Diagnosing Helicobacter Infection in Gastric Biopsy Specimens
Diagnosing Helicobacter Infection in Gastric Biopsy Specimens
Gastric biopsies to rule out HP gastritis are commonly encountered in the practice of gastrointestinal pathology, and the accurate diagnosis of HP infection is important because of the association of longstanding infection with the development of neoplasia and the fact that infected patients can be treated with combination therapy including proton pump inhibitors and antibiotics. While many staining modalities can be used to identify HP in gastric biopsy specimens, our local practice experience and several studies have suggested that routine H&E staining is typically sufficient for identification of the organism, in contrast with the practice advocated by some for routine ancillary staining for all gastric biopsy specimens. H&E staining can vary between laboratories, however, and it is prudent for an individual laboratory to evaluate the ability of its H&E stain to detect HP on positive cases by using special stains.
Our findings indicate that routine ancillary staining of all gastric biopsy specimens for HP is not indicated in our practice. In contrast, immunostaining of cases with moderate or severe chronic gastritis is sufficient to diagnose nearly all cases of HP gastritis when the organisms cannot be seen on routine H&E stain, particularly when the gastric antrum has been sampled. It is interesting that 3 cases of HP gastritis were diagnosed on biopsy specimens containing only oxyntic mucosa. Two of these contained moderate gastritis, and the third was the only case in which HP was found in combination with mild gastritis, indicating that the organism should also be actively sought in this location. Furthermore, our findings suggest that a clinical suspicion of HP gastritis (as indicated by the surrogate finding of a clinical mandate to rule out Helicobacter on the requisition) should have essentially no role in the pathologic suspicion of HP infection. Rather, the presence of the characteristic gastritis of at least moderate severity should prompt a careful search for organisms and, when they cannot be found on H&E preparations, an order for HP immunostaining accompanied by a high pretest probability of infection. As a corollary, when at least moderate gastritis is found and no HP organisms can be found with the H&E stain, a careful search for organisms with an immunohistochemical stain is warranted to avoid overlooking subtle and/or scant positivity. Finally, the finding of 1 case in our series in which an initial HP immunostain was negative but a subsequent stain revealed scattered organisms suggests that when the index of suspicion is high based on the presence of at least moderate gastritis, repeating a negative stain may be prudent. In fact, the presence of the characteristic HP-type gastritis of at least moderate intensity may be sufficient to suggest the presence of the organism with high specificity (98% in our series), and a diagnosis of "H pylori–type gastritis" could potentially be sufficient for clinical treatment to be initiated.
Our findings confirm the assertion by other observers that H&E-stained sections are typically sufficient for diagnosis of HP gastritis. A recent study suggested that pathologists' ability to identify these distinct microorganisms was good no matter their training level. In addition, nonimmunohistochemical methods of HP detection are less reliable than the immunohistochemical stain and will not allow dependable identification of subtle cases. Because they are not organism-specific, such cytochemical stains also highlight any bacteria in the surface mucus, meaning that the characteristic HP morphologic picture still needs to be carefully sought to avoid overdiagnosis. In contrast, the specificity of the immunostain is near 100%. Thus, routine performance of Giemsa or Warthin-Starry staining, while less costly than immunohistochemical analysis, is not warranted either.
Our findings should be viewed in the light of the retrospective nature of the first part of the study, a relatively low disease prevalence in our local population, and the sample size. The overall rate of HP infection in our patient population was 8.4% (28 unique cases in 335 unique patients) during the 4-week period studied. Because all gastric biopsy specimens obtained at our institution are examined in 1 "center of excellence," this seems to be a true representation of the infection rate in patients biopsied endoscopically for our population, but it is lower than a recent report from the United States. Nevertheless, we believe the relative sensitivity and specificity values to be a valid reflection of the usefulness of the methods of organism identification. Whether it may be sufficient to report Helicobacter pylori–type gastritis when at least moderate chronic gastritis is present, as suggested, will likely require additional study with a larger number of HP-positive cases.
A clinical request to rule out Helicobacter is not sensitive or specific for HP gastritis. Our institutional experience with regard to the use of ancillary stains in the evaluation of HP gastritis was validated. In addition, the presence of a moderate or severe gastritis is highly suggestive of HP gastritis, and these findings should be communicated in the pathology report.
