BRIEF COMMUNICATION

Childhood Peutz--J eghers syndrome: Diversity of clinical

features and complications, and literature review

M ARK R O LIVER MBBS, R RRENT SCOTT 1'1DC1'1, ROBIN C ECCLES MD, C YNTHIA TREVENEN MD,

JONATHON B MEDD!NGS MD, ST EVEN R MARTIN MD

MR OLIVER, RB SCOTT, RC ECCLES, C TREVENEN, JB MEDDINGS, SR MARTIN. Childhood Peut7:,Jeghers syndrome: Diversity of clinical features and complications, and literature review. Can J Gastroenterol 1994;8(4): 253,256. This case report of a six-year-olJ child with Peutz-Jeghers syndrome illustra tes the potential diversity of presenting gastrointestinal symptoms and , igns including hematemesis, obstruction and recurrent intussusception. En­doscopy was useful in assessment, while endoscopic polypectomy and surgical resection were both necessary for management. The literature is reviewed and the possible role that this syndrome may have in the development of both gastrointestinal and nongastro intcstinal tumours is highl ighted.

Key Words: lmussusception, Malignancy, Peutz-Jeghers syndrome

Syndrome de Peutz-Jeghers chez l'enfant: diversite des caracteristiques cliniques et des complications et survol de la litterature

RESUME: Ce rapport de cas porte sur un enfant de six ans arre int du syndrome de Peutz-Jeghers er illuscre la divcrsite potenridle des symptomes et signes gastro-incestinaux qui se manifesrent, y compris l'hematemcse, !'obstruction et l'inrussusception recurrence. L'endoscopie s'est revelee utile pour evaluer la situat ion, alors que la po lypectomie enJoscopique er la resection chirurgicale ont tOUtes deux ere n.ecessaires en therapeutiquc. La litterature est passee en revue er le ro le possible de cc synd rome dans le dcveloppement des cumeurs gascro­inrestinales et autres est souligne.

Departments of Medicine, Pathology , Pediarrics and Smgery, Alberra Children's Hospira! and Umversiry of C<ilgary, Calgary, A lberta

Correspondence and re/n·inrs: Dr R Brenr Scort , Department of Pediatrics, Unrversrty of Calgary, Health Science Centre, 3330 Hospir.al Drive NW, Calgary , A lberta T2N -fN I . Telephone ( 403) 220-4556, Fax ( 403) 283-3028

Received for p11blicauon February 7, 1994. Accepted Febr1wry 8, 1994

CAN j GAS-n1.0ENTEROL VOL 8 No 4 JULY/AUGUST 1994

PEUTZ-JEGHERS SYNDROME WAS

first described by Pcutz ( 1) in l 92 J and characterized by Jeghers et al (2) in 1949. Ir is a relatively rare syndrome transmitted as an aucosomal dominant disorder and characterized by gastroin­testinal polyposis and mucocuraneous pigmentation. The polyps arc charac­terist ically hamartomas and can occur in the stomach, small intesti ne and co­lon. Though generally considered co be a benign condition (3 ), significant morbidi ty and morca liry are rela ted to recurrent intussusceprion, as evidenced by several reviews ( 4-7) and the patient described in this report. In addition, both case reports and reviews from large pol yposis registries provide in­creasing evidence ro sugge&t that there is a link between this syndrome and the development of nor only gastrointest i­nal tumours ( 7- 1 I ) but also - perhaps more significantly - a variety of non­gascroinrescinal LL1mours (7, 10,11). This link raises questions about appro­priate surveillance and long term fol­low-up of these patients. This case report describes a young child wirh complications of Peutz-Jeghers syn­drome and reviews the li terature with

253

OLIVER er al

regards co Lhe nawral h isrory and the management of these complications.

CASE PRESENTATION A six-year-old girl presented with a

24 h history of forcefu l, recurrent, bile­stained emesis which progressed Lo frank hematemesis and Lhe loss of ap­proximately 300 mL of blood. The vomiting had heen preceded hy a vague left upper quadrant abdominal d iscom­fort which was relieved by the emesis.

T here were no ocher associated gastro­intestinal or systemic symptoms. A pre­vious episode of bilious emesis and hematemesis two years before setded with conservative managemem and had not been investigated. Family his­tory was nonconcribucory. Clinical evaluat ion showed a six-year-old who appeared well but pale. Her viral signs were stable and the rest of the physical examination was unremarkable.

