Lower GI Pathology

Lower GI Pathology Dr Muhammed Azam FRCPath Part 1 Course January 2020

Plan • MCQs and EMQs • Based on past papers • Certain topics keep coming up.....

1. Select the appropriate condition from the list of options for each of the clinicopathological descriptions.

A. Infective colitis

1. A 64 year old male admitted in ITU for sepsis develops acute onset diarrhoea. Colonic biopsies show a luminal spray of mucus and neutrophils.

The background mucosa shows minimal inflammatory changes.

B. Pseudomembranous colitis

2. A 55 year old female with watery diarrhoea and normal colonoscopy. The colonic biopsies show increased intraepithelial lymphocytes with a thickened sub epithelial collagen plate.

C. Ulcerative colitis

3. A 28 year old male with bloody diarrhoea and abdominal pain. A colonoscopy shows patchy inflammation affecting the right side colon with apthous ulcers. The colonic biopsies show mild crypt distortion with patchy discontinuous inflammation with cryptitis

D. Crohn’s disease

4. A 42 year old female with acute onset bloody diarrhoea and granular and congested rectum on endoscopy. The rectal biopsy shows oedematous mucosa with dispersed ‘sprinkled salt’ inflammatory cells, cryptitis and dilatation and withering of crypts.

E. Lymphocytic colitis

5. A 72 year old male with abdominal pain and bloody diarrhoea.

Sigmoidoscopy shows inflammation in the left side of the colon, most prominent in the sigmoid colon. Biopsies show extensive ulceration with preservation of basal crypts and active inflammation. There is no crypt distortion or crypt abscess formation.

F. Collagenous colitis G. Ischaemic colitis

A. Infective colitis

1. A 64 year old male admitted in ITU for sepsis develops acute onset diarrhoea. Colonic biopsies show a luminal spray of mucus and neutrophils.

The background mucosa shows minimal inflammatory changes.

B. Pseudomembranous colitis

2. A 55 year old female with watery diarrhoea and normal colonoscopy. The colonic biopsies show increased intraepithelial lymphocytes with a thickened sub epithelial collagen plate.

C. Ulcerative colitis

3. A 28 year old male with bloody diarrhoea and abdominal pain. A colonoscopy shows patchy inflammation affecting the right side colon with apthous ulcers. The colonic biopsies show mild crypt distortion with patchy discontinuous inflammation with cryptitis

D. Crohn’s disease

4. A 42 year old female with acute onset bloody diarrhoea and granular and congested rectum on endoscopy. The rectal biopsy shows oedematous mucosa with dispersed ‘sprinkled salt’ inflammatory cells, cryptitis and dilatation and withering of crypts.

E. Lymphocytic colitis

5. A 72 year old male with abdominal pain and bloody diarrhoea.

Sigmoidoscopy shows inflammation in the left side of the colon, most prominent in the sigmoid colon. Biopsies show extensive ulceration with preservation of basal crypts and active inflammation. There is no crypt distortion or crypt abscess formation.

F. Collagenous colitis G. Ischaemic colitis

A. Infective colitis

1. A 64 year old male admitted in ITU for sepsis develops acute onset diarrhoea. Colonic biopsies show a luminal spray of mucus and neutrophils.

The background mucosa shows minimal inflammatory changes.

B. Pseudomembranous colitis

2. A 55 year old female with watery diarrhoea and normal colonoscopy. The colonic biopsies show increased intraepithelial lymphocytes with a thickened sub epithelial collagen plate.

C. Ulcerative colitis

3. A 28 year old male with bloody diarrhoea and abdominal pain. A colonoscopy shows patchy inflammation affecting the right side colon with apthous ulcers. The colonic biopsies show mild crypt distortion with patchy discontinuous inflammation with cryptitis

D. Crohn’s disease

4. A 42 year old female with acute onset bloody diarrhoea and granular and congested rectum on endoscopy. The rectal biopsy shows oedematous mucosa with dispersed ‘sprinkled salt’ inflammatory cells, cryptitis and dilatation and withering of crypts.

E. Lymphocytic colitis

5. A 72 year old male with abdominal pain and bloody diarrhoea.

Sigmoidoscopy shows inflammation in the left side of the colon, most prominent in the sigmoid colon. Biopsies show extensive ulceration with preservation of basal crypts and active inflammation. There is no crypt distortion or crypt abscess formation.

F. Collagenous colitis G. Ischaemic colitis

A. Infective colitis

1. A 64 year old male admitted in ITU for sepsis develops acute onset diarrhoea. Colonic biopsies show a luminal spray of mucus and neutrophils.

The background mucosa shows minimal inflammatory changes.

B. Pseudomembranous colitis

2. A 55 year old female with watery diarrhoea and normal colonoscopy. The colonic biopsies show increased intraepithelial lymphocytes with a thickened sub epithelial collagen plate.

