3. Possibilities of Endoscopic Examination and Sampling of Biopsy Specimens for the Diagnosis of Gastric Mucosa Atrophy

Endoscopic examination plays a key role in the diagnosis of CAG, since the competency of the endoscopist and the adequacy of gastrobiopsy sampling determine the subsequent morphological assessment of the lesion of the gastric mucosa and verification of the diagnosis [59]. The key data for the diagnosis of chronic atrophic gastritis, which can be obtained from the results of endoscopic examination, are the topography of gastritis and the actual identification of atrophy and metaplasia zones [60]. The inflammation of the gastric mucosa is usually considered from the standpoint of a predominant lesion of an organ part: body gastritis, antrum gastritis, pangastritis [61,62]. Clinical interpretation of the topography of inflammation can be as follows. The body gastric mucosa predominantly involved in the inflammatory process may indicate the presence of AIG [63]. In adults, and in cases of introduction of H. pylori infection during adolescence, inflammation begins in the antrum, in the so-called “ecological niche” of the H. pylori bacterium [20]. Further spread of the H. pylori infection in the proximal direction results in the additional involvement of the body of the stomach in the inflammatory process. Pangastritis is formed in this way. Regardless of the etiology, the dominance of gastric lesions is an unfavorable sign in terms of the risk of developing gastric cancer [44].

Virtual or electronic chromoendoscopy are imaging methods allowing a detailed examination of the gastric mucosa. Their use increases the efficiency of diagnosing precancerous changes and makes it easier for the endoscopist to select areas “suspicious” for intestinal metaplasia or dysplasia for taking gastrobiopsy specimens without any dye techniques. The methods are easy to use and less time-consuming than when using dyes [60,71,72].

One of the virtual chromoendoscopy methods is narrow band imaging (NBI) developed by Olympus (Olympus Medical Systems Co., Ltd., Tokyo, Japan). The principle of NBI endoscopy is based on an optical phenomenon in which the depth of penetration of light into tissues depends on the wavelength. NBI uses narrow spectra of blue light (415 nm) and green light (540 nm) due to light filters installed in the illuminator, which allows you to get a clearer, more detailed image of the gastric mucosa [60]. The sensitivity and specificity of NBI endoscopy for the diagnosis of the gastric mucosa atrophy reach 95 and 98.5%, and for the diagnosis of early gastric cancer, they are 83% and 96%, respectively [64].

The standard for the study of biopsy specimens is the OLGA-system protocol which involves taking two fragments from the body of the stomach, two fragments from the antrum and one fragment from the incisura angularis of the stomach, and allows assessing the stage of the process and the risk of developing gastric cancer [75]. In a detailed presentation, modern recommendations are indicated as follows: two biopsies from the antrum of the stomach at a distance of 2 cm from the pylorus along the lesser and greater curvatures, one biopsy from the incisura angularis and two biopsies from the body of the stomach at a distance of 8 cm from the rosette of the cardia along the lesser and greater curvatures [76].

The use of special adhesive strips can be one of the effective approaches to solve the problem of orientation and fragmentation of biopsies. Orientation using specialized adhesive strips made of cellulose acetate can be carried out by fixing tissue fragments to the strip using manual pressing for 5 s. In this case, the first biopsy specimen is placed at the pointed end of the strip, which provides intuitive recognition of the serial number of the biopsy tissue sample (Figure 1).

Figure 1. Adhesive orientation strip for biopsy material with tissue fragments located on it. The sequential order of the tissue fragments in the direction from the pointed end allows the marking of the fragments. The photo presents a sequence of 7 oriented tissue fragments.

4. Histological Examination—“Pitfalls” of a Standard Study

In the OLGA (Operative Link for Gastritis Assessment) predictive system, the severity of mucosal atrophy is commonly referred to as the stage of gastritis [62]. There are five stages: stage 0—there is no atrophy, minimal risk of gastric cancer; stages I and II—there is a moderate risk; stages III–IV—there is a high risk (5–6 times higher than in the population). The grade of gastritis is understood as the intensity of infiltration of the gastric mucosa by inflammatory cells: mononuclear and segmented leukocytes together, and not separately, as in the Modified Sydney system [81,82].

