Mucosal Prolapse Syndrome

Chapter 16 Mucosal Prolapse Syndrome Anne Jouret-Mourin, Maria Leo, and Karel Geboes Abstract Prolapse of the large intestinal mucosa occurs in various situations including at the margin of a colostomy, the apex of hemorrhoids protruding outside the anus, and in the context of diverticular disease. However the best known sites of mucosal prolapse are the anterior wall of the rectum where it gives rise to the solitary ulcer syndrome and the anorectal junction resulting in a peculiar polyp called “cloacogenic polyp.” These are both benign conditions. Common clinical symptoms are constipation and/or red blood loss per annum. The endoscopy of the solitary ulcer can show a variable picture of erythema, a shallow ulcer, or even a polypoïd lesion. The histology is characteristic. The mucosa around the solitary ulcer shows crypt distortion, reactive epithelial cells, and typical fibromuscular obliteration of the lamina propria. Inflammation is usually mild. A “cloacogenic polyp” appears as a villiform tumor mass at the anorectal junction and has a great potential to be confused with other polyps such as adenomas or even carcinoma. It is important to recognize these lesions in order to avoid the morbidity and mortality associated with major surgery (misdiagnosis of neoplasia) or the side effects of long-term medical treatment. Keywords Solitary rectal ulcer syndrome · Inflammatory cloacogenic polyp · Proctitis cystic profunda · Inflammatory cap polyp · Prolapse · Fibromuscular obliteration · Localized colitis cystic profunda A. Jouret-Mourin (*) Department of Pathology, Cliniques Universitaires St Luc, UCL, Brussels, Belgium e-mail: [email protected] M. Leo Department of Pathology, University Hospital San Giovanni di Dio, University of Cagliari, Cagliari, Italy Department of Surgical Sciences, University Hospital San Giovanni di Dio, University of Cagliari, Cagliari, Italy e-mail: [email protected] K. Geboes Department of Pathology, Ghent University Hospital, Ghent, Belgium Department of Pathology, KU Leuven, Leuven, Belgium © Springer International Publishing AG, part of Springer Nature 2018 A. Jouret-Mourin et al. (eds.), Colitis, https://doi.org/10.1007/978-3-319-89503-1_16 221 222 A. Jouret-Mourin et al. Mucosal prolapse is a condition which, despite its characteristic histological findings, is able to mimic both inflammatory conditions and malignancy. The “solitary rectal ulcer syndrome (SRUS)” is the major form of all mucosal prolapse syndromes. The other types are polypoid lesions such as proctitis or rectitis cystic profunda (the localized form of colitis cystic profunda), inflammatory cloacogenic polyp due to prolapse close to the anal canal, and polyps occurring in association with diverticular disease, the so-called inflammatory cap polyp. These situations need to be recognized in order to avoid erroneous diagnoses of neoplasia and for proper treatment of the underlying condition such as defecation anomalies. Solitary Rectal Ulcer Syndrome Pathogenesis The “solitary rectal ulcer syndrome (SRUS)” is an uncommon benign rectal disorder characterized by a spectrum of clinical presentations and variable endoscopic and microscopic findings. It was first described by Cruveilhier in 1830. The term “solitary ulcers of the rectum” was introduced by Lloyd Davies in the late 1930s. The pathogenesis of SRUS has not been completely clarified yet. Mucosal prolapse is the most important factor. The most likely mechanism is a descent of the perineum and a paradoxical or abnormal contraction of the puborectalis muscle in the pelvic floor during straining or defecation, resulting in mucosal prolapse. Another theory suggests that abnormal defecation could result from abnormal pressure gradients produced by the external anal sphincter generating a high intrarectal pressure [1]. The postulated mechanism responsible for rectal prolapse in most cases seems to be excessive straining efforts during which high intra-abdominal pressure might force the anterior rectal mucosa firmly into the contracting puborectalis muscle. The mucosa would be strangulated, causing poor blood flow, venous congestion, edema, mucosal ischemia, and eventually ulceration [2, 3]. Most probably, the pathology of SRUS is related to the coexistence of multiple factors, including direct trauma and local ischemia. In one study it has been suggested that SRUS has the potential to progress to malignancy [4]. Loss of hMLH1 gene (MutL