Solitary rectal ulcer syndrome accompanied by submucosal invasive carcinoma

THE AMERICAN JOURNAL OF GASTROENTEROLOGY Copyright © 1998 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.

Vol. 93, No. 11, 1998 ISSN 0002-9270/98/$19.00 PII S0002-9270(98)00503-6

Solitary Rectal Ulcer Syndrome Accompanied by Submucosal Invasive Carcinoma Kenji Tsuchida, M.D., Naotsuka Okayama, M.D., Mitsuki Miyata, M.D., Takashi Joh, M.D., Yoshifumi Yokoyama, M.D., Makoto Itoh, M.D., Kenji Kobayashi, M.D., and Takaaki Nakamura, M.D. First Department of Internal Medicine, First Department of Surgery, and Department of Pathology, Nagoya City University Medical School, Nagoya, Japan

We report a case of carcinoma in solitary rectal ulcer syndrome. The diagnosis was made by colonoscopic appearance and biopsy. A tumor measuring 0.9 3 0.6 cm was found in a resected solitary rectal ulcer. The lesion exhibited typical histological features of solitary rectal ulcer syndrome, with a well differentiated adenocarcinoma invading submucosal layers and some dysplastic glands. We believe that the adenocarcinoma represents a malignant transformation from solitary rectal ulcer syndrome, because similar to longstanding chronic idiopathic colitis, colorectal dysplasia and carcinoma may develop. (Am J Gastroenterol 1998; 93:2235–2238. © 1998 by Am. Coll. of Gastroenterology)

pation. There was no history of mucoid discharge or bleeding per rectum. Colonoscopy revealed a small ulcerated lesion in the rectum. Biopsy from the edge of the ulcer and adjacent regions showed nonspecific inflammation. In January 1995, the patient was admitted to our hospital for further evaluation. Examination revealed a well nourished woman with normal physical findings except for an induration area palpable on the anterior wall of the rectum 5 cm from the anal verge. Routine laboratory studies were normal, and carcinoembryonic antigen (CEA) was not elevated. Occult blood was not detected in her feces. An air contrast barium enema demonstrated a small, oval lesion measuring 1.9 3 0.8 cm in length and 0.3 cm in depth on the anterior wall of the rectum 4 cm proximal to the anal verge. Nodularity of the distal-rectal mucosa and thickening of the mid Valve of Houston were noted. Multi– centric fold convergency was noted around the lesion (Fig. 1). These findings were compatible with SRUS. Colonoscopy (model CF-230I; Olympus, Tokyo, Japan) revealed a small rectal ulcer on the anterior wall on the mid Valve of Houston. The ulcer was shallow and partially covered with exudate. The ulcer was surrounded by slightly raised mucosa. There were shallow erosions and nodules between the ulcer and anal verge. Irregularity of the surface of the ulcer was definable by the dye spreading method, suggestive of carcinoma accompanying SRUS. Biopsy of the edge and adjacent scar showed fibromuscular obliteration of SRUS and carcinoma in only one of the specimens taken from the edge of the ulcer. Transrectal endoscopic ultrasound (EUS) examination was performed on the ulcerative rectal lesion with a radial endoscopic probe (model CF-UM3; Olympus, Tokyo, Japan) using a frequency of 12 MHz. The normal rectal wall consisted of five layers; individual layers were distinct and not interrupted. This examination revealed the rectal lesion as a relatively hypoechoic mass with echogenic spots that interrupted the continuity of the first (mucosal layer) and second (muscularis mucosa) layers. The third layer (submucosal layer, about 4 cm in diameter) was thickened around the ulcer and narrowed under the ulcer. The fourth layer (muscularis propria) was thickened slightly. The thickness of the entire rectal wall beneath the lesion was increased to

INTRODUCTION Recently, solitary rectal ulcer syndrome (SRUS) has been recognized as having characteristic clinical and pathological manifestations (1). SRUS is hypothesized to be a sequel to or variant of localized colitis cystica profunda (CCP) of the rectum, suggesting that nonulcerating forms of SRUS can be regarded as localized areas of CCP (2). SRUS is accepted as a chronic, benign inflammatory disorder because there have been no reports describing malignant transformation in this syndrome. In contrast to SRUS, there are few reports of coexisting malignancy with CCP (3–5), indicating that CCP has the potential for malignant transformation. CCP is considered to be a premalignant lesion as are ulcerative colitis and Crohn’s disease (6). These facts suggest that SRUS may undergo malignant transformation. We report the first case of SRUS accompanied by dysplasia and well differentiated adenocarcinoma invading the submucosal layer. We speculate that the carcinoma in this case originated from SRUS mucosa. CASE REPORT In December 1994, a 45-yr-old woman visited a local hospital for evaluation of a 10-yr history of severe constiReceived Nov. 6, 1997; accepted Apr. 6, 1998. 2235

