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Lecture 7

Neoplasms of the GI tract

A type of adenoma with equal proportions of tubular and villous architecture. Polypoid in appearnce. Has an intermediate potential for malignancy. Tubulovillous Adenoma
Type of adenoma that generally appears flat/slightly raised or depressed in comparison to surrounding mucosa. Grossly appears as a circular lesion. Has the highest potential for malignant change. Flat/Depressed (Villous) Adenoma
At what size do sporadic adenomas have a 30% chance of containing a carcinoma? Sporadic adenomas > 3cm have a 30% chance of containing a carcinoma
What portions of the colon does a screening sigmoidoscopy examine? Distal left colon
What percentage of colon cancers does a screening sigmoidoscopy detect? 50%
What is the indication for a full colonscopy? Any patients with an adenoma identified on screening sigmoidoscopy because they have an increased risk of having a right-sided colonic neoplasm.
(T or F) Screening sigmoidoscopy/colonoscopy and removal of adenomatous polyps has not reduced the incidence of colorectal carcinomas in the screened population. False
Two inflammatory bowel diseases with increased risk of dedveloping epithelial dysplasia Ulcerative colitis and Crohn's Disease
(T or F) The risk of carcinoma is the same in both colitis-associated dysplasia and sporadic adenomas. False. The risk of carinoma arising in colitis-associated dysplasia is much higher than the risk of carcinoma arising int he dysplastic epithelium of sporadic adenomas, although the two lesions may be histologically indistinguishable.
Why do inflammatory bowel disease patients undergo routine colonoscopies and biopsies? Higher risk of colorectal cancer in IBD patients. Carcinomas arising in IBD are often are hidden by surrounding inflammatory mucsoal changes, making them difficult to detect by gross exmaination by colonoscopy; thefore random biopsies must be taken.
What is an indication for colectomy? The diagnosis of high grade dysplasia of a colonic lesion.
What is the fourth most common cancer in the United States? Colorectal cancer
(T or F) Breast cancer and prostate cancer are more lethal than colorectal cancer. False. Colorectal cancer is the second most common cause of cancer deaths in the US.
Risk factors for colorectal cancer (1) Environment (western countries/western diet) (2) Dietary fiber (3) Genetic predisoposition (4) Chronic inflammatory bowel disease (5) Sporadic adenomas
(T or F) Immigrants to western countries from low incidence areas acquire the incidence rates of the adopted countries. True.
Tumor supressor gene that is mutated in almost all cases (90%) of colorectal carcinomas. This gene stabilizes beta-caten levels, leading to transcriptional activation that influence cellular proliferation and apoptosis. Located on chromosome 5q. APC gene
Genes associated wtih colorectal carcinoma. (1) APC gene mutated in 90% (2) p53 tumor suppressor gene inactivated in 50% (3) k-ras proto-oncogene is activated in 40-50%
Familial syndromes associated with higher risk of colorectal carcinoma. (1) Familial Adenomatous Polyposis (FAP) (2) Hereditary non-polyposis colorectal carcinoma (HNPCC)
Autosomal dominant inherited syndrome due to mutation of APC gene resulting in the development of hundreds of adnomas in the colon and rectum. 100% chance of developing colorectal cancer. Familial Adenomatous Polyposis (FAP)
Autosomal dominant syndrome characterized by the presence of numerous adenomas along with osteomas and fibromatosis of soft tissue. Gardner's Syndrome
Any small mass lesion that protrudes into the lumen of hte GI tract and only involves the superficial layers of the organ. Polyp
Type of polyp consisting of dysplastic epithelium. Adenomatous Polyp
Type of polyp that consists of benign epithelium and stromal tissue. Hamartomatous Polyp
Type of polyp that consists of lymphocytes Lymphoid polyp
Benign tumor of adipocytes Lipoma
Benign tumor consisting of smooth muscle cells. Leiomyoma
What isthe most common cancer of the GI tract? Colorectal Carcinoma
Name the layers of the GI tract (1) epithelium (2) submucosa (3) muscularis propria (4) serosa/adventitia
A variant of adenocarcinomas that is characterized by single cell infiltrates. Histologically, the cells have lare intracytoplasmic mucous vacuoles. Signet cell carcinomas
A variant of adenocarcinoma that secrete copious amount of mucin resulting in large mucin pools. Mucinous Adenocarcinoma
A syndrome characterized by fewer adenomatous polyps (<100) and development of colorectal cancer at a later age than typical FAP. Attenuated adenomatous polyposis (AAPC)
Autosomal dominant syndrome characterized by no or a few colonic adenomas, but still have a greatly increased risk of developing adenocarcinoma and other types of GI and reproductive cancers. Hereditary non-polyposis colorectal carcinoma (HNPCC)
Describe the molecular etiology of HNPCC Loss of function of the DNA replication error repair appartaus resulting in greatly increased mutation rate. Genes involved include hMSH2, hMLH1, hPMS1, hPMS2.
