Fig.15.34 Histologicappearanceofcolonicadenomas.(A)Tubularadenomawithasmoothsurfaceandroundedglands.Inthiscase,cryptdilationandrupture,withassociatedreactiveinflammation,canbeseenatthebottomofthefield.(B)Villousadenomawithlong,slenderprojectionsthatarereminiscentofsmall-intestinalvilli.(C)Dysplasticepithelialcells(top) withanincreasednuclear-to-cytoplasmicratio,hyperchromaticandelongatednuclei,andnuclearpseudostratification.Comparewiththenondysplasticepithelium(bottom). (D)Sessileserratedadenomalinedbygobletcellswithouttypicalcytologicfeaturesofdysplasia.Thislesionisdistinguishedfromahyperplasticpolypbyinvolvementofthecrypts.Comparewiththehyperplasticpolypin
Fig.15.32 cancerisextremelyrareinadenomaslessthan1cmindiameter,somestudiessuggestthatnearly40%oflesionslargerthan4cmindiametercontainfociofinvasivecancer.Inadditiontosize,high-gradedysplasiaisariskfactorforcancerinanindividualpolyp(butnototherpolypsinthesamepatient).
Several syndromes associated with colonic polyps and increased rates of colon cancer have been described. The genetic basis of these disorders has been established and has greatly enhanced the current understanding of sporadic colon cancer (
Table 15.7
Familial adenomatous polyposis (FAP) is an autosomal dominant disorder marked by the appearance of numerous colorectal adenomas by the teenage years. It is caused by mutations of the adenomatous polyposis coli gene (APC). A count of at least 100 polyps is necessary for a diagnosis of classic FAP, and as many as several thousand may be present (
Fig. 15.35 ). Except for their remarkable numbers, these growths are morphologically indistinguishable from sporadic adenomas. Colorectal adenocarcinoma develops in 100% of patients with untreated FAP, often before 30 years of age. As a result, prophylactic colectomy is standard therapy for individuals carrying APC mutations. However, patients remain at risk for extraintestinal manifestations, including neoplasia at other sites. Specific APC mutations are also associated with the development of other manifestations of FAP and explain variants such as Gardner syndrome and Turcot syndrome. In addition to intestinal polyps, clinical features of Gardner syndrome, a variant of FAP, may include osteomas of the mandible, skull, and long bones; epidermal cysts; desmoid and thyroid tumors; and dental abnormalities, including unerupted and supernumerary teeth. Turcot syndrome is rarer and is characterized by intestinal adenomas and tumors of the central nervous system. Two-thirds of http://ebooksmedicine.net
Table 15.7 Common Patterns of Sporadic and Familial Colorectal Neoplasia
FamilialadenomatousAPC/WNTpathwayAPC AutosomaldominantNoneTubular,villous;typicalpolyposis(70%ofFAP)
HereditarynonpolyposisDNAmismatchrepairMSH2, MLH1 AutosomaldominantRightsideSessileserratedadenoma;colorectalcancer patients with Turcot syndrome have APC gene mutations and develop medulloblastomas. The remaining one-third have mutations in one of several genes involved in DNA repair and develop glioblastomas. Some patients with hundreds of adenomas lack APC mutations but instead have mutations of the base excision repair gene MUTYH (also called MUTYH polyposis). The role of these genes in tumor development is discussed later.