Small Bowel

Question 1

What are some important small bowel parasites?

Answer 1

Protozoa:

• Giardia
• Cryptosporidia

Fungi

• Microsporidia

Bacteria:

• Tropherma whipplei (Whipples disease)
• E. Coli

Flatworm:

• Schistosoma

Question 2

Describe Giardia

Answer 2

• Trophozoites (protozoan)
• Pear-shaped
• Binucleate (“Monkey face”)
• Faintly basophilic
• Seen between villi, classically in duodenum
• Does not invade
• Sometimes mild villous blunting and IELs
• Looks like falling leaves in the bowel lumen
• Aquired from contaminated water, faeco-oral route, sexually transmitted
• More commen in children, travel and immunocompromised
• Diarrhoea/Malabsorption - watery and foul-smelling

INVESTIGATIONS:
* Stool - cysts
* PCR

STAINS:
* Masson’s Trichrome
* Giemsa
* CD117+

TREATMENT:
* Metronidozole

Question 3

Des

Describe Cryptosporidia

Answer 3

• Protozoan
• Most common - C. Hominis, C. Parvum
• Acute, watery diarrhoea
• Can last up to four weeks, relapsing and remitting
• Located at apex of epithelial cells along luminal border - dot-like organisms
• Small bowel most common site
• Also colon, stomach, biliary tree, respiratory tract
• Seen in children and immunocompromised patients
• Usually correlates with CD4 counts < 100
• Faeco-oral route
• Basophilic
• Villous blunting
• Mixed inflammatory infiltrate

STAINS:
* Modified Acid-Fast (AFB)
* Giemsa

TREATMENT:
* Nitazoxanide

Question 4

Describe Microsporidia

Answer 4

• Obligate intracellular organism
• Enterocytozoon bieneusi - best seen in electron microscopy
• Usually seen in the setting of AIDS
• Jejunum shows highest parasitic burden
• Bifringent spores seen as intra epithelial inclusions
• Lamina propria macrophages

INVESTIGATIONS:
* Stool examination
* PCR
* Electromicroscope

STAINS:
* Giemsa
* ZN can highlight spores

Treatment:
* Albendazole

Question 5

Describe Whipple Disease

Answer 5

• Bacterial infection
• Tropherma whipplei
• Small bowel –> Oesophagus –> Stomach –> Appendix –> Colon
• Malabsorption, diarrhoes, arthralgias, pain, neurological symptoms, lymphadenopathy
• Lamina propria expanded by foamy macrophages

STAINS:
* PAS +ve
* AFB -ve

Associated with HLA-B27

Question 6

Describe Schistosomiasis

Answer 6

• Mansoni, japonicum, mekongi, hematobium. intercalatum
• Contaminated water in endemic areas
• Focal ulcers
• Eggs may be calcified, surrounded by fibrosis/granuloma

INVESTIGATIONS:
* Eggs in faeces or urine
* Wet mount/Formalin ethyl acetate

TREATMENT
* Praziquantel

Question 7

Describe E. Coli

Answer 7

• Enterohaemorrhagic E. coli - 0157:H7
• Shiga toxin interferes with protein synthesis –> causes cell damage
• Contaminated food
• Most self-limiting
• Can cause** haemolytic-uremic syndrome **and thrombocytopenic purpura

Micro:
* Mucosal haemorrhage, infarct, pseudomembranes
* Neutropholic infiltrates, cryptitis, crypt abscesses

Diagnosis:
* Serotyping
* PCR
* DNA hybridisation
* E coli O157:H7 –> detected from stool culture with selective growth media

Question 8

Describe Coeliac Sprue

Answer 8

• Immune mediated
• Caused by sensitivity to prolamins - Wheat (gliadin), Barley (hordein), Rye (secalin), Oats (avenin)
• Duodenum > Ileum

Associated with:

• **Autoimmune diseases **- Dermatitis herpetiformis, T1SM, Hashimotos, Graves)
• Idiopathic diseases - Dilated cardiomyopathy, epilepsy, MS
• Chromosomal diseases - Downs, Turner, William

Can lead to:

