Gastrointestinal

Disease
TUMOURS OF THE SMALL AND LARGE INTESTINE

Recommended reading – Robbins Basic Pathology

10TH Edition – pp 626-634
 Learning Objectives
SLO# 1 :Classify tumors of small and large intestine
SLO# 2 : List types of intestinal polyps and neoplastic polyps
SLO# 3 :Describe gross and microscopic features of intestinal polyps and
neoplastic polyps
SLO# 4 : Identify clinical features of neoplastic polyps
SLO#5 : Explain the relationship between neoplastic polyps and carcinoma
SLO# 6 : Describe familial polyposis syndrome and hereditary non-
polyposis colonic cancer
SLO# 7: List the risk factors for development of adenocarcinoma colon
SLO#8: Explain two pathogenetic pathway of colon carcinogenesis
SLO#9: Describe gross , microscopic , and clinical features of
adenocarcinoma colon
SLO#10: Identify the screening and diagnostic methods for diagnosis of
colon cancer
SLO #11 : Explain the TNM staging of colorectal cancer
Tumours of the small and large intestine Classification
benign

Intestinal polyps Familial Polyposis Syndrome

◦ Hyperplastic polyps Malignant Tumors
◦ Hamartomatous polyps Adenocarcinoma
(Juvenile & Peutz- Carcinoid
Jeghers polyps) Anal zone carcinoma
◦ Inflammatory polyps
Mesenchymal Tumors
◦ Lymphoid polyps GIT stromal tumors
Neoplastic polyps (benign & malignant)
◦ Adenoma -Tubular Others ( lipoma, neuroma,
angioma, Kaposi sarcoma)
- Villous Lymphoma
- Tubulo-villous
 Intestinal Polyps

Represent 90% of all epithelial polyp found in large

intestine.
Usual age is 60 years or older.
Types: 1. Hyperplastic polyp.
2. Hamartomatous polyp (Juvenile & Peutz-
Jeghers)
3. Inflammatory polyp
4. Lymphoid polyp
 Intestinal Polyps
1. Hyperplastic Polyp
▪Asymptomatic noncancerous growth t

▪ > 50% are located in the rectosigmoid, 20%

in the ascending colon.
▪Smooth, moist, round, small (0.5cm) sessile
lesions.
▪Multiple polyps are frequent.
▪Composed of well-formed glands and crypts
lined by differentiated goblet or absorptive
cells.
▪Pure hyperplastic polyps have no malignant
potential.
 HAMARTOMATOUS
children
2.JUVENILE POLYPS (Retention polyps)
•Children < 5 years,
•predominantly rectum
•Gross: large (1-3 cm. diameter), usually
single, rounded, smooth, pedunculated
•Mic: lamina propria with cystically
dilated glands filled with mucus
•Clinical: rectal bleeding, infarction
 HAMARTOMATOUS POLYPS
PEUTZ-JEGHERS POLYPS
▪Rare, autosomal dominant syndrome
▪Multiple hamartomatous polyps throughout GIT +
melanotic
mucosal & cutaneous pigmentation – lips, oral mucosa,
genitalia, hands
▪Gross: large, pedunculated
▪Mic: connective tissue
+ smooth muscle + glands
▪Clinical: Obstruction, Intussusception.
 3. Inflammatory Polyps

▪Occur in patients with longstanding

IBD,especially in chronic ulcerative colitis.
▪ Usually multiple.
▪ Represent an exuberant reparative
responseto longstanding mucosal injury
called pseudo polyps
▪Mic- connective tissue core +Inflammatory
cells+ cystically dilated glands covered by
regenerating epithelium
Lymphoid polyps

Solitary or multiple tiny elevated

lesions
Common in rectum, also called
rectal tonsils
Micro- lymphoid follicles with
germinal centers located in
mucosa and submucosa
 Neoplastic Polyps
▪TUBULAR ADENOMAS
Predominantly seen in colon
Single/ Multiple
Occurs sporadically and in well defined hereditary
syndromes.
Average age is 60 years
Size: small (sessile) , large(pedunculated)
Micro - Stalk has a central core of fibrovascular tissue,
covered with dysplastic colonic mucosa.
Severe dysplasia and invasive carcinoma in about 5% of
tubular adenoma
Tubular adenoma
 2] Villous Adenoma
Morphology
◦ Size: 1 to 10 cm in diameter.
◦ Most are broad, sessile, velvety lesions projecting 1 to 3
cm.
◦ Frondlike papillary projections of adenomatous
epithelium with a delicate fibrovascular core.
◦ All degree of dysplasia with frank invasive carcinoma in
up to 40%.
3] Tubulo-villous adenoma

Intermediate form of pattern between tubular and

villous adenoma.

Degree of dysplasia and malignant potential is

intermediate between tubular and villous adenomas.
Neoplastic Polyps
▪Clinical features
▪The smaller adenomas are usually asymptomatic,
occult bleeding.
▪Villous adenomas are much more frequently
symptomatic because of overt or occult rectal bleeding
or mucoid material rich in protein and potassium to
produce hypoproteinemia or hypokalemia.
▪Adenomas in the immediate vicinity of the ampulla of
Vater may produce biliary obstruction.
Relationship of Neoplastic Polyps to Carcinoma

Adenoma to carcinoma sequence is documented by

several observations and genetic alterations.

