raised as girls. Pathologic examination revealed gonadal tumors in 6 of the 34 (18%) patients, including a gonadoblastoma in 7 gonads among 5 patients and an association of dysgerminoma with gonadoblastoma in 1 gonad. All 6 patients who developed gonadal tumor had female genitalia. Postoperative course was uneventful except 1 boy. A seminoma was developed in his soritaly scrotal testis at the age of 16 years. CONCLUSION: The prevalence of gonadal tumor in patients with 45,X/46,XY mosaicism may vary according to the phenotype, and high in patients with female phenotype. Considering the increased risk of gonadal tumors in such patients, early investigation and individual management, including prophylactic gonadectomy, are recommended. In male patients, a close follow-up of the preserved testes is mandatory until adulthood.

Local Control of Perineal Rhabdomyosarcoma: Are Current Recommendations Adequate?

Rhabdomyosarcoma (RMS) is a rare malignancy that can develop in nearly any soft-tissue of the body. Location of the primary tumor affects treatment strategy and prognosis, and RMS of the perineal areas can be especially difficult to treat successfully. RMS is treated systemically with chemotherapy. Local control options include surgical excision, radiation treatment, or a combination of the 2. Treating RMS with radiation treatment can be challenging due to the absence of standardized dosage protocols, along with the presence of conflicting recommendations in the literature. Each case of perineal RMS may benefit from a more individualized treatment plan.

Anomalías de la diferenciación sexual: a propósito de un caso / Anomalies of sexual differentiation: presentation of a case

Las disgenesias gonadales mixtas (DGM) son trastornos de la diferenciación sexual poco frecuentes, pero constituyen una causa importante de infertilidad. Presentan un cariotipo en mosaico con fórmula mos 45,X/46,XY y pueden dar lugar a gran variedad de fenotipos, encontrando desde diferentes grados de ambigüedad sexual en recién nacidos, hasta fenotipos masculinos normales, fenotipos femeninos normales o fenotipos del síndrome de Turner (ST). Se presenta el caso de una paciente diagnosticada de ST desde la pubertad a quien no se le detectó la presencia de fragmentos de cromosoma Y. Teniendo en cuenta que las pacientes diagnosticadas de ST con expresión de cromosoma Y (completo o parcial) tienen mayor riesgo de desarrollar gonadoblastoma, es importante resaltar la importancia de diagnosticar la presencia de cromosoma Y, recomendando incluso realizar de forma sistemática técnicas que aumenten la sensibilidad para detectarlo aunque no se haya detectado en el cariotipo

Mixed gonadal dysgenesis is a group of rare disorders of sexual differentiation and is a major cause of infertility. They show a mosaic karyotype 45,X/46,XY and can give rise to a great variety of phenotypes, finding from different degrees of sexual ambiguity in newborns, up to normal male phenotypes, normal female phenotypes or Turner syndrome (TS) phenotypes. The case is presented of a patient diagnosed with TS from puberty and in whom the presence of fragments of Y chromosome was not detected. Given that patients with a diagnosis of TS with Y chromosome expression (full or partial) are at increased risk of developing gonadoblastoma, it is important to emphasise the importance of diagnosing the presence of the Y chromosome, and even recommending systematically performing techniques that increase the sensitivity in order to detect it, even though it has not been detected in the karyotype

The differences between gonadal and extra-gonadal malignant teratomas in both genders and the effects of chemotherapy.

