Case 3 -

Inflammatory "Cap" Polyposis Rhonda K. Yantiss Department of Pathology and Laboratory Medicine Weill Cornell Medical College of Cornell University New York, NY

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Case History A 62 year-old white male presented with a several month history of changing bowel habits and mucoid diarrhea. He underwent a lower colonoscopic examination and was found to have numerous (>10) small sessile polyps in the rectosigmoid region, some of which were biopsied and interpreted to be hyperplastic polyps. His symptoms worsened over the next several months and he re-presented with copious mucoid secretions as well as incontinence of mucoid stool. A second colonoscopic examination revealed an increase in the number of polyps present up to 20 cm from the anal verge. The polyps were sessile, erythematous, and friable, and many were eroded or covered with a fibrinous exudate. Several polyps were sampled and again interpreted to be hyperplastic. A representative biopsy of the intervening colonic mucosa showed "hyperplastic changes". His medical history included coronary artery disease, status post coronary artery bypass graft, aortic and mitral valve replacements, cardiac pacemaker placement, atrial fibrillation, transient ischemic attacks, and hypothyroidism. Medications included aspirin, Synthroid, lisinopril, coumadin, Lipitor, and amiodarone. Two months after the second colonoscopy, the patient was admitted to the hospital with complaints of severe rectal straining, constant bloody/mucoid secretions per rectum, 7-10 bowel movements per day, as well as anal leakage and the use of 15-20 pads/day. He also reported a 20-pound weight loss over the course of six months and an inability to ambulate due to intense anal pressure. He underwent a flexible sigmoidoscopy, which revealed innumerable large, friable sessile polyps from 5-6 cm above the anal verge to the proximal extent of the examination. He underwent a hand-assisted laparoscopic resection of the sigmoid colon and proximal rectum for symptomatic relief. Representative sections were obtained from the lesional areas. Case 3 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 3 - Figure 1 - The resection specimen contained 50-100 erythematous, sessile polyps that were more numerous in the rectum, but also involved the sigmoid colon. The polyps ranged in size from <0.1 cm to 2.5 cm and, in some areas, formed confluent plaques spanning up to 6 cm. Case 3 - Figure 2 - Representative sections of the polypoid lesions demonstrated that the polyps contained numerous cystically dilated crypts that tended to be most prominent in the superficial component of the polyps. Case 3 - Figure 3 - All of the polyps showed attenuation of the surface epithelium or frank ulceration associated with a granulation tissue reaction. Case 3 - Figure 4 - The crypts contained a mucoid exudate with enmeshed inflammatory cells and denuded epithelial cells, which was also adherent to the surface of the polyp. Case 3 - Figure 5 - The superficial crypts were lined by attenuated epithelial cells with mucin depletion. Case 3 - Figure 6 - In other areas, the epithelial cells in the crypt region contain either abundant mucin or eosinophilic cytoplasm, as well as enlarged nuclei with small, but conspicuous nucleoli, and evenly dispersed chromatin. Case 3 - Figure 7 - The crypts near the polyp base showed mild architectural distortion, crypt dilation, and limited serration. The lamina propria did not contain smooth muscle fibrils emanating from the muscularis mucosae, which was of normal thickness. Pathologic Features The resection specimen comprised the distal sigmoid colon and rectum and contained 50-100 erythematous, sessile polyps that were more numerous in the rectum, but also involved the sigmoid colon. The polyps ranged from <0.1 cm to 2.5 cm and, in some areas, formed confluent plaques spanning up to 6 cm. Representative sections of the polypoid lesions demonstrated that they contained numerous cystically dilated crypts that tended to be most prominent in the superficial component of the polyps. All showed attenuation of the surface epithelium or frank ulceration associated with a granulation tissue reaction. The crypts contained a mucoid exudate with enmeshed inflammatory cells that was adherent to the surface of the polyp. The crypts within the mid-region of the polyp were elongated with a slightly serrated luminal contour. The crypts in areas distant from ulceration contained two populations of epithelial cells, including goblet cells and cells with abundant eosinophilic cytoplasm. These cells exhibited slightly enlarged nuclei with evenly dispersed chromatin and prominent nucleoli. In the deeper areas of the polyp, the muscularis mucosae was of normal thickness without splaying into the lamina propria. Diagnosis Inflammatory "cap" polyposis Discussion Cap polyposis is an uncommon disease first described by Williams et al in 1985 and was proposed to represent a response to chronic mucosal prolapse [26]. Since that time, fewer than 50 cases have been reported in the literature. Cap polyposis probably affects men and women with near equal frequency and variations in gender distributions among different studies likely reflect the small number of patients evaluated to date. This disorder may occur within any racial group, but is more commonly reported in eastern and southeastern Asia. It also occurs within a wide age range, affecting patients as young as 12 years of age, as well as older adults. At least 50% of patients do not have a history of chronic constipation or straining prior to the onset of cap polyposis. In one recent review of 11 patients, the male/female ratio was 9/2, with a mean age of 20 years (range: 15-54 years); 64% of patients had a history of chronic constipation. In that study, only two patients had documented abnormal anorectal function, including one with rectal intussusception and one with rectal prolapse [14]. Patients with cap polyposis commonly present with symptoms of mucoid diarrhea, which may be associated with protein wasting, rectal bleeding, or tenesmus [18, 19, 20]. The rectum is involved in more than 80% of cases; however, the disease often affects the sigmoid colon and may even extend into the ascending colon in a retrograde, continuous fashion. Endoscopically, the polyps are usually sessile and vary from a few millimeters to several centimeters. As in the current case, the polyps may form confluent plaques on the mucosal surface. The lesions, which may be solitary or multiple, are often friable and erythematous with ulceration [7, 10]. Cap polyps are characterized by several features. Most are composed of elongated, hyperplastic crypts lined by mucin-depleted epithelial cells that show regenerative changes, including nuclear enlargement and increased mitotic activity. The surface epithelium is often attenuated and may be ulcerated. As a result, there is usually an inflammatory "cap" of granulation tissue on the surface with adherent mucin, fibrin, inflammatory cells, and denuded epithelial cells. The lamina propria shows a variable amount of active inflammation, particularly in the superficial areas underlying erosions or ulcers. Although a small number of smooth muscle fibers may emanate from the muscularis mucosae in some cases, most cap polyps do not contain abundant smooth muscle fibers within the lamina propria. The differential diagnosis includes a number of unrelated entities that share gross and/or histologic overlap with cap polyposis and encompasses forms of colitis to several polyposis syndromes. Ulcerative Colitis Based upon the gross appearance of the colon, ulcerative colitis with pseudopolyps is included in the differential diagnosis of cap polyposis [23]. However, the intervening mucosa is usually endoscopically normal in patients with cap polyposis, whereas patients with ulcerative colitis show erythema or other features of colitis in the non-polypoid mucosa. The histologic features of ulcerative colitis are also distinct from those of cap polyposis. For example, although pseudopolyps in chronic colitis may show features that closely resemble the normal colonic mucosa, or show chronic colitis with or without active disease, cap polyps show predominantly hyperplastic/regenerative changes with cystically dilated crypts or crypts with limited luminal serration, in a background of normal or near-normal lamina propria cellularity with minimal mononuclear cell inflammation, despite the presence of superficial ulceration. In addition, the intervening, non-polypoid mucosa may show mild crypt architectural distortion, but lacks mononuclear cell inflammation in the lamina propria. The presence of active inflammation with ulceration in a background mucosa that lacks chronic inflammation would be distinctly uncommon in patients with new-onset ulcerative colitis. Mucosal Prolapse Syndrome The inflammatory appearance of cap polyps may overlap morphologically with the type of lesions seen in mucosal prolapse or solitary rectal ulcer syndrome leading some investigators to propose that cap polyposis represents one of a spectrum of changes seen in mucosal prolapse [11, 18]. Both conditions show a predilection for the left colon, and, particularly, the rectum. However, the morphologic features of these two entities are sufficiently different to allow their distinction. For example, although cap polyps may be ulcerated with granulation tissue, they do not show other features typical of mucosal prolapse, such as ischemic-type injury or fibromuscularization of the lamina propria. The muscularis mucosae is histologically normal in most cap polyps, whereas it is usually thickened and associated with wisps of smooth muscle that extend into the lamina propria in mucosal prolapse. Cap polyposis has also been reported to involve the proximal colon, including the cecum, which are presumably unaffected by mucosal prolapse, particularly among asymptomatic patients [9, 21]. Although it is likely that cap polyposis and mucosal prolapse