Current Issue : July - September Volume : 2017 Issue Number : 3 Articles : 7 Articles
Background: Haploinsufficiency of the GATA6 transcription factor gene was recently found to be the most\ncommon cause of pancreatic agenesis, a rare cause of neonatal diabetes mellitus. Although most cases are\nde novo, we describe three siblings with inherited GATA6 haploinsufficiency and the rare finding of parental\nmosaicism.\nCase Presentation: The proband was born at term with severe intrauterine growth restriction, the first\nchild of non-consanguineous parents. Diabetes occurred on day of life 1 with pancreatic exocrine insufficiency\nnoted at several months of age. Pancreatic agenesis with absent gallbladder was confirmed when he underwent\ncongenital diaphragmatic hernia and intestinal malrotation repair. A patent ductus arteriosus and pulmonary stenosis\nwere repaired in infancy. Neurocognitive development has been normal. A second pregnancy was terminated\ndue to tetralogy of Fallot and pulmonary hypoplasia secondary to congenital diaphragmatic hernia. The fetus\nalso demonstrated severe pancreatic hypoplasia, gallbladder agenesis and intestinal rotation abnormalities.\nDespite severe hypoplasia, the pancreas demonstrated normal islet histology. Another sibling was found to\nhave multiple cardiac abnormalities, requiring procedural intervention. Given the proband�s spectrum of\ncongenital anomalies, Sanger sequencing of the GATA6 gene was performed, revealing a novel heterozygous\nc.635_660del frameshift mutation (p.Pro212fs). The mutation is predicted to be pathogenic, resulting in\ninclusion of a premature stop codon and likely degradation of the gene transcript by nonsense-mediated\ndecay. The abortus and the sibling with the cardiac defect were both found to have the mutation, while\nthe father and remaining sibling were negative. The mother, who is healthy with no evidence of diabetes\nor cardiac disease, is mosaic for the mutation at a level of 11% in her peripheral leukocytes by next-generation\nsequencing.\nConclusion: We highlight a rare mechanism of pancreatic agenesis, this being only the second report of parental\nmosaicism for a GATA6 mutation and one of a handful of inherited cases. We also further define the phenotypic\nvariability of GATA6 haploinsufficiency, even in individuals carrying the same mutation. Mutations in GATA6 should be\nstrongly considered in cases of diabetes due to pancreatic hypoplasia or agenesis, and potentially affected family\nmembers should be tested regardless of phenotype....
Thyroid transcription factor (TTF-1) is initially identified as a mediator of thyroid-specific gene transcription and transcription of surfactant proteins in lung. Its expression was characteristically seen in the nuclei of lung and thyroid epithelia and their tumors. Cytoplasmic staining with TTF-1 was noted in normal and neoplastic tissue samples including normal hepatocytes and hepatocellular carcinoma (HCC). This study was conducted on 36 archival hepatic specimens, grouped as follows: 36 sections from peri-malignant benign hepatic tissue (chronic hepatitis C); 33 sections from tumor tissue of HCC and 15 sections from foci of liver cell dysplasia. TTF-1 expression was detected in all dysplastic and HCC lesions and in 75% of perimalignant lesions. Marked intensity staining predominates in HCC lesions with more expression in higher grades of HCC, while moderate intensity predominates in dysplastic and perimalignant lesions. HCC lesions showed mainly diffuse staining pattern which is more pronounced in higher grades of HCC, while patchy staining appeared mainly in dysplastic and perimalignant lesions. TTF-1 expression in perimalignant tissue showed marked intensity in higher grades of necroinflammation and in cirrhotic lesions. Patchy staining predominates in higher grades of necroinflammation and in fibrotic lesions, while nodular staining expressed only in cirrhotic nodules. Mean percentage of positive hepatocytes increases significantly in HCC lesions compared to dysplastic and perimalignant lesions. TTF-1 showed lower expression in perimalignant tissue, higher expression in dysplastic lesions and sustained increased expression in hepatocellular carcinoma. So changes in hepatocellular expression of TTF-1 are upregulated in cases of hepatitis C and in HCV induced HCC....
About 80% of hepatocellular carcinoma (HCC) cases are related to Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV). SOX is a family of related transcription factors implicated in cancer development. SOX2 gene has clinical applications including screening in asymptomatic individuals, confirming a suspect diagnosis and early detection of recurrent disease. This study was conducted on 58 biopsy specimens from malignant (24) and peri-malignant (34) hepatic tissues taken from patients suffering of HCC of HCV pathogenesis. Immunohistochemical staining of liver sections using anti-SOX2 monoclonal antibody was performed and the expression parameters were scored and evaluated in relation to hepatitis activity and stage of fibrosis as well as the grade of HCC. HCC showed significantly high percentage of positive SOX2 expression (83.3%) compared to non-malignant hepatic tissue (13.3%), while all cases of dysplasia showed positive expression of SOX2 (100.0%). We also found a highly increase in the percentage of positive SOX2 expression in high grade tumors (100.0%) in comparison to low grade tumors (75.0%). No significant correlations were found between hepatitis activity or the stage of fibrosis with the different parameters of SOX2 expression. In conclusion, lower SOX2 expression in fibrotic and non-malignant tissues and its higher expression in malignant and dysplastic tissues as well as in cirrhotic hepatic tissue indicated that SOX2 up-regulation represents early one of the events in the development of HCV-related hepatocellular carcinoma. Accordingly, SOX2 might prove to be a reliable marker in the diagnosis of premalignant changes associated with HCV infection....
