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□ CASE REPORT □

A Case of Rectal Cancer Arising from Long-StandingProlapsed Mucosa of the Rectum

Takashi Nonaka 1,2, Masahiko Inamori 1,3, Tadaomi Kessoku 2, Yuji Ogawa 2,

Shogo Yanagisawa 2, Tadahiko Shiba 2, Takashi Sakaguchi 2, Eiji Gotoh 4, Shin Maeda 1,

Atsushi Nakajima 1, Kazuhiro Atsukawa 2, Hisao Takahasi 2 and Yoshikiyo Akasaka 5,6

Abstract

Mucosal prolapse syndrome (MPS) has been recognized as a chronic benign inflammatory disorder, char-

acterized mainly by rectal mucosal prolapse. Disorders representing this condition include solitary rectal ulcer

syndrome (SRUS), rectal prolapse, proctitis cystica profunda, and inflammatory cap polyps. The gross ap-

pearance of rectal MPS can be occasionally misinterpreted as rectal cancer. In contrast, there have been a few

reports of colorectal cancer originating from prolapsed mucosa. Herein, we report a case of MPS associated

with two independent rectal cancers extending into the submucosal layer. We speculate that long-standing

MPS may increase the risk of malignant transformation.

Key words: mucosal prolapse syndrome, solitary rectal ulcer syndrome, rectal cancer, malignant transforma-

tion

(Intern Med 50: 2569-2573, 2011)(DOI: 10.2169/internalmedicine.50.5924)

Introduction

Solitary rectal ulcer syndrome (SRUS) is considered as a

rare benign rectal disease that has a wide spectrum of clini-

cal presentations, variable endoscopic findings, and charac-

teristic histopathological features (1-9). Recently, the mu-

cosal prolapse syndrome (MPS) was proposed as a unified

concept, and has been accepted widely, based on the recog-

nition that similar histopathological abnormalities can occur

in other conditions and sites, such as transitional mucosa ad-

jacent to large bowel tumors, prolapsed colostomies, and

prolapsed hemorrhoids (10-12).

Although it has been reported that rectal MPS can occa-

sionally be misinterpreted as rectal carcinoma based on its

clinical presentation, and endoscopic and radiographic ap-

pearances (3-9), few reports have described the occurrence

and characteristics of malignant transformation in this syn-

drome (13-18). Neither the association of cancer with long-

standing MPS nor the malignant potential of MPS has ever

been investigated thoroughly. We report a highly unusual

case of MPS with moderately differentiated tubular adeno-

carcinoma and poorly differentiated adenocarcinoma arising

from the prolapsed mucosa, both of which invaded the sub-

mucosal layer.

Case Report

A 69-year-old man visited our hospital with lower ab-

dominal pain and difficulty in passing stools. The patient

had a history of hypertension and gastric ulcer. The physical

examination was unremarkable. The results of laboratory ex-

aminations, including urinalysis, complete blood cell count

(CBC), and liver and renal function tests were normal. The

serum C-reactive protein level was 0.1 mg/dL, serum carci-

noembryonic antigen (CEA) level was 3.1 ng/mL, and the

１Gastroenterology Division, Yokohama City University School of Medicine, Japan, ２Department of Gastroenterology, Hiratsuka City Hospital,

Japan, ３Office of Postgraduate Medical Education, Yokohama City University Hospital, Japan, ４Department of Medical Education, Yokohama

City University School of Medicine, Japan, ５Department of Pathology, Toho University School of Medicine, Japan and ６Division of Chronic In-

flammatory Diseases, Advanced Medical Research Center, Toho University Graduate School of Medicine, Japan

Received for publication May 30, 2011; Accepted for publication July 25, 2011

Correspondence to Dr. Masahiko Inamori, inamorim@med.yokohama-cu.ac.jp

Intern Med 50: 2569-2573, 2011 DOI: 10.2169/internalmedicine.50.5924

2570

Figure　1.　Thirteen years earlier, the first colonoscopic ex-amination revealed reddened lesions on the anterior wall of the lower rectum.

Figure　2.　The first time biopsy specimen showed mild in-flammation in the lamina propria and upward proliferation of a splayed muscularis mucosa.

Figure　3.　The current endoscopic examination. a: A protruding lesion was seen on the anal side in the reddened mucosa of the rectum. b: A depressed lesion was seen on the oral side, close to the pro-truding lesion.

a b

serum carbohydrate antigen (CA) 19-9 level was 9.3 U/mL.

