GI Pathology Pathology of the Esophagus and Stomach Topics to be covered: Hiatal Hernia Reflux esophagitis Barretts esophagus Esophageal

ageal Varices Zenkers diverticulum Mallory Weiss syndrome Esophageal carcinoma

2/14/11 and 2/16/11

Hiatal Hernia: Herniation of stomach through hiatus (hole) in diaphragm created by separation of diaphragmatic crura Sliding hiatal hernia: Paraesophageal hiatal hernia: Sliding hernia: Stomach slides up through hiatus in diaphragmatic crura. Bell shaped dilation of stomach 95% of cases Paraesophageal hernia: comes up next to esophagus pouch of stomach along the greater curvature may be caused by previous surgery, including operations for previous sliding hernia Clinical: condition of adults o increasing incidence with age o associated with obesity acquired disorder (some sort of weakness in diaphragm muscles hernia) also recognized in infants and children (rare) o ?developmental problem in diaphragm Reflux esophagitis o LES compromised reflux of gastric juices into esophagus strangulation, obstruction (paraesophageal)
Test q: A 39M reports heartburn and occasional upper abdominal pain. An upper endoscopy is performed and a biopsy is taken from just above the diaphragm. The biopsy shows gastric-type mucosa w/mild chronic inflammation. No squamous epithelium or goblet cells are seen. A possible explanation for this finding is: Hiatal hernia. (Other choices: Reflux esophagitis, Barretts esophagus, Zenkers diverticulum, Helicobacter infection) Test q: A 30M w/epigastric pain following eating has upper endoscopy. The rugal folds of the stomach continue into the lower esophagus. A biopsy of this area shows cytologically bland glandular mucosa w/columnar cells w/cytoplasmic mucin, but no goblet cells. An alcian blue stain is negative. The best dx is: Hiatal hernia. (Other choices: Barretts esophagus, Ectopic gastric mucosa, Adenocarcinoma in situ)

Reflux esophagitis (GERD): Mucosal injury of the lower esophagus due to reflux of acidic gastric contents. Reflux esophagitis: decreased LES tone or increased abdominal pressure o CNS depressants o hypothyroidism o pregnancy o obesity o alcohol/tobacco o hiatal hernia o delayed gastric emptying
Test q: Factors associated w/gastroesophageal reflux include all of the following except: Below average BMI. (Other choices: Smoking, Hiatal hernia, Alcohol consumption)

1. Normal esophageal mucosa: stratified squamous mucosa cells at bottom are basal cells (small w/large nucleus, little cytoplasm). As you approach lumen, cells acquire keratin (nucleus smaller, more cytoplasm). 2. Reflux esophagitis: Basal cell hyperplasia. Also inflammatory infiltrate within squamous mucosa. Typically consists of eosinophils. 3. Reflux esophagitis: Eosinophils bright orange granules, bilobed nucleus Microscopic path: elongation of papillae o b/c of basal cell hyperplasia basal zone hyperplasia >20% of thickness eosinophils histology not related to severity of symptoms, but to duration Clinical: adult population over 40 yrs (reported in infants and children, but rare) heartburn, chest pain, regurgitation of gastric contents o accentuated by bending forward, lying supine (reflex easier) dysphagia complications: ulceration, bleeding, stricture, Barretts esophagus
Test q: A 57F has had burning epigastric pain after meals for more than 1yr. Phys exam shows no abnormal findings. Upper GI endoscopy shows an erythematous patch in the lower esophageal mucosa. A biopsy specimen shows basal squamous epithelial hyperplasia, elongation of the lamina propria papillae into the squamous epithelium, and scattered intraepithelial inflammatory cells including some eosinophils. Which of the following is the most likely diagnosis? Reflux esophagitis. (Other choices: Barretts esoph, Esoph varices, Scleroderma, Iron deficiency) REPEATED x2

Barretts esophagus: Replacement of squamous epithelium of lower esophagus by metaplastic intestinal epithelium (in response to prolonged injury by refluxed gastric juices)

Test q: A biopsy from the lower third of the esophagus of a patient w/reflux shows glandular epithelium w/pale-staining cytoplasm. The pathologist is not convinced, based on the hematoxylin and eosin stain, that goblet cells are present. Which of the following special stains, if positive, would be helpful in establishing a diagnosis of intestinal metaplasia? Alcian blue. (Other choices: Mucicarmine, Congo red, Trichrome, Giemsa) Test q: A 38F with a history of symptomatic GE reflux has an upper endoscopy to evaluate her disease and response to medical treatment. A patch of reddened mucosa is seen in the lower 3cm of the esophagus. Biopsies of the mucosa are obtained through the endoscope. Histologic exam of the biopsies shows mucosa w/glands lined by a mixture of columnar cells and goblet cells. The glandular cells have a single layer of small, uniform, roundto-oval nuclei. An Alcian blue stain is performed and is positive (blue) in the goblet cells. The diagnosis is: Barretts esophagus. (Other choices: Adenocarcinoma, Dysplasia, Mallory-Weiss syndrome)

Importance of Barretts? Confers an increased risk factor for adenocarcinoma o develops through a sequence of increasing grades of dysplasia Barretts in perspective: Barretts develops in 10% of patients with symptomatic GERD o (? Why do some patients develop Barretts and others dont) Most adenocarcinomas develop in Barretts but most individuals with Barretts do not develop cancer o Risk low in the grand scheme of things Clinical: Symptoms of reflux Barretts associated with o Long history of reflux (years) o More and longer episodes o More massive reflux Risk of carcinoma: duration of Barretts esophagus length of involved segment Dysplasia: Precursor lesion to invasive carcinoma o abnormal nuclear and architectural changes of epithelium o classified into low and high grade Effective screening tool
Test q: The significance of dysplasia in Barretts esophagus is: It indicates a higher risk of progression to adenocarcinoma than does Barretts w/o dysplasia. (Other choices: All cases of Barretts w/dysplasia will progress to adenocarcinoma over a 5yr period. It indicates the presence of HPV infection, similar to dysplasia of the cervix. It indicates a congenital malformation of the esophagus, similar to cystic renal dysplasia.) Test q: A 35M presents w/heartburn and is counseled on the importance of diagnosis, treatment, and follow-up of GERD. All of the following are thought to be consequences of GERD EXCEPT: Squamous papillomas. (Other choices: Barretts esophagus, esophageal webs, esophageal stenosis) The patient described above undergoes upper endoscopy and biopsy. The biopsy report reads, Esophagus, lower, biopsy. Barretts esophagus (intestinal metaplasia) with low grade dysplasia. The significance of mild dysplasia is: It indicates a significant (15-20%) risk of progression to carcinoma in the next 2-4 years. (Other choices: It indicates low [<5%] risk of progression to adenocarcinoma in the next 5 years. It indicates a high [25-50%] risk of concurrent or subsequent cancer in the next year. It has no significance because all Barretts cases by definition have low grade dysplasia.) Test q: A 55M reports chronic heartburn and has upper endoscopy. A biopsy (shown) of the lower third of the esophagus is performed. The best dx is: Barretts esophagus. (Other choices: Reflux esophagitis, Adenocarcinoma, Squamous dysplasia, Herpes esophagitis)

Treatment options: photodynamic therapy laser ablation (no specimen obtained from these two) endoscopic mucosal resection specimen obtained (figure)
Test q: Previously, patients w/a Barretts esophagus diagnosis were at high risk for having an adenocarcinoma that was not histologically sampled. This is currently uncommon due to what development: Endoscopic ultrasound exam guidance in selecting the site to biopsy in these patients. (Other choices: Tx w/proton pump inhibitors, Photodynamic therapy, Brushing cytology. 2005 Exam 1 #33 worded poorly?)

