GI tract Flashcards
Gastric ectopia of the esophagus: Histology.
Oxyntic mucosa usually.
May undergo intestinal metaplasia.
Gastric ectopia in the esophagus:
A. Synonym.
B. Location.
C. Clinical features.
A. Inlet pouch.
B. Cervical esophagus.
C. Older patients may have peptic symptoms.
Sebaceous ectopia in the esophagus: Synonym.
Fordyce’s granules.
Pancreatic ectopia in the esophagus: Associations (3).
Metaplasia due to reflux.
Trisomy 13 or 18.
Pancreatic ectopia of the esophagus:
A. Gross pathology.
B. Histology.
A. Submucosal mass that may have a central pore.
B. Usually acinar but can contain islet cells also.
Esophageal atresia: Types.
I: No fistula.
II: Proximal fistula only.
III: Distal fistula only.
IV: Proximal and distal fistulae.
Esophageal atresia: Clinical presentation.
Choking during feeding; excessive drooling.
Esophageal atresia: Associated syndromes.
Down’s syndrome.
VATER syndrome.
Congenital esophageal duplication: Gross pathology.
Cyst (most often), diverticulum, or tubule.
May be intramural or extramural.
Congenital esophageal duplication: Histology (2).
Lining: Respiratory, gastric, intestinal, or squamous.
Wall: Two layers of muscularis propria.
Plummer-Vinson syndrome:
A. Clinical triad.
B. Esophageal lesions.
A. Iron-deficiency anemia, cheilitis, glossitis.
B. Proximal webs, predisposition to proximal SCC.
Plummer-Vinson syndrome: Other association.
Autoimmune diseases.
Esophageal web: Histology.
Fibrovascular core without muscle.
Proximal lining: Squamous mucosa.
Distal lining: Squamous or gastric mucosa.
Esophageal ring: Cause.
Constriction due, e.g., to reflux or scleroderma.
Esophageal ring: Types.
Muscular.
Mucosal.
Schatzki ring: Located at or just above the GE junction.
Esophageal ring: Histology.
Mucosal: Fibrovascular core with a little muscularis mucosae.
Muscular: More muscle.
Both are lined by squamous mucosa proximally and often by gastric mucosa distally.
Esophageal hernia: Types.
Sliding.
Paraesophageal.
Esophageal hernia:
A. Gross pathology.
B. Histology.
A. Dilatation, ischemic changes.
B. Chronic inflammation, epithelial regenerative changes, fibromuscular proliferation.
VATER syndrome: Components.
Vertebral anomalies.
Anal atresia.
TracheoEsophageal fistula.
Renal defects.
Esophageal diverticula: Locations.
Above the upper esophageal sphincter (Zenker’s): Most common.
Above the lower esophageal sphincter.
At the midpoint of the esophagus.
Best place to look for inclusions of ___ esophagitis.
A. HSV
B. CMV
A. At the edge of the ulcer, in squamous cells.
B. At the base of the ulcer, in endothelial cells, fibroblasts, or glandular cells.
Pill esophagitis:
A. Main culprits.
B. Histology.
A. Iron, alendronate.
B. Nonspecific ulcer, possibly with prominent endothelial proliferation.
Chemical esophagitis: Locations.
Points of compression: Proximal and distal ends, mid-esophagus.
Radiation esophagitis: Gross pathology.
Large superficial ulcers.
Radiation esophagitis: Histology.
Acanthosis with parakeratosis.
Necrosis.
Atypia of stromal cells: Stellate fibroblasts, plump endothelial cells.
Hyalinized blood vessels.
Esophagitis dissecans superficialis:
A. Endoscopy.
B. Biopsy.
A. Whitish strips of peeling mucosa.
B. Intraepithelial splitting with necrotic superficial epithelium, bacterial and fungal colonies.
Esophagitis dissecans superficialis: Causes.
Bisphosphonates.
Bullous skin diseases.
Esophageal trauma.
Stricture.
Smoking.
“Black esophagus”.
Acute esophageal necrosis: May be associated with severe cardiovascular disease with hemodynamic compromise.
Bullous diseases of the esophagus:
A. Potentially fatal.
B. Rare in this location but more common in the skin.
A. Pemphigus vulgaris.
B. Bullous pemphigoid.
Gross pathology of esophageal bullous diseases:
A. Pemphigus vulgaris.
B. Bullous pemphigoid.
C. Lichen planus.
A. Bleeding and strictures.
B. Blisters.
C. Papules, plaques, or strictures.
Esophageal erythema multiforme: Gross pathology (2).
May resemble peptic or reflux esophagitis.
Pseudomembranes may form.
Esophageal graft-versus-host disease:
A. Typical location.
B. Gross pathology.
A. Upper third.
B. Desquamative lesions may cause a web.
Esophageal pemphigus vulgaris:
A. Location of split.
B. Inflammatory cells.
A. Suprabasal.
B. Eosinophils.
Esophageal bullous pemphigoid:
A. Location of split.
B. Inflammatory cells.
A. Subepithelial.
B. Eosinophils.
Histology of esophageal graft-versus-host disease:
A. Acute.
B. Chronic.
A. Karyorrhexis and apoptosis of epithelial cells; variable infiltrate of T cells.
B. Epidermal atrophy; fibrosis of lamina propria.
Immunofluorescence:
A. Pemphigus vulgaris.
B. Bullous pemphigoid.
A. Intercellular IgG.
B. IgG or IgA at the basement membrane.
Lymphocytic esophagitis:
A. Definition.
B. Cause.
A. At least 30 lymphocytes per hpf.
B. Many, including reflux, candidiasis, achalasia, lichenoid drug eruption.
Eosinophilic esophagitis: Epidemiology (2).
More common in males.
Concurrent eosinophilic enteritis is more common in children.
Eosinophilic esophagitis: Endoscopy (4).
Webs.
Corrugation.
Ulcers, exudates may be seen.
Eosinophilic esophagitis: Histologic definition.
More than 15 eosinophils per hpf.
Eosinophilic esophagitis: Ancillary test.
Serum eotaxin-3.
Reflux esophagitis: Endoscopic grading.
A through D, with A being the mildest.
Reflux esophagitis: Frequency of endoscopically inapparent cases.
30%.
PPI-responsive esophageal eosinophilia.
Eosinophilic esophagitis that responds to proton-pump inhibitors.
Barrett’s esophagus: Age groups.
Under the age of 15.
Over the age of 40.
Barrett’s esophagus: Special stain.
Alcian blue, pH 2.5.
Barrett’s esophagus: Immunohistochemistry.
CK7: Superficial and deep staining.
CK20: Bandlike superficial staining.
Intestinal metaplasia of cardia-type mucosa:
A. Distinction from Barrett’s esophagus.
B. Causes.
A. Depends on endoscopic impression.
B. Reflux, Helicobacter pylori.
Barrett’s esophagus with low-grade dysplasia: Treatments.
Antireflux therapy and close clinical follow-up.
Endoscopic ablation.
Barrett’s esophagus with low-grade dysplasia vs. indefinite for dysplasia: Immunohistochemistry.
Low-grade dysplasia may show more staining with p53, racemase, and Ki67.
Barrett’s esophagus with dysplasia vs. regenerative atypia (5).
Regenerative atypia:
− Background of active inflammation.
− Maturation at the surface.
− Greater uniformity of atypical cells.
− Nuclei and cytoplasm are equally enlarged.
− Cytoplasm tends to be eosinophilic rather than basophilic.
Colchicine and taxane: Histologic effects on the esophagus (4).
Increased mitotic figures, including “ring” types.
Apoptosis.
Nuclear stratification.
Loss of nuclear polarity.
Eosinophilic esophagitis: Genetics.
Familial cases: Mutation in TSLP (thymic stromal lymphopoietin) on 5q22.
Esophageal adenocarcinoma: Ancillary test.
Immunohistochemistry or FISH for HER2 to select patients for trastuzumab therapy.
Esophageal inflammatory fibroid polyp: Histology.
Lining: Benign squamous mucosa, possibly ulcerated.
Stroma:
− Variably cellular and variably edematous.
− Eosinophils and plasma cells.
− Prominent vessels with concentric stromal cells.
Esophageal inflammatory fibroid polyp: Mutation.
Somatic mutations, similar to those of some GISTs, may occur.
PDGFRα may be mutated.
Granular-cell tumor: Histologic features that suggest malignancy (5).
Increased cellularity.
Spindle cells.
Nuclear atypia.
Necrosis.
More than 2 mitotic figures per 10 hpf.
Squamous papilloma of the esophagus: Causes (4).
Human papillomavirus.
Reflux esophagitis.
Eosinophilic esophagitis.
Trauma.
Squamous papilloma of the esophagus: Location.
Mid or lower esophagus in 95% of cases.
Esophageal squamous dysplasia: Schemes of grading (2).
Mild, moderate, severe, or carcinoma in situ.
Low or high.
Esophageal squamous-cell carcinoma: Locations.
Mid or lower esophagus in 90% of cases.
Esophageal squamous-cell carcinoma: Tumor configurations.
Exophytic: Most common.
Ulcerating.
Purely infiltrating: Least common.
Esophageal squamous-cell carcinoma: Morphology of early lesions (2).
May be multifocal.
May be combined with widely scattered variable dysplasia and carcinoma in situ.
Esophageal squamous-cell carcinoma: Effect of irradiation.
Calcification keratinizing cells and foreign-body-giant-cell reaction.