Hemoglobin was 93 g/L, with nor­mal red blood cel l morphology, white blood cel l count and platelet coum. Other laboratory investigations includ­ing prothrombin and act ivated partial thromboplastin rimes, electrolytes, urea, cn:atinine, liver function rests, al­humin, protein and urinalysis were nor­mal.

Initial management included srabi­li:ation with replacement of flu id and electrolyte losses. An upper gastroin­testinal e ndoscopy was performed up to and includi ng the second part of the duodenum. Five sessile, nonulcerated polyps were identified on the greater curvature of the stomach , and a large pedunculated polyp (2 cm in diameter) present in the duodenal bulb was both ulcerated and bleeding. Biopsies of the gastric polyps were taken and were later identified as hamartomas.

T he duodenal polyp was removed endoscopically, as was a hamarcoma with the characteristic h istological fea­tures of Peutz-Jeghers syn<lrome. Fol­lowing endoscopy the patient was re-examined and found to have six small pigmented les ions on the mucou~ membranes of her lower lip which were only visible when the lip was evcrted. She had no cutaneous lesions.

Three weeks after polypectomy, while the patient was sti It asympto-

254

macic, a barium swallow \\'ith small bowel follow-through and a double contrast barium enema were performed to e\'aluate the extent of involvement of the gastrointestinal tract. The former study demonstrated an ileocolonic in­cussusception without ,1gnificant ob­struction. The barium enema also demonstrated an intussusception which began in the midascending co­lon and was reduced, leaving a fil ling defect of 3 cm in diameter in the termi­nal ileum. No other changes suggestive of polyps were identified. A colonoscopy was scheduled to remove the ilea! polyp.

At colonoscopy a small rectal polyp was identified and removed. The re­mainder of the colon and cecum ap­peared normal. The terminal ileum was entenxl; just beyond the ileocecal valve a large pedunculated polyp filled the lumen and \\'as partially obscured by two hroad-based polyps that were ulcer­ated and had a nodular appearance that extended inw the adjacent mucosa. The appearance was similar to, or sug­gestive of, an adenocarcinoma. Endo­scopic polypectomy was deemed unsafe clue to the large size of the lesions. Biopsies were consistent with hamar­toma~. with no evidence of adcno­macous or carcinomatous changes. Because of the risk of recurrent intus­susception and persistent concern about malignancy it was decided to pro­ceed with operative resection.

At surgery, it appeared that polyps in the termina l ileum had acted as a lead point and once again caused an intussuscepcion to the midascen<ling colon. This was easily reduced, and there was no evidence of vascular com­promise. It was interesting co note char the patient had nor complained of any symptoms preoperatively. Approxi­mately lO cm of terminal ileum includ­ing the ileocecal valve, the cecum and the appendix were removed. Palpation of the remaining small intestine did nor disclose further polyps. The patient had an uneventful postoperative period. The gross padwlogical description of rhe opened resecred ileum and cecum rcvenled a large polypoid mass 3. 5 cm in diameter attached to the ilea! mu­cosa hy a shon I cm diameter stalk

approximately 2 cm proximal to the ileocecal valve. In the mucosa around the larger polyp there were multiple small nodular projections measuring ur to 5 mm in diameter. l listological sec­tions from the large polyp revealed elongated vilti(orm projections of 1leal mucosa with irregularly distributed 111,1-

lllre glandular structures separated hy ramifying bundles of smooth muscle. Many of the glandular structures con­tained inspissated eosinophilic secre­tions intermingled with neutrophils. The inflammatory process extended from some of these distended gland\ in to the adjacent lamina propria and muscular stroma. There wa~ nn evi­dence of malignancy. Two of the smaller ilea! nodules were histolog1-cally simi lar co the large hamarrnma­tous polyp; the rest were hyperplastic lympho1J follicles with prominent ger­minnl centres.

The patient has remained well nine months afrer operation. I !er rclati,·e\, parents ,md younger sibling arc asymp­tomatic and demonstrate none of the clinical fealUres of this syndrome, sug· gescing that this girl's disease may he secondary co a new mutation.