homolog) expression was demonstrated in several cases of SRUS in another study underlining the possibility of neoplastic progression [5]. However, no causal relationship has been established yet between SRUS and neoplastic lesions such as adenoma and adenocarcinoma until now. Clinical Presentation Men and women are affected equally, with a predominance in young females with defecation problems. SRUS has been reported in a wide age range (15–85 years) including children and the geriatric age group. Few reports of SRUS have been 16 Mucosal Prolapse Syndrome 223 described in young children however [6]. The clinical presentation is variable, but difficulty in defecating, mucous discharge, rectal bleeding, and abdominal pain are the most common symptoms. In children, the condition usually presents with rectal bleeding, mucous discharge, prolonged straining, tenesmus, and localized pain in the perianal area [7]. SRUS often remains unrecognized for years. The correct diagnosis is usually delayed approximately 5–7 years after the clinical onset. This delay may be responsible for the scarcity of pediatric cases [8]. Clinical examination may reveal an anal fissure in up to 30% of the patients. Endoscopic Data Endoscopy plays a major role in the diagnosis. Endoscopic features are highly variable with hyperemia and ulcerative lesions in up to 78% of the patients or single or multiple polypoid lesions in 25–30% of the patients [9]. Therefore the term “SRUS” might not be appropriate as in fact the lesions are not always solitary nor are they always ulcerative. The classical presentation is usually a lesion located on the anterior wall of the mid-rectum. The distance of the ulcer from the anal margin varies from 3 to 10 cm. Ulcers may range from 0.5 to 4 cm in diameter but are usually 1–1.5 cm. They are shallow and covered by a white, gray, or yellowish slough (Fig. 16.1). The adjacent mucosa may appear granular or nodular. Anorectal manometry, electromyography, and defecography can help to confirm the diagnosis. Anorectal manometry and electromyography provide information about anorectal inhibitory reflex, pressure profiles, defecation dynamics, and rectal compliance. Defecography or defecating proctography is a radiological test that records anorectal anatomy and pelvic floor motion. In SRUS patients this test frequently reveals several abnormalities, including intussusception, rectocele, and internal prolapse [8]. Several studies have also shown the value of anorectal ultrasound in assessing internal anal sphincter thickness, which is increased in patients with SRUS. Fig. 16.1 Endoscopic picture of a solitary rectal ulcer (courtesy Prof O. Dewit) 224 A. Jouret-Mourin et al. Histopathology During endoscopy, biopsies should be obtained from abnormal and normal-looking mucosa. The histopathology of SRUS has been well described in 1969 [10]. The histological pattern is characterized by the presence of a superficial ulceration (in most cases) and the occurrence of crypt distortion, surface serration, and fibromuscular obliteration of the lamina propria with the presence of vertically oriented smooth muscle fibers and bundles in between the crypts (Fig. 16.2). The muscle fibers are in continuity with the muscularis mucosae, which is often thickened (Figs. 16.3 and 16.4). The ulceration, when present, is usually limited to the mucosa. The ulcer base is covered with necrotic cells and granulation tissue. Crypts may be dilated and the distance between the crypts can vary. Some crypts may show a particular triangular form (diamond-shaped crypts), but this is not always present [11]. The epithelial cells of the surface and upper part of the crypts may appear cuboidal with basophilic staining cytoplasm and loss of goblet cells. Less frequently cells are well differentiated. Fibromuscular obliteration of the mucosa results in elongation and dilatation of crypts which are lined by basophilic reactive epithelium (Fig. 16.4). Fig. 16.2 Histopathology shows necrotic material overlying the mucosal surface. In the mucosa, granulation tissue can be seen on the right, and smooth muscle fibers are prominent overall (×20) Fig. 16.3 A drawing illustrating the different histological characteristics of solitary rectal ulcer 16 Mucosal Prolapse Syndrome 225 The proliferative compartment of the crypts may be enlarged. The fibromuscular obliteration of the lamina propria is the most significant change. It is an early feature and has been reported