Pathology of the Bowel Flashcards
What are the two different examples of IBD?
Ulcerative colitis
Crohn disease
What is an example of inflammatory intestinal diseases?
Inflammatory bowel disease
What are examples of colonic polyps and neoplastic diseases?
Non-neoplastic
Neoplastic
What is the histology of the normal colonic mucosa?
It has crypts containing abundant goblet cells that secrete mucin
What else is present in normal histology of the colon?
Underlying submucosa
Small nodules of gut-associated lymphoid tissue
What is IBD?
It is a chronic condition
Complex interactions of a genetically susceptible host, defective mucosal barrier, intestinal dysbiosis, and dysregulated immune response
What is the result of IBD?
Inflammation of the bowel
What are the main types of IBD?
Crohn Disease and ulcerative colitis
What is the incidence of Crohn disease?
70 to 150 per 100000 people per year
Which areas of the GIT does Crohn involve?
Any area of the GIT
Frequently transural
What is the incidence of ulcerative colitis?
20 to 40 per 100000
Which areas does ulcerative colitis affect?
Colon and rectum only
Which layers does ulcerative colitis extend to?
Into mucosa and submucosa
What is one of the causes of IBD?
It is unknown but it can be familial
What is the distribution like of both IBD types?
Crohn –> skip lesions
UC –> Diffuse
What is the stricture like of both IBD types?
Crohn –> yes
UC –> rare
What is the bowel wall appearance of both IBD types like?
Crohn –> thick
UC –> thin
What is the inflammation like in both IBD types?
Crohn –> transmural
UC –> mucosa and submucosa
What are the pseudopolyps of both IBD types like?
Crohn –> moderate
UC –> marked
What are the ulcers in both IBD types like?
Crohn –> Deep, knife-like
UC –> superficial, broad-based
What is the lymphoid reaction in both types od IBD like?
Crohn –> marked
UC –> moderate
What is fibrosis like in both types of IBD like?
Crohn –> marked
UC –> mild to none
Which IBD type has serosistis?
Crohn
Which IBD type has granulomas?
Crohn (35%)
Which IBD type has fistulas?
Crohn
In which IBD type is there fat/vitamin malabsorption?
Crohn
What is the malignant potential of both IBD types, like?
Crohn –> if the colon is involved
UC –> yes
What is the recurrence after surgery with both types of IBD?
Crohn –> common
UC –> no
Which IBD type can have the clinical presentation of toxic megacolon?
UC
What is the genetic risk associated with Crohn?
NOD2
Autophagy related genes (ATG16L1, IRGM)
What is the pathogenesis when it comes to the genetic risk of Crohn?
Ineffective at defending against intestinal bacteria
Bacteria are able to enter through the epithelium into wall of intestine
Trigger inflammatory reactions
What is the mucosal immune response like in IBD?
TH1 type is well recognised in Crohn
TH2 is well recogenised in UC
What mediates TH1?
IL12,
IFN-γ
TNF
What mediates TH2?
Natural killer cells
What are the epithelial defects of IBD?
Disease-associated NOD2 polymorphisms
Barrier dysfunction can activate innate and adaptive mucosal immunity
What factors modify the composition of the microbial population?
Diet and disease
What is the pathogenesis of IBD?
Repeated cycle by which transepithelial flux of luminal bacteria components activate innate and adaptive immune responses
What is the pathogenesis of IBD like in a susceptible host?
Subsequent release of TNF and other immune signs
Directs epithelia to increase tight junction permeability
Further increases the flux of luminal material
Establish a self-amplifying cycle in which a stimulus at any site may be sufficient to initiate IBD
Explain the pathogenesis of IBD (from the diagram) ?
Bacterial components enter the cell, Caught up by dendritic cells
IL23 is released, also IL8 is released and secretes neutrophils
HLA2-TCR connection is made and casues T cell proliferation (TH17, TH2, TH1)
IL23 activates TH17 cells which secrete Il17 and recruit neutrophils
TH2 secrete IL13
T cells become TH1 through IL12, and they then secrete IFN-γ which recruits macrophages
TNF and IL13 act on epithelial barrier
What are the macroscopic features of Crohn? (5)
Regional enteritis
Skip lesions
Aphthous ulcer
Cobblestone appearance
Fissures
Where does regional enteritis arise?
Any area of the GIT
1. Small intestine –> 40%
2. Small intestine & colon –> 30%
3. Colonic involvement only –> 30%
What are skip lesions?
The presence of multiple & separate areas of disease
What is an aphthous ulcer?
Edema and loss of normal mucosal folds
What is the cobblestone appearance?
Diseased tissue is depressed below the level of normal mucosa
Where do fissures usually develop with Crohn?
Between mucosal folds and may extend deeply to become sites of perforation or fistula tracts
What are the macroscopic features of Crohn?
- Intestinal wall is thickened
- Intestinal lumen is narrowed (early cases) and combination of edema and fibrosis (long standing cases)
- Nodular swelling, fibrosis and mucosal ulceration –> cobblestone appearnce
- Extensive transmural disease –> mesenteric fat frequency extends around serosal surface
What causes stenosis of intestinal lumen in early cases of Crohn?
