Case 1 -

Colitis Cystica Profunda and Eroded Polypoid Hyperplasia Associated with Mucosal Prolapse Alyssa Krasinskas, Jeffrey Goldsmith and Susan Abraham

Clinical History: This 45-year-old woman underwent excision of a villiform-appearing tumor in the rectum along with excision of internal and external hemorrhoids. Microscopic Features: Three main abnormalities are seen in the specimen. First, the submucosa is expanded by multiple mucin pools. These are acellular but in many areas are lined by non-dysplastic rectal epithelium and lamina propria. Second, the overlying rectal mucosa contains heaped-up, polypoid tissue with superficial erosions. The colonic crypts in the polyp have a serrated appearance, but the polyp is larger than a typical hyperplastic polyp and the intervening fibrosis of the lamina propria and overlying ischemic-appearing erosions are also both unusual features of hyperplastic polyps. The third histologic abnormality is seen in the rectal mucosa away from the polyp, where the lamina propria is fibrotic and muscularized. Mimics: Colitis cystica profounda vs. invasive adenocarcinoma Eroded polypoid hyperplasia vs. tubulovillous adenoma, serrated adenoma, or hyperplastic polyp Mucosal prolapse changes vs. idiopathic IBD Discussion: Colitis cystica profunda: Colitis cystica profunda is a benign condition characterized by cystic dilatation and downgrowth of mature colonic glands through the muscularis mucosa and into the submucosa or deeper layers of the bowel wall. The term "colitis cystica polyposa" was first used by Virchow in 1863 to describe a case in which multiple polypoid lesions were produced by submucosal cysts [1]. The term "colitis cystica profunda" subsequently came into use in 1957 [2]; most affected patients have both submucosal cysts and associated polypoid lesions. Similar lesions are found in the stomach ("gastritis cystica profunda"), where they are most frequently associated with gastroenterostomy sites [3], and in the small bowel ("enteritis cystica profunda") where they are often associated with Peutz-Jeghers syndrome [4]. Rarely, colitis cystica profunda occurs as an isolated lesion in an otherwise apparently normal colon [5, 6]. However, most cases of colitis cystica profunda occur in association with some form of colonic abnormality. The most common association is with solitary rectal ulcer syndrome [1, 7, 8, 9], in which case the lesions are rectosigmoid in their location. Distal lesions (sometimes termed "proctitis cystica profunda") have also been reported in paraplegics [10], in a patient with a history of self-inflicted rectal trauma [11], and in patients with post-irradiation colonic strictures [12, 13]. Less commonly, diffuse or pancolonic lesions of colitis cystica profunda occur in patients with inflammatory bowel disease – including ulcerative colitis, Crohn's disease, and unclassified forms [14] – or infectious dysentery [1]. A predominant pathogenic mechanism for colitis cystica profunda, especially in distal colorectal lesions, is probably ischemia produced by mucosal trauma [1]. In the case of solitary rectal ulcer syndrome, mucosal prolapse can result in ischemia and ulceration by virtue of traction exerted on the local vasculature [1]. In cases of colitis cystica profunda in patients with infectious or idiopathic inflammatory bowel diseases, inflammatory mucosal ulcerations may allow for the downgrowth of benign regenerative glands into the submucosa, which subsequently become entrapped during re-epithelialization of the ulcers. Guest and Reznick [1] reviewed the clinical features of 144 cases of colitis cystica profunda reported in the literature before 1989. The reported age range is quite wide, from 4 to 76 years (median, 30 years), and males and females are approximately equally affected. The most common presenting symptoms include blood in the stool (68%), mucoid stool (43%), diarrhea (27%), tenesmus (13%), and abdominal discomfort (12%); rarely, it can present as intestinal obstruction [5]. Endoscopically, colitis cystica profunda can be a focal, segmental, or diffuse abnormality. Focal or segmental lesions can mimic mucinous adenocarcinoma. Transrectal ultrasound and other imaging modalities can aid in the distinction between malignancy and colitis cystica profunda by demonstrating