Recently, gastric cancer (GC) has emerged as a major global health concern, with rising incidence and mortality rates, now ranking the fourth among all cancers (1). The pathogenesis of GC involves a multistep progression from chronic gastritis, chronic atrophic gastritis (AG), gastrointestinal metaplasia (GIM), and gastric intraepithelial neoplasia (GIN), representing key precancerous stages, to early gastric cancer (EGC) (2). Early detection of GC and its precursors is critical for improving treatment outcomes and prognosis. Traditional white-light endoscopy (WLE) is limited in detecting subtle lesions, as it primarily visualizes mucosal and submucosal changes, such as atrophy or intestinal metaplasia (3). WLE’s tumor detection miss rate remains high, ranging from 4.6% to 25.8% (4). In contrast, confocal laser endomicroscopy (CLE), a novel imaging technique, enables real-time in vivo histological assessment during endoscopy, termed “optical biopsy” (5). Its principle relies on blue laser illumination and fluorescence detection, with only focal plane light passing through a pinhole to enhance resolution and contrast (6). CLE also provides 1000× magnification, allowing cellular or subcellular visualization of mucosal structures.The Miami Classification system is widely adopted in clinical practice to standardize the interpretation of CLE imaging and establish diagnostic criteria for gastrointestinal mucosal alterations. This framework categorizes mucosal changes into four distinct classes based on three key microstructural features: (1) glandular architecture, (2) cellular morphology, and (3) microvascular patterns. Within this classification, early gastric cancer (EGC) is defined by a diagnostic triad: completely disorganized epithelium, heterogeneous fluorescein leakage, and dark irregular epithelial cells with loss of polarity (7) Here, CLE was employed for intraoperative diagnosis in a female with gastrointestinal symptoms, and demonstrated its clinical use for real-time lesion characterization and improved diagnostic precision.

The diagnostic trajectory is summarized in Table 1 .

Chronic gastritis, characterized by persistent inflammation of the gastric mucosa, is frequently associated with Hp infection, one of its most common etiological factors. Patients typically present with epigastric discomfort or a burning sensation. Left untreated, chronic gastritis carries a risk of malignant transformation, emphasizing the importance of early and accurate diagnosis, as well as the timely pharmacological intervention to control disease progression and improve patient prognosis. CLE significantly altered clinical management in this case. Initial gastroscopic and endosonographic findings identified a slightly hyperechoic mucosal lesion in the gastric antrum, yet failed to definitively characterize its nature. This diagnostic uncertainty necessitated plans for invasive procedures. Critically, CLE provided real-time intraoperative diagnosis of benign inflammation (later corroborated by histopathology), thereby enabling a shift to conservative pharmacotherapy and avoiding unnecessary surgery. Notably, CLE delivers immediate pathological insights days before conventional histopathology, offering clinicians accelerated therapeutic decision-making. Additionally, CLE enables Hp visualization using acriflavine staining, demonstrating 93% sensitivity and 86% specificity for diagnosing Hp-associated gastritis (8).

CLE requires fluorescent agents, typically administered intravenously, with fluorescein sodium being the most common. This agent highlights cellular and subcellular details without nuclear staining. CLE systems are categorized into three types: endoscope-based CLE (eCLE), probe-based CLE (pCLE), and needle-based CLE (nCLE). eCLE integrates a confocal microscope into the endoscope’s distal end but is rarely used due to poor maneuverability. pCLE employs a microprobe inserted through the biopsy channel, though its scanning depth is fixed. nCLE, a miniaturized version of pCLE, allows microscopic imaging of deeper mucosal or visceral tissues during endoscopic ultrasound (EUS) via a 19G needle, overcoming pCLE’s limitation to superficial lesions. Currently, nCLE is the most widely used in clinical practice (9).Compared with conventional biopsy, the combination of conventional biopsy or in vivo pCLE demonstrated significantly higher sensitivity (96.9% vs. 75.0%) (10).This supports pCLE as a valuable adjunct to traditional biopsy, enabling targeted sampling or biopsy replacement in endoscopically suspicious lesions to mitigate tissue damage from repeated procedures.As summarized in Table 2 , CLE exhibits excellent diagnostic performance for gastric precancerous lesions:For high-grade intraepithelial neoplasia (HGIN), CLE achieved a sensitivity of 95.8% and specificity of 97.2% using the Li criterion (11);FICE-guided pCLE demonstrated 95.0% sensitivity and 94.6% specificity in detecting GIM (12).Critically, CLE combined with targeted biopsy (e.g., the Guo criterion (13)) optimizes diagnostic workflows by reducing sampling requirements.Further comparisons with endoscopic techniques ( Table 3 ) reveal:CLE significantly outperformed WLE in early gastric cancer (EGC) diagnosis (97% vs. 72%, *p* < 0.05) (14);For AG, CLE provided higher specificity than autofluorescence imaging (AFI) (84.7% vs. 69.5%, *p* < 0.05) (15).Thus, CLE allows for biopsy reduction while maintaining diagnostic accuracy, demonstrating its clinical utility in risk stratification.CLE offers significant advantages: it reduces biopsy requirements, enhances diagnostic sensitivity, and minimizes complications such as mucosal injury, infection, and bleeding. These attributes make it ideal for long-term monitoring of early gastric cancer (6). It also enables rapid intraoperative assessment of epithelial cells, glandular morphology, and microvascular structures, shortening diagnostic timelines and improving tumor margin evaluation (16, 17).However, CLE has limitations: its narrow field of view restricts examination of the entire gastric cavity, respiratory movements can cause instability, and fluorescein’s inability to stain nuclei limits diagnosis to structural atypia (18). Additionally, its shallow tissue penetration hinders visualization of deeper structures, and high costs and specialized training requirements limit its widespread adoption (19). Despite these limitations, CLE remains a promising imaging technology for detecting gastrointestinal malignancies.

CLE represents a transformative advancement in endoscopic imaging, offering real-time histological evaluation for early detection of precancerous and malignant gastric lesions. While complementary to traditional histopathology, its integration into clinical practice holds promise for improving diagnostic accuracy and patient outcomes. Future research should focus on overcoming technical limitations and expanding its applications in gastrointestinal oncology.