335

□ CASE REPORT □

Juvenile Polyposis Complicated with ProteinLosing Gastropathy

Kentaro Yamashita 1, Mayuko Saito 1, Miki Itoh 1, Eiichiro Yamamoto 1, Satoshi Yamaoka 1,Akira Goto 1, Yoshiaki Arimura 1, Yasuhisa Shinomura 1, Koji Yamaguchi 2 and Takao Endo 3

Abstract

A male patient with chronic bloody stool was diagnosed as juvenile polyposis at the age of 28. He hadthirty to forty colonic polyps and some were removed endoscopically, while gastric polyps were too numer-ous to intervene. As the polyposis advanced gradually, the patient developed intractable anemia and serioushypoproteinemia. Albumin scintigram revealed protein losing gastropathy due to progressive gastric poly-posis. Total gastrectomy was carried out at the age of 34 and the patient has achieved remarkable and sus-tainable improvement.

Key words: juvenile polyposis, protein losing gastropathy

(Inter Med 48: 335-338, 2009)(DOI: 10.2169/internalmedicine.48.1749)

Introduction

Juvenile polyposis (MIM 174900) is a rare hamartoma-tous syndrome characterized by dozens or hundreds of juve-nile polyps of the gastrointestinal tract. The incidence is es-timated to be around 1 in 100,000 to 160,000, and autoso-mal dominant inheritance with variable penetrance has beenobserved in about 40% of patients (1). Recently, SMAD4 (2)and BMPR1A (3), both involved in the TGF beta signalingpathway, have been identified as the causative genes of ju-venile polyposis. Histologically, abundant lamina propriawith inflammatory cell infiltration and edema that cause dis-tortion or cystic dilatation of the epithelial glands is thehallmark of this disease. The most frequently affected site isthe colon (98%), followed by the stomach (14%) and smallintestine (7%) (4). Although uncommon, juvenile polyposislimited or predominant to the stomach has also been re-ported, in which hypoproteinemia due to protein losing gas-tropathy is prevalent (5). Here we present a sporadic case ofstomach-predominant juvenile polyposis developing intracta-ble anemia and protein losing gastropathy that were success-fully treated by total gastrectomy.

Case Report

A 28-year-old Japanese man complaining of occasionalbloody stool for months was referred to our hospital becausepolyposis syndrome was suspected. His past history includedurolithiasis and idiopathic hearing loss while there was nofamily history of gastrointestinal polyposis or cancer. Thepatient had neither hair loss nor skin lesions, indicative ofCronkhite-Canada syndrome. Laboratory data showed ane-mia (hemoglobin 9.2 g/dL), mild hypoproteinemia (totalprotein 6.1 g/dL, albumin 4.0 g/dL) and positive fecal occultblood test. Colonoscopy revealed thirty to forty sessile andpedunculated polyps throughout the entire colon and rectum(Fig. 1). Upper gastrointestinal endoscopy exhibited hun-dreds of polyps predominantly in the body and fundus ofthe stomach (Fig. 2) while the gastric antrum, esophagusand duodenum were preserved. Both serum anti Helicobac-ter pylori antibody and rapid urease test were negative. Dou-ble contrast barium study revealed no polyps in the small in-testine. As biopsy specimens from the gastric and colonicpolyps were pathologically inconclusive, we carried out en-doscopic mucosal resection (EMR). Both gastric and colonpolyps consisted of marked inflammation with edema

１The First Department of Internal Medicine, Sapporo Medical University, Sapporo, ２The First Department of Surgery, Sapporo Medical Univer-sity, Sapporo and ３Department of Internal Medicine, Sapporo Shirakabadai Hospital, SapporoReceived for publication October 6, 2008; Accepted for publication November 27, 2008Correspondence to Dr. Kentaro Yamashita, ykentaro@sapmed.ac.jp

Inter Med 48: 335-338, 2009 DOI: 10.2169/internalmedicine.48.1749

336

Figure 1. Colonoscopy showed a red sessile polyp of the sigmoid colon.