C. Ulcerative colitis

3. A 28 year old male with bloody diarrhoea and abdominal pain. A colonoscopy shows patchy inflammation affecting the right side colon with apthous ulcers. The left colon biopsies show mild crypt distortion with patchy discontinuous inflammation with cryptitis

D. Crohn’s disease

4. A 42 year old female with acute onset bloody diarrhoea and granular and congested rectum on endoscopy. The rectal biopsy shows oedematous mucosa with dispersed ‘sprinkled salt’ inflammatory cells, cryptitis and dilatation and withering of crypts.

E. Lymphocytic colitis

5. A 72 year old male with abdominal pain and bloody diarrhoea.

Sigmoidoscopy shows inflammation in the left side of the colon, most prominent in the sigmoid colon. Biopsies show extensive ulceration with preservation of basal crypts and active inflammation. There is no crypt distortion or crypt abscess formation.

F. Collagenous colitis G. Ischaemic colitis

A. Infective colitis

1. A 64 year old male admitted in ITU for sepsis develops acute onset diarrhoea. Colonic biopsies show a luminal spray of mucus and neutrophils.

The background mucosa shows minimal inflammatory changes.

B. Pseudomembranous colitis

2. A 55 year old female with watery diarrhoea and normal colonoscopy. The colonic biopsies show increased intraepithelial lymphocytes with a thickened sub epithelial collagen plate.

C. Ulcerative colitis

3. A 28 year old male with bloody diarrhoea and abdominal pain. A colonoscopy shows patchy inflammation affecting the right side colon with apthous ulcers. The colonic biopsies show mild crypt distortion with patchy discontinuous inflammation with cryptitis

D. Crohn’s disease

4. A 42 year old female with acute onset bloody diarrhoea and granular and congested rectum on endoscopy. The rectal biopsy shows oedematous mucosa with dispersed ‘sprinkled salt’ inflammatory cells, cryptitis and dilatation and withering of crypts.

E. Lymphocytic colitis

5. A 72 year old male with abdominal pain and bloody diarrhoea.

Sigmoidoscopy shows inflammation in the left side of the colon, most prominent in the sigmoid colon. Biopsies show extensive ulceration with preservation of basal crypts and active inflammation. There is no crypt distortion or crypt abscess formation.

F. Collagenous colitis G. Ischaemic colitis

A. Infective colitis

1. A 64 year old male admitted in ITU for sepsis develops acute onset diarrhoea. Colonic biopsies show a luminal spray of mucus and neutrophils.

The background mucosa shows minimal inflammatory changes.

B. Pseudomembranous colitis

2. A 55 year old female with watery diarrhoea and normal colonoscopy. The colonic biopsies show increased intraepithelial lymphocytes with a thickened sub epithelial collagen plate.

C. Ulcerative colitis

3. A 28 year old male with bloody diarrhoea and abdominal pain. A colonoscopy shows patchy inflammation affecting the right side colon with apthous ulcers. The colonic biopsies show mild crypt distortion with patchy discontinuous inflammation with cryptitis

D. Crohn’s disease

4. A 42 year old female with acute onset bloody diarrhoea and granular and congested rectum on endoscopy. The rectal biopsy shows oedematous mucosa with dispersed ‘sprinkled salt’ inflammatory cells, cryptitis and dilatation and withering of crypts.

E. Lymphocytic colitis

5. A 72 year old male with abdominal pain and bloody diarrhoea.

Sigmoidoscopy shows inflammation in the left side of the colon, most prominent in the sigmoid colon. Biopsies show extensive ulceration with preservation of basal crypts and active inflammation. There is no crypt distortion or crypt abscess formation.

F. Collagenous colitis G. Ischaemic colitis

Infective colitis • Acute, self limiting • Most commonly due to enteric viruses, most common Rotavirus • Bacterial causes include Campylobacter, Shigella, Salmonella • Parasitic causes include Entamoeba histolytica

Infective colitis • Bacterial enterocolitis – Ingestion of preformed toxin • S.aureus, Vibrio, C.perfringens

– Infection by toxigenic organisms • C.difficile

– Infection by enteroinvasive organisms • Shigella, Salmonella

Infective colitis

Infective colitis • • • • • •

Non-specific histology Damage to surface epithelium Decreased epithelial maturation Hyperaemia Oedema of lamina propria Variable polymorph infiltrates in epithelium and lamina propria

Pseudomembranous colitis • C.difficile • Prior antibiotic exposure • Mild diarrhoea or fulminant toxic megacolon • ‘Pseudomembrane’ composed of mucin, inflammatory cells and debris over site of mucosal injury • Toxin A and B modify cytokine pathways inducing cell apoptosis

Pseudomembranous colitis

Microscopic colitis • Criteria for diagnosis: Chronic watery diarrhoea, normal endoscopy, typical histology • Lymphocytic colitis – Equal male and female – Associated with autoimmune diseases – 15-20+ lymphocytes/100 epithelial cells

