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Juvenile Polyposis of the Gastrointestinal Tract

Definition

  • Juvenile polyps, either multiple or involving extra-colorectal sites

Alternate/Historical Names

  • Generalized juvenile gastrointestinal polyposis
  • Juvenile polyposis coli

Diagnostic Criteria

  • Multiple or generalized or familial juvenile polyps (any one of the following):
    • ≥5 colorectal juvenile polyps
      • Most cases have many more (50-200)
      • Note that in sporadic cases, 2 or 3 polyps is common
    • Juvenile polyps in the stomach or small intestine
      • In some cases the stomach is preferentially involved
      • As single juvenile polyps cannot reliably be distinguished from gastric hyperplastic polyps, this effectively requires the identification of multiple polyps for diagnosis
    • 1 polyp anywhere if a first degree relative has juvenile polyposis
    • Some include anyone in a juvenile polyposis kindred who develops GI carcinoma, even if a juvenile polyp cannot be found
  • Polyps are generally similar to sporadic juvenile polyps
    • Spherical polyps with cystic glands and inflammatory stroma (see Sporadic Juvenile Polyps for detailed criteria)
    • 15% may be multilobated, papillary or villous in structure
    • May have intestinal, pyloric and foveolar differentiation
    • Small amounts of smooth muscle may be present
    • Mucosa between polyps may also show inflammation and mild crypt dilation
  • Dysplasia may be present in about 30% of syndromic cases
    • Very rare in sporadic polyps
    • More common in multilobated polyps or those with specialized differentiation
    • Usually within the polyp, without surface involvement
    • Usually low grade but may be high grade
    • Must be distinguished from reactive/regenerative atypia
    • Pure adenomas may occasionally occur
  • Significantly elevated incidence of colorectal and gastric adenocarcinomas
    • Colorectal adenocarcinoma
      • 20% at age 35
      • 68% at age 68
    • Gastric adenocarcinoma
      • 20% in patients with involvement of stomach by polyps
    • Rare cases in duodenum and pancreas
  • Polyps typically present in childhood, see Clinical
  • Robert V Rouse MD
    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Original posting / last update: 12/27/09, 11/23/14

Supplemental studies

Immunohistology

  • No useful stains

Genetic Studies

  • Mutations in:
    • MADH4 5-15%
      • Includes most cases with gastric involvement
    • BMPR1A 25%
    • PTEN 5%
      • These patients probably really have Cowden Syndrome
    • May be useful within a kindred to determine who gets screened

Differential Diagnosis

Juvenile Polyposis Cowden Disease
No associated mucocutaneous lesions Most have facial mucocutaneous lesions
No association with breast hamartomas or carcinomas Frequent breast hamartomas and carcinomas
No association with thyroid carcinomas Frequent thyroid carcinomas
PTEN mutations not seen PTEN mutations in 80%
Ganglion cells not seen in GI polyps Ganglion cells may be present in GI polyps
The gastrointestinal polyps are otherwise largely indistinguishable

 

Juvenile Polyposis Peutz-Jeghers Syndrome
No mucocutaneous hyperpigmentation Mucocutaneous hyperpigmentation
Smooth muscle absent or only small amounts in lamina propria Prominent arborizing smooth muscle bundles in GI polyps
Frequent mucous retention cysts Lacks retention cysts
Lacks pseudoinvasion May have displaced mucosa with pseudoinvasion of underlying muscularis propria
Polyps rare in small intestine Most polyps in small intestine
MADH4 or BMPR1A mutations in 40% STK11 mutations in 50-90%

 

Cronkhite-Canada Syndrome Juvenile Polyposis
Most colorectal polyps sessile Most colorectal polyps polypoid
Hair, nail, skin changes present No associated ectodermal changes
No dysplasia Infrequent cases may have focal dysplasia
Not familial Autosomal dominant, 75% are new mutations without family history
The gastrointestinal polyps are largely indistinguishable

 

Juvenile Polyposis Hereditary Mixed Polyposis
Most cases present in childhood Mean age at presentation 41 years
Usually 50-200 polyps Usually 1-15 polyps, rarely >50
Adenomas infrequent Adenomas common
The gastrointestinal polyps in some cases are indistinguishable

 

Gastric Hyperplastic Polyp Juvenile Polyposis
No association with similar polyps in the colorectum Most cases involve the colorectum
Gastric hyperplastic polyps are indistinguishable from juvenile polyps
In the case of solitary polyps, the distinction is of no significance
Juvenile polyposis has an increased risk of carcinoma and thus should be distinguished
based on multiplicity, colorectal involvement or family history

 

Juvenile Polyposis Serrated Polyposis (Hyperplastic Polyposis)
Polypoid Sessile
Prominent cystically dilated glands Cystic dilation not prominent
Irregular glands Glands are vertically arranged and not complex
Prominent inflamed stroma Stroma is not prominent

 

Juvenile Polyposis Familial Adenomatous Polyposis
Dysplasia, if present is focal Multiple adenomatous polyps, all with cytologic dysplasia
Mucous retention cysts prominent Lacks mucous retention cysts

Clinical

  • Polyps typically present in childhood
    • Mean age 6
  • Carcinoma may present as early as age 15
    • Median ages reported 42-58
  • Polyposis may rarely present in infants
    • Infantile form not familial
    • Frequent associated birth defects
    • Frequently complicated by intussusception
  • Familial cases are autosomal dominant
    • May be associated with hereditary hemorrhagic telangiectasia
    • 66-75% lack family history and appear to be de novo mutations
    • Cowden syndrome must be ruled out, see Differential Diagnosis
  • Unless cleared by genetic study, or if symptomatic, screening of family members should begin around age 15
  • May cause bleeding or intussusception
  • Some cases totally asymptomatic

Bibliography

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