He had no history of enema use or insertion of supposito-

ries, but he had tended to strain at defecation for a long

time. Interestingly, it was his past medical history that

brought him to our hospital this time; he desired further ex-

amination for a positive fecal occult blood test 14 years pre-

viously, and had undergone colonoscopy that revealed

patchy erythematous mucosa on the anterior wall of the

lower rectum (Fig. 1). At that time, biopsy specimens taken

from the lesion had shown evidence of mild inflammation,

reactive epithelial changes with hyperplastic and distorted

crypts, ectatic and congested vessels, and subtle upward pro-

liferation of a splayed muscularis mucosa. Consequently,

this lesion was initially diagnosed as idiopathic proctitis

without dysplasia or malignancy, because its histopathologi-

cal findings were weakly perceived as MPS features

(Fig. 2). Although colonoscopy had been performed repeat-

edly since the first examination, the endoscopic appearances

and histopathological findings on biopsy had remained con-

stant. His last colonoscopy had been conducted five years

previously, and biopsy specimens taken from the same red-

dened lesions had shown no evidence of malignancy. The

present time colonoscopic examination revealed a protruding

lesion on the anal side (Fig. 3a) and a depressed lesion on

the oral side (Fig. 3b) in the aforementioned reddened mu-

cosa of the rectum. Biopsy specimens taken from the pro-

truding lesion revealed a moderately differentiated tubular

adenocarcinoma. As a result, laparoscopic abdominoperineal

rectal resection with regional lymph node dissection was

performed (Fig. 4). Histopathologically, the protruding le-

sion consisted of moderately differentiated tubular adenocar-

cinoma (Fig. 5a), and the depressed lesion consisted of a

poorly differentiated adenocarcinoma (Fig. 5b, 5c), both of

which were discontinuous and extended into the submucosal

layer without vascular or lymphocytic infiltration or lymph

node metastasis. Immunohistochemically, the protruding le-

sion showed negative staining for p53, however, the de-

pressed lesion showed both strong and diffuse positive stain-

ing. Histopathological examination of the background rectal

mucosa surrounding the two cancers revealed the presence

of longitudinal smooth muscle fibers and collagen deposi-

Intern Med 50: 2569-2573, 2011 DOI: 10.2169/internalmedicine.50.5924

2571

Figure　4.　Gross appearance of the resected rectum. The protruding lesion (arrow) was 20 mm in diameter and 4 cm from the anal verge; the depressed lesion (arrowhead) was 15 mm in diameter and 6 cm from the anal verge. Both lesions were discontinuous and independent.

Figure　5.　Histopathological examination. a: Section of the protruding lesion with a background mucosa. Moderately differentiated tubular adenocarcinoma was seen (at left), with MPS mucosa (at right) which showed thickened muscularis mucosa and ingrowth of muscle fibers in the lamina pro-pria (Hematoxylin and Eosin staining, ×4). b: Section of the depressed lesion with a background mu-cosa. The border between poorly differentiated adenocarcinoma (at left) and MPS mucosa (at right) was observed with marked collagenous fiber in the submucosa. Area outlined by the square is shown in panel c (Hematoxylin and Eosin staining, ×4). c: High magnification showed poorly differentiated adenocarcinoma and the border (Hematoxylin and Eosin staining, ×10). d: Azan-Mallory staining for Fig. 5b enhanced marked collagenous fiber in the lamina propria and submucosa (Azan-Mallory stain, ×4). e: Immunohistochemical staining using α-SMA for Fig. 5c enhanced the appearance of the fibromuscular obliteration in the lamina propria (α-smooth muscle actin stain, ×10).

a b c

d e

tion in the lamina propria, namely fibromuscular oblitera-

tion, which is a characteristic histopathological feature in

MPS (Fig. 5d, 5e).

Discussion

Solitary rectal ulcer syndrome (SRUS), although origi-

nally described by Cruveilhier in 1830 (1), gained wide ac-

ceptance only after Madigan and Morson characterized the

lesion both clinically and pathologically in 1969 (2). This

entity is a rare benign disease of the rectum, which pre-

dominantly affects adults over a wide age range, with an es-

timated prevalence of 1 in 100,000 people per year (3-5).

Although the term SRUS has been widely accepted, it is

misleading in that the lesions may neither be ulcerated nor

solitary on macroscopic examination (3-9). For this reason,

recently, the unifying concept of the mucosal prolapse syn-

drome (MPS) was proposed as a common clinicopathologi-

cal term, based on the recognition of clinical and histopa-

thological similarities with other conditions and at other

sites (10-12). In other words, SRUS is now considered as

one entity in the spectrum of MPS.

The underlying etiology of SRUS/rectal MPS is not yet

fully understood. However, several hypotheses have been

proposed, including congenital malformations, paradoxical

contraction of the pelvic floor and external anal sphincter

muscles from excessive straining at defecation, localized

rectal ischemia, inflammation, and rectal pro-

lapse (10, 19-23).

The symptoms of SRUS/rectal MPS are quite variable.

