In most cases of acute intestinal disease, a tissue diagnosis is not needed, and intestinal biopsy is never performed. However, traditionally in patients with chronic diarrhoea a definitive diagnosis has depended on histological examination of intestinal tissue unless an infectious agent is identified. However, this procedure puts patients at risk and has limitations. Philosophically, intestinal biopsies can only be justified if the result alters treatment and/or prognosis.
Biopsy specimens are collected either endoscopically or surgically (by laparotomy or laparoscopy). The clear advantages of endoscopy to the patient and client are balanced by a number of drawbacks, and the client should always be warned that surgical biopsy might ultimately be required for definitive diagnosis.
Relative Advantages of Endoscopic and Surgical Intestinal Biopsy
Allows visualization/biopsy of focal lesions
Permits multiple biopsies
Steroids can be started early (i.e., no convalescence)
Allows biopsy of multiple sites
Permits large, full-thickness biopsies
Allows inspection of other organs
Potential for corrective surgery
Requires general anaesthesia
Requires expensive equipment
Small risk of perforation
Permits reliable access only to duodenum
Jejunum rarely accessible in cats and dogs
Distal ileum only accessible in larger patients
Small, superficial (and potentially crushed) biopsies
May miss lymphangiectasia, lymphoma
Requires general anaesthesia
Poses a surgical risk
Postsurgical risk of dehiscence
Requires delay before steroids
The duodenum and, if possible, the proximal jejunum are biopsied routinely by endoscopy, and ileal biopsies may be obtained via colonoscopy. At laparotomy, full-thickness biopsies are usually taken from at least three sites (the duodenum, the jejunum, and the ileum), as well as inspection and biopsy of extraintestinal organs. The risk of dehiscence after surgical biopsy is not insignificant, especially if the patient is malnourished and/or hypoproteinemic, or the surgeon inexperienced. Administration of plasma may reduce the cardiovascular effects of hypoproteinaemia, but the effect is only transient and really only worthwhile to provide circulatory support during the perioperative period when biopsies are being collected. Best practice is considered to be performance of endoscopic biopsy first unless there is evidence that the disease is beyond the reach of the endoscopy; the surgical option is preferred if there is any possibility of extraintestinal disease or focal intestinal pathology.
Intestinal biopsies should always be taken during endoscopy, even in the absence of gross abnormalities, because microscopic changes may be present. Multiple biopsies (six or more) should be collected, because the size of the specimens, crush artifacts, and fragmentation can make interpretation unreliable if there are too few good samples. The size and quality of endoscopic biopsies depends not just on the equipment available, but also the pressure exerted by the forceps, which is in part dependent on the operator's experience.
Although histopathological assessment of intestinal biopsies remains the gold standard for diagnosis of intestinal disease, it has marked limitations. Biopsy specimens can be normal by light microscopy, which suggests that many diseases have a functional cause (e.g., motility, biochemical), rather than a morphological abnormality. However, problems with sampling and interpretation remain even when there are clear histopathological abnormalities. Agreement between histopathologists often is poor, especially when examining endoscopic biopsies and a standardized approach is required. In the seminal study by Willard et al. (2001), some histopathologists made a diagnosis of lymphoma after assessing tissues from healthy dogs, and there was only reasonable agreement between five independent pathologists in about half of the samples examined. In response, standardized histopathological criteria have been suggested by the WSAVA GI Standardization Group as a means of improving agreement and the group has produced a standardized template so that there is consistency in descriptions. However, this publication does not provide any evidence of the relative importance of each feature, and is not a numerical scoring system as has been misinterpreted in a number of recent papers. Prospective studies looking at weighted scoring systems are required.
WSAVA GI Standardization Group members have also shown that the experience of the endoscopist and the consequent quality of the biopsy, as well as simply the number of biopsies, can influence the reliability of the histological interpretation. Fewer biopsies are needed to reliably detect architectural changes, the better the biopsy quality (i.e., greater size, depth and integrity) although more specimens are still needed the deeper the lesion. There is also emerging evidence that ileal biopsies are more likely to be helpful than duodenal. In summary, if endoscopic biopsies are collected, the clinician should always interpret the results cautiously and in light of the clinical presentation; results should be questioned if the tissue diagnosis does not fit the clinical picture or if the response to apparently appropriate therapy is poor. In some cases, repeat biopsy (i.e., by exploratory laparotomy) may be required.