Edema
What are the microscopic features of Crohn’s?
Crypt abscess
Ulceration
Repeated cycles of crypt destruction
What are crypt abscesses?
Abundant neutophils that infiltrate and damage crypts
What are the results of repeated cycles of crypt destruction?
Distortion of mucosal architecture
Epithelial metaplasia
Paneth cell metaplasia
Noncaseating granulomas
Where does Paneth cell metaplasia occur?
Occur in the left colon (distal colon)
What are the complications of Crohn’s? (6)
Intestinal obstruction
Stricture formation
Perineal disease fluid & electrolyte balance
Malnutrition from malabsorption
Abscess formation
Fistula formation
What is the most common type of small bowel fistula caused by Crohn’s?
Enterocutaneous fistula (opening between the small bowel and the skin)
Which regions of the GIT are affected by UC?
Limited to the colon and rectum
Are skip lesions seen in UC?
Not seen, focal appendiceal or cecal inflammation occasionally may present
What is pancolitis?
Disease of the entire colon
What is ulcerative proctitis?
Disease limited to the rectum or rectosigmoid region
What is back wash ileitis?
Mild mucosal inflammation of the distal ileum
What is the appearance of back wash ileitis like?
Lumpy-bumpy appearance
Which structures does proctitis involve?
Only the rectum
Which structures does proctosigmoiditis involve?
Involves the rectum and sigmoid colon
What structures are involved in distal colitis?
Involves only the left side of the colon
What structures are involved in the pancolitis?
Involves the entire colon
Which structures are involved in the backwash ileitis?
Involves the distal ileum
In what cases may backwash ileitis be present in?
Severe cases of pancreatitis
What are the gross features of the colonic mucosa seen in UC?
Slightly red (erythema)
Granular appearing
Extensive broad-based ulcers
Where are broad-based ulcers located in the large intetsine?
Aligned along the long axis of the colon
What are pseudo polyps, and when are they seen?
A gross feature of UC is isolated instances of regenerating mucosa often bulge into the lumen to create small elevations
What are the gross features of UC in chronic disease?
Mucosal atrophy
Smooth muscle surface lacking normal folds
What are the gross features of UC in fulminant disease?
Colonic dilation & toxic megacolon, which increases the risk of perforation
What causes the gross features of the fulminant disease?
Inflammation and inflammatory mediators can damage the muscularis propria and disturb neuromuscular
What are the histological features of UC that are similar to the ones of Crohn?
Inflammatory infiltrates
Crypt abscesses
Crypt distortion
Epithelial metaplasia
What are the histological features of UC that are DIFFERENT to the ones of Crohn?
Skip lesions are absent
Inflammation is usually limited to mucosa and superficial submucosa
What are the histological features of UC in severe cases?
Mucosal damage accompanied by ulcers –> extend deeply into the submucosa
Muscularis propria is rarely involved
What are acute phase complications of UC?
Severe bleeding
Toxic megacolon
What are the chronic phase complications of UC?
Increased risk of colorectal carcinoma
How much greater is the risk of colorectal carcinoma in chronic cases of UC?
20 to 30 times
What are the extra-intestinal manifestations? (4)
Arthiritis
Uveitis
Skin lesion (pyoderma gangreonosum)
Sclerosing pericholangitis –> Obstructive jaundice
Which IBD kind are extra-intestinal manifestations more common in?
Crohn
What are the other forms of IBD? (6)
Collagenous colitis
Lymphocytic colitis
Ischemic colitis
Behcet’s syndrome
Infective colitis
Intermediate colitis
What are examples of intestinal polyps?
Non-neoplastic
Neoplastic
What are the different kinds of non-neoplastic polyps?
Inflammatory
Hamartomatous
Hyperplastic
What is the example of neoplastic polyp?
Adenoma (potential to progress to cancer)
What is a sessile polyp?
Without stalks; proliferation of cells adjacent to the polyp and the effects of traction on the luminal protrusion
Which kind of polyp is with stalks?
Pedunculated polyps
What are the major types of hamartomatous polyps?
Juvenile polyps
Peutz-jeghers polyps
What is the age category for both Juvenile polyps & Peutz-jeghers polyps?
Juvenile polyps –> younger than 5
Peutz-jeghers polyps –> 10 to 15
What are the mutated genes for both Juvenile polyps & Peutz-jeghers polyps?
Juvenile polyps –> SMAD4, BMPR1A
Peutz-jeghers polyps –> LKB1/STK11
Where are the GI lesions located for both Juvenile polyps & Peutz-jeghers polyps?
Juvenile polyps –> rectum
Peutz-jeghers polyps –> small intestine, colon, stomach
What risks are associated with both Juvenile polyps & Peutz-jeghers polyps?
Juvenile polyps –> adenocarcinoma of colon, small intestine & pancreas
Peutz-jeghers polyps –> colonic adenocarcinoma
What is the gross features of both Juvenile polyps & Peutz-jeghers polyps?
