Small intestine & ampulla

Benign tumors / tumor-like conditions

Peutz-Jeghers polyp

Editorial Board Members: Claudio Luchini, M.D., Ph.D., Aaron R. Huber, D.O.
Devin Allison, M.D.
Krutika S. Patel, M.B.B.S., M.D.

Last author update: 10 April 2023
Last staff update: 10 April 2023

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PubMed Search: Peutz-Jeghers polyp

Devin Allison, M.D.
Krutika S. Patel, M.B.B.S., M.D.
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Cite this page: Allison D, Patel KS. Peutz-Jeghers polyp. website. Accessed October 2nd, 2023.
Definition / general
  • Hamartomatous polyp associated with Peutz-Jeghers syndrome (PJS) and characterized by papillary architecture with arborizing compact bundles of smooth muscle
Essential features
  • > 90% of patients with Peutz-Jeghers polyposis syndrome have an autosomal dominant germline mutation in STK11 (formerly LKB1) (Clin Genet 2007;72:568)
  • Most commonly affects the small bowel but can occur anywhere along the GI tract
  • Morphologically characterized by central cores of arborizing smooth muscle that divide lobules of relatively normal glandular mucosa
  • Moderate to high lifetime cumulative risk of malignancies in Peutz-Jeghers syndrome, with a variable risk for malignancy of the GI tract, breast, pancreas, ovary, lung, cervix, uterus and testes (Gastroenterology 2000;119:1447, Am J Gastroenterol 2010;105:1258)
  • Peutz-Jeghers polyp (PJP)
  • Peutz-Jeghers polyposis syndrome (PJPS)
ICD coding
  • ICD-10: Q85.8 - other phakomatoses, not elsewhere classified
  • ICD-11: LD2D.0 - Peutz-Jeghers syndrome
  • Peutz-Jeghers polyposis syndrome is an autosomal dominant syndrome with variable penetrance and an incidence of 1 case in 50,000 - 200,000 births (Clin Gastroenterol Hepatol 2006;4:408)
  • ~67% of patients present in the second to third decades of life and 33% present in first decade of life
  • Direct precursor is unknown
  • May represent a genetic predisposition to epithelial prolapse and polyp formation (Gut 2006;55:1)
  • Dysplasia in Peutz-Jeghers polyps is rare; however, sections of unaffected colon in Peutz-Jeghers syndrome patients have shown protracted clonal evolution in the crypts which may explain increased cancer risk (Gut 2012;61:839)
  • Autosomal dominant inheritance pattern
  • Germline mutations in tumor suppressor gene serine / threonine kinase 11 (STK11) (formerly called LKB1) located on gene 19p13.3 are found in up to 90% of cases (J Med Genet 2006;43:e18)
  • ~25% of cases are sporadic and are likely due to de novo STK11 mutations or low penetrance variants (Gastroenterology 2000;119:1447)
  • STK11 gene is postulated to be involved in cell polarity, chromatin remodeling, cell cycle arrest and Wnt signaling; mutations in STK11 lead to dysregulation of mTOR pathway
  • Rare cases of Peutz-Jeghers polyp in patients that do not meet criteria for Peutz-Jeghers syndrome
Clinical features
  • Mucocutaneous hyperpigmented macules around the lips, eyes, nostrils, perianal area, mouth and of the buccal mucosa
  • Often presents with abdominal pain due to polyp related obstruction, intussusception or prolapse (Curr Mol Med 2007;7:29)
  • May also develop chronic gastrointestinal bleeding, hematochezia, hematemesis and anemia
  • Diagnosis of a Peutz-Jeghers polyp requires endoscopy with polypectomy and histologic evaluation
  • WHO diagnostic criteria for Peutz-Jeghers syndrome includes:
    • ≥ 3 histologically confirmed Peutz-Jeghers polyps
    • Any number of Peutz-Jeghers polyps with a family history of Peutz-Jeghers syndrome
    • Characteristic, prominent mucocutaneous pigmentation with a family history of Peutz-Jeghers syndrome
    • Any number of Peutz-Jeghers polyps and characteristic, prominent mucocutaneous pigmentation
  • Reference: Gut 2010;59:975
Radiology description
  • Variably sized polyps that often occur in clusters
  • Larger polyps commonly have a more lobular appearance
Radiology images

Images hosted on other servers:

Axial T1 weighted image - enhancement of rounded PJP

Prognostic factors
  • Prognosis for Peutz-Jeghers syndrome is mostly determined by the associated cumulative risk of malignancy, with the lifetime cumulative risk for all types of cancer being > 90%
  • Most common sites of developing malignancy are colorectum (39% cumulative risk), stomach (29%), small intestine (13%), pancreas (100x risk, 11 - 36%), breast (32 - 54%), ovary (21%), cervix (10 - 23%), uterus (9%), testis (9%), lung (7 - 17%) (Gastroenterology 2000;119:1447)
  • Unusual gonadal lesions such as sex cord tumor with annular tubules (SCTAT), calcifying Sertoli cell tumor of the testes and HPV independent gastric type adenocarcinoma of the cervix (formerly known as adenoma malignum) are associated with Peutz-Jeghers polyposis syndrome (Am J Gastroenterol 2005;100:476)
Case reports
  • U.S. Multi-Society Task Force (USMSTF) recommends polypectomies when seen on endoscopy, are symptomatic or are ≥ 10 mm on imaging (Gastroenterology 2022;162:2063)
  • Also recommended are scheduled surveillance of GI tract, breast, pancreas, ovaries, testes and lungs
  • Genetic testing of all asymptomatic first degree relatives
Clinical images

Images hosted on other servers:

