Cardiotoxicidad por irradiación en pediatría / Cardiotoxicity by irradiation in Pediatrics

Introducción: La cardiotoxicidad depende de varios factores y se manifiesta por las alteraciones cardiovasculares inducidas por los tratamientos oncoespecíficos en la función y morfología del corazón. Objetivo: Determinar las manifestaciones de cardiotoxicidad en pacientes pediátricos. Métodos: Estudio descriptivo transversal en el que se incluyeron 79 pacientes tratados en el Instituto de Oncología y Radiobiología de Cuba con irradiación tórax-mediastino, entre enero 2008 a diciembre 2014. La enfermedad de Hodgkin estaba presente en 54 pacientes y en 25, tumores del sistema nervioso central: meduloblastomas en 19 y tumores primarios neuroectodérmicos en 6 pacientes. A todos se les hizo historia clínica con examen físico, electrocardiograma de 12 derivaciones y ecocardiograma 2D pre- y postratamientos. Se analizaron las características demográficas y clínicas. Los enfermos con Hodgkin recibieron irradiación con intensidad de 2 400 centigray y de 2 340 los pacientes con tumores del sistema nervoso central; la poliquimioterapia se realizó con antraciclinas, vincristina, vinblastina y otros. Resultados: La edad promedio de todos los pacientes fue de 7 años con predominio del sexo masculino. No se registraron síntomas o signos de cardiotoxicidad. Conclusiones: En nuestra serie de pacientes la irradiación del área cardiaca aparentemente es bien tolerada, sin aparición temprana de cardiotoxicidad, ni en periodos de seguimiento de hasta 9 años. Aparecieron naúseas y leucopenias transitorias en algunos casos. No existió diferencias en las toxicidades en los grupos de tumores estudiados Es necesario mantener un seguimiento estrecho para descartar la aparición de cardiotoxicidad en años siguientes(AU)

Introduction: Cardiotoxicity depends on various factors and it is evident in cardiovascular alterations induced by oncologic treatments directed to the heart´s function and morphology. Objective: To determine the symptoms of cardiotoxicity in pediatric patients. Methods: Descriptive and cross-sectional study in which there were included 79 patients treated in the Cuban Institute of Oncology and Radiobiology with thorax-mediastine irradiation from January 2008 to December 2014. Hodgkin disease was present in 54 patients, tumors of the central nervous system in 25, medulloblastomas in 19, and neuroectodermic primary tumors in 6. All the patients underwent physical examination, 12 -lead electrocardiogram and pre- and post-treatment 2D echocardiograms to include in the clinical records. The demographic and clinic characteristics were analyzed. Hodgkin disease's patients received irradiation with 2 400 cGy intensity and the patients presenting tumors in the central nervous system with 2 340 cGy. Polychemotherapy was carried out with antracyclines, vincristine, vinblastine and others. Results: Average age of all patients was 7 years with predominance of male sex. Symptoms of cardiotoxicity were not recorded. Conclusions: In the serie of analyzed patients, irradiation in the heart area was apparently well beared by the patients, without early appearance of cardiotoxicity, not even in follow up periods of 9 years. Transitory nausea and leucopenia appeared in some cases. There are no differences in the toxicities of the different tumour's groups studied. It is necessary to keep the regular follow up to rule out the appearence of cardiotoxicity in the next years(AU)

Ewing Sarcoma / 임상소아혈액종양

Ewing sarcoma is the second most frequently occurring malignant tumor of the bone and soft tissue in adolescents and young adults. Genetically, Ewing sarcoma is characterized by balanced chromosomal translocation in which a member of FET gene family is fused with an ETS transcription factor, with the most common fusion being EWSR1-FLI1 (85% of cases). Treatment of Ewing sarcoma is based on multidisciplinary approach (local surgery, radiotherapy and multiagent chemotherapy), which are associated with chronic late effects that may compromise quality of life of survivors. First line treatment includes combination of drugs incorporating doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide, and dactinomycin. The beneficial role of high dose chemotherapy has been suggested in high-risk localized Ewing sarcoma patients, and the studies are being performed to investigate the role in metastatic disease. The 5-year overall survival for localized Ewing sarcoma has improved to reach 65% to 75%. But patients with metastatic disease have a 5-year survival rate of <30%, except for those with isolated pulmonary metastasis (approximately 50%). Patients with recurrent tumor have a dismal prognosis. Novel therapeutic strategies based on understanding of molecular mechanisms are needed to improve the outcome of Ewing sarcoma and to lessen the treatment-related late effects.