Endoscopic mucosal resection:

Esophageal varices: Portal hypertension blood cannot flow through portal system diverted to systemic veins through vessels which bridge the 2 systems o Common in cirrhosis patients Esophagus is one site of such collateral channels o 3 major bridging sites: lower esophagus, rectum, umbilicus Esophageal varices: coronary veins of stomach (portal) submucosal veins in esophagus azygous vein (systemic) Clinical features: Develop in 90% of cirrhotic patients Asymptomatic till they rupture Hematemesis o 40% die in first episode hemorrhage hepatic coma o rebleeding in 50% within a year o account for half of all deaths in cirrhosis Therapy - sclerotherapy, banding, balloon tamponade o Sclerotherapy put sclerosing agent in esophageal veins to clot them o Balloon compress veins

Test q: All of the following are common sites of dilated veins/varices in patients with cirrhosis EXCEPT: Upper part of the esophagus. (Other choices: Anal region, Lower esophagus, Portal vein) Test q: The pathogenesis of esophageal varices in patients w/cirrhosis involves which of the following? Elevated portal vein pressure. (Other choices: Hypoalbuminemia, Decreased production of clotting factors, Decreased detoxifying capacity)

Figures: esophageal varices. Grossly, see dilated, tortuous channels = submucosal veins that acted as collaterals. See ruptured esophageal varix. In microscopic pic, also see dilated submucosal veins dilated, engorged w/blood.

Zenkers diverticulum: Diverticulum = outpouch mass in neck o can be several centimeters in size can accumulate food o dysphagia (b/c compressing esophagus) o food regurgitation o aspiration with resultant pneumonia

Esophageal lacerations (Mallory-Weiss syndrome): Longitudinal tears at the esophago-gastric junction Follows severe retching or vomiting (acute alcohol intoxication) Mallory-Weiss syndrome: self-limiting or catastrophic therapy: o vasoconstrictive medications o balloon tamponade prompt healing with no residua

Left: Endoscopic view: Longitudinal lines/lacerations at the GE junction. Right: Lacerations at lower end of esophagus

Test q: A 60M who is a known chronic alcoholic, following an episode of heavy drinking and vomiting has severe hematemesis. Upper endoscopy shows longitudinal tears in the mucosa at the EG junction w/associated bleeding. The tears do not extend through the muscularis propria of the esophagus. The term for this clinical situation is: Mallory-Weiss syndrome. (Other choices: Boerhaave syndrome, Barretts esoph, Zenkers diverticulum)

Esophageal cancer: Squamous cell: most common cancer worldwide tobacco, alcohol, other factors (?dietary nutrients & toxins, HPV) Males Middle third of esophagus Adenocarcinoma: arises from columnar epithelium common in western countries Barretts = leading cause Males Lower third of esophagus, GEJ

No normal columnar epithelium in esophagus, so when adenocarcinoma arises from the esophagus, it is from Barretts. 1 2 3

1. Squamous cell carcinoma. Cancer trying to make keratin. 2. Adenocarcinoma. Cancer trying to make glands. 3. Esophageal/stomach junction. Cancer perforates through the wall. Symptoms: Insidious onset, symptoms present late dysphagia, pain on swallowing o patients adjust drink more liquid weight loss, debilitation bleeding Aspiration chest pain Prognosis: Very poor except in early cancers that have not gained access to submucosal lymphatics 5 year survival is 70-80% in early cancer vs 10-20% in late cancer
Test q: A 68F has had substernal pain after meals for many years. For the past year she has had difficulty swallowing both liquid and solids. On phys exam there are no remarkable findings. Upper GI endoscopy shows a lower esophageal mass that nearly occludes the lumen of the esophagus. Biopsy of the mass is most likely to show which of the following neoplasms? Adenocarcinoma. (Other choices: Leiomyosarcoma, Squamous cell carcinoma, Non-Hodgkin lymphoma, Carcinoid tumor) REPEATED x2 Test q: This is a surgical specimen from a 52M who presented w/progressive dysphagia (2007 Exam 2, #25 cant see gross photo very well). He has a history of heartburn symptoms. Upper endoscopy performed 6yr ago for the heartburn showed erythema of the distal esophagus. Biopsy of this area was performed and showed cytologically bland columnar epithelium w/occasional goblet cells. The dx for the current specimen is most likely: Esophageal adenocarcinoma. (Other choices: Barretts esophagus, Gastric adenocarcinoma signet ring type, Esophageal squamous cell carcinoma)

Topics to be covered: Heterotopia Acute gastritis Chronic gastritis o Autoimmune gastritis o H. pylori gastritis Peptic ulcer Gastric carcinoma

Heterotopia: Normal tissues present at abnormal location Pancreas in wall of stomach Pancreatic heterotopia: Incidental nodule Inflammation Ulceration Bleeding stricture

Acute gastritis: Transient mucosal inflammatory process Mechanisms of damage: direct epithelial damage o (alcohol, chemo/radiation therapy, NSAIDs) disruption of the protective barriers o mucus layer (?aging, H pylori important here) o bicarbonate secretion (NSAID, H pylori, uremia) o mucosal blood flow (NSAIDs) o prostaglandin secretion (NSAIDs) o epithelial regeneration (chemotherapy) Etiologic factors: NSAIDs (aspirin) alcohol smoking chemotherapeutic drugs/ radiation uremia severe stress (trauma, burns, surgery) corrosives (acid/ alkali) mechanical trauma (nasogastric intubation)

Clinical symptoms: epigastric pain, nausea and vomiting severe cases: ulceration, bleeding with overt hemorrhage, hematemesis, melena o major cause of hematemesis in alcoholics o 25% of patients with chronic aspirin use have bleeding (usually insiduous) Might be detected as occult blood or anemia usually not a massive bleed Chronic gastritis: chronic mucosal inflammation symptoms less severe but more persistent than acute gastritis o abdominal discomfort, nausea o hematemesis uncommon

Etiologic factors: H pylori gastritis (most common cause) o antral gastritis o pangastritis if long-standing Autoimmune gastritis (~10%) o affects the body, spares antrum b/c it targets parietal cells (not in antrum) o leads to atrophic gastritis

