Solitary Amyloidosis of the Sigmoid Colon Featuring

2523

□ CASE REPORT □

Solitary Amyloidosis of the Sigmoid Colon FeaturingSubmucosal Tumor Caused Hematochezia

Naotaka Ogasawara 1, Wataru Kitagawa 2, Konen Obayashi 4, Yoshitsugi Itoh 1,

Hisatsugu Noda 1, Yasushi Funaki 1, Toyoharu Yokoi 3, Makoto Sasaki 1,

Hirokazu Imai 2 and Kunio Kasugai 1

Abstract

A previously a healthy 64-year-old woman complained of a two-week history of hemorrhaging upon defe-

cation. The laboratory and urinalysis findings were normal, and no serum or urine M components were de-

tectable on protein electrophoresis. An air contrast barium enema revealed an elevated lesion measuring -20

mm in diameter with a smooth surface and a depression in the sigmoid colon. Colonoscopy revealed a red

colored and congested tumor. The exposed surface of the submucosal tumor (SMT) center was somewhat

yellow in color and covered with fuzz. All other portions of the colon were normal. The endoscopy and

double-contrast barium revealed a normal upper gastrointestinal tract and a normal small intestine, respec-

tively. A histopathological evaluation of a biopsy specimen obtained from the SMT suggested amyloid depo-

sition. However, the other biopsy specimens of the esophagus, stomach, duodenal bulb, second portion of the

duodenum, terminal ileum and other portions of the colon demonstrated no amyloid deposition. Colonoscopic

ultrasonography (US) revealed the hypoechoic, homogeneous SMT to be mainly localized within the submu-

cosa. An endoscopic submucosal resection (EMR) of the solitary amyloidosis was performed and the immu-

nohistopathology revealed the entire SMT to consist of amyloid light chain kappa amyloid deposition. We

considered that the US followed by EMR contributed to the precise diagnosis of solitary amyloidosis and the

treatment of hematochezia caused by a solitary area of amyloidosis within the sigmoid colon.

Key words: amyloidosis, colon, endoscopic submucosal resection (EMR), submucosal tumor,

ultrasonography (US)

(Intern Med 52: 2523-2527, 2013)(DOI: 10.2169/internalmedicine.52.0944)

Introduction

Amyloidosis is a rare disease caused by deposits of rigid

non-branching protein fibrils that lead to various pathophysi-

ological changes. Although amyloidosis can occur in virtu-

ally any organ system in the body, amyloidosis localized in

the gastrointestinal (GI) tract is relatively rare (1-3). The

signs and symptoms of amyloidosis depend on where in the

GI tract the amyloid is deposited. Patients with intestinal

amyloidosis might clinically present with diarrhea, steator-

rhea, protein-losing enteropathy, hemorrhage, obstruction,

mesenteric ischemia, intussusceptions, pneumatosis intestina-

lis or pseudo-obstruction (4). The clinical manifestations in

the colon can mimic other diseases, such as malignancy, in-

flammatory bowel disease and ischemic and collagenous co-

litis. The endoscopic findings of amyloidosis can indicate

mucosal friability, multiple polypoid lesions, erosion, ulcera-

tions or granular appearances (4). However, a solitary amy-

loidosis of a submucosal tumor (SMT) localized within the

colon is extremely rare. We herein describe a solitary pri-

mary amyloid light chain (AL) amyloidosis localized within

１Department of Gastroenterology, Aichi Medical University School of Medicine, Japan, ２Department of Nephrology and Rheumatology, Aichi

Medical University School of Medicine, Japan, ３Department of Pathology, Aichi Medical University School of Medicine, Japan and ４Diagnostic

Unit for Amyloidosis, Department of Laboratory Medicine, Kumamoto University Hospital, Japan

Received for publication May 9, 2013; Accepted for publication July 7, 2013

Correspondence to Dr. Naotaka Ogasawara, [email protected]

Intern Med 52: 2523-2527, 2013 DOI: 10.2169/internalmedicine.52.0944

2524

Figure　1.　Air contrast barium enema findings. An elevated lesion (–20 mm diameter) with a smooth surface in the sigmoid colon was observed (A, arrowheads). The central portion of the tumor showed a central superficial irregularity and a depressed area (B, arrowheads).

