Hyperplastic polyp with epithelial misplacement (inverted hyperplastic polyp): A clinicopathologic and immunohistochemical study of 19 cases

Hyperplastic polyps of the colon are the most common type of benign colonic polyp. Rarely, these polyps may show misplaced epithelium within the submucosa, thereby simulating an adenoma with pseudoinvasion or even an adenocarcinoma. In this study, we describe the clinical, pathologic, and immunophenotypic features of 19 hyperplastic polyps with misplaced epithelium to identify potential diagnostic pitfalls and gain insight into their pathogenesis. Routinely processed polypectomy specimens from 12 patients with 19 hyperplastic polyps containing foci of misplaced epithelium were evaluated for a variety of morphologic features including pattern and extent of submucosal involvement, continuity of the submucosal epithelium with the mucosa, presence of recent or remote hemorrhage, inflammation, association of misplaced epithelium with lymphoid aggregates, inflammation, and defects in the muscularis mucosae. Clinical and endoscopic data were obtained and correlated with the histologic findings. Immunoperoxidase stains (ABC method) for collagen IV (basement membrane marker), MIB-1 (proliferation marker), and E-cadherin (intercellular adhesion protein) were performed in all cases. The study group consisted of five males and seven females ranging in age from to 52 to 73 years (mean: 63 y). All of the polyps were located in the rectum or sigmoid colon, and their mean size was 0.5 cm (range: 0.2 to 1.0 cm). Most showed misplaced epithelium in a lobular (26%) or a mixed pattern consisting of lobules and irregularly distributed crypts (63%) that, upon deeper levels, was almost always continuous with the mucosal portion of the polyps (95%). Defects in the muscularis mucosae and splaying of the muscle fibers around misplaced epithelium were seen in all cases. Lymphoid aggregates were present adjacent to foci of misplaced epithelium in 37% of cases. Fresh hemorrhage, vascular congestion, and hemosiderin deposits were present in 79, 53, and 42% of cases, respectively. Strong and uniform staining of the misplaced epithelium for MIB-1 and E-cadherin was demonstrated in all cases, similar to that seen in the lower third of the mucosal portion of the polyps. A continuous collagen IV basement membrane pattern of staining was noted around all foci of misplaced epithelium. Hyperplastic polyps with misplaced epithelium probably occur secondary to trauma-induced protrusion of glands through breaks in the muscularis mucosae. Pathologists should be aware of this entity to avoid diagnostic confusion with other, more serious lesions, such as adenomas with pseudoinvasion or well-differentiated adenocarcinoma.