BACKGROUND: A tumor comprising of different types of tissues (such as hair, muscle, bone, etc.) is known as a teratoma. It is a type of germ cell (cells that make sperm or eggs) tumor. When these germ cells have rapid cancerous growth, then such a teratoma is called a malignant teratoma. We have studied the differences between gonadal and extra-gonadal malignant teratomas and the effects of chemotherapy in both genders. METHODS: The samples of 3799 male and 1832 female patients with malignant teratoma samples, between the ages of 1 and 85+ years, were selected from the years 1973 to 2014. Trends in incidence, estimated prevalence, incidence rates, and frequency were calculated in gonadal and extra-gonadal tumors with age adjustment. The five-year observed, expected, and relative survival rates were analyzed to study the prognosis. RESULTS: The gonadal took over a majority percentage of malignant teratomas compared with the extra-gonadal (90% vs. 10% in male; 83% vs. 17% in female). For the male, the total of the gonadal and the extra-gonadal were all significantly decreased from 1973 to 2014 (p < 0.05). For the female, there were no significant trends. As for prevalence, incidence, and frequency, there were two separate peaks of malignant teratomas. One peak was at under 1 year old, which was composed of the extra-gonadal tumor; the other peak was at 20-24 for male and 10-34 for female, which was composed of the gonadal tumor. This separation of the gonadal and extra-gonadal showed a significant difference (p < 0.05). As for the prognosis, the extra-gonadal tumor showed significantly lower survival rates than the gonadal (p < 0.05). In the short term, the survival rate of the chemotherapy group was higher than the supportive care group. However, in the long term, the survival rate of the chemotherapy group was lower than the supportive care group. CONCLUSION: The gonadal and extra-gonadal malignant teratomas show lots of differences. Chemotherapy might not help improve survival rates.

Novel mutation in FTHL17 gene in pedigree with 46,XY pure gonadal dysgenesis.

OBJECTIVE: To identify the genetic cause of a pedigree with four patients with 46,XY pure gonadal dysgenesis (PGD). DESIGN: Genetic mutation study. SETTING: Academic medical center. PATIENT(S): Four first cousins, from three households of a Chinese pedigree, affected by 46,XY PGD. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The patients were studied from clinical and genetic perspectives. Whole-genome sequencing was conducted in family members. RESULT(S): Four first cousins in the third generation were affected by 46,XY PGD. A specific familial characteristic was the prevalence of as high as 100% of gonadal tumors in patients. Whole-genome sequencing identified a new ferritin heavy chain-like 17 (FTHL17) mutation, c.GA442_443TT (p.E148L), which has the potential to interfere with protein function and cause 46,XY PGD. Moreover, the location (Xp21.2) of the FTHL17 gene proves that the family is X-linked recessive. In vitro functional study revealed that the perturbation of FTHL17 caused the decrease of protein expression and cell proliferation. CONCLUSION(S): We describe the first 46,XY PGD pedigree that may be attributed to mutations of the FTHL17 gene. We speculated that the FTHL17 gene is involved in the testis-determining pathway and tumorigenesis.

Teratocarcinoma gigante de mediastino anterosuperior / Giant teratocarcinoma of anterosuperior mediastinum

RESUMEN Los tumores de células germinales no son tan frecuentes, dentro de ellos se encuentra el teratoma como el más usual en ubicación mediastinal, es más habitual en hombres jóvenes cuando es maligno (teratocarcinoma), con una relación por género de 13,5:1, y una edad promedio de 26 años. Se describe la evolución de un hombre de 19 años de edad con un tumor mediastinal, con metástasis pulmonares e infiltración intracardíaca, resecado satisfactoriamente, cuyos síntomas más frecuentes fueron: disnea, dolor retroesternal, fiebre, tos, pérdida de peso y síndrome de vena cava superior. El diagnóstico se realizó por radiografía de tórax y tomografía axial computarizada. Se logró realizar la excéresis total del tumor y las metástasis, así como la tumoración intracardíaca, con reparación de la válvula tricúspide. El paciente ha tenido una evolución satisfactoria durante el primer año de seguimiento.

ABSTRACT Germ cell tumors are not so frequent; among them, teratomas are most common in the mediastinal location. Teratomas in young men are usually malignant (teratocarcinoma), with a gender ratio of 13.5:1, and an average age of 26 years. We describe the evolution of a 19-year-old man with a mediastinal tumor, with pulmonary metastases and intracardiac infiltration, successfully removed; whose most frequent symptoms were: dyspnea, retrosternal pain, fever, cough, weight loss and superior vena cava syndrome. The diagnosis was made by chest x-ray and computed tomography. Total removal of the tumor and metastases was achieved, as well as the intracardiac tumor, with tricuspid valve repair. The patient had a satisfactory outcome during the first follow-up year.

