Foregut Pathology Flashcards
Normal esophagus appearance
o Stratified squamous epithelium
• Basal layer forms 15% of thickness
o Submucosa = has glands; rich in lymphatics
o Striated muscle in upper 1/3 and smooth muscle in lower 2/3
Esophageal varices
See dilated veins
Reflux esophagitis
Most common cause of esophagitis
• Usually adults >40; occasionally children
May be erosive or non-erosive
Symptoms: heart burn, regurgitation, painful swallowing
Histology:
• Basal cell hyperplasia (>20% epithelial thickness)
• Vascular congestion
• Extension of papillae toward surface (into upper 1/3 or epithelium)
• Acute inflammatory cell infiltrate (lymphocytes, eosinophils, neutrophils)
Complications: • Erosion and Ulceration • Squamous Papilloma • Strictures • Barrett’s Esophagus (develops in ~10% patients)
Eosinophilic esophagitis
o Children are likely to have a clinically identifiable allergic cause
o Adults typically DO NOT have a clinically identifiable allergic cause
o Dysphagia in 63%
Histology: • Prominent intraepithelial eosinophils (25 or more in any HPF) • Eosinophilic microabscesses • Basal cell hyperplasia • Intercellular edema • Lamina propria fibrosis
Candida esophagitis
- Most common cause of infectious esophagitis
- Common to see combination infections with CMV or HSV esophagitis
- NOTE: fungal invasion is a requirement for diagnosis since Candida is normal flora in GI tract
Histology:
• Matted pseudohyphae and budding spores in squamous debris (top layer)
Herpes esophagitis
- 2nd most common cause of infectious esophagitis (after Candida)
- Usually an opportunistic infection in immunosuppressed / AIDS patients but also affects young immunocompetent children
- Ulcer with necrotic debris and exudate with neutrophils
Viral inclusions are present in multinucleated squamous cells at margin of ulcer
• Cowdry type A: dense eosinophilic intranuclear and cytoplasmic inclusions with thickened nuclear membrane and clear halo (early stage infection)
• Ground-glass inclusions that fill the nuclei (ulcerative stage)
CMV esophagitis
- Usually immunocompromised patients
- Inclusions are numerous but may be atypical in HIV patients
- Virus present in enlarged endothelium and stromal cells at ulcer base
- Basophilic cytoplasm often has coarse intracytoplasmic granules
- Prominent intranuclear basophilic inclusions surrounded by clear halo (“Owl’s Eye”)
Barrett’s esophagus
Metaplastic change of squamous mucosa to columnar cell type (intestinal type with goblet cells)
Criteria:
• Abnormal epithelium at endoscopy above manometric/anatomic GEJ
• Histologic evidence of columnar epithelium with goblet cells on biopsy
Complications of BE:
Increased risk of esophageal adenocarcinoma
• BUT: <1% of patients with BE develop esophageal adenocarcinoma each year
Carcinoma arising in BE may be multifocal and is preceded by dysplastic lesions:
• Low-grade dysplasia = nuclei still in basal half of cell
• High-grade dysplasia = nuclei in apical part of cell; usually more irregular and round
• Both = show mucus depletion and prominent cytoplasmic basophilia
Esophageal adenocarcinoma
o More common in U.S.
