Autopsy findings in EPG5-related Vici syndrome with antenatal onset.

Vici syndrome is one of the most extensive inherited human multisystem disorders and due to recessive mutations in EPG5 encoding a key autophagy regulator with a crucial role in autophagosome-lysosome fusion. The condition presents usually early in life, with features of severe global developmental delay, profound failure to thrive, (acquired) microcephaly, callosal agenesis, cataracts, cardiomyopathy, hypopigmentation, and combined immunodeficiency. Clinical course is variable but usually progressive and associated with high mortality. Here, we present a fetus, offspring of consanguineous parents, in whom callosal agenesis and other developmental brain abnormalities were detected on fetal ultrasound scan (US) and subsequent MRI scan in the second trimester. Postmortem examination performed after medically indicated termination of pregnancy confirmed CNS abnormalities and provided additional evidence for skin hypopigmentation, nascent cataracts, and hypertrophic cardiomyopathy. Genetic testing prompted by a suggestive combination of features revealed a homozygous EPG5 mutation (c.5870-1G>A) predicted to cause aberrant splicing of the EPG5 transcript. Our findings expand the phenotypical spectrum of EPG5-related Vici syndrome and suggest that this severe condition may already present in utero. While callosal agenesis is not an uncommon finding in fetal medicine, additional presence of hypopigmentation, cataracts and cardiomyopathy is rare and should prompt EPG5 testing.

A novel disorder of sex development, characterized by progressive regression of testicular function and cystic leukoencephalopathy.

We report a novel syndromic disorder of sex development observed in three male siblings, presenting with the association of micropenis without hypospadias, cryptorchidism, very low level of antimüllerian hormone in the neonatal period, and no persistent müllerian duct structures, suggesting a progressive regression of testicular function. The patients described here showed a striking neurological involvement including bilateral periventricular cysts observed in the anterior part of the frontal horns prenatally and increasing in size and number over time, associated with infra and supratentorial parenchymal atrophy, dilated ventricular system, corpus callosum hypoplasia, severe intellectual disability, and epilepsy. Associated features included a distinctive facies, joint contractures, retinopathy, and hearing loss. Pathological examination was consistent with testicular dysgenesis and leukoencephalopathy with spongiosis and microcalcifications. To the best of our knowledge, this disease, characterized by a recognizable pattern of malformations, has not been previously reported. An exhaustive genetic and metabolic evaluation was normal. Autosomal recessive inheritance was considered to be likely, on the basis of SNP studies. We hope that the detailed description provided here of the clinical, radiological, and pathological findings observed in this family will help to identify further unrelated patients, and ultimately, to clarify the genetic basis of this condition. © 2017 Wiley Periodicals, Inc.

The level of epidermal growth factor receptors expression is correlated with the advancement of colorectal adenoma: validation of a surface biomarker.

INTRODUCTION: Data about the expression of Epidermal Growth Factor Receptors (EGFRs) in colorectal adenomas remain scarce. RESULTS: 101 patients were enrolled including 53 controls. All adenomas (n = 38) and CRC (n = 5) were EGFR positive. Hyperplastic polyps (HP) (n = 8) and control colons (n = 53) were EGFR negative in half of cases (p < 0.0001). A well significant gradient of increased EGFR expression was observed between adjacent mucosa, hyperplastic lesions, low grade dysplasia (LGD) (n = 30), high grade dysplasia (HGD) adenomas (n = 9) and cancers (p < 0.0001). EGFR overexpression was reported in 100% of cancers, 77.8% of HGD, and 10% of LGD adenomas. By multivariate analysis in adenomas, associated factors with EGFR overexpression were HGD and tubulo-villous feature. MATERIALS AND METHODS: All patients undergoing colonoscopy in the university center of Saint-Etienne were eligible to the study from December 2015 to March 2016. In patients with colorectal neoplasia (lesions group), biopsies were performed on the lesion before its resection, and on the adjacent and distal colon mucosa. In control group, biopsies were performed in the right and left side colon. The EGFR expression was assessed by immunohistochemical scores (Goldstein grade, intensity of staining, composite score), using a primary mouse monoclonal antibody (EGFR, clone 113, Novocastra). Outcomes were compared using Kruskal-Wallis and/or Mann-Whitney-U tests, appropriately. The associated clinical, endoscopic and histological factors with EGFR overexpression (composite score ≥ 6) were assessed for adenomas by logistic regression. CONCLUSIONS: EGFR are early involved in colorectal carcinogenesis, and their expression is strongly correlated to the neoplasia stage, leading to validate EGFR as an interesting surface biomarker of adenomas.