Transformación de teratoma en rabdomiosarcoma / Transformation of teratoma in rabdomiosarcoma

Los teratomas son tumores germinales malignos compuestos por dos o más capas de tejido, que ocasionalmente se transforman en estirpes con crecimiento agresivo. Se presenta el caso de un paciente de 29 años con un tumor germinal gonadal localizado en testículo, cuya evolución fue desfavorable por presentar transformación en un fenotipo correspondiente a un rabdomiosarcoma. La patología aquí descripta deviene del crecimiento diferencial de un componente ya existente en el tumor original o la transformación en un linaje somático que se hace dominante. Los tumores transformados como el del caso descripto son raros y presentan características diferentes de la mayoría de las neoplasias germinales respecto del comportamiento, el pronóstico y la sensibilidad a los tratamientos establecidos.

Teratomas are malign germ cell tumors composed of two or more tissue layers. When there is specific organ differentiation they are called mature teratoma. They rarely grow aggressively. We report the case of a 29 year-old man with a diagnosis of gonadal germ cell tumor whose evolution was unfavorable owing to transformation into a different phenotype corresponding to a rhabdomyosarcoma. This phenomenon occurs through differential growth of a single histological component of the original tumor or transformation of a somatic lineage that becomes dominant. Transformed tumors such as the one herein described differ from most germ cell neoplasms regarding behavior, prognosis, and susceptibility to established treatments.

[Transformation of teratoma in rabdomiosarcoma]. / Transformación de teratoma en rabdomiosarcoma.

Teratomas are malign germ cell tumors composed of two or more tissue layers. When there is specific organ differentiation they are called mature teratoma. They rarely grow aggressively. We report the case of a 29 year-old man with a diagnosis of gonadal germ cell tumor whose evolution was unfavorable owing to transformation into a different phenotype corresponding to a rhabdomyosarcoma. This phenomenon occurs through differential growth of a single histological component of the original tumor or transformation of a somatic lineage that becomes dominant. Transformed tumors such as the one herein described differ from most germ cell neoplasms regarding behavior, prognosis, and susceptibility to established treatments.

Oncología quirúrgica pediátrica / Pediatric surgical oncology

Las neoplasias suponen la primera causa de muerte en niños mayores de 1 año en países desarrollados. la cirugía pediátrica juega un importante papel terapéutico en el cáncer infantil a distintos niveles: extirpación tumoral, implantación de accesos vasculares, manejo de metástasis y complicaciones. La oncología pediátrica es una especialidad muy dinámica con actualizaciones y cambios en protocolos constantemente. el objetivo de este artículo es la revisión actualizada de los tumores sólidos más frecuentes y con características específicas en relación con la cirugía pediátrica: neuroblastoma, tumor de Wilms, hepatoblastoma, tumores ováricos, testiculares y de partes blandas. El neuroblastoma es el tumor sólido extracraneal más común en la infancia. tanto el neuroblastoma como el tumor de Wilms suelen presentarse como una masa abdominal asintomática. la combinación del grupo de riesgo, edad, factores biológicos y resultados histológicos permite asignar a cada paciente un estadio de riesgo con valor pronóstico, y establecer una estrategia terapéutica específica en cada caso de neuroblastoma. el nefroblastoma o tumor de Wilms es el tumor renal maligno más frecuente en niños. en nuestro medio el nuevo protocolo establecido por la Siop se conoce como UMBrella que se basa en la quimioterapia preoperatoria con el objetivo de reducir masa tumoral seguido de cirugía. En los casos de hepatoblastoma es importante la clasificación preteXt (Pretreatment Extent of Disease) porque define la extensión de parénquima hepático afectada y enfermedad extrahepática dando información sobre la resecabilidad del tumor y su respuesta a la quimioterapia. Ante una masa de tejido blando debe plantearse en primer lugar que se trate de procesos reactivos y tumores benignos, los tumores malignos de partes blandas son raros. dentro de estos, el rabdomiosarcoma se caracteriza por su buena respuesta a quimioterapia, por lo que está en desuso la cirugía con resecciones agresivas o mutilantes. Respecto a los tumores gonadales en la infancia, a diferencia de los adultos, predominan los germinales, en concreto el teratoma. la cirugia tiende a ser conservadora para respetar la fertilidad futura. en las últimas décadas, los avances en tratamientos oncológicos han logrado un aumento de la supervivencia en la mayoría de tumores infantiles, en parte gracias al enfoque multidisciplinar necesario desde el diagnóstico de cada caso