Helicobacter pylori gastritis: major cause of chronic gastritis o Present in 90% of cases of antral gastritis prevalence varies over the world o colonization rates 10-80% 80% in Puerto Rico o high incidence areas: acquired in childhood and persists for decades risk factors related to socio-economic status (poverty, crowding etc) Transmission: humans only known host mode not exactly known environmental spread: ? oral-fecal ? oral-oral Helicobacter pylori: curved or spiral gram negative bacillus 3.5x0.5 mm evolved to survive in gastric mucus o flagella, motile in viscous mucous o urease: ammonia from urea - buffers gastric acid o adhesins: adherence to surface foveolar cells o toxins: CagA (cytotoxin-associated gene A) CagA gene involved in development of gastric carcinoma in pts w/H. pylori
Test q: The pathologic mechanism of Helicobacter-related disease is: Production of urease and other substances that cause mucosal damage. (Other choices: Invasion of the gastric glandular epithelium and stroma w/resulting ulcer formation. Production of acid by the bacteria. An autoimmune phenomenon caused by immunologic similarities between Helicobacter and antigens on the gastric chief cells.)

Pathogenesis: does not invade mucosa adheres to surface foveolar cells o increases acid secretion o disrupts gastric defenses directly damage epithelial cells induces intense inflammation promoting leakage of micronutrients from damaged mucosa to sustain bacillus
Test q: Which of the following concerning H. pylori is true? The organism does not invade the epithelium, but it does produce urease. (Other choices: The organism invades the mucosa and causes a granulomatous response. A dense infiltrate of eosinophils is the typical inflammatory cell response. Infection by the organism peaks in childhood and then declines w/age. On a biopsy, Helicobacter organisms are usually identified in the duodenum.)

All figures above: H. Pylori. 3: Giemsa stain. 4: Silver stain. Organisms are very tiny. Not located in the mucosa swimming along the surface. Diagnosis: breath test: detection of ammonia produced by bacterial urease serum antibodies gastric biopsy Treatment: antibiotics proton pump inhibitors o relapses may occur due to incomplete eradication or re-infection big problem. vaccine development in early stages

Pathology: chronic gastritis o pangastritis, gastric atrophy, adenocarcinoma o gastric ulcers duodenal ulcers gastric adenocarcinoma gastric lymphoma
Test q: Infection w/H. pylori is known to be a significant risk factor for all the following except: Esophageal squamous cell carcinoma. (Other choices: Gastric lymphoma, Chronic gastritis, Duodenal ulcers) Test q: All of the following are concerning H. pylori are true EXCEPT: Asymptomatic carriers of the organism are rare. (Other choices: Infection may be associated w/subsequent development of a lymphoproliferative disorder, The pathogenesis of the organism involves production of urease, The organisms are generally extracellular and are seen in mucus in the gastric pits on biopsy.)

Helicobacter heilmannii: related organism reservoir in cats, dogs, pigs, non-human reservoir causes similar disease in humans Treat pet to prevent re-infection Autoimmune gastritis: accounts for 10% of chronic gastritis serum antibodies o parietal cells o intrinsic factor + + o H ,K -ATPase (proton pump) associated with other autoimmune diseases (ex: Hashimotos thyroiditis) familial
Test q: All of the following are true concerning autoimmune gastritis EXCEPT: It is associated w/a microcytic anemia (Other choices: It accounts for only a small minority of cases of gastritis, Patients have an increased incidence of other autoimmune diseases, Autoantibodies specific for parietal cells or intrinsic factor are commonly present.)

Left: Normal gastric mucosa. See parietal cells and chief cells. Right: Autoimmune gastritis gastric atrophy. Parietal and chief cells absent. Intestinal metaplasia (goblet cells seen) risk for adenoca.

Salient features: Destroys acid-secreting cells. hypo/achlorhydria gastrin release o hypergastrinemia o G cell (endocrine cell) hyperplasia in antrum low intrinsic factor pernicious anemia chief cells reduced serum pepsinogen I mucosal atrophy, intestinal metaplasia, dysplasia, adenocarcinoma Clinical symptoms: F >M median age at diagnosis: 60 years anemia atrophic glossitis, peripheral neuropathy (both b/c of B12 deficiency) other autoimmune diseases: thyroiditis Treatment: immunosuppression glands repopulate parietal cells might come back ? from stem cells that differentiate into parietal and chief cells

Test q: A 51F has been feeling increasingly tired for the past 7mo. There are no remarkable findings on phys exam. Lab studies include Hb 9.5, hematocrit 29.1%, MCV 124, platelet count 268,000, and WBC count 8350. The reticulocyte index is low. Hypersegmented polymorphonuclear leukocytes are found on a peripheral blood smear. Antibodies to which of the following are most likely to be found in this patient? Gastric H+,K+ATPase. (Other choices: Gliadin, Tropheryma whippelii, H. pylori, Intrinsic factor receptor) Robbins explanation: This patient has a megaloblastic anemia w/a high MCV. Delayed maturation of the myeloid cells leads to hypersegmentation of polymorphonuclear leukocytes. She most likely has pernicious anemia, resulting from autoimmune atrophic gastritis. Loss of gastric parietal cells from autoimmune injury causes a deficiency of intrinsic factor. In the absence of this factor, vitamin B12 cannot be absorbed in the distal ileum. Among the various antiparietal cell antibodies are those directed against the acid-producing proton pump enzyme H+,K+-ATPase.

Other forms of gastritis: reactive gastropathy (chemical gastritis) o NSAIDs o reflux of bilious duodenal secretions (post-surgical - antrectomy, gastrectomy) o uremia (chronic renal failure) granulomatous gastritis: Crohns eosinophilic gastritis: allergies to cows milk, soy protein, drugs

Peptic ulcer: Peptic ulcer: ulcers caused by action of gastric acid/peptic juices o imbalance between acid and protective mucosal barrier o develop on a background of chronic gastritis and hyperacidity Etiologic factors: H.pylori (~70% of cases) NSAID use Zollinger Ellison syndrome o caused by endocrine neoplasm that secretes gastrin multiple ulcers in GI tract
Test q: A 38F has had a low-volume watery diarrhea for the past 3mo. She now has mid-epigastric pain. Over-the-counter antacid meds do not relieve the pain. On phys exam, she is afebrile. On palpation, there is no abdominal tenderness and no masses. An upper GI endoscopy shows multiple 0.5mm to 1.1cm, shallow, sharply demarcated ulcerations in the first and second portions of the duodenum. She is given cimetidine. Three months later, repeat endoscopy shows that the ulcerations are still present. Which of the following analytes in serum or plasma is most likely to be increased in this patient? Gastrin. (Other choices: Insulin, Somatostatin, Glucagon, VIP) REPEATED x2

Figures: Peptic ulcers. Grossly, see punched out, clean base b/c digested w/acid, margins welldefined. Rugal folds approach edges of ulcer NOT in malignant. Right: Barium swallow. Sharply punched-out ulcer. Peptic ulcers = CLEAN EDGES. If malignant ulcer, would see tumor around the edges of the ulcer.