What type of cancers are associated with HNPCC? Enometrial, breast, and gastic adenocarcinomas
What type of cancer are females with HNPCC at higher risk for than colorectal cancer? Endometrial carcinoma
(T or F) HNPCC patients have a 100% risk of devloping colorectal cancer in their lifetime. False. Males and females with HNPCC have a 74% and 30% risk, respectively.
What cancers are associated with FAP? Tumors of the small intestine, ampulla of vater, brain, thyroid, desmoid tumors of the abdomen
Autosomal dominant syndrome characterized by the development of hamartomatous polyps with a 2-3 fold increased risk for devlopment of colorectal cancer Juvenile polyposis syndrome (JPS)
Syndrome characterized by the development of hamartomatous polys of the GI tract and melanotic accumulations found in the mouth, lips, hands, and genitalia. The polyps have a slightly increased risk of dysplasia, but higher risk of non-GI malignancies. Peutz-Jegher Syndrome
Syndrome characterized by hamartomatous polyps of the GI tract with increased risk for the development of breast and thyroid cancer. Cowden's Disease
What types of cancers are Peutz-Jegher Syndrome patients at higher risk for? Breast, cervix, gonads, colorectal, and other GI tract tumors.
What screening test should be preformed in an elderly person with symptoms of weakenss/lethargy and a CBC consistent with anemia? Fecal occult blood test (FOBT) which detects hidden blood in stool, indicating bleeding from a GI tract site. High suspicion of colorectal cancer in men or post-menopausal females with unexplanined anemia.
Most common site of distant metasis of colorectal cancer? Liver
What is the second most common site of distant metatasis of colorectal cancer? Lung
(T or F) The most importance prognostic factor of colorectal carcinoma is histological grade. False. Clinical stage is the most important prognostic indicator. There are two different staging criteria: (1) Dukes' Staging System (2) TNM Classification
Dukes' staging system: A Tumor can invade into but not through the muscularis propria. No lymph node metastasis 5-yr survival of 81.2%
Dukes' staging system: B Tumor invades through muscularis propia. No lymph nodes metastasis. 5-yr survival of 64%
Dukes' staging system: C Metastasis to lymph nodes. 5-yr survival of 27.4%
Dukes' staging system: D Distant metastasis. 5-yr suvival of 14.3%
What is the 5-yr survival of TNM stage 0 of colorectal cancer? 75%
What is the 5-yr survival of TNM stage II colorectal cancer? 70%
What is the 5-yr survival of TNM stage III colorectal cancer? 58%
What is the 5-yr survival of TNM stage IV colorectal cancer? 25-33%
What is the 5-yr survival of TNM stage V colorectal cancer? 4-7%
What type of cancer represents 90% of gastric neoplasms? Gastric adenocarcinomas are the most common type of gastric neoplasms. The remaining 10% of gastric neoplasms are predominantly non-Hodgkins' lymphoma, carcinoid tumors, and stromal tumors.
