Peutz-Jeghers Syndrome
Summary
Clinical characteristics.
Peutz-Jeghers syndrome (PJS) is an autosomal dominant condition characterized by the association of gastrointestinal polyposis, mucocutaneous pigmentation, and cancer predisposition. Peutz-Jeghers-type hamartomatous polyps are most common in the small intestine (in order of prevalence: in the jejunum, ileum, and duodenum) but can also occur in the stomach, large bowel, and extraintestinal sites including the renal pelvis, bronchus, gall bladder, nasal passages, urinary bladder, and ureters. Gastrointestinal polyps can result in chronic bleeding and anemia and also cause recurrent obstruction and intussusception requiring repeated laparotomy and bowel resection. Mucocutaneous hyperpigmentation presents in childhood as dark blue to dark brown macules around the mouth, eyes, and nostrils, in the perianal area, and on the buccal mucosa. Hyperpigmented macules on the fingers are common. The macules may fade in puberty and adulthood. Individuals with Peutz-Jeghers syndrome are at increased risk for a wide variety of epithelial malignancies (colorectal, gastric, pancreatic, breast, and ovarian cancers). Females are at risk for sex cord tumors with annular tubules (SCTAT), a benign neoplasm of the ovaries, and adenoma malignum of the cervix, a rare aggressive cancer. Males occasionally develop large calcifying Sertoli cell tumors (LCST) of the testes, which secrete estrogen and can lead to gynecomastia, advanced skeletal age, and ultimately short stature, if untreated.
Diagnosis/testing.
The diagnosis of Peutz-Jeghers syndrome is based on clinical findings. Identification of a heterozygous pathogenic variant in STK11 by molecular genetic testing confirms the diagnosis and allows for family studies.
Management.
Treatment of manifestations: Routine endoscopic surveillance with polypectomy decreases the frequency of emergency laparotomy and bowel loss resulting from intussusception. Diagnosis and management of small-bowel polyps is challenging. New advances in small-bowel imaging include video capsule endoscopy, CT enterography, and MR enterography. Balloon-assisted enteroscopy allows for removal of deep small-bowel polyps. Occasionally intraoperative enteroscopy and enterotomy is needed for removal of large distal small-bowel polyps. Intussusception and malignancies should be treated in the standard manner.
Prevention of primary manifestations: Although not specifically studied in individuals with PJS, the following could be considered based on family history or other clinical factors: prophylactic mastectomy to manage high risk for breast cancer and prophylactic hysterectomy and bilateral salpingo-oophorectomy after age 35 years or after child bearing has been completed to prevent gynecologic malignancy.
Surveillance: Protocols have been suggested for monitoring stomach, small and large bowel, breasts, testicles, ovaries, uterus, and pancreas by various procedures as early as birth and as frequently as once a year.
Evaluation of relatives at risk: If the pathogenic variant in the family is known, offer molecular genetic testing to at-risk relatives so that morbidity and mortality can be reduced by early diagnosis and prevention of disease through appropriate surveillance and consideration of prophylactic measures in affected family members. If the family variant is not known, offer clinical diagnostic evaluations to all at-risk family members, who will benefit from early treatment and appropriate surveillance.
Genetic counseling.
Peutz-Jeghers syndrome is inherited in an autosomal dominant manner. However, approximately 45% of affected individuals have no family history of PJS; the exact proportion of cases caused by a de novo pathogenic variant is unknown as the frequency of subtle signs of the disorder in parents has not been thoroughly evaluated and molecular genetic data are insufficient. The risk to the offspring of an individual with a pathogenic STK11 variant is 50%. Once the STK11 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible.
Diagnosis
Suggestive Findings
Peutz-Jeghers syndrome (PJS) should be suspected in individuals with the following:
- Two or more PJS-type intestinal polyps
- Mucocutaneous macules
- Gynecomastia in males as a result of estrogen-producing Sertoli cell testicular tumors
- History of intussusception, especially in a child or young adult
PJS-type intestinal polyps. The sine qua non of PJS diagnosis is the hamartomatous gastrointestinal polyp, which is histopathologically characterized by distinctive interdigitating smooth muscle bundles in a characteristic arborizing (branching tree) appearance throughout the lamina propria, particularly of small bowel polyps, and lobular organization, particularly of colonic crypts. Pseudo invasion of misplaced crypts is an innate property of the PJS hamartoma, which may reflect the role of STK11 in cell polarity [Tse et al 2013].