A B

the sigmoid colon presenting a SMT that caused constant

hematochezia. The solitary area of amyloidosis of the colon

was removed using endoscopic submucosal resection

(EMR), the hematochezia was cured and the amyloid depo-

sition was thereafter immunohistologically confirmed.

Case Report

A previously healthy 64-year-old woman presented with

the chief complaint of a two-week history of constant hem-

orrhaging on defecation. Her family and medical histories

were unremarkable. Neither lymphadenopathy nor thyroid

swelling were evident and the abdominal findings were nor-

mal. The laboratory and urinalysis data upon admission

were all within normal limits. No serum or urine M compo-

nents were detectable on the protein and immunofixation

electrophoresis. She had no chronic disorders predisposing

her to secondary amyloidosis or amyloid deposition, such as

rheumatoid arthritis, tuberculosis, cardiac disease, multiple

myeloma, malabsorption, and proteinuria. Whole body com-

puted tomography (CT) and positron emission tomography

(PET) as well as radiography of all bones revealed no ab-

normalities. The electrocardiography and echocardiography

findings were normal. An air contrast barium enema re-

vealed an elevated lesion of about 20 mm in diameter with a

relatively smooth surface (Fig. 1A) and a central superficial

irregularity and depression (Fig. 1B) in the sigmoid colon.

Colonoscopy revealed a smooth elevated lesion measuring

about 20 mm in diameter in the sigmoid colon. The tumor

was hard and red in color, with congested features

(Fig. 2A). The cushion sign associated with SMT was not

present. Contact with the colonoscope caused slight oozing

from the surface of the SMT. The exposed surface of the

central tumor was fuzzy, with focal yellowish substances,

which we considered to be the contents of the SMT

(Fig. 2B). We considered that mechanical mucosal abrasion

had caused the absence of the colon epithelial mucosa in the

central portion of the tumor. On the other hand, the basal

part of the SMT was covered with a normal colonic epithe-

lial mucosa that was not edematous or reddish (Fig. 2C, ar-

rowhead) and all of the other parts of the colon were nor-

mal. A histopathological evaluation of a biopsy specimen of

the SMT suggested an amyloid deposition. An amyloid

deposition was not found in other random biopsy specimens

of the terminal ileum or in any other sites of the colon.

Colonoscopic US revealed that the SMT was mainly local-

ized in the second and third layers of the colon, which coin-

cided with muscularis mucosae and submucosal layers, re-

spectively (Fig. 2D). However, the first layer that coincided

with the mucosa was preserved (Fig. 2E, arrowheads). The

first layer was slightly thickened compared with that of nor-

mal colon mucosa, and the EUS findings might be reflected

in the endoscopic findings which showed red colored and

congested features. The tumor was internally hypoechoic

and homogeneous. The fourth layer was obvious (Fig. 2D,

arrow), and we thus considered that the SMT had not in-

vaded the muscularis propria. The endoscopic findings of

the upper GI tract revealed no abnormalities, and no amy-

loid deposition was evident in the random biopsy specimens

obtained from the esophagus, stomach, duodenal bulb and

second portion of the duodenum. The findings of a double-

contrast barium examination of the small intestine were nor-

mal. Therefore, the diagnosis was consistent with solitary

amyloidosis of the sigmoid colon. The findings of both

colonoscopy and colonoscopic US indicated the lesion to be

mainly localized in the submucosal propria layer. Bleeding

from the surface of the SMT was considered to be the cause

of hematochezia, thus indicating a need for removal. The

whole SMT also required a precise diagnosis to exclude the

possibility of malignancy. The patient refused to undergo

surgery, but consented to undergo an EMR. A histopa-

thological examination of the SMT with Hematoxylin and


2525

Figure　2.　The colonoscope and ultrasound (US) findings of the submucosal tumor. The reddish colored tumor surface showed congested features (A). Contact with colonoscope caused a slight ooz-ing from the SMT. The exposed, fuzzy tumor surface had focal yellowish colored features which we considered to be SMT contents (B). The basal part of the SMT was covered with a colonic normal epithelial mucosa; no edematous or reddish areas were seen (C, arrowheads). Colonoscopic US showed that the SMT was mainly localized in the submucosal layer (D). The preserved first layer (E, arrowheads) was slightly thick compared to the normal colon mucosa. Internally, the hypoechoic tu-mor had a homogeneous pattern. The muscularis propria was apparent (D, arrow).

