Peutz–Jeghers syndrome

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Peutz–Jeghers syndrome

Chinmoy Bhate and Robert A. Schwartz

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Peutz–Jeghers syndrome (PJS) is a rare hereditary disorder of polyposis. It is characterized by gastrointestinal polyps, mucocutaneous pigmentation, recurrent abdominal pain from intussusceptions, and an increased risk of intestinal and other malignancies.

Management strategy

The pigmented macules of PJS are typically found around the mouth, eyes, nostrils, and anus; they may also be seen on the hands and feet. These brown to black macules are often round or oval, 1–5 mm in diameter, and irregular in shape. They may occasionally manifest with a blue-gray hue. Clinically and histologically, these are simple lentigines.

Most patients with this autosomal dominant disorder have a germ-line mutation of the STK11/LKB1 (serine/threonine kinase 11) tumor suppressor gene, located at chromosome 19p13.3. A more recently identified second PJS disease locus exists at 19q13.4. The exact mechanism of cancer and hamartoma development remains unclear. Genetic testing may be useful in equivocal cases as well as in counseling of at-risk families; however, it is not required for diagnosis and is not 100% sensitive.

Management is predicated upon the potential for visceral complications and familial inheritance. This includes an evaluation for associated findings, including recurrent intussusceptions, gastrointestinal bleeding, and a variety of malignancies. Disease is most often discovered between the ages of 10 and 30 years. Any child with recurrent, unexplained abdominal pain should raise concern for intussusception, a medical emergency associated with PJS. Gastrointestinal polyps may undergo malignant degeneration. Ovarian neoplasms, especially granulosa cell tumors, may be seen. Both in men and women, sex cord tumors with annular tubules, and sex cord stromal tumors with sexual precocity, may develop. Cancers of the pancreas, stomach, esophagus, lung, uterus, and testes (Sertoli cell) all have an elevated relative risk in patients with PJS. Additionally, women with this disorder appear to carry an increased risk of bilateral breast cancer.

Genetic counseling is indicated. Laboratory studies investigating anemia, iron deficiency, or fecal occult blood are necessary in suspicious cases. Some utilize serum tumor markers, including carcinoembryonic antigen and cancer antigen 19-9 or 125, in addition to endoscopy and ultrasonography, for screening and monitoring. Families should be reassured that the mucocutaneous macules are benign and may improve after puberty. Several therapies have been used with varying responses; however, removal of these mucocutaneous markers may potentially mask the underlying disorder in patients with PJS.

The ruby laser (Q-switched and short pulsed) has been used in the treatment of labial macules without sequelae or recurrences. It may be suitable for children with PJS, since anesthesia is usually not required and no wound care is necessary. The CO2, alexandrite, and argon lasers, as well as intense pulsed light, have also been effective in the treatment of labial macules. Cryosurgery, surgical excision, electrodesiccation, and dermabrasion may lead to scarring and dyspigmentation, often without complete removal of the pigmented macules. Similarly, trichloroacetic acid may not produce total resolution.

Specific investigations

Peutz-Jeghers syndrome: a systematic review and recommendations for management.

Beggs AD, Latchford AR, Vasen HF, Moslein G, Alonso A, Aretz S, et al. Gut 2010; 59: 975–86.

This review covers current genotype–phenotype studies and an outline of consensus recommendations for screening and follow-up from a group of European experts who previously produced guidelines for the management of Lynch syndrome and familial adenomatous polyposis.

Surveillance in PJS aims to (a) reduce polyp burden and the incidence of intussusceptions in young patients, and (b) diminish the burden of cancer. Capsule endoscopy allows for thorough, mildly invasive surveillance of the small bowel for polyposis. Evaluation of the small bowel with upper gastrointestinal endoscopy, colonoscopy, and double-balloon enteroscopy has been useful in preventing the need for subsequent surgical polypectomy. Since double-balloon enteroscopy is often traumatic, it is reserved as a treatment modality.

First-line therapies

imageRuby and alexandrite lasers D

Second-line therapies

imageOther lasers E
imageIntense pulsed light E
imageCryotherapy E

[/level-membership-for-dermatology-category][not-level-membership-for-dermatology-category]

Peutz–Jeghers syndrome

Chinmoy Bhate and Robert A. Schwartz

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Peutz–Jeghers syndrome (PJS) is a rare hereditary disorder of polyposis. It is characterized by gastrointestinal polyps, mucocutaneous pigmentation, recurrent abdominal pain from intussusceptions, and an increased risk of intestinal and other malignancies.

Management strategy

The pigmented macules of PJS are typically found around the mouth, eyes, nostrils, and anus; they may also be seen on the hands and feet. These brown to black macules are often round or oval, 1–5 mm in diameter, and irregular in shape. They may occasionally manifest with a blue-gray hue. Clinically and histologically, these are simple lentigines.

Most patients with this autosomal dominant disorder have a germ-line mutation of the STK11/LKB1 (serine/threonine kinase 11) tumor suppressor gene, located at chromosome 19p13.3. A more recently identified second PJS disease locus exists at 19q13.4. The exact mechanism of cancer and hamartoma development remains unclear. Genetic testing may be useful in equivocal cases as well as in counseling of at-risk families; however, it is not required for diagnosis and is not 100% sensitive.

Management is predicated upon the potential for visceral complications and familial inheritance. This includes an evaluation for associated findings, including recurrent intussusceptions, gastrointestinal bleeding, and a variety of malignancies. Disease is most often discovered between the ages of 10 and 30 years. Any child with recurrent, unexplained abdominal pain should raise concern for intussusception, a medical emergency associated with PJS. Gastrointestinal polyps may undergo malignant degeneration. Ovarian neoplasms, especially granulosa cell tumors, may be seen. Both in men and women, sex cord tumors with annular tubules, and sex cord stromal tumors with sexual precocity, may develop. Cancers of the pancreas, stomach, esophagus, lung, uterus, and testes (Sertoli cell) all have an elevated relative risk in patients with PJS. Additionally, women with this disorder appear to carry an increased risk of bilateral breast cancer.

Genetic counseling is indicated. Laboratory studies investigating anemia, iron deficiency, or fecal occult blood are necessary in suspicious cases. Some utilize serum tumor markers, including carcinoembryonic antigen and cancer antigen 19-9 or 125, in addition to endoscopy and ultrasonography, for screening and monitoring. Families should be reassured that the mucocutaneous macules are benign and may improve after puberty. Several therapies have been used with varying responses; however, removal of these mucocutaneous markers may potentially mask the underlying disorder in patients with PJS.

The ruby laser (Q-switched and short pulsed) has been used in the treatment of labial macules without sequelae or recurrences. It may be suitable for children with PJS, since anesthesia is usually not required and no wound care is necessary. The CO2, alexandrite, and argon lasers, as well as intense pulsed light, have also been effective in the treatment of labial macules. Cryosurgery, surgical excision, electrodesiccation, and dermabrasion may lead to scarring and dyspigmentation, often without complete removal of the pigmented macules. Similarly, trichloroacetic acid may not produce total resolution.

Specific investigations