Note: Individuals with PJS also develop many other polyps; polyps showing adenomatous changes frequently arise in the colon and may cause confusion with familial adenomatous polyposis. The histology of gastric PJS polyps can be similar to gastric hyperplastic polyps, thus highlighting the importance of a gastrointestinal pathologist in reviewing polyp histology.
Establishing the Diagnosis
The diagnosis of PJS is established in a proband with one of the following, based on a European consensus statement [Beggs et al 2010]:
- Two or more histologically confirmed PJS-type hamartomatous polyps
- Any number of PJS-type polyps detected in one individual who has a family history of PJS in at least one close relative
- Characteristic mucocutaneous pigmentation in an individual who has a family history of PJS in at least one close relative
- Any number of PJS-type polyps in an individual who also has characteristic mucocutaneous pigmentation
Identification of a heterozygous pathogenic variant in STK11 by molecular genetic testing (see Table 1) also establishes the diagnosis based on diagnostic criteria from the Mayo Clinic [Riegert-Johnson et al 2008].
Molecular testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing:
- Single-gene testing. Sequence analysis of STK11 is performed first and followed by gene-targeted deletion/duplication analysis. Sequence analysis and gene-targeted deletion/duplication analysis of STK11 may also be performed concurrently to reduce turnaround time.
- A multigene panel that includes STK11 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included and the sensitivity of multigene panels vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
- More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered if serial single-gene testing (and/or use of a multigene panel that includes STK11) fails to confirm a diagnosis in an individual with features of PJS. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation).For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
Table 1.
Molecular Genetic Testing Used in Peutz-Jeghers Syndrome
| Gene 1 | Proportion of Peutz-Jeghers Syndrome Attributed to Pathogenic Variants in Gene | Proportion of Probands with a Pathogenic Variant 2 Detectable by Method | |
|---|---|---|---|
| Sequence analysis 3 | Gene-targeted deletion/duplication analysis 4 | ||
| STK11 | 94%-96% 5 | ~81% 6 | ~15% 7 |
| Unknown 8 | NA | ||
- 1.
See Table A. Genes and Databases for chromosome locus and protein.
- 2.
See Molecular Genetics for information on allelic variants detected in this gene.
- 3.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
- 4.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
- 5.
In a large Dutch study, 73 (96%) of 76 individuals with PJS had an STK11 pathogenic variant [van Lier et al 2010]. In another study 65 (94%) of 69 individuals with PJS had an STK11 pathogenic variant, including 20 (87%) of 23 familial cases and 45 (97.8%) of 46 sporadic cases [Resta et al 2013].
- 6.
van Lier et al [2010], Resta et al [2013]
- 7.
Includes larger deletions, such as whole-gene deletions of STK11 and smaller intragenic deletions [Le Meur et al 2004, De Rosa et al 2010, Borun et al 2015].
- 8.
Of 25 individuals who had PJS but did not have a detectable STK11 pathogenic variant, one had a heterozygous pathogenic variant of the DNA repair enzyme MUTYH that was not observed in 1015 controls [Alhopuro et al 2008]. Of note, pathogenic variants in MUTYH ordinarily cause an autosomal recessive form of adenomatous polyposis coli.
Clinical Characteristics
Clinical Description
Peutz-Jeghers syndrome (PJS) is characterized by the association of gastrointestinal polyposis and mucocutaneous pigmentation. The risk for gastrointestinal and extraintestinal malignancies is significantly increased. Distinct benign and malignant gonadal and gynecologic tumors can also be seen. Variable expressivity is common; for example, some affected individuals in families with PJS may have only polyps or perioral pigmentation.
Gastrointestinal polyposis. Peutz-Jeghers-type hamartomatous polyps can occur anywhere in the GI tract, but occur most commonly in the small intestine. The density of polyps is greatest in the jejunum, followed by the ileum, then the duodenum. Polyps can occur elsewhere in the GI tract, including the stomach and large bowel. Polyps have also been reported in the renal pelvis, urinary bladder, ureters, lungs, nares, and gallbladder.
Adenomas also appear with increased prevalence throughout the gastrointestinal tract.