• Collagenous colitis – Middle aged elderly females – Thickened subepithelial collagen plate (>10mcm)

Microscopic colitis

Microscopic colitis

Ischaemic colitis • Can be mucosal, mural or transmural • Specific causes • Arterial thrombosis – Atheroma, post-vascular surgery, vasculitis, hypercoagulable states • Venous thrombosis – Hypercoagulable states, intraabdominal sepsis, malignancy, cirrhosis • Non-occlusive ischaemia – Cardiac failure, shock, drugs, hypotension • Other – Radiation, amyloidosis, diabetes, herniation

Ischaemic colitis

2. Select the appropriate syndrome from the list of options for each of the conditions described. Each of the options may be used once, more than once or not at all A. Gardner’s syndrome

1. Autosomal dominant disorder characterised by intestinal hamartomatous polyps, facial trichilemmomas, acral keratosis and oral papillomas

B. Turcot syndrome

2. Non hereditary condition characterised by gastrointestinal hamartomatous polyps, nail atrophy and alopecia

C. Peutz-Jeghers syndrome

3. Familial disorder with intestinal adenomatous polyps, osteomas, epidermal cysts and fibromatosis

D. Cowden syndrome

4. Autosomal dominant condition with microsatellite instability, gastrointestinal malignancy and sebaceous neoplasms

E. Cronkhite-Canada syndrome

5. Condition characterised by colonic adenomatous polyposis and CNS tumours

F. Carney triad G. Muir Torre syndrome

A. Gardner’s syndrome

1. Autosomal dominant disorder characterised by intestinal hamartomatous polyps, facial trichilemmomas, acral keratosis and oral papillomas

B. Turcot syndrome

2. Non hereditary condition characterised by gastrointestinal hamartomatous polyps, nail atrophy and alopecia

C. Peutz-Jeghers syndrome

3. Familial disorder with intestinal adenomatous polyps, osteomas, epidermal cysts and fibromatosis

D. Cowden syndrome

4. Autosomal dominant condition with microsatellite instability, gastrointestinal malignancy and sebaceous neoplasms

E. Cronkhite-Canada syndrome

5. Condition characterised by colonic adenomatous polyposis and CNS tumours

F. Carney triad G. Muir Torre syndrome

A. Gardner’s syndrome

1. Autosomal dominant disorder characterised by intestinal hamartomatous polyps, facial trichilemmomas, acral keratosis and oral papillomas

B. Turcot syndrome

2. Non hereditary condition characterised by gastrointestinal hamartomatous polyps, nail atrophy and alopecia

C. Peutz-Jeghers syndrome

3. Familial disorder with intestinal adenomatous polyps, osteomas, epidermal cysts and fibromatosis

D. Cowden syndrome

4. Autosomal dominant condition with microsatellite instability, gastrointestinal malignancy and sebaceous neoplasms

E. Cronkhite-Canada syndrome

5. Condition characterised by colonic adenomatous polyposis and CNS tumours

F. Carney triad G. Muir Torre syndrome

A. Gardner’s syndrome

1. Autosomal dominant disorder characterised by intestinal hamartomatous polyps, facial trichilemmomas, acral keratosis and oral papillomas

B. Turcot syndrome

2. Non hereditary condition characterised by gastrointestinal hamartomatous polyps, nail atrophy and alopecia

C. Peutz-Jeghers syndrome

3. Familial disorder with intestinal adenomatous polyps, osteomas, epidermal cysts and fibromatosis

D. Cowden syndrome

4. Autosomal dominant condition with microsatellite instability, gastrointestinal malignancy and sebaceous neoplasms

E. Cronkhite-Canada syndrome

5. Condition characterised by colonic adenomatous polyposis and CNS tumours

F. Carney triad G. Muir Torre syndrome

A. Gardner’s syndrome

1. Autosomal dominant disorder characterised by intestinal hamartomatous polyps, facial trichilemmomas, acral keratosis and oral papillomas

B. Turcot syndrome

2. Non hereditary condition characterised by gastrointestinal hamartomatous polyps, nail atrophy and alopecia

C. Peutz-Jeghers syndrome

3. Familial disorder with intestinal adenomatous polyps, osteomas, epidermal cysts and fibromatosis

D. Cowden syndrome

4. Autosomal dominant condition with microsatellite instability, gastrointestinal malignancy and sebaceous neoplasms

E. Cronkhite-Canada syndrome

5. Condition characterised by colonic adenomatous polyposis and CNS tumours

F. Carney triad G. Muir Torre syndrome

A. Gardner’s syndrome

1. Autosomal dominant disorder characterised by intestinal hamartomatous polyps, facial trichilemmomas, acral keratosis and oral papillomas

