Outcome of Children and Adolescents With Primary Intracranial Germinoma Treated With Chemotherapy and Reduced Dose-Field Irradiation: A Prospective Brazilian Experience.

PURPOSE: This prospective Brazilian single-arm trial was conducted to determine response to chemotherapy and survival after response-based radiotherapy in children with intracranial germinomas, in the setting of a multi-institutional study in a middle-income country (MIC) with significant disparity of subspecialty care. PATIENTS AND METHODS: Since 2013, 58 patients with histologic and/or serum and CSF tumor marker evaluations of primary intracranial germ cell tumors were diagnosed; 43 were germinoma with HCGß levels ≤200 mIU/mL and five between 100 and 200 mIU/mL. The treatment plan consisted of four cycles of carboplatin and etoposide followed by 18 Gy whole-ventricular field irradiation (WVFI) and primary site(s) boost up to 30 Gy; 24 Gy craniospinal was prescribed for disseminated disease. RESULTS: Mean age 13.2 years (range, 4.7-25.5 years); 29 were males. Diagnosis was made by tumor markers (n = 6), surgery (n = 25), or both (n = 10). Two bifocal cases with negative tumor markers were treated as germinoma. Primary tumor location was pineal (n = 18), suprasellar (n = 14), bifocal (n = 10), and basal ganglia/thalamus (n = 1). Fourteen had ventricular/spinal spread documented by imaging studies. Second-look surgery occurred in three patients after chemotherapy. Thirty-five patients achieved complete responses after chemotherapy, and eight showed residual teratoma/scar. Toxicity was mostly grade 3/4 neutropenia/thrombocytopenia during chemotherapy. At a median follow-up of 44.5 months, overall and event-free survivals were 100%. CONCLUSION: The treatment is tolerable, and WVFI dose reduction to 18 Gy preserves efficacy; we have demonstrated the feasibility of successfully conducting a prospective multicenter trial in a large MIC despite resource disparity.

Suprasellar Germinomas: 2 Case Reports and Literature Review.

BACKGROUND: Germinomas are rare malignant central nervous system tumors, a type of germ cell tumor, according to the 2016 World Health Organization Classification of Brain Tumors. Most of these tumors develop along the midline, most often from the pineal gland, followed by tumors arising in the suprasellar cisterns. Suprasellar germinomas commonly manifest with diabetes insipidus, visual impairment, and hypothalamic-pituitary failure. We present a literature review from the PubMed database and report 2 cases of suprasellar germinomas. CASE DESCRIPTION: Both pediatric patients presented with progressive visual loss; one did not show endocrinologic impairment, and the other presented with hypothyroidism, diabetes insipidus, and generalized edema. Magnetic resonance imaging showed expansive suprasellar masses in both cases, confirmed as germinomas at histopathologic examination. The patients were treated with the same surgical approach, although their outcomes were different because of endocrinologic and post surgical complications. CONCLUSIONS: Suprasellar germinomas are highly curable lesions when diagnosed early. The treatment remains controversial and should be individualized, but the association of chemotherapy and radiotherapy allows reduce adverse effects and shows great results.

[Pineal region tumors in children: is gross-total resection necessary? A single-center experience]. / Tumores de región pineal en niños: ¿es la resección total necesaria? Experiencia en un centro de referencia.

BACKGROUND: Survival of children with pineal region tumors has increased significantly in the last decade; these tumors have an insidious outcome associated with endocrine disorders with high morbidity and mortality, especially after gross resection. The objective was to report the survival, outcome, morbidity and mortality according to type of surgery, histology and treatment in children with pineal region tumors. METHODS: This retrospective study included all patients of 17 years or less with diagnosis of pineal region tumor, who went over a period of 10 years to a children's hospital. A histopathological review was made, and the extent of resection was determined. The survival was also estimated. RESULTS: Forty-six patients were included, out of which 36 had complete medical records and adequate pathologic material. Gross resection was performed in 24 (66.6 %), and biopsy in 12 (33.3 %); 23 (88 %) patients died; hydroelectrolytic imbalance was the cause of 14 deaths (60 %) and the other nine (39.1 %) were secondary to tumor progression. Ten-years survivals among patients treated with gross resection and biopsy were 52 and 75 %, respectively (p = 0.7). Endocrine alterations were observed in 13 patients (36.1 %); in 10 of these (76.9 %) the total resection was performed. CONCLUSIONS: Pineal region tumors in children can be treated with diagnostic biopsy, followed by adjuvant treatment consisting of chemotherapy and radiotherapy.

