GASTROINTESTINAL TRACT lecture 5
The Department of Pathology Small and Large Intestines -2-Types of intestinal polyps
Non neoplastic polyps: Occasionally seen, long standing IBD: UC > Crohn. And has no malignant potential and commonly seen. Comprises 90% of all epithelial polyps and found in >1/2 of all persons over the age of 60. 1- Hamartomatous polyp (rare). a- Juvenile. b- Peutz Jeghers polyp. 2- Inflammatory polyp. 3- Hyperplastic polyps. 4- Lymphoid polypsneoplastic polyps:
Adenomatous polyps Preneoplastic polyps -tubular adenoma (very common) -tubulovillous adenoma (seen less than TA) -villous adenoma (occasionally seen)Benign non-neoplastic polyps
-Hyperplastic polyps -very common. -proliferation of mature goblet cells; size <0.5 cm -commonly found in adults > 60 years old Gross-nipple like -hemispheric -smooth moist protrusions of the mucosa -often multiple -> 1/2 in recto-sigmoid Micro-well formed glands -crypts lined by non-neoplastic cells -goblet cell/absorptive cell differentiation -serrated lumenJuvenile Polyps
-Rare; focal hamartomatous polyps-virtually no malignant potential (exception: Juvenile polyposis syndrome)-commonly found in children younger than age 5usually solitary.-most frequently in rectum.--isolated IP may be found in adults: “retention polyp” which are smaller < 1 cm. with stalks up to 2 cm.-Lamina properia is the bulk of the polyp with cystically dilated glands, surface ulceration-Rare autosomal dominant JP syndrome does carry a risk of adenoma and hence adenocarcinomaHamartomatous Polyp: Peutz Jeghers polyp
Rare Large polyp with arborizing (tree-like) projections with smooth muscle present at the mucosal surface Polyps with no malignant potential, but patients at risk for other malignancies: pancreas, breast, lung, ovary, and uterusNeoplasms of the small intestines
Perplexingly uncommon compared to tumors in other segments of GI tract 3-6% of GI tumors Benign -Adenomas -Leiomyomas -Lipomas -AngiomasMalignant -Adenocarcinoma -Primary lymphoma -Carcinoids -GISTS
Adenoma Adenomatous polyps
-25% of SI benign tumors -mostly in ampulla of vater -familial polyposis coli prone to amp of v adenoma -30-60 yrsNeoplasms of the large intestines Adenomas
All adenomas show dysplastic epithelium All are precancerous May proceed to intramucosal or invasive carcinoma May occur anywhere, most occur in the left colon, specifically, recto-sigmoid Risk of malignant transformation is dependent on polyp size, architecture, severity of dysplasiaCorless
Tubular adenoma
Pedunculated, composed of branching round/ tubular glands on a stalk Can grow up to 4 cm in diameter The larger the polyp the greater the chance of harboring carcinoma. 90% in the colon; rarely in the stomach and SI Solitary in 50% 2 or more in the remaining 50%VILLOUS ADENOMA
VILLOUS ADENOMA -Sessile, broad base rather than a stalk -Composed of numerous , finger-like projections of epithelium -Greater than 50% villous -More than 40% harbor carcinoma TUBULOVILLOUS ADENOMA -features of both adenomas -25-50% (30%) villous-Cancer is rare in TA <1cm in size -The risk of cancer is high (approximately 40%) in sessile villous lesions > 4cm -Severe dysplasia when present is often seen in villous areas
Familial syndromes
Familial syndromes -Familial adenomatous polyposis -Gardner syndrome -Hereditary non polyposis colorectal cancer Average onset of polyps in each of these adenomatous polyp syndromes is the teens and twenties, followed by cancer in 10-15 years unless surgical resections interrupt the natural progression.Familial adenomatous polyposis (FAP)
Rare, autosomal dominant; genetic defect is in the APC gene on Ch 5q21 Patients with 500-2500 polyps (min 100 polyps) FAP - Cancer preventive measures by prophylactic colectomy as soon as possible. early detection of disease in siblings and first degree relatives at riskGardner syndrome a variant of FAP also autosomal dominant polyps similar to FAP but with multiple bone lesions and skin lesions particularly mandible, skull, long bones, epidermal cysts and fibromatosis Turcot syndrome: rare variant, GI polyps and CNS tumors, mostly gliomas
Adenocarcinoma: etiology:
Accounts for 10% of all cancer related deaths peak incidence: 60-79 years (<20%: before 50) worldwide: environment, diet, obesity, physical activity; no causal relationship FAP patients either inherit one defective copy of APC (one hit) or else acquire it during embryogenesis. Deletion of the remaining good APC gene in the colonic stem cell is all that is necessary to start down the road to an adenoma.Genetic Alterations: the path from normal to cancer
APC at Ch 5q21 (normal to hyperproliferative) APC- B catenin -loss of DNA methyl (early adenoma) Mutation of K- ras at Ch 12p12 (intermediate adenoma) loss of DCC gene on Ch 18 (late adenoma) Loss of p53 at Ch 17p13 (invasive cancer)-tumor will infiltrate wall of colon and metastasize to lymph nodes and liver-prognosis is related to size and spread of the lesionSTAGING: Dukes (A,B,C) staging and Astler Coller System - pathologic staging of colorectal cancer:A – mucosa A: 5YSR - 100%B - submucosa or muscularis properia B1; serosa B2B1: 67% B2: 54%C - B1 + lymph node met C1; B2 + lymph node met C2C1: 43%; C2: 23%D - Distant mets to lung and liver Adenocarcinoma: Morphology
Invasive adenocarcinoma The tumor has invaded through the mucosa, into submucosa (in this case it is seen to the level of the muscularis propria) The submucosa contains large lymphatics which are conduits for metastases
Invasive adenocarcinoma arising in villous adenoma
Most worrisome lesions are villous adenoma > 4 cm. When invasive carcinoma occurs, there is no stalk as a buffer zone and invasion is directly into the wall of the colon (submucosa or deeper).
