Histopathology --> Colonic Pathology Flashcards
1
Q
• IBS
A
ill-defined (no associated inflammation).
2
Q
• IBD:
A
Confirmed by use of faecal calprotection, which detects ulceration.
3
Q
Crohn’s Disease → Epi
A
- Common in North America and Northern Europe
- Prevalence from 30 to 100 per 100000
- Family history common, relative risk for a sibling is 13-36 x normal population
- Maximal incidence in young adults 15-30 years
4
Q
Crohn’s Disease →
Definition
A
• Any portion of the GI tract can be affected but pattern of anatomical involvement is important
→ 40-50% involvement of both terminal ileum and caecum
→ 20% of patients disease confined to the colon
5
Q
Crohn’s Disease →
Characteristic features
A
Discontinuous or “skip” lesions on colonoscopy or barium studies are characteristic
6
Q
Crohn’s Disease →
Macroscopic examination
A
- Involved bowel potions and associated mesentery thickened and oedematous
→ Small bowel has serosa in crohns = fat surrounds serosa (characteristic of crohns) = fat wrapping. - Mucosal lesion typically begins as a superficial ulcer → Apthas ulcer (surface)
7
Q
Crohn’s Disease →
Macroscopic examination as disease advances
A
Ulcers enlarge, deepen and eventually coalesce to form transverse and longitudinal ulcers, giving “cobblestone” appearance.
8
Q
Crohn’s Disease →
Complications
A
- Inflammatory mass and anastomotic stricture in a patient with Crohns disease.
- Inflammatory adhesions
- Perforation (very rare)
- Perirectal disease (perianal fistulas and abscesses)
- Malabsorption
- Small bowel adenocarcinoma (difficult to treat)
9
Q
Crohn’s Disease →
Histopathology
A
- Transmural inflammation
- Non-necrotising granulomas (40-60%)
- Crypt abscess with pus
- Ulcers may penetrate deeply forming fissures in the muscularis propria leading to abscess and fistula formation – small bowel can attach to large @ wrong point
10
Q
Crohn’s Disease →
Fibrosis and stricture formations
A
Caused by healing of the penetrating lesions
11
Q
Crohn’s Disease →
Treatment
A
5-Aminosalycilic acid Steroids Immunosuppressive drugs Monoclonal antibodies against anti-TNF (Infliximab) Surgery
12
Q
Crohn’s Disease →
Anti-TNF used in
A
Primarily in patients with fistulae
13
Q
Crohn’s Disease →
Problem with surgery
A
Neoterminal Ileum – the crohns starts to infiltrate other parts
14
Q
Ulcerative Collitis →
Epi
A
- Common in North America and Northern Europe
- Prevalence – 35-50 in 100000
- Family history is common, relative risk for a sibling is 7-17.
- Maximal incidence in young adults in young adults 20-50 yrs. Second peak 60-70 yrs.
15
Q
Ulcerative Collitis → Histologically
A
- Crypt abscesses with neutrophils within the crypt, in the crypt wall and in the lamina propria → stops here
- Crypt architerual distortion, with gland branching
16
Q
Ulcerative Collitis →Complications
A
- Toxic megacolon
- Perforation – in caecum (thinnest portion of bowel)
- Massive haemorrhage
- Colon Cancer (correlation with colonic involvement and duration of disease) → dysplasia and carcinoma
17
Q
Ulcerative Collitis →Toxic Megacolon presentation
A
- High Fever
- Tachycardia
- Diarrhoea
18
Q
Ulcerative Collitis →Toxic Megacolon due to
A
- Paralysis of the motor function of the transverse colon
* Mortality 30%
19
Q
Ulcerative Collitis →Treatment
A
- 5-ASA
- Steroids
- Immunosuppressive drugs High Fever
- Tachycardia
- Diarrhoea
- Surgery (whole colon)
20
Q
Ulcerative Collitis - Dysplasia and carcinoma proportional to
A
Extent and duration of disease = with biliary disease if you pouch = fistula form.