Hyperpigmented macules of the perioral area

Lobular duodenal polyp

Gross description
  • Variable size of polyps; small polyps can be sessile
  • Larger polyps are usually pedunculated with a multilobulated / cerebriform smooth surface and a thick stalk
Gross images

Images hosted on other servers:

Duodenal dilatation, arborizing polyps

Arborizing polyps, pedunculated and sessile

Intraluminal polyp

Microscopic (histologic) description
  • Peutz-Jeghers polyps of the small bowel have distinctive papillary villous architecture with tree-like arborization of compact smooth muscle bundles and relatively normal overlying epithelium (Mod Pathol 2013;26:1235)
  • Epithelial component is usually arranged in a distinct lobular configuration, separated by cores of smooth muscle
  • Epithelium often shows glandular dilation and distortion
  • Secondary erosion and ulceration can be present
  • Epithelial misplacement (pseudoinvasion) can be seen in the submucosa, muscularis propria and even to the serosa due to prolapse and peristaltic kneading; pseudoinvasion is commonly associated with pedunculated polyps
    • This can be mistaken for invasive carcinoma
  • Dysplasia is rare in Peutz-Jeghers polyps but if present, is characterized by complex cribriform architecture, nuclear hyperchromasia, loss of polarity, nuclear crowding and nuclear stratification extending to the surface
Microscopic (histologic) images

Contributed by Krutika S. Patel, M.B.B.S., M.D. and @SueEPig on Twitter
Jejunal Peutz-Jeghers polyp

Jejunal Peutz-Jeghers polyp

Tree-like arborization of smooth muscle in PJP

Tree-like arborization of smooth muscle

Distinct lobular configuration of epithelium in PJP

Distinct lobular configuration of epithelium

Bland epithelial component in PJP

Bland epithelial component

Surface erosion in PJP

Surface erosion

Epithelial misplacement in PJP

Epithelial misplacement

Peutz-Jeghers polyp Peutz-Jeghers polyp

Peutz-Jeghers polyp

Virtual slides

Images hosted on other servers:

Jejunum, Peutz-Jeghers polyp

Molecular / cytogenetics description
  • Cytogenetic evaluation for STK11 mutation via germline sequencing may be helpful in subtle cases

Small bowel, Peutz-Jeghers polyp

Sample pathology report
  • Small bowel, jejunum, polypectomy:
    • Hamartomatous polyp, Peutz-Jeghers type (see comment)
    • Comment: Histologic sections show a hamartomatous polyp with arborizing smooth muscle cores dividing lobular compartments of mucosa, consistent with Peutz-Jeghers polyp. There are no adenomatous changes or malignancy identified.
Differential diagnosis
  • Mucosal prolapse polyp:
    • More common in rectosigmoid colon
    • Smooth muscle shows more disarray and is less compact than Peutz-Jeghers polyp
    • Smooth muscle wrapping around individual crypts favors mucosal prolapse
  • Juvenile polyp:
    • Loose, edematous lamina propria with inflammation is a characteristic feature
    • Smooth muscle arborization is not a prominent feature
    • Marked cystic dilation of epithelial component is more common
    • Genetic testing shows germline mutations in SMAD4 or BMPR1A
  • Inflammatory polyp:
    • Usually associated with branching and cystic dilatation of epithelial component with regenerative mucosa with reactive atypia
    • Edematous lamina propria with acute and chronic inflammatory infiltrate
  • Sporadic hyperplastic polyp:
    • Uncommon, typically occurs in the second portion of the duodenum
    • Histologically resembles colonic microvesicular hyperplastic polyps with epithelial serrations, crypts with narrow bases, mucin droplets and bland cytology
    • Small case series showing association with mutations in BRAF V600E and KRAS (Hum Pathol 2011;42:1953)
  • In addition to histology, clinical and family history often aid in the diagnosis; for Peutz-Jeghers polyps, as for other hamartomatous polyps with syndromic considerations, consultation with genetic counseling is recommended to gather family history and consider germline mutation analysis
Board review style question #1

Which of the following is true about the syndrome associated with the jejunal polyp shown above?

  1. Associated with autosomal recessive inheritance pattern
  2. Associated with germline mutations in SMAD4
  3. Dysplasia is seen in a majority of these polyps
  4. Histology is characterized by papillary architecture with arborizing compact bundles of smooth muscle
  5. More commonly seen in the sigmoid colon
Board review style answer #1
D. Histology is characterized by papillary architecture with arborizing compact bundles of smooth muscle. The image is of a Peutz-Jeghers polyp, which is morphologically characterized by tree-like arborizing smooth muscle cores dividing lobules of relatively normal glandular villous epithelium. Peutz-Jeghers polyposis syndrome patients have autosomal dominant germline mutation in STK11 (formerly LKB1). It most commonly affects the small bowel. Dysplasia is rare in Peutz-Jeghers polyps.

Comment Here

Reference: Peutz-Jeghers polyp
Board review style question #2

The above small intestinal polyp is removed from a patient after an episode of intussusception. They are also noted to have perioral hyperpigmented spots. In which gene does this patient likely have a germline mutation?

  1. APC
  2. PTEN
  3. SMAD4
  4. STK11 (formerly LKB1)
Board review style answer #2
D. STK11 (formerly LKB1). The above polyp is consistent with a Peutz-Jeghers type polyp. Germline mutations in tumor suppressor gene serine / threonine kinase 11 (STK11 - formerly called LKB1) are found in up to 90% of cases and is inherited in an autosomal dominant fashion. Patients with this syndrome often have perioral hyperpigmented macules. SMAD4 mutations are associated with juvenile polyps. APC mutations are seen in familial adenomatous polyposis. And PTEN mutations are associated with Cowden syndrome.

Comment Here

Reference: Peutz-Jeghers polyp
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