The Role of Histopathology in IBD

Idiopathic inflammatory bowel disease (IBD) is a common, disabling chronic condition that affects about 7,000,000 people worldwide – and that number is only increasing (1). Classified into ulcerative colitis (UC) and Crohn’s disease, IBD presents with symptoms including rectal bleeding, abdominal pain, and diarrhea and has many long-term complications, including intestinal strictures and colorectal cancer.

Fortunately, medical therapy for IBD improves continually. However, confident diagnosis and classification of IBD – and exclusion of its mimics – is not always easy. The diagnostic process is multidisciplinary and there is no single specific test. Clinical assessment, imaging, blood tests, and endoscopy all play an important role – but robust histopathology support is essential.

Full ileocolonoscopy is now standard practice for the investigation of suspected new IBD, allowing endoscopists to take biopsies of multiple sites from the ileum to the rectum. The pathologist can then assess the histological appearance at each site, determine the anatomical and intra-site distribution of any abnormalities, and compare the findings with the endoscopic observations. This helps to confirm, refute, or refine the diagnosis at presentation. Biopsy assessment is also important for follow-up after therapy (see Table 1).

There are specific pathological changes in a biopsy that can support a diagnosis of IBD, such as architectural distortion of the mucosa and chronic inflammation (in the form of basal plasmacytosis). There are also features that help distinguish UC from Crohn’s disease; for instance, granulomas (strongly favoring Crohn’s disease) and the anatomical distribution of changes (typically continuous in UC and discontinuous in Crohn’s disease). In addition, histology helps to diagnose or exclude the many clinical mimics of IBD, such as diverticular colitis, tuberculosis, amoebiasis, other chronic infections, ischemia, radiation damage, and drug-induced colitis (2, 3, 4). Colitis as a result of the relatively new immune checkpoint inhibitor antineoplastic drugs can be a very close mimic, as can diverticular colitis.

IBD that is difficult to classify may be labelled “IBD unclassified (IBDU)” in biopsies or “indeterminate colitis” in resections. High-quality pathology helps to reduce the size of these categories, allowing better tailoring of management to the individual patient.

IBD patients have a high risk of dysplasia and malignancy compared with the general population, particularly when the disease is longstanding (5–7). Endoscopically, dysplasia can form an obvious mass or polyp – or it may be flat and difficult to detect. The endoscopist may suspect dysplasia, especially with the assistance of new methods such as dye sprays for highlighting abnormal mucosa. However, no investigation other than histology can reliably diagnose or grade dysplasia. Diagnosis, grading, and assessment of the extent of dysplasia play a major role in determining follow-up – whether observation, local excision, or more radical surgery. Furthermore, the histological classification of IBD-associated dysplasia and its contribution to prognosis is a continually evolving area of knowledge (8). Confirmation of a suspected diagnosis of colorectal carcinoma, small bowel carcinoma, or other type of tumor also requires pathology (9).

Additionally, longstanding IBD and medical therapy increase the risk of some infections. Corticosteroids increase the risk of intestinal cytomegalovirus (CMV) infection, which has the potential to worsen clinical outcomes (10). Diagnosis of CMV relies on several tests, including histopathology.  

Resection of part of the bowel may be necessary for several reasons, including IBD that is refractory to medical therapy, severe fulminant IBD, a stricture, or IBD-related neoplasia. Pathological assessment helps to confirm or refine an existing diagnosis of UC or Crohn’s disease and exclude neoplasia. Specifically, it often helps surgeons decide whether ileal pouch anal anastomosis (IPAA) is appropriate after colectomy, because this procedure is a satisfactory solution for UC, but is contraindicated for Crohn’s disease, in which there is a high risk of pouch breakdown. Therefore, histological confirmation of UC is important prior to IPAA.

There is considerable current interest in the ability of histological abnormalities to predict the clinical course of IBD after drug therapy. Assessing histological activity and histological remission (“histological healing”) complements the assessment of endoscopic and clinical activity in this setting and histological remission is an accurate predictor of a good outcome (though often difficult to achieve in practice). However, the best way to record histological remission or activity in this context is the subject of much discussion. Histological scoring systems exist, some of which – like the Nancy histology index – are relatively simple and others – such as the Geboes score or the Robarts histopathology index – are more complex (11, 12, 13). Publications with titles such as “Histological remission: under the microscope is the cure” (14) exemplify the enthusiasm some clinicians and researchers have for histology. Furthermore, histology may play an important role in the assessment of the effects of new antifibrotic drugs on strictures in Crohn’s disease.

A final consideration is that a good working relationship between clinical teams and pathologists greatly enhances the quality of IBD care. Feedback occurs in both directions, enhancing knowledge, and multidisciplinary meetings are usually rewarding. Unfortunately, clinical teams, pathologists, and managers often perceive IBD clinicopathological meetings as a waste of time if there are more pressing priorities.

In the UK’s National Health Service, histopathology departments, gastroenterology services, and endoscopy units are often understaffed. When a histopathology service is under pressure, outsourcing of biopsies and even resections to offsite laboratories may be a temporary (or longer-term) solution. This process often disproportionately affects gastrointestinal pathology; third-party reporting services may have little opportunity to liaise with clinical colleagues and may have less specialization and experience in IBD diagnosis. As a result, several recent consensus papers have explored the best ways to improve all aspects of IBD care (15, 16, 17).

To optimize their contribution to IBD services, histopathology departments need adequate space and equipment, high-quality staff, and robust funding. Comprehensive training of pathologists and technical staff is also a factor. Above all, there should be enough time for thoughtful and meaningful interpretation of histological samples and for productive communication between pathologists and clinicians. Those responsible for improving IBD services locally and nationally will reap many rewards from a decision to maintain high-quality pathology input as part of the process.