What is the natural history of gastric low-grade dysplasia (GLGD) without follow-up?

Natural History of Gastric Low-Grade Dysplasia Without Follow-Up

Gastric low-grade dysplasia (GLGD) without follow-up has a significant risk of progression to high-grade dysplasia (HGD) or invasive carcinoma, with progression rates ranging from 3-30% depending on lesion characteristics and pathologist confirmation. 1, 2

Progression Risk

• The natural history of gastric low-grade dysplasia shows variable progression rates, with studies reporting 3.8-29.6% of GLGD lesions progressing to higher grades of neoplasia or invasive carcinoma 3, 4
• A long-term follow-up study found that 11% of LGD lesions progressed to HGD or noninvasive carcinoma, while one study showed that 29.6% of gastric intraepithelial neoplasias demonstrated progressive dysplasia 3, 2
• The annual incidence rate of progression from LGD to HGD/carcinoma has been reported to range from 0.4% to 13.4% per year 5

Factors Affecting Progression Risk

• Pathologist confirmation: Diagnosis confirmed by expert GI pathologists or multiple pathologists is associated with higher risk of progression (OR 47.14; 95% CI, 13.1-169.7 when all 3 pathologists agreed) 5
• Persistent LGD: The presence of LGD on consecutive endoscopies is a significant risk factor for progression (OR range 4.48-11.33) 5
• Lesion size: Lesions ≥1 cm have significantly higher risk of harboring HGD/carcinoma (39.4% of lesions ≥1 cm were upgraded to HGD/carcinoma upon resection) 4
• Morphology: Depressed lesions have higher risk of progression (OR 3.81; 95% CI, 1.22-11.9) 4
• Surface features: Presence of erythema is associated with higher risk (OR 2.49; 95% CI, 1.31-4.72) 4

Regression Phenomenon

• A noteworthy feature in the natural history of LGD is the phenomenon of regression, where follow-up biopsies do not demonstrate LGD and the diagnosis is downgraded to non-dysplastic tissue 5
• Potential reasons for regression include:
  • Interobserver variability among pathologists
  • Sampling errors
  • Misdiagnosis
  • Removal of the dysplastic focus by biopsies
  • True regression of the dysplastic area 5
• Factors associated with regression include shorter Barrett's length, active smoking status, proton-pump inhibitor use, incident LGD, older age, and unifocal LGD 5

Diagnostic Challenges

• There is significant interobserver variability in the diagnosis of GI tract dysplasia, particularly between regenerative changes and LGD 5
• Studies have shown that after expert pathology panel review, 73% of initially diagnosed LGD patients were downgraded to non-dysplastic or indefinite for dysplasia 5
• This phenomenon of LGD overdiagnosis has a significant impact on the reported rates of progression 5

Clinical Implications

• Without appropriate follow-up and management, patients with confirmed GLGD are at risk for progression to more advanced neoplasia 1
• High-grade dysplasia is a significant marker for gastric cancer, with 85% of patients with HGD found to have gastric cancer within 15 months in one study 6
• The cancers associated with high-grade dysplasia are usually pathologically favorable and potentially curable if detected early 6

Risk Stratification

• The presence of multiple risk factors dramatically increases progression risk (OR 47.6; 95% CI, 4.27-530.65 when all risk factors of size ≥1 cm, depressed morphology, and erythema are present) 4
• The sensitivity and negative predictive value for having at least one risk factor were 93.8% and 90.9%, respectively 4
• As the number of risk factors increases, the specificity and positive predictive value for HGD/carcinoma also increase 4

Without appropriate follow-up and management, gastric low-grade dysplasia represents a significant risk for progression to more advanced neoplasia, particularly in lesions with high-risk features such as large size, depressed morphology, surface erythema, or confirmation by multiple expert pathologists.