Background: Idiopathic pulmonary arterial hypertension (IPAH) is a rare, fatal disease of unknown pathogenesis.\nEvidence from our recent study suggests that IPAH pathogenesis is related to upregulation of the Wnt/planar cell\npolarity (Wnt/PCP) pathway. We used microscopic observation and immunohistochemical techniques to identify\nexpression patterns of cascading proteinsââ?¬â?namely Wnt-11, dishevelled-2 (Dvl-2), and dishevelled-associated\nactivator of morphogenesis 1 (Daam-1)ââ?¬â?in pulmonary arteries.\nMethods: We analyzed sections of formalin-fixed and paraffin-embedded autopsied lung tissues obtained from 9\nIPAH cases, 7 associated pulmonary arterial hypertension cases, and 16 age-matched controls without pulmonary\narterial abnormalities. Results of microscopic observation were analyzed in relation to the cellular components and\nsize of pulmonary arteries.\nResults: Varying rates of positive reactivity to Dvl-2 and Daam-1 were confirmed in all cellular components\nof pulmonary arteries, namely, endothelial cells, myofibroblasts, and medial smooth muscle cells. In contrast,\nnone of these components was reactive to Wnt-11. No specific expression patterns were observed for endothelial\ncells or myofibroblasts under any experimental conditions. However, marked expression of Dvl-2 and Daam-1 was\nconfirmed in smooth muscle cells. In addition, Dvl-2 was depleted while Daam-1 expression was elevated in IPAH, in\ncontrast with specimens from associated pulmonary arterial hypertension cases and controls.\nConclusions: High Daam-1 expression may upregulate the Wnt/PCP pathway and cause IPAH....
consensus panel recently used clinical evidence and pathologic parameters to rename noninvasive encapsulated follicular variant\nof papillary thyroid carcinoma to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) to better\nreflect the indolent course of this tumor. NIFTP has stringent histopathologic diagnostic criteria established by the panel, including\npapillary-like nuclear features, and submission of the entire tumor capsule to exclude invasion. Fromamolecular standpoint, NIFTP\nis often characterized by RAS-type mutations, similar to other follicular-patterned lesions.While there has been prior evidence in\nthe literature for the low malignant potential of these tumors, projects moving forward will help to independently reinforce the\nreliability of these criteria and nomenclature.With planned inclusion of NIFTP into the latest World Health Organization endocrine\ntumor classification scheme, this nomenclature shift provides a model for pathology efforts to refine diagnostic classifications to\nbetter guide treatment. In this review we discuss this nomenclature change and review the current literature....
The presence of pulmonary parenchymal cysts on computed tomography (CT) imaging presents a significant diagnostic challenge.\nThe diverse range of possible etiologies can usually be differentiated based on the clinical setting and radiologic features. In fact, the\nadvent of high-resolution CT has facilitatedmaking a diagnosis solely on analysis of CT image patterns, thus averting the need for a\nbiopsy.While it is possible to make a fairly specific diagnosis during early stages of disease evolution by its characteristic radiological\npresentation, distinct features may progress to temporally converge into relatively nonspecific radiologic presentations sometimes\nnecessitating histological examination to make a diagnosis. The aim of this review study is to provide both the pathologist and the\nradiologist with an overview of the diseases most commonly associated with cystic lung lesions primarily in adults by illustration\nand description of pathologic and radiologic features of each entity. Brief descriptions and characteristic radiologic features of the\nvarious disease entities are included and illustrative examples are provided for the common majority of them. In this article, we\nalso classify pulmonary cystic disease with an emphasis on the pathophysiology behind cyst formation in an attempt to elucidate\nthe characteristics of similar cystic appearances seen in various disease entities....
Introduction. To investigate whether maternal oral flora might be involved in intrauterine infection and subsequent stillbirth or\nneonatal death and could therefore be detected in fetal and neonatal postmortem bacterial cultures. Methods. This retrospective\nstudy of postmortem examinations from 1/1/2000 to 12/31/2010 was searched for bacterial cultures positive for common oral\nflora from heart blood or lung tissue. Maternal age, gestational age, age at neonatal death, and placental and fetal/neonatal\nhistopathological findings were collected. Results. During the study period 1197 postmortem examinations (861 stillbirths and 336\nneonatal deaths) were performed in our hospital with gestational ages ranging from 13 to 40+ weeks. Cultures positive for oral\nflora were identified in 24 autopsies including 20 pure and 8 mixed growths (26/227, 11.5%), found in 16 stillbirths and 8 neonates.\nMicroscopic examinations of these 16 stillbirths revealed 8 with features of infection and inflammation in fetus and placenta. The 7\nneonatal deaths within 72 hours after birth grew 6 pure isolates and 1 mixed, and 6 correlated with fetal and placental inflammation.\nConclusions. Pure isolates of oral flora with histological evidence of inflammation/infection in the placenta and fetus or infant\nsuggest a strong association between maternal periodontal conditions and perinatal death....
Loading....