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Pathology of the Esophagus


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Pathology of the Esophagus,,,,,,,,,,,,,,,,,,,,,,,,by urs Dr N.D

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Pathology of the Esophagus

  1. 1. Pathology of the esoPhagus Presented by: Dr Barkam Nagaraju MD(General Medicine)
  2. 2. Outline of Content • • • • • • • • Normal anatomy and histology Congenital and acquired malformations Lesions associated with motor dysfunction Esophagitis Barrett esophagus Esophageal varices Benign neoplasms and tumor-like lesions Malignant neoplasms and staging
  3. 3. Normal anatomy/physiology Muscular tube from pharynx (C6) to esophageal-gastric junction, about 25 cm long • Endoscopy: defined as 15-40 cm from incisor teeth • Two areas of increased intraluminal pressure that normally remain contracted at rest: • Upper esophageal sphincter: 3 cm segment at cricopharyngeus muscle • Lower esophageal sphincter (LES): 3-5 cm segment of thickened smooth muscle around diaphragmatic esophageal hiatus, just proximal to histologic EG junction •
  4. 4. Normal Histology and Pathologic Correlations • • • • • • • Mucosa: nonkeratinized squamous; basal zone is 10-15% of thickness Lymphocytes: CD8 T cells in epithelium; CD4 T cells and B cells in lamina propria Muscularis mucosa: smooth muscle between mucosa and submucosa Submucosal mucous glands: mainly proximal & distal esophagus Muscularis propria: skel. muscle upper 1/3 (voluntary swallow); sm. muscle lower 1/3; middle 1/3 mixed Myenteric nerve plexus: between circular inner and longitudinal outer layers of muscularis propria Serosa: mostly absent, facilitating spread of invasive tumors or infections into mediastinum
  5. 5. Esophageal-gastric junction Normal smooth gray-white squamous mucosa of esophagus 3 parts of mucosa? 1) mucosa submucosa 2) muscularis propria 3)
  6. 6. Congenital & Acquired Malformations Ectopias Atresias Stenoses Duplications Webs and Rings
  7. 7. Congenital Malformations  Ectopias; About 4% of persons by endoscopic exam  “inlet patch” of gastric-type epithelium replaces squamous, just below upper esophageal sphincter • Atresias; atresia = segment reduced to thin cord, no lumen • • 1/1000 live births • • usually near tracheal bifurcation, usually with associated tracheal-esophageal fistula • • mechanism: failed septation of foregut • • symptoms: regurgitation, paroxysmal choking, aspiration of liquid into lungs
  8. 8. Ectopic gastric mucosa Endoscopy: red patch within otherwise gray mucosa Biopsy: normal appearing gastric-type mucosa
  9. 9. Atresia and tracheoesophageal fistula: 5 types Which two cause paroxysms of coughing upon baby’s first feeding? B A ________ Which one is the most common type, and causes immediate regurgitation upon baby’s first feeding? _________ C D E All need immediate surgical correction
  10. 10. Congenital & Acquired Malformations  Stenoses:(narrowing of a duct or passage)Usually acquired due to chronic gastro-esophageal reflux, radiation, or ingested caustic substances; result in progressive dysphagia  Duplications: • congenital duplication cysts of 60% occur in lower esophagus  • Lined by epithelium (squamous, gastric, or respiratory type) with smooth muscle wall  • Imaging studies: differential diagnosis includes other thoracic cysts (bronchogenic, thymic, thyroidal)
  11. 11. Acquired Malformations • Webs: • usually women > 40 years old • web: a mucosal fold (2-4 mm thick) • which protrudes into the lumen, causing dysphagia with solid foods • Plummer-Vinson syndrome • dysphagia due to upper esophageal web + Fe deficiency anemia + glossitis • • mucosal abnormalities: glossitis and angular stomatitis (mouth) secondary to mucosal atrophy associated with Fe lack • in P-V syndrome, chronic iron-deficiency anemia precedes development of web, but how or whether Fe deficiency causes the web to form is controversial • associated with increased risk for squamous carcinoma in oral cavity, hypopharynx, and esophagu
  12. 12. WEB Glossitis with angular stomatitis
  13. 13. Plummer-Vinson syndrome: potential sequela upper esophageal web Endoscopic view of esophagus: ulcerated and nodular mass What is the most likely What is the most likely diagnosis for this mass diagnosis for this mass lesion? lesion? Courtesy