Malignant neoplasms constitute the first cause of death in children over 1 year of age in developed countries. Pediatric surgery plays an important therapeutic role in childhood cancer on different sides: removing tumors, placing vascular access devices, metastasis management and complications. Pediatric oncology is a dinamyc specialty with constant updates and changes in protocols. the principal aim of this report is an updated review of more common solid tumors and their specific surgical aspects: neuroblastoma, Wilms' tumor, hepatoblastoma, ovarian tumor, testicular tumor and rhabdomyosarcoma. Neuroblastoma is the most common extracranial solid tumor in chidhood. Wilms' tumor and neuroblastoma usually appears as an asyntomatic abdominal mass. the risk group, age, biological factors and histologic analysis allow to assign a risk stage to each patient, that has prognostic value and determines the specific treatment for each case of neuroblastoma. Nephroblastoma or Wilms' tumor is the most frequent malignant kidney tumor in children. UMBrella is the new protocol of Siop based on preoperative chemotherapy to reduce the size of the tumor and surgery after. The classification PRETEXT (Pretreatment Extent of Disease) is important in cases of hepatoblastoma because defines the extent of hepatic infiltrated parenchyma, so we can know about its resectability and the response to chemotherapy. A soft-tissue mass is probably a reactive process or a benign tumor, since malignant soft-tissue tumors are rare. rhabdomyosarcoma has a good response to chemotherapy, so wide resections and radical surgery are not current techniques. With regard to gonadal tumors in childhood, unlike adults, germ tumors predominate, in particular teratoma. Sparing surgery is the current treatment to preserve future fertility. over the last several decades, the advances in cancer treatment have achieved an increased survival in most of childhood tumors, thanks to multidisciplinary approach from diagnosis

Normal pelvic ultrasound or MRI does not rule out neoplasm in patients with gonadal dysgenesis and Y chromosome material.

INTRODUCTION: Patients with gonadal dysgenesis (GD) with a Y chromosome have an increased risk of gonadal neoplasm. Few data exist on the ability of imaging to detect malignancy in intra-abdominal gonads in these patients. OBJECTIVE: We aimed to determine the correlation between preoperative imaging findings and gonadal pathology in GD patients with Y chromosome material. METHODS: A retrospective review was performed of patients with XY or XO/XY GD who underwent gonadectomy at our institution from 2003 to 2017. Patients were assessed preoperatively with ultrasonography; some additionally underwent MRI. RESULTS: The series consisted of 10 patients, all with female gender and non-palpable gonads. Median age was 13.1 years (range 2.4-18.3 years). Overall, four of the ten patients (40%) had a tumor (gonadoblastoma or dysgerminoma) on final pathology. Four patients had a gonad or gonads that were definitively seen on ultrasonography. All visualized gonads were described as "normal" or "small" with the exception of one patient, who had a normal MRI. Three of the four patients in this group had a tumor on final pathology. The remaining six patients had a gonad or gonads that were not definitively visualized on ultrasound; one patient in this group had a tumor on final pathology. Overall, five of seven gonads (71%) definitively visualized on ultrasound had tumor on final pathology, and two of thirteen gonads (15%) not visualized on ultrasound had tumor on final pathology; this difference was statistically significant (p = 0.012). Three patients were imaged with MRI. Of the gonads that could be visualized on MRI, no definitive abnormalities were seen. All patients imaged with MRI had tumors on final pathology. DISCUSSION: Both ultrasound and MRI are relatively poor at identifying and characterizing intra-abdominal gonads in GD patients. The majority of patients who had a neoplasm had normal imaging findings. Gonads that were definitively visualized on ultrasound were more likely to contain neoplasms that could not be visualized, which perhaps because of tumor growth. No other consistent imaging findings of malignancy were found. Our study included ultrasound evaluations that were completed over 10 years ago and not performed by pediatric ultrasonographers, which may have biased the results. However, results suggest that when discussing gonadectomy with GD patients, one should not be reassured by "normal" imaging findings. Neither ultrasound nor MRI should be relied on for surveillance in GD patients who decide against gonadectomy. CONCLUSION: A normal ultrasound or MRI does not rule out neoplasm in GD patients with intra-abdominal gonads.