What are the two histological types of gastric carcinomas? (1) intestinal type (2) diffuse type
It is the most frequent form of cancer in Japan, but has a decreasing incidence in the United States. The neoplasm is almost always adenocarcinoma. The cancer is twice as common in males than female with a peak incidence in the seventh decade of life. Gastric Cancer
Etiology and Risk factors of Gastric Cancer (1) Chronic gastritis (2) Helicobacter pylori infection (3) lower socioeconmic status (4) Partial gastrectomy (5) Menetrier's disease (6) Gastric adeomas (7) Family history of gastric cancer
Type of metaplastic atrophic gastritis that results in intestinal metaplasia of the gastric mucosa. Metaplasia typically occurs in the border between the antrum and body of the stomach. Mutlifactoral etiology including nutritional, toxins, and infection Environmental metaplastic atrophic gastritis (EMAG)
Type of metaplastic atrophic gastritis with intestinal metaplasia of the gastric mucosa. Intestinal metaplasia typically occurs in both the body and fundus of the stomach. Caused by the autoimmune destruction of parietal and chief cells. Autoimmune metaplastic atrophic gastritis (AMAG)
Disease characterized by hypertrophied gastric mucosa resembling brain gyri. Associated with increased risk for gastric cancer. Menetrier's Disease
What is the lifetime risk of HNPCC patients in developing gastric cancer? 20%
Autosomal dominant syndrome due mutated E-cadherin gene in 30-50% of cases. Characterized by diffuse type (signet ring cell) of gastric cancer. Hereditary Diffuse Gastric Cancer Syndrome
What type of breast cancer are females of Hereditary Diffuse Gastric Cancer Syndrome are at higher risk for? Females have a lifetime risk of 20-40% for developing lobular type breast cancer.
What genes are implicated in gastric cancers? (1) p53 (2) E-cadherin
What is the function of E-cadhering? E-cadherin codes for a cell surface receptor that mediates aspect of cell-cell adhesion and cell-cell communication. Mutated in 30-50% of Hereditary Diffuse Gastric Cancer Syndrome cases.
Periabdominal lymphatic spread of metastatic gastric cancer to supraclavicular node. Virchow's node
A periumbilical mass associated with intraperitoneal spread of gastric cancer. Sister Mary Joseph's node
Bilateral enlargement of ovaries by signet ring cells (diffuse type) gastric cancer. Krukenberg Tumor
Metastatic tumor felt on rectal exam due to growth of intraperitoneally spread gastric tumor in the rectovesical/rectouterine space. Blumer's Shelf
Extensive or widespread metastasis of tumor to the peritoneal surface. Can cause malignant ascites. Peritoneal carcinomatosis
What are the most common sites for distant metastatsis of gastric cancer? (1) Liver (2) Lung. Gastric cancer spread to these sites via a hematogenous route.
What is the 5-yr survival of a completely excised localized gastric cancer with no lymph node metastases at the time of resection? 50%
What is the 5-yr survival of late stage gastric cancer? 25%. Gastric cancers are highly resistant to radiotherpay and chemotherapy.
(T or F) Squamous cell carcinomas represent more than half of all esophageal carcinomas in the US. False. Squamous differentiation represent less than half of all esophageal carcinomas, which is not true worldwide. Squamous cell carcinoma make up majority of esophageal carcinomas worldwide.
Describe the anatomical distribution of esophageal cancers. 1/2 are located in the middle third of the esophagus. 1/3 are located in the lower third of the esophagus. The remainder are located in the upper third of the esophagus.
What countries have the highest rates of esophageal cancers? China and parts of Africa have the highest rates of esophageal cancers.
What population in the US that has the highest rate of esophageal cancer? Highest incidence of esophageal cancer in men (M:F 4:1) and occurs more frequently in African Americans (4 fold higher incidence).
Risk factors for esophageal carcinoma (1) Tobacco smoking (2) Alcohol abuse (3) Dietrary carcinogens and deficiencies (2) Chemical injury (3) Achalasia (4) Plummer-Vinson Syndrome (5) Tylosis (6) Esophageal diverticulae
Syndrome characterized by dysphagia, anemia, esophageal webs. Also has increased risk of esophageal cancer. Plummer-Vinson syndrome
Autosomal dominant syndrome characterized by hyperkeratosis of the hands and feet and increased risk of esophageal cancer. Tylosis
(T or F) Human papilloma virus is not found in the majority of esophageal cancers. True
What gene is implicated in esophageal cancer? p53 tumor suppressor gene
Histologic findings of squamous dysplasia of esophagus (1) increased nuclear size (2) pleomorphism of epithelial cells (3) increased nuclear/cytoplasmic ratio. Esophageal cancer has been documented to arise in patients with these precursor lesions within 3-4 years of diagnosis.
What is the 5-yr survival of late stage esophageal cancer? 5%.