  14. 14. Schatzki’s Ring Circumferential ring in lower esophagus near EG junction; thicker than webs (may contain hyperplastic muscularis propria)  dysphagia barium swallow esophagram endoscopic view
  15. 15. Lesions affecting motor function Achalasia Zenker diverticulum Sliding hiatal hernia Epiphrenic diverticulum Rolling hiatal hernia MalloryWeiss tear
  16. 16. Diverticula Definition: outpouching comprised of all visceral layers (mucosa, submucosa, muscularis) • Sites: hypopharynx, thoracic, epiphrenic • Pathogenesis • Congenital: embryologic defect • Traction: fibrous scarring of soft tissue adherent to serosa, pulling wall of esophagus outward • Pulsion: unclear mechanism; potentially weak area at junction of pharyngeal constrictors (Killian’s triangle) allowing diverticulum to develop in response to increased intraluminal pressure. •
  17. 17. Zenker’s Diverticulum • • • • • • 27 cases described in 1877 by Zenker & Ziemssen Most common esophageal diverticulum Pathogenesis: pulsion explanation favored (increased pressure in lumen forces tissue through weak spot in muscle layer) Location: hypopharynx of older persons (superior to upper esophageal sphincter) May become large and sequester food, with regurgitation or mass effect in the neck Treatment: surgical resection of larger lesions
  18. 18. Zenker’s Diverticulum (pulsion) Barium swallow esophagram Resection of upper esophagus
  19. 19. Less common diverticula • • Traction • Usually small, mid-esophagus • Few symptoms • Pathogenesis: uncertain; motor disorder or postinflammatory fibrosis Epiphrenic • Just above LES, may be wide-mouthed; 1-10 cm. diameter • Pathogenesis: majority of patients have motility disorder (achalasia or diffuse esophageal spasm) • Symptoms: nocturnal regurgitation of large volumes of fluid • Treatment: resection large ones; address motor disorder
  20. 20. Epiphrenic diverticulum
  21. 21. Achalasia • Swallowing disorder defined by 3 major problems • Aperistalsis • Incomplete relaxation LES with swallowing • Increased resting tone of LES (impaired relaxation) • Pathogenesis: normally, distal inhibitory neurons and interruption of cholinergic signals allow relaxation of LES. Degenerative failure of inhibitory neurons  impaired relaxation. Usually primary (idiopathic), but also secondary to malignancy, amyloidosis, sarcoidosis, Chagas disease • Symptoms: • progressive dysphagia; nocturnal regurgitation of food • Treatment: surgical myotomy with balloon dilation of LES • Sequelae: • 5% develop squamous carcinoma • epiphrenic diverticulum, aspiration pneumonitis
  22. 22. Achalasia Pathology: progressive dilation of esophagus, proximal to an abnormal segment which is functionally denervated
  23. 23. Hiatal Hernia • • • • • Definition: pouch of proximal stomach extending >2cm above diaphragmatic hiatus into thorax Incidence: VERY COMMON, 15-50% adults (depending on strictness of definition); incidence increases with age Types • Sliding: 95%; stomach and esophagus bulge through hiatus together • Paraesophageal: 5%; stomach alone herniates adjacent to esophagus Complications • Reflux esophagitis (to be discussed) • Incarceration: more likely in paraesophageal; uncommon in sliding Treatment: surgery for paraesophageal HH; degree of morbidity determines medical vs. surgical therapy for sliding
  24. 24. Hiatal Hernia, sliding type Anatomy: widened space between muscular crura of diaphragm and wall of esophagus Pathogenesis: unknown; possible congenital weakness (some children have HH) combined with acquired defect Symptoms: Only 10-20% of adults with anatomically demonstrable sliding HH have “heartburn” (substernal pain caused by regurgitation of gastric juices into esophagus)
  25. 25. Lacerations (Mallory-Weiss syndrome) • Def: linear lacerations in mucosa near EG junction • Pathogenesis: presumably mechanical trauma due to prolonged retching; failure of E-G muscular relaxation • Risk factors: EtOH binges; prolonged vomiting • Pathology: mucosal defect of variable depth • Complications: mild to massive hemorrhage, ulceration or perforation, mediastinitis, rarely rupture of esophagus (Boerhaave syndrome) • Therapy: usually supportive because bleeding often stops spontaneously. May need endoscopic coagulation, balloon tamponade, or rarely surgery.
