Summary Pathology of the Gastrointestinal tract

The Gastrointestinal Tract
[Congenital Abnormalities]


ESOPHAGUS
ESOPHAGEAL OBSTRUCTION
 Structural (mechanical) obstruction or functional obstruction (caused by disruption of peristaltic
contractions)
 Nutcracker esophagus: loss of coordination of inner circular layer and outer longitudinal layer
smooth muscle  high-amplitude contraction of the distal esophagus
 Diffuse esophageal spasm: repetitive and simultaneous contractions of distal esophagus
 Hypertensive lower esophageal sphincter: lower sphincter dysfunction (high resting pressure of
incomplete relaxation), WITHOUT altered patterns of contraction
 Esophageal dysmotility  epiphrenic diverticulum (above the lower sphincter)
 Impaired relaxation or spasm of the cricopharyngeal muscle  Zenker (or pharyngoesophageal)
diverticulum (above the upper sphincter)
o In ages >50 yo
o Can accumulate food  mass production  regurgitation and halitosis
 Mechanical obstruction causes: progressive dysphagia ( starts with inability to swallow solids)
 Esophageal stenosis (lumen narrowing): benign
o Caused by chronic gastroesophageal reflux or irradiation  inflammation and scarring
 fibrous thickening of the submucosa  atrophy of the muscularis propria and
secondary epithelial damage
 Esophageal mucosal webs
o Idiopathic ledge-like protrusions of the mucosa, composed of fibromuscular connective
tissue and overlying epithelium, semi-circumferential lesions
o In women >40 yo
o Associated with gastroesophageal reflux, chronic graft-versus-host disease or blistering
skin disease
o In the upper esophagus: mucosal webs + iron deficiency anemia + glossitis + cheilosis 
Paterson-Brown-Kelly or Plummer-Vinson syndrome
o Symptoms: nonprogressive dysphagia associated with incompletely chewed food
 Schatzki (or esophageal) rings:
o Circumferential lesions
o Include the mucosa, submucosa , and hypertrophic muscularis propria
o A rings: covered by squamous mucosa, located above the gastroesophageal junction
o B rings: contain gastric cardia-type mucosa, located at the squamocolumnar junction

ACHALASIA
 Triad: incomplete LES relaxation + increased LES tone + esophagus aperistalsis
 Normal relaxation of lower esophageal sphincter (LES) caused by: release of NO and vasoactive
intestinal polypeptides from inhibitory neurons, and interruption of normal cholinergic signaling
 Primary achalasia: distal esophageal inhibitory neuronal ganglion degeneration 
o Increased tone and inability to relax the LES
o Degeneration of the extraesophageal vagus nerve

, Secondary achalasia
o In Chagas disease, caused by Trypanosoma cruzi infection  destruction of myenteric
plexus, peristalsis failure, and esophageal dilation
o Associated immune-mediated destruction of inhibitory esophageal neurons: with HSV1
infection or Sjögren syndrome
 Treatment: laparoscopic myotomy, pneumatic balloon dilation, botulinum neurotoxin (Botox,
inhibit LES cholinergic neurons)

ESOPHAGITIS
LACERATIONS
 Mallory-Weiss tears:
o Longitudinal mucosal tears ranging from mm too cm, near the gastroesophageal
junction (Can also be located in proximal gastric mucosa
o Caused by retching and vomiting secondary to acute alcohol intoxication
o Causes upper GI bleeding (hematemesis)
 Boerhaave syndrome
o Less common, more serious
o Transmural tearing and rupture of distal esophagus
o Causes severe mediastinitis and severe chest pain (mistaken for MI)
o Requires surgery

CHEMICAL AND INFECTIOUS
 Damage of the mucosa caused by: alcohol, acids or alkalis (secondary to accidental ingestion of
household cleaning products by children), hot fluids, smoking
 Pill-induced esophagitis: mucosal injury caused by dissolved medication in the esophagus rather
than in the stomach, located at site of strictures
 Iatrogenic esophagitis: caused by chemotherapy, radiation therapy, graft-versus-host disease
 Symptoms: odynophagia (pain on swallowing), hemorrhage, stricture, perforation
 Infections mainly caused by HSV (in healthy individuals), also by CMV and fungi (in
immunocompromised)
 Histology
o Dense neutrophils infiltrates (but NOT in chemicals-induced injury)
o With irradiation: intimal proliferation and luminal narrowing of submucosal and mural
blood vessels (radiation-induced vascular damage)
o Infections: pathogenic organisms invade the lamina propria  cause ulcers (containing
nonpathogenic oral bacteria) and necrosis of overlying mucosa
o Candida: gray-white pseudomembrane (fungal hyphae and inflammatory cells covering
the mucosa)
o Herpes viruses  punched-out ulcers, nuclear viral inclusions with degenerating
epithelial cells at the margin of the ulcer
o CMV  shallow ulcerations, inclusions within the capillary endothelium and stroma cells
o G-V-H disease: basal epithelial cell apoptosis, mucosal atrophy, submucosal fibrosis, NO
inflammatory infiltrates