→ Inflamm in pelvis difficult to manage
21
Q
Colorectal Polyps → Definition
A
Proturbent growth – from surface not specific for underlying pathology
Epithelial (very common)
Mesenchymal (uncommon)
Benign or Malignant
22
Q
Colorectal Polyps → Classification
A
Inflammatory
Hamartomatous
Neoplastic
Others
23
Q
Colorectal Polyps →Inflammatory
A
Pseudopolyps
Benign lymphoid polyps
24
Q
Colorectal Polyps →Hamartomatous
A
Juvenile polyp
Peutz-Jegher
25
Colorectal Polyps →Neoplastic
Adenoma
| Adenocarcinoma
26
Colorectal Polyps → Others
Hyperplastic
Lipoma
Leimyoma
27
Inflammatory Pseudopolyps: Pseudo because
Not ademonas
28
Inflammatory Pseudopolyps: Found in
UC and Crohns
29
Inflammatory Pseudopolyps: Macroscopically
Look like adenomas
30
Inflammatory Pseudopolyps: Microscopically
Inflammatory tissue, hyperplastic mucosa
31
Hamartomatous Polyps: Hamartoma
Benign tumour-like lesion
| Two or more differentiated tissue elements normally present in the organ
32
Hamartomatous Polyps:Types
Juvenile
| Peutzjegher
33
Hamartomatous Polyps: Juvenile
Most common paediatric
| GI polyps
34
Hamartomatous Polyps:Peutz-Jegher
GI polyps
| Pigmentations of oral mucosa, lips, palms genitalia
35
Juvenile Polyps: Histologically
Cystic glands with normal or inflamed epithelium
36
Juvenile Polyps: Germ Line
SMAD4 mutation (18q21-2) (25-30%)
37
Juvenile Polyps:Present in age
Children age 8 but in adults also
38
Juvenile Polyps:Present in
Rectum
39
Juvenile Polyps: Clinical manifestations
Bleeding (up to 95%), prolapse (because its in the rectum).
40
Peutz-Jeghers Polyps doinanceDominance
Autosomal dominant
41
Peutz-Jeghers Polyps Occur
Throughout the GI tract
42
Peutz-Jeghers Polyps Common in
Small bowel compared to large bowel
43
Peutz-Jeghers Polyps Complications
Intussusception and partial or complete obstruction
44
Peutz-Jeghers Polyps Adenoma/Carcinoma in PJP
Carcinoma develops from dysplastic foci (73% GI tract)
45
Neoplastic Polyps: Adenoma definition
All are dysplastic
Disregulated proliferation
Failure to fully differentiate
Premalignant
46
Neoplastic Polyps: Classification
Tubular – tubular growth
Tubulovillous -outgrowth
Villous – more than 75% villous
47
Neoplastic Polyps: Flat/Depressed
High malignant potential (even if small)
High incidence of severe dysplasia
Associated with familial colon cancer syndromes, HNPCC (50%) or FAP
48
Neoplastic Polyps Malignant potential of adenomas is proportional to
Villosity (25-85%) of villous adenomas may contain cancer
49
Neoplastic Polyps Size
30% of villous adenomas >5cm may contain cancer)
| Degree of dysplasia (severe)
50
HyperPlastic Polyp: Commonest in
Adults
51
HyperPlastic Polyp: Presentation
Asymptomatic, any age but increase in 60s and 70s, mostly rectosigmoid
52
HyperPlastic Polyp: Size
Small >5mm, sissile nodule
53
HyperPlastic Polyp: Malignant potential
Benign, no malignant potential unless they are mixed (hyperplastic – adenomatous polyps, Serrated Aenomas) – disorder of maturation rather than proliferation.
54
Leiomyoma: Presents with
Intersusception
55
Leiomyoma: Found in
Rectum, as well as jejunum, ileum
| Muscularis Mucosa
56
Leiomyoma: Symptoms
Anaemia
Bleeding due to ulceration
Epigastric pain
57
Colorectal Cancer → Epi
Peaks a 75-80 yrs
Carcinoma colon F>M
Carcinoma rectum M>F
58
Colorectal Cancer → Location %
Right colon 25%
Left colon 15%
Rectosigmoid 50% (status of carcinogens)
59
Colorectal Cancer →Right Colon characteristics
Polypoid
Mass
Discomfort/anaemia (premenopausal and male – find out why?)