Juvenile polyps –> pedunculated, smooth surfaced red lesions (less than 3cm)
Peutz-jeghers polyps –> 10 to 15multiple GI hamartomatous polyps, mucocutaneous hyperpigmentation
What are the microscopic features of both Juvenile polyps & Peutz-jeghers polyps?
Juvenile polyps –> dilated glands filled with mucin & inflammatory debris
Peutz-jeghers polyps –> arborizing network of CT, SM, lamina propria, glands lined by normal appearing intestinal epithelium
What are Peutz-jeghers polyps?
Large, pedunculated, and have lobulated contours
What is the most common and clinically important neoplastic polyp?
Colonic adenomas
Where do majority of colorectal adenocarcinomas arise from?
Adenomas
What are colorectal adenomas characterised by?
Presence of epithelial dysplasia
What is screening like for adenomas?
All precursors to colorectal cancer
Persons with family history are encouraged to get screened earlier in life
When should all adults start undergoing colonoscopies?
Starting at age 50
In the case that a family history of adenomas is present, screening…
The screening colonoscopy should be started at least ten years the youngest age at which a relative was diagnosed
What are the gross features of adenomas?
0.3 to 10cm
Pedunculated or sessile
The surface of both types has a texture resembling velvet or raspberry
What does the raspberry-like pattern of adenomas indicate?
Abnormal epithelial growth
What are the histological features of adenomas?
Epithelial dysplasia
Slender fibromuscular stalks
What are the hallmarks of epithelial dysplasia in adenoma cases?
Nuclear hyperchromasia
Nuclear stratification
Nuclear elongation
What does the slender fibromuscular stalks contain?
Prominent blood vessels derived from the submucosa
What is the stalk covered by?
Non-neoplastic epithelium (common)
Dysplastic epithelium (less common)
What are the classifications of adenomas?
Tubular adenomas
Villous adenomas
Tubulovillous adenomas
What are tubular adenomas like?
Smalla nd pedunculated polyps
Rounded or tubular glands
Active inflammation is occasionally present
Crypt dilation and rupture also seen
What are villous adenomas like?
Often large and sessile
Covered by slender villi, reminiscent of the small intetsine
What are tubulovillous adenomas like?
Have a mixture of tubular and villous elements
Low grade epitehlial dysplasia
What is the most common malignancy of the GIT?
Adenocarcinoma of the colon
What is the epidemiology of adenocarcinoma of the colon?
2nd leading cause of cancer-related deaths worldwide
2nd most commonly diagnosed cancer among men and 3rd among women
What is the average survival rate of 5 years for adenocarcinoma of the colon?
35%
What is the distribution of the adenocarcinoma based on location?
45% rectum
25% sigmoid colon
15% cecum & ascending
10% transverse
5% descending
What are the risk factors of adenocarcinoma?
Increasing age (> 60)
Family history of colorectal cancer
IBD
Low fiber diet or increased fat and meat consumption
Which factors decrease the risk of developing adenocarcinoma?
Fruits & fiber diet
Exercise
NSAIDs (protective effect)
How are NSAIDs a protective factor for adenocracinoma?
Inhibition of COX-2 enzyme, which is highly expressed in 90% of colorectal carcinomas and adeomas
What are adenomas known to do, especially in response to injury?
Promote epithelial proliferation
What are the red flags of adenocarcinoma for people > 40?
Unexplained weight loss and abdominal pain
Unexplained rectal bleeding
Unexplained iron deficiency
Change in bowel habit
What are the red flags of adenocarcinomas at any age?
Anal, rectal or abdominal mass
Fecal occult blood
What is the pathogenesis of adenocracinomas?
- Mutation of the APC (both copies)
- With the loss of APC function, β-catenin accumulates and translocates to the nucleus, activated transcription of genes, like those encoding for MYC and cyclin D1, promote proliferation
- Activation mutation in KRAS oncogene
- Mutations in other tumor suppressor genes such as SMAD2 and SMAD4
- Tumor suppressor gene TP53 is mutated
Where does the APC protein normally bind to?
Binds to and promotes degradation of β-catenin
What are the kind of mutations that affect tumor suppressor genes?
Chromosomal deletions
Expression of telomerase
What are the gross features of adenocarcinoma tumor in the proximal colon?
- Grow as polyploid, exophytic mass, extend along one wall of the large-caliber cecum and ascending colon
- These tumors rarely cause obstruction
What are the gross features of adenocarcinoma in the distal colon?
- Tend to be annular lesions that produce napkin ring
- Cause constrictions and luminal narrowing
What are the general microscopic characteristics of adenocarcinoma?
- Most tumors composed of tall columnar cells that resemble dysplastic epithelium found in adenomas
- Glands often filled with necrotic debris
- Other may produce abundant mucin –> poor prognosis
- The invasive component of these tumors is elicited a strong stromal desmoplastic response
What are the survival rates of the adenocarcinomas stages?
Stage 1 –> 80 to 95%
Stage 2 –> 72 to 85%
Stage 3A –> 60%
Stage 3B –> 40%
Stage 3C –> 25%
Stage 4 –> 5%