Gonadal tumour risk in 292 phenotypic female patients with disorders of sex development containing Y chromosome or Y-derived sequence.

OBJECTIVE: Phenotypic female disorders of sex development (DSD) patients with Y chromosome or Y-derived sequence have an increased risk of gonadal germ cell tumours (GCTs). The objective of the study was to evaluate tumour risk of DSD, summarize the clinical characteristics of patients with GCTs and propose management suggestions. METHODS: Medical records of 292 patients diagnosed DSD and undergoing bilateral gonadectomy at Peking Union Medical College Hospital from January 1996 to March 2016 were retrospectively reviewed. Tumour histopathological types, risks and clinical characteristics were evaluated. RESULTS: The tumours in DSD included gonadoblastoma, seminoma, dysgerminoma, Sertoli cell tumour, yolk sac tumour and choriocarcinoma. The overall GCTs risk was 15·41% and 46, XY pure gonadal dysgenesis (46, XY PGD) carried the highest risk up to 23·33%, followed by complete androgen insensitivity syndrome (CAIS). The risk of mixed gonadal dysgenesis (GD) or 46, XY 17 alpha-hydroxylase/17, 20-lyase deficiency (46, XY 17 OHD) was <10%, and no tumour was found in five testis regression patients. The ages (years) of tumour diagnosed ranged from 11 to 29 [18 (15, 21) years]. The median age of androgen insensitivity syndrome (AIS) with tumours was comparatively late [19 (18, 24) years], while GCTs occurred during adolescence in 46, XY PGD [17 (15, 20) years] and mixed GD [15 (15, 17) years]. Sex hormone levels were generally unaffected by gonadal GCTs. The positive tumour marker rate before surgery was 58·82% (10/17). Elevated lactate dehydrogenase (LDH) was observed in six cases with dysgerminoma/seminoma. Remarkably elevated α-fetoprotein (AFP) or human chorionic gonadotropin (hCG) was seen in cases with yolk sac tumour or choriocarcinoma, respectively. Mild hyperandrogenism was observed in seven cases with GCTs. Fourteen of 17 pelvic masses found before operation was later proved malignant. CONCLUSION: Disorders of sex development patients with Y chromosome materials have a significantly increased risk of GCTs. Gonadoblastoma and dysgerminoma/seminoma are the most prevalent GCTs and 46, XY PGD carries the highest tumour presence and malignancy risk. AIS could postpone bilateral gonadectomy until or after adolescence, while others with streak gonads should undergo surgery as soon as diagnosis. Specific serum tumour markers could be used in predicting GCTs and monitoring. Optimal care and close follow-up are required.

Swyer syndrome in a woman with pure 46,XY gonadal dysgenesis: a rare presentation.