B. Turcot syndrome

2. Non hereditary condition characterised by gastrointestinal hamartomatous polyps, nail atrophy and alopecia

C. Peutz-Jeghers syndrome

3. Familial disorder with intestinal adenomatous polyps, osteomas, epidermal cysts and fibromatosis

D. Cowden syndrome

4. Autosomal dominant condition with microsatellite instability, gastrointestinal malignancy and sebaceous neoplasms

E. Cronkhite-Canada syndrome

5. Condition characterised by colonic adenomatous polyposis and CNS tumours

F. Carney triad G. Muir Torre syndrome

FAP syndromes Syndrome

Colorectal polyps

Extracolonic lesions

Genetics

Risk of colorectal malignancy

FAP

>100

Gastric fundic polyps, duodenal adenomas

Auto Dom APC mutation

100%

Gardner’s syndrome

>100

Osteomas, fibromas, desmoid tumours etc

Auto Dom APC mutation

100%

Turcot’s syndrome

>100

CNS tumours Auto Dom (medullobalstomas) APC mutation

100%

Attenuated FAP

<100

Similar to FAP

Auto Dom APC mutation

80%

MYH associated polyposis

15-100

Uncertain

Auto Rec MYH mutation

High risk

Cowden’s syndrome • Autosomal dominant – PTEN gene mutations on chromosome 10 • 90-100% - mucocutaneous lesions like trichilemmomas, acral keratosis, papillomas • 35-45% - GI hamartomatous polyps • Breast carcinoma, thyroid neoplasms • ?risk of GI malignancy

Cronkhite-Canada syndrome • Non familial • GI hamatomous polyposis • Ectodermal abnormalities– Alopecia – Onychodystropy – Cutaneous hyperpigmentation

Cronkhite Canada Syndrome

Cronkhite Canada Syndrome

Hamartomatous – juvenile type polyps

3. Select the appropriate term from the list of options for each of the polyps described.

A. Tubulovillous adenoma

1. Polyp with low grade dysplasia and approximately 10% villous architecture

B. Tubular adenoma

2. Polyp with high grade dysplasia and approximately 60% villous architecture

C. Villous adenoma

3. A 3 mm polyp in the rectum with a serrated architecture and no dysplasia

D. Serrated adenoma

4. A 25 mm polyp in the ascending colon with a serrated architecture and no dysplasia. The bases of the crypts show dilatation and branching.

E. Sessile serrated polyp

5. A 30 mm polyp in the rectum with oedematous lamina propria, ulcerated surface and many cystically dilated glands

F. Mixed hyperplastic polyp – serrated adenoma

6. A 14 mm polyp is the transverse colon with a serrated architecture and low grade dysplasia

G. Juvenile polyp H. Hamartomatous polyp I. Hyperplastic polyp

A. Tubulovillous adenoma

1. Polyp with low grade dysplasia and approximately 10% villous architecture

B. Tubular adenoma

2. Polyp with high grade dysplasia and approximately 60% villous architecture

C. Villous adenoma

3. A 3 mm polyp in the rectum with a serrated architecture and no dysplasia

D. Serrated adenoma

4. A 25 mm polyp in the ascending colon with a serrated architecture and no dysplasia. The bases of the crypts show dilatation and branching.

E. Sessile serrated polyp

5. A 30 mm polyp in the rectum with oedematous lamina propria, ulcerated surface and many cystically dilated glands

F. Mixed hyperplastic polyp – serrated adenoma

6. A 14 mm polyp is the transverse colon with a serrated architecture and low grade dysplasia

G. Juvenile polyp H. Hamartomatous polyp I. Hyperplastic polyp

A. Tubulovillous adenoma

1. Polyp with low grade dysplasia and approximately 10% villous architecture

B. Tubular adenoma

2. Polyp with high grade dysplasia and approximately 60% villous architecture

C. Villous adenoma

3. A 3 mm polyp in the rectum with a serrated architecture and no dysplasia

D. Serrated adenoma

4. A 25 mm polyp in the ascending colon with a serrated architecture and no dysplasia. The bases of the crypts show dilatation and branching.

E. Sessile serrated polyp

5. A 30 mm polyp in the rectum with oedematous lamina propria, ulcerated surface and many cystically dilated glands

F. Mixed hyperplastic polyp – serrated adenoma

6. A 14 mm polyp is the transverse colon with a serrated architecture and low grade dysplasia

G. Juvenile polyp H. Hamartomatous polyp I. Hyperplastic polyp

A. Tubulovillous adenoma

1. Polyp with low grade dysplasia and approximately 10% villous architecture

B. Tubular adenoma

2. Polyp with high grade dysplasia and approximately 60% villous architecture

C. Villous adenoma

3. A 3 mm polyp in the rectum with a serrated architecture and no dysplasia

D. Serrated adenoma

4. A 25 mm polyp in the ascending colon with a serrated architecture and no dysplasia. The bases of the crypts show dilatation and branching.