DISCUSSION Patients with Peutz-Jeghers syn•

drome manifest a variety of symptoms that depend upon the site, size and number of polyps in the gastrointesti­nal tract, and can range from anemia, vomi t ing, melena and hemacemesis tn

obstruction due co an intussuscepcion. The patient described in this report not only demonstrated many of these symr· toms but was also shown ro have the unusual entity of an asymptomatic in­tussusception on two occasions. It 1s

well recognized chat in Peutz-Jcghers syndrome intussusceptions may not cause complete obstruction and can be tran~ienc (5), but they are usually asso­ciated with symptoms ( 4-7). It is plau­sible chat thb patient had a 'loo~e· intussuscepcion and hence did not yet have any symptoms related co 1scher111a or obstruction.

The complication of intussuscer· tion is by for the most common caused significant morhidity and mortality rl'· laced tn this disorder. Dormondy (4,5)

CAN J GA'iTROENTER~1L VOL 8 NO 4 JULY/AUGUST 1994

replmed chat m a series nf 21 pauenh 11•1 Lh Peut:-Jegher, syndrome , 14 re­quired ~ 3 lapawcom1cs over a follow-up period nf Lhrce LO 60 ycms. Spigelman l't al ( 12) nmed chat repeat laparowmy l11r 1mussusccption was u1mmon 111 pa­tiems with Peurz-Jeghers syndrome; chey reponcJ that the pwccdure was performed on 54 occas il> n s in 23 patients. A 49-year follow-up of 12 members of a family affected by Peut:­Jcghers syndrome reported thaL o ne pa­tient de,·clnpcd short bowel syndrome (dcpcndcm lll1 parcnrcral nutriLion) and duce others died as cccnagcn, as a consequence of the comp I icm ions of mtussusceptinn (7).

Convemional mcrhod:- used to re­duce the incidence of repeat laparo­tomy and cnmplicat1nm rclmcd LO

repeated 111Lussusceptinn 111cludc palpa­tion .md trans1 lluminauon m chc time of surgl'ry (Lhe fl1rmcr was used in thb patient). t-. lore reu:mly IL has became apparent that there may be a rnle for mmll>pcrat1ve encernscnpy in patients (including children) with Peutz­Jeghers syndrome who have recurrent sympwms suggestive of 111tussuscepcion or cxLensive polyposb documented ra­d1ol0g1call} ( 12, 13). The procedure has the advanwge of accurately assessing the extent of small imesttnal involve­ment, pcrmnttng chc removal of smaller polyps by e ndoscopic pnlypec­tomy and guiding rhe surgeon w chose polyps rbm musl he removed by cntem­tnmy. ln the shon Lenn, incraopcrative cnteroscopy appears co reduce the fre­quency of ,uhscqucm repeat 1ntus­,u,ccpuun and may pmvc LO reduce the mc1dcncc of porcmial cnmplicatiom ,uch as shnn howcl syndrome. l low­C\'er, ic is nor wnhouc ri,ks such ,ls tor­sion of Lhe mesem cry m ovcrdi ,tcnsinn of Lhe gut.

Though the patient described 111 th 1, report did nm have clinical or histo­logical c,·1dencc ul either ga.strrnntcsc1-nal or nongast rointcsLinal cancer, there are several rcpon-, nf patients with PcUL:-Jeghcrs syndrome who have hccn afllicted wi th a wide vnricly of ma lig­nam gasLn>1ntcM111al cunmurs mvolv­mg Lhe stomach, small intes tine and colon, and nnngastrointcscin,11 malig­nancies nf l he Cl'rv1x, hrl':tsl, ovary, ccs-

