world cancer report - iarc

Diagnostic criteria for hereditary nonpolyposis colorectal cancer
There should be at least three relatives with colorectal cancer:
•One should be a first degree relative of the other two
•At least two successive generations should be affected
•At least one colorectal cancer should be diagnosed before age 50
•Familial adenomatous polyposis should be excluded
•Tumours should be verified by pathological examination
Table 5.5 Criteria for hereditary nonpolyposis colorectal cancer syndrome.
The occurrence of colorectal cancer in
three successive generations and at a
young age in at least one person is among
the so-called Amsterdam criteria, which
suggest the possibility of hereditary nonpolyposis
colorectal cancer syndrome,
and justifies colorectal exploration and
genetic testing (Table 5.5). The detection of
diffuse polyposis in the colon (Fig. 5.32)
justifies genetic testing for familial adenomatous
polyposis syndrome.
Occult bleeding in the stools of asymptomatic
persons can be explored by the faecal
occult blood test (FOBT). However,
this test is reserved for mass screening
interventions with assessment of its sensitivity
and specificity. In other situations,
endoscopy is the gold standard method of
detection and should be preferred to the
barium enema (Fig. 5.35), which while
detecting large tumours is less reliable for
the detection of small and flat lesions.
Helical CT scan is proposed in most cases
as a complementary investigation, helping
to assess local tumour invasion and
regional and distant metastases. In elderly
persons with a poor health status, a
colo-scanner with a water enema is a less
aggressive procedure than colonoscopy.
A major advantage of endoscopy is the
ease with which tissue can be sampled by
forceps biopsy and the ability to detect
small or flat neoplastic lesions, such as
described by the Japanese school and
classified as II type (IIa or elevated, IIb or
completely flush, IIc or depressed).
Detection of such lesions requires a high
definition fibroscope with a contrast
enhancement system and the use of chromoendoscopy
(Colorectal cancer screen-
200 Human cancers by organ site
ing, p163). The depressed IIc type is a
precursor of advanced cancer. Flexible
sigmoidoscopy explores the distal colon;
colonoscopy explores the whole of the
colon. Another advantage of endoscopy is
the potential for interventional procedures
and the resection of adenomatous
polyps.
Pathology and genetics
Abnormalities of the colonic epithelium,
cell atypia and architectural disorders
have been classified as premalignant (lowgrade
and high-grade dysplasia) or malignant
(cancer). The current trend is to
adopt a classification of tissue samples
based upon the term “neoplasia” [6]. The
following grades are considered: absence
of neoplasia, indeterminate for neoplasia,
certain for neoplasia with the two grades
of light and severe cell atypia and intramucosal
cancer. However, there is no
invasion of lymph nodes when the lesion is
limited to the mucosa. Therefore there is a
tendency to use the term “cancer” only
when there is a submucosal extension of
the lesion. Epithelial abnormalities in polypoid
neoplasia are usually called “adenoma”
(Fig. 5.33). Only a small fraction of
polypoid or flat lesions progress to carcinoma.
The major malignant histological type is
adenocarcinoma (Fig. 5.34). Other less
common epithelial tumour types include
mucinous adenocarcinoma, signet-ring
tumours, squamous cell carcinomas,
adenosquamous carcinomas and undifferentiated
carcinomas.
Genetic susceptibility to colorectal cancer
may be attributable to either the polyposis
Fig. 5.32 Surgical specimen of the colon from a
patient suffering from polyposis coli.
Fig. 5.33 A polypoid tubulovillus adenoma of the
colon; the adenomatous proliferation (arrow)
forms the head of the polyp, the stalk of which is
lined by normal colonic mucosa.
T
T
Fig. 5.34 Moderately differentiated adenocarcinoma
of the colon (T), infiltrating the submucosa.
or the nonpolyposis syndromes. The major
polyposis syndrome is familial adenomatous
polyposis, caused by a germline
mutation in the adenomatous polyposis
coli (APC) gene. Familial adenomatous
polyposis can be associated with nervous
system tumours (Turcot syndrome) or with
desmoid tumours (Gardner syndrome).
The APC gene, on chromosome 5q21-22,
produces the APC protein, a negative regulator
that controls β-catenin concentration
and interacts with E-cadherin, a mem-