Esophageal fibrovascular polyp: Histology.
Lining: Benign squamous epithelium.
Core: Collagenous or myxoid; sometimes contains fat.
Esophageal squamous-cell carcinoma: Main determinants of survival (2).
Depth of invasion.
Nodal status.
Tylosis:
A. Inheritance.
B. Clinical features (3).
A. Autosomal dominant.
B. SCC of the esophagus, hyperkeratosis of palms and soles, oral leukoplakia.
Esophageal squamous-cell carcinoma: Main variants (3).
Verrucous.
Sarcomatoid.
Undifferentiated.
Sarcomatoid carcinoma of the esophagus: Epidemiology.
Much more common in males than in females.
Sarcomatoid carcinoma of the esophagus: Histology of metastases.
May include any or all of the component of the primary tumor.
Esophageal squamous-cell carcinoma: Prognosis (2).
Generally poor, but better with polypoid tumors.
Undifferentiated carcinoma of the esophagus:
A. Histology.
B. Immunohistochemistry.
A. Undifferentiated cells with vesicular nuclei, prominent nuclei; cytoplasm is often abundant and eosinophilic.
B. Typically cytokeratin positive.
Verrucous carcinoma of the esophagus: Possible associations (2).
Achalasia.
Ingestion of acid.
Verrucous carcinoma of the esophagus: Surface.
Show parakeratosis and hyperkeratosis.
Verrucous carcinoma of the esophagus vs. benign papillomatous lesions.
Benign papillomatous lesions exhibit no pushing pattern of invasion at the deep margin.
High-grade neuroendocrine carcinoma of the esophagus: Histology (3).
Small-cell subtype: Similar to other small-cell neuroendocrine carcinomas.
Large-cell subtypes also exist.
Neuroendocrine carcinoma may coexist with more common types, e.g. SCC.
High-grade neuroendocrine carcinoma of the esophagus vs. metastatic neuroendocrine carcinoma (3).
TTF-1 to exclude pulmonary primary.
Clinical history may be required.
Distinction may be clinically irrelevant.
Melanoma of the esophagus: Possible changes in adjacent squamous mucosa (4).
Melanosis.
Melanocytosis.
Junctional activity.
Melanoma in situ.
Gastric duplication:
A. Location (2).
B. Gross pathology.
A. Usually intramural and on the greater curvature of the stomach.
B. Cystic mass that usually does communicate with the gastric lumen.
Gastric duplication: Lining.
More often gastric mucosa but can contain small-intestinal, respiratory, or pancreatic epithelium.
Gastric pyloric stenosis: Epidemiology (2).
More common in males and in firstborn children.
Gastric pyloric stenosis: Normal thickness of pyloric sphincter.
0.5 cm.
Pancreatic heterotopia in the stomach:
A. Origin.
B. Gross pathology.
A. Accessory pancreatic bud.
B. Umbilicated submucosal mass with duct.
Pancreatic heterotopia in the stomach: Histology.
Usually contains ducts, acini, and islet cells.
Can under the histologic changes that occur in the pancreas, e.g. inflammation, dysplasia, tumors.
Pancreatic heterotopia in the stomach: Name given to a lesion that consists of ducts only.
Adenomyoma.
Pyloric stenosis: Possibly associated mutation.
Duplication of 9q.
Sarcomatoid carcinoma of the esophagus: Immunohistochemistry.
Cytokeratin is positive in fewer than half of cases.
Vimentin is strong in the stromal component.
Sarcomatoid carcinoma of the esophagus: Histology.
Carcinomatous component: Squamous, glandular, or undifferentiated.
Mesenchymal: Spindle cells or with heterologous differentiation.
Gastric xanthelasma: Associations (3).
Duodenal reflux, gastritis, previous gastric surgery.
Not associated with hyperlipidemia.
Acute erosive gastritis: Associations (6).
NSAIDs.
Chemotherapy.
Alcohol.
Heavy smoking.
Physiologic stress.
Nasogastric intubation.
Mild acute erosive gastritis: Histology.
Active gastritis with edema.
Moderate acute erosive gastritis: Histology.
Mucosal erosion with fibrinopurulent exudate.
Severe acute erosive gastritis: Histology.
Confluent erosions; may resemble ulcer.
Reactive gastropathy: Causes.
Ethanol.
NSAIDs.
Steroids and other drugs.
Physiologic stress.
Reflux of duodenal contents.
Reactive gastropathy vs. gastric antral vascular ectasia.
Gastric antral vascular ectasia: Fibrin thrombi in the dilated capillaries.
Diffuse antral Helicobacter pylori-associated gastritis:
A. Epidemiology.
B. Location.
A. Whites in the United States.
B. Typically antral.
Diffuse antral Helicobacter pylori-associated gastritis: Histology.
Active chronic antral gastritis, sometimes with lymphoid aggregates, intestinal metaplasia.
Multifocal antral Helicobacter pylori-associated gastritis:
A. Epidemiology.
B. Location.
A. Minorities in the United States; Scandinavians.
B. Antral-body junction.
Diffuse antral Helicobacter pylori-associated gastritis: Histology (3).
Minimal chronic inflammation associate with islands of intestinal metaplasia or pyloric pseudometaplasia.
Minimal active inflammation.
Lymphoid follicles with germinal centers may persist.
Types of intestinal metaplasia.
Type I: Goblet cells and enterocyte-type absorptive cells.
Type II: Goblet cells and gastric foveolar cells.
Helicobacter heilmannii:
A. Associations (3).
B. Morphology.
A. Gastritis, carcinoma, gastric MALT lymphoma.
B. Twice as long (7 μm) as H. pylori; tightly coiled.
Autoimmune gastritis: Location.
Body and fundus.
Autoimmune gastritis: Histology.
Oxyntic epithelium: Atrophy, pyloric pseudometaplasia, intestinal metaplasia.
Enterochromaffin cells: Hyperplasia, dysplasia, or carcinoid tumors.
Autoimmune gastritis: Laboratory findings (2).
Hypergastrinemia.
Autoantibodies to parietal cells or to intrinsic factor.
Atrophic autoimmune pangastritis: Location.
Body and antrum.
Atrophic autoimmune pangastritis: Histology.
Epithelium: Inflammation (sometimes with. Any lymphocytes), atrophy, apoptosis.
Neuroendocrine cells: Decrease.
Atrophic autoimmune pangastritis: Laboratory findings (2).
No hypergastrinemia.
No antibodies to parietal cells or to intrinsic factor.
Lymphocytic gastritis: Associations (3).
Helicobacter pylori.
Celiac disease.
Lymphocytic colitis.
Others.
Lymphocytic gastritis: Histology.
Surface: More than 25 lymphocytes per 100 gastric foveolar cells.
Background: Chronic gastritis.
Collagenous gastritis: Associations (3).
Collagenous colitis.
Celiac disease.
Anemia in some younger patients.
Collagenous gastritis: Histology.
Thickened subepithelial collagen plate, sometimes with lymphocytic gastritis.
Eosinophilic gastritis: Epidemiology.
Children, adolescents.
Eosinophilic gastritis: Histology.
Eosinophils not associated with other inflammatory cells and causing mucosal architectural change or crypt injury.
Eosinophils may infiltrate muscularis mucosae or deeper layers.
Peptic ulcer: Histologic layers.
Neutrophils and débris.
Fibrin and necrotic matter.
Active granulation tissue.
Fibrous scar that interrupts the muscularis mucosae.
Hypertrophic gastropathy: Thickness of mucosa.
Greater than 1 to 1.5 mm.
Ménétrier’s disease: Symptoms (4).
Abdominal pain.
Diarrhea.
Weight loss.
Peripheral edema.
Ménétrier’s disease: Chemical abnormalities (2).
Hypoproteinemia.
Hypochlorhydria.
Ménétrier’s disease: Associations (3).
Eosinophilia.
Pulmonary infections.
Thrombosis.
Ménétrier’s disease: Possible infectious association.
CMV: Children and some cases in the immunosuppressed.
Ménétrier’s disease: Gross pathology (2).
Thick gastric wall with cerebriform rugae.
Antral sparing.
Ménétrier’s disease: Histology (4).
Hyperplasia is in the superficial mucosa:
− Hyperplastic foveolar cells secrete much mucus.
− Expansion of pits produces cysts.
− Hyperplastic muscularis mucosae.
The fundic glands are atrophic.
Mixed inflammation.
Zollinger-Ellison syndrome:
A. Cause.
B. Epidemiology.
A. Gastrinoma.
B. Can affect anyone but is most common in between ages 20 and 50.
Zollinger-Ellison syndrome: Symptoms.
Abdominal pain, diarrhea.
Zollinger-Ellison syndrome: Gross pathology.
Thick gastric wall with giant rugae.
Antral sparing.
Zollinger-Ellison syndrome: Histology.
Hyperplasia is in the specialized glands.
Thickness ratio of pits to glands exceeds 5 to 1.
The foveolar epithelium is atrophic.
Complications of Zollinger-Ellison syndrome:
A. Histologic.
B. Clinical.
A. Hyperplasia of enterochromaffin-like cells, dysplasia of neuroendocrine cells, carcinoid tumors.
B. Peptic ulcers.
Ménétrier’s disease vs. gastric hyperplastic polyp.
May depend on clinical history, especially in small biopsies.
Gastritis glandularis et cystica profunda: Synonyms.
Diffuse cystic (glandular) malformation.