Thyroid dysfunction in patients with childhood-onset medulloblastoma or primitive neuroectodermal tumor

PURPOSE: We investigated the clinical characteristics of patients who developed thyroid dysfunction and evaluated the risk factors for hypothyroidism following radiotherapy and chemotherapy in pediatric patients with medulloblastoma or primitive neuroectodermal tumor (PNET). METHODS: The medical records of 66 patients (42 males) treated for medulloblastoma (n=56) or PNET (n=10) in childhood between January 2000 and December 2014 at Seoul National University Children’s Hospital were retrospectively reviewed. A total of 21 patients (18 high-risk medulloblastoma and 3 PNET) underwent high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) RESULTS: During the median 7.6 years of follow-up, 49 patients (74%) developed transient (n=12) or permanent (n=37) hypothyroidism at a median 3.8 years of follow-up (2.9–4.6 years). Younger age ( < 5 years) at radiation exposure (P=0.014 vs. ≥9 years) and HDCT (P=0.042) were significantly predictive for hypothyroidism based on log-rank test. However, sex, type of tumor, and dose of craniospinal irradiation (less vs. more than 23.4 Gy) were not significant predictors. Cox proportional hazard model showed that both younger age (< 5 years) at radiation exposure (hazard ratio [HR], 3.1; vs. ≥9 years; P=0.004) and HDCT (HR, 2.4; P=0.010) were significant predictors of hypothyroidism. CONCLUSIONS: Three-quarters of patients with pediatric medulloblastoma or PNET showed thyroid dysfunction, and over half had permanent thyroid dysfunction. Thus, frequent monitoring of thyroid function is mandatory in all patients treated for medulloblastoma or PNET, especially, in very young patients and/or high-risk patients recommended for HDCT/ASCR.

Embryonic Tumor with Abundant Neuroepithelium and True Rosettes (ETANTR): Case Report and Literature Review

The embryonal tumor with abundant neuropil and true rosettes (ETANTR) is an extremely rare variant of the primitive neuroectodermal tumor (PNET). About 80 cases have been reported since its first description in the literature, in 2000. The ETANTR occurs in very young patients, especially children under 6 years of age. It is found mainly in the cerebral cortex. Headache, focal neurological signs, seizures, increased head circumference and psychomotor developmental delay are the most frequent symptoms of ETANTR. Histologically, it displays the features of an ependymoblastoma and a neuroblastoma, showing areas of neuroepithelium fibrillar rosettes with ependymoblastic zones and interposed undifferentiated neuroepithelial cells. The ETANTR is distinguishable from other embryonal tumors due to the abundance of neuroepithelium. Genetic studies have demonstrated the presence of polysomy of chromosome 2 and chromosome 19q13.42 amplification. This is an extremely aggressive tumor with a mean survival ranging from 9 to 48 months. We present the first report in Brazil, published in indexed literature, of an ETANTR case involving a young child.

O tumor embrionário com neurópilo abundante e rosetas verdadeiras (TENARV) é uma variante muito rara do tumor neuroectodérmico primitivo (TNEP), com cerca de 80 casos publicados desde a sua primeira descrição na literatura, em 2000. O TENARV ocorre em pacientes muito jovens, especialmente crianças abaixo de 6 anos de idade, atingindo principalmente o córtex cerebral. Cefaleia, sinais focais, crise convulsiva, aumento do perímetro cefálico e atraso do desenvolvimento psicomotor são os sintomas mais frequentes da TENARV. Histologicamente, este tipo de tumor apresenta as características combinadas de um ependimoblastoma e um neuroblastoma, demonstrando áreas de neuroepitélio fibrilar com rosetas ependimoblásticas de permeio e zonas de células neuroepiteliais indiferenciadas. O TENARV é distinguível de outros tumores embrionários pela abundância de neuroepitélio. Estudos genéticos demonstram a presença de polissomia do cromossomo 2 e amplificação do cromossomo 19q13.42. Trata-se de um tumor extremamente agressivo, com sobrevida média entre 9 e 48 meses. Apresentamos o primeiro relato brasileiro, publicado em literatura indexada, de um caso de TENARV acometendo uma criança jovem.