Found in first part of duodenum, anterior wall lesser curve of stomach, border of body and antrum Pathology: usually solitary (80% of cases) round to oval, sharply punched out margins not heaped (as opposed to malignant ulcer) radiating mucosal folds clean base Clinical symptoms: Epigastric pain o burning, aching o worse at night o 1-3 hours after meals o relieved by food nausea, vomiting, belching, bloating iron deficiency anemia, hemorrhage, perforation Clinical course: chronic, recurring lesions untreated will last for decades treatment - heal in a few weeks o antibiotics, PPI do not undergo malignant transformation complications: bleeding, perforation, strictures

Malignant tumors of the stomach: adenocarcinoma 90 - 95% lymphomas <5% carcinoids <5% o arise from endocrine cells of the stomach stromal tumors <5% Adenocarcinoma: Intestinal type: chronic gastritis, int. metaplasia, dysplasia geographic variation in incidence forms mass - can resect form glands Adenocarcinoma: Intestinal Type Epidemiology: Wide geographic variation o common in Japan, Chile, Eastern Europe o less common in Western countries major cause of cancer deaths worldwide incidence has fallen dramatically in US o environmental factors important (nutrition) o second generation immigrants have risk of native US residents Dietary factors: presence of harmful procarcinogens o nitrosamines, benzopyrene lack of refrigeration preserved, cured, smoked, salted foods contamination of water with nitrates cigarette smoking lack of protective anti-oxidants o Vitamin C, E, beta-carotene vegetables and fruits
Test q: Wide variation in gastric carcinoma rates are seen between various countries. These are thought to relate to: Environmental factors, especially diet. (Other choices: Genetic factors, esp. HLA types. Screening and early detection efforts. The decreased incidence of Helicobacter infection in tropical countries.)

Diffuse type: CDH1 mutations, no precursor lesions no geographic variation in incidence just depends on gene incidence diffuse thickening of wall infiltrates as single cells

Predisposing factors: arises on a background of chronic gastritis (helicobacter pylori, autoimmune gastritis) forms a mass o Relatively well-defined margins amenable to resection

All figures: Adenocarcinoma, intestinal type. 1. Stomach tumor forms mass. 2. Different case. Forms glands. 3. High power view of same biopsy: see glands

Adenocarcinoma: Diffuse Type does not arise in background of chronic gastritis and intestinal metaplasia associated with CDH1 mutations which encodes for e-cadherin o E-cadherin holds cells together if absent, cells do not hold or form glands. Infiltrate as individual cells. does not form a mass o creeps through the wall and causes diffuse thickening due to tumor infiltration and desmoplasia (reactive fibrosis in response to infiltrating glands leather bottle stomach, linitus plastica) o difficult to clear margins bc they infiltrate insiduously as single cells Microscopically, diffuse-type is composed of single infiltrating cells, often with signet-ring morphology. Signet ring cells have a large mucin vacuole which compresses the nucleus to one side of the cell. A mucicarmine stain is positive (bright red) in these cells.

All figures: Adenocarcinoma, diffuse type. 1. No mass. Rugal folds are getting erased. 2. Not forming glands each one infiltrates as single cell. Some have intracytoplasmic mucin. Vacuoles compress nucleus to the side of the cell. 3. Single cells, not forming glands, sheets of cells

Test q: A 42F presents w/abdominal distention and a several week history of vomiting and abdominal pain. A CT scan shows a diffusely thickened stomach wall and ascites. On upper endoscopy, the mucosal folds are thickened and a 1cm ulcer is seen. A biopsy of the ulcer is performed and shows inflamed stroma w/an infiltrate of round, single cells w/large, pale eosinophilic-staining mucin vacuoles which compress the crescent-shaped nucleus to the side of the cell. The diagnosis is: Adenocarcinoma, diffuse type. (Other choices: Adenocarcinoma, intestinal type. Peptic ulcer disease. Intestinal metaplasia. Non-Hodgkin lymphoma, mucosa associated lymphoid tissue type.) Test q: A 45F has a 6mo history of intermittent abdominal pain and nausea. Upper endoscopy is performed and the stomach mucosa appears thickened and focally nodular. A biopsy is performed and shows small single cells infiltrating through the lamina propria of the stomach. Many of these cells have a high nucleus-to-cytoplasm ratio, pleomorphic nuclei, and minimal cytoplasm. Some have a large vacuole that compresses the nucleus to the side of the cell. The cells appear primarily as single cells, but occasionally clusters of infiltrating cells are seen. A mucin stain is performed and it is positive. The best dx is: Adenocarcinoma, diffuse type. (Other choices: Adenocarcinoma, intestinal type. Non-Hodgkin lymphoma of mucosa associated lymphoid tissue [MALT] type. Plasmacytoma.) Test q: A 67F has experienced severe nausea, vomiting, and a 9kg weight loss over the past 4mo. On phys exam, she has mild muscle wasting. Upper GI endoscopy shows that the entire gastric mucosa is eroded and has an erythematous, cobblestone appearance. Upper GI radiographs show that the stomach is small and shrunken. Which of the following is most likely to be found on histologic exam of a gastric biopsy specimen? Diffuse type adenocarcinoma. (Other choices: Intestinal type adenocarcinoma, GI stroma tumor, Granulomatous inflammation)

Gastric carcinoma: insidious disease o remains asymptomatic till late in the course o symptoms are non-specific anorexia, weight loss, anemia, hemorrhage

Prognosis: depends on stage o depth of invasion o lymph node involvement o distant metastases does not depend on histologic type (stage for stage) o however, diffuse type presents at a late stage
Test q: A 45F presents w/palpable abdominal mass. Ultrasound demonstrates a 9cm left ovarian mass. A staging CT scan shows a diffuse thickening of the stomach wall. Upper endoscopy and biopsy of the stomach was performed. The biopsy shows infiltrating single cells with atypical nuclei which are compressed to the side of the cell by a single large vacuole. A mucicarmine stain shows bright red staining in the vacuoles. An immunohistochemical stain is positive for keratin in these cells. Based on these findings, what is the most likely explanation for the ovarian mass? It is a metastatic adenocarcinoma of gastric origin. (Other choices: It is likely a follicular carcinoma [which has metastasized to the stomach] arising in struma ovarii. Since it is a large mass, it is probably a serous carcinoma which has metastasized to the stomach. It is probably unrelated as the ovary is almost never involved by metastatic carcinoma. Since the tumor cells are keratin positive, the tumor in the stomach is most likely a squamous cell carcinoma of ovarian origin.)

Pathology of the Small and Large Intestines: Topics to be covered: Meckels diverticulum Hirschprungs disease Pseudomembranous colitis Celiac disease Ischemic bowel Diverticular disease Idiopathic Inflammatory bowel disease Tumors (adenomas, carcinoma) Meckels diverticulum: true diverticulum: includes all layers of the intestinal wall developmental: failure of complete involution of the vitelline duct which links the developing gut lumen to yolk sac present in 2% of the population
Test q: A Meckels diverticulum may be classified as a true diverticulum because: It has all the layers of the small intestine. (Other choices: It is congenital, It may have heterotopic epithelia tissue, It ends as a blind pouch.)