o Malignant epithelial tumor with glandular differentiation
o Most common in the distal esophagus
Gross appearance:
• Flat or raised patches
• Masses >5 cm can develop
• Tumors can infiltrate diffusely or ulcerate and invade deeply
Histology:
• Well-differentiated:
• Neoplastic cells are arranged in glands
• Mucin-producing
• Resemble intestinal carcinomas
• Often have foci of BE with dysplasia nearby
• Rarely = cases have diffusely infiltrative signet-ring cells or small poorly differentiated cells
Risk factors:
• Chronic reflux
• Barrett’s esophagus (majority of cases arise from BE)
• Also: obesity, tobacco use, male gender, prior radiation therapy, Caucasian race
Squamous cell carcinoma
Most common type worldwide
• High incidence areas: Northern China, Iran, Russia, Finland, France, Switzerland
• Low incidence areas: United States and Canada
Malignant epithelial neoplasm with squamous differentiation
o Carcinoma of middle and upper 1/3rd of esophagus
Gross: • Exophytic (protruding mass) • Excavated or ulcerative type • Flat (diffuse infiltrating form that spreads within the wall → thickening, rigidity and luminal narrowing) Precursor lesion is dysplasia
Histology:
Well-differentiated carcinomas: tumor appears to resemble normal stratified epithelium
• May produce keratin (see keratin pearls = whorled pink structures)
Poorly differentiated carcinomas: disorganized sheets of cells
o Male to Female ratio is ~4:1
o Risk factors include: alcohol and tobacco
Spread:
• Via lymphatics
• Local invasion of mediastinal structures
• Regional lymph nodes
Acute gastritis: causes and histology
Causes:
• Drug: Ethanol, aspirin/NSAIDs, steroids,
• Bile acids, uremia, shock, stress (trauma/burns/surgery)
• Other acute infectious gastritides (streptococci, E. coli, virus, etc.)
Gross appearance:
• Edematous mucosa, usually covered with large amounts of mucus
• Small hemorrhages and erosions
o Most common in pylorus and antrum (along lessor curvature)
Histology Mild: o Modest edema in lamina propria o Slight vascular congestion o Intact epithelium o Scattered neutrophils Severe: o Erosion and hemorrhage in mucosa
Chronic Helicobacter pylori gastritis
Gross:
o Redness of gastric mucosa
o Mild nodularity
Histology
o Superficial lamina propria: lymphocyte and plasma cell infiltrates
o Lymphoid aggregates with germinal centers = nodular appearance
o Neutrophils show active infection
o May develop mucosal atrophy
o Intestinal metaplasia with goblet cells
o May see H. pylori on surface epithelium or deep within gastric pits
Complications:
o Peptic ulcer
o Gastric adenocarcinoma
o MALT lymphoma
Autoimmune chronic gastritis
< 10% of cases of chronic gastritis
• Women more often affected than men (~3:1)
• 90% have autoantibodies to parietal cells, while 60% have anti- intrinsic factor antibodies
o Anti-parietal cell antibodies are to the K+/H+ ATPase proton pump
• Loss of parietal cells → hypo/achlorhydria and loss of intrinsic factor
• Low acid → gastrin release → hyperplasia of antral G-cells
• Low intrinsic factor disables intestinal Vit B12 → pernicious anemia
Gross:
o Red, slightly depressed areas with atrophy on gastric body/fundus
o Antrum may have focal erosions
Histology:
o Deep lymphoplasmacytic infiltrates within lamina propria
o Glandular damage and atrophy in gastric body/fundus
o Often extensive intestinal metaplasia
o H. pylori organisms are almost never identifiable
Complications:
o Carcinoid tumors
o Epithelial dysplasia → adenocarcinoma
Peptic ulcer
Most common location = 1st part duodenum; also in gastric pylorus/antrum
Gross:
• Round to oval shape
• Sharply punched out defect
• Variable depth
Histology:
• Acute: acute necrosis with underlying zone of granulation tissue (budding young capillaries and proliferating fibroblasts) and zone of collagen deposition with healing
• Chronic: scar tissue
Complications:
• Perforation leading to peritonitis
• Deep penetration into pancreas, liver or omentum
• Duodenal ulcers can penetrate posteriorly into trunk of gastroduodenal artery leading to life- threatening hemorrhage
• Scarring and stricture leading to gastric outlet obstruction
Gastric Carcinoma
o Most common = pyloric area; along the lesser curvature
o Tumors can be fungating, ulcerating, nodular or linitis plastica-type
Histology:
Intestinal type:
• Exophytic, may undergo ulceration
• Resembles colon adenocarcinoma; gland-forming
Diffuse type:
• Diffuse, plaque-like thickening; luminal narrowing; may involve entire stomach (linitis plastica)
• Infiltrating single cells; some have signet-ring features
• Can become metastatic → ovary (Krukenberg tumor)
