(21) Pathology of the lower GI tract Flashcards
What is a diverticulum?
Outpocketing/protrusion of the colonic mucosa and submucosa through weaknesses of muscle layers in the colon wall
Give 3 types of diverticulosis
- sigmoid diverticulosis (acquired)
- diverticulosis of the right colon (acquired and congenital)
- giant diverticulum
What are the 2 classifications of diverticula
- congential
- acquired/false/pseudo
Whereabouts do diverticula occur most commonly?
Sigmoid colon
Diverticula are located between which taenia coli?
Located between the mesenteric and anti-mesenteric taenia coli
(also between the anti-mesteric taenia coli in 50% of cases)
How often do diverticula extend into the proximal colon?
Caecum = 15%
Describe the epidemiology of diverticulosis?
- common in the developed Western world
- rare in Africa, Asia and South America
- commoner in urban areas compared to rural areas
- changing prevalence in migrant populations
- relationship with fibre content of diet
- male = female
- less common in vegetarians
At what age is diverticulosis common?
Increases with age
Rare under the age of 40
40-60 = 10% >60 = 30% >90 = 50%
What are the 2 main points of pathogenesis behind diverticulosis?
- increased intra-luminal pressure
- points of relative weakness in the bowel wall
Increased intra-luminal pressure is part of the pathogenesis of diverticulosis. Give more detail
- irregular, uncoordinated peristalsis
- overlapping (valve-like) semicircular arc of bowel wall
Weakness in the bowel wall is part of the pathogenesis of diverticulosis. Give more detail
- penetration by nutrient arteries between mesenteric and anti mesenteric taenia coli
- age-related changes in connective tissue
Describe the pathology in diverticulosis
- thickening of muscularis propria
- elastosis of taeniae coli
- redundant mucosal folds and ridges
- sacculation and diverticula
What is the earliest change in diverticulosis?
Thickening of the muscularis propria = “prediverticular disease”
Elastosis of taeniae coli is part of what happens in diverticulosis. What does it specifically lead to?
Shortening of the colon
What percentage of diverticular disease is asymptomatic?
90-99%
What are the potential symptoms of diverticular disease?
- cramping abdominal pain
- alternating constipation and diarrhoea
also acute and chronic complications (10-30%)
What are the acute complications associated with diverticular disease?
- diverticulitis/peridiverticular abscess (20-25%)
- perforation
- haemorrhage
What are the chronic complications associated with diverticular disease?
- intestinal obstruction (strictures: 5-10%)
- fistula (urinary bladder, vagina)
- diverticular colitis (segmental and granulomatous)
- polypoid prolapsing mucosal folds
What is colitis?
Inflammation of the colon
What are the different classifications of colitis?
- usually mucosal inflammation
- occasionally transmural inflammation
- or predominantly submucosal/muscular inflammation
Also acute (day to weeks) or chronic (months to years)
Give an example of a transmural forms of colitis
Crohn’s disease
Give an example of a submucosal/muscular form of colitis
Eosinophilic colitis
Give 7 types of ACUTE colitis
- acute infective colitis
- antibiotic associated colitis
- drug induced colitis
- acute ischaemic colitis
- acute radiation colitis
- neutropenic colitis
- phlegmonous colitis
Give 3 organisms that can cause acute infective colitis
- campylobacter
- salmonella
- CMV
Give an example of an antibiotic-associated colitis
PMC (pseudomembranous colitis)
Name 2 classifications of acute ischaemic colitis
- transient
- gangrenous
Give 8 types of CHRONIC colitis
- chronic idiopathic inflammatory bowel disease
- microscopic colitis
- ischaemic colitis
- diverticular colitis
- chronic infective colitis
- diversion colitis
- eosinophilic colitis
- chronic radiation colitis
Give 2 classifications of microscopic colitis
- collagenous
- lymphocytic
Give 2 examples of chronic infective colitis
- amoebic colitis
- TB
Name 3 types of idiopathic inflammatory bowel disease
- ulcerative colitis
- crohn’s disease
- indeterminate colitis (10-15%)
What is the incidence of IBD?
UC = 5-15 cases per 100,000
CD = 5-10 cases per 100,000
Describe the geographical variation in IBD incidence
- incidence highest in Scandinavia, UK, Northern Europe, USA
- lowest in Japan, Southern Europe, Africa
What is the peak age of incidence of IBD?
20-40 years of age
Which gender is IBD most common in?
CD more common in females (3:1)
UC equally common in males and females
Incidence of UC is increasing in what type of areas?
