Endoscopic Characteristics in Predicting Prognosis of Biopsy-Diagnosed Gastric Low-Grade Intraepithelial Neoplasia

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Endoscopic Characteristics in Predicting Prognosis of Biopsy-Diagnosed Gastric Low-Grade Intraepithelial Neoplasia

Gastric cancer (GC) remains a significant public health burden in China, ranking third in both incidence and mortality among malignancies. Early detection of GC, particularly at the stage of early gastric cancer (EGC), is critical due to its high curability and 5-year survival rates exceeding 90% after resection. However, the identification and management of precancerous lesions such as low-grade intraepithelial neoplasia (LGIN) pose clinical challenges. Endoscopic forceps biopsy (EFB) is the standard for diagnosing gastric lesions, but discrepancies between biopsy and final histology are common. Up to 25% of EFB-diagnosed LGINs are later upgraded to high-grade intraepithelial neoplasia (HGIN) or adenocarcinoma upon resection. This underscores the need to identify endoscopic and histological predictors that distinguish malignancies initially misdiagnosed as LGIN from true LGIN lesions and to determine factors associated with LGIN progression.

Study Design and Patient Selection

This retrospective cohort study analyzed 182 patients diagnosed with gastric LGIN by EFB at Peking Union Medical College Hospital (Beijing, China) between 2007 and 2017. Inclusion criteria required at least two endoscopies within the first year of follow-up. Exclusions included prior gastrointestinal cancers, remnant stomachs, or abdominal radiotherapy/chemotherapy. Initial endoscopic images were independently reviewed by three experienced endoscopists to document lesion characteristics (number, location, size, gross morphology, surface features, margins) and background mucosa (atrophy, intestinal metaplasia [IM], inflammation). Histological diagnoses followed the revised Vienna classification, with categories 4 (HGIN/EGC) and 5 (submucosal cancer) classified as malignant.

Definitive diagnoses were based on the most severe histology within the first year of follow-up, including findings from subsequent EFBs or resections. Patients with malignancies detected within this period were classified as initially misdiagnosed. For progression analysis, 98 patients with confirmed LGIN after excluding misdiagnoses were followed for >1 year (median 33 months). Progression was defined as histological upgrade to malignancy during follow-up.

Key Findings

Predictors of Initially Misdiagnosed Malignancies

Among 182 patients, 48 (26.4%) were confirmed to have malignancies (46 via resection, 2 via repeated EFBs) during the first year. Multivariate logistic regression identified three independent predictors of misdiagnosis:

  1. Single lesion: Lesions occurring in isolation carried a 24-fold higher risk of malignancy compared to multiple lesions (OR=24.04, 95% CI: 2.19–263.87).
  2. Lesion size:
    • 10–20 mm: OR=3.26 (95% CI: 1.00–10.62)

    • 20 mm: OR=29.12 (95% CI: 3.31–255.84)

  3. Marked intestinal metaplasia (IM): OR=7.74 (95% CI: 1.59–37.54).

Other significant endoscopic features linked to malignancy included depressed morphology (72.9% vs. 33.6% in true LGIN; P<0.001), nodularity (60.4% vs. 9.7%; P<0.001), irregular margins (67.4% vs. 17.8%; P<0.001), and spontaneous bleeding (14.6% vs. 3.7%; P=0.016).

The combination of these predictors demonstrated strong diagnostic accuracy (AUC=0.871), with 68.7% sensitivity and 92.5% specificity. Lesions with two predictors had a 55.2% probability of malignancy, rising to 80% with three predictors.

Progression Risk of Confirmed LGIN

Among 98 patients with confirmed LGIN followed long-term, 12 (12.2%) progressed to malignancy over a median 33 months. Cox regression identified four progression predictors:

  1. Whitish appearance: HR=28.62 (95% CI: 3.26–251.19)
  2. Irregular margins: HR=15.72 (95% CI: 3.06–80.88)
  3. Marked IM in background mucosa: HR=66.94 (95% CI: 6.03–743.10)
  4. Persistent LGIN diagnosis (>2 EFBs within first year): HR=16.65 (95% CI: 3.58–77.44).

Kaplan-Meier analysis revealed significantly higher progression rates for lesions with whitish color (log-rank P=0.015), irregular margins (P=0.002), marked IM (P<0.001), and repeated LGIN diagnoses (P<0.001). In contrast, lesion location, atrophy, or inflammation showed no prognostic value.

Clinical Implications

The high misdiagnosis rate (26.4%) underscores limitations of EFB in assessing LGIN. Endoscopic features such as solitary lesions >10 mm, depressed morphology, and marked IM should raise suspicion for malignancy, warranting early resection or intensified surveillance. For confirmed LGIN, whitish discoloration, irregular borders, and persistent LGIN on follow-up biopsies signal high progression risk, necessitating shorter surveillance intervals (3–6 months).

Notably, marked IM emerged as a dual-risk marker—predictive of both initial misdiagnosis and progression. This aligns with the Correa cascade, where IM represents a key step in gastric carcinogenesis. In regions with high GC prevalence, LGIN lesions with IM require aggressive management.

Limitations and Strengths

The retrospective design introduced selection bias, particularly in follow-up compliance (26.9% lost to follow-up). Reliance on endoscopic photographs rather than real-time imaging may have reduced diagnostic accuracy. However, the study mitigated bias through blinded endoscopic reviews and rigorous exclusion of pre-malignant conditions.

Conclusion

Integrating endoscopic and histological predictors improves risk stratification for biopsy-diagnosed LGIN. Single lesions >10 mm with marked IM should be treated as potential malignancies. For confirmed LGIN, vigilant monitoring is essential for lesions exhibiting whitish color, irregular margins, or persistent LGIN on follow-up. These findings support tailored surveillance protocols to enhance early GC detection and reduce progression-related mortality.

doi.org/10.1097/CM9.0000000000001637

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