Gastritis glandularis et cystica profunda: Histology.
Mucosal and submucosal cysts lined by mucous cells.
Pyloric or Brunner-type glands.
Fundic-type glands (rare).
Gastritis glandularis et cystica profunda: Significance.
May increase risk for gastric carcinoma.
Fundic-gland polyp: Causes (5).
Idiopathic (sporadic).
Familial adenomatous polyposis.
Attenuated familial adenomatous polyposis.
MUTYH-associated polyposis syndrome.
Proton-pump inhibitors.
Fundic-gland polyps: Mutations (2).
APC.
β-Catenin.
Fundic-gland polyposis associated with FAP syndrome:
A. Number of polyps.
B. Location.
A. Hundreds.
B. Mostly on the greater curvature, with antral sparing.
Gastric adenocarcinoma with chief-cell differentiation: Histology.
Anastomosing cords of oxyntic epithelial cells that infiltrate generally only the mucosa.
Gastric adenocarcinoma with chief-cell differentiation: Prognosis.
May persist or recur if incompletely excised.
No reports of metastasis; may be benign.
Gastric carcinoma: Main types (2).
Intestinal: Exophytic; resembles colonic carcinoma.
Diffuse: Infiltrative.
Gastric dysplasia: Main types (2).
Flat.
Adenomatous.
Gastric adenomas: Types (5).
Common: Tubular, tubulovillous, villous.
Rare: Antral-foveolar type, pyloric-type.
Intestinal type of gastric adenocarcinoma:
A. Epidemiology (2).
B. Associations (2).
A. Found more often in elderly men and in countries with high incidence of gastric cancer.
B. Dietary practices; H. pylori.
Intestinal type of gastric adenocarcinoma: Histologic origin.
Intestinal metaplasia; dysplastic precursor.
Diffuse type of gastric adenocarcinoma:
A. Epidemiology.
B. Associations (2).
A. More common in younger patients and in women.
B. H. pylori (possibly); germline mutations of CDH1 (E-cadherin).
Diffuse type of gastric adenocarcinoma:
A. Histologic origin.
B. Prognosis.
A. May arise from undifferentiated cells in the neck of the gastric gland.
B. Worse than that of the intestinal type.
Early gastric carcinoma:
A. Definition.
B. Survival.
A. Invasion of submucosa but not of muscularis propria.
B. 95%.
Gastric carcinoma: Molecular testing.
Testing for HER2 for selection of patients for trastuzumab therapy.
Also relevant to adenocarcinomas of the gastric cardia, gastroesophageal junction, and the lower esophagus.
Gastric carcinoma: Best predictor of survival.
Depth of invasion.
Gastric carcinoma: Survival for tumors that involve the subserosa.
50%.
Gastric neuroendocrine tumors: Types.
1: Associated with atrophic gastritis.
2: Associated with Zollinger-Ellison syndrome.
3: Sporadic.
4: High-grade neuroendocrine carcinoma.
Gastric neuroendocrine tumors: Categories.
Sporadic tumors.
Tumors arising in a background of hypergastrinemia.
Sporadic gastric neuroendocrine tumors:
A. Number.
B. Behavior.
A. Usually solitary.
B. Can invade or metastasize.
Hypergastrinemia-related gastric neuroendocrine tumors:
A. Relative frequency.
B. Number.
C. Behavior.
A. More common than sporadic tumors.
B. Multiple.
C. Indolent.
Hypergastrinemia-related gastric neuroendocrine tumors:
A. Cause.
B. Histologic origin.
A. Achlorhydria.
B. Enterochromaffin-like cells: Progression from hyperplasia to nodular hyperplasia to dysplasia to neoplasia.
Gastric neuroendocrine tumors:
A. Which ones respond to antral resection?
B. Which ones tend to be larger?
A. Hypergastrinemia-related tumors.
B. Sporadic tumors.
Gastric neuroendocrine tumors: Grading scheme of the WHO.
Grade 2: 2-20 mitotic figures per hpf, and >2-20% of nuclei are positive for Ki-67.
Grade 1: Fewer of both.
Grade 3: More of both.
Gastric neuroendocrine tumors: Classification of smaller Grade 1 tumors.
Smaller than 1 cm and confined to mucosa and submucosa: Benign well-differentiated NET.
1-2 cm and confined to mucosa and submucosa: Well-differentiated NET of uncertain malignant potential.
Diagnostic criteria of well-differentiated (gastric) neuroendocrine carcinoma.
A grade 1 tumor that is larger than 2 cm
- or -
That invades the muscularis propria or beyond
- or -
That has metastasized.
Diagnostic criteria of high-grade (gastric) neuroendocrine carcinoma.
Any tumor of grade 2 or grade 3.
Gastric neuroendocrine tumors: Histologic distinction between sporadic and hypergastrinemia-related.
Hypergastrinemia-related tumors: Immunohistochemistry shows endocrine-cell hyperplasia in the adjacent mucosa.
Classification of gastric neuroendocrine proliferations by size.
Linear hyperplasia: A line of at least 5 endocrine cells.
Nodular hyperplasia: At least 5 endocrine cells form a cluster smaller than 150 μm.
Endocrine-cell dysplasia: 150 μm-0.5 mm.
Neuroendocrine tumor: Larger than 0.5 mm.
Classification of gastric neuroendocrine proliferations: When applicable (2).
When analyzing the mucosa adjacent to a gastric neuroendocrine tumor.
Not to be performed on antral mucosa.
Gastric lymphoma:
A. Most common type.
B. Most common location.
A. Diffuse large B-cell lymphoma.
B. Antrum.
Gastric marginal-zone lymphoma: Possible cell types (6).
Small lymphocytes with round nuclei.
Centrocyte-like cells.
Monocytoid B cells.
Plasma cells.
Centroblasts, immunoblasts.
Gastric marginal-zone lymphoma: Definition of lymphoepithelial lesion.
At least three B lymphocytes within the epithelium of the gastric glands.
Gastric marginal-zone lymphoma vs. lymphocytic gastritis (2).
Lymphocytic gastritis:
− Usually no lymphoepithelial lesions.
− Intraepithelial lymphocytes are T cells, not B cells.
Normal rotation of bowel during development.
Counterclockwise around the superior mesenteric artery.
Intestinal malrotation: Gross pathology (2).
Small intestine may be pushed to one side of abdomen.
Cecum may be on left side.
Intestinal malfixation: Gross pathology.
Fixation band may cause intestinal torsion and infarction.
Omphalocele: Causes (2).
Failure of the intestines to return to the abdominal cavity during the 10th week of development.
Incomplete closure of the abdominal wall during the 4th week of development.
Omphalocele: Associations.
Other malformations of the gastrointestinal tract.
Cardiovascular defects.
Omphalocele: Gross pathology (3).
Extra-abdominal viscera are covered by a membranous sac consisting of peritoneum and amnion.
Stomach and liver may accompany intestines.
Umbilical cord arises from the center of the sac.
Gastroschisis: Possible cause.
Vascular accident before 12 weeks of development.
Gastroschisis: Gross pathology.
Extra-abdominal viscera are not covered.
Umbilical cord is not affected.
Intestinal atresia:
A. Most common location.
B. Least common location.
A. Duodenum.
B. Colon.
Intestinal atresia: Risk factors (2).
Twin gestation.
Maternal use of cocaine.
Intestinal atresia: Presentation.
Bilious vomiting in soon after birth.
Intestinal atresia: Variations in gross pathology (3).
Imperforate septum occlude lumen.
Absence of lumen: Fibrotic cord.
Absence of bowel segment and its mesentery.
Intestinal stenosis: Variations in gross pathology (2).
Perforate septum.
Narrow lumen.
Intestinal atresia and stenosis: Histology (2).
Proximal to the defect: Ischemia, necrosis, granulation tissue, submucosal fibrosis, hypertrophy of lamina propria (all due to dilatation).
Blind segment: Meconium, lanugo, mucin.
Meckel’s diverticulum:
A. Cause.
B. Prevalence.
A. Failure of involution of the vitelline duct.
B. 1% to 4%.
Meckel’s diverticulum: Prevalence (3).
On the antimesenteric surface of the small bowel.
Infants: Within 30 cm of the ileocecal valve.
Adults: Within 100 cm of the ileocecal valve.
Meckel’s diverticulum:
A. Length.
B. Histology.
A. 2-15 cm.
B. Usually normal small-bowel mucosa; 80% contain ectopic pancreatic or gastric tissue.
Volvulus:
A. Definition.
B. Most common location.
A. Twisting of a segment of bowel around its mesentery.
B. Sigmoid colon.
Volvulus: Predisposing factors (3).
Congenitally long mesentery.
Meckel’s diverticulum.
Congenital band.
Volvulus: Gross pathology and histology.
Variable ischemia; possible necrosis.
Intussusception:
A. Epidemiology.
B. Predisposing factors (2).
A. Twice as common in males.
B. None in children; intraluminal mass in adults.
Intussusception: Histology (2).
Ischemia.
Recurrent cases: Intramural vascular proliferation can mimic vascular tumor.
Gastric marginal-zone lymphoma: Translocation.
t(11;18).
API2−MALT1.
Enterohemorrhagic Escherichia coli: Seasonal distribution of infections.
Most common in the summer.
Enterohemorrhagic E. coli: Effect of toxin.
Inhibits protein synthesis, thereby damaging epithelial and endothelial cells.