Urban areas
How does cigarette smoking after risk of IBD?
UC = O.5 x (protective) CD = 2 x
How does oral contraceptive affect risk of IBD?
UC = 1.4 x CD = 1.6 x
Other than smoking and the oral contraceptive, give 4 other risk factors for IBD
- childhood infections
- MMR
- domestic hygiene
- appendicectomy
What is the risk of UC if 1st degree relative has UC? (IBD familial clustering)
8 x
What is the risk of CD if 1st degree relative has CD? (IBD familial clustering)
10 x
What is the risk of UC if 1st degree relative has CD? (IBD familial clustering)
3.8 x
What is the risk of CD if 1st degree relative has UC? (IBD familial clustering)
- 7 x
What is the typical clinical presentation of ulcerative colitis? (symptoms)
- diarrhoea (>66%) with urgency/tenesmus
- constipation (2%)
- rectal bleeding (>90%)
- abdominal pain (30-60%)
- anorexia
- weight loss (15-40%)
- anaemia
What are the complications associated with ulcerative colitis?
- toxic megacolon and perforation
- haemorrhage
- stricture (rare)
- carcinoma
What are the clinical features of Crohn’s disease?
- chronic relapsing disease
- affects all levels of GIT from mouth to anus
- diarrhoea (may be bloody)
- colicky abdominal pain
- palpable abdominal mass
- weight loss/failure to thrive
- anorexia
- fever
- oral ulcers
- peri-anal disease
- anaemia
Describe the distribution of Crohn’s disease?
- ileocolic (30-55%)
- small bowel (25-35%)
- colonic (15-25%)
- peri-anal/ano-rectal (2-3%)
- gastro-duodenal (1-2%)
Where in the GIT does Crohn’s most commonly occur?
Ileocolic region
What are the complications associated with Crohn’s disease?
- toxic megacolon
- perforation
- fistula
- stricture (common)
- haemorrhage
- carcinoma
- short bowel syndrome (repeated restriction)
Give the main differences in the distribution of UC and CD
- UC = affects colon, appendix and terminal ileum
- CD = affects all parts of the GI tract
- UC = continuous disease
- CD = skip lesions
Give the differences between UC and CD in terms of structures involved
- UC = rectum always involved
- CD = rectum normal in 50%
- UC = terminal ileum involved in 10%
- CD = terminal ileum involved in 30%
Describe the mucosa in UC vs CD
UC = granular red mucosa with flat, undermining ulcers
CD = cobblestone appearance with apthoid and fissuring ulcers
Describe the serosa in UC vs CD
UC = normal serosa
CD = serositis (fat wrapping)
Are the strictures in UC/CD?
UC = strictures rare
CD = strictures common
Are here fistulae in UC/CD?
UC = no spontaneous fistulae
CD = fistulae in >10%
How common are anal lesions in UC/CD?
UC = anal lesions in 25%
CD = anal lesions in 75%
What type of inflammation do you get in UC/CD?
UC = mainly mucosal inflammation
CD = transmural inflammation
Do you get crypt abscesses in UC/CD?
UC = crypt abscesses common
CD = crypt abscesses less common
Do you get crypt distortion in UC/CD?
UC = crypt distortion severe
CD = crypt distortion less severe
Do you get granulomas in UC/CD?
UC = granulomas absent
CD = sarcoid-like granulomas present in 60%
Do you get inflammatory polyps in UC/CD?
UC = inflammatory polyps common
CD = inflammatory polyps less common
Where might you get extra-intestinal manifestations of IBD?
- hepatic
- skeletal
- muco-cutaneous
- ocular
- renal
- haematological
- systemic
What are the potential hepatic manifestations of IBD?
- fatty change
- granulomas
- PSC
- bile duct carcinoma
What are the potential skeletal manifestations of IBD?
- polyarthritis
- sacro-ileitis
- ankylosing spondylitis
What are the potential muco-cutaneous manifestations of IBD?
- oral apthoid ulcers
- pyoderma gangrenosum
- erythema nodosum
What are the potential ocular manifestations of IBD?
- iritis/uveitis
- episcleritis
- retinitis
What are the potential renal manifestations of IBD?
- kidney stones
- bladder stones
What are the potential haematological manifestations of IBD?
- anaemia
- leucocytosis
- thrombocytosis
- thrombo-embolic disease
What are the potential systemic complications of IBD?
- amyloid
- vasculitis
What is the prevalence of colorectal cancer in ulcerative colitis?