Diverticula in GI tract: True diverticulum o contains all layers of wall o usually congenital/ developmental False diverticulum o contains only mucosa and submucosa which herniate through muscularis propria, usually due to increased intraluminal pressure (propulsion diverticulum) o acquired (eg. colonic diverticulosis) Meckels diverticulum pathology: blind pouch located o 2 feet from the ileocecal valve o anti-mesenteric border usually lined by intestinal epithelium 50% have gastric or pancreatic ectopic tissue o peptic ulcers, pancreatitis etc. Clinical features: Silent in most people Pain (similar to acute appenditis) Bleeding Perforation o peptic ulceration o pancreatitis o tumor: carcinoids, lymphoma

Meckels diverticulum, blind pouch

Test q: An 18M presents w/severe RLQ abdominal pain. Following phys exam and lab studies in the ED, he is taken to the OR for an appendectomy. The appendix is grossly normal. Further evaluation is indicated to exclude the possibility of what clinical mimic of acute appendicitis? Inflamed Meckels diverticulum. (Other choices: Fibrous obliteration of the tip of the appendix, Appendiceal carcinoid tumor, PMC) Test q: The gross photo below is of distal small intestine (2007 Exam 2, #11 cant see picture very well). The dx is: Meckels diverticulum (Other choices: Vovulus, Intussuseption, Infarction)

Hirschprungs disease: absence of ganglion cells in the submucosal (Meissners) and myenteric (Auerbachs) plexuses o aka: congenital aganglionic megacolon Failure of migration of neuronal cells from the neural crest Pathology: variable length of colon involved rectum always involved o short-seg: rectum and sigmoid o long-seg: beyond the sigmoid aganglionic segment narrowed/obstructed proximal segment hypertrophies, then dilates (gives up), wall thins out o stercoral ulcers (ulcers caused by fecal impaction), enterocolitis, perforation

Above: Ganglion cells in between muscle fibers. In Hirschprungs, dont see these anymore.

Epidemiology: sporadic: 1 in 5,000 -8,000 live births familial: increased frequency in siblings of index cases M:F = 4:1 association with Downs syndrome (~10% of cases) and other neurologic abnormalities (~5%) Clinical features: failure to pass meconium in infancy constipation/ paradoxial diarrhea abdominal distension complications o enterocolitis o perforation
Test q: An infant has severe constipation and abdominal distention. Colonoscopy is performed. On biopsy of the colon, which of the following findings would be most supportive of a dx of Hirschprungs disease? Absence of ganglion cells in the submucosal plexus. (Other choices: Foci of mucosal necrosis w/adherent plaques of mucus, acute inflammatory cells, and necrotic debris; Ulceration and crypt abscesses, Small atrophic crypts and lamina propria fibrosis) Test q: In colorectal biopsies of children w/chronic constipation, the histologic diagnosis of Hirschprungs disease is based upon what histologic finding? The absence of ganglion cells. (Other choices: Hypoplasia of nerve fibers, Flattening of the villi of the colorectal mucosa, The presence of intraepithelial eosinophils, A stromal lymphoplasmacytic infiltrate) Test q: A 2M w/chronic constipation undergoes endoscopy w/biopsy. What histologic finding would support a dx of Hirschprungs disease? Absence of ganglion cells in a segment of the colon or rectum. (Other choices: Flattening of the villi and lymphocytic infiltration of the epithelium in the duodenum. Presence of exudate composed of neutrophils, mucus, and necrotic debris in a patchy distribution in the colon overlying foci of mucosal necrosis. Thickening of the BM in the colon w/a mild lymphocytic infiltrate in the epithelium.)

Pseudomembranous colitis (PMC): endoscopic appearance of a membrane adherent to the colonic mucosa pseudo - because it is not a membrane (thin layer of epithelial lined connective tissue) but rather composed of inflammatory exudate and debris Used synonymously with antibiotic-associated colitis (C. difficile colitis) But endoscopic pseudomembranes can also be seen with other causes of severe mucosal injury o Ischemic colitis o necrotising infections Staphylococcus, shigella Antibiotic-associated/C. difficile colitis: Follows course of broad spectrum antibiotics o alter the normal gut flora o provide proliferative advantage to toxin- producing strains of C. difficile may also occur without antibiotic use o following surgery o superimposed on chronic debilitating illness Endoscopic appearance of membrane/PMC C. difficile following antibiotics is most common cause, but can be from these other causes.

Figures: PMC Right: C. difficile colitis colonic crypts are inflamed, eventually burst and lets off exudate (wispy) forms pseudomembrane.

Test q: A 62M sees his physician bc he has had fever and back pain for the past 2 days. Phys exam shows tenderness of the right costovertebral angle. Lab studies show leukocytosis and pyuria w/WBC casts. He is treated w/cefotaxime, clindamycin, and nafcillin for 16 days. He now develops severe lower abdominal pain and severe diarrhea. Clostridium difficile toxin is identified in a stool specimen. Which of the following conditions is he most likely to have now developed? Pseudomembranous colitis. (Other choices: Appendicitis, Collagenous colitis, Diverticulitis, Ischemic colitis) REPEATED x2 Test q: A 70M was admitted to the hospital for pneumonia and was treated successfully with intravenous antibiotics. Shortly following discharge from the hospital, the patient returns with abdominal pain, fever, and diarrhea. Colonoscopy was performed and revealed multiple plaques of gray-white exudate throughout the colon. What lab test would be useful in confirming the diagnosis? Stool Clostridium difficile toxin assay (Other choices: Aspergillin antibody by gel diffusion, Acid-fast bacteria stain of a colon biopsy, Rotavirus antigen screen, Stool ova and parasite analysis.) Test q: Antibiotic-associated (pseudomembranous) colitis is caused by: Exotoxins (Other choices: Intestinal epithelial cell necrosis caused by toxic properties of b-lactam antibiotics, Invasion of the mucosa by C. difficile, Ischemia)

Malabsorption Common causes in US: Celiac disease Pancreatic insufficiency o Chronic alcoholism o Cystic fibrosis Crohns disease Celiac disease: Gluten-sensitive enteropathy Nontropical sprue Celiac sprue Pathogenesis: Sensitivity to gluten (gliadin) alcohol-soluble, water-insoluble protein - component of wheat, oat, barley, rye Cell-mediated immunity Accumulation of cytotoxic T cells (CD8+) within epithelium and helper T cells (CD4+) in lamina propria release of cytokines damage to intestinal epithelial cells
Test q: Celiac disease is thought to result from: The action of T-cells, possibly initiated by infection by a virus (Other choices: Direct toxicity of gluten to enterocytes, Production of an autoantibody that damages enterocytes by plasma cells derived from B-cells reactive for the gliadin protein, An autoimmune phenomenon in patients w/ulcerative colitis)

