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Human Pathology: Case Reports (2016) 4, 9–12

A classical case of Peutz–Jeghers syndrome withbrief review of literature

T. Santosh a,⁎, M.K. Patro b, J. Nayak b, B. Behera b

aDepartment of Pathology & Lab medicine, AIIMS, Raipur, Chhattisgarh, IndiabDepartment of Pathology, MKCG Medical College, Berhampur, Odisha, India

Received 17 April 2015; revised 7 June 2015; accepted 9 June 2015

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Keywords:Peutz–Jeghers syndrome;Intussusception

Abstract PJS is an autosomal dominant genetic disease associated with melanin pigment spots on theoral mucosa, lips, nasal alae, palm and soles, as well as hamartomatous polyps in the alimentary canal.Polyps are often a cause of intussusception in the affected patients. Cancers of gastrointestinal system,uterus and breast are common in patients with PJS. Long-term follow-up is required to preventintussusception in children and cancer in adults. We report a classical case of Peutz–Jeghers syndromepresenting with jejunoileal intussusception in a 9 year old child.© 2016 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

dying from a gastrointestinal cancer is 13 times higher and

1. Introduction

Peutz–Jeghers syndrome (PJS) is a rare disorder charac-terized by typical pigmented perioral macules, pigmentedspots in the buccal mucosa which are present in 90% ofpatients [1,2], and multiple hamartomatous polyps predom-inantly in the gastrointestinal (GI) tract, rarely more than 20[3]. Polyps may occasionally be absent. Polyps vary in sizefrom a few millimeters to 7 cm. Most patients have acharacteristic clinical course of recurrent episodes of polypinduced bowel obstruction and bleeding. The disease affectsmales and females equally. In addition to polyposis, the riskof gastrointestinal and extra-gastrointestinal malignancies issignificantly increased in PJS patients [4]. The relative risk of

⁎ Corresponding author. Tel.: +91 8895495670.E-mail addresses: born_vss@yahoo.co.in (T. Santosh),

anojkpatro@gmail.com (M.K. Patro), nayakjayanti86@gmail.com. Nayak), born.vss@gmail.com (B. Behera).

ttp://dx.doi.org/10.1016/j.ehpc.2015.06.002214-3300/© 2016 Published by Elsevier Inc. This is an open access article under the

risk of any other malignancy (especially cancer of thereproductive organs, breast, pancreas and lung) is 9 timeshigher than in the general population [5].

2. Case report

A 9 year old girl was apparently alright before, presentedwith slight intermittent episodes of abdominal pain withoutlocalization and vomiting. On examination the child was toxic,restless with rapid pulse. Marked tenderness was present in theupper abdomen and a palpable, mobile firm to hardmass of thesize of a fist was felt. Abdominal ultrasonography revealedintussusception. An emergency laparotomy was performed.Jejunoileal intussusception showing approximately 15 cm ofjejunum invaginating in to the ileum was found (Fig. 1). Theintussusception could not be released, hence it was resectedand sent for histopathology.

Gross specimen of small intestine measured 15 × 4 cm inlength with grayish dull appearing serosa. There was no

CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Fig. 1 Intraoperative demonstration of jejunoileal intussusception.

10 T. Santosh et al.

gangrene. On cut opening lumen showed multiple peduncu-lated polyps ranging from 1 to 3 cm in diameter. Twolarge pedunculated polyps were found as the leading pointfor the intussusceptum. The polyps were reddish gray incolor, smooth surface and cut section was congestedwithout any focal hemorrhage and necrosis (Fig. 2).Histopathology revealed complex arborizing cores withsmooth muscle bundles supporting aggregates of benigncystically dilated glands suggestive of hamartomatous polyp.Atypia or malignancy is not observed in the neoplasticglands (Fig. 3A and B). Lymph nodes examined showedreactive hyperplasia.

Family history did not reveal history of PJS/any otherpolyposis syndrome in the family members. On carefulre-examination of the child multiple pigmented patches wereseen over buccal mucosa (Fig. 4). The girl was discharged well

Fig. 2 Two large polyp as the leading point of the intussusceptum.

on the 8th post-operative day with a diagnosis of Peutz-Jegherssyndrome with an advice for regular follow ups. On follow upshe was found to be absolutely alright without any complica-tions for last 8 months till the manuscript was prepared.

3. Discussion

Peutz in 1921 published the first case with GI familialpolyposis with pigmentations and later in 1949 documentedthat these are associated with increased risk of malignancy[1,6]. PJS is a rare disease with an incidence of 1 in 30,000 to120,000 live births [7]. It is an inherited GI hamartomatouspolyposis syndrome with mucocutaneous pigmentation. Themost distinctive clinical feature are melanin pigmentations(black–brown spots) in the lips and buccal mucosa.Pigmentations can also be seen in other parts of the body,such as fingers, toes, hands, feet and the mucosa of the nose,conjunctiva and rectum. Some patients do not present withthe full spectrum of the disease. Multiple hamartomatouspolyps in the gastrointestinal tract are the hallmark of PJS.Mostly gastrointestinal polyps are found in the smallintestine. They can also be found in the stomach and largeintestine [7].