ccs and thyrrnd (8- l l ). The true 111c1-dencc of ma lign.m cy in Lhis condition is unknown; hm\·e,·er, rcccnr reports frum Giardcllo cl al (10) and Spigel­man cl al ( 11) uLili:ed sLrict criteria for the defintt1on of Pcut:-Jcghcrs syn­drome, and in Lhcir series of patients ha,·c ,hown a ,ignific.incly incre,ised incidence of bmh gastrointesti na l nnd nongas1ro1ntcstin,1l rumours. Giardcllo and colleagues rcpmted Lhar 111 1 1 indi­viduals with PcuLz-Jeghcrs syndrome (mc,m ,lgt• at d1.1gm1-,1s 17±16 years, with mean f<>llow-up of 2 1± 15 years) mal1gnanLy developed in 15: four had gm,t m inrestina l carc inomas, 10 had nongasLrointcstinnl cmcmomas and one had multipk• myeloma. In addi ­rnm, adcnnmatous polyps were found in the swmach and colon 111 Lhrcc mher patients. The rcl.1u,·e risk of develop­ing cancer 111 their series of pac1cms was 18 times grcaLer Lhan in the general populac111n (P<0.0001 ). Spigelman CL al ( 11 ) reponed 72 pmicnts wiLh PeuLz­Jcghcrs syndmme on the polyposis reg­istry at St Marb I it)sp1ral in London, England . Sixteen developed malignan­cies (nine gasm>1ntcst111al and seven nongastro imesLinal) , of whom all huL one died from cancer. The relative risks of death frum gastrointestina l cancer and nongasLroincestinal cancers were 13 and 9, respect ively. Lifc-whlc analy­sb showed LhaL Lhe ch,m ce of dying of mal1gnanq was 481\1 hy 57 years of age.

Dcspitl' a degree of selection bias these studies suggcsl that Pcutz-Jeghcrs syndrome may he a premalignam cnn­diLion with an increased risk of devel ­op111g hoch ga:,ero1111csunal and nongastmmtcsr111al cancer. This sug­gests chm the gene locus conl mil mg chc devclopmem of Peut:-Jeghers syn­drome has an important role regulating cellular differemiatinn a nd growth in other tissues 111 additmn to Lhose of Lhe gastroimcstina l tract. T here 1s evi­dence that 111 some cases adenomaluu, chnngcs 111 Lhe swmach, small 111LCMlllC and colon cc)CXisL wnh the hcntgn hamartomacnus polyps, suggesr111g Lhat Lhcrc mny he ,1 progression from hamnr­wma m adenoma and then to carci­nt1ma (7, I 0).

Ohviously, large long term pmspcc­m 'l' sLUd1es will he requi red tn dd111e

CAN J G.-,smnl::Nl FROI Vn1 8 Nl H JULY/Allc,UsT t 994

Childhood Peulz-Jeghers syndrome

Lhe real risk cif malignancy accurately. C urrcnL li1 craLure suppo n s a need for long term surveillance for malignancy. The nmure of that survei llance sLill re­quires a full cosL-bcnefiL analysis; how­c\'er, 111 the adult female pnpulat1tm 1c sho uld probahly include annual hreasL and g} necnlogical cxamin,nions and pcrh,1ps mammography, pel vic uhra­stiund and cervical smears ( 11 ). IL is suggcsLcd that gastrrnntcsunal surveil­lance 111cludc two yearly lipper en­doscopy, colonoscopy and small howcl fol low-through procedures. l n paticnls wiLh polyps greater Lhan 1.5 cm in di­arncLer, or with polyps and abdom111al p,1in, int rnopl'rntive enreroscnpy may he useful to rl·duce the rme nf compli­cat ions uf imussusceplton ( 11 ). Ir is nor yet esL,1hlishcd at what age surveillance should begin. Clearly ll is common for pac1cms to prl·scm early in the first dec­;1dc nf I ifc with anemia, rectal bleeding, hcmatcmes1s, mterm111enr ahdom111al pnin and vomiting, or intussusccpt ion ( 4,5, 10). Giardcllo and rn-workers ( 10) csummcd chm the mean intcrv,1l (± SD) hecwccn diagnosis of Lhe syn­Jmmc anJ d1agno:..1, of cancer \\'a:, 25±20 yea rs ( range nne co 64), and in Spigclman 's seric:. ( 11) the maiomy of malignancies was drngnoscd 111 pnncnts 111 thei r second and Lhird decades of li fe. Fcmini:ing g,madal tumour, have hecn descrihed in fi ve prepubenal children as young a, ,1gc three 1\•1th Pl'ut:­Jcghers syndrome. A hoy ( l 4) a nd two sbter:.. ( 15) had sex t.nrd Lumour with annular whulcs, and anmhcr hoy ( 16) and a g irl ( 17) had Sl'rtoli cell cumour. Thus, even in chi ldren, screening should probahly 111clude annual phy,i­cal ex,1mi nat1nn (including n pelvic ul ­trasound in fema les) looking for evidence tll gonadal en la rgemem, gynecomasLia o r precocious puberty.