E. Sessile serrated polyp

5. A 30 mm polyp in the rectum with oedematous lamina propria, ulcerated surface and many cystically dilated glands

F. Mixed hyperplastic polyp – serrated adenoma

6. A 14 mm polyp is the transverse colon with a serrated architecture and low grade dysplasia

G. Juvenile polyp H. Hamartomatous polyp I. Hyperplastic polyp

A. Tubulovillous adenoma

1. Polyp with low grade dysplasia and approximately 10% villous architecture

B. Tubular adenoma

2. Polyp with high grade dysplasia and approximately 60% villous architecture

C. Villous adenoma

3. A 3 mm polyp in the rectum with a serrated architecture and no dysplasia

D. Serrated adenoma

4. A 25 mm polyp in the ascending colon with a serrated architecture and no dysplasia. The bases of the crypts show dilatation and branching.

E. Sessile serrated polyp

5. A 30 mm polyp in the rectum with oedematous lamina propria, ulcerated surface and many cystically dilated glands

F. Mixed hyperplastic polyp – serrated adenoma

6. A 14 mm polyp is the transverse colon with a serrated architecture and low grade dysplasia

G. Juvenile polyp

H. Hamartomatous polyp I. Hyperplastic polyp

A. Tubulovillous adenoma

1. Polyp with low grade dysplasia and approximately 10% villous architecture

B. Tubular adenoma

2. Polyp with high grade dysplasia and approximately 60% villous architecture

C. Villous adenoma

3. A 3 mm polyp in the rectum with a serrated architecture and no dysplasia

D. Serrated adenoma

4. A 25 mm polyp in the ascending colon with a serrated architecture and no dysplasia. The bases of the crypts show dilatation and branching.

E. Sessile serrated polyp

5. A 30 mm polyp in the rectum with oedematous lamina propria, ulcerated surface and many cystically dilated glands

F. Mixed hyperplastic polyp – serrated adenoma

6. A 14 mm polyp is the transverse colon with a serrated architecture and low grade dysplasia

G. Juvenile polyp

H. Hamartomatous polyp I. Hyperplastic polyp

A. Tubulovillous adenoma

1. Polyp with low grade dysplasia and approximately 10% villous architecture

B. Tubular adenoma

2. Polyp with high grade dysplasia and approximately 60% villous architecture

C. Villous adenoma

3. A 3 mm polyp in the rectum with a serrated architecture and no dysplasia

D. Serrated adenoma

4. A 25 mm polyp in the ascending colon with a serrated architecture and no dysplasia. The bases of the crypts show dilatation and branching.

E. Sessile serrated polyp

5. A 30 mm polyp in the rectum with oedematous lamina propria, ulcerated surface and many cystically dilated glands

F. Mixed hyperplastic polyp – serrated adenoma

6. A 14 mm polyp is the transverse colon with a serrated architecture and low grade dysplasia

G. Juvenile polyp H. Hamartomatous polyp I. Hyperplastic polyp

Adenomatous polyps • Tubular adenoma (<20% villous component) • Tubulovillous adenoma (20-80% villous component) • Villous adenoma (>80% villous component)

Serrated lesions • • • •

Hyperplastic polyp Sessile serrated polyp (adenoma) Traditional serrated adenoma Mixed hyperplastic polyp - adenoma

Hyperplastic polyps • Left >right • Males> females • Usually less than 10 mm • Frequent k-ras mutations

Sessile serrated polyp

“These lesions have multiple aliases (serrated adenoma, serrated polyp or serrated lesion among others), they hang out in a bad neighbourhood (the poorly prepped right colon), they hide behind a mask of mucus, they are difficult for witnesses (pathologists) to identify, they are difficult for police (endoscopists) to find, they are difficult to permanently remove from society (high incomplete resection rate), they can be impulsive (progress rapidly to CRC) and enforcers (gastroenterologists) don’t know how best to control them (uncertain surveillance recommendations). There is no wonder that there is a need to …… detect these deviants and eradicate them from colonic society. These lesions should be on the endoscopists’ most wanted list”

Sessile Serrated Polyps: Detection, Eradication, and Prevention of the Evil Twin Joshua C. Obuch,1 Courtney M. Pigott,1 and Dennis J. Ahnen1,2 Current Treatment Options Gastroenterology 2015 13(1) 156-170

Sessile serrated polyp • • • • •

Right > Left Females> males Usually > 10 mm Cytologically bland BRAF mutation

Serrated adenomatous lesions

4. Sections from a pedunculated polyp received through the bowel cancer screening programme show an invasive carcinoma arising within a tubulovillous adenoma. The carcinoma infiltrates into and appears limited to the stalk of the polyp. No vascular invasion is seen. The deep margin is 3 mm away. Which of the following best describes the level of submucosal infiltration?

A. B. C. D. E. F.

Kikuchi level sm1 Kikuchi level sm2 Kikuchi level sm3 Haggit level 1 Haggit level 2 Haggit level 3

4. Sections from a pedunculated polyp received through the bowel cancer screening programme show an invasive carcinoma arising within a tubulovillous adenoma. The carcinoma infiltrates into and appears limited to the stalk of the polyp. No vascular invasion is seen. The deep margin is 3 mm away. Which of the following best describes the level of submucosal infiltration?