Microscopic Pathology: Villous blunting (total/ subtotal) Elongation of crypts increased mitoses o Mucosal thickness remains the same

Intraepithelial lymphocytes Lamina propria lymphocytosis

Clinical features: Can present anytime from infancy to adulthood Diarrhea, bloating Failure to thrive, weight loss, fatigue Manifestations of malabsorption Diagnosis: Circulating anti-gliadin, anti-endomysial, anti-tissue transglutaminase antibodies o anti-TTG is most specific Diagnostic histological changes in a biopsy Improvement of symptoms and mucosal histology on withdrawal of gluten, relapse on challenge Prognosis: Remain well if adhere to gluten-free diet Increased risk of malignancy o lymphomas o adenocarcinoma o esophageal squamous cell carcinoma
Test q: The dx of Celiac disease is supported by all of the following findings EXCEPT: Elongation of the duodenal villi. (Other choices: The presence of intraepithelial lymphocytes within the duodenum, A positive test for serum anti-gliadin antibodies, Improvement of symptoms with a gluten-free diet, A lymphoplasmacytic infiltrate in the lamina propria) Test q: A 28F describes diarrhea, fatigue, and bloating that have become progressively worse over the course of several months. Phys exam, stool culture, and ova/parasite analysis do not provide an explanation for the patients symptoms. Upper endoscopy w/a biopsy of the duodenum is performed. The biopsy shows flattened mucosa w/loss of the normal villous architecture. There is an intraepithelial infiltrate of lymphocytes. Which of the following lab studies would help to confirm the diagnosis that is suspected based on the histologic findings? Serum anti-gliadin and antiendomysial antibodies. (Other choices: C-reactive protein and homocysteine, Amylase and lipase, Intrinsic factor and H+/K+/ATPase enzyme autoantibodies, Anti-smooth muscle and anti-lactoferrin autoantibodies) Test q: A 30F sees her physician because of diarrhea and fatigue. She has noticed a 3kg weight loss over the past 6mo. Lab studies are negative for blood, ova, and parasites in the stool. A biopsy specimen is obtained from the upper jejunem. The patient is put on a special diet w/no wheat or rye grain product. Her symptoms improve dramatically. Which of the following is most likely to be seen in the biopsy specimen? Villous blunting and flattening. (Other choices: Lymphatic obstruction, Noncaseating granulomas, Foamy macrophages within the lamina propria, Crypt abscesses.) REPEATED x2 Test q: A 36M reports chronic diarrhea and bloating which have become increasingly severe over the past 2mo. His past med history is unremarkable and he is not able to relate the symptoms to any specific trigger. He is HIV negative. Upper endoscopy is performed. The esophagus and stomach are unremarkable. The duodenum appears somewhat erythematous. Biopsies of the duodenum are obtained and show flattened mucosa (loss of the villous architecture) and increased intraepithelial lymphocytes, up to 4-5 lymphocytes per 10 epithelial cells in some areas. Which of the following should be most strongly suspected? Celiac disease. (Other choices: H. pylori infection, Ischemic bowel disease, Chronic atrophic gastritis)

Ischemic bowel disease: Effects of ischemia depend on o level of occlusion (presence of distal anastomosis) o the rapidity of occlusion Acute ischemia o major vessel: necrosis of large segment o medium sized vessel: no effect due to distal anastomosis o small end-arteries: focal, ischemic lesions Slow insiduous ischemia o no effect due to rich anastomosis o atrophy, strictures Etiopathogenesis: Arterial thrombosis atherosclerosis, vasculitis Arterial embolism cardiac vegetations, aortic atheroembolism, angiographic procedures Non-occlusive ischemia- cardiac failure, dehydration, vasoconstrictive drugs Miscellaneous radiation injury Venous occlusion o hypercoaguable states o mechanical - volvulus, stricture, herniation Pathology: Infarction: variable degrees o Mucosal o Transmural Atrophy, strictures (chronic)

Figure: Mucosal ischemia. Colonic mucosa is usually full of goblet cells absence of them here. Dont see epithelial lining the surface. Pink haze to the mucosa. This sample is relatively early later, see ulcerations/erosions. Clinical features: Older individuals - preexisting cardiac and vascular conditions Young individuals: heavy exercise, cocaine Severe pain, tenderness, N/V, bloody diarrhea Peristaltic sounds decrease Abdominal rigidity Great risk of death if unrecognized as emergency o window between onset of symptoms and perforation small
Test q: One yr after having an acute MI, a 55M sees his physician because of severe abdominal pain and bloody diarrhea. On phys exam, the abdomen was diffusely tender and bowel sounds were absent. Abdominal plain films showed no free air. Lab studies showed a normal CBC and normal levels of amylase, lipase, and bilirubin. His condition deteriorated and he developed irreversible shock. At autopsy, which of the following is likely to be found? Intestinal infarction. (Other choices: Acute appendicitis, Acute pancreatitis, Acute cholecystitis, Pseudomembranous colitis) Robbins explanation: The patients history of MI suggests that he had severe coronary atherosclerosis. Atheromatous disease most likely involved the mesenteric vessels as well, giving rise to thrombosis of the blood vessels that perfuse the bowel. The symptoms and signs suggest infarction of the gut.

Diverticular disease of colon: Acquired, propulsion diverticula decreased lack of dietary fiber, decreased stool bulk increased intraluminal pressure herniation of mucosa and submucosa through weak points

Pathology: Sigmoid colon affected commonly Hypertrophy of the muscularis propria o Narrowing of lumen Usually multiple diverticula along the tenia coli o Contain mucosa and submucosa Clinical features: 50% incidence over age 60 Usually asymptomatic Only 20% develop symptoms o cramping, abdominal discomfort, distension o constipation, alternating constipation/diarrhea o intermittent blood loss, anemia Complications o hemorrhage, diverticulitis, obstruction

Above: Diverticular disease of colon. Mucosa has herniated through the muscularis is at the serosa. Can perforate, bleed, get infected.

Test q: A 65F goes to her physician for a routine health maintenance exam. A stool sample is positive for occult blood. CT scan of the abdomen shows numerous air-filled 1-cm outpouchings of the sigmoid and descending colon. Which of the following complications is most likely to develop in this patient? Pericolic abscess. (Other choices: Adenocarcinoma, Bowel obstruction, Malabsorption, Toxic megacolon) Robbins explanation: This patient has colonic diverticulosis, which may be accompanied by intermittent minimal bleeding and, rarely, by severe bleeding. One or more diverticula may become inflamed (diverticulitis) or, less commonly, may perforate to produce an abscess, peritonitis, or both.