46,XY pure gonadal dysgenesis (Swyer syndrome) is a rare cause of disorder of sexual development. It is a genetic aberration characterized by a 46,XY karyotype which are phenotypical females, with female genitalia at birth, and normal Müllerian structures. The condition usually becomes apparent first in adolescence with delayed puberty and primary amenorrhea. Herein the authors present the case of a 27-year-old woman with primary amenorrhea and undeveloped breasts. The patient had pure 46,XY gonadal dysgenesis with hypoplastic uterus, estrogen treatment for amenorrhea, and no neoplastic changes on the histopathology report. The authors highlight the high risk of neoplastic transformation of the patient with gonadal dysgenesis, and 46,XY karyotype should be referred for bilateral gonadectomy. Once the diagnosis of Swyer syndrome is established, early treatment is crucial to prevent the development of gonadal malignancy and to enable a normal sex life, and even carry a fetus in an immature uterus.

Malignant extra-cranial germ cell tumors in children and adolescents. Results following the guidelines of SFOP/SFCE 95 Protocol.

Between September 1995 and December 2010, 99 new consecutive assessable patients with extra-cranial MGCT were treated according to SFOP/SFCE TGM95 Protocol. A "watch and wait" strategy for completely resected stage I-II was observed in cases with preoperative high tumor markers levels. Metastatic disease or alpha fetoprotein levels > 15 000 ng/ml cases were treated by VIP chemotherapy (etoposide, ifosfamide and CDDP) 4-6-courses. All other cases were treated by VBP (vinblastine, bleomycin, and CDDP) 3-5 courses. Median age for the whole group was 11.1 (r: 0-17) years. Males: 49, females: 50. Stage I: 19 patients, stage II: 16, stage III: 31 and stage IV: 3. Gonadal disease occurred in 77 cases. Of 21 completely resected stage I-II patients with MGCT who did not receive chemotherapy after surgery, 6 presented disease progression and were successfully treated by chemotherapy and remained disease-free. There were no significant differences in outcome according to age, gender, initial site, staging, and histological variant or high levels of alpha-fetoprotein. Initial non-responsiveness to VIP chemotherapy was the only significant unfavorable prognostic feature. With a median follow-up of 64 (r: 5-204) months, at 10 years EFS and OS estimates for the whole group were 0.82 (SE = 0.05) and 0.90 (SE = 0.03) respectively. Therapy results of MGCT treated with the SFOP/SFCE 95 strategy were excellent. Initial non-response to front line chemotherapy was the only significant adverse prognostic feature. The "watch and wait" strategy for completely resected disease with initial positive markers proved to be safe with optimal outcome.

Malignant extra-cranial germ cell tumors in children and adolescents: Results following the guidelines of SFOP/SFCE 95 Protocol

Between September 1995 and December 2010, 99 new consecutive assessable patients with extra-cranial MGCT were treated according to SFOP/SFCE TGM95 Protocol. A "watch and wait" strategy for completely resected stage I-II was observed in cases with preoperative high tumor markers levels. Metastatic disease or alpha fetoprotein levels > 15 000 ng/ml cases were treated by VIP chemotherapy (etoposide, ifosfamide and CDDP) 4-6-courses. All other cases were treated by VBP (vinblastine, bleomycin, and CDDP) 3-5 courses. Median age for the whole group was 11.1 (r: 0-17) years. Males: 49, females: 50. Stage I: 19 patients, stage II: 16, stage III: 31 and stage IV: 3. Gonadal disease occurred in 77 cases. Of 21 completely resected stage I-II patients with MGCT who did not receive chemotherapy after surgery, 6 presented disease progression and were successfully treated by chemotherapy and remained disease-free. There were no significant differences in outcome according to age, gender, initial site, staging, and histological variant or high levels of alpha-fetoprotein. Initial non-responsiveness to VIP chemotherapy was the only significant unfavorable prognostic feature. With a median follow-up of 64 (r: 5-204) months, at 10 years EFS and OS estimates for the whole group were 0.82 (SE = 0.05) and 0.90 (SE = 0.03) respectively. Therapy results of MGCT treated with the SFOP/SFCE 95 strategy were excellent. Initial non-response to front line chemotherapy was the only significant adverse prognostic feature. The "watch and wait" strategy for completely resected disease with initial positive markers proved to be safe with optimal outcome.

