Clinical Course, Genetic, and Immunohistochemical Characterization of Solid Pseudopapillary Tumor of the Pancreas (Frantz Tumors) in a Brazilian Cohort.

Frantz tumors or solid pseudopapillary pancreatic neoplasm (SPN) are rare exocrine neoplasms that carry a favorable prognosis; they represent up to 3% of all tumors located in the region of the pancreas and have specific age and gender predispositions. In recent years, the rising curve of diagnosis is entitled to the evolution and access of diagnostic imaging. In this paper, we have retrospectively reviewed and described the clinical course of 40 patients with SPN from three institutions in Brazil, who had their diagnosis between 2005 and 2020, and analyzed the clinicopathological, genetic, and surgical aspects of these individuals. In accordance with the literature, most patients were women, 60% with unspecified symptoms at diagnosis, with tumors mainly located in the body and tail of the pancreas, of whom 70% underwent a distal pancreatectomy with sparing splenectomy as a standard procedure, and none of the cases have experienced recurrence to date. Surgery still remains the mainstay of treatment given the low metastatic potential, but more conservative approaches as observed in this cohort are evolving to become the standard of care. Herein, we present an in-depth analysis of cases focusing on the latest literature and report some of the smallest tumor cases in the literature. To our knowledge, this is the first report evaluating germline genetic testing and presenting a case of detected Li-Fraumeni syndrome.

Cancer risk-reducing surgery: Brazilian society of surgical oncology guideline part 1 (gynecology and breast).

BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Fourteen questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reduction bilateral salpingo-oophorectomy, hysterectomy, and mastectomy, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO, and it should serve as an important reference for the management of families with cancer predisposition.

The germline mutational landscape of BRCA1 and BRCA2 in Brazil.

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.

Detection of Cerebral Vasculopathy by Transcranial Doppler in Children With Neurofibromatosis Type 1.

Neurofibromatosis type 1 is characterized by nerve sheath neurofibromas associated with a number of additional clinical features, including cerebrovascular disease. The aim of this study was to use transcranial Doppler as a screening method for identifying cerebral vasculopathy in children with neurofibromatosis type 1. Forty children with neurofibromatosis type 1, aged 5 to 18 years old, were examined by transcranial Doppler. Patients presenting with hemodynamic features of arterial stenosis/occlusion on transcranial Doppler underwent magnetic resonance angiography to confirm the findings. Magnetic resonance angiography was performed on 4 children who exhibited a transcranial Doppler hemodynamic pattern indicative of cerebral vasculopathy. Among these cases, 2 presented internal carotid artery stenosis/occlusion, 1 had bilateral middle cerebral artery stenosis, and 1 presented a normal magnetic resonance angiography result. Transcranial Doppler can be used routinely in the investigation of cerebrovascular disease in neurofibromatosis type 1 patients, where magnetic resonance angiography can be subsequently applied to confirm the diagnosis, further contributing to the prevention of cerebrovascular events.

19q13.33→qter trisomy in a girl with intellectual impairment and seizures.

Rearrangements in chromosome 19 are rare. Among the 35 patients with partial 19q trisomy described, only six have a breakpoint defined by array. The 19q duplication results in a variable phenotype, including dysmorphisms, intellectual disability and seizure. In a female patient, although G-banding at 550 band-resolution was normal, multiplex ligation-dependent probe amplification (MLPA) technique and genomic array showed a 10.6 Mb terminal duplication of chromosome 19q13. Fluorescent in situ hybridization (FISH) revealed that the duplicated region was attached to the short arm of chromosome 21 and silver staining showed four small acrocentrics with nucleolar organization region (NOR) activity, suggesting that the breakpoint in chromosome 21 was at p13. This is the first de novo translocation between 19q13.33 and 21p13 described in liveborn. The chromosome 19 is known to be rich in coding and non-coding regions, and chromosomal rearrangements involving this chromosome are very harmful. Furthermore, the 19q13.33→qter region is dense in pseudogenes and microRNAs, which are potent regulators of gene expression. The trisomic level of this region may contribute to deregulation of global gene expression, and consequently, may lead to abnormal development on the carriers of these rearrangements.

Crianças portadoras de neurofibromatose tipo 2: o pediatra geral pode reconhecer esta entidade? / Children with neurofibromatosis type 2: can the general pediatrician recognize this entity?