Salmonella spp.: Location of replication.
Within intracellular vacuoles of enterocytes and macrophages.
Typhoid fever:
A. Complications (3).
B. Mortality in the untreated.
A. Massive hemorrhage, perforation, peritonitis.
B. About 15%.
Salmonella spp.: Incubation period for gastroenteritis.
A few hours.
Salmonella spp.: Gross pathology of gastrointestinal infections.
Longitudinal oval ulcers with elevated edges, located over Peyer’s patches.
Campylobacter spp.: Frequent association.
Drinking untreated mountain water.
Campylobacter spp.: Incubation period for diarrhea.
Up to 1 week.
Frequent location of colitis due to ___.
A. Enterohemorrhagic E. coli.
B. Campylobacter spp.
A. Right colon.
B. Ileocecal valve.
Campylobacter spp.: Cause of severe systemic illness.
Campylobacter fetus.
Bacteria that cause focal active colitis (3).
Shigella spp.
Campylobacter spp.
Salmonella spp. (sometimes).
Bacteria that cause hyperplasia of lymphoid follicles.
Salmonella spp.
Yersinia enterocolitica.
Bacterial enterocolitis vs. idiopathic inflammatory bowel disease (5).
Idiopathic inflammatory bowel disease: − More diffuse active inflammation. − Less hemorrhage. − Basal plasmacytosis. − More crypt-architectural distortion. − Fewer suppurative granulomas (than seen in yersiniosis).
Causes of diarrhea in AIDS patients.
Infections.
AIDS enteropathy.
AIDS-related enteropathy: Definition (4).
Chronic diarrhea.
Malnutrition.
Wasting.
No evidence of gastrointestinal infection.
AIDS-related enteropathy: Complications (2).
Malabsorption due to loss of microvilli.
Death due to large ulcers proceeding from erosions.
Giardiasis: Associated inherited immunodeficiencies (2).
Common variable immunodeficiency.
Selective IgA immunodeficiency.
Sites of gastrointestinal infection by ___.
A. CMV.
B. HSV.
A. Esophagus, stomach, intestines.
B. Esophagus, low rectum, anus, perianal skin.
Cholera: Incubation period.
A few hours to 2 days.
Coccidiosis: Organisms (3).
Cyclospora cayetanensis.
Cystoisospora belli.
Cryptosporidium spp.
Cyclospora infection: Associations.
Travelers’ diarrhea.
Ingested of contaminated fresh fruit.
Region of the gastrointestinal tract most frequently affected by ___.
A. Mycobacterium tuberculosis.
B. Mycobacterium avium complex.
A. Ileocecal region.
B. Anywhere.
Histology of mycobacterial gastroenteritis:
A. Mycobacterium tuberculosis.
B. Mycobacterium avium complex.
A. Necrotizing granulomas, Langhans’ giant cells.
B. Foamy macrophages stuffed with bacteria fill the lamina propria.
Yersinia enterocolitica: Risk factors for fatal infection.
Immunosuppression.
Iron overload.
Adenovirus: Histology of colitis.
Dystrophic goblet cells with amorphous nuclei that rarely contain diagnostic (smudgy) inclusion bodies.
Candida spp.: Definition of blastoconidium.
A budding yeast form, 3-5 μm.
Gastrointestinal histoplasmosis: Types of inflammation (2).
Granulomatous.
Histiocytic.
Gastrointestinal syphilis:
A. Site.
B. Histology.
A. Rectum or anus.
B. Dense mononuclear infiltrate that includes many plasma cells; lymphoid aggregates; no crypt-architectural distortion or marked acute inflammation.
Use of ___ stain to detect intestinal protozoa.
A. Giemsa (3)
B. trichrome
A. Cryptosporidium, Cystoisospora, microsporidia.
B. Giardia (distinction from mucus).
Mycobacterium-avium-complex enteritis vs. Whipple’s disease.
Whipple’s disease:
− “Fat vacuoles”.
− Positive for PAS-D, not for AFB.
Intestinal spirochetosis: Stains.
Silver stain.
Immunohistochemical stain for Treponema spp.
Candida spp.: True hypha vs. pseudohypha.
True hypha: No indentation at true septa.
Pseudohypha (elongated blastoconidium): Indentation at false septa.
Whipple’s disease: Main sites (3).
Gastrointestinal system.
Joints.
Central nervous system.
Whipple’s disease: Prognosis.
Often fatal without antibiotics.
Whipple’s disease: Gross pathology of the bowel (3).
Mucosa: Yellow plaques, shallow ulcers.
Wall: Thickening.
Whipple’s disease: Gross pathology outside the bowel (3).
Lymphadenopathy.
Hepatosplenomegaly.
Plaques in mesenteric fat and peritoneum.
Whipple’s disease: Histology (3).
Foamy macrophages filled with bacilli.
“Fat vacuoles”, some of which are dilated lymphatic vessels.
Foreign-body granulomas or lipogranulomas.
Whipple’s disease: Inflammatory infiltrate.
Little or none.
Waldenström’s macroglobulinemia in the bowel: Histology.
Foamy macrophages.
Dilated lymphatics filled with eosinophilic matter.
Gliadin-containing cereal grains.
Wheat, rye, barley.
Celiac disease can cause deficiency of which nutrients (3)?
Iron.
Folate.
Calcium.
Celiac disease: Preferred tests.
Antibodies to tissue transglutaminase.
In those who lack the above: Antibodies to deaminated gliadin peptides.
Celiac disease: HLA types.
DQ2: 98%.
DQ8: 2%.
Celiac disease: Typical number of intraepithelial lymphocytes.
More than 40 per 100 enterocytes.
Celiac disease: Histology of crypts (3).
Elongation and hyperplasia.
Increased mitotic activity.
Celiac disease: When to consider workup for clonality.
When there are ulcers in the small intestine.
In cases of refractory sprue.
Normal length ratio of villi to crypts.
3:1 to 5:1.
Celiac disease: Endoscopic finding.
Scalloping of the valvulae conniventes.
Lymphocytic enterocolitis.
Concurrent lymphocytic colitis.
Celiac-disease-like changes in the proximal small intestine.
No response to gluten-free diet.
Refractory sprue: Definition and cause.
No response to gluten-free diet for 12 months.
Allergic reaction to protein other than gluten.
Types of refractory sprue: Intraepithelial lymphocytes.
Type II:
− Some may appear atypical.
− Loss of CD8 and CD5.
− Monoclonality of T-cell receptors.
Types of refractory sprue: Treatment.
Type I: Azathioprine, prednisone, budesonide, or mesalamine.
Type II: May respond to cladribine, anti-CD52, or chemotherapy and stem-cell transplantation.
Types of refractory sprue: Prognosis.
Type II: 50% mortality rate; most cases progress to enteropathy-associated T-cell lymphoma.
Tropical sprue: Treatment.
Broad-spectrum antibiotics and vitamins.
Autoimmune enteritis:
A. Gene and chromosome.
B. Associations (2).
A. FOXP3 on the X chromosome.
B. X-linked type: Immune dysregulation, polyendocrinopathy.
Autoimmune enteritis: Targets of autoantibodies (4).
Enterocytes.
Goblet cells.
Parietal cells.
Smooth-muscle cells.
Autoimmune enteritis: Clue to diagnosis (3).
No goblet cells.
No increase in intraepithelial lymphocytes.
No response to gluten-free diet.
Abetalipoproteinemia:
A. Histology.
B. Peripheral blood.
A. Enterocytes with intracytoplasmic vacuoles.
B. Acanthocytes.
Celiac disease: Progression of recovery.
From distal to proximal, with the duodenum recovering last.
Primary adenocarcinoma of the small intestine: Risk factors (6).
Familial adenomatous polyposis.
Attenuated FAP.
MUTYH-associated polyposis syndrome.
Lynch’s syndrome.
Peutz-Jeghers syndrome.
Crohn’s disease.
Primary adenocarcinoma of the small intestine: Locations.
Most: Near major duodenal papilla.
Associated with Crohn’s disease: Ileum.
Gastrointestinal carcinoid tumors: Sites (5).
Appendix (#1).
Ileum.
Rectum.
Stomach.
Colon.
Carcinoid tumors of the bowel: Presentations (4).
Incidental.
Weight loss.
Obstruction.
Carcinoid syndrome.
Carcinoid syndrome associated with carcinoid tumors of the bowel:
A. Prevalence.
B. Most common site of carcinoid tumor.
A. 10%.
B. Ileum.
Carcinoid syndrome:
A. Hormonal mediators.
B. Associated lesion.
A. 5-HT, 5-HIAA.
B. Lesion of right heart in 50% of cases.
Significance ___ in carcinoid tumors of the bowel:
A. cytologic features
B. vascular invasion
C. perineural invasion
None of these factors predict behavior of the tumor.
Atypical carcinoid: Synonyms (2).
Grade 2 neuroendocrine tumor.
Intermediate-grade neuroendocrine tumor.
Grade 2 neuroendocrine tumor: Criteria (2).
2-20 mitotic figures per 10 hpf.
More than 2% to 20% of nuclei positive for Ki-67.
Carcinoid tumors of the bowel: Relevance of immunohistochemistry to site.
Hindgut tumors are often negative for chromogranin.
Gangliocytic paraganglioma: Cellular components (3).
Neuroendocrine cells.
Spindle cells with Schawann-cell differentiation.
Ganglion cells.