The malignant potential of Peutz-Jeghers-type hamartomatous polyps is unknown; however, the polyps can cause significant complications including bowel obstruction, rectal prolapse, and/or severe gastrointestinal bleeding with secondary anemia requiring multiple emergency laparotomies and bowel resections. The age of onset of symptoms from polyps is variable, with some children developing symptoms within the first few years of life. In one series, 68% of affected individuals had undergone emergency laparotomy by age 18 years. By age ten years, 30% of individuals with PJS had undergone a laparotomy [Hinds et al 2004]. One small single-center retrospective study of 15 individuals concluded that endoscopic management of small-bowel polyps in PJS using double-balloon endoscopy decreased the occurrence of urgent laparotomy by decreasing the mean number of resected polyps larger than 20 mm with each procedure [Sakamoto et al 2011].
Significant interfamilial variability in the age at which polyps first appear is observed, suggesting that the natural history of polyps in a family may be a predictor of severity for offspring. In studies from MD Anderson Cancer Center, the median age at which GI symptoms first appeared was ten years, while the median age at first polypectomy was 13 years [Amos et al 2004]. These data have prompted an earlier start date for surveillance procedures to detect and remove gastrointestinal polyps to decrease malignancy and complications of bowel obstruction [van Lier et al 2010, Latchford et al 2011].
Mucocutaneous pigmentation. Melanocytic macules (MM) are rarely present at birth; they become pronounced in most children before the fifth year, but then may fade in puberty and adulthood. Children often present with dark blue to dark brown mucocutaneous macules around the mouth, eyes, and nostrils, in the perianal area, and on the buccal mucosa. Hyperpigmented macules on the fingers are also common. In one series, 94% of individuals with PJS had perianal MM, 73% had MM that affected the digits, 65% had MM on the buccal mucosa, and 21% had MM at other sites [Utsunomiya et al 1975].
Histologically, increased melanocytes are observed at the epidermal-dermal junction, with increased melanin in the basal cells. No malignancy risk is associated with MM.
Gonadal tumors. Females with PJS are at risk for ovarian sex cord tumors with annular tubules (SCTATs) and mucinous tumors of the ovaries and fallopian tubes. Symptoms include irregular or heavy menstrual periods and, occasionally, precocious puberty due to hyperestrogenism. SCTATs in PJS are bilateral multifocal small tumors with focal calcification and a typically benign course [Young 2005]. In contrast, sporadic SCTATs are large, unilateral, and associated with a 20% risk of malignancy.
In an Italian series of 61 females with PJS, three had ovarian cancer, one was a malignant SCTAT [Resta et al 2013]. In a Dutch series of 69 females with PJS, 2 females had malignant Sertoli cell ovarian tumors and one had ovarian small cell cancer [van Lier et al 2010].
Males occasionally develop large cell calcifying Sertoli cell tumors (LCST) of the testes derived from sperm cord cells. These tumors may secrete estrogen and can lead to gynecomastia, advanced skeletal age, and ultimately short stature, if untreated. Multifocal calcifications are typically seen on testicular ultrasound. Malignant transformation is unusual. Aromatase inhibitors help reverse the hormonal effects of Sertoli cell tumors including reduction of gynecomastia and slowing of linear bone growth and bone age [Crocker et al 2014]. In a series including 64 males with PJS, one testicular seminoma was reported [van Lier et al 2010].
Malignancy. Individuals with PJS are at increased risk for intestinal and extraintestinal malignancies.
Table 2.
Cumulative Risk of Cancers in Peutz-Jeghers Syndrome
| Cancer Site | General Population Risk | Peutz-Jeghers Syndrome | |
|---|---|---|---|
| Risk | Mean Age at Diagnosis | ||
| Colorectal | 5% | 39% | 42-46 years |
| Stomach | <1% | 29% | 30-40 years |
| Small Bowel | <1% | 13% | 37-42 years |
| Breast | 12.4% | 32%-54% | 37-59 years |
| Ovarian (mostly SCTAT) | 1.6% | 21% | 28 years |
| Cervix (adenoma malignum) | <1% | 10% | 34-40 years |
| Uterus | 2.7% | 9% | 43 years |
| Pancreas | 1.5% | 11%-36% | 41-52 years |
| Testicular (Sertoli cell tumor) | <1% | 9% | 6-9 years |
| Lung | 6.9% | 7%-17% | 47 years |
Adapted from Syngal et al [2015]
SCTAT = sex-cord tumor with annular tubules
Colorectal and gastric cancers can arise from adenomas that are commonly found in individuals with PJS. A marked increase in cancer incidence after age 50 years is notable.
