FaCD Online Syndrome Fact Sheet

Last updated: 30 Jan 2013

Name: Peutz-Jeghers syndrome

Synonym: PJS, Hamartous Intestinal Polyposis

Mode of Inheritance: AD

Genes

STK11, mapped to 19p13.3

Tumor features

biliary tract cancer (incl. gallbladder)
bladder polyps
breast cancer
cervix, adenoma malignum
endometrial cancer
gastrointestinal cancer
gastrointestinal polyps, Peutz-Jeghers type
nasal polyps
ovarian sex cord tumor
testicular Sertoli-Leydig cell tumor

Tumor features (possible)

adrenal cancer
anal cancer
bone tumor
desmoplastic small cell tumor, intra-abdominal
esophageal cancer
fallopian tube cancer
gastric fundic gland polyps
glioma of the brain
hepatocellular cancer (hepatoma)
liposarcoma
lung/bronchial cancer
melanoma, cutaneous
multiple myeloma (Kahler's disease)
non-Hodgkin lymphoma
ovarian gonadoblastoma
ovarian mucinous cystadenoma
ovarian Sertoli-Leydig cell tumor
ovarian teratoma
pancreatic adenocarcinoma
paraganglioma, nonchromaffin (incl.: glomus tumor/chemodectoma)
paranasal sinuses, squamous cell cancer of the
renal tumor
thyroid cancer, papillary

Non-tumor features

lips, pigmentation of
oral mucosa, pigmentation of
pigmentation of fingers/palmoplantar regions
vulvar lentigines

Non-tumor features (possible)

peritoneal pigmentation

Comment

Peutz-Jeghers syndrome was named after Peutz and Jeghers who first reported on this typical combination of features[1-4]. Hallmarks of the disorder are the hamartous gastrointestinal polyps, which because of the presence of smooth muscle can be distinguished from the juvenile type and which may show adenomatous changes)[5;6] and mucocutaneous pigmentation (lips, buccal region, vulva, toes and fingers). The pigmentation appears in the first decade and usually disappears in the course of time (generally from the 3d decade).
These dermatological features can also be observed in the Laugier-Hunziker syndrome, usually a sporadic but sometimes familial condition not associated with increased cancer risk[41,42]. In this syndrome, a spotty pigmentiation of the nails may be observed as well. Interestingly, peritoneal pigmentation ahs been reported as well[52].
Polyps in the nasopharynx, bronchioli and urinary tract have also been reported in PJS. Typically patients present clinically in the first decade with intestinal complications: bleeding, intussusception, obstruction, volvulus.[7-9]. Burkart et al studied patients with apparantly single PJS type polyps. Most of the patients had a personal or family history of PJS associated cancer, suggesting that non-PJS associated single PJS type polys are probably very rare[28].

Cancer risk in Peutz-Jeghers syndrome is increased[10-13,29,31,34,35,45]: the most frequent tumors are gastrointestinal cancer, adenoma malignum of the cervix[14,15,45], breast cancer[16,45], generally benign ovarian or testicular sex cord tumor with annular tubules (SCTAT, often multifocal[17-19], uni- or bilateral malignant SCTAT is rare[20,39,47].

A range of other tumors have been reported as well[10-13],including lung cancer (adenocarcinoma[38,45]), pancreatic cancer[45], malignant melanoma[21,45], ovarian Sertoli-Leydig cell tumors[22,45], mucinous cystadenoma[25,36], gonadoblastoma[26,44], mature teratoma[37] and mixed serous/borderline cancer[27], malignant mixed mullerian tumour of the fallopian tube[40], biliairy tract/gallbladder cancer[23,30,45], nasal polyposis[32], paraganglioma[51], ganglioglioma of the brain[33], anal squamous cell cancer[43], intra-abdominal desmoplastic small cell tumor[24], liposarcoma[45], NHL[45], squamous cell cancer of the paranasal sinus[45], adrenocortical cancer(at age 16 months)[48] and papillary thyroid cancer (at ages 6, 22 and 25 years)[48-50].

Hearle et al analyzed the incidence of cancer in 419 individuals with Peutz-Jeghers syndrome. The risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was estimated at 2%, 5%, 17%, 31%, 60%, and 85%, respectively[34].
Mehenni analyzed a group of 149 PJS patients. Overall cancer risks at ages 30, 40, 50, 60, and 70 years were estimated at 6%, 18%, 31%, 41%, and 67%, respectively. There were similar overall cancer risks between male and female carriers[35].<>br> Van Lier et al reported on 133 Dutch PJS patients. The cumulative risk for developing cancer at ages 40, 50, 60, and 70 years was estimated at 20%, 36%, 58% and 76%, respectively[45].


Clinical criteria[46]:

• In case of a positive family history of PJS:
• at least 1 PJS type hamartous polyps(histologically confirmed),or
• characteristic prominent mucocutaneous pigmentation



• In absence of a PJS family history:
• at least 3 PJS type polyps (histologically confirmed), or
• at least 1 PJS type polyp (histologically confirmed) and characteristic prominent mucocutaneous pigmentation

Links

Johns Hopkins guide on PJS 18 1 08
PJS Support Group 24 1 08
The Network for Peutz Jeghers and Juvenile Polyposis Syndrome 24 1 08

References

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[3] Peutz JLA. Over een zeer merkwaardige, gecombineerde familiaire polyposis van de slijmvliezen van den tractus intestinalis met die van de neuskeelholte en gepaard met eigenaardige pigmentaties van huid- en slijmvliezen. Ned Tijdschr Geneesk 1921;134-146.
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[5] Narita T, Ohnuma H, Yokoyama S. Peutz-Jeghers syndrome with osseous metaplasia of the intestinal polyps. Pathol Int 1995; 45:388-392.
[6] Perzin KH, Bridge MF. Adenomatous and carcinomatous changes in harmartomatous polyps of the small intestine (Peutz-Jeghers syndrome): report of a case and review of the literature. Cancer 1982; 49:971-983.
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