Pathology of non-specific inflammatory bowel disease
NEIL MORTENSEN
The only two absolute distinguishing pathological features between Crohn's disease and ulcerative colitis are the presence of significant small bowel disease and the finding of giant cell granulomata in the former.
ULCERATIVE COLITIS
Ulcerative colitis is a mucosal disease that almost invariably involves the rectum and spreads proximally. The extent of the disease may increase and, rarely, decrease again, giving recognizable periods of activity and remission. Inflammation is limited to the mucosa, except in acute and severe colitis. There may be little visible from the serosal aspect of the bowel on gross inspection. The mucosa is usually congested and friable, with a velvety texture; there may be varying degrees of ulceration. The left side of the colon is usually affected and improvement following steroid enemas can produce an artificial sparing of the rectum or sigmoid. True sigmoid sparing or right-sided disease is rare.
Microscopy shows a diffuse infiltration of acute and chronic inflammatory cells limited to the mucosa (Fig. 1) 1037. The glandular pattern is distorted with goblet cell depletion, and crypt abscesses are numerous. In inactive disease, glands may be shortened and atrophic. Long-standing disease may be associated with dysplasia of the epithelium, which can be graded as mild, moderate, or severe. Severe dysplasia (precancer) is frequently associated with cancer elsewhere in the colon and when detected in rectal or colonoscopic biopsies, proctocolectomy must be considered. It is now also accepted that Crohn's disease is associated with an increased risk of cancer even in bypassed small intestine.
CROHN'S DISEASE
Crohn's disease of the large intestine has been recognized as a separate entity since the definitive description of Lockhart Mummary and Morson. Since then, many cases previously labelled as ulcerative colitis have been reclassified as Crohn's disease of the large intestine. Crohn's disease is restricted to the colon in some 20 per cent of patients; another 60 per cent have ileocolonic involvement. It is usually a right-sided disease but limited left-sided disease can occur, especially associated with anal disease in the elderly.
In the colon, Crohn's disease is characteristically a granulomatous condition with transmural aggregates of inflammatory cells and penetrating fissuring ulceration (Fig. 2) 1038. The bowel wall is thickened and the serosa opaque. Strictures and fistulae occur between bowel segments and there are large fleshy lymph nodes in the mesentery or pericolic fat. The mucosa is oedematous and characteristically traversed by linear ulcers, giving a cobblestone appearance to the surface. Areas of non-involved bowel separate the disease segments (skip lesions), although there may be cases with diffuse disease. Careful inspection of normal looking mucosa may reveal tiny aphthoid ulcers, which start as ulcerating lymphoid follicles; these may be the initial lesion in the disease. Rectal sparing and anal disease are common features. The key distinguishing feature on microscopy is the granulomata which are scattered throughout the bowel wall, together with fissuring, ulceration, and a regular glandular pattern with a normal goblet cell population. Granulomata are only found in 60 per cent of patients, however, and fissures are seen in only 30 per cent. Fibrosis in the submucosa is common; there may be neural proliferation, pyloric gland metaplasia, and a vasculitis.
BIOPSY AND NON-SPECIFIC INFLAMMATORY BOWEL DISEASE
Rectal biopsy is often more helpful in establishing a diagnosis in ulcerative colitis than in Crohn's disease, because of the problems of sampling error. A normal rectal biopsy is strong evidence against the diagnosis of ulcerative colitis, but it must be stressed that normal appearances on sigmoidoscopy do not imply normal histology. In Crohn's disease the chance of obtaining an abnormal specimen on biopsy increases as the diseased segment becomes closer to the anal canal, but even when disease is restricted to the ileum, abnormal rectal biopsies can be found in up to 12 per cent of patients. Multiple colonscopic biopsies make it possible to document precisely the extent and distribution of colonic disease, particularly in those with mild ulcerative colitis and Crohn's disease. Because of the small size of the colonic biopsies granulomata are detected less frequently than in rectal biopsies.
Histopathology in severe colitis
Distinction between Crohn's disease and ulcerative colitis is most difficult when the disease is severe. Ulcerative colitis can become transmural, with deep ulceration and fissures. The irregularity in goblet cell depletion is then less obvious and the histopathology can be confusingly similar to that of Crohn's disease. Occasionally this distinction is not made, even after study of the operative specimen, and the diagnosis can only be finally resolved when the rectum is removed or when disease appears in the small intestine. In some cases the features overlap so much that the disease has to be labelled ‘indeterminate colitis’.
CLINICAL DIFFERENTIATION BETWEEN ULCERATIVE COLITIS AND CROHN'S DISEASE
The differences in distribution and histological appearances of the two diseases make it convenient to recognize ulcerative colitis and Crohn's disease as separate entities. The main clinical differences are shown in Table 1 327. Differences are seen in anatomical distribution, in the type of ulceration, and the continuity or discontinuity of the disease. Fibrosis is not a feature of ulcerative colitis and fibrous strictures rarely occur (Table 2) 328.
In Crohn's disease, fibrosis can cause fibrotic strictures with obstructive symptoms. Since ulcerative colitis causes a severe diarrhoea, there may be secondary or thrombosis of haemorrhoids. Crohn's disease tends to affect adjacent structures with fistulation into the bladder, fallopian tube, ureter, or other intra-abdominal structures. A chronic retroperitoneal abscess can spread to the psoas sheath, and the characteristic anorectal lesions of Crohn's disease can spread to the external genitalia or give rise to a rectovaginal fistula. All types of non-specific inflammatory bowel disease can give rise to extraintestinal manifestations, usually associated with an exacerbation of inflammation in the gut.
FURTHER READING
Lockhart Mummery HE, Morson BC. Crohn's disease (regional enteritis) of the large intestine and its distinction from ulcerative colitis. Gut 1960; 1: 87–105.
Morson BC, Dawson IMP. Gastrointestinal Pathology. 2nd edn. Oxford: Blackwell 1979.
Price AB. Overlap in the spectrum of non-specific inflammatory bowel disease—colitis indeterminate. J Clin Pathol 1978; 3: 567–77.