Breast cancer and ovarian cancers can occur at early ages in Peutz-Jeghers syndrome. The breast cancer risk in women with PJS may approach that of women who have a pathogenic variant in BRCA1 or BRCA2. Some families with PJS report relatives with early-onset breast cancer, suggesting that some family members with a pathogenic variant may on occasion develop breast or other cancers without having symptoms from the hamartomatous polyps.
Cervical cancer. Adenoma malignum is a rare well-differentiated adenocarcinoma of the uterine cervix. Presenting symptoms include bleeding or a mucoid, watery vaginal discharge. Histologic diagnosis can be difficult on small pathologic samples. The five-year survival after surgery is 60% [Tsuda et al 2005].
Genotype-Phenotype Correlations
Data on genotype-phenotype correlation related to STK11 pathogenic variants are conflicting. Further analysis of pooled registry data is needed to better characterize genotype-phenotype correlations and confirm malignancy risks.
In a study of 297 individuals with PJS, the type or site of the STK11 pathogenic variant did not influence cancer risk [Lim et al 2004]. Initial reports that pathogenic variants in exon 3 [Lim et al 2004] or exon 6 [Mehenni et al 2007] were associated with an increased cancer risk have not been replicated by subsequent studies. A review of 419 affected individuals found that the variant type and site within the functional domains of the expressed protein did not affect cancer risk [Hearle et al 2006a].
In contrast, Amos et al [2004] found that individuals who had pathogenic STK11 variants that predicted premature truncation and those who tested negative for pathogenic variants had similar ages of onset for first-reported polyps or polypectomy, and those with missense variants had later onset for these symptoms. Salloch et al [2010] similarly found that persons with pathogenic STK11 variants that predicted premature truncation had more gastrointestinal surgeries, a higher polyp count, an earlier age of first polypectomy, and a greater risk of melanoma than persons with other pathogenic variants.
The risk for small-bowel intussusception was not influenced by STK11 variant status [Hearle et al 2006b].
Pathogenic variants affecting protein kinase domain XI correlated with a 90% (9/10) incidence of GI polyp dysplasia compared to an 11.8% (2/17) incidence of polyp dysplasia in individuals with pathogenic variants affecting other regions of the protein [Wang et al 2014].
Penetrance
To date all reported individuals with pathogenic variants in STK11 have shown clinical manifestations.
Nomenclature
The following terms have also been used for PJS:
- Polyp and spots syndrome
- Inherited hamartomatous polyps in association with mucocutaneous melanocyte macules
- Hutchinson Weber-Peutz syndrome
- Perioral lentiginosis (sometimes used inappropriately as a synonym for PJS)
Prevalence
Birth prevalence has not been reliably established; estimates range widely from 1:25,000 to 1:280,000 [Tchekmedyian et al 2013].
PJS can occur in any racial or ethnic group.
Differential Diagnosis
Table 3 summarizes the differential diagnosis of Peutz-Jeghers syndrome (PJS).
Juvenile polyposis syndrome (JPS) is characterized by a predisposition to multiple hamartomatous polyps in the gastrointestinal (GI) tract, specifically in the stomach, small intestine, colon, and rectum. The term "juvenile" refers to the type of polyp, not the age of onset of polyps. Juvenile polyps are hamartomas that show a normal epithelium with a dense stroma, an inflammatory infiltrate, and a smooth surface with dilated, mucus-filled cystic glands in the lamina propria. Most individuals with JPS have some polyps by age 20 years. The number of polyps is highly variable. Most are benign. The risk of developing GI cancers in families with JPS ranges from 9% to 50%. Although most of this increased risk is attributed to colon cancer, cancers of the stomach, upper GI tract, and pancreas have been reported. JPS is distinguished from PJS by the lack of melanotic macules and the histology of polyps. Approximately 20% of individuals with JPS have pathogenic variants in SMAD4; about 20% have pathogenic variants in BMPR1A. JPS is inherited in an autosomal dominant manner.