  26. 26. Mallory-Weiss laceration Endoscopy: laceration straddling the squamo-columnar junction Surgical resection of distal esophagus and proximal stomach for uncontrolled hemorrhage caused by Mallory-Weiss laceration
  27. 27. Esophagitis Reflux Esophagitis Infectious Esophagitis Chemical/Physical Esophagitis Eosinophilic Esophagitis Eosinophilic Esophagitis
  28. 28. Reflux esophagitis • • • • • • Def: mucosal injury secondary to reflux of acidic gastric contents into lower esophagus; clinical term is GERD (gastroesophageal reflux disease) Incidence: 5% U.S. adults (millions of people!) Clinical features: “heartburn”, chest pain mimicking MI, regurgitation, dysphagia Complications: ulceration, stricture, Barrett’s metaplasia Pathogenesis: decreased LES tone or increased abdominal pressure Risk factors • sliding hiatal hernia • delayed gastric emptying ⇒ increased gastric volume • obesity • CNS depressant drugs; EtOH abuse, smoking
  29. 29. Histopathology of Reflux Esophagitis Evidence of mild acute injury: • Reactive squamous hyperplasia • Scattered eosinophils or neutrophils within mucosa PBD 8th ed, Elsevier 2010 More severe acute reflux injury: mucosal ulceration Evidence chronic reflux injury: • basal zone hyperplasia (early) • Barrett intestinal metaplasia (later) Chronic Reflux: hyperplastic basal layer comprises > 20% of mucosal thickness (normal basal layer is < 20% of mucosal thickness)
  30. 30. • most commonly seen in immunocompromised patients • three organisms comprise >90% esophageal infections 1) Candida: Endoscopy shows white patches Silver stain: pseudohyphae in squamous mucosa 2) Herpes simplex, ground glass nuclei, intranuclear inclusions in squamous cells, multinucleated cells 3) CMV, large intranuclear basophilic inclusions in endothelial or stromal cells; dot-like cytoplasmic inclusions
  31. 31. Infectious Esophagitis • most commonly seen in immunocompromised patients • three organisms comprise >90% esophageal infections 1) Candida: Endoscopy shows white patches  Silver stain: pseudohyphae in squamous mucosa
  32. 32.  2) Herpes simplex, ground glass nuclei, intranuclear inclusions in squamous cells, multinucleated cells
  33. 33.  3) CMV, large intranuclear basophilic inclusions in endothelial or stromal cells; dot-like cytoplasmic inclusions
  34. 34. Chemical/Physical Esophagitis Causes: Ethanol abuse, heavy smoking Acid or alkali (accidental or suicide attempt) Very hot tea Chronic uremia Chemotherapy Post-radiation therapy for tumors Post-arsenic ingestion Post-radiation Therapy (stricture)
  35. 35. Eosinophilic Esophagitis  Path: abundant intraepithelial eosinophils  Symptoms: dysphagia (adults); reflux-like (children)  Associations: hypersensitivity (atopic dermatitis, allergic rhinitis, asthma)  Peripheral blood eosinophilia  Must prove absence of reflux to make this diagnosis Fig. 17-5B, PBD 8thth,2010 Fig. 17-5B, PBD 8 , 2010
  36. 36. Barrett esophagus (BE) • Definition (2 criteria): • • • (1) endoscopic evidence of abnormal mucosa above EG junction (clinical criterion) (2) intestinal metaplasia of squamous mucosa in biopsies of esophagus (pathologic criterion) Pathogenesis • Precise molecular mechanisms unclear • Acid reflux ⇒ inflammation⇒ chronic mucosal injury ⇒ metaplasia into more acid-resistant epithelium • Clinical: BE develops in 10-20% those with symptomatic chronic reflux esophagitis; usually presents ages 40-60 after years of chronic GERD. • MAJOR CONCERN: a minority of patients with BE develop epithelial dysplasia which may progress into adenocarcinoma. Life-long risk of adenocarcinoma is 10-15% in patients with BE, but this risk is 40x that of general population!