The probability of carcinoma occurring in a neoplastic

polyp is related to:
The larger the polyp becomes, the bigger the risk
1. The size of the polyp. of it developing into colon cancer

2. The relative proportion of its villous features.

3. The presence of significant cytological atypia
(dysplasia) in the neoplastic cells.
 Familial Polyposis Syndrome
▪Patients have genetic tendencies to develop neoplastic polyps, most
often autosomal dominant.
▪ Familial polyposis coli (FPC)
▪Genetic defect – APC gene mutation
too much
▪Innumerable neoplastic polyps in the colon (500 to 2500)
▪Polyps are also found elsewhere in alimentary tract
▪Most polyps are tubular adenomas
▪The risk of colorectal cancer is 100% by midlife.
▪ Gardener’s syndrome
▪Polyposis coli, multiple osteomas, epidermal cysts, and fibromatosis.
▪ Turcot syndrome
▪ Polyposis coli, glioma and fibromatosis
Hundreds of polyps in colon Three tubular adenomas in a single
microscopic field
Hereditary non-polyposis
colonic cancer(HNPCC)
▪Lynch syndrome
▪Autosomal dominant
▪germ-line mutations of DNA mismatch repair genes
like MSH2 or MLH1.
▪Occurs in younger age < 50 years
▪Associated with other primary cancers like
endometrial ca , ovarian ca ,etc.
 Malignant Tumours of Large Intestine:
Adenocarcinoma
The wall of the large intestine is lined with simple columnar
epithelium. Both the small intestine and the large intestine have
goblet cells, but they are abundant in the large intestine

Constitutes 98% of all cancers in the large intestine.

Worldwide distribution, highest incidence in west.
Incidence is correlated with the socioeconomic status of
countries
Peak incidence in the sixth to seventh decade.
Common in males than female, 2:1 ratio
Predisposing factors: IBD, polyposis syndrome and
diverticular diseases.
Dietary factors:
- Low content of unabsorbable vegetable fibre.
- High content of refined carbohydrates.
- High fat content.
- Increased intake of nitrites, nitrates (nitrosamines).
- Reduced intake of vit A, C & E.
Adenoma – carcinoma sequence:
Increased risk of malignancy
a) Increased Number of adenomas- familial polyposis coli
b) Size- large size
c)Type of adenoma - villous component
 Colorectal carcinogenesis

Two pathogenetically distinct pathways both result from

accumulation of multiple mutations

◦ The APC/B-catenin pathway

◦ Microsatellite instability (MSI) Mechanism
Malignant Tumours of Large Intestine
Adenocarcinoma
Colorectal carcinogenesis
Microsatellite instability (MSI) Mechanism
▪Defective DNA mismatch repair
▪Basic mutation is loss of DNA repair gene result in
repetitive DNA sequences(microsatellites) – unstable
during replication termed microsatellite instability.
▪The significant DNA repair genes are
▪i) TGF-β receptor gene - normally inhibits cell
proliferation but in mutated form allows the
uncontrolled proliferation of colonic epithelium
in adenoma
▪ii) BAX gene - normally causes apoptosis but a defect in
it results in loss of apoptosis and dysregulated growth
 Colorectal Carcinoma
Morphology
▪Proximal colon (ascending colon) –
polypoid, exophytic
▪Distal colon (descending) – annular
encircling lesions – napkin-ring
constriction of bowel
 CA COLON
MICROSCOPY
▪Well-differentiated to Undifferentiated
adenocarcinoma
▪Signet-ring appearance
▪Carcinomas in anal zone – squamous cell
carcinomas

Malignant glands

Muscle layer
 Colorectal Carcinoma

▪Clinical features
hypochromatic, microcytic

Left-sided lesions
▪-present earlier – obstruction and change in bowel
habits.
▪ Poorer prognosis- infiltrative growth pattern
Right-sided lesions
▪ present with weakness, malaise, weight loss,
unexplained anaemia (secondary to early bleeding).
 Colorectal Carcinoma

Spread: - direct extension.

- metastasis through:
- lymphatic
- blood vessels
-favoured sites are regional
-lymph node,liver, lungs, bones.
 CA COLON - DIAGNOSIS The pre-operative evaluation should
include a complete blood count,
carcinoembryonic antigen (CEA),
colonoscopy, and chest radiograph.

➢Digital rectal testing

➢Fecal testing for occult blood loss
➢Sigmoidoscopy, colonoscopy, Contrast CT
➢Serum markers – carcinoembryonic antigen (CEA)
➢ - related to tumour size and extent of spread.
➢ - helpful in monitoring for recurrence of tumour
after resection.
➢Pitfalls of CEA – not sensitive, not specific (may be + in
ca lung, breast, ovary, pancreatitis, ulcerative colitis etc)
 TNM STAGING OF COLORECTAL CANCER – BASED ON DEPTH
OF INVASION

Tis – T1 – tumor
carcinoma invades
in situ submucosa

T2 – tumor
extends into T3 –
muscularis invasion
propria
of
subserosa

T4 – invasion into adjacent organs/peritoneum N0, N1, N2 – M0, M1