Histopathology - Upper + Lower GI pathology Flashcards
Hirschsprung’s disease biopsy findings
Hypertrophied nerve fibres but no ganglia
Where is volvulus more likely to occur in
children
eldelry
children - small bowel
elderly - sigmoid colon
Where does diverticular disease occur more commonly?
90% occur in L colon
How does diverticular disease present in endoscopy
empty spaces - look at photo in lecture
Secretory diarrhoea vs exudative diarrhoea
secretory - toxin
exudative - invasion + mucosal damage
Histology of pseudomembranous colitis
Volcanic eruption of pus coming from the surface of the bowel at the mucosa
C. diff mx
Metronidazole (1)
Vancomycin (2)
Where is ischaemic colitis more likely to occur?
In watershed zones
Splenic flexure (SMA + IMA) Rectosigmoid (IMA + internal iliac artery)
CD pathology
Whole GIT can be affected (mouth to anus) – most common in terminal ileum + caecum (R side)
Skip lesions cobblestone appearance
Transmural inflammation – entire thickness of the bowel wall
Non-caseating granulomas – collections of macrophages but not necrotic or caseating (bottom L)
Sinus/fistula/fissure formation common
CD extra-intestinal manifestations
Arthritis
Uveitis
Stomatitis/ cheilitis
Skin
- Erythema nodosum
- Erythema multiforme
- Pyoderma gangrenosum
UC
Slightly more common than CD
Superficial inflammation confined to the mucosa
Bowel wall normal thickness
No granulomas
No abscesses/fissures/fistulae
Shallow ulcers
Pseudopolyps (islands of regenerating mucosa bulge into the lumen - can fuse to form mucosal bridges)
May see backwash ileitis + appendiceal involvement
bloody diarrhoea + mucus
crampy abdo pain relieved by defecation
Which conditions is UC associated with?
PSC
Adenocarcinoma
Toxic megacolon
UC mx
o Mild
o Moderate
o Severe
o For remission
o Mild – prednisolone + mesalazine (5 ASA)
o Moderate – prednisolone + 5- ASA + steroid enema BD
o Severe – admit, NBM, IVF, IV hydrocortisone, rectal steroids
o For remission – all 5-ASA (1st line), azathioprine (2nd line)
Carcinoid syndrome vs carcinoid crisis
Syndrome
- Bronchoconstriction
- Flushing
- Diarrhoea
Crisis
- Vasodilation
- Hypotension
- Tachycardia
- Bronchoconstriction
- Hyperglycaemia
caused by endochromaffin cell tumours which produce 5-HT commonly found in the bowel
Ix - 24h urine 5-HIAA (main metabolite of serotonin)
Mx - octreotide
Adenomas - RF for cancer
- Large adenoma (most important RF)
- Increased villous component
- Dysplasia
Tubular adenoma vs villous adenoma macroscopic appearance
Look at pics on ppt (week 15)
Villous adenoma looks like a line of test tubes
How does an adenoma progress to a carcinoma?
o Normal colon at risk mucosa after “first hit” mutation in 1st copy of APC (adenomatous polyposis coli) gene (those with FAP are born with this mutation)
o At risk adenocarcinoma after “second hit” mutation remaining APC gene
o Progression to carcinoma follows activation of
KRAS
LOF
Mutations of p53
Peutz Jeghers mutation
AD
LKB1
Familial syndromes implicated in lower GI disease
• Peutz Jeghers
• FAP – Familial adenomatous polyposis
o Gardner’s
o Turcot
• HNPCC – hereditary non-polyposis colon cancer
FAP buzzwords
• FAP – Familial adenomatous polyposis
Chr 5q21 APC tumour suppressor gene
At birth –> hypertrophy of the retinal pigment epithelium
Young people getting colorectal cancer
At least 100 polyps required for dx
Average - 1000 polyps –> will develop into adenocarcinoma if not resected
Prophylactic colectomy
increased risk of cancer elsewhere - ampulla of Vater, stomach
What is Gardner’s syndrome?
o Same clinical/pathological/etiologic features as FAP with high cancer risk
o Distinctive extra-intestinal manifestations
Multiple osteomas of skull + mandible
Epidermoid cysts
Desmoid tumours
Dental caries, unerupted supernumerary teeth
Post-surgical mesenteric fibromatoses
Most common hereditary colon cancer syndrome
HNPCC (hereditary non-polyposis colorectal cancer) / Lynch syndrome
HNPCC vs FAP
HNPCC is more common
In HNPCC there are few polyps, in FAP there are at least 100
In HNPCC there are multiple synchronous cancers (endometrium, ovary, small bowel, prostate, breast)
In HNPCC the mutation is in the DNA mismatch repair genes, in FAP the mutation is in the APC tumour suppressor gene
Both syndromes –> onset of colorectal cancer at an early age
Where are the carcinomas in HNPCC usually found?