in 93% of patients [11, 12]. It is however not always present and may lack in very early cases. Fibrosis of the lamina propria and vascular ectasia with congestion are also considered as typical lesions of SRUS, having been found in 95% of the patients in various studies. Vascular thrombosis and fibrin deposition are less common [13]. Misplacement of mucus-filled or empty but dilated glands in the submucosa, probably as a result of repetitive ulceration and healing, may lead to a polypoidal appearance on macroscopic examination. This appearance has been described as a localized colitis cystic profunda (Fig. 16.5). In general, the density of the lamina propria cellular infiltrate is not or mildly increased. Fig. 16.4 Histopathology shows the thickening of muscularis mucosae and the fibromuscular obliteration of the lamina propria (×20) Fig. 16.5 Microphotograph illustrating misplacement of dilated glands (×20) 226 A. Jouret-Mourin et al. In summary, the distinctive features of SRUS include thickening of the muscularis mucosae, perpendicular muscularization of the lamina propria, diamond-shaped crypts, and a serrated architecture with sometimes erosions and ulceration. Routine staining is sufficient to reach the diagnosis. Special staining for fibrosis or immune histochemistry for the detection of smooth muscle fibers can sometimes help. Differential Diagnosis The redness, ulceration, and nodular feature may result in endoscopic misinterpretation and an erroneous diagnosis of IBD with inflammatory polyps or villous adenoma. Some of the histological changes occurring in SRUS, including crypt distortion, can also make it challenging to differentiate SRUS from IBD [14]. However, the absence of cryptitis, of crypt abscesses, and of granulomas, the presence of fibromuscular obliteration, and the absence of lesions in biopsies obtained proximal to the rectal abnormalities, associated with the different clinical setting, can help to differentiate between the two conditions. Fibromuscular proliferation may resemble Peutz-Jeghers lesions, but the fibromuscular pattern is organized in a perpendicular fashion in SRUS rather than in arborized pattern. A common histological mistake is the erroneous diagnosis of serrated polyp because obliteration of the mucosa by proliferating muscularis mucosae results in elongation, dilatation, and distortion of crypts mimicking those observed in a serrated polyp. The characteristic feature of a thickened muscularis mucosae from which smooth muscle fibers and fibroblasts run perpendicularly up between the crypts in SRUS and the particular triangular form (diamond-shaped crypts) help to establish correct diagnosis. Localized rectal or anal ulcers can also be caused by the abuse of drugs, such as suppositories and local trauma. The major differential diagnosis is neoplasia or malignancy of the rectum [14]. Crypt distortion, misplacement of crypts into the submucosa, and the reactive features of epithelial cells may rise suspicion of neoplasia. The misplaced epithelium in prolapse localized in the submucosa is usually accompanied by lamina propria or surrounded by the smooth muscle. To avoid such a misdiagnosis and reach the correct diagnosis of SRUS, it is therefore imperative for clinicians, endoscopists, and pathologists to keep this entity in their differential diagnosis, even in the absence of an ulcer at endoscopy, and to give to the pathologist the clinical context and the site of the lesion. Inflammatory Cloacogenic Polyp The inflammatory cloacogenic polyp (myoglandular polyp, proctitis cystic profunda) is generally the result of mucosal prolapse closer to the anal canal due to recurrent mucosal injury. 16 Mucosal Prolapse Syndrome 227 Clinical and Endoscopic Presentation The polyp is usually a rounded elevated lesion. It tends to be present in middle-aged and older patients and essentially in patients presenting with hemorrhoids. Yet, inflammatory cloacogenic polyps have been described in children. In general, there may be a female preponderance [15]. Rectal bleeding is the most common symptom, but tenesmus and mucoid stools can be described by the patients. It can also be discovered fortuitously. A few cases have been described in association with a solitary rectal ulcer syndrome. Histopathology The inflammatory cloacogenic polyp is covered by hyperplastic thickened rectaltype mucosa with smooth muscle fibers in between the crypts and by anal transitional or squamous