Giardello et al [8] proposed diagnostic criteria for PJSwhich requires histopathological confirmation of hamarto-matous gastrointestinal polyps and two of the followingfeatures: small bowel polyposis, positive family history andpigmented skin or mucosal brown macules.

PJS shows an autosomal dominant pattern of inheritancewith both familial (80%) and sporadic (25%) transmissions.Two independent groups of investigators identified themutated gene responsible for PJS [9,10]. The gene waslocalized to chromosome 19p34-p36 and is known as STK11, a serine-threonine kinase involved in growth controlregulation. Not all patients with PJS have a mutation in thisgene. Mutations of chromosomes 6q and 19q have beensuggested in a few families [11]. In the present case thediagnosis was confirmed because of the hamartomatoussmall intestinal polyps and mucocutaneous hyperpigmenta-tions. No family history of PJS was detected in the presentcase suggesting a sporadic new mutation.

Complications induced by polyps include colicky ab-dominal pain, bleeding, and bowel obstruction due tointussusception. The time for commencement of abdominalsymptoms vary from as early as the first year of life to the ageof 40 years [12]. By the age of 10 years, 30% of patientswith PJS already require a laparotomy [13].

These patients are prone to many extra-intestinal tumorslike testicular sertoli cell tumors, ovarian tumors like sexcord tumors with annular tubules, granulosa theca celltumors, cystadenomas, breast tumors like carcinoma breast,papilloma with squamous metaplasia, cholangioma, pancre-atic adenocarcinoma, adenoma malignum, bronchial carci-noids, papillomas in bladder and pelvis [14].

Fig. 3 A and B: Arborizing branching smooth muscle bundles between glands characteristic of PJS (H & E).

11Peutz-Jegher’s syndrome

If the polyps are symptomatic or are of significant size(greater than 1.5 cm in diameter) a laparotomy withenteroscopy is recommended. Almost half the patientsunderwent two or more laparotomies, which resulted in asizable percentage of patients suffering from short bowelsyndrome as a consequence of the repeated bowel resections.

Fig. 4 Buccal mucocutaneous hyperpigmentations.

Recently, intraoperative endoscopy and endoscopic poly-pectomy, rather than segmental resection of the bowel, havebeen recommended. Periodic endoscopic screenings areadvocated every 2 years [13]. The new mouth to anus (M2A)capsule endoscopy will probably become the most usefulscreening tool in the near future.

4. Conclusion

Peutz–Jeghers syndrome, an autosomal dominant disordercharacterized by hamartomatous GI polyposis and mucocutane-ous hyperpigmentations. The increased risk ofmalignancies bothGI and non-GI in cases of PJS suggests a regular monitoring ofthe cases and also screening of first degree relatives.

References

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[2] Jeghers H, McCusick VA, Katz KH. Generalized intestinal polyposisand melanin spots of the oral mucosa, lips and digits. A syndrome ofdiagnostic significance. N Engl J Med 1949;241:993-1005.

[3] Tomlinson IP, Houlston RS. Peutz-Jeghers syndrome. J Med Genet1997;34(12):1007-11.

[4] Boardman LA, Thibodeau SN, Schaid DJ, Lindor NM, et al. Increasedrisk for cancer in patients with the Peutz-Jeghers syndrome. Ann InternMed 1998;128(11):896-9.

[5] Spigelman AD, Murday V, Phillips RK. Cancer and the Peutz-Jegherssyndrome. Gut 1989;30(11):1588-90.

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[6] Swati BP, Biren JP, Hitesh AP, et al. Peutz-Jeghers syndrome. GujaratMed J 2013;68(2):106-8.

[7] Lindor NM, Greene MH. The concise handbook of family cancersyndromes. Mayo Familial Cancer Program. J Natl Cancer Inst 1998;90(14):1039-41.

[8] GiardielloFM,WelshSB,HamiltonSR,OfferhausGJ, et al. Increased risk ofcancer in the Peutz-Jeghers syndrome. N Engl J Med 1987;316(24):1511-4.

[9] Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, et al.Peutz-Jeghers syndrome is caused by mutations in a novel serinethreonine. Nat Genet 1998;18(1):38-43.

[10] Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, et al. Aserine/threonine kinase gene defective in Peutz-Jeghers syndrome.Nature 1998;391(6663):184-7.

[11] Hemminki A, Tomlinson I, Markie D, Jarvinen H, Sistonen P, et al.Localization of a susceptibility locus for Peutz-Jeghers syndrome to19p using comparative genomic hybridization and targeted linkageanalysis. Nat Genet 1997;15(1):87-90.

[12] Fernandez MJ, Martinez MI, Fernandez JR, Trabazo S, Gamborino E,Forteza Vila J. Peutz-Jeghers syndrome in a neonate. J Pediatr 1995;126(6):965-7.

[13] Hinds R, Philp C, Hyer W, Fell JM. Complications of childhood Peutz-Jeghers syndrome: implications for pediatric screening. J PediatrGastroenterol Nutr 2004;39(2):219-20.

[14] Cecilia M. Fenoglio-Preiser: Peutz-Jeghers syndrome. Gastrointestinalpathology: an atlas and text. 3rd ed. Philadelphia: Lippincott Williamsand Wilkin; 2008. p. 704-11.