multiple cysts limited to the submucosa and lack of lymph node involvement [7]. Gross features of colitis cystica profunda include a frequently polypoid appearance and enlargement of the submucosa, which can appear mucoid. Histologically, the condition is characterized by the presence of multiple cystically dilated, mucin-filled crypts in the submucosa, and occasionally in the muscularis propria or serosa. The stroma surrounding misplaced crypts usually consists of lamina propria, which is helpful in distinguishing it from adenocarcinoma, which often has a desmoplastic stroma. Furthermore, misplaced glands in colitis cystica profunda often grow in a lobular configuration, without jagged borders or unusual irregularly shaped glandular profiles more typical of adenocarcinoma. Misplaced crypts show either normal or reactive appearing colonic epithelium. A mild degree of mucin depletion, pseudostratification and increased mitotic activity may be present. However, loss of nuclear polarity, increased N/C ratio and atypical mitosis should alert one to the possibility of adenocarcinoma. The presence of lamina propria surrounding misplaced glands, and the lack of "dysplastic" appearing epithelium, are key features that help distinguish colitis cystica profunda from invasive adenocarcinoma Rectal prolapse/solitary rectal ulcer syndrome (SRUS): In complete prolapse, all layers of the rectum visibly protrude through the anal orifice. In occult prolapse, there is internal intussusception of the rectal mucosa without visible protrusion form the anus. Rectal prolapse in adults is 3 – 10 times more common among women [15]. Common clinical associations include straining at defecation and poor tone of the pelvic musculature. Complete rectal prolapse usually requires surgical correction in order to avoid further damage to the anal sphincter and pelvic floor muscles. Commonly, anterior sling rectopexy is performed whereby the the rectum is mobilized to the tip of the coccyx and is attached to the presacral fascia by means of a nonabsorbable plastic mesh [15]. SRUS is most common among women in their third and fourth decades and can be associated with either overt or occult prolapse. Symptoms (typically chronic) include constipation, mucorrhea, bleeding, or tenesmus. Endoscopically, ulcers in SRUS are most commonly single, small, and shallow; however, ~1/3 of patients lack an ulcer, and occasionally the ulcers are multiple or large. The ulcers in ~85% of patients are located in the anterior rectum, often in the distal aspect. Frequently, there is also nodularity of the surrounding rectal mucosa. Histologically, the ulcers themselves have a nonspecific appearance, but biopsies from non-ulcerated mucosa show characteristic fibromuscular hyperplasia in the lamina propria. Strands of smooth muscle extend upward from the muscularis mucosa, surrounding crypts and imparting an angulated contour to the crypts ("diamond-shaped crypts"). The etiology of ulceration in SRUS is hypothesized to relate to excessive straining at defecation: the anterior rectal mucosa is forced downward against the pelvic floor, which causes trauma and focal ischemia. Management is usually conservative – education to avoid straining at defecation, a high fiber diet, and bulk laxatives – and leads to remission of symptoms in a majority of cases [7, 9]. Medical options include local steroid applications or 5-ASA products. These do not treat the underlying defecatory disorder but can promote macroscopic healing [15]. Some patients undergo surgical resection because of obstructing lesions [5], confusion with carcinoma, or severe symptoms. Eroded polypoid hyperplasia: The mucosa in rectal prolapse/SRUS often assumes a hyperplastic or villiform appearance. These polyps share characteristics of mucosal prolapse-induced polyps throughout the GI tract. In the rectum, they are variably termed "polypoid prolapsing mucosal folds [16]," "prolapse-induced inflammatory polyps [17]," or "eroded polypoid hyperplasia [18]." Mucosal prolapse polyps in the anal-transitional zone are termed "inflammatory cloacogenic polyps," in the colon proper as "inflammatory cap polyps," in the sigmoid as "diverticular disease-associated polyps," and in the stomach as "gastric antral vascular ectasia" or "watermelon stomach." The