Large Bowel Pathology PDF

‫وفاء رضا الصباغ‬.‫د‬.‫م‬.‫أ‬ 10/19/2022 dr.Wafaa Redha Al-Sabbagh 1 objectives  Outline the pathology of Hirschprung disease  - Differentiate between Crohn’s disease and ulcerative colitis  - List the different type...

‫وفاء رضا الصباغ‬.‫د‬.‫م‬.‫أ‬ 10/19/2022 dr.Wafaa Redha Al-Sabbagh 1 objectives  Outline the pathology of Hirschprung disease  - Differentiate between Crohn’s disease and ulcerative colitis  - List the different types of intestinal polyps  - Discuss the pathology of Diverticular disease  - List the different familial cancer syndromes of the colon and explain the underlying molecular events  - Enumerate the common malignant tumors of the colon and describe the morphology &staging of CRC  - Describe the morphology, C/P and complications of acute appendicitis  Define and classify Heamorrhoids, list tumors of anal canal 10/19/2022 dr.Wafaa Redha Al-Sabbagh 2 Hirschprung disease  Hirschsprung disease (or congenital aganglionic megacolon) is caused by congenital absence of ganglion cells in the rectum and sigmoid colon, resulting in intestinal obstruction.  males more than females  can be associated with Down syndrome.  presentation: delayed passage of meconium, or constipation, abdominal distention, and vomiting.  Grossly, the affected segment is narrowed, and there is dilation proximal to the narrow segment (megacolon).  Microscopically : absence of ganglion cells in Auerbach and Meissner plexuses, and the diagnosis is established when rectal biopsy demonstrates the absence of ganglion cells.  Treatment is resection of the affected segment. 10/19/2022 dr.Wafaa Redha Al-Sabbagh 3 10/19/2022 dr.Wafaa Redha Al-Sabbagh 4 10/19/2022 dr.Wafaa Redha Al-Sabbagh 5 Inflammatory Bowel Disease (IBD)  Inflammatory bowel disease (IBD) is a chronic condition resulting from complex interactions between intestinal microbiota and host immunity in genetically predisposed individuals resulting in an inappropriate mucosal immune activation 10/19/2022 dr.Wafaa Redha Al-Sabbagh 6 Inflammatory Bowel Disease (IBD)  There are 2 categories of IBD:  Crohn’s disease (CD) (or regional enteritis)  Ulcerative colitis (UC)  Colitis of indeterminate type describes cases that cannot be clearly classified.  Caucasians develop IBD more frequently than non- Caucasians.  The incidence of IBD is increasing.  Age distribution varies with the disease:  CD has a bimodal distribution with peaks at age 10–30 and 50–70  UC peaks at age 20–30 10/19/2022 dr.Wafaa Redha Al-Sabbagh 7 Presentation  episodes of bloody diarrhea or stools with mucus, crampy lower abdominal pain, or fever  CD may present with malabsorption or extraintestinal manifestations. It may mimic appendicitis. CD may cause perianal fistulas  Damage to the ileal mucosa can cause deficiencies of vitamin B12 and folate  risk of colorectal carcinoma (CRC) in CD and UC are equivalent for similar extent and duration of disease  Diagnosis of IBD requires endoscopic biopsy and clinicopathologic correlation 10/19/2022 dr.Wafaa Redha Al-Sabbagh 8 Crohn’s Disease Versus Ulcerative Colitis 10/19/2022 dr.Wafaa Redha Al-Sabbagh 9  CD UC 10/19/2022 dr.Wafaa Redha Al-Sabbagh 10 Crohn Disease morphology  most common sites involved are the terminal ileum, ileocecal valve, and cecum . Disease is limited to the small intestine alone in about 40% of case  multiple, separate, sharply delineated areas of disease, resulting in skip lesions  Strictures are common  cobblestone appearance in which diseased tissue is depressed below the level of normal mucosa  Fissures 10/19/2022 dr.Wafaa Redha Al-Sabbagh 11  microscopic features  active Crohn disease show abundant neutrophils that infiltrate and damage crypt epithelium.  crypt abscess and destruction  distortion of mucosal architecture: bizarre branching shapes and unusual orientations of crypts.  Noncaseating granulomas in approximately 35% of cases 10/19/2022 dr.Wafaa Redha Al-Sabbagh 12 Ulcerative Colitis morphology  always involves the rectum and extends proximally in a continuous fashion to involve part or the entire colon  colonic mucosa may be slightly red and granular-appearing or exhibit extensive broad-based ulcers  Pseudopolyps: regenerating mucosa  mural thickening is absent, the serosal surface is normal, and strictures do not occur  Histologic features are similar to those in colonic CD : inflammatory infiltrates, crypt abscesses, crypt distortion, and epithelial metaplasia.  