Hereditary mixed polyposis syndrome (HMPS) (OMIM 601228). A family history of JPS is found in 20%-50% of individuals with hereditary mixed polyposis syndrome. HMPS is an autosomal dominant condition with variable penetrance consisting of multiple types of colorectal polyps including juvenile and adenomatous polyps. Affected individuals are at increased risk for colorectal cancer. HMPS can be caused either by mutation of BMPR1A or by a duplication of 15q15.3q22.1 that leads to increased expression of GREM1 [Jaeger et al 2012]. Some families with mixed hereditary polyposis syndrome have SMAD4 pathogenic variants.
PTEN hamartoma tumor syndrome (PHTS), an autosomal dominant cancer syndrome caused by mutation of PTEN, includes Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, PTEN-related Proteus syndrome, and a Proteus-like syndrome. The extraintestinal manifestations are more pronounced than intestinal polyposis. The features of Cowden syndrome that distinguish it from PJS include facial trichilemmomas, mucosal papillomas, acral keratoses, macrocephaly, and tumors of the thyroid, breast, and endometrium. The distinguishing features of Bannayan-Riley-Ruvalcaba syndrome include macrocephaly, intestinal polyposis, and lipomas. Proteus-like syndrome is undefined but refers to individuals with significant clinical features of Proteus syndrome who do not meet the diagnostic criteria for Proteus syndrome.
Unexplained hamartomatous mixed polyposis. In a study of 49 unrelated persons with unexplained hamartomatous mixed polyposis, Sweet et al [2005] determined that 22% had various germline pathogenic variants.
- Of 14 individuals with juvenile-type polyposis: two had pathogenic variants in ENG (encoding endoglin), a gene associated with hereditary hemorrhagic telangiectasia; one had a hemizygous deletion encompassing PTEN and BMPR1A; and one had a SMAD4 pathogenic variant.
- Of 23 individuals with hyperplastic/mixed polyposis, two had PTEN pathogenic variants.
- Of nine individuals with an unknown hamartomatous polyposis, pathogenic variants were seen in STK11 (4), BMPR1A (2), and SMAD4 (1).
Carney complex is an autosomal dominant disorder characterized by skin pigmentary abnormalities; myxomas, endocrine tumors or overactivity, and schwannomas. Pale brown to black lentigines are the most common presenting feature of Carney complex and typically increase in number at puberty. Cardiac myxomas occur at a young age, may occur in any or all cardiac chambers, and manifest as intracardiac obstruction of blood flow, embolic phenomena, and/or heart failure. Other sites for myxomas include the skin, breast, oropharynx, and female genital tract. Primary pigmented nodular adrenocortical disease, which causes Cushing syndrome, is the most frequently observed endocrine tumor, occurring in approximately 25% of affected individuals. Large-cell calcifying Sertoli cell tumors are observed in one third of affected males within the first decade and in almost all adult males. Up to 75% of individuals have multiple thyroid nodules, most of which are thyroid follicular adenomas. Clinically evident acromegaly from a growth hormone (GH)-producing adenoma is evident in approximately 10% of adults. Psammomatous melanotic schwannoma, a rare tumor of the nerve sheath, occurs in an estimated 10% of affected individuals. Despite some clinical overlap between Carney complex and Peutz-Jeghers syndrome, no individuals with Carney complex have been found to have pathogenic variants in STK11. About 60% of individuals have pathogenic variants in PRKAR1A.
Table 3.