Yet, even if the limitations of biopsy, especially endoscopic biopsy, and histopathology are ignored, another question remains: What is the value of a histopathological diagnosis, especially if it does not alter how the patient is treated?
Historically, inflammatory bowel disease (IBD) was defined by histological evidence of mucosal inflammation on intestinal biopsy. However, a diagnosis of 'intestinal inflammation' is of no greater value than a diagnosis of 'dermatitis' in pruritic patients; not all of them should be treated with steroids! The known, potential causes of intestinal inflammation (i.e., infection and food allergy) need to be excluded before a diagnosis of idiopathic IBD can be made. Extensive laboratory testing and imaging should therefore be undertaken in these cases. However, since no tests can absolutely rule out all the known causes of intestinal inflammation, patients need to undergo empirical treatment trials to help rule out infectious and food-related causes of enteritis. Similarly, a selamectin trial may be used to rule out a diagnosis of sarcoptic mange if skin scrapes are negative. Logically, a positive response to antiparasiticides (e.g., fenbendazole), antibiotics or exclusion diets can be considered to reflect a diagnosis of either occult parasitism, or antibiotic-responsive diarrhoea (i.e., a specific infection or the small intestinal bacterial overgrowth syndrome), or dietary sensitivity, respectively. Idiopathic IBD has then been assumed to reflect steroid-responsive intestinal inflammation assuming the case had already failed the other empirical therapeutic trials.
Whilst biopsy of solid tumours is indicated and should be diagnostic, it can be argued that biopsy evidence of intestinal inflammation does not alter what is then done, as empirical trials are still needed before a diagnosis of idiopathic IBD can be made. Similarly, small cell alimentary lymphoma of older cats may be diagnosed by endoscopic biopsy but is not always reliably differentiated from severe lymphoplasmacytic enteritis, and the prognosis for both conditions treated with prednisolone and chlorambucil is almost identical. This suggests an absolute histological diagnosis is not necessary as it does not alter treatment.
In conclusion, even if we can define histopathological evidence of intestinal inflammation in endoscopic biopsies, it cannot be used alone to make a diagnosis of IBD as there are other causes of intestinal inflammation. It is the clinician's role to identify these causes before considering immunosuppressive treatment.
1. Casamian-Sorrosal D, et al. Comparison of histopathologic findings in biopsies from the duodenum and ileum of dogs with enteropathy. Journal of Veterinary Internal Medicine. 2010;24:80.
2. Day MJ, et al. Histopathological standards for the diagnosis of gastrointestinal inflammation in endoscopic biopsy samples from the dog and cat: a report from the world small animal veterinary association gastrointestinal standardization group. Journal of Comparative Pathology. 2008;138:S1–S40.
3. Elwood C. Best practice for small intestinal biopsy. Journal of Small Animal Practice. 2005;46:315.
4. Kiselow MA, et al. Outcome of cats with low-grade lymphocytic lymphoma: 41 cases (1995–2005). Journal of the American Veterinary Medical Association. 2008;232:405.
5. Shales CJ, et al. Complications following full-thickness small intestinal biopsy in 66 dogs: a retrospective study. Journal of Small Animal Practice. 2005;46:317.
6. Willard MD, et al. Effect of sample quality on the sensitivity of endoscopic biopsy for detecting gastric and duodenal lesions in dogs and cats. Journal of Veterinary Internal Medicine. 2008;22:1084.
7. Willard MD, et al. Interobserver variation among histopathologic evaluations of intestinal tissues from dogs and cats. Journal of the American Veterinary Medical Association. 2002;220:1177.
8. Willard MD, et al. Quality of tissue specimens obtained endoscopically from the duodenum of dogs and cats. Journal of the American Veterinary Medical Association. 2001;219:474.