Introducción: la supervivencia de los niños con tumores de la región pineal se ha incrementado en la última década; estos tienen una evolución insidiosa asociada con los desórdenes endocrinológicos y una alta morbilidad y mortalidad, sobre todo después de la resección. El objetivo es reportar la supervivencia, la morbilidad y mortalidad según el tipo de cirugía, la histología y el tratamiento en un grupo de niños con tumores de la región pineal. Métodos: estudio retrospectivo que incluyó a todos los pacientes con diagnóstico de tumor de la región pineal menores de 17 años de edad que acudieron en un periodo de 10 años a un hospital de pediatría. Se realizó una revisión histopatológica, se determinó la extensión de la resección y se estimó la supervivencia. Resultados: se incluyeron 46 pacientes, 36 de los cuales tenían expediente completo y material de patología adecuado. La resección total se realizó en 24 (66.6 %) y biopsia en 12 (33.3 %); fallecieron 23 pacientes (88 %) y fue el desequilibrio hidroelectrolítico la causa de 14 defunciones (60 %) y la progresión tumoral la causa de las 9 defunciones restantes (39.1 %). La sobrevida a 10 años de los pacientes tratados con resección total y biopsia fue del 52 y 75 %, respectivamente, con una p = 0.7; se presentaron alteraciones endocrinológicas en 13 (36.1%) pacientes de los cuales a 10 (76.9 %) se les realizó la resección de la tumoración. Conclusión: los tumores de la región pineal en niños se pueden tratar con biopsia diagnóstica seguida de tratamiento adyuvante con quimioterapia y radioterapia.

An intrasellar germinoma with normal tumor marker concentrations mimicking primary lymphocytic hypophysitis.

Intracranial germinomas (GE) are malignant neoplasms most commonly found in the suprasellar region, which may cause anterior and particularly posterior pituitary hormone deficits with central diabetes insipidus (DI). Differential diagnosis of pituitary stalk thickening includes granulomatous, inflammatory, infectious, and neoplastic lesions. Although careful analysis of clinical, laboratory, and imaging findings may facilitate the diagnosis, transsphenoidal biopsy is indicated to confirm the disease, as the correct diagnosis directs the appropriate treatment.

An intrasellar germinoma with normal tumor marker concentrations mimicking primary lymphocytic hypophysitis / Germinoma intrasselar com marcadores tumorais normais mimetizando hipofisite linfocítica primária

Intracranial germinomas (GE) are malignant neoplasms most commonly found in the suprasellar region, which may cause anterior and particularly posterior pituitary hormone deficits with central diabetes insipidus (DI). Differential diagnosis of pituitary stalk thickening includes granulomatous, inflammatory, infectious, and neoplastic lesions. Although careful analysis of clinical, laboratory, and imaging findings may facilitate the diagnosis, transsphenoidal biopsy is indicated to confirm the disease, as the correct diagnosis directs the appropriate treatment.

Germinomas intracranianos (GE) são neoplasias malignas comumente na região suprasselar, podendo causar deficiência hormonal da hipófise anterior, em particular da hipófise posterior, com diabetes insípido central (DI). Entre os diagnósticos diferenciais do espessamento de haste hipofisária, incluem-se doenças granulomatosas, inflamatórias, infecciosas e neoplásicas. Embora as avaliações clínica, laboratorial e a ressonância magnética selar sugiram o diagnóstico, a biópsia transesfenoidal está indicada para confirmação, visto que o diagnóstico correto direciona o tratamento.

Germ cell tumor presenting as sellar mass with suprasellar extension and long history of hypopituitarism.