Reconstrucción del húmero con aloinjerto masivo tras resección en bloque por sarcoma de Ewing. Evolución a largo plazo. A propósito de un caso / Reconstruction of the humerus with massive allograft after block resection by Ewing's sarcoma. Long-term evolution. A case report

El Sarcoma de Ewing es un tumor óseo primitivo maligno que fue descrito por Ewing en 1921. Representa aproximadamente el 5% de todas las neoplasias malignas del hueso. Tiene el pronóstico menos favorable de todas las neoplasias malignas del hueso. Desde finales de los años 70 se han desarrollado técnicas de salvataje, con la finalidad de preservar la vida, limitar el daño, mantener la funcionalidad en la medida de lo posible y optimizar la calidad de vida evitando al máximo las complicaciones. La reconstrucción del húmero, posterior a resecciones amplias, es un reto. Presentamos el caso de paciente masculino de 7 años, portador de Sarcoma de Ewing en el húmero el cual fue tratado con resección en bloque extensa del húmero y reconstrucción con aloinjerto masivo de tibia. Presentamos su manejo y evolución a largo plazo(AU)

Ewing´s Sarcoma is a malignant bone tumor that was first describe by Ewing in 1921. Represents about 5% of all malignant neoplasms of bone. Have the least favorable prognosis of all malignancies of bone. Since the late 70s salvage techniques have been developed, in order to preserve life, limit damage, maintain functionality as far as possible and optimize quality of life posible with minimal complications. Therefore, the reconstruction of the posterior humeral wide resections still challenging. We present the case of 7 years old male patient, with Ewing´s Sarcoma in the humerus which was treated with wide resection and reconstruction humeral block with massive tibia bone allograft. We present handling and long-term evolution(AU)

Primitive neuroectodermal tumors of kidney: Our experience in a tertiary care center.

OBJECTIVES: Primitive neuroectodermal tumors (PNET) are rare highly aggressive neoplasms. The diagnosis is made by histopathology with the support of immunohistochemistry (IHC) and cytogenetics. The aggressive multimodality treatment is recommended for the management of these tumors. The purpose of our study is to review our experiences in the diagnoses and treatment of PNET of the kidneys. MATERIALS AND METHODS: We retrospectively reviewed the data of all the patients, who were treated for the PNET of the kidneys at our institute between April and March 2011 and compared with the available literature. RESULTS: A total of eight patients were treated for PNET of the kidney. Out of the eight patients, four were males and four females. Nearly 50% of our patients had inferior vena caval thrombus at the time of presentation. The diagnosis was made on histopathology supported by IHC. Out of the eight patients, one patient had intraoperative death due to massive pulmonary thromboembolism and another died on the 7th post‑operative day due to disseminated intravascular coagulation and multiorgan failure. Rest six patients were treated with post‑operative chemotherapy or a combination of chemotherapy and radiotherapy. For these six patients, overall median survival was 45 months with a 3 year disease‑free survival of 66% and 5 year survival of 44%. CONCLUSIONS: PNET of the kidneys are rare peripheral neuroectodermal tumors with an aggressive clinical course. These tumors carry a very poor prognosis. An aggressive treatment approach using a combination of surgery, chemotherapy and radiotherapy is recommended for a reasonable survival in these tumors.