• Iron deficiency anaemia (microcytic)
• B12 deficiency (macrocytic anaemia)
• Osteopenia/Osteoporosisa - altered absorption of calcium and vitamin D3
• Growth retardation, tooth enamel defects, stomatitis, hypertransaminasemia

Aetiology:

• HLA DQ2 (98%)
• HLA DQ8
• Ingestion of gluten

Microscopy:

• Shortening of villi (villous atrophy)
• Intraepithelial lymphocytes (>30 per 100 enterocytes or >12 in villous tips)
• Loss of brush border at surface of epithelium
• Increased mitotic activity in crypts
• Crypt elongation and hyperplasia
• May see thickened subepithelial collagen band (collagenous sprue is refractive to treatment with no antibodies)

Classification:

• Marsh Classification
• Based on: IEL, Crypts (normal or increased), Villi (atrophy)
• 0 (normal) to 3c (Destructive)

IHC:
* 70% intraepithelial lymphocytes express CD8

DIAGNOSIS:

Histology of duodenal biopsy and serology

• tTGA (tissue transglutaminase) - highest sensitivity
• EMA (endomysial antibody) - almost absolute specificity
• AGA (IgA class antigliadin) 0 now obsolete

PROGNOSIS:

• Excellent prognosis with gluent free diet
• Enteropathy associated T cell lymphoma in small bowel - seen in pateints with long lasting, well controlled coeliac
• Increased risk of small bowel adenocarcinoma

Question 9

Describe Tropical Sprue

Answer 9

• AKA Post infective sprue
• May be caused by E. coli or haemophilus
• Tropics (not jamaica), africa, india
• Causes malabsorption within weeks of acute diarrheal enteric infection
• **Ileum **> Duodenum
• No increased risk to intestinal lymphoma

Treatment:

• Broad spectrum antibiotics (tetracycline)
• Folic acid
• Vitamin B12

Question 10

Describe CVID

Answer 10

• Common Variable Immunodeficiency syndrome
• Primary immune defect
• Reduction in B cells, causing hypogammaglobulinemia (IgG)
• IgA or IgM deficiency
• Frequent infections, recurrent giardiasis

Manifestations:

• Recurrent respiratory infections
• Chronic lung disease (bronchiectasis)
• Autoimmune disease’
• GI disorders

Micro:

• Absence of plasma cells in the lamiba propria (but can be present in some cases)
• Lymphoid aggregates
• Mild villous blunting
• Increased IELs
• May see Giardia

Treatment:

• Immunoglobulin replacement therapy

Question 11

Describe Abetalipoproteinaemia

Answer 11

• Rare autosomal recessive disorder
• Interferes with normal absorption of fat and fat-soluble vitamins

Symptoms:

• Diarrhea
• Steatorrhea
• Ataxia (Posterior column of spinal cord involved)
• Retinitis pigmentosa

Aetiology:

• MTP deficiency - mutation in microsomal triglyceride transfer protein

Micro:

• Marked fat vacuoles in apical villous cytoplasm
• Normal villi

Lab Features:

• Acanthocytosis on periperal blood smears (burr cells)
• Decreased serum cholesterol
• Low levels of LDL and VLDL
• Low Triglycerides
• Increased high-density lipoprotein cholesterol levels

Treatment:

• High doses Vitamin E

Question 12

Describe Microvillous Inclusion Disease

Answer 12

• AKA Davidson’s disease or Congenital microvillus atrophy
• Autosomal recessive
• Disorder of intestinal brush border
• Intractable watery diarrhoea with steatorrhoea in infants
• Require TPN
• Rarely live beyond 2 years of age

AETIOLOGY:
* Mutations in the MYO5B gene
* Small amount have STX3 gene mutations

MICRO:
* severe villous abnormality and crypt hypoplasia
* Resembling coeliac sprue without lymphocytosis
* Increased enterocyte apoptosis and proliferation
* Bubbly vaculated apical cytoplasm
* Extensive or patchy absence of brush border
* Definitive diagnosis on electron microscopy - shows microvillus inclusions

IHC:
* PAS
* CD10

CD10 and PAS stain positive within the enterocytes (cytoplasmic staining).
Normal should just be linear brush border staining,

• CEA

Question 13

Describe Diaphragm disease

Answer 13

• Small bowel pathology related to NSAID use

Macro:

• Small bowel with multiple tight short diaphragm like strictures caused by prominent raised fold of bowel.
• Ulceration at crests of the folds.