OBJECTIVE: Primary central nervous system germ cell tumors are rare neoplasms usually located in the pineal and/or suprasellar region. Pure germinomas do not usually secrete beta-human chorionic gonadotropin hormone (beta-HCG) or alpha-fetoprotein (AFP) and diagnosis is made a few weeks or months after beginning of symptoms. CASE: Here we report a case of a pure germinoma in a 20 year-old woman presenting as a sellar mass with suprasellar extension, abnormal serum beta-HCG and a long history of polyuria and polydipsia (4 years), that was initially diagnosed as a pituitary macroadenoma. CONCLUSION: This presentation highlights the importance of thinking in alternative diagnosis to pituitary adenoma when diabetes insipidus is the initial symptom.

Rare sellar lesions.

Sellar masses are associated most commonly with pituitary adenomas. Many other neoplastic, inflammatory, infectious, and vascular lesions, however, may affect the sellar region and mimic pituitary tumors. These lesions must be considered in a differential diagnosis. This article describes the characteristics of rare sellar masses that provide clues to their differential diagnosis.

[Primary intracranial germ cell tumors in children: evaluation of fourteen cases]. / Tumores de células germinativas intracranianos na infância: avaliação de 14 casos.

This study evaluates the diagnosis, therapy and survival of 14 patients with primary intracranial germ cell tumors during the period from 1991 to 2001. There were 11 males and 3 females. Mean age was 12.2 years old (20 days-18 years). On admission, the most common symptoms were headache (10/14), vomiting (6/14) and visual (6/14). The tumor was in pineal and hypothalamic region in 10 cases, suprasellar in 3 cases, and in the cerebral parenchyma in 1 case. Histologically there were 1 embryonal carcinoma, 5 germinomas, 2 mature teratomas, 1 immature teratoma and 5 mixed germ cell tumors. Treatment differed among the patients according to the type of tumor. Three patients died after tumor progression or relapse and one patient died from another condition. The remaining patients are alive and without disease.

Tumores de células germinativas intracranianos na infância: avaliação de 14 casos / Primary intracranial germ cell tumors in children: evaluation of fourteen cases

This study evaluates the diagnosis, therapy and survival of 14 patients with primary intracranial germ cell tumors during the period from 1991 to 2001. There were 11 males and 3 females. Mean age was 12.2 years old (20 days-18 years). On admission, the most common symptoms were headache (10/14), vomiting (6/14) and visual (6/14). The tumor was in pineal and hypothalamic region in 10 cases, suprasellar in 3 cases, and in the cerebral parenchyma in 1 case. Histologically there were 1 embryonal carcinoma, 5 germinomas, 2 mature teratomas, 1 immature teratoma and 5 mixed germ cell tumors. Treatment differed among the patients according to the type of tumor. Three patients died after tumor progression or relapse and one patient died from another condition. The remaining patients are alive and without disease.

Este estudo avalia o diagnóstico, a terapia e a sobrevida de 14 pacientes com tumor de células germinativas intracraniano durante o período entre 1991 e 2001. Onze pacientes eram do sexo masculino e três do feminino. A média de idade do grupo foi 12,5 anos (20 dias-18 anos). Na admissão, os mais comuns sintomas foram cefaléia (10/14), vômitos (6/14) e visuais (6/14). Os tumores estavam localizados em região hipotalâmica/hipofisária em 10 casos, suprasselar em 3 casos e intraparenquimatosa em 1 caso. Histologicamente, havia 1 caso de carcinoma embrionário, 5 de germinomas, 2 de teratoma maduro, 1 de teratoma imaturo e 5 de tumores mistos. O tratamento foi variável, dependendo da histologia da lesão. Três pacientes morreram após a progressão tumoral ou recidiva e um paciente morreu devido causa não relacionada ao tumor. Os demais estão vivos e sem doença.

Post-chemotherapy residual mass in non-seminomatous testicular cancer. The role of retroperitoneal lymph node dissection.