CT and MRI appearances of peripheral primitive neuroectodermal tumors / 实用放射学杂志

Objective To explore CT and MRI features of peripheral primitive neuroectodermal tumors (pPNET) .Methods CT and MRI findings were retrospectively analyzed in 9 cases with pPNET confirmed by pathology .Of them ,8 patients underwent CT imaging ,and 5 patients underwent MR imaging .Results The lesions occurred in head and neck in 2 cases ,chest in 3 cases ,scrotum in 1 case ,right scapular region in 1 case ,and lower extremity in 2 cases .The lesions were more solitary (7/9) with round ,lobular or irregular shape .The longest diameter was between 1 .6 cm -13 .8 cm ,and the median diameter was 6 .2 cm .8 cases had blurred boundary .On CT plain scanning ,the lesions were mixed density with predominant isodensity .On MR imaging ,the lesions were slightly T1 hypointensity and heterogeneous T2 hyperintensity .Enhancement patterns were varied ,and the common way was mild‐to‐moderate heterogeneous enhancement .3 cases of them were closely associated with bone ,and showed osteolytic bone destruction . Conclusion The CT and MRI features of pPNET has lack characteristics ,CT and MR imaging have some value for localization diagnosis .

The diagnostic value of CT and MRI on peripheral primitive neuroectodermal tumors / 中国医师进修杂志

Objective To evaluate the imaging performance and characteristics of peripheral primitive neuroectodermal tumors (pPNET), in order to raise awareness of the disease and the diagnostic accuracy. Methods Thirteen patients with pPNET who confirmed by puncture or pathology were enrolled in this study. The CT and MRI features were retrospectively analyzed. Four patients received simple routine CT examination, and 9 patients had MRI examination based on X-ray, CT examination. Results The part of body involved was more widely.Two patients occurred in the sinuses, 1 patient in the chest wall, 1 patient in the lung, and 3 patients in the abdominal and pelvic(1 patient involved the pelvic floor through the pelvic wall lesions to basins), 1 patient in the spine, and 5 patients located in the extremities. The characteristics of pPNET by CT and MRI in soft tissue of 8 patients showed single large soft tissue mass, and the biggest was 11.2 cm × 10.6 cm. In bonds and joints of 5 patients, CT and MRI showed wide range of soft tissue mass, mixed internal signal/density with obviously uneven enhancement, significant bone destruction and dissolvable osseous changes, and no obvious tumor bone and calcification. Conclusions Each site has its relative imaging characteristics of pPNET. CT and MRI can show lesions involving the scope, internal structure, with or without adjacent tissue invasion and metastasis, and provide guidance for clinical treatment and selecting treatment regimen. But in the end, it depends on the diagnosis of pathological and immunohistochemical examination.

Tumor neuroectodérmico primitivo do terceiro ventrículo associado a metástase leptomeníngea / Primitive Neuroectodermal Tumor of the Third Ventricle Associated with Leptomeningeal Metastases

Os tumores neuroectodérmicos primitivos (PNET) são tumores malignos, não diferenciados, raramente apresentados na idade adulta, principalmente os de localização supratentorial. Apresentamos neste artigo o caso de um paciente de 19 anos, que nos chegou transferido de outro hospital com o diagnóstico de hidrocefalia. A existência do PNET associado a carcinomatose leptomeníngea foi comprovada como causa da hidrocefalia.

Primitive neuroectodermal tumors (PNET) are malignant tumors exceptionally present in adulthood, especially those with supratentorial location. In this article, we present the case of a young man who was transfer fromanother institutionwith the diagnosis of hydrocephalus; during his stay, we corroborated the presence of supratentorial PNET associated to leptomeningeal carcinomatosis that was a cause of hydrocephalus.

