Polyps and Polyposis syndromes

1. Hamartomatous Polyps
1. Juvenile Polyps
   
2. Peutz-Jeghers Syndrome
3. Phosphatase and tensin homolog gene mutation (PTEN)
1. Bannayan-Riley-Ruvalcaba Syndrome
   
2. Cowden Syndrome
3. Gorlin Syndrome
2. Adenomatous Polyps
1. Familial Adenomatous Polyposis Syndrome
2. Gardner Syndrome
3. Lynch Syndrome
4. MYH-associated
5. Turcot Syndrome
   
3. Inflammatory Polyps
4. Mixed Polyposis Syndromes
5. Other
1. Bourneville Tuberous Sclerosis

Hamartomatous Polyps

• Hamartomas are benign
• The most common tumors of childhood, occur in 1-2%
• Ages 2-6 (rare under 12mo)
• Composed of mucus filled glandular and stromal elements with inflammatory infiltrate surrounded by a thin epithelium
• Prone to bleeding due to bulky and vascular nature
• Typically outgrow their blood supply leading to mucosal ulceration
• Often removed through autoamputation which can also result in self limited bleeding (occasionally endoscopic polypectomy is required)
• Prolapse can occur with a protruding pedunculated mass associated with mucus discharge and pruritis
  

• Prevalence 2%
• Most commonly presents with painless rectal bleeding
• Occasionally mistaken for prolapse or "hemorrhoid"
• If polyp is protruding, can be associated with mucus discharge and pruritis
• May autoamputate and self-resolve
• Age 2-6, rare under 12mo
• Polyps typically measure 0.5-5cm
• 50% of patients have more that one polyp
• 70% occur in rectum or rectosigmoid colon (90% distal to splenic flexure)
  
• Benign, negligible risk for future malignancy
• Patients with <5 polyps & no family history should be reassured, but note that juvenile polyps may be the first manifestation of a hamartomatous polyposis syndrome and the development of additional symptoms in the future should prompt re-investigation.
• Treatment: Colonoscopy and polypectomy
• Pathology shows dilated cysts with mucin, glandular, and stromal elements with inflammatory infiltrate, abundant lamina propria. Dilated cysts, irregular crypts with inflamed and expanded stroma
• Gross appearance consistent with a pedunculated, vascular polyp that is covered by a thin epithelium. Prone to bleed as they outgrow their blood supply leading to mucosal ulceration and occasionally autoamputation with bleeding from remaining central arterial supply.

Juvenile Polyposis Syndrome, JPS

• Greater than 5 juvenile polyps (typically 50-200)
• Autosomal dominant with variable penetrance (often a family history)
• SMAD4 (18q21.1) or BMPR1A (10q23.2) found in 40-60% of patients
• ENG (9q 33–34) less common
• Patients with SMAD4 should be evaluated for hereditary hemorrhagic telangiectasia (eval for vascular malformations of brain and lung), may not have typical findings of HHT, 10% have clubbing
• JPS patients can have extraintestinal findings: Cardiac, Vascular/Skin, Cranial/Skeletal, Endocrine, Behavior, Neuro/epilepsy, Urologic, Ocular
• Diagnosis requires one of the following:
• i. lifetime total of 5 or more juvenile polyps
• ii. Juvenile polyps outside of the colon
• iii. any number of polyps with a family h/o JPS
• Increased risk of malignant transformation (10-50%) increases with polyp burden. Lifetime risk 38-68%
• Recommendations:
• Routine EGD/Colonoscopy and Genetic testing at 12-15 years (earlier if Sx present) followed by annual colonoscopy until all polyps resected (then space to 1-5yrs)
• Colectomy is indicated if Cancer, dysplasia, or high polyp burden that cannot be managed endoscopically
• Consider colectomy if poor adherence, missed screening, or additional findings: PLE, anemia.
  
• Colectomy usually not performed for a single dysplastic polyp.
  