Gangliocytic paraganglioma:
A. Frequent site.
B. Behavior.
A. Ampullary region.
B. Uncertain malignant potential.
Mixed carcinoid-adenocarcinoma:
A. Gross pathology.
B. Portion made up by adenocarcinoma.
A. Often large and infiltrating.
B. Typically more than 50%.
Mixed carcinoid-adenocarcinoma:
A. Differential diagnosis.
B. Prognosis.
A. Benign epithelial differentiation within a carcinoid tumor.
B. Acts like adenocarcinoma.
Frequent histologic feature of carcinoid tumors of the ___.
A. Small intestine.
B. Rectum.
C. Duodenum.
A. Insular growth.
B. Trabecular growth.
C. Psammoma bodies.
Carcinoid tumors of the bowel: Relevance of risk of metastasis to size of tumor.
Less than 1 cm: 2%.
1-2 cm: 50% (ileal), 15% (rectal).
More than 2 cm: 80%.
Carcinoid tumors of the bowel: Best indicator of behavior.
Metastasis.
Typical behavior of ___.
A. Gastrinoma.
B. Insulinoma.
A. Malignant.
B. Benign.
Hirschsprung’s disease: Risk factors (2).
Male sex.
Down’s syndrome.
Hirschsprung’s disease: Forms (3).
Short-segment (most common): No more than 3 cm of distal rectum.
Long-segment: Extends beyond sigmoid colon.
Ultra-short: Less than 2 cm; diagnosed by manometry, not by histology.
Hirschsprung’s disease: Typical histology (3).
No ganglion cells.
Hypertrophic mural nerves (>40 μm).
Thickened muscle layers.
Hirschsprung’s disease: Special stains (4).
Acetylcholinesterase: Nerve fibers extend into lamina propria.
Calretinin: Absence of staining.
NSE for ganglion cells.
S-100 for Schwann cells.
Long-segment Hirschsprung’s disease: Histology and special stain.
Mural nerves may not be hypertrophic.
Acetylcholinesterase stain may be falsely negative.
Hirschsprung’s disease: Mutations.
RET, endothelin receptor B.
Hirschsprung’s disease vs. hypoganglionosis.
Hypoganglionosis: Some ganglion cells but still too few.
Intestinal neuronal dysplasia: Histology.
Hyperplastic plexus.
Giant ganglia containing more than 8 neurons.
Eosinophilic gastroenteritis: Definition (3).
Gastrointestinal symptoms.
Eosinophilic infiltration of the gastrointestinal tract.
No known cause such as specific allergy or parasites.
Eosinophilic gastroenteritis: Frequent associations (3).
Peripheral eosinophilia.
Elevated serum IL-5.
History of allergies.
Eosinophilic gastroenteritis: Types (3).
Mucosal: Diarrhea and malabsorption.
Submucosal: Obstruction.
Mural and serosal: Ascites, eosinophilic peritonitis.
Eosinophilic gastroenteritis: Main histologic features (3).
Sheets of eosinophils.
Mucosal changes.
Fibrosis.
Allergy to cow’s milk: Histology (2).
Villous atrophy.
Neutrophils and eosinophils.
Systemic mastocytosis of the gastrointestinal tract:
A. Associated mutation.
B. Definition of mast-cell aggregate.
A. D816V in KIT.
B. More than 15 mast cells.
Systemic mastocytosis of the gastrointestinal tract: Histological confounder.
Obscuring eosinophils (80% of cases).
Idiopathic constipation: Histology (3).
Ganglion cells are present.
Argyrophilic neurons may be lost.
Interstitial cells of Cajal may be decreased.
Acute graft-versus-host disease:
A. Timing.
B. Initial site of involvement.
A. Usually occurs within 100 days after transplantation.
B. Skin.
Gastrointestinal graft-versus-host disease: Initial histology.
Necrosis of single cells in the bases of crypts gives rise to lacunae that contain apoptotic débris.
Gastrointestinal graft-versus-host disease: Intermediate histology.
Apoptosis in many crypts; crypt abscesses; ulcers with secondary fungal infection.
Gastrointestinal graft-versus-host disease: Late histology.
Mucosal atrophy, fibrosis, or regeneration.
Gastrointestinal graft-versus-host disease vs. effect of mycophenolate mofetil.
Mycophenolate mofetil:
− More likely to have eosinophils.
− Less likely to have apoptotic débris within lacunae.
Graft-versus-host disease: Mediating cell.
The cytotoxic T cell.
Crohn’s disease of the small bowel: Gene.
IBD-1, a.k.a. NOD2/CARD15.
Ulcerative colitis: Feared acute complications (2).
Toxic megacolon.
Perforation.
Crohn’s disease: Gross pathology (3).
Fat-wrapping.
“Stovepipe” bowel.
“Cobblestoning” of mucosa.
Crohn’s disease: Radiography.
“String sign” due to luminal stenosis.
Crohn’s disease: Histology of inflammation (4).
Required for diagnosis:
− Non-necrotizing granulomas and/or
− Transmural lymphoid aggregates away from a deep ulcer.
Other features:
− Neutrophilic infiltrates and crypt abscesses.
− “Rosary bead” of lymphoid aggregates along the serosa.
Crohn’s disease: Histology of stromal changes (3).
Hypertrophy of muscularis mucosae.
Submucosal neuronal hyperplasia.
Mural fibrosis.
Crohn’s disease: Serologic test.
Antibodies to Saccharomyces cerevisiae are found in about half of patients.
Ulcerative colitis: Site.
Always involves the rectum.
Does not have to involve the whole colon; “backwash” ileitis is not a required finding.
Ulcerative colitis: Histology of inflammation (2).
Dense lymphoplasmacytic and neutrophilic infiltrate that usually goes no deeper than the submucosa.
Cryptitis, crypt abscesses, crypt regeneration, and crypt-architectural distortion.
Ulcerative colitis: Features that may make it “primary inflammatory bowel disease of an indeterminate type” (2).
Pancolitis with involvement of the terminal ileum.
Ulcers that extend into the muscularis propria.
Ulcerative colitis: Antibody.
pANCA.
Lymphocytic colitis: Number of lymphocytes.
More than 15 per 100 superficial epithelial cells.
Diversion colitis: Leading cause.
Hartmann pouch constructed during a proximal partial colectomy.
Diversion colitis: Histology (4).
Large lymphoid aggregates and follicles.
Dense lymphoid infiltrate in the lamina propria.
Mild active inflammation may be seen.
Normal crypt architectural except in longstanding cases.
Diversion colitis: Treatment (3).
Restoration of fecal stream.
Enemas of short-chain fatty acids.
Surgical excision in refractory cases.
Causes of active ileitis (4).
Minimal and focal:
− Bowel preparation.
− Trauma and prolapse.
Significant:
− Crohn’s disease.
− NSAIDs.
Ileal pouch:
A. Purpose.
B. Clinical indications.
A. To restore continence after colectomy.
B. Ulcerative colitis, FAP.
Ileal pouchitis: Clinical features.
Bloody and foul-smelling effluent.
Fever and malaise.
Ileal pouchitis: Histologic features (4).
Granulation tissue.
Architectural change.
Ulcers.
Loss of normal lymphoid follicles.
Ileal pouch: Histologic features that suggest Crohn’s disease (3).
Ulcers and non-necrotizing granulomas in the afferent limb.
Pyloric-gland metaplasia.
Risk for colon cancer in ___.
A. Ulcerative colitis.
B. Crohn’s disease.
A. 20% in 30 years.
B. 3% in 20 years.
Dysplasia in inflammatory bowel disease: Gross pathologic types (2).
Flat dysplasia.
Dysplasia-associated lesion or mass: Polyp or plaque.
Dysplasia in inflammatory bowel disease: Grading.
Negative for dysplasia.
Indefinite for dysplasia.
Low-grade dysplasia.
High-grade dysplasia.
Dystrophic goblet cell.
One in which the mucin vacuole does not communicate with the lumen.
Dysplasia-associated lesion or mass vs. sporadic adenoma: Histology.
Not possible to make the distinction.
Clinical features favoring dysplasia-associated lesion or mass over sporadic adenoma (2).
Patient under 40 with UC for more than 10 years.
Lesion larger than 1 cm in area of colitis with dysplasia in the adjacent flat mucosa.
Ancillary studies favoring dysplasia-associated lesion or mass over sporadic adenoma (3).
IHC: Positive for p53, negative for bcl-2.
Molecular: Loss of heterozygosity in chromosome 3p.
Radiation colitis:
A. Dose of radiation.
B. Other risk factors (3).
A. Usually more than 450 Gy.
B. Diabetes, cardiovascular disease, chemotherapy.
Radiation colitis: Symptoms (3).
Diarrhea.
Abdominal pain.
Bowel obstruction in chronic radiation colitis.
Acute radiation colitis: Histology (5).
Edema.
Vascular ectasia.
Acute cryptitis.
Superficial ulcers.
Epithelial cytomegaly and atypia.
Chronic radiation colitis: Histology (5).
Stromal fibrosis with atypical fibroblasts.
Thickened subepithelial collagen.
Glandular atrophy and distortion.
Vascular changes.
Increased plasma cells in the lamina propria.
Ischemic colitis: Clinical features.
Usually acute onset.
Abdominal pain, nausea, vomiting, diarrhea, or lower-gastrointestinal bleeding.
Ischemic colitis: Pharmacological causes (2).
NSAIDs.
Oral contraceptives.