PURPOSE: To determine the role of RPLND for residual masses following chemotherapy in patients with non-seminomatous germ cell tumors (NSGCT) stage T1N2 and T1N3 (IIB and IIC). MATERIALS AND METHODS: We have preformed retrospective analysis of 11 patients who underwent RPLND for residual masses following chemotherapy in an oncologic reference center between January 1997 and December 2002. All patients harbored either pure nonseminomatous or mixed tumors in the testis tissue and had undergone 4 cycles of primary chemotherapy with bleomycin, etoposide and cisplatin. The residual masses were assessed by abdominal computed tomography preoperatively. RESULTS: There were perioperative complications in 3 cases owing to vascular iatrogenic lesion. One of who died in the early postoperative period due to extensive iliac thrombosis. The other 2 patients had an inferior vena cava injury owing to the difficulty in removing the attached lymph nodes. The injuries were repaired by continuous suture with Prolene 5-0. All patients had tumors in the final pathological report and were referred to other 2 cycles of chemotherapy with the same drugs. Seven patients (63.3%) had complete response and remained free of the disease in a mean follow up of 38.3 months (ranging from 12 to 72). The remaining 3 patients had disease progression, 2 of which died 6 and 12 months after surgery, respectively, and one patient missed the follow-up after salvage chemotherapy. CONCLUSION: Retroperitoneal lymph node dissection for residual masses after chemotherapy is a high-morbidity procedure, even by experienced surgeons, although it remains an efficient modality of treatment in advanced germ cell carcinoma. The high frequency of tumor found in the RPLFN following chemotherapy might have been caused by the small number of patients in this study.

Post-cheotherapy residual mass in non-siinomatous testicular cancer: the role of retroperitoneal lymph node dissection

PURPOSE: to determine the role of RPLND for residual masses following chiotherapy in patients with non-siinomatous germ cell tumors (NSGCT) stage T1N2 and T1N3 (IIB and IIC). MATERIALS AND METHODS: We have preformed retrospective analysis of 11 patients who underwent RPLND for residual masses following chiotherapy in an oncologic reference center between January 1997 and Deciber 2002. All patients harbored either pure nonsiinomatous or mixed tumors in the testis tissue and had undergone 4 cycles of primary chiotherapy with bleomycin, etoposide and cisplatin. The residual masses were assessed by abdominal computed tomography preoperatively. RESULTS: There were perioperative complications in 3 cases owing to vascular iatrogenic lesion. One of who died in the early postoperative period due to extensive iliac thrombosis. The other 2 patients had an inferior vena cava injury owing to the difficulty in rioving the attached lymph nodes. The injuries were repaired by continuous suture with Prolene 5-0. All patients had tumors in the final pathological report and were referred to other 2 cycles of chiotherapy with the same drugs. Seven patients (63.3 percent) had complete response and riained free of the disease in a mean follow up of 38.3 months (ranging from 12 to 72). The riaining 3 patients had disease progression, 2 of which died 6 and 12 months after surgery, respectively, and one patient missed the follow-up after salvage chiotherapy. CONCLUSION: Retroperitoneal lymph node dissection for residual masses after chiotherapy is a high-morbidity procedure, even by experienced surgeons, although it riains an efficient modality of treatment in advanced germ cell carcinoma. The high frequency of tumor found in the RPLFN following chiotherapy might have been caused by the small number of patients in this study.

Recaída tardía de los tumores germinales no seminomatosos de testículo estadio I / Late relapses of stage I nonseminomatous testicular germ-cell tumors

Las recaídas tardías de los tumores no seminomatosos de testículos constituyen una rara entidad (2 a 3 por ciento de los casos). Este trabajo analiza todos los casos de tumores germinales no seminomatosos de testículos diagnosticados en el Hospital de Clínicas (Servicio de Oncología Clínica) y en el Instituto Nacional de Oncología, durante un período de 15 años (1985-1999); 21 de los 69 pacientes encontrados fueron definitivamente incorporados al estudio al reunir los criterios de inclusión como tumores no seminomatosos estadio I. En un solo caso se observó una recaída tardía (más allá de los dos años) siendo este caso el que motivó la actual revisión. Se describen asimismo los principales aspectos relacionados con el manejo terapéutico y la evolución de los mismos. La existencia de 2 por ciento-3 por ciento de recaídas tardías en los pacientes con tumores germinales que alcanzan una remisión completa de su enfermedad, subrayan la importancia de continuar con el seguimiento más allá de los 2 años(AU)