Jejuno-ileal diverticulitis: Etiopathogenicity, diagnosis and management.

INTRODUCTION: Although diverticular disease of the duodenum and colon is frequent, the jejuno-ileal diverticulosis (JOD) is an uncommon entity. The perforation of the small bowel diverticula can be fatal due to the delay in diagnosis. PRESENTATION OF CASE: We report the case of a 79-year-old man presenting with generalized abdominal pain and altered bowel habits. Physical examination revealed a severe diffuse abdominal pain. A CT scan of the abdomen and pelvis with oral contrast showed thickening of the distal jejunal loop and thickening and infiltration of the mesenteric fat and the presence of free air in the mesentery suggesting a possible perforation adjacent to the diverticula. A midline laparotomy was performed. The jejunal diverticula were found along the mesenteric border. Forty centimeters of the jejunum were resected. Histopathology report confirmed the presence of multiple jejunual diverticula, and one of them was perforated. The patient tolerated the procedure and the postoperative period was uncomplicated. DISCUSSION: The prevalence of small intestinal diverticula ranges from 0.06% to 1.3%. The etiopathogenesis of JOD is unclear, although the current hypothesis focuses on abnormalities in the smooth muscle or myenteric plexus, on intestinal dyskinesis and on high intraluminal pressures. Diagnosis is often difficult and delayed because clinical symptoms are not specific and mainly imaging studies performs the diagnosis. CONCLUSION: Because of the relative rarity of acquired jejuno-ileal diverticulosis, the perforation of small bowel diverticulitis poses technical dilemmas.

Squamous cell carcinoma of middle rectum: Literature review.

INTRODUCTION: Squamous cell carcinoma SCC of the rectum is a distinct entity. We report a very rare case of squamous cell carcinoma of the middle rectum. PRESENTATION OF CASE: The patient was a 62-year-old woman who presented with a history of rectal bleeding and discomfort. Colonoscopy revealed a polypoid tumour of the middle rectum. Biopsies of this mass revealed a poorly differentiated SCC of the rectum. CT scan of the chest, abdomen and pelvis was negative for distal metastases. The patient received combined chemo-radiation followed by surgical excision. The postoperative period was uncomplicated. DISCUSSION: The pathogenesis of rectal SCC remains unclear and diagnosis is often delayed. Diagnostic criteria have been proposed. MRI of the rectum and trans-rectal endoscopic ultrasound R-EUS provide essential information to plan a therapeutic approach. The squamous cell carcinoma antigen level is not suitable for initial diagnosis of rectal SCC. Most authors conclude that the surgery is the gold standard treatment. Tumour stage is the most important prognostic predictor of SCC. CONCLUSION: Squamous cell carcinoma of the rectum is a distinct entity. Before the final choice of treatment is made, digestive surgeons should bear in mind this rare tumour.

The study of synovities with articular inflammatory liquid, through clinical-statistical, histological and immunohistochemical methods.

