Case 3 -

Colonic Muco-Submucosal Elongated Polyp Ian S. Brown, Envoi Pathology, Herston, Queensland, Australia

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Clinical History: Male 60 years. Colonoscopy performed for investigation of a positive fecal occult blood test. Solitary 25 mm long filiform polyp removed from the sigmoid colon. No history of previous colorectal disease. Case 3 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 3 - Figure 1 Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: The scanned image displays a colorectal polyp with 3 key features: 1) An elongate, cylindrical shape with a narrow base. 2) A lining of non-neoplastic large intestinal mucosa displaying minimal architectural disturbance but no inflammation. 3) The presence of an expanded submucosa in the stalk, devoid of inflammation. Lymphangiectasia, venous congestion and mild stromal edema are evident. Differential Diagnoses: 1) Polypoid prolapsing mucosal fold. 2) Filiform polyposis - related to inflammatory bowel disease or occuring without an identifiable cause. 3) Inverted colonic diverticulum. 4) Residual stalk of a pedunculated polyp. 5) Other forms of colorectal mucosal prolapse eg inflammatory myoglandular polyp. 6) filiform neoplasm eg filiform traditional serrated adenoma and inflammatory fibroid polyp. Final Diagnosis: Colonic Muco-Submucosal Elongated Polyp Case Discussion: This case illustrates an incidentally discovered endocopically filiform/cylindrical polyp. The key histological findings are: 1) an elongate, cylindrical shape with a narrow base ; 2 ) a lining of non-neoplastic large intestinal mucosa displaying minimal architectural disturbance but no inflammation; and 3) The presence in the stalk of an expanded submucosa devoid of inflammation. These features are typical of what has been termed Colonic Muco-Submucosal Elongated Polyp (CMSEP). The differential diagnosis includes the following lesions: 1) Polypoid prolapsing mucosal fold (PMF) - also known as the 'Kelly polyp' is a form of mucosal prolapse polyp that has a strong association with sigmoid diverticular disease [1, 2] and most likely arises due to traction prolapse of the concertinaed haustral folds found in this condition. The main clinical differences from CMSEP are the more frequent association with diverticular disease and frequent multiplicity of PMF polyps, while CMSEP is usually single. Macroscopically, PMF is broad based and 'leaf like' appearance and is often red or dark brown in appearance due to haemorrhage and haemosiderin deposition [1, 2] while CMSEP is slender based, cylindrical and exhibits no evidence of previous haemorrhage. Microscopically, PMF polyps demonstrate evidence of mucosal prolapse with crypt architectural abnormality, fibromuscular obliteration of the lamina propria and thickening, reduplication and splaying into the lamina propria by muscularis mucosae. This is often accompanied by active chronic inflammation and hemorrhage and hemosiderin deposition [2]. Not infrequently mucosal glands become inverted into the submucosa at the tip of the polyp. By contrast, CMSEP lack mucosal prolapse features and inflammation Despite clinicopathological differences, it is probable a kinship exists between PMF polyps and CMSEP based on a common traction prolapse etiology. Additionally, we have encountered polyps with hybrid feature in being elongate and cylindrical but exhibiting mucosal prolapse features and mucosal inversion at the tip. Furthermore, we have seen concurrence of typical examples of both forms of polyp in resections for severe diverticular disease. 2) Other mucosal prolapse related polyps – these include inflammatory 'cap' polyps, inflammatory cloacogenic polyp and inflammatory myoglandular polyps. Inflammatory 'cap' polyps differ from CMSEP in being broad based, usually multiple, localised to the rectosigmoid region and covered by a cap of granulation tissue and fibrin [3]. Inflammatory cloacogenic polyp is restricted to the anal transition zone [4] and this characteristic site, in association with ulceration and inflammation, allows distinction from CMSEP. Inflammatory myoglandular polyps differ from CMSEPs by the prominence of smooth muscle proliferation and inflammation with granulation tissue in the mucosal lamina propria [5]. 3) Filiform polyposis (FP) - is believed to represent a non-specific mucosal/submucosal reaction to previous injury, in particular, inflammatory bowel disease (IBD), although examples do occur outside this condition [6, 7, 8, 9]. In contrast to CMSEP, filiform polyposis presents as numerous polyps that generally display an irregular fibrovascular proliferation in the stalk, sometimes including entrapped nerves and reduplicated smooth muscle [6, 8]. Mucosal inflammation is typical in inflammatory bowel disease associated cases. 4) Inflammatory pseudopolyp – typically seen in the setting of inflammatory bowel disease and pathologically distinct from CMSEP by the presence of chronic inflammion and fibrosis. 5) Filiform patterns associated with neoplasms – These may include mucosal based lesions such as serrated adenoma [10, 11] or submucosal based lesions such as perineurioma or inflammatory fibroid polyp. The associated neoplasm allows separation from CMSEP. 6) Inverted colonic diverticulum (ICD) - is a (probably) under recognised lesion, which if biopsied or resected, will reveal a normal mucosa and congested submucosa, [12]. ICD is seldom >10mm and lacks the abundant submucosal tissue typical of CMSEP. Sometimes adipose tissue (derived from the mesentery) comprises the bulk of this lesion. 7) Residual stalk from a previous pedunculated polyp presents as a polyp with normal mucosa and expanded submucosa [13]. The history of previous polypectomy and changes related to this such as diathermy artefact, stromal hemosiderin and fibrosis allow distinction of this lesion from CMSEP. 