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AJG – Vol. 93, No. 11, 1998 mucosa. Around the ulcer, characteristic features of SRUS were seen at the margins and also remotely from the ulcer. These features were 1) obliteration of lamina propria by fibroblasts and smooth muscle from the muscularis mucosa; 2) thickening of the muscularis mucosa; and 3) erosion of the mucosae (Fig. 2). However, submucosal pools of mucin lined with an epithelium (i.e., colitis cystica profunda), were not observed. No invasion into veins or lymph vessels and no metastasis to regional lymph nodes was observed. DISCUSSION

FIG. 1. The findings on air contrast barium enema in January 1995, demonstrating nodularity of distal rectal mucosa and thickening of the mid Valve of Houston. Small oval niche measuring 1.9 3 0.8 cm with multicentric fold convergence in the right anterior wall of the lower and mid rectum.

14 mm. No lymph nodes were detected around the lesion. These findings on EUS examination were compatible with SRUS. There were no findings consistent with malignancy such as a solid hypoechoic mass or a transmural infiltrating lesion. Based on these examinations, the lesion was diagnosed as SRUS accompanied by adenocarcinoma. The invasive depth of the cancer lesion was presumed to be restricted to the submucosal layer based on the colonoscopic findings. A low anterior resection (LAR) with anorectal anastomosis and diverting colostomy was performed in April 1995. The colostomy was subsequently closed, and the patient recovered uneventfully. The patient remains well and has no evidence of tumor recurrence since her discharge from the hospital in June 1995. Pathological examination Grossly, the resected ulcer specimen was shallow oval, and 0.9 3 0.6 cm. A scar was present adjacent to the ulcer, around which the mucosa was slightly elevated. Histological sections of the tissue stained with hematoxylin and eosin revealed well differentiated adenocarcinoma invading the submucosal layers at the center of the ulcer. There were some dysplastic glands between the carcinoma and SRUS

Solitary rectal ulcer syndrome is recognized as a chronic benign inflammatory disorder characterized by rectal bleeding, diarrhea, constipation, and anorectal pain (1). Although the term SRUS has been widely accepted (7), it is misleading in that lesions are not always ulcerated or solitary on macroscopic examination (1). Colitis cystica profunda is characterized by the presence of mucus-filled cysts and occurs mainly in the rectum (8). SRUS and localized CCP with ulceration are recognized to be related disorders (9). These disorders are occasionally misdiagnosed as mucinous adenocarcinoma, which they resemble clinically and microscopically (10). It is believed that SRUS results from repeated mucosal trauma with ischemia of the rectal wall from straining at defecation (11), although its pathogenesis is not clearly known. Self-inflicted trauma has also been cited as an etiological factor in the development of SRUS (12), although it is generally felt that the histological features of SRUS are not consistent with those of a purely traumatic cause (13). Rectal examination of SRUS patients may reveal single or multiple nodules that frequently have a rubbery consistency, and the findings are similar in both SRUS and localized CCP (9). The lesions are most often located on the anterior rectal wall 3–12 cm from the anal margin and are usually ,4 cm in diameter (11, 14). The radiological manifestations of SRUS are: thickened, edematous Valves of Houston; an increase in the retrorectal space; mucosal abnormalities including nodularity, thickened longitudinal folds, or ulceration; and filling defects suggesting a mass or polyps (15). Our patient had all of these findings consistent with SRUS, but the accompanying carcinoma was not detected before surgery. Colonoscopy is one of the most important examinations in diagnosing SRUS. The mucosa surrounding an SRUS ulcer is usually edematous, slightly hyperemic, and often friable (1, 12, 15). Endoscopic differential diagnosis is lengthy because of the variable findings of the lesion (15). In our case, the dye spreading method (16) clearly defined irregurality in the ulcer and the scar. This method helped us to diagnose the carcinoma accompanying SRUS. Our patient’s ulcer did not penetrate beyond the submucosal layer of the rectal wall and was distinct from the rectal carcinoma by transrectal EUS, which visualized the individual wall layers and depicted the mural extent of the