  37. 37. Barrett gross pathology: red granular mucosa Metaplasia = gray hatched areas Long segment (>3cm) Short segment (< 3cm, near EG jct) Long segment
  38. 38. Natural History of Barrett Esophagus Not completely predictable, but well-studied • Four histopathologic categories predict risk for future development of adenocarcinoma • Negative for dysplasia (intestinal metaplasia only) • Indefinite for dysplasia (unclear: inflammation or dysplasia) • Low-grade dysplasia • High-grade dysplasia • Some things are known • Low-grade dysplasia progresses to high-grade within 5 years in 10-30% patients. ** • Many low-grade dysplasias are not present on subsequent endoscopic biopsies (regression or sampling error?) * • High-grade dysplasia progresses to invasive adenocarcinoma in 30-60% patients within 5 years. ** • * Sharma, Barrett’s Esophagus, NEJM 361:2548, 2009 ** Spechler, Barrett’s Esophagus, NEJM
  39. 39. Barrett esophagus: histopathology 1 Diagnosis: intestinal metaplasia, negative for dysplasia Diagnosis: intestinal metaplasia, indefinite for dysplasia (reactive inflammatory changes vs. lowgrade dysplasia
  40. 40. Barrett’s: histopathology 2 Diagnosis: intestinal metaplasia with low grade dysplasia Diagnosis: intestinal metaplasia with high grade dysplasia
  41. 41. Proposed Treatment Algorithm for Patients with Barrett's Esophagus Sharma P. N Engl J Med 2009;361:2548-2556
  42. 42. Esophageal Varices • Definition: permanently dilated submucosal veins • Pathogenesis • Normal venous circulation: GI tract to liver to inferior vena cava • Chronic portal venous hypertension ⇒ development of collateral bypass channels (portal venous blood diverted into esophageal plexus, then azygos veins, then superior vena cava) • Clinical setting: cirrhosis with portal venous hypertension • Clinical presentation • • 40% die during first bleeding episode • If survive first episode, 50% re-bleed in one year • • No symptoms until varices rupture!! Cause of death: hypovolemic shock ⇒ multi-organ failure Rx: replace intravascular volume, give packed RBCs, stop bleeding
  43. 43. Esophageal varices: pathology Dilated blue varices beneath intact squamous mucosa Hemorrhage secondary to ruptured varices (KMC autopsy) EG junction
  44. 44. Benign neoplasms & tumorlike lesions • Esophageal benign neoplasms are mostly of mesenchymal origin (non-epithelial): leiomyomas, lipomas, hemangiomas, neurofibromas. • Two distinctive lesions: • Fibrovascular polyp • Squamous papilloma
  45. 45. Esophageal Carcinoma  •Squamouscell carcinomas •Adenocarcinomas •Worldwide, squamouscell carcinomas constitute 90% of esophageal cancers, but in the United States there has been a very large increase (three-to fivefold in the last 40 years) in the incidence of adenocarcinomas associated with Barrett esophagus.