However, skip lesions are absent, and inflammation generally is limited to the mucosa and superficial submucosa  Granulomas are not present 10/19/2022 dr.Wafaa Redha Al-Sabbagh 13 Diverticulosis  Colonic diverticulosis is an acquired outpouching of the bowel wall, characterized by herniation of the mucosa and submucosa through the muscularis propria (pseudodiverticulum).  Incidence increases with age  Major risk factor is a low-fiber diet, which leads to increased intraluminal pressure  Most common location is sigmoid colon  it can cause constipation alternating with diarrhea, left lower quadrant abdominal cramping and discomfort, occult bleeding and an iron deficiency anemia, or lower gastrointestinal tract hemorrhage.  Complications include diverticulitis, fistulas, and perforation with accompanying peritonitis. 10/19/2022 dr.Wafaa Redha Al-Sabbagh 14 Polyps  Hamartomatous polyps include nonfamilial juvenile polyps and polyps associated with a familial (Peutz-Jeghers) syndrome. Nonsyndromic polyps do not have malignant potential. Juvenile polyps characteristically are located in the rectum  Hyperplastic polyps are the most common histologic type; they occur most often in the left colon and are usually < 5 mm.  Serrated polyps occur more often in the right colon with serrated histology and risk of progression to cancer  Tubular and villous adenomas have long been known to have malignant potential. Microscopically, they show cellular dysplasia and either pure tubular, pure villous or tubulovillous histology 10/19/2022 dr.Wafaa Redha Al-Sabbagh 15 Familial Syndromes with risk of colon cancer  Familial adenomatous polyposis (FAP), also called adenomatous polyposis coli (APC), is due to an autosomal dominant mutation of the APC gene on chromosome 5q21  thousands of colonic adenomatous polyps; the diagnosis is made with discovery of >100 adenomatous polyps on endoscopy  Complications: by age 40, virtually 100% will develop an invasive adenocarcinoma and increased risks for developing duodenal adenocarcinoma and adenocarcinoma of the papilla of Vater 10/19/2022 dr.Wafaa Redha Al-Sabbagh 16   Gardner syndrome is an autosomal dominant variant of familial adenomatous polyposis characterized by numerous colonic adenomatous polyps, multiple osteomas, fibromatosis, and epidermal inclusion cysts  Turcot syndrome is a rare variant of familial adenomatous polyposis characterized by numerous colonic adenomatous polyps and central nervous system tumors (gliomas)  Cowden syndrome: PTEN mutation, Hamartomatous polyps, risk of colon cancer.  Benign skin tumors, benign and malignant thyroid and breast lesions 10/19/2022 dr.Wafaa Redha Al-Sabbagh 17   Hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch syndrome, is due to an autosomal dominant mutation of a DNA nucleotide mismatch repair gene that predisposes for colon cancer. It is associated with an increased risk of cancer at other sites, including the endometrium and the ovary.  Peutz-Jeghers syndrome is an autosomal dominant condition characterized by multiple hamartomatous polyps (primarily in the small intestine); melanin pigmentation of the oral mucosa; and increased risk of cancer at numerous sites including the lung, pancreas, breast, and uterus.  LKB1/STK11 gene mutation  Juvenile polyposis: SMAD4 mutation. Juvenile polyps; increased risk for gastric, small-intestinal, colonic, and pancreatic adenocarcinoma 10/19/2022 dr.Wafaa Redha Al-Sabbagh 18 Neoplasia  Colonic adenocarcinoma is the third most common tumor in the United States, in terms of incidence and mortality. Risk factors include:  Dietary factors (low fiber, low fruits/vegetables and high in red meat and animal fat)  Colon polyps (isolated adenomatous polyps, hereditary polyposis syndromes)  Other colon disease (Lynch syndrome, ulcerative colitis)  Diagnosis of colonic adenocarcinoma is established via endoscopy with biopsy 10/19/2022 dr.Wafaa Redha Al-Sabbagh 19   Cancer genetics:  Mutations of the APC gene cause activation of the Wnt pathway, leading β-catenin to translocate to the nucleus where it causes the overexpression of growth- promoting genes.  