Entre septiembre de 1995 y diciembre 2010 se registraron 99 nuevos pacientes evaluables consecutivos con tumores germinales malignos (TGM) extra-cerebrales. Los pacientes fueron tratados prospectivamente según los lineamientos del Protocolo SFOP/SFCE TGM95. Se siguió una estrategia de watch and wait para la enfermedad estadio I-II completamente resecada. La enfermedad con metástasis y los casos con niveles de alfa fetoproteína > 15 000 ng/ml fueron tratados con etopósido, ifosfamida y CDDP, 4-6 cursos. El resto fue tratado con vinblastina, bleomicina y CDDP, 3-5 ciclos. La mediana de edad fue de 11.1 (r: 0-17) años. Varones: 49, niñas: 50. Estadio I: 19 casos; II: 16; III: 31y IV: 33. De 21 enfermos con estadios tumorales I y II con resección completa inicial que no tuvieron tratamiento adyuvante, seis progresaron, todos fueron exitosamente tratados con quimioterapia y permanecieron libres de enfermedad. No hubo diferencias significativas en los resultados de supervivencia según edad, género, sitio inicial, estadificación, variante histológica o niveles elevados de alfa-fetoproteína. La resistencia primaria a la quimioterapia VIP fue el único factor pronóstico desfavorable significativo. Con una mediana de seguimiento de 64 (r: 5-204) meses, a 10 años las probabilidades de supervivencia libre de eventos y supervivencia global para todo el grupo fueron respectivamente de 0.82 (EE = 0.05) y 0.90 (EE = 0.03). Los resultados con la estrategia SFOP/SFCE 95 fueron excelentes. La ausencia de respuesta a la quimioterapia de primera línea fue el único factor pronóstico adverso significativo. La estrategia de watch and wait probó ser segura y eficaz.

Gonadal malignancy in 202 female patients with disorders of sex development containing Y-chromosome material.

The objective of this study was to examine risks for gonadal malignancy in a large sample of adult female patients with disorders of sex development (DSD). A retrospective-observational study was conducted from July 1992 to March 2015 and 202 women with DSD were enrolled. Tumor risks for different types of DSD were measured. We found that the patients' total gonadal-malignancy risk was 18.3% (37/202). Tumors included gonadoblastoma (n = 11), seminoma (n = 8), dysgerminoma (n = 5), choriocarcinoma (n = 1), sertoli cell tumors (n = 11), and leydig cell tumors (n = 1). The incidence of gonadal malignancy in patients with complete androgen insensitivity syndrome (CAIS), pure 46, XY gonadal dysgenesis, 45 X/46 XY mixed gonadal dysgenesis, 17α-hydroxylase/17, 20-lyase deficiency and partial androgen insensitivity syndrome (PAIS) were 27.1% (13/48), 22.4% (15/67), 10.9% (5/46), 10% (2/20) and 9.5% (2/21), respectively. Our results suggest that the incidence of gonadal malignancy increases with age for female patients with Y-chromosome material. Upon diagnoses, immediate, prophylactic gonadectomies should be considered for adult female patients with DSD containing Y chromosome material if they cannot receive regular follow-ups.

Activin-ßC modulates gonadal, but not adrenal tumorigenesis in the inhibin deficient mice.