Ischemic colitis: Infectious mimics.
Enterohemorrhagic E. coli.
Clostridium difficile.
Mild ischemic colitis: Histology (4).
Superficial hemorrhage.
Patchy mucosal necrosis.
Dilated vessels
“Decapitated” glands.
Severe ischemic colitis: Histology (3).
Crypt dropout.
Acute inflammation, including cryptitis.
Coagulative necrosis.
Late lesions of ischemic colitis: Histology.
Replacement of mucosa by granulation tissue and fibrosis.
Microscopic colitis: Causes (3).
Idiopathic.
Drugs, e.g. ticlopidine.
Infection, e.g. Brainerd diarrhea.
Microscopic colitis: Epidemiology.
Collagenous colitis is more common in women.
Collagenous colitis: Histology (3).
Thickened subepithelial collagen.
Increased intraepithelial lymphocytes.
Increased plasma cells in the superficial lamina propria.
Microscopic colitis: Possible aberrant histologic findings (6).
Subepithelial giant cells. Cryptitis. Ulcers. Paneth-cell metaplasia. Pseudomembranes. Architectural change.
Collagenous colitis: Possible complication.
“Fracture” of colon during endoscopic insufflation, leading to pneumatosis coli.
Cord colitis syndrome: Association.
Cord-blood stem-cell transplantation.
Cord colitis syndrome: Histology.
Granulomatous inflammation and changes similar to those of idiopathic inflammatory bowel disease.
Affects upper and lower gastrointestinal tract.
Cord colitis syndrome:
A. Treatment.
B. Possible cause.
A. Usually responds to antibiotics.
B. Bradyrhizobium enterica.
Syndromes of mucosal prolapse: Endoscopy.
Mucosal erythema, ulcer, or polypoid lesion.
Syndromes of mucosal prolapse: Histology (4).
Fibromuscular obliteration of the lamina propria.
Mucosal architectural change and misplacement.
Mucosal capillary ectasia.
Sometimes: Erosion with inflammatory pseudomembrane.
Collagenous colitis: Significance of metaplasia.
Paneth-cell metaplasia:
− Seen in collagenous colitis with more severe diarrhea.
− May cause confusion with idiopathic inflammatory bowel disease.
Entamoeba histolytica: Chemical resistance.
Resists gastric acid and chlorination.
Entamoeba histolytica: Complications of infection in the colon (3).
Granulomatous masses that can mimic carcinoma.
Perforation.
Fistulae.
Entamoeba histolytica: Most frequent sites of ulcers in the large intestine.
Cecum.
Appendix.
Rectosigmoid.
Entamoeba histolytica: Typical orientation of colonic ulcers.
Perpendicular to the long axis of the colon.
Entamoeba histolytica vs. histiocytes.
Histocytes:
− Smaller.
− Larger, more irregular nucleus.
− Less intense staining with PAS.
Aoncotheca philippinensis:
A. Synonym.
B. Geography.
A. Capillaria philippinensis.
B. Asia, Middle East, Africa.
Aoncotheca philippinensis:
A. Disease.
B. Diagnosis.
A. Protein-losing enteropathy.
B. Identification of eggs, larvae, or worms in stool.
Aoncotheca philippinensis: Sites of infection (2).
Jejunum, upper ileum.
Strongyloides stercoralis: Histology of autoinfection.
Filiform larvae in the bowel wall.
Diphyllobothrium latum: Residence.
Small intestine.
Trichuris trichiura:
A. Residence.
B. Morphology of adult.
A. Cecum, ascending colon.
B. Whiplike, 4 cm.
Lymphangiectasia: Forms.
Primary: Congenital obstruction.
Secondary: Inflammation, malignancy.
Lymphangiectasia: Manifestations (2).
Protein-losing enteropathy.
Lymphatic obstruction.
Pneumatosis intestinalis: Forms.
Acute: Gas-forming intestinal organisms.
Chronic: Pulmonary disease.
Pneumatosis intestinalis: Causative bacteria (3).
Clostridium perfringens.
Enterobacter aerogenes.
Escherichia coli.
Pneumatosis intestinalis: Association in infants.
Necrotizing enterocolitis.
Pneumatosis intestinalis: Manifestations in adults (3).
Diarrhea.
Flatulence.
Increased mucus in the stool.
Pneumatosis intestinalis: Radiography.
Ring of gas in the wall of the bowel.
Pneumatosis intestinalis: Typical location of gas-filled cysts.
Near the mesenteric border.
Pneumatosis intestinalis: Histology.
Gas-filled cysts that usually have no endothelial lining.
Variable inflammatory response.
Overlying mucosa may show ischemic changes.
Melanosis coli: Pigment and its location.
Lipofuscin in histiocytes of the lamina propria.
Melanosis coli: Special stains (3).
Positive: PAS, AFB, Fontana-Masson.
Negative: Iron stains.
Brown-bowel syndrome:
A. Pigment and its location.
B. Typical association.
C. Symptoms.
A. Lipofuscin in smooth-muscle cells.
B. Deficiency of vitamin E.
C. Abdominal pain, diarrhea.
Pseudomelanosis duodeni: Pigment and its location.
Iron in the tips of duodenal villi.
Pseudomelanosis duodeni: Associations (4).
Iron-containing compounds.
Hypertension.
Diabetes mellitus.
End-stage renal disease.
Inflammatory polyp of the colon: Histology (4).
Variable mixture of inflamed stromal tissue and hyperplastic epithelium.
Fibromuscular hyperplasia.
Thick-walled or ectatic blood vessels.
Sometimes: Bizarre stromal cells.
Serrated adenoma:
A. Typical location.
B. Distinguishing histology (2).
A. Left colon.
B. Eosinophilic cytoplasm, gastric foveolar metaplasia.
Sessile serrated polyp: Histologic features (10).
Basal dilatation of crypts.
Branching of crypts.
Horizontal orientation of crypts.
Prominent serration.
Misplacement of glands.
Epithelial-to-stromal ratio exceeding 50%.
No thickening of basement membrane at surface.
Persistent atypia in the upper third of the crypt.
Mitotic figures in the upper third of the crypt.
Dystrophic goblet cells.
Sessile serrated polyp: Number of histologic features needed for diagnosis.
4.
Sessile serrated polyp: Significance (2).
May progress to colon cancers with microsatellite instability.
Multiple in the serrated polyposis syndrome.
Sessile serrated polyp: Surveillance interval (3).
Less than 10 mm: 5 years.
At least 10 mm: 3 years.
With cytologic dysplasia: 3 years.
Serrated adenoma: Surveillance interval.
3 years.
Colon cancer: Major molecular pathways (2).
Chromosomal instability: 85%.
Mutator phenotype (microsatellite instability): 15%.
Colon cancer of the chromosomal-instability pathway:
A. Typical ploidy.
B. Affected chromosomes (3).
C. Associated syndrome.
A. Aneuploid.
B. 5, 17, 18.
C. Familial adenomatous polyposis.
Colon cancer of the mutator-phenotype pathway:
A. Typical gross pathology (2).
B. Typical ploidy.
C. Associated syndrome.
A. Large, right-sided.
B. Diploid.
C. Lynch’s syndrome.
Lynch’s syndrome: Sites of non-colonic carcinomas (6).
Central nervous system.
Urinary tract.
Biliary tract.
Ovary.
Stomach, small intestine.
Endometrium.
Lynch’s syndrome: Amsterdam II criteria.
At least 3 relatives with LS-related tumors.
Colo-rectal carcinoma in 2 generations.
LS-related tumor occurring in patient under 50.
Familial colorectal cancer syndrome, type X:
A. Definition.
B. Mutant protein.
A. Applied to one who fulfills the Amsterdam II criteria but has no mutated mismatch-repair gene.
B. Some: Epithelial-cell adhesion molecule (EPCAM).
Colonic adenocarcinoma: Grading.
I: Well-formed glands in a desmoplastic stroma.
II: Less well-formed glands; focal cribriform pattern.
III: No glands; solid sheets.
Mucinous adenocarcinoma of the colon: Prognosis.
Worse, but only if at least 75-80% of the tumor has extracellular mucus.
Colorectal cancer of Lynch’s syndrome: Histology.
Many lymphocytes around and within the tumor.
Poorly differentiated: Undifferentiated or medullary.
Many tumors are of the mucinous or signet-ring type.
Bethesda criteria for colorectal carcinoma: Purpose.
To determine which tumors should be tested for MSI-H.
Bethesda criteria for colorectal carcinoma: The criteria (5).
Patient under 50.
LS-related tumor at any time, any age.
MSI-H histology in a patient under 60.
Colorectal carcinoma in a first-degree relative.
Patient with at least 2 relatives with an LS-related tumor at any age.
Effect of MSI-H histology on ___.
A. Prognosis.
B. Treatment.
C. Surveillance.
A. Better prognosis.
B. Irinotecan is used rather than 5-FU.
C. Surveillance for other LS-related tumors.
Another reason why testing for MSI-H should be done.
To catch those who have MSI-H but do not meet the Amsterdam II criteria.
Tests for MSI-H (3).
PCR for microsatellite stability.
IHC for enzymes of mismatch repair.
Sequencing of genes of mismatch repair.
Colorectal carcinoma: Relevance of site of tumor to prognosis.
Worse if left-sided.
Causes of loss of MSH6 by immunohistochemistry (3).
Germline mutation of MSH2/MSH6.