Adenocarcinoma: Clinical features
Right colon adenocarcinoma -usually -asymptomatic for a long period of time -signs and symptoms of iron deficiency anemia due to surface ulceration and resulting blood loss Polypoid, fungating non-obstructing right colon caLeft colon adenocarcinoma -generally annular -narrow the lumen -change in bowel habits or obstruction -blood in stool (maybe obvious/bright red or occult) -originating from ruptured vessels at the edge of the ulceration
Malignant -Adenocarcinoma -Primary lymphoma -Carcinoids -Gastrointestinal stromal tumors (GISTS)
1- MALT lymphoma (sporadic) -GI primary extranodal site -1-4% of all GI malignancies 30-40 yrs Location in: Stomach: 50-60% SI: 25-30% Distal colon: up to 10%
Primary lymphoma
Arises from lymphoid aggregates in the wall with no evidence of other primary sites Gastric lymphomas are most common and have better prognosis than SI or LI if early refractory (celiac) sprue associated with TCL; mostly in jejunumEtiology:
Due to random changes brought about by t(11;18) H. pylori reactive T helper cells produces cytokine that allows growth of monoclonal B cell population Therefore Tx: H. pylori sporadic but occur more frequently on certain populations: 1. pxs with H. pylori 2. natives of Mediterranean region 3. pxs with immunodeficiency states 4. HIV infected individuals 5. pxs in immunosuppressive therapy 6. patients with refractory sprue2- sprue associated lymphoma
Rare T cell tumors (Refractory sprue) Long standing malabsorption syndrome, of gluten enteropathy, and occur in young ages, 30-40 years, following 10-20 years MS. Of T cell origin. 3- Mediterranean lymphoma: B cell lymphoma, in children and young adults, type of heavy chain disease (alpha), with plasma cell infiltration of the wall and of poor prognosis.4- Burkitt’s lymphoma: non African type in children and young adults, affects the retroperitoneum and ovaries also. Characterized by monotonous cells with round nuclei and multiple nucleoli, and interspersed macrophages giving a starry sky appearance.
Malignant -Adenocarcinoma -Primary lymphoma -Carcinoids -Gastrointestinal stromal tumors (GISTS)
Carcinoidsarise from NE cellscommon in SI (50% of SI malignancies; 2% of colorectal malignancies)5 YSR: 90%5 YSR with liver mets: 50% if widespread – death*Most common sites in the order of frequency:Appendix-Ileum (SI)-Rectum-Stomach-Colon*Appendiceal and rectal carcinoids almost never metastasize. *90% of ileal, gastric and colon carcinoids have already met to L.Ns at time of diagnosis
Carcinoid syndrome
may secrete bioactive amines (serotonin: diarrhea, flushing of face, broncho -spasm, cyanosis -carcinoid syndrome) Also diarrhea, hepatomegaly, cardiac fibrosis, and diffuse fibrosis. Carcinoid syndrome occurs in about 1% of all patients with carcinoid tumors and 20% of those with widespread metastasis. Excess elaboration of serotonin 5HT and 5 HIAA; present in blood and urine. 5-HIAA is deactivated in the liver. Therefore in GI carcinoids, liver metastases have to be present for the development of the syndrome. Not true for ovary and lung carcinoids. Other products: Histamine, bradykinin and prostaglandinsMorphology:
Form polypoid masses, solid tan in colour and firm. Microscopically show islands and trabeculae of cells that are monotonous with granular cytoplasm, and of uniform shape in low grade types of benign behavior while it is in aggressive types of small cells or spindle cells. Positive for chromogranin A, neuron specific enolase and synaptophysin. Electron microscopy: Neuro - Secretory granulesMalignant -Adenocarcinoma -Primary lymphoma -Carcinoids -Gastrointestinal stromal tumors (GISTS)
Gastrointestinal stromal tumor (GIST) uncommon arise in wall of bowel. portrude into lumen; ulcerate; GI bleed mostly slow growing; cured by surgery 30% recurrence/liver mets within 10 years may progress to high grade sarcoma all are potentially malignant and may be low risk or high risk high risk if > 5 cm in size and if mitosis >10/10 hpf
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Neoplasms of appendix
Mucocele: benign dilatation of the lumen by mucinous secretions. Mucinous cyst adenoma- proliferation of benign neoplastic cells-dilatation by mucinous material -may rupture Mucinous cyst -adenocarcinoma -invasion of neoplastic cellsPseudomyxoma peritonei
term describing distention of the peritoneal cavity by the presence of semisolid, mucin containing adenocarcinoma cellsPeritoneum
Inflammation 1. Sterile peritonitis due to bile or pancreatic juices 2. Surgical procedures 3. Endometriosis 4. Rupture of GI tract (Ruptured appendicitis, acute salpingitis, or diverticulitis)