pathogenesis is related to traction, distortion and twisting of mucosa as a result of peristalsis-induced trauma which leads to torsion of blood vessels and tissue damage, localized ischemia and repair in the form of lamina propria fibrosis. The classic histologic features of prolapse-induced polyps include: 1) Fibromuscular hyperplasia in the lamina propria, 2) Thickening, splaying, and vertical extension of the muscularis mucosa into the lamina propria, 3) Crypt abnormalities (elongation, hyperplasia, architectural distortion, and serration) and 4) Variable degrees of stromal and epithelial inflammation. Polyps in SRUS can at times mimic adenomas, hyperplastic polyps, or serrated adenomas. Gopal et al described a 36-year-old woman with many (50 – 60) small rectal polyps that were clinically concerning for either rectal carpeting by a villous adenoma or juvenile polyposis [18]. Recently, Ball et al studied the histology in 26 patients with SRUS [19]. Ten (38%) cases had features mimicking serrated adenoma including hypermucinous epithelium, exaggerated serration in the lower portion of crypts, branching of crypts, and horizontal extension of crypt bases along muscularis mucosa. None were truly dysplastic. Unlike serrated adenomas, the mucosa in SRUS also showed areas of ischemic change including erosion and fibrosis. Interestingly, in 2 of 10 (20%) cases that mimicked serrated adenoma the authors found focal superficial loss of the hMLH1 DNA mismatch repair protein. They hypothesized that this might indicate a propensity for neoplastic progression in some cases of SRUS as a result of repeated trauma and repair. However, in practice it is much more important to avoid overcalling dysplasia or neoplasia in SRUS than to be concerned about pre-neoplastic molecular changes. References: Guest CB, Reznick RK. Colitis cystica profunda; review of the literature. Dis Colon Rectum 1989;32:983-988. Goodall HB, Sinclair IS. Colitis cystica profunda. J Pathol 1957;73:33-42. Franzin G, Novelli P. Gastritis cystica profunda. Histopathology 1981;5:535-547. Dippolito AD, Aburano A, Bezouska CA, et al. Enteritis cystica profunda in Peutz-Jeghers syndrome. Report of a case and review of the literature. Dis Colon Rectum 1987;30:192-198. Bentley E, Chandrasoma P, Cohen H, et al. Colitis cystica profunda: presenting with complete intestinal obstruction and recurrence. Gastroenterology 1985;89:1157-1161. Kim WH, Choe GY, Kim YI, et al. Localized form of colitis cystica profunda—a case of occurrence in the descending colon. J Korean Med Sc 1992;7:76-78. Valenzuela M, Martin-Ruiz JL, Alvarez-Cienfuegos E, et al. Colitis cystica profunda: imaging diagnosis and conservative treatment: report of two cases. Dis Colon Rectum 1996;39:587-590. Vora IM, Sharma J, Joshi AS. Solitary rectal ulcer syndrome and colitisi cystica profunda—a clinico-pathological review. Indian J Pathol Microbiol 1992;35:94-102. Stuart M. Proctitis cystica profunda. Incidence, etiology, and treatment. Dis Colon Rectum 1984;27:153-156. Peterkin GA 3rd, Moroz K, Kondi ES. Proctitis cystica profunda in paraplegics. Report of three cases. Dis Colon Rectum 1992;35:1174-1176. Lifshitz D, Cytron S, Yossiphov J, et al. Colitis cystica profunda: self-inflicted by rectal trauma? Report of a case. Dig Dis 1994;12:318-320. Ng WK, Chan KW. Postirradiation colitis cystica profunda. Arch Pathol Lab Med 1995;119:1170-1173. Gardiner GW, McAuliffe N, Murray D. Colitis cystica profunda occurring in a radiation-induced colonic stricture. Hum Pathol 1984;15:295-298. Zidi SH, Marteau P, Piard F, et al. Enterocolitis cystica profunda lesions in a patient with unclassified ulcerative enterocolitis. Dig Dis Sci 1994;39:426-432. Gopal DV. Diseases of the rectum and anus: a clinical approach to common disorders. Clin Cornerstone 2002;4:34-48. 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. Chetty R, Bhathal PS, Slavin JL. Prolapse-induced inflammatory polyps of the colorectum and anal transitional zone. Histopathology 1993;23:63-67. Gopal DV, Young C, Katon RM. Solitary rectal ulcer syndrome presenting with rectal prolapse, severe mucorrhea and eroded polypoid hyperplasia: case report and review of the literature. Can J Gastroenterol 2001;15:479-483. 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;129:1037-1040.