R colon
proximal to the splenic flexure
Where is the mutation HNPCC ?
DNA mismatch repair genes
Which staging system is used to stage colorectal cancer?
A B1 B2 C1 C2 D
Duke’s staging system
A
Limited to mucosa
B1
Extends into muscularis propria, no lymph node involvement
B2
Transmural extension, no lymph node involvement
C1
Extends into muscularis propria + lymph node involvement
C2
Transmural extension + lymph node involvement
D
Distant mets
Colorectal cancer mx
o Caecum, ascending colon, proximal transverse
o Transverse colon
o Descending colon + distal transverse
o Sigmoid cancer
o Rectal cancer/low sigmoid cancer
<1-2cm above anal sphincter (lower 1/3 of rectum)
>1-2cm above anal sphincter
• If it’s a transmural invasion
o Caecum, ascending colon, proximal transverse R hemicolectomy
o Transverse colon extended R hemicolectomy
o Descending colon + distal transverse L hemicolectomy
o Sigmoid cancer sigmoid colectomy
o Rectal cancer/low sigmoid cancer
<1-2cm above anal sphincter (lower 1/3 of rectum) abdomino-perineal resection
>1-2cm above anal sphincter anterior resection
• If it’s a transmural invasion you will likely get radiotherapy, chemotherapy + excision
• What sort of colon polyps most commonly predispose to adenocarcinoma of the colon?
Adenomas
What is the z line?
the point at which the epithelium of the oesophagus transitions from being squamous (proximal 2/3) to being columnar (distal 1/3)
Where is H pylori gastritis usually found?
Antrum of the stomach + pyloric canal
Difference between the body and the antrum of the stomach
glands in lamina propria
body - specialised (secrete acid + enzyme, produce IF)
No goblet cells*
antrum - non-specialised, produce gastrin
- goblet cells are present in the intestine therefore presence of goblet cells in the stomach is a feature of intestinal metaplasia
Normal villus: crypt ratio
> 2:1
Layers of the oesophagus
o Epithelium muscularis mucosa submucosa with connective tissue + fat muscularis externa (muscularis propria)
Layers of the stomach
Mucosa (epithelium lamina propria muscularis mucosa) submucosa muscularis propria
How would you describe the epithelium of the normal duodenum?
Glandular epithelium with goblet cells
Villous: crypt ratio –> >2:1
Ulcer vs erosion
Ulcer = through muscularis mucosa (into submucosa)
Erosion = before muscularis mucosa, not past lamina propria (not into submucosa)
What is Barret’s oesophagus?
The same as columnar lined oesophagus (CLO)
• Replacement of squamous epithelium by
metaplastic columnar epithelium
without goblet cells: gastric metaplasia (CLO)
with goblet cells: intestinal type metaplasia (CLO with IM)
Risk: can lead to adenocarcinoma (metaplasia -> dysplasia -> cancer)
Define
metaplasia
dysplasia
cancer
1) Metaplasia = not pre-malignant because reversible (can progress to dysplasia)
(2) Dysplasia = changes showing some of the cytological and histological features of malignancy but with NO invasion through the BM (this is the stage that screening identifies at)
(3) Adenocarcinoma = abnormal cells invade through the BM
2 pathways to development of GI cancer
Adenoma-carcinoma pathway
o Lower GI
o Polyp pathway - adenomas becoming malignant
Metaplasia-Dysplasia patway
o upper GI pathway
o Oesophagitis/ chronic gastritis –.> Metaplasia (i.e. CLO ± IM) –> dysplasia –> cancer
Defining feature of SCC of the oesophagus
cells from keratin
(other histological features include:
Invasion of the submucosa
Cells have intracellular bridges)
SCC vs adenocarcinoma of the oesophagus
SCC
- Upper 2/3 of oesophagus (middle > lower > upper)
- Developing countries
- Smoking, Alcohol, HPV (16,18)
Adenocarcinoma
- lower 1/3 of oesophagus
- Developed countries
- GORD, Barrett’s
Histology of acute vs chronic gastritis
Acute = neutrophils
Chronic = lymphocytes, plasma cells
Causes of acute vs chronic gastritis
Acute
Chemicals
Infection
Chronic ABCD Autoimmune [body] Bacterial [antrum] Chemicals [antrum] IBD
What does presence of lymphoid follicles in a stomach biopsy indicate?
