Definition/General
Introduction:
Peutz-Jeghers polyps are hamartomatous polyps characteristic of Peutz-Jeghers syndrome
They contain branching smooth muscle core covered by normal epithelium
They occur throughout the GI tract
They are associated with increased cancer risk.
Origin:
Results from STK11/LKB1 gene mutations
Leads to hamartomatous proliferation
Smooth muscle hyperplasia forms characteristic core
Normal epithelium covers the polyp
Autosomal dominant inheritance pattern.
Classification:
Part of Peutz-Jeghers syndrome spectrum
Hamartomatous polyps (not neoplastic)
Based on size: small (<1 cm), large (>1 cm)
Location: small bowel most common, colon, stomach.
Epidemiology:
Rare condition (1 in 25,000-300,000)
Equal gender distribution
Childhood to adult presentation
Small bowel most common site (90% of PJS patients)
Multiple polyps characteristic.
Clinical Features
Presentation:
Intussusception (most common complication)
Intestinal obstruction
GI bleeding
Mucocutaneous pigmentation
Abdominal pain
Associated malignancies.
Symptoms:
Crampy abdominal pain
Intestinal obstruction symptoms
Recurrent intussusception
Chronic anemia (bleeding)
Perioral pigmentation (pathognomonic)
Growth retardation (children).
Risk Factors:
STK11/LKB1 mutations (germline)
Family history of PJS
Autosomal dominant inheritance
De novo mutations (15% cases)
Consanguineous parents.
Screening:
Genetic testing (STK11/LKB1)
Upper and lower endoscopy
Capsule endoscopy
MR enterography
Cancer surveillance protocols
Family screening.
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Gross Description
Appearance:
Pedunculated polyps with broad stalks
Lobulated surface
Multilobulated appearance
Soft consistency
Pink to red coloration
Size varies (0.5-5 cm typically).
Characteristics:
Broad-based attachment
Cerebriform surface
Lobular architecture
Non-ulcerated surface typically
Multiple polyps throughout GI tract
Largest in small bowel.
Size Location:
Jejunum and ileum most common
Duodenum less frequently
Size: 0.5-5 cm (average 2-3 cm)
Multiple polyps (10-20 average)
Largest polyps in small bowel.
Multifocality:
Multiple polyps throughout GI tract
Small bowel: 90% of patients
Colon: 50% of patients
Stomach: 25% of patients
Number increases with age.
Microscopic Description
Histological Features:
Branching smooth muscle core (pathognomonic)
Normal epithelium covering polyp
Arborizing smooth muscle bundles
No dysplasia typically
Lamina propria between muscle and epithelium.
Cellular Characteristics:
Smooth muscle cells in branching pattern
Normal intestinal epithelium
Goblet cells and absorptive cells present
No cellular atypia
Normal maturation pattern.
Architectural Patterns:
Tree-like branching of smooth muscle
Epithelium follows muscle contours
Preserved crypt architecture
Lamina propria between muscle and epithelium
Pseudoinvasion possible.
Grading Criteria:
No grading system (hamartomatous)
Size assessment
Presence of dysplasia (rare)
Pseudoinvasion vs true invasion
Secondary changes evaluation.
Immunohistochemistry
Positive Markers:
Smooth muscle actin (SMA, muscle core)
Desmin (smooth muscle)
Caldesmon (smooth muscle)
CDX2 (intestinal epithelium)
CK20 (epithelium).
Negative Markers:
CD117 (excludes GIST)
S-100 (excludes nerve sheath tumor)
p53 (usually negative)
Beta-catenin (membrane pattern).
Diagnostic Utility:
Confirms smooth muscle nature of core
Demonstrates normal epithelium
Excludes other polyp types
Identifies dysplastic changes if present
Confirms hamartomatous nature.
Molecular Subtypes:
Classic PJ polyps: STK11 mutations
STK11-negative cases: other genetic causes
Sporadic cases: rare, usually syndromic.
Molecular/Genetic
Genetic Mutations:
STK11/LKB1 mutations (90% of PJS cases)
Germline mutations
Loss of heterozygosity
Truncating mutations most common
Large deletions possible.
Molecular Markers:
mTOR pathway dysregulation
AMPK pathway affected
Cell polarity disruption
p53 accumulation (dysplastic areas)
Beta-catenin localization.
Prognostic Significance:
Cancer risk: 15x increased overall
GI cancers: stomach, small bowel, colon
Extraintestinal cancers: breast, cervix, ovary, testis
Lifetime cancer risk: 85-95%.
Therapeutic Targets:
Polyp surveillance and removal
mTOR inhibitors (experimental)
Cancer screening protocols
Prophylactic surgery (selected cases)
Genetic counseling.
Differential Diagnosis
Similar Entities:
Juvenile polyp
Inflammatory polyp
Adenomatous polyp
Hyperplastic polyp
Lipoma
GIST.
Distinguishing Features:
PJ polyp: branching smooth muscle core
Juvenile polyp: inflammatory stroma, no muscle
Adenoma: dysplastic epithelium
Hyperplastic: serrated architecture
Lipoma: adipose tissue.
Diagnostic Challenges:
Identifying characteristic muscle pattern
Distinguishing from inflammatory polyps
Recognizing pseudoinvasion
Assessing for dysplastic changes
Correlation with clinical syndrome.
Rare Variants:
Dysplastic PJ polyps
Adenomatous change in PJ polyps
Carcinoma arising in PJ polyps
Atypical smooth muscle patterns.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Small bowel polyp, [size] cm, from [jejunum/ileum]
Diagnosis
Peutz-Jeghers type hamartomatous polyp
Histological Features
Hamartomatous polyp with characteristic branching smooth muscle core and normal epithelium
Smooth Muscle Core
Arborizing smooth muscle bundles extending from stalk into polyp head
Epithelial Changes
Normal intestinal epithelium without dysplasia
Size
Polyp measures [X] cm in greatest dimension
Special Studies
SMA: positive (smooth muscle core), CDX2: positive (epithelium)
STK11 mutation analysis: [recommended for syndrome confirmation]
[other study]: [result]
Recommendations
Clinical correlation with Peutz-Jeghers syndrome, genetic counseling, cancer surveillance
Final Diagnosis
Small intestinal Peutz-Jeghers hamartomatous polyp