Pathology of the Small Bowel

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Pathology of the Small Bowel

• Linan Wang, MD
• wanglx2_at_upmc.edu
• 12/14/04

NOTE This presentation was modified by Dr. Wang
12/14/2004 to include labels on images. JBM
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A Quick Review of Normal Anatomy

• 6-7 meters in length
• Duodenum (first 25 cm) is retroperitoneal and has
  no real mesentery
• Jejunum arbitrarily constitutes the proximal 40
  of introperitoneal portion
• Ileum the remainder
• Arterial supply mainly from celiac and superior
  mesenteric artery

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• Normal Small Bowel
• Gross Appearance
• Luminal Surface

Quick review
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A Quick Review of Normal Histology

• The wall of all parts of small intestine has 5
  layers mucosal, submucosal, muscular,
  subserosal, and serosal

• Mucosa
• Epithelium
• Lamina Propria

Muscularis mucosa
Lumen
Submucosa

• Muscularis Propria
• Inner circular
• Outer Longitudinal

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Things You Need to Remember If You Plan To Become
A Pathologist

• Villus-to-crypt height ratio is about 4 to 51
• Intraepithelial lymphocytes/ epithelial cells
  ratio is less than 20/100.
• Brunners gland is mainly located in duodenum
• Peyers patches in terminal ileum can be
  prominent

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Quick review Normal Small Bowel-Microscopic
Appearance
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General Concepts

• Main Function of the GI Tract
• To digest food and provide nutrients to the body
• Problems
• Portal of entry for infectious organisms
• Malfunction Malnutrition
• Susceptible to toxic injury
• Susceptible to vascular compromise (ischemia) and
  hemorrhage
• Normal mucosa is highly proliferative may make
  a mistake and lead to cancer

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General Concepts

• Histologic diagnosis primarily based on HE
  stained tissue sections
• Histochemical stains (based on chemical
  reactions) can help
• Giemsa stain highlights H. pylori
• Trichrome stain highlights fibrosis
• Immunohistochemical (IHC) stains are very helpful
  and specific (based on antigen-antibody
  reactions)
• Cytokeratin IHC stain highlights epithelial cells
• Chromogranin IHC stain highlights neuroendocrine
  cells

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Pathology Made Easy 8 General Pathologic
Processes

• Vascular
• Inflammatory Reactive/Infectious/Immunologic
• Trauma
• Anatomical/Congenital
• Metabolic/Nutritional
• Idiopathic
• Neoplastic
• Anything Else
• VITAMIN A

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My Approach to Reach Pathologic Diagnosis

• Gross appearance
• Microscopic appearance
• Architecture (low magnification)
• Cytology (high magnification)

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SMALL BOWEL Meckel Diverticulum

• Most common intestinal congenital anomaly (1-2)
• Clinically
• Incidental finding
• May present with GI bleeding or pain
• Embryologic remnant forming antimesenteric
  outpouching in terminal ileum (usually within
  85cm of the ileocecal valve)
• Lined by gastric, small intestinal and/or
  pancreatic-type tissue

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Meckel Diverticulum
Terminal Ileum
Meckel Diverticulum
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Meckel Diverticulum
Meckel Diverticulum
Ileum
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Meckels Diverticulum Histologic Appearance
Gastric Mucosa lining This diverticulum is
located in the small bowel but it is lined w/
gastric-like mucosa.
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SMALL BOWEL Anatomic/Congenital

• Major causes of intestinal obstruction, local
  ischemia / infarction
• Adhesions
• Intussusception bowel within bowel
• Volvulus twisting of the bowel
• Herniation
• Inguinal hernia
• Incisional hernia

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Four different types of small bowel obstruction.
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Small Bowel Intussusception
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Small Bowel Infarct
Mesentery
Small bowel
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Small Bowel Adhesion
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QUESTIONS???
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SMALL BOWEL Enterocolitis (Gastroenteritis)

• Diarrheal diseases of the bowel
• Infectious
• Usually acquired by ingestion (fecal-oral
  transmission).
• Necrotizing Enterocolitis
• AIDS Enteropathy
• Drug-induced injury
• Radiation-induced injury

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Pathology of Infectious Enterocolitis