3.7%
risk of CRC at 10 years = 2%, 20 years = 8%, 30 years = 18%
What is the prevalence of colorectal cancer in pancolitis (severe form of ulcerative colitis)?
5.4%
What are the risk factors for CRC in UC?
- early age of onset
- duration of disease >8-10 years
- total or extensive colitis
- PSC (primary sclerosing cholangitis)
- family history of CRC
- severity of inflammation (pseudopolyps)
- presence of dysplasia
What are the stages in the development of colorectal cancer in ulcerative colitis?
- inflamed mucosa
- low grade dysplasia
- high grade dysplasia
- colorectal cancer
As part of colitis surveillance, there should be CRC screening colonoscopy at 10 years. What would indicate lower risk?
- extensive colitis with NO ACTIVE endoscopic/histological inflammation
- OR left-sided colitis
- OR crown’s colitis of >50% colon
As part of colitis surveillance, there should be CRC screening colonoscopy at 10 years. What would indicate intermediate risk?
- extensive colitis with MILD ACTIVE endoscopic/histological inflammation
- OR post-inflammatory polyps
- OR family history CRC in FDR aged 50+
As part of colitis surveillance, there should be CRC screening colonoscopy at 10 years. What would indicate higher risk?
- extensive colitis with MODERATE/SEVERE ACTIVE endoscopic/histological inflammation
- OR stricture in past 5 years
- OR dysplasia in past 5 years declining surgery
- OR PSC/transplant for PSC
- OR family history CRC in FDR aged
What are colorectal polyps?
Mucosal protrusions, due to mucosal or submucosal pathology or a lesion deeper in the bowel wall
What are the different characteristics that colorectal polyps can have?
- solitary or multiple (polyposis)
- pedunculated, sessile or flat
- small or large
- neoplastic, hamartomatous, inflammatory or reactive
- benign or malignant
- epithelial or mesenchymal
Give 6 different types of non-neoplasic polyps in the colo-rectum
- hyperplastic polyps
- hamartomatous polyps
- polyps related to mucosal prolapse
- post-inflammatory polyps
- inflammatory fibroid polyps
- benign lymphoid polyps
Give 2 types of hamartomatous polyps
- Peutz-jeghers polyps
- Juvenile polyps
Give 3 polyps related to mucosal relapse
- inflammatory cloacogenic polyps
- inflammatory cap polyps
- inflammatory myoglandular polyps
What are post-inflammatory polyps also known as?
Pseudopolyps
Give some characteristics of hyperplastic polyps
- common
- 1-5mm in size
- often multiple
- located in rectum and sigmoid colon
- small distal HPs have NO malignant potential
Small distal hyperplastic polyps have NO malignant potential BUT…
Some large right sided hyperplastic polyps (sessile serrated lesions) may give rise to microsatellite unstable carcinoma (10-15% of all colorectal cancer)
Where are hyperplastic polyps located?
In the rectum and sigmoid colon
Give some characteristics of juvenile polyps
- often spherical and pedunculated
- 10-30mm
- commonest type of polyp in children
- typically occur in rectum and distal colon
- sporadic polyps have no malignant potential
What is the commonest type of polyp in children?
Juvenile polyp
Where do juvenile polyps typically occur?
Rectum and distal colon
Juvenile polyps are associated with increased risk of which cancers?
Colorectal and gastric cancer
What is Peutz-Jeghers syndrome also known as?
Hereditary intestinal polyposis syndrome
What is Peutz-Jeghers syndrome?
Inherited polyposis, characterised by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa
What type of genetic inheritance pattern does Peutz-Jeghers syndrome show?
Autosomal dominant
Peutz-Jegher syndrome involves a mutation in which gene?
STK11 gene on chromosome 19
What is the prevalence of Peutz-Jeghers syndrome?
1 in 50,000 - 1 in 120,000 births
How would a patient with Peutz-Jeghers syndrome typically present?
Present clinically in teens or 20s with abdominal pain (intussusception), gastrointestinal bleeding and anaemia
Give 2 features of Peutz-Jeghers syndrome
- multiple gastro-intestinal tract polyps (predominantly small bowel)
- muco-cutaneous pigmentation (1-5mm macules peri-oral, lips, buccal mucosa, fingers and toes)
Describe the typical distribution of polyps in Peutz-Jeghers syndrome
- small bowel (96%)
- colon (27%)
- rectum (24%)
- stomach (24%)
Polyps also described in gallbladder, urinary bladder and nasopharynx!
What are the 2 categories of neoplastic polyps?