60
Colorectal Cancer →Left Colon characteristics
Anular, obstructing
Bleeding/mucus
Colicky pain
Change of bowel habit
61
Colorectal Cancer →Screening
```
Colonoscopy:
1. UC
2. FAP/HNPCC
3. Adenomatous Polyps
Faecal occult bloods (False positives) + 55 yrs
Flexible sigmoidoscopy
Genetic testing (close relatives)
```
62
Colorectal Cancer → Spread
Direct
Lymphatic
Vascular (Liver, lungs, bones)
63
Colorectal Cancer → Complications
```
Obstruction
Perforation
Bleeding
Pericolic abscess
Fistulae
Intussusception
```
64
Colorectal Cancer →Staging (see notes)
Dukes classification
| TNM staging
65
Colorectal Cancer → Survival Dukes @ 5 yrs
```
A = 99%
B = 75%
C = 35%
```
66
Familial colorectal Cancer Syndrome: HNPCC (hereditary non-polyposis carcinoma) Dominance
Dominant
67
Familial colorectal Cancer Syndrome: HNPCC (hereditary non-polyposis carcinoma) Age
Carcinoma develops younger
68
Familial colorectal Cancer Syndrome: HNPCC (hereditary non-polyposis carcinoma) Location
Right sided
69
Familial colorectal Cancer Syndrome: HNPCC (hereditary non-polyposis carcinoma) Genetics
Abnormalities in 4 mismatched repair genes (microsatellite instability)
70
Familial colorectal Cancer Syndrome: HNPCC (hereditary non-polyposis carcinoma) Identifying HNPCC
Amsterdam Criteria (see lecture notes)
71
Familial colorectal Cancer Syndrome: HNPCC (hereditary non-polyposis carcinoma) Epi
Relatively rare condition 1/8000
72
Familial colorectal Cancer Syndrome: HNPCC (hereditary non-polyposis carcinoma) Without intervention
Virtually all people with this condition will develop colon cancer
73
Familial colorectal Cancer Syndrome: HNPCC (hereditary non-polyposis carcinoma) Characterised by
Multiple polyps throughout the entire colon (up to thousands)
74
Familial colorectal Cancer Syndrome: HNPCC (hereditary non-polyposis carcinoma) Surgery
Colectomy as thousand of polyps so cant do polpectomy
75
Section 3 → Malabsorption Pathogenesis
* Autoimmune condition
* Immunological response to gluten and related prolamines
* Causing villous atrophy of the lining of the small bowel
* Genetically susceptible people
* Heavily dependent on human leukocyte antigen (HLA) → specifically HLA DQ2 and DQ8 haplotypes
76
Section 3 → Malabsorption Presentation
```
2 categories:
1. Classical
• Symptoms of malabsorption
→ Weight loss
→ Chronic diarrhoea
→ FTT
2. Non-classical
• IBS type symptoms
→ Abdominal pain
→ Altered bowel habit
→ Anaemia
```
77
Section 3 → Malabsorption Investigations
Serological tests
Duodenal biopsy
Ensure counselling is carried out prior to testing
78
Section 3 → Malabsorption Serological tests
```
IgA
• Total
• Anti tTG
Endomysial Antibody (EMA)
Deamidated gliadin peptide (DGP)
HLA typing
Anti tTG IgG – if IgA deficient
```
79
Section 3 → Malabsorption Counselling
Gluten free diet and risk of untreated
80
Section 3 → Malabsorption Duodenal biopsy
Via endoscopy
3 + biopsy
• Previously beyond D2
• Now also recommended biopsies from D1
Location of each biopsy must be communicated with the pathologist
Different normal architecture of the villi in D1
81
Section 3 → Malabsorption Histology
Modified Marsh criteria
1. Increased IELs with norma villous architecture (MARSH type 1) is non-specific for CD but diagnosis strengthened by strongly positive serology]
2. Increased IELs with crypt hyperplasia (Marsh type 2) compatible with CD: diagnosis strengthened by positive serology; if serology negative, reconsider CD after exclusion of other disorders
3. MOST IMPORTANT → The most important → villous atrophy with crypt hyperplasia and increased intraepithelial lymphocytes (IELS) >30/100 epithelial cells – characteristic CD
82
Section 3 → Malabsorption Guidelines
Joint BSPGHAN and Coeliac UK guidelines for the diagnosis and management of coeliac disease in children.
Increasing prevalence
• Estimated 1/100 people
• 10-20% of this figure are diagnosed
No current universal screening but the new guidelines suggest that we should have a low threshold for investigating
• Symptomatic children
• Associated conditions
83
Section 3 → Malabsorption Symptoms/Signs
```
Persistent diarrhoea
Constipation
Faltering growth/weight gain
Abdominal pain/distension
Dental enamel defects
Delayed menarche
Unexplained anaemia/ iron deficient
Dermatitis herpetiformis
Osteporosis/path fracture
Recurrent apthous stomatitis
Unexplained liver disease
Weakness
```
84
Section 3 → Malabsorption Associated conditions
```
Type 1 diabetes (>8%)
Selective IgA defiency (1.7-7.75)
Chromosome disorders e.g. downs + turners
Autoimmune thyroiditis
Autoimmune liver disease
Intussusception
```
85
Section 3 → Malabsorption Family history
First-degree relative (10%)
HLA-matching sibling (30%-40)
Monozygotic twin (70%)
86
Section 3 → Malabsorption Gluten rechallenge
3 months gluten challenge prior to testing
Minimum of 4-6 weeks if symptomatic
Needs to be adequate gluten in diet 10-15g/day
Follow up for 2 years post challenge with serology at 6 monthly intervals
87
Section 3 → Malabsorption Treatment
```
Gluten free diet (GFD) diet after diagnosis
• Food with gluten 20 ppm or less
• Education to improve compliance
Lifelong dietician input
• Within 2 weeks of diagnosis
• FU 3-6 monthly
Case summary in notes
Advise families to join coeliac UK
Pneumococcal vaccine
Aimto normalise serology within 12 months
```
88
Section 3 → Malabsorption Monitoring
```
Paeds gastroenterologist and paeds dietician
Symptoms
Growth
Adherence to GFD
Bloods:
• Micronutrient status
• Calcium and iron
• Anti TTG antibodies
Transition to adult care when appropriate
```