• Viral common cause (not covered in this
  lecture)
• Bacterial
• Enteroinvasive organisms
• Yersinia enterocolitica
• Salmonella
• Campylobacter jejuni
• Toxin-producing organisms (not covered in this
  lecture)
• Vibrio Cholera
• Clostridium difficile (C. diff colitis)
• Ingestion of pre-formed toxin (not covered in
  this lecture)
• Staph aureus
• Clostridium botulinum
• Parasites / Protozoa

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Pathology of Infectious EnterocolitisBacteria

• Enteroinvasive organisms
• Proliferate, invade and destroy enterocytes
• Results in an ulcerative and inflammatory
  response
• Yersinia enterocolitica
• Produces mucosal ulceration, hemorrhage, bowel
  wall thickening
• Can enter Peyers patches and regional lymph
  nodes produce necrotizing granulomas
• Can mimic Crohns disease
• Can become systemic peritonitis, pharyngitis,
  pericarditis

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Yersinia Enterocolitis
Ileo-cecal valve (lesion)
Cecum (Normal)
Ileum (Normal)
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Yersinia Enterocolitis
Residual lymphoid Tissue
Fissure
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Pathology of Infectious EnterocolitisBacteria

• Salmonella (S. typhi, S. paratyphi)
• Pass though enterocytes
• Enter lamina propria, Peyers patches
• Produce endotoxins villus blunting, mucosal
  ulcerations
• S. typhi can enter blood and disseminate
  throughout the body typhoid fever
• Campylobacter jejuni
• Can cause villus blunting, multiple superficial
  ulcers, purulent exudate

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Salmonella Enterocolitis
Erosions
Normal Mucosa
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Salmonella Enterocolitis
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Salmonella Enterocolitis
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C. Jejuni Enterocolitis
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Pathology of Infectious EnterocolitisParasites /
Protozoa

• Worms (not further covered in this lecture)
• Roundworms
• Strongyloides, Ascaris, Hookworms
• Flatworms
• Tapeworms
• Flukes
• Protozoa
• Giardia
• Cryptosporidia
• Entamoeba histolytica
• Infects the colon (not further covered in this
  lecture)

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Entamoeba histolytica
Residual Epithelium
Ulcer
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Entamoeba histolytica
Engulfed RBCs
Amoeba
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Note RBCs w/in amoeba size of amoeba is many
timesthat of lymphocytes.
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Pathology of Infectious EnterocolitisProtozoa

• Giardia lamblia
• Intestinal protozoan (small bowel)
• Source Contaminated water
• Seen in hikers who do not sterilize their
  drinking water
• Produces diarrhea, malabsorption
• Pathology Extracellular, attaches to surface,
  normal or blunted villi with mixed inflammation
• Diagnosis
• Stool OP (ova parasites)
• Biopsy

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Giardia - EM
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Pathology of Infectious EnterocolitisProtozoa

• Cryptosporidia
• Intestinal protozoan (smallgtlarge bowel)
• Source
• Fecal-oral route, contaminated water
• Produces watery diarrhea, malabsorption in
  immunosuppressed patients
• Immunocompetent Short course (days)
• Immunosuppressed Can be life-threatening
• Pathology
• Oocysts attach to surface (merozoites released
  into cell are not seen histologically)
• Mixed inflammation
• Diagnosis
• Stool OP
• Biopsy

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Cryptosporidia
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Strongyloides
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EnterocolitisNecrotizing Enterocolitis

• A complication of prematurity and low birth
  weight
• Usually occurs within the first few days of age
• Primarily affects the terminal ileum and
  ascending colon (can involve entire small and
  large bowel in severe cases)
• Acute ischemic process with inflammation, edema,
  hemorrhage and necrosis affecting mucosa or full
  intestinal wall thickness
• Can cause gangrene and perforation

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Necrotizing Enterocolitis
Fibrous Band (Adhesion)
Necrosis of small and large bowel.
Consequent fibrous adhesion ? intestinal
obstruction.
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EnterocolitisAIDS (HIV) Enteropathy

• ?? Direct mucosal damage by HIV infection
• Symptoms watery diarrhea
• Differential Diagnosis infectious etiologies
• Parasites (Cryptosporidium)
• CMV
• Small bowel gt colon
• Nonspecific findings on biopsy
• Focal villous blunting
• Mildly increased lamina propria and
  intraepithelial chronic inflammation
• Apoptotic and mitotically active enterocytes