Figure 2. Gastroscopy at the initial presentation. Multiple polyps were seen in the gastric body (panel A) while only a few polyps were observed in the antrum (panel B).

A

B

Figure 3. Microscopic finding of a colon polyp (×100, Hematoxylin and Eosin staining). Edema and inflammatory cell infiltration were obvious in the lamina propria mucosa. Colonic glands showed cystic or serrated change.

Figure 4. Gastroscopy six years after the initial　presentation. Gastric polyp was not only increased in the upper stomach (panel A), but also it invaded the gastric antrum, which had been nearly intact six years previously (panel B).

A

B

throughout the lamina propria mucosa, dilated glands withoccasional cystic change, and the epithelium without dyspla-sia (Fig. 3). We diagnosed this case as juvenile polyposisand performed germline mutation analysis of genes associ-ated with polyposis syndrome. Mutation of SMAD4, SKT11,PTEN and APC were all negative by direct sequencing.After the diagnosis, the patient had started oral iron sup-

plementation and additional six colon polyps were removedendoscopically at the age of 32. In spite of these treatments,hemoglobin, total protein and albumin levels were graduallylowered to 6.6, 3.9 and 2.1 g/dL respectively, causing fa-tigue and intractable systemic edema. Follow-up endoscopyrevealed the gastric polyps have grown and sprawled to the

antrum affecting the entire stomach (Fig. 4). Colon polypsalso grew, but less remarkably than the gastric polyps.Technetium-labeled albumin scintigraphy exhibited that pro-tein was lost mainly through the stomach, suggesting proteinlosing gastropathy due to progressive gastric polyposis(Fig. 5). Polypectomy for seventeen colon polyps and totalgastrectomy were carried out in April 2007 at the age of 34,six years from the initial presentation. The consequence wassignificant, such that the hemoglobin and albumin level re-covered to the normal range on the 20th day after the sur-gery without transfusion. Numerous gastric polyps through-

Inter Med 48: 335-338, 2009 DOI: 10.2169/internalmedicine.48.1749

337

Figure 5. Technetium-labeled albumin scintigraphy (two hours after injection) showed a pool of isotopes along the greater curvature of the stomach (arrowheads), suggesting al-bumin leak through the stomach.

Figure 6. The total gastrectomy specimen. Nearly the entire stomach was covered with numerous polyps. Arrows denote the large pedunculated polyp of the antrum causing ball valve syndrome.

Figure 7. Microscopically, the gastric polyps consisted of prominent edema and inflammatory cell infiltration (×100, Hematoxylin and Eosin staining, panel A). A part of the large polyp of the antrum showed dysplastic change (×200, Hematoxylin and Eosin staining, panel B).

B

A

out the stomach were histologically consistent with juvenilepolyposis, and a large pedunculated polyp in the antrumprotruded through the pyloric ring, causing ball valve syn-drome (Fig. 6). The large gastric polyp of the antrum aswell as several large colon polyps embraced moderate dys-plasia (Fig. 7). Pathological examination of the entire stom-ach revealed no other dysplasia than in the antral polyp. Thelatest data of hemoglobin, total protein and albumin were13.2, 6.7, and 3.7 g/dL respectively and the patient has beenin excellent condition as of this writing, September 2008.

Discussion

Sachatello et al (6) classified juvenile polyposis into threecategories (i) juvenile polyposis of infancy, (ii) juvenilepolyposis coli, and (iii) generalized juvenile polyposis. Juve-nile polyposis of infancy is the most serious phenotype di-agnosed in infancy, characterized by massive polyposisthroughout the gastrointestinal tract, congenital abnormalityand a poor prognosis. Juvenile polyposis coli is the mostcommon type in which polyps are limited to the colon. Ifjuvenile polyps are found outside as well as in the large in-

