Looking through a keyhole: serrated neoplasia in the vermiform appendix.

Appendectomy is one of the most common surgical procedures in the United States, usually performed on an emergency basis for signs and symptoms of acute appendicitis or incidentally during surgery for other conditions, with a minor subset of patients having a mass lesion of the appendix. Nevertheless, because the appendix is currently inaccessible by endoscopy, we have minimal information regarding the biologic potential and evolution of mucosal alterations in the appendix, except by inference. Other lumina in the gastrointestinal tract can be scrutinized with increasing sensitivity using white-light endoscopy or advanced endoscopic methods, including magnification endoscopy, chromoendoscopy, and other techniques, allowing lesions of interest to be biopsied and followed up. In contrast, the cellular events in the appendix of a given patient remain invisible until there is trouble. As a result, our knowledge of the biologic potential of epithelial alterations in this organ is akin to peering through a keyhole. Advances in knowledge have been made by painstaking reviews of series of patients with careful clinical follow-up in an attempt to develop a longitudinal understanding that would permit us to make sense of the changes we see at the microscope. Contributing to the challenges is the relatively limited sampling that is standard in most institutions. The majority of published guidelines for histologic sampling recommend including a longitudinal section or cross-section of the appendiceal tip and 2 additional cross-sections, ideally of the middle portion and from the proximal margin of resection. Few institutions routinely sample the entire resected appendix , except when neoplasms are detected on examination of initial sections. Located shortly beyond the ileocecal valve with its orifice opening into the cecum, the vermiform appendix is lined by mucosa histologically similar to colonic mucosa, lacking the villous architecture of the small intestine. Therefore, pathologists have traditionally chosen to apply terms used in pathologic diagnosis of colon to similar lesions found in the appendix. Nevertheless, the appendix is not the colon. Compared with the colon, the appendix has considerably more mucosal-associated lymphoid tissue, along with specialized follicle-associated epithelial units, including M cells, to present luminal antigens to the immune system. The extensive follicular architecture distorts the appendiceal crypts in many areas, leading to variable crypt length, distribution, and architecture, including focal interdigitation with lymphoid tissue or areas without crypts. Appendiceal crypts also contain scattered Paneth cells and numerous endocrine cells. 1 Although the amount of lymphoid tissue varies with the age …