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FIG. 2. Section through the main lesion in the rectum demonstrates formation of dense collagen in the submucosa. The border between a well differentiated adenocarcinoma (at left) and SRUS mucosa (at right) is observed. Muscle fibers derived from the muscularis mucosa pass up among colonic glands (hematoxylin and eosin stain; original magnification 3 10).

neoplastic lesion. The thickening of the muscularis propria of the rectal wall was reported as a typical finding of SRUS on EUS examination (17, 18). In the present case, the findings of EUS were compatible with SRUS; however, the coincidental carcinoma was not detected because the carcinoma was small and the echogenicity was similar to that of the SRUS lesion. The correct diagnosis of SRUS depends on recognition of specific histopathological features termed “fibromuscular obliteration” on biopsy specimens (1, 11, 19). More than half of the patients can be diagnosed simply by clinical history, and the remainder by biopsy (20). On the other hand, nodules grasped by biopsy forceps often fail to produce a specimen of sufficient depth to provide a conclusive histopathological diagnosis when the consistency of the lesion is firm (21). In our case, there were two reasons why the accompanying carcinoma was not detected before surgery. First, the typical findings of carcinoma were not obtained by radiological and ultrasonographic examination. Second, carcinoma cells were noted in only one of nine biopsy specimens because the edge of the ulcer was too firm to grasp sufficient specimens with biopsy forceps. It is important that detailed colonoscopic examination be performed and that lesional tissue for biopsy be grasped slowly using forceps with a needle. In the present case, it is speculated that SRUS existed for $10 yr based on her history of self-digitation. This speculation is supported by air contrast barium enema and colonoscopic findings that showed evidence for repeated ulceration with multiple scar formation and fold convergence. Long term chronic idiopathic colitis increases the risk of colorec-

tal dysplasia and adenocarcinoma (6). There have been studies of CCP accompanied by adenocarcinoma (3–5), but no reports of SRUS with carcinoma. However, it is possible that the chronic inflammation of SRUS increase the risk of colorectal dysplasia and adenocarcinoma as well. We report the first case of SRUS with well differentiated adenocarcinoma invading submucosal layers with dysplastic glands adjacent to the carcinoma. In our patient, the possibility of malignant transformation of SRUS is supported by the coexistence of dysplastic areas and adenocarcinoma with SRUS. In conclusion, we reported a clinically and histologically typical case of SRUS with a focus of well differentiated adenocarcinoma invading submucosal layers at the center of the rectal ulcer. A long term history of SRUS may be of significance for an increased risk of subsequent dysplasia and carcinoma. Reprint requests and correspondence: Kenji Tsuchida, M.D., First Department of Internal Medicine, Nagoya City University Medical School, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467, Japan.

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AJG – Vol. 93, No. 11, 1998 14. Misumi A, Sera Y, Matsuda M, et al. Solitary ulcer of the rectum: Report of a case and review of the literature. Gastroenterologia Japonica 1981;16:286 –94. 15. Feczo PJ, O’Connell DJ, Riddell RH, et al. Solitary rectal ulcer syndrome: Radiologic manifestations. Am J Roentgenol 1980;135: 499 –506. 16. Kudo S. Endoscopic mucosal resection of flat and depressed types of early colorectal cancer. Endoscopy 1993;25:455– 61. 17. Outryve MJV, Pelckmans PA, Fierens H, et al. Transrectal ultrasound study of the pathogenesis of solitary rectal ulcer syndrome. Gut 1993; 34:1422– 6. 18. Hulsmans FJH, Tio TL, Reeders PWAJ, et al. Transrectal US in the diagnosis of localized colitis cystica profunda. Radiology 1991;181: 201–3. 19. Saul SH, Sollenberger LC. Solitary rectal ulcer syndrome. Its clinical and pathological underdiagnosis. Am J Surg Pathol 1985;9:411–21. 20. Kennedy DK, Hughes ESR, Masterton PJ. The natural history of benign ulcer of the rectum. Surg Gynecol Obstet 1977;144:718 –20. 21. Martin JK, Culp CE, Weiland LH. Colitis cystica profunda. Dis Colon Rectum 1980;23:488 –91.