  46. 46. SquamousCell Carcinoma  •Mucosal epithelial dysplasia •Carcinoma in situ •Invasive cancer •Polypoidexophyticmasses that protrude into the lumen; •Necrotizing cancerous ulcerations that extend deeply and sometimes erode into the respiratory tree, aorta, or elsewhere; •Diffuse infiltrative neoplasms
  47. 47.  A,Large ulcerated squamous cell carcinoma of the esophagus. B,Low power view of cancer invasion of the submucosa. A B
  48. 48. Adenocarcinoma    •Barrett esophagus is the only recognized precursor of esophageal adenocarcinoma. •Large nodular masses •Deeply ulcerative •Diffusely infiltrative features •Mucin-producing glandular tumors Clinical Features •Esophageal carcinoma is insidious in onset and produces dysphagiaand obstruction gradually and late. •Weight loss, anorexia, fatigue, and weakness appear, followed by pain, usually related to swallowing. •Diagnosis is usually made by imaging techniques and endoscopic biopsy. •Surgical excision is rarely curative. •Esophageal cancer confined to the mucosa or submucosais amenable to surgical treatment.
  49. 49. Fibrovascular polyp Presentation: dysphagia; lesion usually in upper 1/3 esophagus Histopathology: abundant vascularized connective tissue covered by squamous mucosa Is this a neoplasm or exuberant hyperplasia?
  50. 50. Squamous papilloma Low magnification: fronds of thickened squamous epithelium supported by connective tissue cores Some have HPV-related cytologic changes or evidence of HPV DNA by in-situ hybridization methods If squamous papilloma identified, respiratory tract should be examined for HPV-related papillomatosis (especially children)
  51. 51. Malignant neoplasms of esophagus: overview Malignant tumors of esophagus comprise 6% of all gastrointestinal cancers, but account for 10% GI cancer mortality • Problem: often asymptomatic until late, when they are deeply invasive or already metastatic • Worldwide: 90% squamous / 10% adenocarcinoma • U.S.: 50% squamous / 50% adenocarcinoma; incidence of adenocarcinoma rising steadily since 1970, almost always arising in Barrett esophagus •
  52. 52. Squamous Carcinoma Descriptor Adenocarcinoma M:F = 4:1; high incidence Iran, China, Puerto Rico (environmental initiators) Epidemiology M:F = 7:1; >95% from Initiators: environmental carcinogens; promoters: nutritional deficiencies (vitamins A, B1, B2, B6, trace metals) Pathogenesis Barrett dysplasia: Ethanol, tobacco, achalasia, chronic esophagitis, PlummerVinson syndrome Clinical Risk Factors chronic reflux esophagitis tobacco, obesity 20% upper third 50% middle third 30% lower third Anatomic Distribution >95% lower third 5 yr. survival: 5-10% --75% 5 yr. survival if T1 lesion --25% 5 yr. survival for all cases subjected to surgery Prognosis 5 yr. survival: 25% >80% 5 yr. survival with esophagectomy for T1 lesion Barrett metaplasia; <5% from submucosal glands early mutation or overexpression of p53; amplfication cERB-B2, cyclin D, cyclin E
  53. 53. Staging esophageal carcinoma
  54. 54. Squamous carcinoma: putative carcinogenesis Fig. 1.21, Tumors of Digestive System, IARC Press, 2000.
  55. 55. Squamous CA: gross pathology Exophytic polypoid (obstructing lesion) Ulcerated stricture (dysphagia) Early, superficial T1 lesion, good prognosis
  56. 56. Adenocarcinoma: gross pathology Barrett associated adenocarcinoma: circumferential papillary lesion (left) ulcerated polypoid lesion (right)
  57. 57. Adenocarcinoma: early invasive lesions developing in setting of high grade dysplasia High-grade dysplasia with single dysplastic cell invading lamina propria (intramucosal adenocarcinoma = T1) Adenocarcinoma invading submucosa, T1 lesion (circled), arising in Barrett intestinal metaplasia with high-grade dysplasia (right half) left photo courtesy University of Washington department pathology; right photo courtesy University of Pittsburgh
  58. 58. Invasive Adenocarcinoma arising in Barrett esophagus Intestinal metaplasia with dysplasia (red) Malignant glands invading into submucosa (black) Fig. 17-11B, Pathologic Basis of Disease, 7th ed, Elsevier 2005