are both non-neoplastic, inflammatory processes, it is probable that these entities are unrelated. Hamartomatous Polyposis The polyps of cap polyposis may show morphologic features that raise the possibility of a hamartomatous polyposis syndrome, such as juvenile polyposis, Cowden's syndrome or Cronkhite-Canada syndrome. Juvenile polyps show cystically dilated crypts within an inflamed stroma rich in eosinophils, often with surface ulceration and granulation tissue. The cystically dilated crypts of these polyps are evenly distributed throughout the polyp and the lesions may occur in extracolonic sites. In contrast, cystically dilated crypts in cap polyposis are more prominent toward the surface of the polyp, which also contains elongated crypts with luminal serration. Adherent mucin with inflammatory cells is also more commonly seen in cap polyps than in juvenile polyps. Polyps seen in Cowden's syndrome or Cronkhite-Canada syndrome may show features that, in isolation, mimic the features of cap polyposis, but they contain numerous mucus-filled cystically dilated crypts distributed throughout all areas of the polyp, more closely resembling juvenile polyps. Both of these disorders are also associated with extracolonic lesions involving the upper gastrointestinal tract as well as extraintestinal manifestations and dermatologic abnormalities. For instance, Cowden's disease is associated with breast cancer, thyroid disease, facial anomalies, renal cell carcinoma, lymhomas, papillomatosis of the lips and oropharynx, retinal gliomas, and skeletal changes as well as facial tricholemmomas, melanoma, and Merkel cell carcinoma [5, 25]. Cronkhite-Canada syndrome may produce clinical symptoms, such as protein wasting and diarrhea, similar to cap polyposis, but is also associated with skin hyperpigmentation, vitiligo, alopecia, onychodystrophy, glossitis, and cataracts [3, 6]. Knowledge of the clinical scenario usually allows distinction among these entities. Cap polyposis may resolve spontaneously; however, most patients require some form of medical or surgical management [12, 16, 24]. Those with fewer than 10 polyps may be managed successfully with polypectomy alone in approximately 60% of cases. More extensive, symptomatic disease may be treated with a combination of stool softeners, anti-inflammatory agents (5-aminosalicylic acid, sulfasalazine, prednisolone) or antibiotics (metronidazole). Recently, some authors have reported endoscopic and histologic resolution of disease following infliximab therapy, suggesting a role for inflammatory mediators, such as TNF- a, in the progression of this disease [2, 13]. Rare patients with concomitant H. pylori gastritis have also been successfully managed with H. pylori eradication therapy [1, 15, 17]. Resection of the involved colon is usually reserved for patients who fail medical therapy. Recurrent symptomatic disease has been reported in up to 37% of cases following limited resection of the affected colon [22]. The pathogenesis of cap polyposis is unknown. Its usual involvement of the rectum and/or sigmoid colon, clinical association with constipation and straining upon defecation, and histologic features have led investigators to suggest that these polyps are related to mucosal prolapse or intraluminal trauma [4, 8, 12, 18]. Most investigators believe that it represents a non-neoplastic inflammatory response to mucosal prolapse and consider it to be part of a spectrum of changes in mucosal prolapse syndrome. However, most patients with cap polyposis do not have a history of chronic constipation; larger series indicate that this disease usually occurs in patients in whom mucosal prolapse is infrequent, such as younger male patients without underlying colonic motility disorders [14]. Some reports have also described cap polyposis in association with diverticular disease, colorectal carcinoma, and colitis, suggesting that it may be a non-specific mucosal response to another underlying disorder [22, 26]. The most intriguing hypotheses regarding the pathogenesis of cap polyposis implicate an infectious organism in the development of this disorder. Shimizu et al reported a case of cap polyposis in association with an E. coli colonic infection [22]. Although broad-spectrum antibiotics have proven ineffective in the treatment of most patients with cap polyposis, metronidazole is temporarily effective in ameliorating symptoms in some cases [8]. Several investigators have independently reported the successful resolution of cap polyposis in patients receiving H. pylori eradication therapy. Five such cases have been reported to date, all in patients who failed other forms of medical (steroids, metronidazole, bowel rest) or surgical therapy. In each case, the patient was found to have H. pylori-associated gastritis during the course of the illness, which was treated. All of the patients experienced a resolution of colonic symptoms after successful H. pylori eradication [1, 15, 17]. 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