8) Other – Hamartomatous polyps, particularly those occurring in Peutz -Jeghers syndrome, might be a diagnostic consideration. An arborizing muscle proliferation and other syndromic features allow easy distinction from CMSEP. Summary table – differential diagnosis non neoplastic colorectal polyps comprised of mucosa and submucosa Diagnosis Clinical setting Macroscopic/endoscopic Microscopic CMSEP Usually no pre-existing disease Solitary, filiform/cylindrical Normal/minimally abnormal mucosa covering an expanded submucosa. Prolapsing mucosal fold Sigmoid diverticular disease broad based/‘leaf like’; dark due to hemorrhage Mucosal prolapse change in mucosa; hemosiderin; mucosal inversion into submucosa Mucosal prolapse syndrome Often rectum or recto-sigmoid colon region typically broad based and often with ulceration Prominent fibromuscular obliteration of lamina propria with thickened, reduplicated muscularis mucosae. Filiform polyposis Inflammatory bowel disease (sometimes other association) Multiple, filiform + branching polyps Active chronic inflammation in mucosa/submucosa in Inflammatory pseudopolyp Inflammatory bowel disease; other inflammatory process Often multiple Inflammation and fibrosis in mucosa/submucosa Inverted colonic diverticulum Diverticular disease (may be right sided) Usually single, small (<10mm) and dome shaped Minimal submucosa Stalk of pedunculated polyp Previous polypectomy at site Solitary, filiform/cylindrical Fibrosis + hemosiderin and cautery artefact Hamartomatous polyp Clinical syndrome Multiple, lobulated Arborizing smooth muscle, other Review of the Literature: Colonic muco-submucosal elongated polyp (CMSEP) was the descriptive name given by Matake et al to series of colorectal polyps characterised by a pedunculated, elongated shape and composed mainly of expanded submucosa with an essentially normal mucosal lining [14]. Since their initial description in 1994, CMSEP have been infrequently reported and until recently this has been exclusively by Japanese authors [14, 15, 16, 17, 18] . CMSEPs are usually an incidental discovery at the time of screening colonoscopy for adenomatous polyps or as a result of positive faecal occult blood test. In one series, the prevalence of CMSEP was reported to be 0.39% of all colorectal polyps [15]. A review of 50 Japanese cases, including meeting abstracts, [18] revealed a mean age of polyp presentation of 62 years and slight male predominance 58% to that encountered in our series. Just over half of the polyps (52%) were discovered at either routine screening colonoscopy or on investigation of faecal occult blood loss. Altered bowel habit and abdominal pain were also frequent presenting complaints. Co-existent diverticular disease has been noted in approximately 15% of patients [19] . Most polyps were located in the transverse colon (28%) and sigmoid colon (26%) [18] . Recently, Alizart et al reported a series of 13 CMSEP in a Western cohort [20]. While the basis for discovery, male predominance and average age were similar to the Japanese experience, there was a greater preponderance for the sigmoid colon location, although diverticular disease was noted in only 1 case. In the reported cases, the mean polyp size is 35mm (range of 5-240mm). Clearly, CMSEP can reach impressive size, but it is important to realise that the vast majority are in the range 10-30mm [15, 17, 20] . Occasionally, surface ulceration and capillary congestion may encountered in otherwise typical CMSEP [18, 20] and might account for fecal occult blood loss. The etiology of CMSEP is unknown. Traction of these surface layers during peristalsis may be responsible [15, 19, 20]. This is implicated in pathogenesis of giant fibrovascular polyp of the oesophagus, which shows analogous pathological features to CMSEP. What might initiate the traction is unknown as an underlying mucosal lesion is consistently not identified in CMSEP. The prominent central submucosal venous plexus in CMSEP could potentially elevate the mucosa sufficiently to initiate the process; however, prominent submucosal veins are a common finding in all forms of pedunculated polyps so a local vascular abnormality is speculative. A focal functional abnormality could be also be responsible. CMSEP does not appear to portend any clinical significance and is usually an incidental finding. It could be responsible for occult blood loss in some patients. Recurrence of these lesions is not reported. Conclusion: The differential diagnosis of non neoplastic colorectal polyps composed of mucosa and submucosa is broad. Colonic muco-submucosal elongated polyp is a pedunculated, elongated shape and composed mainly of expanded submucosa with an essentially normal mucosal lining. This lesion has no great clinical significance; however, it may attain impressive size and is likely to become more frequently encountered by pathologists. References: Kelly JK. Polypoid prolapsing mucosal folds in diverticular disease. Am J Surg Pathol. 1991;15:871-878. Tendler DA, Aboudola S, Zacks JF, et al. Prolapsing mucosal polyps: an underrecognized form of colonic polyp--a clinicopathological study of 15 cases. Am J Gastroenterol. 2002;97:370-376. Williams GT, Bussey HJR, Morson BC. Inflammatory cap polyps of the large intestine. Br J Surg. 1985;72(Suppl):133. Lobert PF, Appelman HD. Inflammatory cloacogenic polyp. A unique inflammatory lesion of the anal transitional zone. Am J Surg Pathol. 1981;5:761-766. Nakamura S, Kino I, Akagi T. Inflammatory myoglandular polyps of the colon and rectum. A clinicopathological study of 32 pedunculated polyps, distinct from other types of polyps. Am J Surg Pathol. 1992;16:772-779. Lee CG, Lim YJ, Choi JS, et al. 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