Deficiency of MLH1/PMS2 + somatic mutation of MSH6.
Previous chemotherapy.
Familial adenomatous polyposis:
A. Inheritance.
B. Onset of polyps.
C. Natural course.
A. Autosomal dominant.
B. Usually around puberty.
C. Death from colorectal carcinoma.
Familial adenomatous polyposis:
A. Gene and its location.
B. Mutations associated with attenuated FAP.
A. APC on 5q21.
B. Mutations near the 3’ end, near the 5’ end, or in exon 9.
Familial adenomatous polyposis: Ocular abnormality.
Congenital hypertrophy of the retinal pigmented epithelium.
Familial adenomatous polyposis: Leading cause of death after colectomy.
Periampullary carcinoma.
Gardner’s syndrome:
A. Benign tumors (3).
B. Extra-colonic sites of malignant tumors (2).
A. Osteomas, epidermal cysts, fibromatosis.
B. Duodenum, thyroid.
Turcot’s syndrome vs. pseudo-Turcot’s syndrome.
Turcot’s: Familial adenomatous polyposis with medulloblastoma.
Pseudo-Turcot’s: Lynch’s syndrome with glioblastoma.
Muir-Torre syndrome:
A. Defective protein.
B. Location of colonic adenomas.
A. Mismatch-repair enzymes.
B. Proximal colon.
Muir-Torre syndrome: Skin tumors.
Sebaceous neoplasms.
BCC.
SCC.
MUTYH-associated polyposis syndrome:
A. Inheritance.
B. Gene and its function.
A. Autosomal recessive.
B. MYH encodes an enzyme of excision repair.
MUTYH-associated polyposis syndrome: Relation to familial adenomatous polyposis (2).
Mutation of MYH predisposes to acquired mutation of APC.
Can mimic FAP or attenuated FAP clinically.
Familial adenomatous polyposis:
A. Earliest lesion in the colon.
B. Gastric polyps.
A. The one-gland adenoma.
B. Fundic-gland polyps, adenomas.
Familial adenomatous polyposis: When workup should occur in patient with no known risk factors or family history.
When a patient has had a cumulative total of 10 of more adenomas.
Familial adenomatous polyposis: Molecular test.
Gene sequencing to determine exact location of mutation of APC gene.
Peutz-Jeghers syndrome:
A. Inheritance.
B. Onset of polyps.
A. Autosomal dominant.
B. During infancy.
Peutz-Jeghers syndrome: Gene and its location.
STK-11 on 19q13.3.
Peutz-Jeghers syndrome: Characteristic gonadal tumors (2).
Ovarian sex-cord tumor with annular tubules.
Testicular Sertoli-cell tumors.
Peutz-Jeghers syndrome: Other sites of malignancy (2).
Pancreas, breast.
Peutz-Jeghers syndrome: Benign finding.
Hyperpigmentation of skin and mucous membranes.
Isolated juvenile polyps:
A. Maximum.
B. Frequent fate of polyps.
A. Up to 5 juvenile polyps in the colon and rectum.
B. Auto-amputation.
Juvenile polyposis syndrome: Criteria (3).
Any of the following:
At least 6 juvenile polyps.
Presence of juvenile polyps throughout the GI tract.
Any juvenile polyp in one with a family history of juvenile polyposis syndrome.
Juvenile polyposis syndrome: Forms.
Nonfamilial: May be associated with other congenital anomalies.
Familial: Many varieties, mostly autosomal dominant.
Juvenile polyposis syndrome:
A. Onset.
B. Presentations (3).
A. Childhood.
B. Rectal bleeding, bowel obstruction, prolapse of polyp into anal canal.
Juvenile polyposis syndrome:
A. Number of polyps.
B. Sites of polyps.
A. Between 6 and several hundred.
B. Distal colon and rectum (90%), stomach.
Juvenile polyp: Gross pathology.
Globose or mushroom-shaped and often ulcerated.
Juvenile polyp: Histology (4).
Hamartomatous overgrowth of lamina propria.
Dilated glands may form cysts.
Inflamed stroma and (often) surface.
Sometimes: Increased ganglion cells and hypertrophic nerves.
Juvenile polyp: Incidence of dysplasia.
Up to 20%.
Juvenile polyposis syndrome: Genes and their locations (2).
SMAD4 (MADH4) on 18q21.1.
BMPR1A on 10q23.3 (if concurrent hereditary hemorrhagic telangiectasia).
PTEN hamartoma-tumor syndromes (2).
Cowden’s syndrome.
Ruvalcaba-Myhre-Smith syndrome.
Cowden’s syndrome:
A. Inheritance.
B. Sites of tumors (4).
A. Autosomal dominant.
B. Gastrointestinal tract, thyroid, breast, skin of face.
Cowden’s syndrome: Facial anomalies (3).
Arched palate.
Beaked nose.
Retinal gliomas.
Peutz-Jeghers syndrome: Sites of gastrointestinal polyps.
Mostly in the small intestine but also in the colon.
Cowden’s syndrome: Onset of tumors.
Between ages 20 and 40.
PTEN hamartoma-tumor syndromes: Histology of polyps (4).
May resemble juvenile polyps.
May resemble rectal mucosal prolapse.
Ganglioneuromas and lipomas may occur.
PTEN: Location of gene.
10q23.
Cronkhite-Canada syndrome:
A. Inheritance.
B. Onset.
A. Not inherited.
B. Late adulthood.
Cronkhite-Canada syndrome: Findings outside the gastrointestinal tract (3).
Alopecia.
Hyperpigmentation.
Nail dystrophy.
Cronkhite-Canada syndrome: Mortality and typical cause of death.
60%; cachexia.
Cronkhite-Canada syndrome:
A. Sites of polyps.
B. Gross pathology.
A. Anywhere in the GI tract, but esp. in stomach and colon.
B. May mimic primary IBD; cut surface is often gelatinous.
Cronkhite-Canada syndrome:
A. Histology of polyps.
B. Histology of adjacent mucosa.
A. Similar to that of juvenile polyps.
B. Edematous and may be rich in eosinophils.
Intestinal ganglioneuromatosis: Causes (5).
Juvenile polyposis syndrome.
PTEN hamartoma-tumor syndromes.
Tuberous sclerosis.
Neurofibromatosis.
MEN IIB.
Serrated polyposis syndrome: Possible genetic abnormalities (2).
Defect in hypermethylation of DNA.
Mutation in MYH.
Benign fibroblastic polyp of the colon: Synonym.
Colorectal perineurioma.
Benign fibroblastic polyp of the colon: Histology (2).
Small, tightly packed spindle cells in the lamina propria.
Spindle cells are often oriented parallel to the muscularis mucosae.
Mucosa may resemble hyperplastic polyp or SSP.
Benign fibroblastic polyp of the colon: Immunohistochemistry.
Negative: Neural markers, including S100.
Elastosis and elastofibromatous change of the colon: Histology.
Increased elastin fibers and fibrous tissue, often centered on a blood vessel.
Can cause a polypoid mass.
Mucosal neuroma:
A. Distinction from ganglioneuroma.
B. Immunohistochemistry.
A. A ganglioneuroma contains ganglion cells as well as spindle cells.
B. Positive for S100.
Mucosal neuroma: Associations.
Most cases: None (sporadic).
Neurofibromatosis.
Ruvalcaba-Myhre-Smith syndrome: Findings outside the gastrointestinal tract (4).
Macrocephaly.
Mental deficiency.
Characteristic facies.
Penile macules.
Peutz-Jeghers syndrome: Histology of colonic polyps.
Hamartomatous overgrowth of muscularis mucosae.
Arborizing architecture.
Dysplasia is rare.
Gastrointestinal stromal tumor:
A. Most common sites.
B. Presentation.
A. Stomach, small intestine.
B. Ulceration and bleeding in about half of cases.
Gastrointestinal stromal tumor: Carney’s triad.
Epithelioid GIST.
Pulmonary chondroma.
Extraadrenal paraganglioma.
Gastrointestinal stromal tumor: Criteria for very low risk (2).
Smaller than 2 cm.
Fewer than 5 mitotic figures per 50 hpf.
Gastrointestinal stromal tumor: Criteria for low risk (2).
2-5 cm.
Fewer than 5 mitotic figures per 50 hpf.
Gastrointestinal stromal tumor: Criteria for intermediate risk (2,2).
Smaller than 5 cm, 6-10 mitotic figures per 50 hpf.
5-10 cm, fewer than 5 mitotic figures per hpf.
Gastrointestinal stromal tumor: Criteria for high risk (2,1,1).
Larger than 5 cm, more than 5 mitotic figures per 50 hpf.
Any tumor larger than 10 cm.
Any tumor with more than 10 mitotic figures per hpf.
Risk of adverse outcome of high-risk gastrointestinal tumor in the ___.
A. Stomach.
B. Small intestine.
A. 46%.
B. 77%.
Colorectal gastrointestinal stromal tumors.
Rare but tend to show high-risk histology.
Gastrointestinal stromal tumor: Recommended immunohistochemical panel.
CD117.
CD34.
Desmin, actin.
S-100.
Gastrointestinal stromal tumor: Useful newer stain.
DOG-1 is both sensitive and specific for GIST.
Gastrointestinal stromal tumor: Most frequently mutated genes (2).
KIT.
PDGFRA.
Gastrointestinal stromal tumor: Locations of mutations in KIT.
Exons 9, 11, 13, 17.