INTRODUCTION: The examination of the synovial is very useful in the positive and differential diagnostic of many articular diseases and especially in the conditions of acute monoarthritis. MATERIALS AND METHODS: The study focused on the establishment of clinical-statistical, histopathological and immunohistochemical correlations on a group of cases anatomo-pathologic diagnosed with synovity with articular inflammatory liquid. The group was divided in five subgroups: rheumatoid polyarthritis, uric arthropathy (gout), TBC arthritis, sarcoidosis and villo-nodular synovity. RESULTS AND DISCUSSION: During the clinical-statistical study the number of arthritis with articular inflammatory infiltration was pursued, the specific location of them and the correlation of the clinical dates with paraclinical ones. In the histopatological and immunohistochemical analysis was pursued the presence of the inflammatory infiltration through the implication of both types of B- and T-lymphocytes in different proportions taking into consideration the cause of the synovity. CONCLUSIONS: The synovial biopsy is indicated at patients at whom the diagnostic is not established after the clinical evaluation. The examination of the synovial tissue can be the only way of establishing a definitive diagnostic in inflammatory arthropathies.

Study of malignant fibrous histiocytoma: clinical, statistic and histopatological interrelation.

INTRODUCTION: Malignant fibrous histiocytoma (MFH) is a malignant tumor of soft parts observed at approximately 70% of cases situated at the level of the outsides. PATIENTS AND METHODS: Our study is formed of 14 cases of patients in a period of three years (2007-2010), diagnosed anatomo-pathological with malignant fibrous histiocytoma at the County Hospital of Oradea. The histopathological examination together with the immunohistochemical one is of vital importance in the establishment of the positive diagnostic and furthermore in the establishment of the differential diagnostic with carcinomas, plasmacytomas, osteosarcomas, fibrosarcomas and lymphosarcomas, fact that arouse the doctors to administrate the correct treatment to a specific patient. DISCUSSION: MFH is a tumor of late adulthood that occurs in men more commonly than women. Computer tomography and MRI have been widely used in the diagnosis and staging of MFH. MFH is secondary to another process such as radiation, surgery, fracture, osteonecrosis, Paget's disease, non-ossifying fibroma or fibrous dysplasia 20% of the time. MFH arising from a previous abnormality is usually more aggressive and has a poorer prognosis than primary MFH. Primary osseous MFH is a central lesion found in the diaphysis or metaphysis of the bone that causes aggressive bone destruction and a soft tissue mass. The most common sites in order are the distal femur, proximal tibia, proximal femur and proximal humerus. Primary osseous MFH is less common. MFH is found in the extremities 70-75% of the time and 50% of all cases are in the lower extremity. Other less common sites include the retroperitoneum, and the head and neck. In our study, of 14 patients with malignant fibrous histiocytoma, the highest incidence is during the sixth decade of life and there is a male to female ratio of 8 to 6. In the specialty literature, malignant fibrous histiocytoma tend to occur in children and teenagers but can also occur in older adults as secondary lesions in bone infarcts and radiation fields. This tumor is clinically similar to osteosarcoma and fibrosarcoma, although malignant fibrous histiocytomas have been classified as different from the osteosarcoma group because of a different histology (no tumor bone production). Treatment is similar to that of osteosarcoma. CONCLUSIONS: During our study, the average age was of 61 years in comparison with the specialty literature where the average age was of 50 years. The same as in the specialty literature the cases of fibrous malignant histiocytoma studied are more frequently present at men. Regarding the situation, our study shows the affectation of the long bones especially the femur followed by the radius. The histopathological examination together with the immunohistochemical one is of vital importance in the establishment of the positive diagnostic and furthermore in the establishment of the differential diagnostic with carcinomas, plasmacytomas and lymphosarcomas.

Study of clinical-morphological correlations in carcinoid tumors of the colon.

INTRODUCTION: The incidence of carcinoid tumors of the digestive tract increased in the last 30 years. The aim of the study is to find clinical and morphologic correlations in cases with digestive carcinoid tumors. MATERIALS AND METHODS: A retrospective study on 76 cases with digestive carcinoid tumors divided in five groups according to their location on the segments of the digestive tract. RESULTS: The subgroup of colon carcinoid is analyzed and clinical-morphological correlations are obtained between the demographic data of the patients (age, gender and environment), tumor location, clinical expression and morphologic features. CONCLUSIONS: Due to the newly discovered techniques of investigation, the incidence of digestive carcinoid tumors has risen in association with other pathologies for which we make these investigations.