GI Pathology

GI Pathology

2/14/11 and 2/16/11

Pathology of the Esophagus and Stomach – Topics to be covered: • Hiatal Hernia • Reflux esophagitis • Barrett’s esophagus • Esophageal Varices • Zenker’s diverticulum • Mallory Weiss syndrome • Esophageal carcinoma 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, Barrett’s esophagus, Zenker’s 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: Barrett’s 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, Barrett’s 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: Barrett’s esoph, Esoph varices, Scleroderma, Iron deficiency) REPEATED x2

Barrett’s 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: Barrett’s esophagus. (Other choices: Adenocarcinoma, Dysplasia, Mallory-Weiss syndrome)

Importance of Barrett’s? • Confers an increased risk factor for adenocarcinoma o develops through a sequence of increasing grades of dysplasia Barrett’s in perspective: • Barrett’s develops in 10% of patients with symptomatic GERD o (? Why do some patients develop Barrett’s and others don’t) • Most adenocarcinomas develop in Barrett’s but most individuals with Barrett’s do not develop cancer o Risk low in the grand scheme of things Clinical: • Symptoms of reflux • Barrett’s associated with o Long history of reflux (years) o More and longer episodes o More massive reflux

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: Barrett’s esophagus. (Other choices: Reflux esophagitis, Adenocarcinoma, Squamous dysplasia, Herpes esophagitis)

Risk of carcinoma: • duration of Barrett’s 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 Barrett’s esophagus is: It indicates a higher risk of progression to adenocarcinoma than does Barrett’s w/o dysplasia. (Other choices: All cases of Barrett’s 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: Barrett’s esophagus, esophageal webs, esophageal stenosis) The patient described above undergoes upper endoscopy and biopsy. The biopsy report reads, “Esophagus, lower, biopsy. Barrett’s 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 [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