Ulcerative colitis is a mucosal inflammation characterized by crypt abscesses, mucosal depletion, lack of granuloma (except those related to mucin or foreign bodies), and prominent vascularity (Odze 2003). The rectum is almost always involved, with continuous disease present to variable extents proximally. Rectal urgency, tenesmus, and, occasionally, severe constipation represent the classical complaints of rectal involvement. The left-sided or extensive disease typically has chronic diarrhea with nocturnal defecation and crampy abdominal pain (Dignass et al. 2012a). Terminal ileum involvement is rare with the exception of a minor degree of inflammation associated with backwash ileitis (Odze 2003). Endoscopically, diffused pinpoint ulcers and friability are seen, and the mucosa surrounding the ulcers is usually abnormal. Frequently, bloody diarrhea and predefecation urgency are characteristic complaints (Itzkowitz 1986).

The diagnosis of Crohn’s diseases may be relatively easy when the different gastrointestinal tract areas or extraluminal complications such as strictures, abscesses, or fistula are involved. However, approximately a third of Crohn’s disease patients have a pure colonic location (Louis et al. 2001; Peyrin-Biroulet et al. 2010; Veloso et al. 1996; Freeman 2003; Nikolaus and Schreiber 2007). Crohn’s disease is typically a patchy, segmental inflammatory process that has less severe disease in the distal colon compared to the proximal colon (Odze 2003). Crohn’s disease often spares the rectum and results in a deeper, transmural disease. Submucosal granuloma formation is the hallmarks of the disease but is by no means pathognomonic. Endoscopically, aphthous ulcers with relatively normal surrounding mucosa may be seen early in the course of the disease. More severe inflammation may cause cobblestone appearance of the mucosa with longitudinal fissures , fistula formation, and strictures. Perianal disease can occur in up to 10 % of new-onset Crohn’s disease (Burisch et al. 2014; Peyrin-Biroulet et al. 2012; Bouguen et al. 2010). Bloody diarrhea is somewhat less common than in ulcerative colitis, and postprandial colicky pain is often described. If terminal ileum is involved, fever and palpable right-lower-quadrant mass may be detected (Itzkowitz 1986). Upper gastrointestinal tract involvement as well as a less pronounced degree of mucosal architectural changes, and mucin depletion, compared to ulcerative colitis can also be found (Odze 2003).

A definitive diagnosis of inflammatory bowel disease is not always straightforward. Historically, most cases of indeterminate colitis are related to fulminant colitis (i.e., severe colitis with systemic toxicity and often associated with colonic dilatation), a condition in which the classic features of ulcerative colitis or Crohn’s disease may be obscured by severe ulceration with early superficial fissuring ulceration, transmural lymphoid aggregates, and relative rectal sparing (Odze 2003). Recently, the pathologists use the term “indeterminate” colitis when a definite diagnosis cannot be established at the time of surgical sign out (Price 1978). This may be due to either insufficient data or prominent overlapping features between these two disorders (Marcello et al. 1997; Yu et al. 2000; Nicholls and Wells 1992; Farmer et al. 2000). Indeterminate colitis has been associated with worse prognosis (than ulcerative colitis) because of the higher frequency of relapses (Stewenius et al. 1996), the increased risk of colon cancer (Stewenius et al. 1995), and less favorable outcomes after ileal pouch-anal anastomosis (Tyler et al. 2013). Approximately 80 % of cases, the true nature of the patient’s underlying inflammatory bowel disease usually becomes apparent within a few years (Meucci et al. 1999).

The international guidelines have recommended that for a definitive diagnosis of inflammatory bowel disease, the pathologist requires the following: (a) a minimum set of patient’s information about clinical history and endoscopic pattern and (b) biopsy sampling and handling procedures of adequate quality in both the endoscopy room and histology laboratory (Dignass et al. 2012a, b; Magro et al. 2013; Van Assche et al. 2010; Bernstein et al. 2010; Kornbluth and Sachar 2010; Mowat et al. 2011). Recently, Canavese et al. demonstrate that the recommended guidelines for diagnosing IBD are frequently disregarded in clinical practice (Canavese et al. 2015). Three hundred forty-five cases from 13 centers were retrospectively analyzed. The diagnosis was conclusive only in 47 % of the cases. The date of onset and treatment were available for 13 % and 16 % of the cases, respectively. Endoscopy information was accessible for 77 % of the cases. Endoscopic mapping was completed in 13 % of the cases. In no cases were the biopsies oriented on acetate strips. The authors concluded that multidisciplinary education should be emphasized for making an adequate diagnosis of inflammatory bowel disease and managing the condition.

Biomarkers may be helpful in classifying ulcerative colitis and Crohn’s disease. Anti-neutrophil cytoplasmic antibodies (ANCA) and anti-saccharomyces cerevisiae (ASCA) have been widely used; for instance, ANCA are detected in the serum of 60–70 % of ulcerative colitis patients, but in only 10–40 % of Crohn’s disease patients. ASCA are present in 50–60 % of Crohn’s disease patients and has a sensitivity of 67 % and a specificity of 92 % as a serum marker for Crohn’s disease. Interestingly, of the Crohn’s disease patients who are ANCA positive, most have left-sided colitis with clinical, endoscopic, and/or histologic features of ulcerative colitis. Furthermore, biomarkers is also very helpful in the prediction of further development of ulcerative colitis and Crohn’s disease in unclassified patients, determination of disease activity, risk stratification, and prediction of response to therapy (Bouguen et al. 2015; Lewis 2011; Iskandar and Ciorba 2012).