A. B. C. D. E. F.

Kikuchi level sm1 Kikuchi level sm2 Kikuchi level sm3 Haggitt level 1 Haggitt level 2 Haggitt level 3

Haggitt levels

Kikuchi levels

Sm1 2% risk of LN metastasis

Sm2 8% risk of LN metastasis

Sm3 23% risk of LN metastasis

5. Select the appropriate pathological tumour and nodal stage from the options for each of the colorectal tumours described. Each option may be used once, more than once or not at all.

A. pT3N2, Dukes C2

1. Caecal adenocarcinoma with intramural extension into terminal ileum and infiltration into subserosal fat; 3/22 lymph nodes involved, apical node clear.

B. pT1N0, Dukes A

2. Low rectal adenocarcinoma infiltrating into the levator muscles; lymph nodes free of tumour.

C. ypT2yN1, Dukes C1

3. Large rectal adenocarcinoma with macroscopic tumour perforation through the mesorectal fat into the retroperitoneum, 2/13 nodes involved, apical node clear

D. pT4N0, Dukes B

4. Rectal adenocarcinoma with preoperative long course chemoradiation. Residual tumour infiltrating into but not beyond muscularis propria. A total of 7 lymph nodes retrieved of which 3 show carcinoma and one contains mucin lakes with no demonstrable tumour cells. Apical node clear

E. pT3N1, Dukes C1

5. Polypoid adenocarcinoma infiltrating into the submucosa. No lymph nodes involved.

F. pT4N1, Dukes C1

G. ypT2yN2, Dukes C1 H. pT4N0, Dukes B

A. pT3N2, Dukes C2

1. Caecal adenocarcinoma with intramural extension into terminal ileum and infiltration into subserosal fat; 3/22 lymph nodes involved, apical node clear.

B. pT1N0, Dukes A

2. Low rectal adenocarcinoma infiltrating into the levator muscles; lymph nodes free of tumour.

C. ypT2yN1, Dukes C1

3. Large rectal adenocarcinoma with macroscopic tumour perforation through the mesorectal fat into the retroperitoneum, 2/13 nodes involved, apical node clear

D. pT4N0, Dukes B

4. Rectal adenocarcinoma with preoperative long course chemoradiation. Residual tumour infiltrating into but not beyond muscularis propria. A total of 7 lymph nodes retrieved of which 3 show carcinoma and one contains mucin lakes with no demonstrable tumour cells. Apical node clear

E. pT3N1, Dukes C1

5. Polypoid adenocarcinoma infiltrating into the submucosa. No lymph nodes involved.

F. pT4N1, Dukes C1 G. ypT2yN2, Dukes C1 H. pT4N0, Dukes B

A. pT3N2, Dukes C2

1. Caecal adenocarcinoma with intramural extension into terminal ileum and infiltration into subserosal fat; 3/22 lymph nodes involved, apical node clear.

B. pT1N0, Dukes A

2. Low rectal adenocarcinoma infiltrating into the levator muscles; lymph nodes free of tumour.

C. ypT2yN1, Dukes C1

3. Large rectal adenocarcinoma with macroscopic tumour perforation through the mesorectal fat into the retroperitoneum, 2/13 nodes involved, apical node clear

D. pT4N0, Dukes B

4. Rectal adenocarcinoma with preoperative long course chemoradiation. Residual tumour infiltrating into but not beyond muscularis propria. A total of 7 lymph nodes retrieved of which 3 show carcinoma and one contains mucin lakes with no demonstrable tumour cells. Apical node clear

E. pT3N1, Dukes C1

5. Polypoid adenocarcinoma infiltrating into the submucosa. No lymph nodes involved.

F. pT4N1, Dukes C1 G. ypT2yN2, Dukes C1 H. pT4N0, Dukes B

A. pT3N2, Dukes C2

1. Caecal adenocarcinoma with intramural extension into terminal ileum and infiltration into subserosal fat; 3/22 lymph nodes involved, apical node clear.

B. pT1N0, Dukes A

2. Low rectal adenocarcinoma infiltrating into the levator muscles; lymph nodes free of tumour.

C. ypT2yN1, Dukes C1

3. Large rectal adenocarcinoma with macroscopic tumour perforation through the mesorectal fat into the retroperitoneum, 2/13 nodes involved, apical node clear

D. pT4N0, Dukes B

4. Rectal adenocarcinoma with preoperative long course chemoradiation. Residual tumour infiltrating into but not beyond muscularis propria. A total of 7 lymph nodes retrieved of which 3 show carcinoma and one contains mucin lakes with no demonstrable tumour cells. Apical node clear

E. pT3N1, Dukes C1

5. Polypoid adenocarcinoma infiltrating into the submucosa. No lymph nodes involved.

F. pT4N1, Dukes C1

G. ypT2yN2, Dukes C1 H. pT4N0, Dukes B

A. pT3N2, Dukes C2

1. Caecal adenocarcinoma with intramural extension into terminal ileum and infiltration into subserosal fat; 3/22 lymph nodes involved, apical node clear.