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EnterocolitisDrug-induced Intestinal Injury

• Small bowel mucosa can be directly injured by
  drugs
• Can lead to diarrhea, abdominal discomfort,
  malabsorption
• Most common agent NSAIDs
• Non-specific findings on biopsy
• Increased acute and/or chronic inflammation
  within the lamina propria
• Mild villus atrophy
• Superficial mucosal erosions
• If severe, can lead to ulceration / stricture
• Must not be confused with IBD

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EnterocolitisRadiation-induced Intestinal Injury

• Small bowel mucosa can be directly injured by
  radiation
• Acute injury Can produce diarrhea, abdominal
  discomfort, malabsorption
• Chronic injury Vague abdominal symptoms,
  malabsorption
• Ischemic-type findings on biopsy
• Acute Regenerative epithelial features, crypt
  loss, hemorrhage, edema, inflammation
• Chronic Architectural distortion, fibrosis,
  atypical stromal and endothelial cells

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Radiation-induced Intestinal Injury
Normal
Enteritis
Normal
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Radiation-induced enteritis
Severely blunted villi, hemorrhage (red)
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QUESTIONS???
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SMALL BOWEL Malabsorption Syndromes

• Abnormal absorption of fat, proteins, vitamins,
  carbohydrates, minerals, electrolytes and water
• Results from defective intraluminal digestion,
  terminal digestion, and/or transepithelial
  transport
• Consequences of malabsorption can affect many
  organ systems and produce various symptoms
• Diarrhea, steatorrhea, abdominal cramps/pain,
  weight loss
• Anemia
• Osteopenia
• Dermatologic processes
• Neuropathy

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Malabsorption Syndromes

• Most common in the USA
• Celiac disease
• Pancreatic insufficiency (not covered in this
  lecture)
• Inflammatory Bowel Disease (Crohns disease)
• Infection
• Cryptosporidiosis
• Giardiasis
• MAI
• Whipples disease
• Numerous other causes
• (see Robbins Table 18-8)

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Malabsorption SyndromesCeliac Disease

• AKA Celiac sprue, gluten sensitive enteropathy,
  nontropical sprue
• Immunologic process
• Patients form antibodies against gliadin (gluten)
  and other antigens in wheat products
• Leads to an immune response at the location where
  these antigens are encountered upon absorption
  in the small bowel
• Cell-mediated immunity with accumulation of
  intraepithelial cytotoxic T-cells and lamina
  propria helper T-cells
• Association with HLA DQw2 / HLA-B8 and northern
  European descent

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Malabsorption SyndromesCeliac Disease

• Clinical Features
• Diarrhea, anemia and weight loss
• Circulating antibodies
• anti-gliadin, anti-endomysial (tissue
  transglutaminase) and anti-reticulin antibodies
• Can present in infancy (failure to thrive)
• Many adults diagnosed in their 40s
• Treatment Gluten-free diet
• Long-term risk for lymphoma, especially if
  refractory to diet

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Malabsorption SyndromesCeliac Disease

• Pathology
• Grossly (endoscopically) may see Scalloped
  Folds
• Increased lamina propria lymphoplasmacytic
  inflammation
• Increased intraepithelial lymphocytes
• Villous blunting / mucosal atrophy / total loss
  of villi
• Crypt hyperplasia
• Affects proximal small bowel gt distal
• These features are NOT specific for Celiac
  disease (need correlation with serum antibodies)

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Celiac Disease Gross appearance Scalloped
folds
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Celiac Disease
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Malabsorption SyndromesTropical Sprue

• Unrelated to gluten ingestion
• Limited to tropics (living in or visiting)
• May be related to enterotoxigenic organisms (E.
  coli and haemophilus)
• Responds to antibiotics
• Have folate or vitamin B12 deficiency
• Variable morphology ranging from near-normal to
  severe diffuse enteritis

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Malabsorption SyndromesWhipple Disease

• Rare systemic condition often affects small
  bowel, CNS and joints
• Tends to occur in 30-40 y.o. white males
  (malefemale 101)
• Presents with diarrhea, malabsorption, arthritis,
  CNS complaints
• Lymphadenopathy and hyperpigmentation is common
• Caused by Tropheryma whippelii
• Responds to antibiotic therapy
• Small bowel biopsy
• Lamina propria macrophages stuffed with
  diastase-resistant PAS granules
• Immunohistochemical stain to T. whippelii is
  positive
• Rod-shaped bacilli seen by electron microscopy
• Similar macrophages can be seen elsewhere

