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We read with interest the article by Matsumoto et al reporting their observations on the presence of serrated adenomas in familial adenomatous polyposis (FAP) patients in relation to germline APC mutations (Gut 2002;50:402–4). Their small colonoscopic study identified three FAP patients with serrated adenomas; all had less than 100 polyps and they concluded that serrated adenomas may be characteristic of attenuated FAP.
It is our practice to perform prophylactic colectomy with ileorectal anastomosis or ileoanal pouch formation in patients with FAP in the second or third decade or as soon as possible after a new diagnosis is established. An expert histopathologist performs a meticulous examination of the colectomy specimen, including a formal polyp count. Thereafter any rectal remnant is surveyed six monthly by flexible sigmoidoscopy with endoscopic snare polypectomy and argon plasma coagulation of suspicious lesions.
A simple search of the St Mark’s polyposis registry has revealed eight patients in whom serrated adenomas have been identified. In five patients the lesion was present in the colectomy specimen, in two the diagnosis was made on flexible endoscopic surveillance, and in one case a serrated adenoma was present in a polyp surgically excised from the rectum (table 1).
As in Matsumoto’s study, in the majority of the St Mark’s cases the serrated adenoma was located distally either in the sigmoid colon or rectum. However, in our patients serrated adenomas were not restricted to those with the attenuated phenotype. Seven of the St Mark’s patients with serrated adenomas have classical FAP with more than 100 colonic polyps in the colectomy specimen. (In one of these patients preoperative colonoscopy reported a low polyp count.) The genetic mutations have been identified in three of our patients and all were in exon 15, rather than more proximally.
Serrated adenomas may be a feature in FAP but they are not characteristic of the attenuated phenotype. Colonoscopy alone may underestimate the number of colorectal polyps, especially in difficult cases. We believe that dye spray colonoscopy by an experienced endoscopist and careful examination of colectomy specimens are necessary to completely characterise the FAP phenotype.
The clinical significance of the presence of serrated adenomas in FAP patients has yet to be determined. Further studies in this interesting area are required.
Patient characteristics of eight patients in whom serrated adenomas were identified in St Mark’s polyposis registry
Authors’ reply
We would like to thank Drs Gallagher and Phillips for their comments on our article. They raise the point that experienced colonoscopists should assess colorectal lesions in familial adenomatous polyposis (FAP) using a dye spraying technique. It has been shown previously that conventional colonoscopy would underestimate the number of adenomas in patients with attenuated FAP.1 In two of the three subjects with polyps less than 100 in number, chromoscopy identified numerous and diminutive areas of flat configuration in the colorectum where tubular adenomas were confirmed histologically. While chromoscopy identified numerous non-polypoid areas of tubular adenomas in two of the three subjects with serrated adenomas, their sparse colorectal polyposis and the APC gene mutation were compatible with FAP of the attenuated form.2,3
Another important issue raised by Drs Gallagher and Philips is the fact that in their histological survey of resected specimens three patients with serrated adenomas had an APC mutation at the proximal part of exon 15. This discrepancy may have arisen from differences in the procedure of assessment for colorectal adenomatosis. In our 15 colectomised specimens of FAP however, we have not yet found any serrated adenomas. Based on the comments of Drs Gallagher and Philips, other colectomised specimens are under investigation at our institute. Until many more patients with FAP or attenuated FAP are identified, the correlation between serrated adenomas and the genotype of FAP remains controversial.