A precursor lesion of esophageal adenocarcinoma. The lesion is characterized by columnar metaplasia of esophageal squamous epithelium in the lower esophagus. Barrett Esophagus
Risk factors of esophageal adenocarcinoma (1) Gastroesophageal reflux (2) Barrett Esophagus (3) Epithelial dysplasia (4) White male (5) Tobacco use (weak association) (6) Obesity
(T or F) Helicobactor pylori infection and NSAID use are risk factors for esophageal adenocarcinoma. False. There is an inverse correlation of H. pylori infection and NSAID use.
What gene is implicated in esophageal adenocarcinoma? p53 tumor suppressor gene
What is the indication for prophylatic esophagectomy? High grade dysplasia of esophageal epithelium due to the high risk of developing esophageal adenocarcinoma.
(T or F) Aspiration is not a common symptom of esophageal adenocarcinoma. True. Aspiration due to tracheoesophageal fistula is rare in adenocarcinoma of the esophagus. Tracheoesophageal fistuals are more common in squamous cell carcinoma of the esophagus.
What is the indication for endoscopic surveillance of the esophagus? Patients with identified Barrett esophagus must undergo endoscopic surveillance for high grade dysplasia and early cancers. These lesions can be surgically excised with a cure rate that approaches 50%.
Tumors with both epithelial differentiation and neuroendocrine differentiation, with bland histologic features and the elaboration of catecholamines and/or peptide hormones. Carcinoid tumors
(T or F) Carcinoid tumors only occur in the colon. False. Carcinoid tumors can occur in any part of the GI tract, although are not commonly found in the colon.
(T or F) Histologic grading is an important prognostic factor of carcinoid tumors. False. It is not possible to predict the biological behavior of carcinoid tumors form their histologic appearance.
Prognostic indicators of carcinoid tumors (1) size of tumor (2) depth of local invasion. These criteria vary with the site of the tumor.
What is the preferred site of metastasis of GI carcinoid tumors? Liver
Where do majority of malignant carcinoid tumors arise in the GI tract? The most aggressive carcinoid tumors arise in the distal small intestines. These tumors will metastasize 22% of the time.
Manifestation of carcinoid syndrome Carcinoid syndrome occurs with mestastasis of carcinoid tumor to the liver, which allows for elaboration of vasoactive peptides and amines. (1) Flushing (2) Diarrhea/abdominal cramping (3) Bronchospasm (4) Valvular lesions of the right side of the heart
Histological appearance of well differentiated neuroendocrine neoplasms Cells are monomorphous. Nuclei are round to oval with "salt & pepper" morphology. The cytoplasm is lightly esoinophilic and abundant. Most cells have a polygonal shape. Mitoses are rare. Common growth patterns: insular, trabecular, tubular, and solid.
Immunohistological stains used to identify neuroendocrine cells from non-neuroendocrine cells (1) Chromogranin and neuron specific enolase (2) Silver stains (Grimelius stain, Masson stain) (3) Any stain for specific peptide hormone secreted by the neoplasm
Tumor that represents <5% of gastric cancers. They are of MALT type and are associated with H. pylori infections. Lymphoma of mucosa associated lymphoid tissue (MALT). The stomach is a rare primary site of malignant lymphoma.
Tumor characterized by mutliple non-healing uclers of the small intestine in patients with sprue-like illness (symptoms of malabsorption). The tumor is of T cell origin. Enteropathy-associated T cell Lymphoma (EATL)
Most common site of GIST tumors Stomach
Neoplasm composed of cells with spindle cell morphology. Typically have a mutation in the c-kit gene. Gastrointestinal stromal tumor (GISTs)
Characteristics of malignant GISTs arising from the stomach (1) > 5cm in diameter (2) > 5 mitotic figures per 50 standard high power microscopic fields
Criteria for maligant GIST tumor of the small intestine A large GIST of the small intestine with ANY evidence of mitotic activity
Most common tumors of the small intestine The small intestine is an uncommon site of neoplasia. Malignant lymphoma, carcinoid tumors, and GISTs are among the more common neoplasms of the small intestine.
(T or F) The most common neoplasm found in the anal canal are primary lesions. False. The most common neoplasm affecting the anal canl is the direct extension of adenocarcinoma arising in the distal rectum.
(T or F) Human papilloma virus is a known risk factor of squamous carcinoma of the anus. True.
Created by: UVAPATH2