D

A B C

TumorE

Eosin (H&E) staining revealed the essentially homogeneous

deposition of an eosinophilic amorphous material located

mainly in the submucosa (Fig. 3A). The direct fast scarlet

(DFS) stained the deposited material an orange-red color

(Fig. 3B), and polarizing microscopy revealed green bire-

fringence of this material (Fig. 3C), thus indicating amyloi-

dosis. Such deposits were not evident in the epithelium of

any small blood vessels (Fig. 3B, arrowheads). Immunohis-

tochemical staining revealed that the amyloid protein was

the AL type derived from immunoglobulin kappa light chain

(Fig. 3D). According to these findings, we concluded that

the primary solitary AL amyloidosis localized within the

sigmoid colon featured a SMT, which was removed using

EMR. The patient was subsequently followed up as an out-

patient and has remained free from either hematochezia or

other clinical symptoms for eight months.

Discussion

Common endoscopic features of colonic amyloidosis

comprise ulcerations, diffusely distributed petechiae, nod-

ules, luminal narrowing, a loss of haustrations and thick mu-

cosal folds (5). The reported preferential types and locations

of amyloid deposits are associated with the type of amyloid

fibril protein (6, 7). The AA type of amyloid protein is de-

posited mainly in the lamina propria mucosa of the GI tract.

Therefore, endoscopic findings of serum amyloid A protein

(AA) amyloidosis are usually characterized by a fine granu-

lar appearance and mucosal friability, and it often presents

as bleeding, diarrhea and hyponutrition caused by malab-

sorption. On the other hand, AL amyloid protein is usually

obvious in the muscularis mucosa of the GI tract and in the

blood vessel walls in the submucosa and muscularis propria,

which often harbor massive, nodular deposits. This type of

deposition manifests as multiple, elevated, yellowish-white

colored lesions resembling SMTs, with hypertrophic folds

on endoscopy. Amyloid light chain amyloidosis often causes

constipation, abdominal distension and paralytic ileus due to

the decreased enterokinesis. However, GI hemorrhage is not

a prominent feature of intestinal AL amyloidosis, especially

in the absence of clinical disease elsewhere in the

body (5, 8). The endoscopic findings of our patient revealed

features of SMT, which were similar to the characteristic

findings of AL amyloidosis. However, AL amyloidosis fea-

turing a solitary SMT as in the present patient is extremely

uncommon compared with the typical AL amyloidosis. Our

patient had no constipation, abdominal distension or para-

lytic ileus, but she had hematochezia, which was considered

to be rare among the usual types of AL amyloidosis. Al-

though there have been some reports on GI hemorrhage

caused by AL amyloidosis localized within GI

tract (2, 5, 9, 10), there was only one report similar to our

case, namely showing solitary AL amyloidosis featuring

SMT limited to the colon which caused hematochezia (3).

The number of case reports of solitary amyloidosis in the

GI tract has recently increased due to improvements in both


2526

Figure　3.　The histopathological and Hematoxylin and Eosin staining of the SMT. The homogenous deposition of eosinophilic amorphous material (A), without a normal colon epithelial mucosa on the central portion of the tumor (A, arrowheads) is shown. The direct fast scarlet (DFS) stained the de-posited material an orange-red color (B). The eosinophilic amorphous material was not deposited in the epithelium of the small vessels (B, arrowheads). Polarizing microscopy showed green bi-refrin-gence of the deposited material stained by DFS (C). Immunohistochemical staining for AL kappa protein was positive (D).