Micro:

• Thin circumferential membranes
• Resemble plica circularis
• Composed of mucosa and submucosa with accompanying fibrosis

Treatment:

• Cessation of NSAIDs

Question 14

Describe Small bowel Adenomas

Answer 14

INTESTINAL TYPE
* Similar to tubular adenoma of colon

FOVEOLAR
* Tubulovillous architecture
* Characteristic mucinous cap
* Prone to high grade dysplasia

PYLORIC GLAND
* Tightly packed tubules
* Monolayer of cuboidal cells with granular eosinophilia cytoplasm
* NO spivsl mucinous cap

Duodenum is most prone to developing adenomas

Molecular:

• Non-ampullary duodenal adenomas (60%) —> associated with FAP or MUTYH-associated polyposis

Question 15

Describe Gangliocytic Paraganglioma

Answer 15

• Rare tumour of periampullary region
• Second part of the duodenum
• Unencapsulated
• Submucosal

Three characteristic cell types:
* Epithelioid
* Spindle-shaped
* Ganglion-like

• Ususally benign
• 7% can metastasise

IHC:

Epithelial cells
* CD56
* Synaptophysin
* Chromogranin-A
* Somatostatin
* Progesterone receptor
* Pancreatic polpeptide

Ganglion cells
* CD56
* Synaptophysin
* Chromogranin-A
* Somatostatin
* Pancreatic polpeptide
* S100

Spindle cells
* S100
* BCL2

Question 16

Describe Enteropathy-Associated T-Cell Lymphoma

Answer 16

Features of coeliac disease
* Increased IELs
* Crypt Hyperplasia
* Villous atrophy

• T-Cell lymphoma that occurs in coeliac disease
• Jejunum > Ileum/Duodenum
• Stronger association with** refractory disease **
• Aggressive clinical course

Micro:

• Pleomorphic infiltrate
• Medium to large sized neoplastic cells
• Angular nuclei, anaplasia, mitotic figures, necrosis

Molecular:

• Clonal TCR gene rearrangement

IHC:

Positive
* CD3
* CD7
* CD30
* CD103
* Perforin
* Granzyme B

Negative
* CD20
* EBER

Loss of some T cell markers:
* CD2
* CD4
* CD5
* CD8

Question 17

Describe Follicular Lymphoma, Duodenal-Type

Answer 17

• Lymphoma derived from follicular B lymphocytes
• Ususally affects second part of duodenum
• May involve jejunum and ileum
• Confined to mucosa/submucosa
• No systemic involvement
• Excellent prognosis
• Local treatment
• Indolent course
• <10% progress to nodal disease

Micro:

• Almost always low grade (grade 1 - 2)
• Lamina propria infiltrated
• Neoplastic follicles lack tingible body macrophages and mantle zones

Molecular:
* t(14;18)

IHC:
* CD10+
* CD20+
* BCL2+
* Low Ki-67

Question 18

Describe Well-Differentiated Neuroendocrine Tumours

Answer 18

• Majority of tumours are non-functioning

Functional:

Gastrinoma
* Gastrin expressing NET in duodenum
* Causes Zollinger-Ellison syndrome - hypergastrinaemia, peptic ulcer, diarhoea
* Associated with MEN type 1

Somatostatinomas
* Somatostatin expressing NET in the ampulla
* Psammoma bodies
* Causes Diabetes, stones, diarrhoea
* Associated with Neurofibromatosis 1

Carcinoid syndrome
* Occurs when liver mets present
* Diarrhoea, bronchospasm, flushing, tricuspid valve fibrosis

Micro:
* Monotonous tumour cells
* Round/oval nuclei
* Salt and pepper chromatin
* Trabecular, nested, corded, ribbons, acinar and/or pseudoglandular architecture

Grading:
1: <2 mitoses/2mm, Ki-67 <3%
2: 2-20 mitoses/2mm, Ki-67 3-20%
3: >20 mitoses/2mm, Ki-67 >20%

IHC:

• AE1/3+
• Cam5.2+
• CK7-
• CK20-
• Chromogranin A+
• Synaptophysin+