• Refer to specialty center, if available
• JPS in infancy (rare) presents with hemorrhage and anemia, diarrhea, PLE, intussusception. Gene mutations typically in both BMPR1A and PTEN regions. Despite colectomy, death usually occurs before age 2
• ^{https://www.espghan.org/dam/jcr:de39387d-8655-4832-8036-7bb21212b8ce/2019_Management_of_Juvenile_Polyposis_Syndrome_in_Children.pdf}
  

Peutz-Jegher Syndrome (PJS)

• Rare Autosomal dominant condition associated with mucocutaneous pigmentation and hamartomatous polyps throughout the GI tract
• STK11(LKB1) mutation located on chromosome 19p13.3 (90% of patients)
• Polyps most common in the jejunum. Can lead to bleeding, intussusception, obstruction often requiring surgical intervention at an early age.
• Pigmented lesions may occur in the buccal mucosa, mouth, nostrils, perianal area, hands and feet. Pigmentation may fade after puberty but typically persists in the buccal mucosa (Lip freckling is not pathognomonic)
• Clinical diagnosis made by having one of the following:
• i. two or more histologically confirmed PJ polyps
• ii. any PJ polyp with family h/o PJS in close relative
• iii. Characteristic mucocutaneous pigmentation with family h/o PJS in close relative
• iv. Any PJ polyps in a patient with characteristic mucocutaneous pigmentation
• In at risk patients or patients with known family history, recommend screening for pigmented lesions and GI symptoms in infancy with Genetic testing by Age 3.
• 68% of PJS patients had undergone laparotomy for bowel obstruction by age 18.
• Endoscopic eval of the upper, lower, and small bowel should be performed starting at age 8 and every 3 years thereafter. (or as soon as symptoms present). The small bowel should be assessed with VCE or MR Enterography.
• Polypectomy of small bowel polyps >1.5cm should be performed by advanced endoscopists with skill in Balloon Assisted Enteroscopy (BAE) of the small bowel.  This is because of the high risk of perforation associated with the muscularis mucosa invaginating into the large pedunculated stalk of the polyps.greater risk with cautery.
  
• Intussusception associated with a PJS polyp should be urgently referred for surgical reduction and polypectomy (laparoscopy, laparotomy and interoperative enteroscopy). Radiologic or endoscopic attempts at reduction are not appropriate.
• PJS patients are thought to have increased risk for cancers in adulthood (not childhood) esp breast cancer in females - screening should start at age 18
• Large-cell calcifying Sertoli cell tumors and PJS may be associated and testicular US has been recommended q2yrs from age 4-12, Also recommend screening for gynecomastia
• Pathology of polyp shows Frond-like elongated branching arborizing strands of smooth muscle
• Latchford A, Cohen S, Auth M, Scaillon M, et al.: Management of Peutz-Jeghers syndrome in children and adolescents: a position paper from the ESPGHAN Polyposis Working Group . J Pediatr Gastroenterol Nutr 2019; 68: pp. 442-452

^{PTEN Hamartoma Tumor Syndrome}

• Phosphate and Tensin Homolog (PTEN)
  
• Mutations in PTEN gene on 10q23.3
• Extraintestinal manifestations predominate over intestinal polyps
• Bannayan-Riley-Ruvalcaba Syndrome (BRRS)
  
• Presents in childhood with hamartomas in the colon and ileum
• Can have intussusception, rectal bleeding, hypoalbuminemia
• Extraintestinal manifestations include: macrocephaly, developmental delay, abnormal metacarpals and phalanges, pectus excavatum, scoliosis, genital pigmentation, lipomatosis, hemangiomatosis. 
  
• IF family history is identified, recommend genetic testing in early childhood.
  
• BRRS patients require regular colonoscopy and small bowel surveillance
• Cowden
• Rare in childhood
• Extraintestinal manifestations include: macrocephaly, papillomatous papules, mucocutaneous lesions/facial trichilemmoma, and acral keratosis.
• Proteus is also rare
• Typically associated with hemi-hypertrophy and congenital malformations but GI Sx unlikely.
• Cowden and Proteus are typically asymptomatic and no cases of cancer have been described before adulthood.
  
• ACG has recommended screening endoscopy and small bowel evaluation start at age 15.
• PTEN patients, in general, have increased lifetime risk of cancer (breast, thyroid, endometrial, kidney) and recommend screening start at age 18.
• https://www.gastrojournal.org/article/S0016-5085(22)00151-2/fulltext
  

Adenomatous polyps

Familial Adenomatous Polyposis Syndrome (FAP)