REFERENCES t. Pclll: JA. On a n·r) rcm.1rl...1hlc t.,1,l• 1,r

famili .11 polypo~i, of the muLlJUs mcmhrnnc, mtc,tinal 1rac1 .md n.hopharym. accompanic,I hy pecult,tr pig1m:ntat 1011 of the ,!..in nnd mucous mcmhranc. Ned T11d,chr l,cncc,kd 19!1;10:t H-46.

2. Jcghcr,; M, McCusicl.. VA . Katz KM. Gcncr.ilr:cd imc,unal polYI""'' and mL·l.111111 'l"ll' 11f thl· or.11111111:w,a. lip,

255

O LI VER er lli

and <ligits; ;i syndrome of diagnostic "Harrisburg family" with a 49 year bowel cndoscor y. Br J Surg significance. N Engl J Med follow-up. G astroenterology 1990;77:301-2. 1949;24 I: I 03 1-6. 1988;95: 15 35-40. I 3. Tycgnt GNJ, M:1thus-Vle1gcr EMM.

3. Long JAJr, Oryfuss JR. The 8 . Reid JO. lntestim1l carc inoma in the I ntra-nrermivc cndn~copy: techmque Peut.:-Jeghcrs syndrome: ;i 39 ye:-ir Peut:-Jcghers syndrome. JAMA indicm inns and results. G;1,trointcst clinical and radio logical fo llow- I 974;229:883-4. Endosc 1986;32: 381-4. up rcpon . N Engl J Med 9. Lia11os DA, Domis R, Dahlin D, 14. Dubois RS, Hoffman WI I, Krishman 1977;297: 1070. Bartho lomew L. Docs Pcutz-Jcghers T l I, ct al. Fcmmizing sex cord rnmor

4. DormnnJ y TL. Gastrl)intestinal syndrome predisr osc to with annular tuhu le, in a boy with polyrnsb with mucocutancous gastroimcstinal ma lignancy? Peutz-Jeghcrs syndrome. J Pcd iatr pigmentation ( Pcut z-Jcghers A lmer look. Arch Surg 1982; IOI :568-71. syndrome). N Engl J MeJ 198 1;11 6:11 8 1-4. 15. Solh I IM, Ramez SA. Najjm SS. 1957;256(Pt 1): 109 3- 102. 10. G iardcllo F, W e lsh S, Hamilton S, Pcutz-Jcghcrs syndrome associated

5. Dormand y T L. G,1stromtcstinal ct al. Increased risk of cancer m the with precocious puhen y. J Pcd iatr polyposi, with mucocurnnenus Pcutz-Jcghcrs synJw mc. N Engl 1983; 103:593-5. pigmcn t.ll ion ( Pcutz-Jeghcrs J Med 1987;3 16: 15 11-4. 16. Cantu JM, Rinem 11, Ocampo-C.11npo, syndrome). N Engl J Med I I. Spigelman AD, Murday V, Phillips R, ct al. Peu tz-Jeghcrs syndrome with 1957;256(Pc 2 ): 1141 -90. RKS. C ancer and Pcutz-Jeghcrs femin izing Senoli cell tumor. Cancer

6. Bailey D. Polyposis of gastrointestinal synd rome. Gut 1989;30: I 588-90. I 980;46:223-8. t race: The Pcut:-Jcghcrs ~yndromc. 12. Spigelman AD, Thompson JPS, 17. C hristian CD, McLougl in TG, Rr Med J l 957;2:433-9. Phillips RKS. T oward decrc,,sing Cmhcan ER, Eisenberg MM .

7. Foley TR, McG,mity TJ , Ah, AB. the re larxmnomy race in rhc Pcutz-Jcghcrs synd rome .t~soci:n cd Pcutz-Jcghcrs synd rome: a Pcut:-Jeghcrs syndrome: 1 he with func rion mg ovarian tumor. cl in icopat ho logic survey of the ro le of preoperative small JAMA 1964;190:935-8.

256 CAN J Gi\:-TROENTI:Rm VOL 8 No 4 JULY/ALJGU:,T 1994

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