Activins and inhibins are involved in the regulation of several biological processes, including reproduction, development and fertility. Deregulation of the inhibin/activin signaling pathway has been implicated in the progression of reproductive and adrenal cancers. Deletion of the inhibin α-subunit results in up-regulation of the circulating levels of activins and this leads to the development of sex-cord stromal tumors followed by a cancer associated-cachexia in mice. When gonadectomy is performed, development of adrenocortical carcinomas is observed. We previously showed that overexpression of activin-ßC modulates the development of sex-cord stromal tumors and reduces cancer-cachexia in the inhibin-deficient mice by antagonizing the activin signaling pathway. The adrenal cortex and gonads share in common a large subset of genes, consistent with their common embryonic lineage. Additionally, it has been shown that adrenocortical carcinomas adopt an altered cellular identity resembling the ovary. Therefore, a study to assess the impact of overexpression of activin-ßC on the onset of adrenocortical carcinoma in gonadectomized inhibin-deficient mice was warranted. Within the current study we evaluated markers of apoptosis, proliferation, tumor burden, survival analysis and serum levels of activin-A in gonadectomized mice versus sham operated controls. Results showed that overexpression of activin-ßC modulated the development of reproductive tumors but had no effect on adrenal tumorigenesis. Our data reinforces the importance of activin-ßC in reproductive biology and suggest that activin-ßC is a tumor modulator with gonadal specificity.

Androgen insensitivity syndrome.

PURPOSE OF REVIEW: Androgen insensitivity syndrome (AIS) can present with a wide range of phenotypes, and its management requires a multidisciplinary approach from diagnosis in infancy to adulthood. This review provides an update on some clinical and genetic aspects in AIS. Additional outcome data on surgical and psychosexual findings are presented, together with a discussion on the risk of development of gonadal tumours in AIS. RECENT FINDINGS: This review covers clinical features of AIS, including recent trends in sex of rearing, aspects of androgen receptor gene mutations and longer term outcomes in both complete and partial forms of AIS. SUMMARY: More follow-up studies are needed to optimize management in AIS, especially in the partial form. Predicting the risk of gonadal tumours is key to determining the timing of gonadectomy or whether to retain the gonads in the long term.

Myoid gonadal stromal tumor: a clinicopathologic study of three cases of a distinctive testicular tumor.

OBJECTIVES: To report three new cases of testicular myoid gonadal stromal tumor to better characterize its features. METHODS: The clinicopathologic findings (including follow-up) were evaluated and a review of the literature was performed. RESULTS: The patients were 38, 43, and 59 years old, and tumor sizes were 1.2, 1.3, and 3.2 cm. All were unilateral, well circumscribed, adjacent to the rete testis, and composed exclusively of spindled cells with elongated nuclei and occasional nuclear grooves arranged in fascicles with admixed variably ectatic blood vessels. Nucleoli were inconspicuous, and the cytoplasm was scant, ill-defined, and pale/lightly eosinophilic. No sex cord component was present. Mitotic figures ranged from zero to five per 10 high-power fields. Significant atypia, lymphovascular invasion, and necrosis were absent. All were consistently positive for smooth muscle actin, S100 protein, FOXL2, and steroidogenic factor 1 but negative for h-caldesmon, calretinin, and SOX9. Inhibin and calponin were focally positive. All patients were alive and well at 5, 31, and 58 months postorchiectomy. Combining our cases with those previously reported (n = 6) shows that this neoplasm occurs mostly in younger men (mean, 37 years), and all follow-up thus far (mean, 25 months) has been benign. CONCLUSIONS: Myoid gonadal stromal tumors are small (<4 cm) indolent testicular tumors distinctly different from other sex cord-stromal tumors and are adequately managed by orchiectomy.

The therapeutic potential of blocking the activin signalling pathway.

Members of the transforming growth factor ß (TGF-ß) family regulate fundamental physiological process, such as cell growth, differentiation and apoptosis. As a result, defects in this pathway have been linked to uncontrolled proliferation and cancer progression. Here we explore the signal transduction mechanism of TGF-ß focusing on therapeutic intervention in human diseases. Like TGF-ß, another member of the TGF-ß superfamily, activin has been proven to play an important role in maintenance of tissue homeostasis and dysregulation leads to disease. Several studies showed elevated levels of activin are responsible for the development of gonadal tumours and a cachexia-like weight loss syndrome. Discussing the recent advances in approaches developed to antagonise the activin pathway and the encouraging results obtained in animal models, this review presents a therapeutic rationale for targeting the activin pathway in conditions such as cachexia, neuromuscular and/or musculoskeletal disorders.