Page 602 - Textbook of Pathology, 6th Edition

586 and connective tissue tumours. The number of polyps in duration changes the bacterial flora of the bowel, thus
Gardner’s syndrome is generally fewer than in the familial resulting in production of carcinogenic substances.
polyposis coli but their clinical behaviour is identical. 3. Adenoma-carcinoma sequence. There is strong evidence
to suggest that colonic adenocarcinoma evolves from pre-
Turcot’s Syndrome existing adenomas, referred to as adenoma-carcinoma
Turcot’s syndrome is combination of familial polyposis coli sequence (Fig. 20.45). The following evidences are cited to
and malignant neoplasms of the central nervous system. support this hypothesis:
i) In a case with early invasive cancer, the surrounding
Juvenile Polyposis Syndrome tissue often shows preceding changes of evolution from
adenoma → hyperplasia → dysplasia → carcinoma in situ →
Juvenile polyposis is appearance of multiple juvenile polyps invasive carcinoma.
in the colon, stomach and small intestine but their number is ii) Incidence of adenomas in a population is directly propor-
not as high as in familial polyposis coli. Family history in tionate to the prevalence of colorectal cancer.
some cases may show autosomal dominant inheritance iii) The risk of adenocarcinoma colon declines with endoscopic
pattern, while it may be negative in others. They resemble removal of all identified adenomas.
the typical juvenile polyps as regards their age (under 5 iv) Peak incidence of adenomas generally precedes by some
years), sex distribution and morphology. They lack the years to a few decades the peak incidence for colorectal
malignant potential. cancer.
v) The risk of malignancy increases with the following
OTHER BENIGN TUMOURS adenoma-related factors:
Some non-epithelial benign tumours that may rarely occur a) Number of adenomas: familial polyposis coli syndrome
in large intestine are leiomyomas, leiomyoblastoma, neuri- almost certainly evolves into malignancy.
lemmoma, lipoma and vascular tumours (haemangioma, b) Size of adenomas: large size increases the risk.
lymphangioma). c) Type of adenomas: greater villous component associated
with higher prevalence.
MALIGNANT COLORECTAL TUMOURS 4. Hereditary non-polyposis colonic cancer (HNPCC or
Lynch syndrome). HNPCC is an autosomal dominant
A. Colorectal Carcinoma condition in which colorectal cancer is seen in at least two
SECTION III
Colorectal cancer comprises 98% of all malignant tumours generations of first-degree relatives before the age of 50 years,
of the large intestine. It is the commonest form of visceral without evidence of familial polyposis coli. There are germline
cancer accounting for deaths from cancer in the United States, mutations in mismatch repair genes, human mutL homolog
next only to lung cancer. The incidence of carcinoma of the abbreviated as hMLH2 located on chromosome 2 and hMLH1
large intestine rises with age; average age of patients is about on chromosome 3 resulting in DNA instability. In HNPCC,
60 years. Cancer in the rectum is more common in males colon cancer appears at a relatively younger age (<50 years),
than females in the ratio of 2:1, while at other locations in association with multiple primary cancers at different sites
the large bowel the overall incidence is equal for both sexes. (e.g. endometrium, ovary), preferred location in proximal
colon and better prognosis than other sporadic colon cancer
ETIOLOGY. As with most other cancers, etiology of cases.
colorectal carcinoma is not clear but a few etiological factors 5. Other factors. Presence of certain pre-existing diseases
have been implicated:
Systemic Pathology
such as inflammatory bowel disease (especially ulcerative
1. Geographic variations. The incidence of large bowel colitis) and diverticular disease for long duration increase
carcinoma shows wide variation throughout the world. It is the risk of developing colorectal cancer subsequently. It may
much more common in North America, Northern Europe be recalled here that low fibre diet is implicated in the
than in South America, Africa and Asia. Colorectal cancer is pathogenesis of diverticular disease as well. Besides, there
generally thought to be a disease of affluent societies because is an etiologic role of tobacco smoking in development of
its incidence is directly correlated with the socioeconomic colorectal cancer in youger patients.
status of the countries. In Japan, however, colon cancer is
much less common than in the US but the incidence of rectal GENETIC BASIS OF COLORECTAL CARCINOGENESIS.
cancer is similar. Studies by molecular genetics have revealed that there are
2. Dietary factors. Diet plays a significant part in the sequential multistep mutations in evolution of colorectal
causation of colorectal cancer: cancer from adenomas by one of the following two
i) A low intake of vegetable fibre-diet leading to low stool mechanisms:
bulk is associated with higher risk of colorectal cancer. 1. APC mutation/ β β β β β-catenin mechanism. This pathway of
ii) Consumption of large amounts of fatty foods by multiple mutations is generally associated with
populations results in excessive cholesterol and their morphologically identifiable changes as described above in
metabolites which may be carcinogenic. adenoma-carcinoma sequence. These changes are as under:
iii) Excessive consumption of refined carbohydrates that i) Loss of tumour suppressor APC (adenomatous polyposis coli)
remain in contact with the colonic mucosa for prolonged gene located on the long arm of chromosome 5 (5q) is present