B. pT1N0, Dukes A

2. Low rectal adenocarcinoma infiltrating into the levator muscles; lymph nodes free of tumour.

C. ypT2yN1, Dukes C1

3. Large rectal adenocarcinoma with macroscopic tumour perforation through the mesorectal fat into the retroperitoneum, 2/13 nodes involved, apical node clear

D. pT4N0, Dukes B

4. Rectal adenocarcinoma with preoperative long course chemoradiation. Residual tumour infiltrating into but not beyond muscularis propria. A total of 7 lymph nodes retrieved of which 3 show carcinoma and one contains mucin lakes with no demonstrable tumour cells. Apical node clear

E. pT3N1, Dukes C1

5. Polypoid adenocarcinoma infiltrating into the submucosa. No lymph nodes involved.

F. pT4N1, Dukes C1 G. ypT2yN2, Dukes C1 H. pT4N0, Dukes B

A. pT3N2, Dukes C2

1. Caecal adenocarcinoma with intramural extension into terminal ileum and infiltration into subserosal fat; 3/22 lymph nodes involved, apical node clear.

B. pT1N0, Dukes A

2. Low rectal adenocarcinoma infiltrating into the levator muscles; lymph nodes free of tumour.

C. ypT2yN1, Dukes C1

3. Large rectal adenocarcinoma with macroscopic tumour perforation through the mesorectal fat into the retroperitoneum, 2/13 nodes involved, apical node clear

D. pT4N0, Dukes B

4. Rectal adenocarcinoma with preoperative long course chemoradiation. Residual tumour infiltrating into but not beyond muscularis propria. A total of 7 lymph nodes retrieved of which 3 show carcinoma and one contains mucin lakes with no demonstrable tumour cells. Apical node clear

E. pT3N1, Dukes C1

5. Polypoid adenocarcinoma infiltrating into the submucosa. No lymph nodes involved.

F. pT4N1, Dukes C1 G. ypT2yN2, Dukes C1 H. pT4N0, Dukes B

T staging – colorectal carcinoma • • • •

pT1 – Submucosa pT2 – Into but not beyond muscularis propria pT3 – Subserosal fat/mesorectum pT4 – Serosal involvement/involvement of adjacent organs

• pN1 – 1-3 LN • pN2 – 4+ LN

T staging • Intramural extension into adjacent small bowel loop does not affect T staging • Extramural invasion into adjacent organs – pT4a • Mesorectal invasion with involvement of non peritonealised margin – pT3 • Macroscopic tumour perforation – pT4b

Other parameters • • • • •

M – Metastasis G – Grade R – Completeness of excision L – Presence of lymphatic invasion V – Presence of venous invasion

Modifiers • • • • • •

‘c’ – Clinical ‘p’ – Pathological ‘y’ – Denotes post chemo/radiotherapy ‘r’ – Recurrent tumour ‘a’ – Tumour diagnosed at autopsy ‘(m)’ – Multiple tumours

GIST immunohistochemistry • • • • • • •

KIT (CD117) ................. Almost 95% positive DOG1 ........................... > 95% CD34 ............................ 65% positive (40–72%) Desmin ......................... Negative (0.2%) Smooth muscle actin .... Variably positive (34%) S100 ............................. Variably positive (14%) Cytokeratin ................... Very rarely positive.

GIST • 80% have cKIT mutation – 2/3 exon 11 – best response to imatinib – 1/8 exon 9 – some response with dose escalation – Others – exon 13 and 17

• 10% PDGFRA mutation • 10% other mutations

6. A 52 year old female is found to have a pelvic mass arising from the rectum, which is resected. The mass measures 12 cm in maximum dimension and has a uniform solid cut surface. On histological examination, this is a predominantly spindle cell lesion, with the cells showing minimal nuclear pleomorphism, no necrosis and up to 3 mitoses per 50 hpf. The cells have the following immunoprofile: AE1/AE3 negative, SMA focally positive, desmin negative, S100 negative, CD117 negative, CD34 positive and DOG1 positive. What is the risk of progressive disease for this tumour?

A. B. C. D. E.

None Low Intermediate High Very high

6. A 52 year old female is found to have a pelvic mass arising from the rectum, which is resected. The mass measures 12 cm in maximum dimension and has a uniform solid cut surface. On histological examination, this is a predominantly spindle cell lesion, with the cells showing minimal nuclear pleomorphism, no necrosis and up to 3 mitoses per 50 hpf. The cells have the following immunoprofile: AE1/AE3 negative, SMA focally positive, desmin negative, S100 negative, CD117 negative, CD34 positive and DOG1 positive. What is the risk of progressive disease for this tumour?