Nearly all patients describe a symptom complex consisting

of rectal bleeding, passage of mucus, tenesmus, perineal and

abdominal pain, constipation, sensation of incomplete defe-

cation, straining on defecation, and rectal pro-

Intern Med 50: 2569-2573, 2011 DOI: 10.2169/internalmedicine.50.5924

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Table　1.　Clinical Features of Patients with MPS Accompanied by Carcinoma

case(Ref) author/year Age/Sex Presenting symptoms Macroscopic findings Location Histological type of tumor Depth of tumor invasion

1 (13) Silver H/1969 49/F rectal pain, bleeding andan abnormal discharge

a tender ulcer with elevated edges rectum well differentiated mucinous adenocarcinoma ND

2 (14) Burt CA/1970 76/F rectal bleeding andmucous stool

a large polypoid mass sigmoid Papillary - mucinous adenocarcinoma subserosa

3 (15) Bhuta I/1976 27/M rectal bleeding andtenesmus

multiple elevated tumor masseswith ulceration

rectum adenocarcinoma in situ

4 (16) Li SC/1998 59/M constipation a mass rectum adenocarcinoma ND

5 (16) Li SC/1998 53/F rectal bleeding irregular nodules rectum adenocarcinoma ND

6 (16) Li SC/1998 26/M ND a mass rectum adenocarcinoma ND

7 (17) Tsuchida K/1998 45/F constipation a small ulcerated lesion rectum well differentiated tubular adenocarcinoma submucosa

8 (18) Mönkemüller KE/1999 19/F constipation, tenesmus,and lower abdominal pain

a rectal stricutre surrounded by patchygranular hyperemic mucosa

rectum poorly differentiated mucinous adenocarcinoma ND

9 Nonaka T/2011 69/M lower abdominal pain anddifficulty in defecating

a protruding lesion and a depressed lesionin the patchy erythematous mucosa

rectum moderately differentiated tubular adenocarcinoma,and poorly differentiated adenocarcinoma

submucosa

ND: not described

lapse (7, 8, 23). However, up to 26% of patients can be as-

ymptomatic (6), therefore SRUS/rectal MPS is occasionally

discovered incidentally as in the present case.

The macroscopic findings of SRUS/rectal MPS also vary.

The macroscopic appearance of SRUS/rectal MPS can be

classified into ulcerative (55.1%), polypoid (24%) and flat

(20.9%) types (8). Madigan and Morson reported multiple

lesions in 30% of cases of SRUS (2). Endoscopic misdiag-

nosis occurs frequently because of these variable find-

ings (6-8).

Although the gross appearances of SRUS/rectal MPS vary

greatly, the histopathological findings are highly characteris-

tic. The rectal mucosa in cases of SRUS/rectal MPS shows a

characteristic fibromuscular proliferation within the lamina

propria, accompanied by the thickening and fraying of the

muscularis mucosa, collagen deposition in the lamina prop-

ria, varying degrees of chronic and occasionally active in-

flammation, and reactive epithelial changes (2, 10, 16, 24).

The correct diagnosis of SRUS/rectal MPS depends on a

recognition of these specific histopathological features, espe-

cially the “fibromuscular obliteration”.

SRUS/rectal MPS can occasionally be misdiagnosed as

rectal carcinoma based on its clinical presentation, and en-

doscopic and radiographic appearances, and in some in-

stances, histopathological appearances, due to the presence

of atypical proliferating epithelium ‘as a part’ reactive epi-

thelial changes. Numerous reports focusing on distinction of

MPS from rectal carcinoma have been published (3-9), how-

ever, there are only a few reports describing the occurrence

and characteristics of malignant transformation in SRUS/rec-

tal MPS (13-18) (Table 1). Occasionally, SRUS-like histopa-

thologic feature was produced by underlying malig-

nancy (16). In contrast, there was no report that implied ma-

lignant transformation in MPS based on long-term endo-

scopic observation. The relationship between MPS and col-

orectal cancer remains unclear, although the association of

colorectal cancer with long-standing inflammatory bowel

disease has been established (25-27). A previous report sug-

gested that long-standing chronic idiopathic colitis was asso-

ciated with an increased risk of colorectal dysplasia and ade-

nocarcinoma (28). The mechanism of transformation in MPS

is obscure, but it can be in the same manner as the above

conditions. Furthermore, Ball et al reported that parts of

SRUS showed focal loss of hMLH1 gene expression, indi-

cating the potential for preneoplastic change (29). We specu-

late that the rectal cancer in the present case represents a

malignant transformation from long-standing rectal MPS,

based on the long-term endoscopic observation.

Conclusion

In conclusion, we reported a highly unusual case of MPS

with two independent rectal cancers extending into the sub-

mucosal layer. Intentional colonoscopy and repeated biopsy

for MPS may facilitate the correct diagnosis of such cases,

because long-standing MPS may be associated with an in-

creased risk of malignant transformation.

The authors state that they have no Conflict of Interest (COI).

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