Incidence and Survival of Pediatric Soft Tissue Sarcomas: Comparison between Adults and Children / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Pediatric-type sarcomas such as rhabdomyosarcoma (RMS), Ewing sarcoma (EWS), primitive neuroectodermal tumor (PNET), and desmoplastic small round-cell tumor (DSRCT) are rare in adults, with limited studies on their prognosis and optimal treatment strategies. We aimed to examine the outcome of children and adult patients with RMS, EWS, PNET, and DSRCT and relevant prognostic factors. MATERIALS AND METHODS: We retrospectively reviewed 220 pediatric-type sarcoma patients at a single institution between 1985 and 2011. Comparisons were made in order to examine differences in demographics, disease characteristics, and survival. Survival analyses were performed using the Kaplan-Meier method with log-rank tests and Cox proportional hazards models. RESULTS: A total of 220 consecutive patients were identified at our institute. Median age was 15.6 years (range, 0 to 81 years) and there were 108 children (49%) and 112 adult patients (51%). According to histological classification, 106 patients (48.2%) had RMS, 60 (27.3%) had EWS, 50 (22.7%) had PNET, and 4 (1.8%) had DSRCT. With a median follow-up period of 6.6 years, the estimated median overall survival (OS) of all patients was 75 months (95% confidence interval [CI], 27.2 to 122.8 months) and median event-free survival (EFS) for all patients was 11 months (95% CI, 8.8 to 13.2 months). No significant difference in OS and EFS was observed between adults and children. In multivariate analysis, distant metastasis (hazard ratio [HR], 1.617; 95% CI, 1.022 to 2.557; p=0.040) and no debulking surgery (HR, 1.443; 95% CI, 1.104 to 1.812; p=0.012) showed independent association with worse OS. CONCLUSION: Metastatic disease and no surgical treatment are poor prognostic factors for OS among pediatric-type sarcomas for both adults and children.

Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor in an Adolscence, Manifested as Isolated Cervical Mass / 임상소아혈액종양

Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/PPNET) arises from bone or soft tissue of many sites of body, but ES/PPNET, as primary lesion, in the soft tissue of neck is very uncommon. The authors experienced a case of ES/PPNET in a 17-year-old girl, which was manifested as isolated cervical mass in the soft tissue without any other suspected primary lesion or metastasis. We report the case with a brief review of the literature.

Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor in an Adolscence, Manifested as Isolated Cervical Mass / 임상소아혈액종양

Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/PPNET) arises from bone or soft tissue of many sites of body, but ES/PPNET, as primary lesion, in the soft tissue of neck is very uncommon. The authors experienced a case of ES/PPNET in a 17-year-old girl, which was manifested as isolated cervical mass in the soft tissue without any other suspected primary lesion or metastasis. We report the case with a brief review of the literature.

A Case of Primitive Neuroectodermal Tumor of the Adrenal Gland

Primitive neuroectodermal tumors(PNETs) are a group of small round cell tumors that may arise in the central or peripheral nervous system. In the extracranial location, these neoplasms may occur anywhere and at any age group, but most likely in the bone and soft tissue of children and young adults. The incidence of adrenal gland involvement is very rare. This tumor is diagnosed by histopathological, immunohistochemical, and molecular pathological examinations. PNETs are highly aggressive tumors, locally recurrent and rapidly metastasizing to lung, liver, lymph node, and brain. The outcome is poor with a 5 year survival rate below 40% in spite of aggressive combined treatment including surgery, chemotherapy, and radiation therapy. We experienced a case of PNET of adrenal gland, mimicking ruptured Wilms tumor on the US and CT scan.

CT and MRI evaluation of peripheral primitive neuroectodermal tumors / 中国癌症杂志

Purpose:We present the imaging and pathological features of pPNET tumor in six patients,to add to the knowledge of this tumor. Methods:Retrospective analysis of six pPNETs integrated with data of radiography and pathology. Results:The CT appearance of the tumor arising in soft tissue showed a large,ill-defined,non-calcified mass and heterogeneous appearance with hypodense cystic areas. The tumors demonstrated heterogeneous contrast enhancement. The pPNET arising in bone demonstrated extensive lytic lesion with large soft tissue mass,no newly-born bone and demonstrated heterogeneous contrast enhancement. MRI in SE sequences on T 1 W demonstrated homogeneous intensity for muscle and showed enhancement pattern of multiple internal septa and envelope. On T 2 W image,the tumors were heterogeneous with hyperintense signal. Conclusions:The study of clinic and radiology on pPENT does not show specificity. CT and MRI findings on pPENT can provide more information of it's internal structure,involved area,adjacent vascular and nervous structures. CT and MRI can also be useful in detection of recurrent and metastatic disease and very useful in preoperative staging,and in the planning of the surgical appproach.

