Introduction
Ulcerative colitis (UC) is an idiopathic (with an unknown cause) inflammatory disease affecting the large intestine (colon and rectum). It is a chronic (long-term) disease primarily involving adults aged 30 to 40. It comprises relapsing and remitting mucosal inflammation. As a result, it leads to diffuse friability, superficial mucosal (mucosa is the membrane lining various organs), erosions on the colon wall, and bleeding. Therefore, UC presents with chronic bloody diarrhea. It is the most prevalent inflammatory bowel disease (IBD) worldwide. The treatment aim is to resolve symptoms and maintain disease remission (reduction or disappearance of disease).
The pathology of ulcerative colitis is essential for a specific diagnosis, determining the disease activity, and evaluating healing and risk of relapse. Further, it is critical in assessing treatment response and diagnosing long-standing UC complications.
What Is the Pathophysiology of Ulcerative Colitis?
To understand the pathology of UC, one must have a thorough knowledge of the structure of the large intestine. The colon mucosa is lined by a single cell layer with a brush border that maintains gut balance and functions as an immune defense between bacteria and immune cells. The correct activity of the intestinal cells is essential, as their dysfunction plays a central role in UC pathology. A frequent microscopic pattern in UC is the architectural distortion of the intestinal epithelium. The intestinal cell layer has invaginations known as ‘Crypts of Lieberkühn.’ UC leads to the shortening and reduced branching of the crypts. Paneth cells are specialized secretory cells (secrete intestinal juices) found in the crypts. Long-standing UC leads to Paneth cell metaplasia (transformation of cells). These changes can be detected microscopically in every removed fragment of the diseased colon.
What Are the Pathological Features of Ulcerative Colitis?
The pathology of UC can be divided into macroscopic (gross) and microscopic features.
-
Macroscopic Features: UC consists of diffuse (continuous and symmetrical) inflammation in the colon mucosa. The resected specimen is granular, edematous (swollen), and reddish (with or without ulceration). These mucosal changes involve the rectum and various parts of the colon. The bowel wall maintains its thickness, denoting the absence of transmural (occurring across the entire colon wall) inflammation. Long-standing and severe cases have a typical ‘cobblestone' appearance. Mucosal growths may also be seen in long-standing UC.
-
Microscopic Features: UC exhibits a pattern of chronic colitis, which refers to the infiltration of inflammatory cells and mucosal injury. Various immune cells involved in UC are neutrophils (released immediately), lymphocytes, and plasma cells. Active inflammation involves neutrophil-mediated mucosal injury. It can happen through neutrophils infiltrating the crypts (cryptitis), collections of neutrophils within crypt cavities (crypt abscesses), or infiltration of surface mucosa (ulceration).
Lymphocytes and plasma cells characterize chronic inflammation (non-active) in UC. Chronic inflammation ensues with architectural mucosal distortion, lymphocyte and plasma cell ingression, and cell metaplasia in the colon. Architectural distortion is represented by crypt shortening. While Paneth cells are a component of the right colon, their presence in the left colon is due to chronic crypt injury, leading to metaplasia. Microscopically, these changes in chronic UC are diffuse and uniform in distribution. In longstanding UC, there is extensive crypt distortion and increased immune cell infiltration.
What Is the Importance of Pathology of Ulcerative Colitis?
The severity of UC is determined based on signs, symptoms, and laboratory tests. The pathological severity assessment is done by pathologists. Pathological quantification of the degree of inflammation is a rough estimate due to limited sampling and can lack reproducibility. Still, it is useful, as chronic inflammation is a risk factor for colorectal cancer (CRC). Further, patients with chronic UC are at an increased risk for developing CRC. The established risk factors include prolonged disease duration, extensive colonic involvement, family history of CRC, and young age. Mucosal dysplasia (abnormal cell changes) is the most reliable marker of an increased risk of CRC in UC patients.
Dysplasia should be differentiated into low (LGD) and high degrees (HGD). In LGD, crypt architecture shows minimal distortion. On the other hand, HGD shows greater architectural complexity. Dysplasia related to UC develops in chronic inflammation areas. Also, dysplasia and cancerous lesions in UC can be flat and ill-defined. The criteria for pathological assessment of inflammation are based on the standardized histological activity index (HAI). The degree of inflammation is given as (0) inactive/absent, (1) mild, (2) moderate, or (3) severe. The mild UC cases show lymphocytes and plasma cells, infiltration of surface/C=crypts by neutrophils, and crypt abscesses (in less than 50 percent of the crypts). In moderate UC cases, cryptitis and crypt abscesses involve more than 50 percent of crypts. Finally, severe UC cases have erosions or ulcerations.
How Does Pathology Help in Ulcerative Colitis Disease Activity?
Assessment of UC disease activity is essential for developing adequate treatment responses in patients. Disease activity and treatment response can be assessed using biomarkers, endoscopy, and histology (microscopy). At present, clinical decision-making is based on clinical and endoscopic approaches. Recent studies suggest histology is an important prognostic factor and a treatment target in UC patients. Epithelial damage with neutrophils and plasma cell infiltration is suggested as markers of disease activity and relapse prediction. A recent study revealed that histological remission had lower clinical relapse rates than those with histological activity. Histological remission was also a superior predictor of clinical relapse compared with endoscopic and clinical remission. Furthermore, mucosal inflammation during follow-up in UC patients had a greater risk of CRC cancer than in those with mucosal healing. As a result, regular colonoscopic surveillance examinations with biopsies can identify dysplasia (precursor of CRC).
With medical treatment or spontaneous healing, UC may become inactive. Histologically, inactive colitis has marked architectural abnormalities without active inflammation. Mucosal healing is characterized by the resolution of crypt architecture and inflammatory cell infiltration. However, the mucosa can still show some damage, such as decreased crypt density with branching and shortening of crypts. The most common abnormalities are atrophy, irregularity of the crypts, thickening of the muscle layer, and metaplasia.
Conclusion
Ulcerative colitis is a complex disease requiring a multidisciplinary approach. Pathological evaluation and resected intestinal specimens play a vital role in the management of ulcerative colitis patients. Despite the evolution of advanced endoscopic procedures, recent studies confirm the value of pathology in predicting clinical outcomes. Further, pathological interpretation of surveillance biopsies in ulcerative colitis also plays a role in clinical management.