Idiopathic inflammatory bowel disease (IBD): Chronic, relapsing inflammatory disorders of unknown etiology Two well-defined entities o Crohns disease o Ulcerative colitis both can have extraintestinal manifestations, much more common with Crohns Some cannot be classified neatly - indeterminate

Etiology of IBD: Unknown (idiopathic) Autoimmune disease of unregulated and exaggerated local responses to commensal microbes of the gut in genetically susceptible individuals Ulcerative colitis
Involves colon; not SI Continuous involvement Disease limited to mucosa and submucosa No granulomas Wall thin no strictures, fissures, fistula No creeping fat (b/c not transmural process)

vs

Crohns:
SI & colon; any part of GIT (Terminal ileum most often involved) Segmental (skip lesions) Transmural: mucosa, sub-mucosa, muscularis, serosa Granulomas present Wall thickening strictures, fissures & fistula Creeping fat on mesentery

Test q: Features favoring a dx of Crohns colitis over ulcerative colitis include: Fistulae and granulomas. (Other choices: Continuous involvement of the colon of left-sided colitis and a cecal patch, Pseudopolyps and normal colon wall thickness, Abdominal pain and cramps.)

Ulcerative Colitis Gross Pathology: Continuous involvement of colon w/no skip lesions * * cecal and appendiceal involvement can occur in discontinuity with left sided colitis or proctitis (cecal patch) * untreated cases starts distally with variable proximal extent o UC is left-sided disease begins in rectum and moves up backwash ileitis with pancolitis ulcerated beefy red mucosa wall thickness is normal or thin no fissures/fistulas/strictures/serositis pseudopolyps Microscopic pathology: Changes limited to mucosa/submucosa o inflammation chronic lymphoplasmacytic acute cryptitis, crypt abscesses o crypt architectural distortion No transmural inflammation No granulomas

Figures: Ulcerative Colitis. Left: UC continuous involvement Right: Pseudopolyps can be seen in both UC and Crohns

Clinical features: Relapsing bloody diarrhea abdominal pain and cramps may be preceded by stress, infections (C. difficile) Course of ulcerative colitis: 60% have mild disease 97% will have at least 1 relapse during a 10 year period relapses vary in severity, frequency and duration 30% will require colectomy for medically unresponsive disease Toxic megacolon - perforation Course of disease: Dysplasia and cancer o Risk depends on extent and duration of disease o Pancolitis of 10 years duration confers a 10-20 fold increased risk o 30% risk of cancer 35 years after diagnosis Crohns disease: Segmental disease Affects all parts of the GIT Small intestine (terminal ileum) involved most frequently Transmural inflammation all layers Fissures, fistula, strictures common

Test q: A 38M has a history of intermittent abdominal pain and diarrhea which is sometimes bloody. Colonoscopy demonstrates reddened and focally ulcerated mucosa in the rectum and left colon. An endcoscopic biopsy was performed and is shown in the photo below. The best diagnosis is: Idiopathic inflammatory bowel disease. (Other choices: Pseudomembranous colitis, CMV colitis, Diverticulosis, Hirschprungs disease)

All figures above: Crohns disease. Left can see cobblestone appearance, strictures, muscle hypertrophy, narrowing of the lumen. Right can see fat creeping. Gross Pathology: Segmental involvement of small and large intestine o Terminal ileum most common site sharply demarcated areas of involvement with skip areas linear ulcers, cobblestone mucosa thickened wall fissures/ fistulas/ strictures common creeping of mesenteric fat Microscopic Pathology: Mucosal changes similar to UC transmural inflammation with fissures/ fistula lymphoid aggregates/ follicles non-necrotising granulomas Figure: Granuloma collection of epithelioid cells (macrophages that have been recruited and lost their property to migrate immobile) Clinical features: Commonly, insiduous onset with attacks of mild diarrhea, fever, abdominal pain Uncommonly, abrupt onset with acute pain, fever, diarrhea anemia due to occult or overt bleeding

 Uveitis, polyarthritis, sacroileitis, ankylosing spondylitis etc Course of the disease: strictures - obstruction fistulas to bowel, skin, bladder, vagina malabsorption (common cause in US) dysplasia/ cancer : 5-10 fold risk o Risk depends on extent of involvement (same as UC for pancolitis)
Test q: A 48F w/chronic, relapsing bloody diarrhea and abdominal pain develops a colonic stricture and a segment of colon is resected. The surgical specimen shows patchy adherent fibrin on the serosa. Opening the specimen demonstrates a thickened wall. The mucosa is elevated in patches w/a cobblestone appearance. There are linear fissures in the mucosa in these areas and a mucosal bridge is seen near the strictured area. Histologically, the mucosa is focally ulcerated and there are collections of neutrophils within crypts and branching crypts are seen. Collections of submucosal histiocytes are seen. The most likely etiology of the stricture is: Crohns colitis. (Other choices: PMC, UC, Amebic colitis) Test q: A 30F has had several episodes of diarrhea, some of which have been bloody. Colonoscopy is performed. The colon mucosa is reddened in the rectum, sigmoid colon, and the right colon. The transverse and left colon have normal appearing mucosa. Longitudinal fissures are seen in the sigmoid colon. Mucosal biopsies are collected. They show expansion of the lamina propria by chronic inflammatory cells, architectural distortion of the crypts (crypts of variable size and spacing), and occasional collections of neutrophils within the colonic crypts. The most likely dx is: Crohns disease. (Other choices: Celiac disease, PMC, UC) Test q: The specimen seen in the photograph (2007 Exam 2, #28 cant see picture very well) is a colon segmental resection from a patient with a history of abdominal pain and diarrhea who recently developed obstructive symptoms. The specimen was opened and the metal probe was placed through existing openings. The most likely diagnosis is: Crohns colitis. (Other choices: Adenomatous polyposis, Amebic colitis, PMC)

Surveillance: Surveillance for dysplasia to detect cancers early at a potentially curative stage Pancolectomy for high grade dysplasia o If there is high grade dysplasia, there is a greater probability that patient will have cancer at another site. Tumors of the small and large intestine: The small intestine in an uncommon site for benign and malignant tumors The colon and rectum harbor more primary neoplasms than any other organ in the body o Polyps are extremely common nd o Colon cancer is the 2 most common cause of death from cancer Hyperplastic polyp: Small <0.5 cm may be multiple Common rectosigmoid Star-shaped glands in cross-section, corkscrew in longitudinal section Benign
Test q: A 55M has a screening colonoscopy. The colon mucosa is unremarkable except for a single 4mm polyp in the sigmoid colon. The polyp is removed endoscopically. Histologically, it is composed of enlarged, irregular glands. The lumens of the glands are irregular and often star-shaped. The glandular epithelial cells forming the glands have a single layer of small round nuclei and abundant cytoplasm. The best dx is: Hyperplastic polyp. (Other choices: Adenocarcinoma, Adenoma, Juvenile polyp)

Above: Typical epigastric polyp. Proliferation in base of crypts, acquires star-shaped appearance.