The stage of gastritis is a predictive indicator that is used and clinically interpreted much more often than the degree [83]. The degree is usually treated in the same way as the indicator “inflammation” in the Modified Sydney system. The higher grade, the more pronounced the inflammatory cell infiltration, the more cytokines are formed in the gastric lamina propria, the more intense the transformation of specialized cells of the gastric glands into epithelium of intestinal phenotype—intestinal metaplasia—metaplastic atrophy. Therefore, the grade of gastritis is an indirect indicator of the intensity of the patient’s inflammatory response and, therefore, a high degree reflects the acceleration of the development of the carcinogenesis cascade (Correa’s cascade) from chronic inflammation to gastric cancer [84,85].

The assessment of a gastritis stage (severity of atrophy of the glands) is quite subjective. Atrophy is a concept that is not quite accurately identified for a practicing pathologist, which causes insufficient reproducibility of conclusions by different specialists [86]. An additional difficulty for the identification of atrophy is the inflammatory infiltrate, which persists even under the conditions of H. pylori eradication and spreading glands. The term “indefinite atrophy” is used to designate such a condition [87,88].

Another thing is intestinal metaplasia, a morphologically striking phenomenon, reproduced by pathologists with a high degree of agreement. The OLGIM (Operative Link on Intestinal Metaplasia Assessment) system has been developed for a predictive assessment of the risk of developing gastric cancer based on the identification of intestinal metaplasia in the biopsy specimen. If inflammation and indefinite atrophy can regress with timely and rational therapy, then intestinal metaplasia has no tendency to reverse development [89].

Intestinal metaplasia is a stigma of atrophy and is defined as the transformation of gastric glandular epithelium into intestinal epithelium. By prevalence, intestinal metaplasia is categorized as limited if the pathological process is located in one anatomical region of the stomach, or as extensive if two regions of the stomach are involved. According to the type of mucins in the lining epithelium, intestinal metaplasia is divided into complete and incomplete. Complete (type I) intestinal metaplasia is similar to the epithelium of the small intestine, and incomplete (type ΙΙ and type ΙΙΙ) intestinal metaplasia is similar to the epithelium of the large intestine (Figure 2).

Figure 2. Various types of intestinal metaplasia of the gastric mucosa. (a) complete intestinal metaplasia (type I) with a well-defined magenta stained brush border between the goblet cells stained with purple or blue. (b) incomplete intestinal metaplasia (type II) with the presence of mucus-producing epithelium between goblet cells, with the production of magenta stained neutral (in this case) or blue stained sialomucins. (c) incomplete intestinal metaplasia (type III) with production of sulfomucins by cylindrical cells brownish black stained with HID (high iron diamine) stain. (a,b)—PAS stain with alcian blue (pH = 2.5), (c)—high iron diamine with alcian blue (pH = 2.5). ×200.

Relatively recently, the corpus-predominant gastritis index has been included in the diagnostic practice. It is calculated from the totality of microscopic signs of gastritis in the Modified Sydney system. If these signs have higher gradations in the body of the stomach in comparison with the antrum, then the patient has a high risk of developing gastric cancer. The scholars believe that this indicator is more accurate than the staging of atrophy/metaplasia according to the OLGA and OLGIM systems of grading [90].

Immunohistochemical examination in the diagnosis of atrophy has a supporting role. As a rule, the phenomenon of gland decrease is well visualized during routine histopathological examination. Gastrointestinal mucins can be used to better identify the glandular structures, especially in the case of a pronounced inflammatory infiltrate, to assess the level of functional maturity of cells. Of particular importance is the identification of the transformed cell phenotype, the so-called metaplastic atrophy [18,91,92].

Distinguishing its two main types—intestinal and pseudopyloric (pyloric) metaplasia according to modern diagnostic approaches, the emphasis is shifting towards the diagnosis of SPEM (spasmolytic polypeptide-expressing metaplasia) as a special cell line associated with the risk of developing gastric adenocarcinoma rather than the ordinary intestinal metaplasia [76].

5. Conclusions

The active introduction of OLGA/OLGIM system into the clinical practice allows the assessment of an individual’s risk of developing gastric cancer in a patient with chronic gastritis. The significant problem is the decrease in the informativeness of the histopathological assessment of chronic gastritis due to fragmentation and orientation of the biopsy material, which requires the use of special approaches. An additional opportunity in the study of biopsy specimens of the gastric mucosa is the identification of signs of gastritis specific for autoimmune inflammation and H. pylori infection. Modern approaches with the use of immunohistochemical markers in the examination of biopsies of the gastric mucosa play an auxiliary role in the identification of atrophy and intestinal metaplasia, and they may be important in determining the cell phenotype in ambiguous diagnostic cases.