epithelium overlying fibrous tissue. The surface may be ulcerated. The epithelium can look atypical, and sometimes displaced glands are present in the submucosa. The crypts are elongated, hyperplastic, or distorted. They can show a serrated pattern (Fig. 16.6). The lamina propria is edematous and contains fibroblasts and chronic inflammation. Hemosiderin deposits may be observed. The muscularis mucosae are disorganized (Fig. 16.7). Differential Diagnosis The inflammatory cloacogenic polyp has the greatest potential to be confused with other polyps such as villous polyps, both at endoscopy and on histology. Dysplasia would not be expected to be present in the inflammatory cloacogenic polyp. However Fig. 16.6 Inflammatory cloacogenic polyp (×5) 228 A. Jouret-Mourin et al. Fig. 16.7 Inflammatory cloacogenic polyp (×10) the exclusion of dysplasia may sometimes be difficult especially when there are features of epithelial regeneration such as cuboidal basophilic epithelial cells and an enlarged proliferating compartment. A prolapsing hemorrhoid in which the overlying mucosa can also show features of prolapse can be a differential diagnostic issue, but usually underlying hemorrhoids can easily be identified on microscopy. Other Manifestations of Polypoid Mucosal Prolapse Colonic polyps due to mucosal prolapse can be observed in association with diverticular disease and especially in the elderly population. Mucosal prolapse mechanisms may occur also in a context of ileostomies and/or colostomies. Inflammatory cap polyps are usually found in the rectosigmoid. They may be multiple. The histology is characterized by the presence of tortuous, elongated crypts, usually lined with attenuated epithelial cells, with a densely inflamed lamina propria. The surface is ulcerated and covered with a grayish cap. Hence the name “cap polyp.” The cap is composed of necrotic material. The etiology is unknown but the lesion has been linked to prolapse [16]. Inflammatory cap polyposis may mimic pseudomembranous colitis or IBD. It is important to obtain sufficiently deep biopsy specimens in order to observe mucosal prolapse changes in the base. References 1. Abid S, Khawaja A, Bhimani SA, et al. The clinical, endoscopic and histological spectrum of the solitary rectal ulcer syndrome: a single-center experience of 116 cases. BMC Gastroenterol. 2012;12:72. 2. Ertem D, Acar Y, Karaa EK, Pehlivanoglu E. A rare and often unrecognized cause of hematochezia and tenesmus in childhood: solitary rectal ulcer syndrome. Pediatrics. 2002;110(6):e79. 3. Sharara AI, Azar C, Amr SS, et al. Solitary rectal ulcer syndrome: endoscopic spectrum and review of the literature. Gastrointest Endosc. 2005;62:755–62. 16 Mucosal Prolapse Syndrome 229 4. Li SC, Hamilton SR. Malignant tumors in the rectum simulating solitary rectal ulcer syndrome in endoscopic biopsy specimens. Am J Surg Pathol. 1998;22:106–12. 5. Ball CG, Dupre MP, Falck V, et al. Sessile serrated polyp mimicry in patients with solitary rectal ulcer syndrome: is there evidence of preneoplastic change? Arch Pathol Lab Med. 2005;129:1037–40. 6. Dehgani SM, Haghighat M, Imanieh MH, Geramizadeh B. Solitary rectal ulcer syndrome in children: a prospective study of cases from southern Iran. Eur J Gastroenterol Hepatol. 2008;20:93–5. 7. Al-Brahim N, Al-Awadhi N, Al-Enezi S, et al. Solitary rectal ulcer symdrome: a clinicopathological study of 13 cases. Saudi J Gastroenterol. 2009;15:188–92. 8. Torres C, Khaikin M, Bracho J, et al. Solitary rectal ulcer syndrome: clinical findings, surgical treatment, and outcomes. Int J Color Dis. 2007;22:1389–93. 9. Vaizey CJ, Van den Bogaerde JB, Emmanuel AV, et al. Solitary rectal ulcer syndrome. Br J Surg. 1998;85:1617–23. 10. Madigan MR, Morson BC. Solitary ulcer of the rectum. Gut. 1969;10:871–81. 11. Warren BF, Dankwa EK, Davies JD. Diamond–shaped crypts and mucosal elastin: helpful diagnostic features in biopsies of rectal prolapse. Histopathology. 1990;17:129–34. 12. 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;97:370–6. 13. Londsdale RN. Microvascular abnormalities in the mucosal prolapsed syndrome. Gut. 1993;34:106–9. 14. Singh B, Mortensen NJ, Warren BF. Histopathological mimicry in mucosal prolapse. Histopathology. 2007;50:97–102. 15. Bass J, Soucy P, Walton M, et al. Inflammatory cloacogenic polyps in children. J Pediatr Surg. 1995;30:585. 16. Campbell AP, Cobb CA, Chapman RW, et al. Cap polyposis: an unusual cause of diarrhoea. Gut. 1993;34:562–4.