Guidance on the Effective Use of Upper GI Histopathology
Guidance on the Effective Use of Upper GI Histopathology
Any suspicious mass, ulcer or mucosal irregularity should be extensively sampled to evaluate for neoplasia (figure 2). The diffuse (signet ring or poorly cohesive) type of gastric adenocarcinoma may present without any mucosal abnormality and cause great diagnostic difficulty. Poor gastric distension on insufflation, in addition to systemic features of malignancy, may be the only diagnostic clues. This finding alone should trigger a careful search for minor mucosal changes and multiple biopsies. Poor gastric preparation for endoscopy may also hinder detection of a subtle mucosal abnormality.
(Enlarge Image)
Figure 2.
Endoscopy (upper) of a gastric ulcer in the upper body. Histology (lower) shows inflamed and ulcerated gastric mucosa, with a discohesive population of malignant cells lying within ulcer slough (inset, high power), indicating diffuse type adenocarcinoma manifesting as a malignant ulcer.
Underestimation of the significance of a lesion is a recognised risk of forceps biopsy, in comparison with the more substantial specimen provided by endoscopic resection. Another issue is the possibility of multiple deep forceps biopsies creating submucosal fibrosis, potentially creating a false non-lifting signing if subsequently endoscopic mucosal resection is being considered. This problem has also been reported in the colon. Despite these potential problems, on balance, when a gastric ulcer or suspected malignancy is noted, it is recommended that at least eight biopsies should be taken to minimise the risk of a false negative diagnosis on the basis of undersampling. Gastric ulcers require endoscopic follow-up with repeat biopsy until healing is confirmed, to avoid missing malignancy, a well recognised problem with upper gastrointestinal endoscopy, mainly related to missed gastric cancer.
The management of gastric polyps has been the subject of recent BSG guidelines. These recommend sampling of all gastric polyps detected at endoscopy with additional sampling of intervening non-polypoid mucosa except those clinically suspected to be fundic gland polyps (figure 3), which are by far the most common gastric polyps encountered currently, other types being collectively rare by comparison. If the endoscopist is confident that all polyps evident are typical fundic gland polyps, biopsy confirmation is not necessary. It is recommended that gastric polyps >1 cm in diameter, those <1 cm with biopsy proven dysplasia and those causing symptoms, should be removed completely. However, whether to monitor and biopsy or completely remove hyperplastic polyps is contentious, balancing the risks of developing neoplasia versus those of the polypectomy procedure, and practice varies widely. In the setting of multiple, small (<1 cm) hyperplastic polyps, it is reasonable to biopsy and offer surveillance endoscopy, although American Society for Gastrointestinal Endoscopy guidelines suggest multiple non-adenomatous polyps do not require surveillance if adequate sampling is done at initial endoscopy. If histology of a polyp reveals an adenoma, complete endoscopic removal should be confirmed given the significant risk of progression to cancer, and the adjacent and surrounding mucosa extensively sampled to look for background chronic atrophic gastritis, intestinal metaplasia and 'flat' dysplasia. Further surveillance in a year is indicated.
(Enlarge Image)
Figure 3.
Endoscopy (upper) of multiple fundic gland polyps involving the gastric body. Histology (lower) shows characteristic cystic dilatation of specialised fundic glands.
Guidelines on the management of neuroendocrine tumours (NETs), including those of the stomach, have also been published recently and endorsed by the BSG. Briefly, gastric NETs now have a well established classification based on pathogenesis. Types I and II are associated with hypergastrinaemia, secondary to chronic atrophic gastritis in type I and primary in type II. Type III gastric NETs are sporadic and have normal serum gastrin levels. Types I and II essentially behave in a benign fashion and can be managed conservatively. Type III gastric NETs are aggressive tumours which require surgical resection. Given differing management strategies, accurate classification of type is important. Background mucosal biopsies taken at initial endoscopy or follow-up and submitted separately to any polyps will be helpful to look for features of chronic atrophic gastritis, helping classify as above alongside serum gastrin levels.
The relevance of endoscopic gastritis and whether random biopsies of the normal stomach are justified are both controversial topics. Endoscopic appearances of gastritis do not correlate with symptoms. One study found equivalent rates of endoscopic gastritis and atrophic gastritis in healthy volunteers and patients with dyspepsia. Many publications recommend gastric biopsy to characterise gastritis and exclude precancerous conditions which cannot be distinguished endoscopically, with at least four biopsies covering proximal and distal stomach on greater and lesser curvatures. The justification is that a finding of extensive atrophy or intestinal metaplasia is a risk factor for gastric adenocarcinoma and could merit surveillance. However those authors acknowledge that the cost-effectiveness of this approach has not been demonstrated. By contrast, The Royal College of Pathologists document, 'Histopathology and cytopathology of limited or no clinical value', suggests that there is no support for biopsy of the normal stomach and that biopsy for histological categorisation of gastritis is unlikely to change management. That document emphasises the importance of agreeing a local policy. Our view is that in the absence of high-risk factors such as family history, it is not necessary to biopsy for histological assessment a stomach endoscopically showing no abnormality or only gastritis, as we can find no evidence that such biopsies influence management.
Helicobacter Pylori. Helicobacter pylori status should be checked by urease test in the presence of visible gastroduodenal inflammation (and treated if present). A urease test is significantly cheaper than histological assessment and provides a result before the patient leaves the endoscopy unit. Non-invasive tests such as the urea breath test and faecal antigen sampling avoid the need for endoscopy solely to assess H pylori status. Resistant infection may require endoscopy and biopsy sent to microbiology for culture and sensitivities. For these reasons, gastric biopsy taken only to look for H pylori histologically is not recommended.