• The gene responsible for FAP is APC located on chromosome 5q21
• Involved with WNT signaling (cell division, differentiation, and migration)
• Typically a germline mutation inactivates one of the APC alleles - leading to adenoma formation
• If family specific genetic testing is positive, the gene mutation predicts future disease and patient should undergo colonoscopy screening w/ dye spray q5yrs starting at age 12. (Sooner if symptomatic).
• If known family history and no genetic mutation identified, patient should undergo colonoscopy screening w/ dye spray q5yrs starting at age 12. (Sooner if symptomatic). Important to note size and number of polyps including location (rectal vs colonic, etc)
• Symptoms may include increased bowel movements, looser stools, mucous discharge, rectal bleeding, "protrusion", and abdominal or back pain.
• Polyp characteristics that are more likely to be associated with dysplasia or malignancy include: ulceration, surface bleeding, or adenoma diameter >10mm.
• Treatment
• Colectomy is the only effective therapy
• Practice recommendations vary and there is no unified concensus regarding timing of colectomy (mid-late teens), however, recommend performing colectomy early:
• In patients with family members who had early onset of severe disease/poor outcomes
• Before or when there are many adenomas >5-10 mm
• Biopsy showing high degree of dysplasia
• More than 500 polyps >2 mm in size
• TNTC / carpeting of the colon with polyps.
• Biopsy should not delay colectomy as biopsy of large polyps may still miss malignancy in any other reamining polyp
• If patient undergoes subtotal colectomy with ileorectal anastomosis (IRA), the rectum remains at risk for cancer and the patient will require q6mo surveillence w/ polypectomy for life
• Role of EGD unclear as the youngest person with upper GI malignancy is reported as age 17.
• May be some role in NSAIDS and COX-2 inhibitors in delaying progression of FAP.
• Medical therapy does not replace prophylactic colectomy for FAP.
• Sulindac: reduces number and size of rectal polyps after colectomy but does not eliminate all polyps and residual cancer risk remains.
• Celecoxib: lowers colorectal and duodenal adenoma burden but carries increased cardiovascular risk.
• Vitamin C, DFMO, and oral calcium: evidence is inconsistent or inconclusive; not established alternatives to surgery.
• Aspirin was ineffective in small trials.
  
• Fish oil may help
• Desmoid tumors may devleop in up to 30% of FAP patients.
  
• Non-metastatic but locally invasive myofibroblastic lesions
• Typically occur in abdominal wall or intraabdominally can result in obstruction of small bowel, ureter, or vasculature. 
• A leading cause of mortality in FAP patients
• Surgical resection has high morbidity and mortality and typically stimulates further growth
• Patients usually have bi-allellic APC mutations (unlike patients with sporadic desmoid tumors )
• Look for FAP in patients presenting with desmoid tumors
•  Hyer Warren, Cohen Shlomi, Attard Thomas, et al.: Management of familial adenomatous polyposis in children and adolescents: position paper from the ESPGHAN Polyposis Working Group . JPGN 2019; 68 (3): pp. 428-441.

MYH-Associated polyposis

• MYH-associated polyposis (MAP) is caused by a compound heterozygous mutation in the MYH gene on chromosome 1p
• Autosomal recessive
• It is characterized by adenomatous polyposis of the colorectum and a higher risk of colorectal cancer (CRC)
• Individuals with MAP exhibit varying numbers of colorectal polyps and generally lack extracolonic features.
• The average age of CRC diagnosis in MAP patients is 50 years.
  
• Colonic polyposis typically manifests in the 40s
• MYH polyposis has no specific pediatric implications
• Because of the risk of cancer, surveillance colonoscopies should begin at age 25 in individuals affected by MAP
• This condition is estimated to account for 0.4% to 3% of all colonic cancers.

Lynch Syndrome (hereditary nonpolyposis colon cancer) 

• Lynch syndrome is an inherited condition with high penetrance for early-onset colorectal cancer (CRC).
• It is caused by alterations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2).
• It is associated with various cancers, including colorectal, endometrial, ovarian, gastric, renal tract, brain, small bowel, and bile duct cancers.
• There are no specific pediatric complications described.
• The median age for CRC development in Lynch syndrome is approximately 44 years, and it's uncommon before age 25.
• A high proportion of CRCs in Lynch syndrome are right-sided (proximal to the splenic flexure).
• Amsterdam II or Bethesda criteria help identify affected families for genetic testing in early adulthood.
• Colonoscopic surveillance should begin at age 20-25 for at-risk individuals.
• Colonoscopic surveillance is recommended every 1-2 years due to the accelerated adenoma-carcinoma sequence in Lynch syndrome.

