Granulomas in the diagnosis of intestinal Crohn's disease: amyth exploded?

Mention granuloma , certainly to the average gastroenterologist and probably to many pathologists, in the context of intestinal pathology, and the diagnosis of Crohn’s disease is established irrevocably, it seems, often to the detriment of the patient. Now no selfrespecting pathologist is going to deny the importance of granulomas in the differential diagnosis of inflammatory bowel disease, and major reviews and interobserver studies have confirmed their importance in the differential diagnosis of chronic inflammatory bowel disease. Nevertheless, increasingly pathologists are questioning the absolute sensitivity and the specificity of granuloma demonstration in the diagnosis of intestinal Crohn’s disease, especially in biopsy pathology. For many years pathologists have recognized the variable nature of the histopathology of Crohn’s disease. The most characteristic microscopic features of the disease are its multifocal involvement and a triad of histological features: focal ulceration (which is often fissuring and may result in fistula formation), transmural inflammation in the form of lymphoid aggregates and granulomas. These three features are generally regarded as the hallmarks of intestinal Crohn’s disease. However, in small bowel Crohn’s disease, only in 50% of cases will granulomas be demonstrable. They are especially unusual in duodenal and ileoscopic biopsies from Crohn’s disease patients, although it is said that their presence is of much diagnostic utility in these biopsy specimens. The frequency of granulomas, both between patients and within individual patients, increases as one travels down the gastrointestinal tract, in Crohn’s disease, with the anus being the most likely site for their demonstration, when there is disease present. They are less commonly seen in patients with a long clinical history and are, conversely, commoner in younger patients with a shorter duration of disease. Their presence does not influence recurrence rates or prognosis in small intestinal Crohn’s disease. Granulomas are usually related to areas of ulceration and transmural inflammation: they are less often seen in isolation away from areas of active disease. So, the sensitivity of the presence of granulomas, in the establishment of a diagnosis of Crohn’s disease, is variable according to the site of biopsy material, clinical data, notably the age of the patient and the length of disease, and the presence of other associated pathological features. If the sensitivity of granulomas in the diagnosis of Crohn’s disease, is, perhaps, lower than many might have expected, what of the specificity? In this situation, definition and context become overwhelmingly important. In last month’s Histopathology, Mahadeva and colleagues emphasize the importance of position and quality of the granuloma in the differential diagnosis of chronic inflammatory bowel disease. They have shown that, unlike Lee and his colleagues before them, pericryptal granulomatous inflammation, whether defined by isolated giant cells or by well-formed granulomatous pathology, is not a specific feature of Crohn’s disease and can be seen in otherwise classical ulcerative colitis. In pathological practice, others have essentially concurred with their conclusions. Granulomas are, it would seem, only useful for the differential diagnosis of Crohn’s disease and ulcerative colitis, when they are well-formed, isolated, especially basally oriented in the mucosa, and away from inflamed crypts. Are there other situations in which the presence of granulomas might suggest Crohn’s disease and yet the pathology and clinical data demand an alternative diagnosis? First, small granulomas, often Address for correspondence: Professor Neil A Shepherd, Department of Histopathology, Gloucestershire Royal Hospital, Great Western Road, Gloucester GL1 3NN, UK. e-mail: neil.shepherd@gloucr-tr.swest. nhs.uk