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