DNA mismatch repair deficiency causes microsatellite instability, which is another genetic carcinogenesis pathway 10/19/2022 dr.Wafaa Redha Al-Sabbagh 20   The pattern of spread in colonic adenocarcinoma includes:  lymphatic spread to mesenteric lymph nodes, with distant spread to liver, lungs, and bone 10/19/2022 dr.Wafaa Redha Al-Sabbagh 21 TNM Staging of Colorectal Cancer  Stage I (T1-2N0M0): tumors that invade submucosa through muscularis mucosa (T1) or invade muscularis propria (T2)  Stage II : (T3N0M0) tumors that have penetrated through the muscularis propria into pericolorectal tissue or T4 (tumor invade visceral peritoneum or other organs) but have not spread to the lymph nodes  Stage III (TXN1M0): regional lymph node involvement  Stage IV (TXNXM1): metastasis to distant sites 10/19/2022 dr.Wafaa Redha Al-Sabbagh 22 Morphology  Tumors in the proximal colon often grow as polypoid, exophytic masses that extend along one wall of the large- caliber cecum and ascending colon; these tumors rarely cause obstruction. By contrast, carcinomas in the distal colon tend to be annular lesions that produce “napkin ring” constrictions and luminal narrowing  Most tumors are composed of gland forming tall columnar cells that resemble dysplastic epithelium found in adenomas. The invasive component elicits a strong stromal desmoplastic response.  Others may produce abundant mucin that accumulates within the intestinal wall, and these carry a poor prognosis  10/19/2022 dr.Wafaa Redha Al-Sabbagh 23 10/19/2022 dr.Wafaa Redha Al-Sabbagh 24 Clinical features  Cecal and other right-sided colon cancers most often are called to clinical attention by the appearance of fatigue and weakness due to iron-deficiency anemia. Thus, it is a clinical maxim that the underlying cause of iron-deficiency anemia in an older male or postmenopausal female is gastrointestinal cancer until proven otherwise. Left-sided colorectal adenocarcinomas may produce occult bleeding, changes in bowel habits, or cramping left lower- quadrant discomfort. 10/19/2022 dr.Wafaa Redha Al-Sabbagh 25   Carcinoid tumors are neuroendocrine tumors that often produce serotonin. Locations include the appendix (most common) and the terminal ileum. Metastasis to the liver may result in carcinoid heart disease. Histologically, carcinoid tumors appear similar to other neuroendocrine tumors, with nests of small uniform cells.  Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the GI tract. Most cases have a KIT mutation. The peak incidence is in decade 7. Treatment is resection and a tyrosine-kinase inhibitor 10/19/2022 dr.Wafaa Redha Al-Sabbagh 26 ACUTE APPENDICITIS  Acute appendicitis is most common in adolescents and young adults  Pathogenesis : Acute appendicitis is thought to be initiated by progressive increase in intraluminal pressure that compromises venous outflow  50% to 80% of cases, acute appendicitis is associated with overt luminal obstruction, usually by a small, stone-like mass of stool, or fecalith, or, less commonly, a gallstone, tumor, or mass of worms 10/19/2022 dr.Wafaa Redha Al-Sabbagh 27 Morphology  subserosal vessels are congested, and a modest perivascular neutrophilic infiltrate is present within all layers of the wall.  diagnosis of acute appendicitis requires neutrophilic infiltration of the muscularis propria  focal abscesses may form within the wall (acute suppurative appendicitis) 10/19/2022 dr.Wafaa Redha Al-Sabbagh 28 Hemorrhoids  Hemorrhoids are tortuous, dilated anal submucosal veins caused by increased venous pressure. Risk factors include constipation and prolonged straining during bowel movements, pregnancy, and cirrhosis. Complications include painful thrombosis and streaks of bright red blood on hard stool 10/19/2022 dr.Wafaa Redha Al-Sabbagh 29 Anus  Condyloma acuminatum is the most common tumor of the anal region. It is caused by HPV infection  Anal intraepithelial neoplasia (AIN) is a precursor to anal squamous carcinoma  HPV infection causes the majority of anal cancers. 10/19/2022 dr.Wafaa Redha Al-Sabbagh 30