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QUESTIONS???
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Malabsorption SyndromesInflammatory Bowel Disease

• Chronic, relapsing inflammatory disorders of
  unknown etiology (idiopathic)
• Crohns disease
• Regional enteritis
• Can affect entire GI tract
• Commonly affects the terminal ileum
• Ulcerative colitis
• Affects the colon mainly (not covered in this
  lecture)

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Crohns Disease

• Clinical features extremely variable
• Intermittent attacks of abdominal pain, diarrhea
  and fever
• May have extraintestinal manifestations
• Arthritis
• Sacroiliitis
• Primary sclerosing cholangitis
• Long-term complications
• Fibrosing strictures
• Fistulas
• Malabsorption
• Adenocarcinoma (5-6x risk)

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Gross Pathology of Crohns Disease

• Segmental thickening of the bowel wall
• Skip lesions
• Luminal narrowing
• Creeping fat
• Mucosal alterations
• Serpiginous linear ulcers
• Cobblestone appearance
• Deep fissuring ulcers
• Fistula / sinus tracts

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Crohns disease Gross appearance
Normal
Crohns
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Crohns diseaseCreeping Fat
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Crohns, Luminal Narrowing
Crohns
Normal
Thickened wall
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Crohns, Cobblestone Appearance
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Real Cobblestone Street
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Crohns, Aphthoid Ulcer
Aphthoid Ulcer
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Adenocarcinoma arising in Crohns
Normal
Polypoid Adenocar- cinoma
Crohns Stricture
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Histopathology of Crohns Disease

• Inflammation
• Mucosal
• Increased lamina propria acute and chronic
  inflammation
• Gland lift-off
• Acute cryptitis
• Occasional crypt abscesses
• Associated with muscularis propria hypertrophy
  and submucosal neuronal hyperplasia
• Transmural chronic inflammation
• Lymphoid aggregates throughout bowel wall and in
  the subserosa
• Ulceration usually abrupt transition to
  adjacent normal mucosa
• Superficial (shallow)
• Deep (fissuring)

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Histopathology of Crohns Disease (continued)

• Chronic mucosal damage (the hallmark of IBD)
• Architectural distortion
• Villus blunting
• Crypt branching
• Mucosal atrophy
• Pseudopyloric metaplasia
• Paneth cell metaplasia (in colon)
• Transmural fibrosis
• Granulomas seen in childrengtadults
• Noncaseating
• Transmural (mucosal, submucosal, intramural,
  subserosal)
• Also present within regional lymph nodes

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Crohns disease Histopathology
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Crohns disease Histopathology
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Crohns, Non-necrotizing Granuloma
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QUESTIONS???
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SMALL BOWELIschemic Injury

• Vulnerable to ischemic injury
• Arterial thrombosis
• Arterial embolism
• Venous thrombosis
• Hypoperfusion due to shock
• Can lead to bowel perforation and acute
  peritonitis (high mortality)

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SMALL BOWELIschemic Injury

• Gross features
• Can be well-demarcated
• Dusky and hemorrhagic
• Pathologic features
• Ischemic necrosis mucosal, mural or transmural

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Small Bowel Ischemia Gross appearance
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Small Bowel Mucosal Ischemia (Ischemic necrosis)
-Hypoperfusion -Early arterial occlusion
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Small Bowel Congestion and Ischemia - Venous
obstruction
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Cholesterol Emboli
Cholesterol Cleft
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SMALL BOWELAngiodysplasia

• Focal tortuous dilatation of mucosal and
  submucosal blood vessels
• Usually affects the right colon
• Difficult to detect if in the small bowel
• Good indication for wireless capsule endoscopy
• Rare, but account for 20 of lower GI bleed
• Pathogenesis speculative

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Gross Appearance of Angiodysplasia
Angiodysplasia
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Angiodysplasia (microscopic)
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Angiodysplasia (microscopic)
Epithelium
Vein
Artery
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SMALL BOWELPeptic Ulcer Disease