REFLUX ESOPHAGITIS
 Submucosal glands secrete mucin and bicarbonate  protect mucosa from acidity
 LES tone  prevents reflux of acidic gastric content
 Gastroesophageal reflux disease (GERF): most frequent cause of esophagitis
o Caused by decrease LES tone or increased intraabdominal pressure (coughing, bending,
straining)

, o Associated with alcohol, tobacco, obesity, CNS depressants, pregnancy, hiatal hernia
 Histology:
o Sometimes only hyperemia (redness)
o Eosinophils followed by neutrophils infiltration in the mucosa
o Basal zone hyperplasia (>20 % of epithelial thickness), elongation of lamina propria
papillae (extend into upper thirds of the epithelium)
 Clinical features
o Most common in individuals >40 yo
o Heartburn, dysphagia, and regurgitation of sour-tasting gastric content
o Chronic GERD: severe chest pain (mistaken for MI)
 Complications: ulceration, hematemesis, melena, stricture, Barrett esophagus
 Hiatal hernia:
o Symptoms similar to GERD: heart-burn, regurgitation of gastric juices
o Separation of diaphragmatic crura and protrusion of stomach into the thorax through
the resulting gap

EOSINOPHILIC ESOPHAGITIS
 Abundant intraepithelial eosinophils, mainly superficially
 Unlike GERD
o NO prominent acid reflux
o NO relief with high doses of proton pump inhibitors
 Atopic symptoms: atopic dermatitis, allergic rhinitis, asthma

ESOHAGEAL VARICES
 Portal hypertension  collateral channels (varices) development where portal and caval
systems communicate  submucosal (and subepithelial) congested venous plexus
 Caused by
o Cirrhosis associated with alcoholic liver disease
o Hepatic schistosomiasis
 Varices: dilated veins within the submucosa of the distal esophagus and proximal stomach
o Collapse in the absence of blood (not visible postmortem)
 Variceal rupture  hemorrhage into the esophageal wall  ulcerated and necrotic mucosa
o Lead to death most of the times
 Prophylaxis with beta-blockers  reduce portal blood flow  reduce risk of hemorrhage

BARRETT ESOPHAGUS
 Is a complication of GERD
 Intestinal metaplasia within the esophageal stratified squamous mucosa, with goblet cells
 Precursor lesion to cancer  increases the risk of developing esophageal adenocarcinoma
o But most individuals DO NOT develop esophageal tumors
 Histology
o Several patches of red/velvet mucosa extending upward from the gastroesophageal
junction
o Mucosa: alternation between pale squamous (esophageal) and brown columnar (gastric)
o Goblet cells: mucous vacuoles, pale blue on H&E stain
 When dysplasia is present
o Atypical mitoses, nuclear hyperchromasia, irregular clumped chromatin, increased
nuclear-to-cytoplasm ratio, no epithelial cells maturation
o High-grade: more severe cytologic changes, abnormal glands (irregular shapes, budding,
glands-within-glands or cribriform shapes)

,  Progress  epithelial cells invade the lamina propria --> intramucosal (invasive)
carcinoma




Arrow: transition from Barrett metaplasia to low-grade dysplasia (nuclear stratification and
hyperchromasia)
Gland-within-gland in high-grade dysplasia

ESOPHAGEAL TUMORS
 Adenocarcinoma or squamous cell carcinoma (more common)
 Leiomyoma: mesenchymal tumor, most common benign tumor of the esophagus
 Diagnosis usually takes place after lymphatic infiltration (late stage)

ADENOCARCINOMA
 Mainly arise from Barrett esophagus
 Most common in men
 Risk factors
o Obesity-related GERD  Barrett esophagus
o Tobacco use, radiations
 Reduced risk with:
o Diet rich in fresh fruits and vegetables
o H. pylori infection (cause gastric atrophy  reduced acid secretion and reflux  reduce
incidence of Barrett esophagus)
 Barrett esophagus  dysplasia  invasive carcinoma  + genetic and epigenetic mutations (in
early stages: TP53 mutation, and CDKN2A or p16/INK4a downregulation by hypermethylation)
 adenocarcinoma
 Histology
o In the distal third of the esophagus, and may involve the gastric cardia
o Flat or raised patches of around 5 cm in intact mucosa
o Barrett esophagus adjacent to the tumor
o Tumors produce mucin and form glands
o Infiltration of signet-ring cells (similar to diffuse gastric cancers)

SQUAMOUS CELL CARCINOMA
 Most common in men, >45 yo
 Risk factors:
o Alcohol, tobacco, consumption of hot beverages, Plummer-Vinson syndrome,
mediastinal radiations, diets poor in fruits or vegetables, consumption of fermented
milk (fungus-contaminated food)
o HPV infection
 Amplification of transcription factor gene SOX2, overexpression of cyclin D1, loss of function of
tumor suppressors (TP53, E-cadherin, NOTCH1)
 Histology
o In the middle third of the esophagus
o Well differentiated