The clinical history provided by the clinicians is of utmost importance to the histopathologist. It is particularly relevant in gastrointestinal pathology when assessing biopsies suspected of IBD. Due to the very many mimics of IBD, we regard IBD as strictly a clin-icopathological diagnosis in which the clinician and the pathologist must shoulder the responsibility in the right cooperative environment. A great improvement in the diagnosis can be achieved by a positive interaction between the pathologist and the gastroenterologist. In addition, multiple colonic biopsies have been shown by many studies to be far superior in arriving at a diagnosis than a single biopsy. It is imperative to emphasise again that the final diagnosis usually depends on the collaboration of all data including pathologic, radiologic, clinical features and endoscopic .
Several studies have shown that the histological appearances are not alone sufficient in predicting the diagnosis in up to 30% of cases of UC and 60% of CD . When reporting endoscopic biopsies for a suspected IBD, it is important to assess certain parameters in reaching the diagnosis such as mucosal architecture, lamina propria cellularity, neutrophil poly-morph infiltration and epithelial changes.
Increase in intraepithelial lymphocytes, presence of thickened subepithelial collagen, and changes of mucosal prolapse should be excluded before reporting the biopsy as normal . It is crucial that the reporting pathologist should be familiar with the normality in large bowel biopsies and changes accepted to be within normal limits. The normal surface of the large bowel is almost flat and in IBD the surface may be irregular and sometime attain a villi-form architecture; however, normal crypt architecture does not entirely exclude the diagnosis of IBD [46, 83]. Most of the times, in a resected specimen, normal architecture can be found overlying a fragmented or duplicated muscularis mucosa which clearly indicates previous mucosal damage; thus, a clinical history, especially of IBD, is crucial in these types of biopsies for arriving at the correct diagnosis rather than reporting the biopsy as normal .
In UC, one of the most differentiating features from CD is that the inflammation is mainly mucosal but sometimes spills over into the submucosa, thus it is usually assessable by endoscopic biopsies . The crypts in UC are classically infiltrated by neutrophil polymorphs in a uniform manner; therefore, any isolated involvement of crypts and spared mucosa is strongly suggestive of CD . One has to keep in mind that neutrophil polymorph infiltration does not have to be an indication of inflammatory changes, because vigorous bowel preparation can lead to mild neutrophil polymorph infiltration within crypts, and also occasional polymorphs within otherwise normal lamina propria are not uncommon .
over CD; however, focal crypt abscess formation can occur in UC, CD and infectious colitis . Focal erosions on a background of a relatively unremarkable mucosa should raise the possibility of CD . Diverticular colitis should be kept in mind whenever sigmoid colitis resembling UC but with rectal sparing is seen .
In a normal large bowel, the crypts are straight, parallel and extend from above the muscularis mucosae into the surface. However, some normal variations are seen in the region of lymphoid follicles . The average 1 mm length of muscularis mucosa should normally contain seven to eight crypts, which are usually closely packed . In IBD, this number will be reduced to an average of three to five per 1 mm of muscularis mucosae and the crypts are usually short and irregular in shape . However, increased spacing between crypts is normally seen in the caecum and distal rectum and should not be confused with inactive IBD.
Crypt branching is commonly seen in IBD; however, some focal crypt branching (less than 10% of all crypts) is not uncommon but two or more abnormally branching crypts within 2 mm of muscularis mucosae is regarded as abnormal . Lamina propria should be assessed for changes in cellularity and the presence of granulomas. In normal lamina propria, inflammatory cells are more concentrated in the upper third than the lower third together with some lymphoid follicles, which may occupy the full thickness of the lamina propria. In contrast to IBD where basal plasmacytosis is common [83, 87].
Muciphages are commonly seen in large-bowel biopsies examined for IBD and some authors suggest that they reflect previous occult and clinically unimportant mucosal damage and that, in an otherwise normal colorectal mucosa, they have no diagnostic significance [88, 89]. Granulomas in intestinal biopsies are classically linked to CD; however, a well-formed epithelioid granuloma is a specific but nonsensitive feature of CD, being seen in up to 50% of cases and in as few as 18% of CD . Mucin depletion is a non-specific feature of IBD, but the presence of severe mucin/goblet cell depletion occurs more in UC than CD .
Paneth cell metaplasia together with pseudo-pyloric metaplasia (cells of the ulcer-associated cell lineage) appears in epithelium, which has been subjected to chronic insults, but their diagnostic value is unclear. Paneth cells can be seen in colonic crypts in inflammatory bowel disease; however, one should be wary of the fact that Paneth cells can be a normal finding in biopsies from the caecum and ascending colon .
In UC, changes resembling features of a hyper-plastic polyp is sometimes seen . Artefacts such as effects of bowel preparation and trauma to the biopsy can produce certain changes which can be confused with features of IBD. Bowel preparation can produce a mild increase in the number of mitotic figures, causing surface degeneration with increased apoptotic bodies within the crypt epithelium. It can also lead to mild neutrophilic infiltrate within the glands together with some degree of goblet cell depletion [92, 94, 53].
In defining the accuracy of diagnosis in IBD, it has been shown that multiple colonic biopsies give the best diagnostic improvement and it has also been shown that, in the interpretation of large-bowel biopsies, there is no significant difference between expert and non-expert pathologists [29, 30].
A constellation of features such as the presence of granulomas, especially submucosal, focal or patchy inflammation and discontinuous crypt distortion helps in diagnosing CD. For UC, the symptoms are diffuse crypt distortion, diffuse cryptitis, basally concentrated chronic inflammatory cell infiltrate, reduced crypt numbers, severe architectural distortion, villous surface, severe diffuse transmucosal lamina propria inflammation and mucin depletion are highly suggestive of the disease [95, 53]. An appendiceal involvement is rare in cases of total colitis and more common as a skip lesion in distal colitis especially in UC [96, 97].
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