IDH1 mutations in a Brazilian series of Glioblastoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Albert Einstein Jewish HospitalUniversidade de São Paulo Faculdade de Medicina Department of NeurologyUniversidade de São Paulo Faculdade de Medicina Department of PathologyCancer Institute of São PauloFundação Pio XII Barretos Cancer HospitalFederal University of São Paulo School of Medicine Department of NeurologyFederal University of São Paulo School of Medicine Department of PathologyNove de Julho HospitalAlbert Einstein Jewish HospitalUNIFESP, EPM, Department of NeurologyUNIFESP, EPM, Department of PathologyFAPESP: 04/12133-6SciEL

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.

We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification

Nevus composto do colo uterino: relato de caso Compound nevus of the uterine cervix: case report

O nevus composto do colo uterino representa um achado muito raro. Relatos excepcionais de lesões melanocíticas benignas e malignas da endo e exocérvice uterina têm sido publicados. Relatamos o achado ocasional do nevus composto da exocérvice uterina em uma paciente de 47 anos de idade que não apresentava queixas ginecológicas. O diagnóstico foi sugerido pelo exame colposcópico e confirmado à histopatologia. Devido à possibilidade de transformação maligna dessas lesões e à dificuldade de seguimento da paciente, o tratamento foi concluido com a realização de histerectomia total abdominal.<br>Compound nevus of the uterine cervix is very rare. Benign and malignant melanotic lesions of endo and exocervix have been rarely documented. The present case of compound nevus in the uterine exocervix was found in a 47-year-old woman without gynecologic complaints. Diagnosis was suspected by colposcopic evaluation and confirmed trough histopathological examination. The treatment was concluded with total abdominal hysterectomy based on the possible malignant transformation of these lesions and the difficult patient follow-up

Malignant transformation of pleomorphic xanthoastrocytoma: case report Transformação maligna de xantoastrocitoma pleomórfico: relato de caso

We report a case of a pleomorphic xantoastrocytoma which manifested itself as a cystic isodense lesion in the right fronto-temporal lobe in a 26 year-old woman. It appeared as a soft yellow tumor with cystic cavities on surgery. Five months after this surgery, the patient was submitted to a new operation, which revealed a friable tumor, easily differentiated from the normal parenchyma, with cystic components. The histopathological examination demonstrated pleomorphic xanthoastrocytoma with malignant transformation. Histologically, the tumor at first procedure was composed of pleomorphic astrocytes with multinucleated and foamy cells. A rare case of malignant transformation in pleomorphic xanthoastrocytoma is presented, discussed and illustrated in this paper.<br>Um caso raro de transformação maligna de xantoastrocitoma pleomórfico é apresentado, discutido e ilustrado neste estudo. Descrevemos um caso de xantoastrocitoma pleomórfico diagnosticado como lesão isodensa no lobo fronto-temporal direito, em uma paciente de 26 anos. Na cirurgia, encontrou-se tumor mole, de cor amarelada, com cavidade cística. Cinco meses após o procedimento, a paciente foi submetida a nova intervenção que revelou um tumor friável, facilmente diferenciado do parênquima normal, com componentes císticos. O exame histopatológico demonstrou um xantoastrocitoma pleomórfico com transformação maligna. O tumor, no primeiro procedimento, era formado por astrócitos pleomórficos com células vacuolizadas e multinucleadas

Lack of KBTBD4 mutations in molecularly classified Brazilian medulloblastomas

Medulloblastoma is the most frequent malignant brain tumor in children, representing 20% of all childhood brain tumors. Currently, medulloblastomas are molecularly classified in 4 subgroups that are associated with distinctive clinicopathological features. KBTBD4 mutations were recently described in a subset of MBGRP3 and MBGRP4 medulloblastomas subgroups. However, no other studies reported KBTBD4 mutations in medulloblastomas. Thus, our aim was to investigate KBTBD4 mutations in a Brazilian series of medulloblastoma. We evaluated 128 medulloblastoma patients molecularly classified from 4 Brazilian reference centers. DNA from formalin-fixed, paraffin-embedded samples was screened for KBTBD4 hotspot mutations by Sanger sequencing. Most of the patients were male, average age was 16.5 years old and average overall survival was 55.9 months. The predominant histological subtype was the classic subtype, followed by nodular/desmoplastic, and the predominant medulloblastoma molecular subtype was the MBSHH subgroup (46%), followed by MBGRP3 and MBGRP4 (19%/each), and MBWNT (16%). Among the 128 samples, 111 were successfully sequenced. No KBTBD4 mutations were identified in 111 samples. Our findings suggest that KBTBD4 mutations are uncommon in Brazilian MBGRP3 and MBGRP4 medulloblastomas subgroups. Further studies in a larger series of MBGRP3 and MBGRP4 medulloblastomas are warranted to better assess role of KBTBD4 mutations.We thank Barretos Cancer Hospital and FINEP for partially funding the present study. Leticia Ferro Leal is supported by Public Ministry of Labor Campinas (Research, Prevention and Education of Occupational Cancer) in Campinas, Brazil. Rui Manuel Reis is sponsored by the National Council for Scientific and Technological Development (CNPq, Brazil)