A

C D

B

endoscopic and biopsy techniques. However, to our knowl-

edge, only a few case reports have described a solitary amy-

loidosis limited to the colon (2, 10, 11). Among these, some

tumors were surgically resected because of a suspicion of

malignant changes. One case report described a solitary

amyloidosis located within the lamina propria layer of the

colon that was identified by colonoscopic US and then re-

sected by using EMR (3). Generally, US has been the most

useful tool to determine whether or not to apply an endo-

scopic approach to treat SMT. The colonoscopic US find-

ings of our patient revealed that that the SMT was localized

mainly in the submucosal layer and that the muscularis

propria was preserved. These findings suggested that the le-

sion could be feasibly removed using EMR or endoscopic

submucosal dissection (ESD). The patient refused to have

the tumor surgically removed, but consented to endoscopic

treatment. We selected the EMR procedure rather than ESD

for removing the SMT, based on the main purpose of mak-

ing a precise diagnosis of the SMT and to achieve volume

reduction of the SMT which might help to stop her hemato-

chezia. Moreover, the SMT was located in a difficult posi-

tion of the sigmoid colon for an ESD procedure. The SMT

was also located immediately adjacent to the muscularis

propria layer based on the EUS findings, and an ESD proce-

dure was considered to have a high risk of intestinal perfo-

ration. Therefore, as an ESD was considered to be too diffi-

cult to remove the SMT, it was removed using an EMR pro-

cedure. The hematochezia disappeared, and the patient re-

mained free of symptoms during the eight months of follow-

up at our outpatient clinic. Removal of the solitary SMT us-

ing an EMR procedure improved the quality of life of our

patient by eradicating the hematochezia.

Biewend et al. (12) reviewed 290 cases of a localized AL

amyloidosis, and found 190 cases that included follow-up

evaluations (range of follow-up period, from 6 months to 23

years). Only four of these cases (2%) developed systemic

amyloidosis during the observation period. The authors rec-

ommended the long-term monitoring of patients without any

specific therapy for localized AL amyloidosis (12, 13).

However, there was no report related to the metachronous or

ectopic recurrence of solitary AL amyloidosis localized

within the GI tract. After removal of the solitary amyloido-

sis using an EMR procedure, our patient received no further

treatment for AL amyloidosis according to her wishes.

We herein described a rare case of solitary AL amyloido-

sis located within the sigmoid colon which presented with

features of hematochezia caused by a SMT that was preci-

sely diagnosed and treated using US and EMR, respectively.


2527

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

References

1. Dey C, Duvoisin B. CT findings in primary amyloidosis of the

colon. J Comput Assist Tomogr 13: 1094-1095, 1989.

2. Hirata K, Sasaguri T, Kunoh M, Shibao K, Nagata N, Itoh H.

Solitary “amyloid ulcer” localized in the sigmoid colon without

evidence of systemic amyloidosis. Am J Gastroenterol 92: 356-

357, 1997.

3. Watanabe T, Kato K, Sugitani M, et al. A case of solitary amyloi-

dosis localized within the transverse colon presenting as a submu-

cosal tumor. Gastrointest Endosc 49: 644-647, 1999.

4. Ebert EC, Nagar M. Gastrointestinal manifestations of amyloido-

sis. Am J Gastroenterol 103: 776-787, 2008.

5. Spier BJ, Einstein M, Johnson EA, Zuricik AO 3rd, Hu JL, Pfau

PR. Amyloidosis presenting as lower gastrointestinal hemorrhage.

WMJ 107: 40-43, 2008.

6. Tada S, Iida M, Yao T, et al. Gastrointestinal amyloidosis: radi-

ologic features by chemical types. Radiology 190: 37-42, 1994.

7. Tada S, Iida M, Yao T, Kawakubo K, Okada M, Fujishima M. En-

doscopic features in amyloidosis of the small intestine: clinical

and morphologic differences between chemical types of amyloid

protein. Gastrointest Endosc 40: 45-50, 1994.

8. Mumford AD, O’Donnell J, Gillmore JD, Manning RA, Hawkins

PN, Laffan M. Bleeding symptoms and coagulation abnormalities

in 337 patients with AL-amyloidosis. Br J Haematol 110: 454-

460, 2000.

9. Dias VC, Tavares I, Goncalves R, Macedo G. AL-amyloidosis pre-

senting as massive gastrointestinal bleeding. Am J Gastroenterol

104: 2374-2376, 2009.

10. Matsui H, Kato T, Inoue G, Onji M. Amyloidosis localized in the

sigmoid colon. J Gastroenterol 31: 607-611, 1996.

11. Deans GT, Hale RJ, McMahon RF, Brough WA. Amyloid tumour

of the colon. J Clin Pathol 48: 592-593, 1995.

12. Biewend ML, Menke DM, Calamia KT. The spectrum of localized

amyloidosis: a case series of 20 patients and review of the litera-

ture. Amyloid 13: 135-142, 2006.

13. Utz JP, Swensen SJ, Gertz MA. Pulmonary amyloidosis. The

Mayo Clinic experience from 1980 to 1993. Ann Intern Med 124:

407-413, 1996.

Ⓒ 2013 The Japanese Society of Internal Medicine

http://www.naika.or.jp/imonline/index.html

Documents

Solitary Amyloidosis of the Sigmoid Colon Featuring