Germinoma localizado nos núcleos da base e tálamo com invasäo do tronco cerebral: relato de caso / Germinoma localizated in basal ganglia and thalamus with brain stem invasion: case report

Descrevemos o caso de um paciente com diagnóstico de germinoma nos núcleos da base e tálamo, com invasao do tronco cerebral, ressaltando as características observadas nos exames de tomografia computadorizada e de ressonância magnética, os possíveis diagnósticos diferenciais, e a necessidade da comprovaçao anátomo-patológica, por tratar-se de localizaçao pouco frequente de um tumor com possibilidade de evoluçao favorável após tratamento com quimio e radioterapia.

[Female pseudohermaphroditism. Mixed germ cell tumor of the ovary. A case report]. / Pseudohermafroditismo femenino. Tumor de células germinales de ovario, mixto. Presentación de un caso.

It is known as Pseudohermaphroditism or intersexual state, those entities in which external genitalia are ambiguous or are not according with gonadal o genetic chromosomic sex. They can have diverse etiology. Continual exposition to estrogens or androgens may induce female or male dysmorphism, and also development of benign or malignant tumors at target organs. We present a case of a young woman, 15 years old, with virilization, who attend medical consultation for progressive abdominal growing. The presence of ambiguous, genitalia since birth, was not a previous reason of concern. Diagnostic, findings, management and follow up for about 4 months are described and also a topic review. Genitalia develop during first trimester of intrauterine life, under influence of sexual steroids, and changes of sexual development can emerge as consequence of endocrine or morphologic disorders and the later ones, related to karyotypic abnormalities. Sexual steroid and their metabolites can demonstrate individually, different biological effects, suggesting the presence of individual receptors. The presence of cooperative effects between each steroid produce even more complexity to the evaluation of each steroid. Various mutations principally at gene receptors of sexual steroids, cause resistance to them. At female pseudohermaphroditism in difference from male P. there is no errancy at genetic gonadal transmission. These women are intrauterine exposed to excessive quantities of androgens, and they have normal internal genitalia but external ambiguous genitalia. The involved androgen comes from external factors, a it occurs at mother who receives progesterone to avoid abortion, but it is due frequently to androgen storage, caused by enzymatic blockade at steroidogenesis (adrenogenital syndrome).

Pseudohermafroditismo femenino. Tumor de células germinales de ovario, mixto: presentación de un caso / Female pseudohermaphroditism. Mixed germinal coll ovarian tumor: one case presentation

Se conoce como Pseudohermafroditismo o estado intersexual a las entidades en las que el aspecto de los genitales externos es ambiguo o está en desacuerdo con el sexo cromosómico gonadal o genético y, puede tener etiologías diversas. La exposición continua a estrógenos o a andrógenos puede inducir dismorfismo femenino así como el desarrollo de tumor es benignos y o malignos en los órganos blancos. Se presenta el caso de una joven de 15 años con virilización, que acude a consulta médica por presentar tumor de crecimiento progresivo en abdomen. La presencia de genitales ambiguos desde su nacimiento no había sido motivo de consulta previa. El diagnóstico, hallazgos, manejo y seguimiento en cuatro meses son descritos, así como la revisión del tema

Germinoma da glândula pineal / Pineal gland germinoma

Os autores apresentam um caso de germinoma da glândula pineal tratado por remoçao cirúrgica e radioterapia. Os tumores da pineal ocupam um segmento relativamente pequeno, aproximadamente 0,5 por cento dos tumores intracranianos. Sao discutidas as características clínicas, patológicas e cirúrgicas e tratamento complementar com radioterapia.

Disseminated form of an intracranial germinoma: report of one case

The authors report a case of a suprasellar germinoma with a diffusely involvement of the ventricular system. The proper diagnostic and therapeutic procedures for the management of this lesion are also discussed.