Table 5. Extracolonic Tumor Risks in Familial Adenomatous Polyposis continued...
Density of colonic polyposis
Researchers have found that dense carpeting of colonic polyps, a feature of classic FAP, is seen in most patients with APC mutations, particularly those mutations that occur between codons 169 and 1393. At the other end of the spectrum, sparse polyps are features of patients with mutations occurring at the extreme ends of the APC gene or in exon 9. (Refer to the Attenuated Familial Adenomatous Polyposis (AFAP) section of this summary for more information.)
Desmoid tumors are proliferative, locally invasive, nonmetastasizing, fibromatous tumors in a collagen matrix. Although they do not metastasize, they can grow very aggressively and be life threatening. Desmoids may occur sporadically, as part of classical FAP, or in a hereditary manner without the colon findings of FAP.[15,26] Desmoids have been associated with hereditary APC gene mutations even when not associated with typical adenomatous polyposis of the colon.[26,27]
Most studies have found that 10% of FAP patients develop desmoids, with reported ranges of 8% to 38%. The incidence varies with the means of ascertainment and the location of the mutation in the APC gene.[26,28,29]APC mutations occurring between codons 1445 and 1578 have been associated with an increased incidence of desmoid tumors in FAP patients.[27,30,31,32] Desmoid tumors with a late onset and a milder intestinal polyposis phenotype (hereditary desmoid disease) have been described in patients with mutations at codon 1924.
A desmoid risk factor scale has been described in an attempt to identify patients who are likely to develop desmoid tumors. The desmoid risk factor scale was based on gender, presence or absence of extracolonic manifestations, family history of desmoids, and genotype, if available. By utilizing this scale, it was possible to stratify FAP patients into low-, medium-, and high-risk groups for developing desmoid tumors. It was concluded that the desmoid risk factor scale could be used for surgical planning. Validation of the risk factors comprising this scale were recently supported by a large, multiregistry, retrospective study from Europe.
The natural history of desmoids is variable. Some authors have proposed a model for desmoid tumor formation whereby abnormal fibroblast function leads to mesenteric plaque-like desmoid precursor lesions, which in some cases occur prior to surgery and progress to mesenteric fibromatosis after surgical trauma, ultimately giving rise to desmoid tumors. It is estimated that 10% of desmoids resolve, 50% remain stable for prolonged periods, 30% fluctuate, and 10% grow rapidly. Desmoids often occur after surgical or physiological trauma, and both endocrine and genetic factors have been implicated. Approximately 80% of intra-abdominal desmoids in FAP occur after surgical trauma.[37,38]
The desmoids in FAP are often intra-abdominal, may present early, and can lead to intestinal obstruction or infarction and/or obstruction of the ureters. In some series, desmoids are the second most common cause of death after CRC in FAP patients.[39,40] A staging system has been proposed to facilitate the stratification of intra-abdominal desmoids by disease severity. The proposed staging system for intra-abdominal desmoids is as follows: stage I for asymptomatic, nongrowing desmoids; stage II for symptomatic, nongrowing desmoids of 10 cm or less in maximum diameter; stage III for symptomatic desmoids of 11 to 20 cm or for asymptomatic, slow-growing desmoids; and stage IV for desmoids larger than 20 cm, or rapidly growing, or with life-threatening complications.