Peutz-jeghers syndrome Q85.8

Rare, autosomal dominantly inherited polytopic tumor syndrome with a monitoric lentiginosis (leading clinical symptom) of the lips, nose and buccal mucosa as well as intestinal hamartous polyps and carcinomas manifesting mainly in the small intestine. Association with other tumors of internal organs is possible (see below).

Note: Peutz-Jeghers syndrome belongs to the family of familial lentiginosis syndromes. This further includes the following syndromes:

• Carney complex (syndrome)
• PTEN-Hamartoma syndrome
• LEOPARD syndrome/Noonan syndrome

From the gastroenterological point of view the syndrome is counted among the "Hamartous Polyposis Syndromes" .

Worldwide occurrence among numerous ethnic groups, no gender preference. Incidence: 1/60.000-300.000 inhabitants.

Autosomal-dominantly inherited mutations of the Peutz-Jegher syndrome gene(STK11/LKB1) mapped to gene locus 19p13.3, with consecutive disruption of serine-threonine protein kinase 11, which modulates cell proliferation.

Loss of heterozygosity (LOH) of the chromosomal region where the STK11 gene is located has been demonstrated in 70% of hamartomatous polyps and adenocarcinomas of Peutz-Jeghers syndrome.

Lentigines from birth or in early childhood; intestinal polyps 2nd-3rd decade of life (mean age of onset of the disease: 35 years)

Especially perioral and periorbital areas, red lips, oral mucosa (cheek mucosa) and conjunctiva are affected.

Nails with brown longitudinal stripes

Polyposis mainly affects the small intestine, more rarely the stomach and large intestine.

Intraoral lentiginosis: Bizarre, dark to black-brown, spatter-like hyperpigmentation (lentigines).

Less commonly, nail pigmentation (diffuse or longitudinal streaks).

Abdominal discomfort due to small bowel polyposis is expected in some of the patients (early adulthood).

Furthermore, there is an increased risk for a wide spectrum of malignancies:

• Pancreatic carcinoma (C25.9) - the lifetime risk is about 40% (see below Pancreatic carcinoma familial)
• Bronchial carcinoma
• Endocrine tumors
• Neuroendocrine carcinoma
• Thyroid carcinoma
• Colon carcinoma
• Genital carcinoma: cervix, ovaries, testis

• Cronkhite-Canada syndrome
• Gardner syndrome I
• LEOPARD syndrome;
• Lentiginosis
• Carney complex.

For cosmetic reasons, the lentigines can be covered with camouflage (e.g. Dermacolor, Unifiance). In case of severe cosmetic impairment, laser therapy of the pigment spots can be attempted.

Regular lifelong monitoring and, if necessary, treatment of the polyposis is important.

Clinical screening for non-intestinal tumours.

Pigmentation spots of the skin are partially regressible.

Oral lentiginosis remains constant.

Malignant degeneration of the small intestinal hamartomas is rare.

Important is the high association (90% of patients) with other internal neoplasms.

Thus, endoscopic GI prevention is of great importance from the age of 20.

1. Blank A et al (1981) Pigmentary polyposis (Peutz-Jeghers syndrome). Dermatologist 32: 296-300
2. Burgdorf WHC et al (1988) Autosomal dominant genodermatoses and their association with internal carcinomas. Dermatologist 39: 413-418
3. Campos FG et al (2015) Colorectal cancer risk in hamartomatous polyposis syndromes. World J Gastrointest Surg 7:25-32
4. Cowgill SM et al (2003) The genetics of pancreatic cancer. Am J Surg 186: 279-286
5. Grady WM (2003) Genetic testing for high-risk colon cancer patients. Gastroenterology 124: 1574-1594
6. Hutchinson J (1896) Pigmentation of lip and mouth. Arch Surg (London) 7: 290
7. Jeghers H, McKusick VA, Katz KH (1949) Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits. New Eng J Med 241: 993-1005 u. 1031-1036
8. Peutz JLA (1921) Very remarkable case of familial polyposis of mucous membrane of intestinal tract and nasopharynx accompanied by peculiar pigmentations of skin and mucous membrane. Nederl Monatschr Geneesk 10: 134-146
9. Wilson DM et al (1986) Testicular tumors with Peutz-Jeghers syndrome. Cancer 57: 2238-2240
10. Zhou Fet al (2014) Multiple genital tract tumors and mucinous adenocarcinoma of colon in a woman with Peutz-Jeghers syndrome: a case report and review of literatures. Int J Clin Exp Pathol 7:4448-4453