Hereditary Cancer Syndromes Showing Signs and Symptoms that Overlap with PJS
| Syndrome | Gene(s) | Pigmentation | GI Tumors | Sertoli Cell Tumors | Cancers | Other |
|---|---|---|---|---|---|---|
| PJS | STK11 | Facial++ Mucosal+++ | Adenoma+ Hamartoma+++ | +/– | Colon, gastric, cervical, ovarian, breast, pancreatic, lung | Hyper-estrogenism |
| JPS | SMAD4 BMPR1A | – | Adenoma+ Hamartoma+++ | – | Colon | Heart defects? |
| CS | PTEN | Axillary+ Inguinal+ Facial+ | Adenoma+ Hamartoma+++ | – | Breast, thyroid, endometrium | Trichilemmoma, skin hamartoma, hyperplastic polyps, macrocephaly, breast fibrosis |
| CC | PRKAR1A | Facial+ Mucosal+ | – | ++ | Thyroid | Myxomas of skin & heart |
| FAP | APC | – | Adenoma+++ | – | Colon, brain | Desmoid tumors, osteomas, CHRPE |
| HNPCC | MLH1 MSH2 MSH3 MSH6 PMS1 PMS2 | Adenoma+ | – | Endometrial, gastric, renal pelvis & ureter, ovarian | Sebaceous adenoma |
- +
= presence of sign/symptom (# of +s indicates relative frequency of sign/symptom for the condition); ± = an occasional or rare sign/symptom; ? = anecdotal association; CC = Carney complex; CHRPE = congenital hypertrophy of the retinal pigment epithelium; CS = Cowden syndrome; FAP = familial adenomatous polyposis; HNPCC = hereditary non-polyposis colorectal cancer; JPS = juvenile polyposis syndrome
The differential diagnosis of oral pigmented lesions includes the following:
- The Laugier-Hunziker syndrome is characterized by the presence of perioral, digit and nailbed lentiginosis (small, well-demarcated; dark-brown to blue-black in color). It occurs in 1:8,300 to 1:29,000 births. This condition usually develops in adults and the hyperpigmentation is progressive. Laugier-Hunziker syndrome has not been associated with any known exposure and has not been reported to occur in families [Wang et al 2012].
- A fixed drug reaction
- A normal variant, especially in African Americans [Bishop et al 2004]
The differential diagnosis of some of the rare tumors observed in PJS includes:
- Sex cord tumors with annular tubules (SCTAT); 50% are associated with Peutz-Jeghers syndrome; the remainder may occur as an isolated finding.
- Calcifying Sertoli tumors of the testes and adenoma malignum of the cervix in women; these may also occur as an isolated finding or in other disorders.
Management
Evaluations Following Initial Diagnosis
To establish the extent of disease and need for clinical follow up in an individual diagnosed with Peutz-Jeghers syndrome (PJS), the following initial evaluations are recommended:
- Upper endoscopy plus small bowel examination (MR enterography or wireless capsule endoscopy) beginning at age eight years or when symptoms occur
- Colonoscopy beginning at age eight years
- In women, gynecologic and breast examinations and (after age 18 years) MRI
- In men, testicular examination and testicular ultrasound examination, if clinically indicated
- Consultation with a clinical geneticist and/or genetic counselor
Treatment of Manifestations
Polyps. Once the burden of gastrointestinal polyps has been established by endoscopy and imaging studies, prophylactic polypectomy of polyps >1cm is performed. This strategy has two goals:
- To decrease the sequelae of large polyps including bleeding, anemia, obstruction, and intussusception
- To reduce the risk for cancer by the malignant transformation of PJS-type polyps
The luminal polyp-related complications arise in childhood whereas cancer in PJS is typically seen in adulthood. Some evidence indicates that routine endoscopy and intraoperative enteroscopy with polypectomy decreases the frequency of emerging laparotomy and bowel loss [Pennazio & Rossini 2000, Edwards et al 2003, Oncel et al 2004]. From St. Mark’s PJS registry of 51 affected individuals who underwent surveillance endoscopies, none had emergency surgical interventions and no GI luminal cancers were diagnosed [Latchford et al 2011]. In surveillance endoscopies in affected individuals by age 18 years, 17/28 had large gastroduodenal or colonic polyps (>1 cm). These studies demonstrate that endoscopic surveillance and polypectomy in PJS is safe.
Distal small-bowel polyps that are beyond the reach of conventional endoscopy have been difficult to manage. Until recently, barium contrast upper-gastrointestinal series with a small-bowel follow through has been recommended. However, recent advances allow better diagnosis and eradication of small-bowel polyps, oftentimes without laparotomy and with a decrease in the radiation burden related to frequent surveillance:
- Video capsule endoscopy (VCE) allows for better visualization of the small-bowel polyps than barium x-rays and is recommended as a first-line surveillance procedure. In children, the capsule can be deployed in the duodenum after upper endoscopy [Parsi & Burke 2004, Burke et al 2005, Mata et al 2005, Schulmann et al 2005]. See Note.
- Magnetic resonance enterography (MRE) is a reliable procedure for the detection of larger small-bowel polyps with similar sensitivity to VCE and avoids the radiation exposure of CT enterography [Caspari et al 2004, Gupta et al 2010]. CT and MR enteroclysis