A neurofibromatose tipo 2 é uma desordem autossômica dominante causada pela inativação ou perda de ambos os alelos do gene supressor de tumor NF2. Neste artigo estão sumarizados a epidemiologia, genética características clínicas, e os critérios para avaliar e diagnosticar o quadro nas pessoas de risco...

Estudo clínico e molecular de pacientes com síndrome de Rett / Clinical and molecular study of patients with Rett syndrome

Objetivo: Estudar clinicamente pacientes brasileiras com síndrome de Rett, formas clássica e atípicas; pesquisar mutações de ponto no gene MECP2 e estabelecer correlação entre as principais mutações de ponto encontradas e o fenótipo das pacientes. Método: Foi realizada a avaliação clínica de 105 pacientes, incluindo 2 pares de gêmeas monozigóticas, seguindo um rigoroso protocolo clínico. A avaliação molecular do gene MECP2 foi realizada através de DNA extraído de sangue periférico e amplificação de sua região codificadora, que foi seqüenciada em seqüenciador automático. Resultados: Das pacientes estudadas, 68 por cento apresentavam a forma clássica; 27 por cento, formas atípicas e 5 por cento não puderam ser classificadas, dadas a idade e a clínica apresentadas. Foram encontradas mutações de ponto patogênicas em 64,1 do total das pacientes, 71,4 por cento das pacientes com a forma clássica, 50 por cento das pacientes com a forma atípica e 40 por cento das pacientes não classificadas. Foram encontradas 4 variações não descritas previamente, cuja natureza sugere que sejam patogênicas. As mutações mais freqüentes foram T158M (13 pacientes); R306C (11 pacientes e gêmeas), R168X (9 pacientes e gêmeas); R270X (7 pacientes); R294X (6 pacientes); R255X (5 pacientes). Observou-se uma freqüência maior de mutações de ponto identificadas entre as pacientes clássicas e um início precoce do quadro clínico nas pacientes sem mutações identificadas. As pacientes com mutação que geram um códon de parada prematura da leitura apresentaram um início mais precoce da doença e pontuações maiores na escala de Kerr do que as com mutações que trocam aminoácidos. As pacientes com mutações no sinal de localização nuclear (SLN) apresentaram um início precoce dos sintomas e as com mutações no domínio de repressão a transcrição após o SLN, apresentaram quadros menos graves...

Methylenetetrahydrofolate reductase (MTHFR): incidence of mutations C677T and A1298C in Brazilian population and its correlation with plasma homocysteine levels in spina bifida.

Homocysteine (Hcy) is converted to cysteine or is remethylated to methionine by methylenetetrahydrofolate reductase (MTHFR). MTHFR plays a central role in the metabolism of folate. Two common polymorphisms in the MTHFR gene (C677T and A1298C) have been described and studies suggest that these polymorphisms are positively associated with the occurrence of spina bifida (SB). Among Brazilians, the incidence of 677T allele homozygosity is 4%. We compared Hcy levels with the genotypes obtained for the mutations C677T and A1298C in the gene MTHFR. Levels of plasma Hcy were higher in children with SB than in controls (average 7.95 vs. 5.55 (micromol/L); P < 0.001). There was no significant difference in the levels of Hcy for these children's mothers and controls (average 7.76 vs. 8.36 (micromol/L); P = 0.27). Eighty one (61.8%) of the affected children were white and 50 (38.2%) were non-white. A similar ratio was observed in the mothers. In the control group, 51 children (40.5%) were white and 75 (59.5%) were non-white, and 52 mothers (41.3%) were white and 74 (58.7%) were non-white. There was no significant difference in the homozygous frequency for the mutated allele 677T among different racial groups. We obtained a prevalence of TT homozygosity of 10/131 (7.64%) in affected children and 13/126 (10.32%) in controls. With respect to the mutation A1298C, the homozygous prevalence for the wild allele was greater among non-white individuals than in white individuals both in case and control groups. Hyperhomocysteinemia is a risk factor for SB. However, in our population, the increase in plasma levels of Hcy is not explained by the presence of the homozygous TT. It is possible that low folic acid intake combined with other genetic factors plays a more important role in the cause of this disease.