Highly suggestive that the patient has had an H. pylori infection (i.e. the presence of lymphoid follicles is not part of the normal stomach mucosa)
H. pylori infection induces the development of lymphoid follicles in germinal centres –> MALT –> lymphoma
o If someone has H. pylori as well as lymphoma, you will see crypts that are full of neutrophils good because if you treat H. pylori, the lymphoma could be reversed
Helicobacter strain associated with chronic inflammation + cancer
cag-A-positive H.pylori
Needle like
appendage –> injects toxin into intercellular
junctions –> bacteria attach more easily
2 types of cancer that arise from chronic stimulation by H pylori
- CLO-IM-Dysplasia in the stomach Adenocarcinoma (atrophic)
- Chronic infection Lymphoma (MALToma) (non-atrophic)
Types of ulcers in
- Antrum-predominant gastritis
- Body-predominant atrophic gastritis
- Antrum-predominant gastritis duodenal ulcer
* Body-predominant atrophic gastritis gastric ulcer
Gastric ulcer mx
All ulcers should be biopsied to exclude malignancy
Gastric vs duodenal ulcer
Gastric –> body of stomach, worse with food
Most are caused by H. pylori
Duodenal –> antrum of stomach, relieved with food
Almost all are cause by H. pylori
Duodenal ulcer 4x more common than gastric ulcer
Why does gastric intestinal metaplasia happen?
In response to long term damage
isn’t cancerous/pre-cancerous but can lead to dysplasia + is associated with an increased risk of cancer
in intestinal metaplasia there will be goblet cells
Commonest type of gastric cancer
Adenocarcinoma
Treatment of H pylori
CAP (Clarithromycin, Amoxicillin, PPI)
What are the two types of gastric adenocarcinomas?
• Intestinal
o Well-differentiated
o Mucin-containing big glands
o Big well-formed glands
• Diffuse
o Poorly differentiated
o Individual cancerous cells spread throughout the stomach
o Single cells with no attempt at gland formation
o Types = Linitis plastica, Signet ring cell carcinoma (spreads all over stomach)
What type of lymphoma is MALT
B cell NHL
How does H. pylori cause duodenal ulcers?
Almost all duodenal ulcers are caused by H. pylori
antrum predominant gastritis causes duodenal ulcers
H pylori –> antral infection –> increased stomach acid production –> acid spills over into duodenum –> chronic inflammation –> gastric metaplasia of the duodenal epithelium –> gastric epithelium in the duodenum can now become infected with H. pylori –> duodenitis + ulcer
Normal range of intraepithelial lymphocytes
<20 lymphocytes per 100 enterocytes
Coeliac disease classic histology findings
Villous atrophy (flattening/flat)
Normal villous: crypt ratio >2:1
Crypt hyperplasia
Increased intraepithelial lymphocytes
commonest cause = malabsorption
o Lymphocytes in coeliac disease are the cells that are causing damage to the villi
What is coeliac disease?
T cell mediated autoimmune disease
Abnormal T cell response to gliadin
DQ2 DQ8 HLA associations
young children, Irish women
Typical rash seen in coeliac disease
Dermatitis herpetiformis
How do you diagnose coeliac disease?
Antibodies + imaging + biopsy
Antibodies
- Anti-Endomysial (best sensitivity + specificity)
- Anti - TTG (also check IgA since these are IgA ab and IgA deficiency might give you a false negative result)
- Anti-gliadin ab
duodenal biopsy ON gluten free diet showing
Villous atrophy (flattening/flat)
Crypt hyperplasia
Increased intraepithelial lymphocytes
OFF gluten –> normal villi
Most serious complication of coeliac disease
Enteropathy associated T cell lymphoma (EATL)
type of NHL
found in the duodenum
(n.b. lymphomas in the stomach are due to H. pylori and are B cell lymphomas)
• Most oesophageal and gastric cancers arise from pre-existing adenomas – yes or no
o No – most gastric + oesophageal gastric cancers arise from a flat dysplasia pathway – chronic inflammation metaplasia dysplasia cancer
o This statement would be true for colonic tumours (adenoma-carcinoma pathway)