A. B. C. D. E.

None Low Intermediate High Very high

Other Lower GI topics • Colon bx in infants – Milk allergy – Hirschsprung’s disease

• Rectal biopsy with easinophilic material – amyloid (Congo Red) • Genes involved in HNPCC • Diversion colitis • Graft versus host disease

Genes in HNPCC • Mismatch repair genes – MLH1 or MSH2 (90%) – MSH6 (7-10%) – PMS2 (less common)

• 80% develop colorectal carcinoma • Also increased risk of: – Endometrial carcinoma (33%) – Ovarian carcinoma (5%) – Cancers of small bowel, stomach, urinary tract and brain

Diversion colitis • History of previous surgery leaving rectal stump • Due to lack of short chain fatty acids • Histology: abnormal crypt architecture, fissuring, crypt abscesses • Increased lymphoid aggregates

Graft versus Host disease • Post stem cell transplant • Acute – within 100 days • Acute GVHD grading: – 1 - apoptosis (collection of eosinophilic globules and nuclear debris) – 2 - apoptosis and crypt abscesses – 3 - total necrosis of individual crypts – 4 - total denudation of areas of bowel

EXTRA QUESTIONS • Taken from all the resources available • GI definitely ‘under represented’ • Hopefully this should cover most topics

MCQ • A 29 year old woman was found to have multiple polyps on colonoscopy. Her father died of colorectal carcinoma aged 50.

• Identify the gene she is most likely to have a mutation of • A APC • B p53 • C MLH1 • D cKIT • E MSH2

MCQ • A 40 year old woman presents with a colonic polyp which is found on histology to be an adenocarcinoma. Her father died aged 40 from colon cancer.

• Identify the familial syndrome she is most likely to have inherited.

• A FAP • B HNPCC • C Marfans syndrome • D Muir Torre syndrome • E Gardner’s syndrome

MCQ • A 35 year old male is diagnosed with Lynch syndrome (HNPCC).

• Identify the most common genetic mutation related to this condition.

• A p53 • B MSH2 • C MLH3 • D PMS2 • E APC

MCQ • A 32 year old woman complains of abdominal pain. She is found to have an 8cm small bowel tumour. Following resection, immunohistochemistry is performed. The tumour cells are positive for CD34, SMA and CD117.

• Identify the correct diagnosis.

• A Gastrointestinal stromal tumour • B Leiomyoma • C Leiomyosarcoma • D Fibromatosis • E Hodgkin’s lymphoma

EMQ • Causes of diarrhoea • A 32 year old female. Recent travel to Russia. Had a few episodes of diarrhoea on return. Now weight loss. Otherwise well.

• Answer: Giardia

EMQ • B 78 year old lady admitted with confusion and diagnosed with urinary tract infection. Started on ciprofloxacin.

Develops high volume watery diarrhoea.

• Answer: Pseudomembranous colitis

EMQ • C 72 year old male post coronary artery bypass graft surgery. Develops abdominal pain and acidosis.

• Answer: Ischaemic colitis

EMQ • D 52 year old male with HIV. Develops chronic diarrhoea, weight loss and skin pigmentation. On duodenal biopsy, PAS positive bacilli seen in macrophages.

• Answer: Whipple’s disease

EMQ • 29 year old woman with diarrhoea, weight loss, tremor and increased appetite.

• Answer: Hyperthyroidism

EMQ • Intestinal polyps • A Pedunculated polyp with arborising branching architecture • Answer: Peutz-Jeughers polyp • B 5 year old girl with pedunculated polyp • Answer: Juvenile polyp • C 21 year old male with hundereds of polyps throughout the entire bowel • Answer: Familial Adenomatous Polyposis

MCQ • A 78 year old man complains of dysphagia and weight loss. A gastroscopy is performed and a biopsy taken from an ulcerated lesion. Histology shows ulceration with ‘Cowdry A’ bodies • Identify the correct diagnosis • A Eosinophilic oesophagitis • B Barretts oesophagus • C Candida infection • D Squamous cell carcinoma • E Herpes simplex virus

MCQ • A 45 year old man is on methotrexate for long term psoriasis. He complains of dysphagia and a gastroscopy is performed. Histology shows squamous lined mucosa containing moderate numbers of neutrophils.

• Identify the most appropriate further investigation.

• A PAS • B HSV immunohistochemistry • C Giemsa • D Perls stain • E CD117

EMQ • Tumours matched with associated conditions • T cell lymphoma of SI and Coeliac disease • H pylori and MALToma of the stomach • Barretts oesophagus and adenocarcinoma

MCQ and EMQ • Genes • APC as first step in adenoma-carcinoma sequence • HNPCC genes – MSH 2 – MLH 1 – MSH 6 – PMS 2

60% 30% 7-10% <5%

EMQs • APR anatomy – Skin – Peritoneal reflection – Mesorectal v intramesorectal v muscularis – Dentate line

GOOD LUCK