CT and MRI Features of Peripheral Primitive Neuroectodermal Tumors / 实用放射学杂志

Objective To study the CT and MRI features of peripheral primitive neuroectodermal tumor(PNET).Methods CT and MRI appearances of 10 patients with PNET pathologically proved were analyzed retrospectively.All cases underwent CT scan and 2 cases underwent MR imaging examination.There were 5 men and 5 women,the age ranged from 11 years to 54 years old(mean 24 years).Results The tumors were located in the chest wall(n=4),abdomen and sinus(n=2,each),cervical vertebra and humerus(n=1,each).The lesions in the chest wall and abdomen appeared as larger masses(5~16 cm in diameter).The masses were circular and lobulated with heterogeneous density and in company with bone destruction or periosteal reaction.The solid masses were enhanced after contrast medium administration.The lesions in the sinus showed the soft tissue mass with bone erosion.The lesions in bone demonstrated local iso-intensity on T1WI,hyper-intensity on FSE T2WI and on FATSAT T2WI.There were distant metastasis in 3 cases.Conclusion The clinical and imaging features of pPNET in chest wall were more specific than in other locations.CT and MRI can showed intra-tumor structure,and are helpful in delineated the extent of tumor,predicting resectability and monitoring treatment.

Clinical,MRI and pathological features of supratentorial primitive neuroectodermal tumors / 临床神经病学杂志

Objective To investigate the clinical,MRI and pathological features of supratentorial primitive neuroectodermal tumor(PNET).Methods The clinical manifestations of 21 PNET patients were analyzed,the skull imaging examination were taken,including MRI with diffuse weighing imaging(DWI) and measured apparent diffusion coefficient(ADC) of tumor and its edema zone before surgery.After operation,the brain tumor tissues were routine and immunohistochemical staining.The relationship between the histopathologic changes and ADC were analyzed.Results In the group,the age of onset of 11cases(52%) were below 20 years old.Clinical manifestation include headache,dizziness and vomiting(16 cases),visual disorder(5 cases),dysosphresis or epilepsy(3 cases).MRI showed single PNET lesion in all the cases and which located at each brain region,the most of them were located at frontal,temporal,parietal lobes(18 cases),and could growing to cross a brain region.MRI T1WI showed that the lesions were iso-signal and lowiso-signal in 15 cases,interspersed high signal in 6 cases.T2WI showed that the lesions were iso and high mixed signal companing capsule change and necrosis,4 cases with lighter tumor edema,5 cases with vascular air flow sign.The imaging enhanced tumors showed uneven enhancement,and 4cases with meningeal tail sign.The pathological examination showed that PNET cell form was main differentiated to neuron(10 cases) and neuroglia(8 cases).There was no statistical significance between ADC and different cell differentiation.Immunity histochemistry showed that the positive of NSE,Syn and GFAP were more offen.Conclusions In the group,the age of onset is below 20 years old.Manifestations of supratentorial PNET are intracranial pressure incresing,visual disorder and dysosphresis.MRI features are mixed isgnal,vascular air flow sign and meningeal tail sign in the tumor.The tumor edema is lighter.The tumor is differentiation mainly toward nerurons and neuroglias in the pathology.There is no positive relationship between ADC and types of tumor differentiation.

Two Cases of Primitive Neuroectodermal Tumors in Infancy

The authors are reporting two cases of huge primitive neuroectodermal tumors involving cerebral hemisphere. These are highly malignant neoplasm, both clinically and histologically. They are rapidly growing tumors, with a brief duration of symptoms and a rapidly progressive course. The patients were discharged after subtotal resecton of tumor mass with an uneventful course, but one was dead within 2 months after the operation. These tumors usually occur in children and young adult. We have experienced two cases surgically treated in infancy.