2 - Pathology of Neoplastic Bowel Diseases.pdf

UNITED ARAB EMIRATES UNIVERSITY FACULTY OF MEDICINE AND HEALTH SCIENCES Department of Pathology Pathology of Neoplastic Bowel Diseases Dr. SUHAIL AL-SALAM  Small Intestinal Neoplasms Very uncommon. - small intestinal malignancy obstructive jaundi...

UNITED ARAB EMIRATES UNIVERSITY FACULTY OF MEDICINE AND HEALTH SCIENCES Department of Pathology Pathology of Neoplastic Bowel Diseases Dr. SUHAIL AL-SALAM  Small Intestinal Neoplasms Very uncommon. - small intestinal malignancy obstructive jaundice. - may progress to carcinoma Adenocarcinoma - commonest in duodenum. Usually periampullary - celiac disease is predisposing factor. - Occasionally associated with neurofibromatosis type I Neuroendocrine tumors Appendix and small intestine – sometimes multicentric Well-differentiated, malignant neuroendocrine tumor of the small intestine, Often extensive local spread, but metastasis infrequent. regional lymph nodes liver: bone skin thyroid May produce vasoactive peptides such as substance P, serotonin, and gastrin. May cause carcinoid syndrome if they metastasize to liver and destroy liver function sufficiently so that liver is unable to metabolize the vasoactive peptides.  Non-Hodgkin Lymphoma 1. B-cell : i) MALT lymphoma – commoner in the West ii) Immunoproliferative small intestinal disease (IPSID) - also called alpha chain disease or Mediterranean lymphoma. 2. T- cell : Enteropathy-associated T cell Lymphoma - usually associated with celiac disease after 10-20 years of malabsorption. - poor prognosis – 11% 5-yr survival Adenomatous Polyps Frequency increases with age Less common in blacks than whites Familial predisposition Most asymptomatic May result in bleeding from twisting or vascular obstruction If large may cause: change in bowel habit intussusception Pathogenesis Conventional adenoma has a neoplastic progression (adenoma - carcinoma sequence) that includes APC, beta catenin, KRAS and TP53 mutations About 5% of conventional adenomas also have high levels of microsatellite instability (MSI-H) Traditional serrated adenoma is associated with BRAF or KRAS mutations and progress with beta catenin mutation or CpG island methylation Sessile serrated adenoma is associated with BRAF mutation and progress with high levels of microsatellite instability through MLH1 hypermethylation. Etiology Conventional adenoma is associated with smoking, high BMI and a diet of red meat Sessile serrated adenoma is associated with a high fat and meat diet, smoking, alcohol and high BMI Decreased risk of conventional adenoma is associated with dietary fiber intake, fruit consumption and folate intake Only a weak association between fiber and adenoma Location: Conventional adenomas are more common in the left hemicolon Sessile serrated adenoma is more common in the proximal colon Traditional serrated adenoma is more common in the rectosigmoid colon Incidence of adenomatous polyps 30–35% of adults at autopsy Most 5 mm diameter Mixed Hyperplastic–Adenomatous Polyps Thought to have a malignant potential because of presence of adenoma-like areas with abnormal proliferation Juvenile Polyp Most frequent colonic polyp in children 33% of cases in adults Commonly: presents with rectal bleeding autoamputation, with polyp passed per rectum Multiple Juvenile Polyposis Rare Can be life threatening Associated with: adenomatous polyps adenocarcinoma of: large bowel duodenum stomach pancreas  Juvenile polyp Often ulceration covered by granulation tissue at surface Cystically dilated glands beneath surface: filled with mucus devoid of atypical features separated by inflamed and edematous stroma Peutz–Jeghers Polyps lack of atypia disorganization of glands several cell types (including Paneth cells) smooth muscle fibers from muscularis mucosae: result in hamartomatous appearance Pattern of glandular disorganization and epithelial misplacement: simulates invasion should not be confused with malignancy May be associated with: adenomatous polyps with marked atypia colorectal adenocarcinoma Adenocarcinoma of Large Bowel Males = females Mean age 62 years Presentations: often indicate advanced disease rectal bleeding changed bowel habit anemia due to chronic blood loss vague abdominal pain intestinal obstruction: common when tumor in left colon rare if tumor in cecum or ascending colon signs suggestive of appendicitis: presentation of 25% of cecal carcinomas perforation: rare at site of carcinoma in cecum due to distention caused by obstructing rectosigmoid carcinoma  Location: 50% rectosigmoid area: relative incidence decreasing with shift in location toward proximal colon correlations between clinical features and anatomic subsite: right-sided more common in:  elderly  blacks  diverticular disease Multicentric in 3–6% of cases  Pathogenesis Environmental factors: dietary: particularly fat and animal protein influence intestinal microflora and ultimately chemical composition of intraluminal content Genetic factors: predisposition in: familial polyposis: nearly 100% by age 50 years hereditary nonpolyposis colorectal cancer syndrome (Lynch syndrome): 50% risk to first-degree relative of affected patient in direct genetic lineage due to germline mutations in genes responsible for repair of DNA mismatches  Lynch syndrome is due to inherited mutations in genes that affect DNA mismatch repair, a process that fixes mistakes made when DNA is copied. These genes (MLHL, MSH2, MSH6, PMS2, and EPCAM) normally protect you from getting certain cancers, but some mutations in these genes prevent them from working properly. Torre–Muir syndrome: often multiple associated with: multiple sebaceous tumors keratoacanthomas Familial colorectal carcinoma: defined by two or more first-degree relatives with colorectal carcinoma risk for first-degree relatives of affected individuals increased threefold mutant alleles of Hras1 minisatellite may predispose to this Epithelial polyps: Inflammatory bowel disease: particularly ulcerative colitis pelvic irradiation: usually for carcinoma of cervix Ureteral implantation sites Gross Pathology polypoid ulcerative/infiltrating Microscopic Well differentiated Moderately differentiated Poorly differentiated Signet ring carcinoma THANK YOU DO YOU HAVE ANY QUESTION?