• Chronic ulcers due to exposure to peptic-acid
  juices in the
• Duodenum (1st portion)
• Stomach (antrum)
• Lower esophagus (GERD)
• Associated with hypersecretion of gastric acid
  and pepsin (except for peptic ulcers of the
  stomach)
• Associated with H. pylori infection
• Not a precursor of malignancy
• Clinically abdominal pain, melanotic stool, risk
  of hemorrhage

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• Peptic Ulcer Disease Duodenum
• Mucosal erosion with mixed inflammation
• Gastric foveolar metaplasia
• Focal Brunners gland hyperplasia

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QUESTIONS???
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SMALL BOWELTumors

• Metastatic tumors are most common
• Primary tumors are uncommon
• (most common)
• Adenomas
• Mesenchymal tumors (not covered here)
• Gastrointestinal stromal tumors
• Leiomyomas
• Adenocarcinoma (Ampulla of Vater)
• Carcinoid Tumors (Endocrine cell tumors)
• Tumor-like lesions
• Heterotopic gastric mucosa
• Heterotopic pancreas

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TumorsAdenomas

• Most often occur in ampulla of Vater and
  periampullary region
• Morphologically similar to those of the colon
  (villous, tubulovillous, villous)
• Large ones frequently undergo malignant
  transformation
• Can be associated with familial adenomatous
  polyposis (discussed in pathology of the colon)
• Composed of dysplastic (adenomatous) epithelium

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Small Bowel Ampullary Adenoma Gross Appearance
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Small Bowel Ampullary Adenoma
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TumorsAdenocarcinoma

• 0.4 per 100,000 per year median age 67
• Most arise in duodenum (ampullary region), more
  than jejunum and ileum combined
• Ampullary Adenocarcinoma
• May present with obstructive jaundice
• Often arises from pre-existing adenoma
• May be polypoid, infiltrating or stenosing grossly

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Small Bowel Adenocarcinoma
Benign Mucosa
Adenocarcinoma
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TumorsEndocrine tumors

• Arise from endocrine cells that can generate
  bioactive compounds (hormones)
• All are potentially malignant (most common
  malignant tumor of the small bowel)
• May be functional
• Gastrinoma Zollinger Ellison Syndrome
  duodenum
• Carcinoid syndrome diarrhea, flushing
• Nonfunctional terminal ileum
• Aggressive behavior correlates with (carcinoid
  tumor)
• Site of origin
• Tumors in ileum, stomach, and colon are
  frequently malignant and multicentric
• Tumors in duodenum tend to be low grade
• Tumors in appendix and rectum are rarely
  malignant
• Depth of local penetration (beyond submucosa)
• Size of tumor (gt 2 cm) aggressive and
  malignant-like when larger - metastases

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Tumors Endocrine tumors

• Usually small, well-defined submucosal
  elevations, often yellowish in color, covered by
  a flattened mucosa, which may ulcerate or form a
  polypoid projection
• Monotonous round cells with minimal mitotic
  activity or pleomorphism
• Immunostain positive for neuroendocrine markers
  (chromogranin, synaptophysin and neuron-specific
  enolase)

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Small Bowel Carcinoid Tumor
Benign
Carcinoid
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Small Bowel Carcinoid tumor
Carcinoid
Benign Mucosa
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TumorsMetastases

• By far the most common tumor in the small
  intestine (compared with primary small intestinal
  tumors)
• Mainly include metastatic melanoma, lung and
  breast carcinomas

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Small Bowel Metastatic Tumor Gross Appearance
Tumor
Benign
Tumor
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SMALL BOWELLymphoma

• Primary GI lymphomas exhibit no evidence of lymph
  node, spleen, or bone marrow involvement at
  diagnosis
• Tend to remain localized for prolonged periods
  before progressing
• Overall survival good compared with carcinoma
• May present with intussusception or malabsorption
  when there is diffuse involvement
• Types of GI Lymphomas
• MALT (mucosal associated lymphoid tissue)
  lymphoma
• Most common GI lymphoma
• Affects stomach gt small bowel gt colon
• B-cell origin
• Sprue-associated lymphoma
• Complication of long-standing malabsorption
  syndromes and refractory Celiac sprue
• T-cell origin

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Small Bowel T-cell lymphoma
Residual Epithelium
Lymphoma
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QUESTIONS???
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REFERENCE BOOK

• Kumar, Robbins and Cotran Pathologic Basis of
  Disease, 7th Edition