testine in adolescent or adult patients, it is termed general-ized juvenile polyposis. In addition, juvenile polyposis ofthe stomach was recently proposed as the fourth category ofjuvenile polyposis (5). In juvenile polyposis of the stomach,polyposis should be limited to the stomach, at least at theinitial presentation. Since the first case of juvenile polyposisof the stomach was reported in 1979 (7), twelve cases havebeen reported and Hizawa et al (5) summarized them. Sevenpatients had hypoproteinemia and 10 patients required gas-trectomy because of refractory protein losing gastropathy orgastric cancer. The results of gastrectomy were satisfactory,but four patients thereafter developed colonic lesions includ-ing juvenile polyp, adenoma, and cancer. Although the cur-rent case might be categorized as generalized juvenile poly-posis, the stomach-predominance and the clinical course re-sembled juvenile polyposis of the stomach. It is still contro-versial whether juvenile polyposis of the stomach is a dis-tinct entity and should be distinguished from generalized ju-venile polyposis. The present case suggests, however, thatso-called ‘juvenile polyposis of the stomach’ might be asubtype of generalized juvenile polyposis.Germline mutations of SMAD4 and BMPR1A are ob-

served in a subset of juvenile polyposis cases, and theprevalence of each mutation is estimated at 20% (8). To datethere is no known genotype-phenotype correlation in juve-nile polyposis. Although Friedl et al (9) suggested an asso-ciation between massive gastric polyposis and SMAD4

Inter Med 48: 335-338, 2009 DOI: 10.2169/internalmedicine.48.1749

338

germline mutation in comparison with BMPR1A mutation orno mutation, there is no subsequent study supporting thishypothesis and the present case does not harbor germlinemutation of the gene. Mutation analysis in further general-ized juvenile polyposis cases might resolve the conundrumof whether juvenile polyposis of the stomach is an inde-pendent category.When the present patient developed significant anemia

and hypoproteinemia during the course, there was a debateabout treatment strategy. As there were hundreds of gastricand dozens of colonic polyps, we thought total gastrectomy

and polypectomy for the large colonic polyps would be rea-sonable. An alternative was total gastrectomy and subtotalcolectomy because (i) the anemia might be due to colonpolyps, (ii) removing all colonic polyps seemed impossible,and (iii) the patient carries an increased risk of colon cancer.However, simultaneous gastrectomy and colectomy was tooinvasive and a future colectomy is feasible, if necessary. Webelieve that close follow-up and colon polypectomy willprevent advanced colon cancer and sustain an excellent con-dition.

References

1. Chow E, Macrae F. Review of juvenile polyposis syndrome. JGastroenterol Hepatol 20: 1634-1640, 2005.

2. Howe JR, Roth S, Ringold JC, et al. Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 280: 1086-1088, 1998.

3. Howe JR, Bair JL, Sayed MG, et al. Germline mutations of thegene encoding bone morphogenetic protein receptor 1A in juve-nile polyposis. Nature Genet 28: 184-187, 2001.

4. H�fting I, Pott G, Stolte M. The syndrome of juvenile polyposis.Leber Magen Darm 23: 107-108, 111-112 (in German).

5. Hizawa K, Iida M, Yao T, Aoyagi K, Fujishima M. Juvenile poly-posis of the stomach: clinicophathological features and its malig-nant potential. J Clin Pathol 50: 771-774, 1997.

6. Sachatello CR, Hahn IS, Carrington CB. Juvenile gastrointestinalpolyposis in a female infant: report of a case and review of the lit-erature of a recently recognized syndrome. Surgery 75: 203-214,1974.

7. Watanabe A, Nagashima H, Motoi M, Ogawa K. Familial juvenilepolyposis of the stomach. Gastroenterology 77: 148-151, 1979.

8. Merg A, Howe JR. Genetic conditions associated with intestinaljuvenile polyps. Am J Med Genet 129C: 44-55, 2004.

9. Friedl W, Uhlhaas S, Schulmann K, et al. Juvenile polyposis: mas-sive gastric polyposis is more common in MADH4 mutation carri-ers than in BMPR1A mutation carriers. Hum Genet 111: 108-111,2002.

Ⓒ 2009 The Japanese Society of Internal Medicinehttp://www.naika.or.jp/imindex.html