Gastrointestinal stromal tumor: Relevance to location of mutation in KIT to treatment.
Exon 11: Usually responsive to imatinib.
Exon 9: Only half of patients respond; a higher do may be needed.
Exons 13 and 17: Usually no response.
Gastrointestinal stromal tumor: Locations of mutations in PDGRA.
Exons 12, 14, 18.
Gastrointestinal stromal tumor: Most common mutation in PDGFRA and relevance to treatment.
D842V in exon 18 is highly resistant to imatinib and sunitinib.
CD117-negative gastrointestinal stromal tumor:
A. Incidence.
B. Immunohistochemistry (1,3).
A. 4% of GISTs.
B. Positive for DOG-1; negative for CD117, c-Kit, and CD34.
CD117-negative gastrointestinal stromal tumor:
A. Frequent chromosomal abnormality.
B. Frequent histology.
C. Frequent sites (2).
A. Loss of 14 or of 14q.
B. Epithelial.
C. Omentum, peritoneum.
CD117-negative gastrointestinal stromal tumor: Treatment.
Some tumors respond to imatinib.
Fibromatosis: Immunohistochemistry.
Depending on staining technique, may show false positivity for CD117.
Gastrointestinal leiomyosarcoma: Most frequent sites (3).
Stomach, small intestine, colon.
Gastrointestinal schwannoma: Frequent histologic feature.
Cuff of lymphocytes.
Malignant neuroectodermal tumor:
A. Synonym.
B. Mutations.
A. Osteoclast-rich tumor resembling clear-cell sarcoma.
B. EWSR-CREB1 or EWSR-ATF1.
Malignant neuroectodermal tumor: Immunohistochemistry (1,1,1).
Positive: S-100.
Variable: Melanoma markers.
Negative: CD117.
Familial gastrointestinal stromal tumor:
A. Inheritance.
B. Genetic basis.
A. Autosomal dominant.
B. Germline mutation in KIT and PDGFRA.
Familial gastrointestinal stromal tumor: Possible associations (4).
Nevi.
Perineal hyperpigmentation.
Urticaria pigmentosa.
Systemic mast-cell disease.
Familial gastrointestinal stromal tumor: Course.
Indolent.
Carney-Stratakis syndrome: Tumors (3).
Multiple epithelioid GISTs in the stomach.
Paragangliomas.
Pheochromocytomas.
Carney-Stratakis syndrome:
A. Gene.
B. Treatment.
A. Succinate dehydrogenase.
B. Relatively resistant to imatinib.
Gastrointestinal stromal tumors associated with neurofibromatosis, type I:
A. Site.
B. Histology (2).
C. Behavior.
A. Small intestine.
B. Spindle-cell type; “skeinoid” fibers.
C. Usually benign.
Gastrointestinal stromal tumors in children:
A. Gender preference.
B. Site and histology.
C. Behavior.
A. More frequent in females.
B. Gastric; epithelioid.
C. Indolent.
Mantle-cell lymphoma of the gastrointestinal tract: Incidence (2).
Involvement of gastrointestinal tract occurs in 10-20% of patients with mantle-cell lymphoma.
Involvement of gastrointestinal tract is clinically occult in up to 80% of cases.
Intestinal lymphomas that can present as lymphomatous polyposis (3).
Mantle-cell lymphoma.
Marginal-zone lymphoma.
Follicular lymphoma.
Enteropathy-associated T-cell lymphoma: Typical gross pathology.
Ulcers and strictures in the jejunum.
Enteropathy-associated T-cell lymphoma: Histologic types (2).
Pleomorphic.
Monomorphic.
Pleomorphic enteropathy-associated T-cell lymphoma: Immunohistochemistry.
Positive: CD3.
Negative: CD4, CD5, CD56.
CD8 is negative in 20% of cases.
Monomorphic enteropathy-associated T-cell lymphoma: Immunohistochemistry.
Positive: CD3, CD56, CD8.
Enteropathy-associated T-cell lymphoma: Association with celiac disease.
Much stronger with the pleomorphic type.
Intestinal reactive lymphoid hyperplasia: Most frequent sites (3).
Terminal ileum.
Duodenum.
Rectum.
Terminology of anal squamous intraepithelial lesions.
Anal canal: LGAIN, HGAIN.
Perianal skin: LSIL, HSIL.
Anal carcinoma: Location.
Above the dentate line.
Anal carcinoma: Typical histology (2).
SCC or some variant thereof (95%).
Half of the SCCs are nonkeratinizing.
Anal carcinoma: Basaloid squamous-cell carcinoma.
Consists of tumor islands with peripheral palisading, but not to the degree of BCC.
Anal carcinoma: Uncommon histology (3).
Colorectal-type carcinoma.
Salivary-type carcinomas.
Undifferentiated neuroendocrine-type carcinomas.
Paget’s disease of anal mucosa: Stains (4).
PAS.
Mucicarmine.
Alcian blue.
Often: CEA.
Paget’s disease of anal mucosa: Origins (3).
Apocrine cells.
Adenocarcinoma of the rectosigmoid.
Adenocarcinoma of the anal canal.
Adenocarcinoma involving the anal canal: Origins (5).
Rectum.
Anal canal.
Perianal duct or glands.
Paget’s disease.
Chronic perianal fistula.
Adenocarcinoma arising in a perianal fistula: Type.
Usually mucinous adenocarcinoma.
Anal melanoma may mimic ___ clinically.
a hemorrhoid
How many appendices resected for appendicitis turn out to be normal?
About 15%.
Mucocele of the appendix.
Gross term only.
Most cases are due to mucinous cystadenoma or cystadenocarcinoma.
Non-neoplastic cause of appendiceal mucocele:
A. Name.
B. Size.
C. Typical cause.
A. Retention cyst.
B. Less than 1 cm (anything larger is a neoplasm until proved otherwise).
C. Sterile obstruction of the appendiceal lumen.
Mucinous cystadenoma of the appendix: Association.
About 20-25% are associated with a separate primary colonic adenocarcinoma.
Mucinous cystadenoma of the appendix: Gross pathology.
Appendix often resembles a sausage.
Expansion of mucin may produce diverticula.
Mucinous cystadenoma of the appendix: Histology.
Lining: Columnar cells showing dysplasia, usually low-grade.
Contents: Mucin.
Adenocarcinoma of the appendix: Gross pathology.
Forms a mass that may be confined to the base of the appendix or that may expand so as to obliterate the appendix.
Adenocarcinoma of the appendix: Histology.
Mucinous cystadenocarcinoma: Mucinous cystadenoma with invasion.
Nonmucinous adenocarcinoma: Identical to that of colonic adenocarcinoma.
Pseudomyxoma peritonei:
A. Causes.
B. Composition.
A. Benign or malignant neoplasms of the appendix.
B. May contain almost no cells.
Pseudomyxoma peritonei: Predictors of worse prognosis (4).
Diffuse distribution.
Malignant primary tumor.
Cellular mucus.
High-grade dysplasia or malignancy.
Pseudomyxoma peritonei: Typical causes of death (2).
Sepsis.
Bowel obstruction.
Not cancer.
Pseudomyxoma peritonei: Relevance to ovarian mucinous tumors (2).
Ovarian mucinous tumors can accompany pseudomyxoma peritonei.
The appendix is still the usual the source of pseudomyxoma peritonei.
Myxoglobulosis:
A. Significance.
B. Histology (2).
A. May be found in appendiceal mucoceles, including mucinous neoplasms.
B. Lamellated and often calcified; appendiceal lining may show pseudosynovial metaplasia.
Carcinoid tumors of the appendix: Variants.
Insular.
Tubular.
Goblet-cell.
Goblet-cell carcinoid: Synonyms.
Crypt-cell carcinoma.
Goblet-cell adenocarcinoma.
Goblet-cell carcinoid: Histology.
Cells that resemble mature goblet cells form discrete clusters, strands, and microglands.
Goblet-cell carcinoid: Immunohistochemistry.
Positive: Pancytokeratin.
Negative or focal: Neuroendocrine markers.
Goblet-cell carcinoid: Signs of differentiation into a carcinoma of higher grade (4).
Solid growth.
Complex infiltrative pattern.
Nuclear atypia with increased mitotic activity.
Dissecting mucus.
Tubular carcinoid: Immunohistochemistry.
Positive for neuroendocrine markers.
Often positive for glucagon.
Carcinoid tumor of the appendix vs. fibrous obliteration.
Fibrous obliteration: Neuroendocrine cells are few and scattered.
Tubular carcinoid vs. signet-ring carcinoma.
Signet-ring carcinoma:
− More infiltrative.
− More pleomorphism.
− More mitotic activity.
Carcinoid tumors of the appendix: Indications for right hemicolectomy (5).
Size greater than 2 cm.
Invasion beyond muscularis propria.
Vascular invasion.
Incomplete excision.
Coexisting adenocarcinoma.
Cancers that metastasize to the stomach:
A. Most common origins (3).
B. Endoscopy.
A. Melanoma, lung, breast.
B. Target-shaped lesion.
Pancreaticobiliary carcinoma vs. primary ampullary carcinoma (2).
Primary ampullary carcinoma:
− Usually arises in an adenoma.
− Better prognosis.
Cancers that metastasize to the small intestine:
A. Most common origin.
B. Endoscopy.
C. Another frequent metastasis.
A. Melanoma.
B. Obstructive mass.
C. Bronchogenic SCC to the proximal jejunum.