Juvenile polyp: Hamartomatous proliferation children under 5 years sporadic, single, usually in the rectum Large (1-3 cm) with a stalk rounded, smooth, lobulated surface

Figure: Juvenile Polyp Dilated glands, proliferation of the stroma

Test q: A 2M is brought to the pediatrician because of an anal mass discovered by his parents while changing his diaper. A 2.5cm rounded polyp is noted prolapsed through the anus. The lesion has a stalk and it is resected. The stalk is composed of rectal mucosa. The polyp has an ulcerated surface and the center has fibrotic stroma w/dilated rectal glands. Most of the glands have round lumens. The glandular epithelium is composed of cells w/a single layer of nuclei and no nuclear enlargement or pleomorphism compared to the stalk. The most likely diagnosis is: Juvenile polyp. (Other choices: Tubular adenoma, Villous adenoma, Hyperplastic polyp, Peutz-Jeghers polyp.)

Peutz-Jeghers syndrome: autosomal dominant multiple hamartomatous polyps in entire GI tract mucosal and cutaneous pigmentation around lips and face risk of cancer of pancreas, breast, lung, ovary and uterus Adenomas: Very common o incidence increases with age well-defined familial predisposition Premalignant precursor lesion Carcinoma in adenoma: Risk correlated with o polyp size o villous lesions o severity of dysplasia 40% risk in villous lesions >4 cm

Figure: Stepwise progression of malignancy leads to adenocarcinoma in the colon.

Test q: Concerning the progression of colonic adenomas to adenocarcinoma, which of the following is true? Adenocarcinomas may have abnormalities of both K-RAS and P53. (Other choices: Mutations are only observed in adenocarcinomas adenomas are genetically normal. Villous adenomas are less likely than tubular adenomas to progress to adenocarcinoma. Colonoscopy is recommended for patients over the age of 50 because, while pts under 50 may have adenomas, colorectal carcinoma does not occur before age 50.)

1. Tubular adenoma w/stalk 2. Villous adenoma looks like sea animal. Huge lesions. 3. Adenoma absence of goblet cells, maturation.
Test q: Which of the following colon polyps, by definition, is dysplastic? Tubular adenoma. (Other choices: Hyperplastic polyp, Juvenile polyp, Polyp of the solitary rectal ulcer syndrome)

Familial adenomatous polyposis (FAP): Innumerable gastrointestinal polyps, usually thousands At least 100 polyps necessary to make the diagnosis 100% incidence of adenocarcinoma, occurs at a young age APC gene on chromosome 5q21
Test q: A 29M has stools positive for occult blood and undergoes colonoscopy. Hundreds of polyps are seen w/intervening normal mucosa. Biopsy of several of these demonstrates tubular adenomas or tubulovillous adenomas. This patient likely has: A mutation of the APC gene. (Other choices: Ulcerative colitis, Retention polyps, Hyperplastic polyps, Peutz-Jegers syndrome.)

 Figures: FAP Polyps Microscopically, adenomatous epithelium shows a decrease in the amount of cytoplasmic mucin, nuclear enlargement, nuclear pseudostratification, and nuclear hyperchromatism.

Treatment: Impossible to screen Prophylactic colectomy is treatment of choice

Test q: This is a partial colectomy specimen from a 15y/o (2007 Exam 2, #38 photo hard to see). Histologically, the lesions shown in the gross photo have epithelium w/enlarged, stratified nuclei in cells w/decreased cytoplasmic mucin and decreased cytoplasmic volume. This patient most likely has which of the following? FAP syndrome. (Other choices: Lynch syndrome, Peutz-Jehgers syndrome, Cowden disease)

Colorectal cancer: 60-80 years <20% occur before 50 years, unless there is UC or a familial polyposis syndrome Common in the US, Europe. Gross pathology: Right colon: tend to be larger, polypoid, exophytic masses, obstruction uncommon Left colon: annular encircling lesions - napkin ring constriction of the colon

1. Cancer in cecum. Bottom adenoma. 2. Thickening colon cancer. Constricting lesion. No exophytic lesion. 3. Adenocarcinoma tries to form glands. Glands trying to infiltrate the lower layers in bottom right. Clinical features: Asymptomatic for years o ex: growing in cecum Insiduous onset Fatigue, weakness, iron deficiency anemia Bleeding Changes in bowel habit Crampy, lower abdominal discomfort Prognosis: Depends on stage o Depth of invasion o Lymph node involvement o Distant metastases
Test q: The most important prognostic factor in colorectal carcinoma is: Tumor stage. (Other choices: Tumor grade, Tumor site right vs. left, Patient age)

Leftover test questions:

Test q: At upper endoscopy, a 52F has a gastric mass. The mass involves the wall of the stomach and is round and well-circumscribed. The overlying mucosa is uninvolved, except for a small ulcer. The patient is taken to surgery and the mass is resected. It is grossly a round, firm, tumor that measures 4cm in diameter. It does not invade the mucosa. Histologic sections show a spindle cell neoplasm with cells with mild nuclear pleomorphism. There are 3 mitotic figures per 50 high power fields. Immunohistochemical stains are performed. The tumor cells are negative for keratin, negative for actin, and positive for c-kit (CD117). The diagnosis is: GI stromal tumor. (Other choices: Sarcomatoid carcinoma, Leiomyoma, Leiomyosarcoma) Test q: A 45F has had increasing abdominal distention for the past 6wk. On phys exam, there is an abdominal fluid wave and bowel sounds are present. Paracentesis yields 1000mL of slightly cloudy serous fluid. Cytologic exam of the fluid shows malignant cells c/w adenocarcinoma. The patients med history indicates that she had no major med illnesses and no surgical procedures. Which of the following conditions is most likely to be related to the malignant effusion? HNPCC syndrome. (Other choices: Angiodysplasia, Crohns disease, Diverticulosis, Hirschprungs disease) Test q: An 11-month-old previously healthy infant has not produced stool for 1 day. The mother notices that the infants abdomen is distended. On phys exam, the infants abdomen is very tender and bowel sounds are nearly absent. An abdominal plain film radiograph shows no free air, but there are distended loops of bowel w/air-fluid levels. Which of the following is most likely to produce these findings? Intussusception. (Other choices: Meckel diverticulum, Duodenal atresia, Hirschprung disease, Pyloric stenosis) Robbins explanation: The infant has signs and symptoms of acute bowel obstruction. Intussusception occurs when one small segment of small bowel becomes telescoped into the immediately distal segment. This disorder can have sudden onset in infants and may occur in the absence of any anatomic abnormality. Test q: A 41M has been HIV+ for the past 8yr and has been receiving HAART for the past year. For the past 2wk, he has experienced pain when swallowing. He has had no episodes of hematemesis and no nausea or vomiting. There are no remarkable findings on phys exam. The CD4+ lymphocyte count is now 285/L. Which of the following conditions is most likely to produce these findings? Herpes simplex esophagitis. (Other choices: Esophageal squamous cell carcinoma, Achalasia, Lower esophageal fibrosis w/stenosis, GERD) From Robbins: A patient who is HIV+ and has low CD4+ cell counts is at great risk of developing infections. Herpes simplex and Candida are the most likely upper GI infections involving the esophagus.