- benign
- malignant
Give 5 benign polyps
- adenoma
- lipoma
- leiomyoma
- haemangioma
- neurofibroma
Give 6 malignant polyps
- carcinoma
- carcinoid
- leiomyosarcoma
- GIST
- lymphoma
- metastatic tumour
What are adenomas?
- benign epithelial tumours
- commonly polypoid but may be “flat”
Adenomas are a precursor of what?
Colorectal cancer (at least 80%)
Adenomas are present in what proportion of the population?
25-35% >50 years
Multiple in 20-30% of patients
Where are adenomas found?
Evenly distributed around the colon but larger in recto-sigmoid and caecum
Describe the macroscopic appearance of adenomas
Pedunculated, sessile or “flat”
What are the different architectural types of adenoma?
- villous
- tubulo-villous
- tubular
What is the histological grade of adenoma?
High vs low grade dysplasia
A small % of adenomas progress to what over an average of 10-15 years?
Adenocarcinoma
What gives an increased risk of adenoma undergoing malignant change?
- “flat” adenomas
- most malignant polyps are >10mm in size
- villous and tubulo-villous
- severe (high grade) dysplasia
- HNPCC associated adenomas
What is the lifetime risk of colorectal cancer?
1 in 18 - 1 in 20
What is the UK prevalence, incidence and mortality of colorectal cancer?
prevalence = 77,000 incidence = 35,300 mortality = 16,220
What are the risk factors for colorectal cancer?
- diet (dietary fibre, fat, red meat, folate calcium)
- obesity/physical activity
- alcohol
- NSAIDs
- HRT and oral contraceptives
- schistosomiasis
- pelvic radiation
- UC and CD
What is FAP?
Familial adenomatous polyposis - inherited condition in which numerous adenomatous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs when left untreated.
What kind of genetic pattern does FAP show?
Autosomal dominant
FAP makes up what percentage of colorectal cancer?
FAP is caused by a mutation in which gene?
APC tumour suppressor gene
HNPCC makes up what percentage of colorectal cancers?
1-2%
What kind of genetic pattern does HNPCC show?
Autosomal dominant
What is the lifetime risk of large bowel cancer in HNPCC?
50-70%
As well as colorectal cancer, there is an increased risk of which other cancers in HNPCC?
- endometrial
- ovarian
- gastric
- small bowel
- urinary tract
- biliary tract
HNPCC is caused by mutations in which gene?
DNA mismatch repair genes
Which site in the large bowel is cancer most likely to occur?
Rectum (29%)
Sigmoid colon (18%)
Caecum (13%)
Give 6 different types of colorectal cancer
- adenocarcinoma
- adenosquamous carcinoma
- squamous cell carcinoma
- neuroendocrine carcinoma & MANEC
- undifferentiated (large cell) carcinoma
- medullary carcinoma
Name a subtype of colorectal adenocarcinoma
Mucinous adenocarcinoma (10-20% of adenocarcinomas)
What is the most common type of colorectal cancer?
Adenocarcinoma (>95%)
How are colorectal cancers graded?
- well differentiated (10-20%)
- moderately well differentiated (60-80%)
- poorly differentiated (10-20%)
Give 5 different types of spread of colorectal cancer
- direct invasion of adjacent tissues
- lymphatic metastasis (lymph nodes)
- haematogenous metastasis (liver and lung)
- transcoelomic (peritoneal) metastasis
- iatrogenic spread
Give 2 examples of iatrogenic spread of cancer
- needle track recurrence
- port site recurrence
Give 2 examples of staging systems used (colorectal cancer)
- Dukes stage
- TNM stage
What does staging of cancers do ?
- may be clinical (imaging) or pathological
- describes extent of local and distant tumour spread
Name the main 5 layers of tissue
- mucosa
- submucosa
- muscularis propria
- subserosa
- serosa
A tumour involving the peritoneal surface would be what stage?
pT4a
What does Dukes stage A mean?
Adenocarcinoma confined to the bowel wall with no lymph node metastasis
What does Dukes stage B mean?
Adenocarcinoma invading through the bowel wall with no lymph node metastasis
What does Dukes stage C mean?
Adenocarcinoma with regional lymph node metastasis regardless of depth of invasion
What does Dukes stage D mean?
Distant metastasis present
How frequent are the different stages of cancer using Dukes staging?
A = 10-20% B = 30-40% C = 40-50% D = 15-25%
What are the 5 year survival rates for the different stages of cancer using Dukes staging?
A = >90%
B = 60-80%
C = 40-50%
D =
