ICC-2 [060]

Cancer colon

Magda Assaf, PhD

Professor of Pathology
Aims NEWGIZA UNIVERSITY

To describe colorectal malignancies in terms of their

histological type, causes and effects

Intending learning outcomes

By the end of this lecture students should be able to:
• Describe the aetiology and pathogenetic mechanisms that
lead to the development of colon cancer.
• List the common sites of metastasis of primary GI tumours
• Recognize the grade and stage of a tumour in light of the
given data and the microscopic images.

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Malignant tumours of the GI tract

The prognosis of a malignant tumour depends mainly on its

grade and stage

Higher grade and stage tumours tend to be more aggressive

What are the specific markers used to diagnose GIT carcinoma?

Serum à CEA
Tissue à CDX -2

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Grade of a malignant tumour

How well differentiated the tumour is

Grade 1 – well differentiated (tumour looks like cell of

origin)

Grade 2 and 3 – moderate& poor differentiation

Grade 4 – undifferentiated

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Grading

Well- differentiated adenocarcinoma Moderately differentiated adenocarcinoma

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Moderately to poorly differentiated

adenocarcinoma

Poorly differentiated adenocarcinoma Poorly differentiated adenocarcinoma,

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Tendency towards glandular formations Glands are not visible 6
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B
Identify
A
B
C

What is the grade?

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Stage
How far the tumour has spread
• TNM (Tumour, Node,Metastasis)
• Dukes’ classification

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Staging of colorectal cancer

1. T.N.M. staging
• Tis: Carcinoma in situ.
• T1: Tumor invades into submucosa
• T2: Tumor invades musculosa
• T3: Tumor invades till subserosa
• T4: Tumor invades visceral peritoneum and
may involve nearby tissue or organ

• N0: no lymph node metastasis

• N1: metastasis in 1- 3 pericolic or peritoneal nodes
• N2: metastasis in 4 or more pericolic or peritoneal nodes
• N3: metastasis in any nodes along the course
of major blood vessels.

• M0: no distant metastasis

• M1: distant metastasis

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TNM staging of colorectal cancer

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2. Dukes’ staging of colorectal cancer

Dukes’ A
Tumour confined to bowel wall
Dukes’ B
Tumour extending through the bowel wall
Dukes’ C
Regional lymph nodes involved

Dukes’ D
Metastatic disease

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Staging of cancer colon

2. Modified Dukes’ staging

Correlates Tumour invasion with both number of metastatic Lymph
Nodes and distant Metastasis

Dukes’ stage T N M
Stage A T1
Stage B1 T2 NO
Stage B2 T3 or T4 MO
Stage C1 T2 N1, 2 or 3
Stage C2 T3 or T4
Stage D Any T Any N M1

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Describe this tumour 18

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 Cauliflower mass NEWGIZA UNIVERSITY

Size of the
tumour

Extent of infiltration
through the wall

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Lymph node metastasis by

Adenocarcinoma

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Hepatic metastasis by colorectal carcinoma

CT scan showing multiple lesions Post-mortem liver specimen

Of varying sizes showing multiple metastatic nodules

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Why is staging important?

Examples:
• colonic T1N0M0 would have surgical resection alone

• colonic T3N2M0 would get surgery plus adjuvant chemotherapy

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Cancer colon
Aetiology and predisposing factors
• Diet:
- Low vegetable fiber intake [Vegetable fibers are thought to increase the bulk
of the stools thus diluting the concentrations of putative carcinogens and at
the same time speed the transit through the large intestine thus decreasing
the mucosal exposure to possible offenders].
- High content of refined carbohydrates
- Diminished vitamin A, C, and E (protective micronutrients)
- Excess fat intake enhances synthesis of cholesterol and bile acids by liver
which may be converted to potential carcinogens by bacterial flora of large
intestine.
• Genetic factors:
- Genes known to increase likelihood of adenoma formations
- Genetic cancer syndromes (FAP, HNPCC)
• Inflammatory bowel disease
FAP: Familial Adenomatous Polyposis [mutation of APC gene]
HNPCC:
M. Assaf Hereditary Non-Polyposis Colorectal Cancer [ alteration of DNA of mismatch repair gene]
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Carcinoma of the colon, presenting symptoms