Stomach
Ulcer or Malignancy
Any suspicious mass, ulcer or mucosal irregularity should be extensively sampled to evaluate for neoplasia (figure 2). The diffuse (signet ring or poorly cohesive) type of gastric adenocarcinoma may present without any mucosal abnormality and cause great diagnostic difficulty. Poor gastric distension on insufflation, in addition to systemic features of malignancy, may be the only diagnostic clues. This finding alone should trigger a careful search for minor mucosal changes and multiple biopsies. Poor gastric preparation for endoscopy may also hinder detection of a subtle mucosal abnormality.
(Enlarge Image)
Figure 2.
Endoscopy (upper) of a gastric ulcer in the upper body. Histology (lower) shows inflamed and ulcerated gastric mucosa, with a discohesive population of malignant cells lying within ulcer slough (inset, high power), indicating diffuse type adenocarcinoma manifesting as a malignant ulcer.
Underestimation of the significance of a lesion is a recognised risk of forceps biopsy, in comparison with the more substantial specimen provided by endoscopic resection. Another issue is the possibility of multiple deep forceps biopsies creating submucosal fibrosis, potentially creating a false non-lifting signing if subsequently endoscopic mucosal resection is being considered. This problem has also been reported in the colon. Despite these potential problems, on balance, when a gastric ulcer or suspected malignancy is noted, it is recommended that at least eight biopsies should be taken to minimise the risk of a false negative diagnosis on the basis of undersampling. Gastric ulcers require endoscopic follow-up with repeat biopsy until healing is confirmed, to avoid missing malignancy, a well recognised problem with upper gastrointestinal endoscopy, mainly related to missed gastric cancer.
Gastric Polyps
The management of gastric polyps has been the subject of recent BSG guidelines. These recommend sampling of all gastric polyps detected at endoscopy with additional sampling of intervening non-polypoid mucosa except those clinically suspected to be fundic gland polyps (figure 3), which are by far the most common gastric polyps encountered currently, other types being collectively rare by comparison. If the endoscopist is confident that all polyps evident are typical fundic gland polyps, biopsy confirmation is not necessary. It is recommended that gastric polyps >1 cm in diameter, those <1 cm with biopsy proven dysplasia and those causing symptoms, should be removed completely. However, whether to monitor and biopsy or completely remove hyperplastic polyps is contentious, balancing the risks of developing neoplasia versus those of the polypectomy procedure, and practice varies widely. In the setting of multiple, small (<1 cm) hyperplastic polyps, it is reasonable to biopsy and offer surveillance endoscopy, although American Society for Gastrointestinal Endoscopy guidelines suggest multiple non-adenomatous polyps do not require surveillance if adequate sampling is done at initial endoscopy. If histology of a polyp reveals an adenoma, complete endoscopic removal should be confirmed given the significant risk of progression to cancer, and the adjacent and surrounding mucosa extensively sampled to look for background chronic atrophic gastritis, intestinal metaplasia and 'flat' dysplasia. Further surveillance in a year is indicated.
(Enlarge Image)
Figure 3.
Endoscopy (upper) of multiple fundic gland polyps involving the gastric body. Histology (lower) shows characteristic cystic dilatation of specialised fundic glands.
Guidelines on the management of neuroendocrine tumours (NETs), including those of the stomach, have also been published recently and endorsed by the BSG. Briefly, gastric NETs now have a well established classification based on pathogenesis. Types I and II are associated with hypergastrinaemia, secondary to chronic atrophic gastritis in type I and primary in type II. Type III gastric NETs are sporadic and have normal serum gastrin levels. Types I and II essentially behave in a benign fashion and can be managed conservatively. Type III gastric NETs are aggressive tumours which require surgical resection. Given differing management strategies, accurate classification of type is important. Background mucosal biopsies taken at initial endoscopy or follow-up and submitted separately to any polyps will be helpful to look for features of chronic atrophic gastritis, helping classify as above alongside serum gastrin levels.
Gastritis
The relevance of endoscopic gastritis and whether random biopsies of the normal stomach are justified are both controversial topics. Endoscopic appearances of gastritis do not correlate with symptoms. One study found equivalent rates of endoscopic gastritis and atrophic gastritis in healthy volunteers and patients with dyspepsia. Many publications recommend gastric biopsy to characterise gastritis and exclude precancerous conditions which cannot be distinguished endoscopically, with at least four biopsies covering proximal and distal stomach on greater and lesser curvatures. The justification is that a finding of extensive atrophy or intestinal metaplasia is a risk factor for gastric adenocarcinoma and could merit surveillance. However those authors acknowledge that the cost-effectiveness of this approach has not been demonstrated. By contrast, The Royal College of Pathologists document, 'Histopathology and cytopathology of limited or no clinical value', suggests that there is no support for biopsy of the normal stomach and that biopsy for histological categorisation of gastritis is unlikely to change management. That document emphasises the importance of agreeing a local policy. Our view is that in the absence of high-risk factors such as family history, it is not necessary to biopsy for histological assessment a stomach endoscopically showing no abnormality or only gastritis, as we can find no evidence that such biopsies influence management.
Helicobacter Pylori. Helicobacter pylori status should be checked by urease test in the presence of visible gastroduodenal inflammation (and treated if present). A urease test is significantly cheaper than histological assessment and provides a result before the patient leaves the endoscopy unit. Non-invasive tests such as the urea breath test and faecal antigen sampling avoid the need for endoscopy solely to assess H pylori status. Resistant infection may require endoscopy and biopsy sent to microbiology for culture and sensitivities. For these reasons, gastric biopsy taken only to look for H pylori histologically is not recommended.