Primary appendiceal mucinous adenocarcinoma in two first-degree relatives: case report and review

Carcinomas of the appendix are exceedingly rare tumors and have an annual age-adjusted incidence of around 0.4 cases per 100,000. Appendiceal adenocarcinoma accounts for < 0.5% of all gastrointestinal neoplasms and, of these, mucinous adenocarcinomas account for the majority. Published accounts of familial instances of primary appendiceal tumors are strikingly rare. We report two siblings who both developed primary mucinous adenocarcinomas. A genetics evaluation was conducted to determine if there was a recognizable underlying single gene disorder; no DNA mismatch repair defect was evident, and no other diagnosis was apparent. A review of appendiceal cancers seen at Mayo Clinic from l997 to the present was conducted to search for additional familial cases. Among 316 cases of primary appendiceal cancer of any histologic type, this sib pair was the only family reporting a second affected family member. The occurrence of appendiceal cancer in siblings may represent a random occurrence. An exceedingly rare predisposition syndrome cannot be ruled out

The Association Between IGF-1 Levels and the Histologic Severity of Nonalcoholic Fatty Liver Disease

Objectives: The mechanisms responsible for the development of nonalcoholic fatty liver disease (NAFLD) and progression to nonalcoholic steatohepatitis (NASH) are incompletely understood. Growing evidence suggests that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may have roles in the development and progression of NAFLD. We hypothesized that lower serum IGF-1 levels would be associated with increased liver fat accumulation, inflammation, and fibrosis in a group of meticulously phenotyped obese subjects with liver biopsies. Methods: A retrospective, cross-sectional study was performed at Massachusetts General Hospital, Boston, MA, USA and St. Mary's Hospital, Richmond, VA, USA. Liver biopsies were performed in 142 subjects during NAFLD work-up or bariatric surgery and were graded by a single, blinded pathologist. Main outcome measures included liver histology and serum IGF-1. Results: Mean age was 52±10 years and body mass index (BMI) was 43±9 kg/m2. Mean serum IGF-1 was lower in subjects with lobular inflammation (112±47 vs. 136±57 ng/ml, P=0.01), hepatocyte ballooning (115±48 vs. 135±57 ng/ml, P=0.05), higher fibrosis stage (stage 2–4 vs. 0–1; 96±40 vs. 125±51 ng/ml, P=0.005), and NASH (109±45 vs. 136±57 ng/ml, P=0.002). All results remained significant after controlling for age, BMI, and a diagnosis of diabetes, and all but hepatocyte ballooning (trend, P=0.06) remained significant after excluding individuals with cirrhosis. Steatosis was not significantly associated with mean serum IGF-1 levels. Conclusions: Low serum IGF-1 levels are associated with increased histologic severity of NAFLD when rigorously controlled for age, BMI, the presence of diabetes, and after the exclusion of subjects with cirrhosis. Further investigation is warranted to determine the differential effects of GH and IGF-1 on the development and progression of NAFLD, which could further elucidate pathophysiology and identify therapeutic targets

A rare combination of an endocrine tumour of the common bile duct and a follicular lymphoma of the ampulla of Vater: a case report and review of the literature

Carcinoid tumours of the common bile duct represent an extremely rare entity. Similarly, primary follicular lymphomas of the ampulla of Vater constitute an infrequent neoplasia. Herein, we report the first case of a synchronous development of a carcinoid tumour of the common bile duct and an ampullary follicular lymphoma that was treated surgically with a Whipple's procedure, due to inability to establish definitive preoperative diagnosis despite the extensive diagnostic investigation

A specific cadherin phenotype may characterise the disseminating yet non-metastatic behaviour of pseudomyxoma peritonei

Pseudomyxoma peritonei (PMP) is a rare neoplasm of mainly appendiceal origin, characterised by excess intra-abdominal mucin production leading to high morbidity and mortality. While histological features are frequently indolent, this tumour disseminates aggressively throughout the abdominal cavity, yet seldom metastasises. This study determined the expression of several markers of colorectal differentiation (carcinoembryonic antigen (CEA), cytokeratins (CK20 and CK7), epithelial membrane antigen), mucin production (MUC-2, interleukin-9 (IL-9), IL-9 receptor (IL-9Rα)), and cell adhesion (N- and E-cadherin, vimentin) in PMP tissue (n=26) compared with expressions in normal colonic mucosa (n=19) and colorectal adenocarcinoma (n=26). Expressions of CEA and cytokeratins were similar for PMP as those in colorectal adenocarcinomas with the exception that the CK20−/CK7− pattern was rare in PMP (Fisher's exact test: P=0.001). Similarly, expressions of mucin-related proteins were comparable for adenocarcinoma and PMP, with the exception that IL-9 expression was uncommon in adenocarcinoma (P=0.009). Pseudomyxoma peritonei demonstrated a specific pattern of adhesion-related protein expressions of increased N-cadherin, reduced E-cadherin, and increased vimentin (P=0.004), a phenotype suggesting a possible epithelial–mesenchymal transition state. Primary PMP cell cultures were successfully maintained and demonstrated marker expressions similar to those seen in in vivo tissues. These early characterisation studies demonstrate similarities between PMP and colorectal adenocarcinoma, but also reveal a specific cadherin phenotype that may characterise the distinct non-metastasising behaviour of PMP, and form the basis for future mechanistic and therapy-targeting research

Histological findings of autoimmune hepatitis

Histology of autoimmune hepatitis (AIH), chronic active hepatitis, is characterized by portal inflammation with interface hepatitis. Although the basic histology of AIH is similar to that of virus-related chronic hepatitis, hepatitic changes are usually prominent in AIH compared with chronic viral hepatitis. Clinicopathological diagnosis of AIH requires exclusion of other causes of liver disease, including hepatitis virus, alcohol, drugs, metabolic disorders, and other autoimmune diseases. At present, some criteria systems considering clinicopathological findings are proposed to categorize patients as having either definite or probably/atypical AIH. Among the pathological items of a simplified AIH scoring system of the International AIH Group, in addition to evident chronic hepatitis with interface hepatitis and hepatic rosette formation, emperipolesis, indicating the close immunological interaction of lymphocytes and hepatocytes, is noted but is sometimes difficult to evaluate. In addition to classical AIH, showing chronic active hepatitis, some AIH patients show a clinically acute hepatitis-like clinical course. These patients have mostly acute exacerbation from chronic active AIH, but acute-onset AIH cases, which histologically exhibit diffuse lobular hepatitis and/or confluent necrosis including perivenular zonal necrosis (zone 3 necrosis, centrizonal necrosis), are also encountered. © 2014 Springer Japan. All rights reserved.(Book Chapter