Constitutional mismatch repair deficiency syndrome (CMMRD)

• Cause: Bi-allelic mutation in one of the DNA repair genes (MLH1, MSH2, MSH6, or PMS2). worst manifestation of Lynch
  
• Characteristics:
• Adenomatous polyps (mainly in the colon, but can appear throughout the gastrointestinal tract).
• Café-au-lait macules and other stigmata mimicking neurofibromatosis type 1.
• Increased Cancer Risk (especially during the first decade of life):
• Brain tumors
• Colonic polyposis
• Colorectal cancer
• Small bowel cancers
• Leukemias
• Lymphomas
• https://gastro.org/clinical-guidance/surveillance-and-management-of-biallelic-mismatch-repair-deficiency-bmmrd-syndrome/
  

Gardner Syndrome

• Gardner syndrome is associated with pathogenic variants in the APC gene.
• It is classically characterized by:
• Multiple colorectal polyps
• Desmoid tumors
• Soft tissue tumors, including:
• Fibromas
• Osteomas (typically mandibular)
• Epidermoid cysts
• Lipomas
• Gardner syndrome shares many characteristics with Familial Adenomatous Polyposis (FAP).
• Up to 20% of FAP patients present with the extraintestinal manifestations once associated with Gardner syndrome.

Some (but not all) cases of Turcot syndrome are related to APC : These patients present with colorectal polyposis and primary brain tumors (Type 1 - glioblastoma,  Type 2 - medulloblastoma)

Attenuated FAP

• A significantly increased risk of colorectal cancer
• Fewer polyps than classic FAP (average: 30 polyps)
• Average age of cancer diagnosis: 50-55 years
• Upper GI tumors and extraintestinal manifestations may be present but are less common.

Other

• Autosomal Dominant with variable penetrance
• Mutations in Tuberous Sclerosis loci 1 and 2
• Classic Triad:
• Intellectual disabililty
• Epilepsy
• Adenoma Sebaceum in the presence of hamartoma lesions
• Distal colon may reveal PJS type polyps or adenomas
  

Polyps and Fecal Calprotectin

Fecal calprotectin levels are often elevated in children with juvenile colorectal polyps, and this elevation correlates significantly with polyp size. Although juvenile polyps are non-inflammatory, surface irritation and localized inflammation can activate neutrophils, leading to increased calprotectin. Recent multicenter research confirms this association, showing that larger polyps are linked to higher fecal calprotectin levels and that levels normalize after polyp removal. Additional studies and case reports support its potential as a non-invasive biomarker for detecting and monitoring juvenile polyps

^§ The word polyp has a layered etymology that traces through both Ancient Greek and Latin, with each language contributing to its evolving meaning. In Greek, the term πολύπους (polypous) literally means “many-footed,” combining polys (“many”) and pous (“foot”), and was originally used to describe sea creatures like octopuses or cuttlefish. Latin adopted this word as polypus, retaining its zoological meaning but also extending it metaphorically to describe abnormal growths, particularly nasal tumors, due to their bulbous shape and stalk-like appearance that resembled tentacled marine animals. This metaphorical use laid the foundation for the modern medical definition of a polyp as a protruding growth from a mucous membrane. Thus, the word’s journey from Greek to Latin to English reflects a semantic shift driven by visual analogy, where the form of certain tissue growths evoked the image of many-limbed sea creatures.

References

Kim, Y. B., Kim, J. Y., Choi, S., Lee, Y. M., Choi, S. Y., Kim, S. C., Jang, H.-J., Lee, Y., Jeong, I. S., Yi, D. Y., Kang, Y., Lee, K. J., Choe, B.-H., & Kang, B. (2023). Fecal calprotectin levels significantly correlate with polyp size in children and adolescents with juvenile colorectal polyps. Pediatric Gastroenterology, Hepatology & Nutrition, 26(1), 34–42. https://doi.org/10.5223/pghn.2023.26.1.34

https://www.calprotectin.co.uk/wp/wp-content/uploads/2018/02/FCAL-P002_Elevated-Faecal-calprotectin-in-Children-with-Colonic-juvenile-polyps.pdf

https://journals.sagepub.com/doi/pdf/10.1177/2333794x15623716

Kliegman, R. M., St. Geme, J. W., Blum, N. J., Shah, S. S., & Tasker, R. C. (Eds.). (2019). Nelson textbook of pediatrics (21st ed.). Elsevier.

Waasdorp Hurtado, C., & Sondheimer, J. M. (Eds.). (2011). The NASPGHAN fellows concise review of pediatric gastroenterology, hepatology and nutrition (1st ed.). Castle Connolly Graduate Medical Publishing.

Huang, J., & Walker, W. A. (Eds.). (2005). Review of pediatric gastrointestinal disease and nutrition. BC Decker.

Etymonline. (n.d.). Polyp. Online Etymology Dictionary. Retrieved August 9, 2025, from https://www.etymonline.com/word/polyp