1. Change in bowel habits, most common symptom (74%)

2. Rectal bleeding in combination with change in bowel habits (51%)
[blood /rectum]
3. Rectal or abdominal mass (24.5- 12.5%)
4. Iron deficiency anemia (9.6%)
5. Abdominal pain is the least common symptom (3.8%)

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Cancer colon
Pathogenesis

Two separate pathogenic pathways

• Adenoma-carcinoma sequence
• Inflammation-dysplasia sequence

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I. Adenoma-Carcinoma Sequence

• Initial lesion is benign tumour – adenoma

• The degree of dysplasia increases over time
• Eventually invades through basement
membrane
• At which point is an adenocarcinoma

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Adenoma- carcinoma sequence

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Adenoma- carcinoma sequence NEWGIZA UNIVERSITY

Genetic mutations of APC, K- ras and p 53 genes

MMR genes: mismatch repair genes
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Adenoma Carcinoma sequence

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Adenomatous polyp showing an

invasive adenocarcinoma (à)

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Cancer colon
Pathogenesis, continued

II. Inflammation-dysplasia sequence (a less common

pathway)
• Inflammatory bowel disease causes chronic
inflammation of large bowel
• Comprises both Ulcerative colitis and Crohn’s disease
• Inflammation leads to epithelial cell damage
• Increases epithelial cell turnover
• Increases risk of dysplasia and then malignancy

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Normal Dysplasia

Inflammatory bowel disease

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Colonic adenocarcinoma

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An omental biopsy shows diffuse infiltration by

adenocarcinoma with signet ring cells. Which is
the most likely primary site?

A. Stomach
B. Liver
C. Rectum
D. Kidney
E. Oesophagus

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An omental biopsy shows diffuse infiltration by

adenocarcinoma with signet ring cells. Which is
the most likely primary site?

A. Stomach
B. Liver
C. Rectum
D. Kidney
E. Oesophagus

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A 56 year old woman has an ultrasound scan of

the liver that reveals multiple deposits consistent
with metastases.
A liver biopsy shows squamous cell carcinoma.
Which of the following is the most likely primary
site of the malignancy ?
A. Colon
B. Oesophagus
C. Ovary
D. Pancreas
E. Stomach

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A 56 year old woman has an ultrasound scan

of the liver that reveals multiple deposits
consistent with metastases.A liver biopsy
shows squamous cell carcinoma.
Which of the following is the most likely
primary site of the malignancy?

A. Colon
B. Oesophagus
C. Ovary
D. Pancreas
E. Stomach

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A 68 year old lady was admitted to hospital with

symptoms and signs of large bowel obstruction.
At laparotomy there was evidence
of an obstructing lesion at the
rectosigmoid junction.
An anterior resection was
preformed.

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1. What is the most likely histological diagnosis

A. adenocarcinoma
B. squamous cell carcinoma
C. adenoma
D. signet ring cell carcinoma
E. GIST

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1. What is the most likely

histological diagnosis

A. adenocarcinoma
B. squamous cell carcinoma
C. adenoma
D. signet ring cell carcinoma
E. GIST

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The histopathology report states:

Sections show a moderately differentiated
adenocarcinoma which extends through the
wall into the subserosa but does not breach
the serosal surface. Three lymph nodes
show metastatic adenocarcinoma. The high
tie node is free of tumour (nodes above root of
Inferior mesenteric artery)

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2. What is the Dukes’ staging of this tumour

A. A
B. B
C. C1
D. C2
E. D

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2. What is the Dukes’ staging of this tumour

a. A
b. B
c. C1
d. C2
e. D

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Case study
A 65 year old man has recently noticed bleeding/rectum.
Endoscopy reveals the presence of a malignant fungating mass in
the colon. MRI has shown multiple hepatic nodules suggestive of
metastasis.

Which is the most specific immunohistochemical marker used to

confirm malignancy of primary colon origin in the hepatic nodules?

A. C-kit
B. CEA
C. GOG-1
D. CDX-1
E. P-53

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Objectives
By the end of this lecture students should be able to:
• Describe the aetiology and pathogenetic mechanisms that
lead to the development of colon cancer.
• List the common sites of metastasis of primary GI tumours
• Recognize the grade and stage of a tumour in light of the
given data and the microscopic images.

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