Discussion
Gastric biopsies to rule out HP gastritis are commonly encountered in the practice of gastrointestinal pathology, and the accurate diagnosis of HP infection is important because of the association of longstanding infection with the development of neoplasia and the fact that infected patients can be treated with combination therapy including proton pump inhibitors and antibiotics. While many staining modalities can be used to identify HP in gastric biopsy specimens, our local practice experience and several studies have suggested that routine H&E staining is typically sufficient for identification of the organism, in contrast with the practice advocated by some for routine ancillary staining for all gastric biopsy specimens. H&E staining can vary between laboratories, however, and it is prudent for an individual laboratory to evaluate the ability of its H&E stain to detect HP on positive cases by using special stains.
Our findings indicate that routine ancillary staining of all gastric biopsy specimens for HP is not indicated in our practice. In contrast, immunostaining of cases with moderate or severe chronic gastritis is sufficient to diagnose nearly all cases of HP gastritis when the organisms cannot be seen on routine H&E stain, particularly when the gastric antrum has been sampled. It is interesting that 3 cases of HP gastritis were diagnosed on biopsy specimens containing only oxyntic mucosa. Two of these contained moderate gastritis, and the third was the only case in which HP was found in combination with mild gastritis, indicating that the organism should also be actively sought in this location. Furthermore, our findings suggest that a clinical suspicion of HP gastritis (as indicated by the surrogate finding of a clinical mandate to rule out Helicobacter on the requisition) should have essentially no role in the pathologic suspicion of HP infection. Rather, the presence of the characteristic gastritis of at least moderate severity should prompt a careful search for organisms and, when they cannot be found on H&E preparations, an order for HP immunostaining accompanied by a high pretest probability of infection. As a corollary, when at least moderate gastritis is found and no HP organisms can be found with the H&E stain, a careful search for organisms with an immunohistochemical stain is warranted to avoid overlooking subtle and/or scant positivity. Finally, the finding of 1 case in our series in which an initial HP immunostain was negative but a subsequent stain revealed scattered organisms suggests that when the index of suspicion is high based on the presence of at least moderate gastritis, repeating a negative stain may be prudent. In fact, the presence of the characteristic HP-type gastritis of at least moderate intensity may be sufficient to suggest the presence of the organism with high specificity (98% in our series), and a diagnosis of "H pylori–type gastritis" could potentially be sufficient for clinical treatment to be initiated.
Our findings confirm the assertion by other observers that H&E-stained sections are typically sufficient for diagnosis of HP gastritis. A recent study suggested that pathologists' ability to identify these distinct microorganisms was good no matter their training level. In addition, nonimmunohistochemical methods of HP detection are less reliable than the immunohistochemical stain and will not allow dependable identification of subtle cases. Because they are not organism-specific, such cytochemical stains also highlight any bacteria in the surface mucus, meaning that the characteristic HP morphologic picture still needs to be carefully sought to avoid overdiagnosis. In contrast, the specificity of the immunostain is near 100%. Thus, routine performance of Giemsa or Warthin-Starry staining, while less costly than immunohistochemical analysis, is not warranted either.
Our findings should be viewed in the light of the retrospective nature of the first part of the study, a relatively low disease prevalence in our local population, and the sample size. The overall rate of HP infection in our patient population was 8.4% (28 unique cases in 335 unique patients) during the 4-week period studied. Because all gastric biopsy specimens obtained at our institution are examined in 1 "center of excellence," this seems to be a true representation of the infection rate in patients biopsied endoscopically for our population, but it is lower than a recent report from the United States. Nevertheless, we believe the relative sensitivity and specificity values to be a valid reflection of the usefulness of the methods of organism identification. Whether it may be sufficient to report Helicobacter pylori–type gastritis when at least moderate chronic gastritis is present, as suggested, will likely require additional study with a larger number of HP-positive cases.
A clinical request to rule out Helicobacter is not sensitive or specific for HP gastritis. Our institutional experience with regard to the use of ancillary stains in the evaluation of HP gastritis was validated. In addition, the presence of a moderate or severe gastritis is highly suggestive of HP gastritis, and these findings should be communicated in the pathology report.
