This article discusses the indications for gastrointestinal biopsies, how WSAVA guidelines can support proper collection and submission, and how to set realistic expectations for biopsy interpretation—particularly when distinguishing between chronic inflammation and lymphoma.

When and Why GI Endoscopic Biopsies Are Indicated

GI endoscopic biopsies are most indicated in dogs and cats with chronic gastrointestinal signs that have persisted for more than three weeks, particularly when signs are progressive, severe, or haven’t improved with reasonable initial treatments. Typical presentations include chronic vomiting, chronic diarrhea, unexplained weight loss, hyporexia, and lab abnormalities, such as hypoalbuminemia or panhypoproteinemia consistent with protein-losing enteropathy (PLE).

Both WSAVA and the American College of Veterinary Internal Medicine (ACVIM) emphasize that biopsies should not be the initial diagnostic tool. Instead, they are most useful after non-invasive tests, such as fecal analysis, blood tests, imaging, dietary trials, and parasite therapeutic management, have been performed. Experts similarly suggest that biopsies should be performed only when there is a specific clinical question whose answer would change the direction of the treatment plan, such as distinguishing between inflammatory disease and cancer. This is an important conversation to have with pet owners before any biopsy procedure.

Defining Biopsy Sites

The WSAVA GI Standardization Guidelines highlight that clearly labeling each biopsy site is essential for accurate histopathology. For diagnosis, a biopsy “site” refers to a specific anatomic area with characteristic histological features. In general practice, GI biopsies should be submitted as separate sites, each labeled accordingly:

• Stomach - antrum

• Stomach - pylorus

• Small intestine - duodenum

• Small intestine - jejunum

• Small intestine - ileum

• Large intestine - cecum

• Large intestine - colon

Combining samples from multiple regions into a single container or using nonspecific terms such as “small intestine” may hinder the pathologist’s ability to apply WSAVA grading criteria and to identify region-specific disease patterns. In addition, site mislabeling is a common, yet avoidable error in biopsy collection.

This distinction is especially significant in cats, as ileal disease can exist even when duodenal samples don’t show abnormalities—particularly in cases of small cell lymphoma or chronic lymphocytic enteropathy. Submitting samples separately from each site enables regional comparisons and enhances diagnostic accuracy. This can also be a deciding factor when choosing between endoscopic and surgical biopsy.

Managing Expectations: Chronic Inflammation vs. Lymphoma

Differentiating severe chronic inflammation from early or low-grade lymphoma remains one of the most challenging aspects of gastrointestinal biopsy interpretation. WSAVA guidelines acknowledge that histopathology alone may be insufficient in some cases due to overlapping morphologic features, including dense lymphocytic infiltration, architectural distortion, and epithelial changes.

One point of significance is the method of biopsy acquisition. Endoscopic samples are naturally less invasive because they only collect tissue from the mucosal layer of the GI tract. However, they are also limited in that they can miss disease deeper in the submucosal or muscular layers of the GI wall. This means that ultrasound and other imaging prior to sampling is especially valuable, helping to identify patients who have disease in locations outside of endoscopic reach or have visible changes in the deeper layers of the intestinal tract.

It’s also important to set realistic expectations before submitting biopsies. A diagnosis of “chronic enteropathy” or “lymphoplasmacytic inflammation” does not rule out lymphoma and may still warrant additional testing, depending on the case. Molecular tests, such as immunohistochemistry (IHC) and PCR for antigen receptor rearrangements (PARR), can enhance diagnostic confidence, but the results must be interpreted alongside histologic findings and clinical data, as false positives and indeterminate results can occur.

Optimizing Sample Collection and Handling

The WSAVA GI Standardization Group recommends collecting a minimum of six to eight high-quality biopsies per site during endoscopy, as gastrointestinal lesions are often focal or patchy. Biopsy quality is often more important than quantity, particularly when orientation and fixation are suboptimal.

Proper orientation is critical, but sample size is most important. Larger biopsy samples are much easier for laboratory teams to orient, especially because pathologists rely on the assumption that the material being evaluated for review represents the full spectrum of disease for the patient. Poorly oriented samples may preclude meaningful WSAVA scoring and result in non-diagnostic reports.

Samples should be promptly fixed in 10% neutral buffered formalin using an adequate volume (approximately 10:1 formalin to tissue). Excessive manipulation, crushing, or stretching should be avoided, as artifacts can obscure pathologic changes.

Submitting a succinct yet thorough clinical history is equally essential. WSAVA guidelines emphasize that signalment, duration and severity of signs, lab results, imaging findings, prior treatments, and specific diagnostic questions all improve how pathologists interpret biopsies and help guide decisions about additional testing.

Diagnostic Collaboration Improves Outcomes

Submitting GI biopsies carefully and following WSAVA guidelines makes it easier to differentiate inflammation from neoplasia. Clear site labeling, good sample quality, proper handling, and strong veterinarian-pathologist communication all help reduce ambiguous findings and increase confidence in the diagnosis.

This collaborative approach allows for more targeted therapy, more accurate prognostic guidance, and improved long-term management for patients with chronic or complex gastrointestinal disease.

Gastrointestinal biopsies remain a powerful diagnostic tool in small animal practice, but their value depends on how effectively they are used. Applying the WSAVA GI Standardization Guidelines enhances diagnostic accuracy and interpretive clarity. When paired with appropriate pre- and post-biopsy testing and open collaboration with diagnostic pathologists, a clear and complete GI biopsy submission improves patient outcomes in challenging gastrointestinal cases.