Case 3 -

Sporadic adenoma and 'pseudo-dysplasia' due to IV cyclosporin therapy Neil Shepherd

Case History: This 73 year old man had ulcerative colitis that failed to respond to medical therapy. A total colectomy was performed. Case 3 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer This is an extraordinary case. Firstly, the flat mucosa shows the characteristic "pseudo-dysplasia" associated with IV cyclosporin therapy. This is a notable catch. Secondly, there is an obvious polypoid lesion which is also present in these sections. The overall morphology and the immunohistochemical features would indicate that this is, believe it or not, a sporadic adenoma arising in a colon affected by ulcerative colitis and is not a true focus of polypoid dysplasia or dysplasia-associated lesion or mass (DALM). This case is difficult diagnostically but there are two important points. The first is that IV cyclosporin therapy, for fulminant ulcerative colitis, produces mucosal changes that strongly mimic dysplasia (Hyde et al, 2002). The second is one that all pathologists must bear in mind – CONTEXT. Whilst this case serves to highlight the difficulties in differentiating sporadic adenoma from polypoid dysplastic change in ulcerative colitis and that this remains a most controversial area of GI pathology with gastro-intestinal pathologists differing as to whether morphological and immunohistochemical parameters can adequately differentiate these two (Torres et al, 1998; Mueller et al, 1999), one should always bear in mind the circumstantial evidence and context. Is the lesion in an area affected by ulcerative colitis, is the ulcerative colitis long-standing and extensive and is the patient of an age where one would expect sporadic adenomas? In this case that evidence clearly favours a sporadic adenoma because this 73 year old man has only a two year history of ulcerative colitis... Pathologists do worry about how to differentiate sporadic adenomas from DALMs complicating ulcerative colitis. However, in the last two years, there have been quite radical challenges to the traditional management of neoplasia in UC, namely that a diagnosis of high grade dysplasia and/or the presence of a DALM demands radical surgery. Firstly, it has become clear that careful colonoscopy, using chromo-endoscopy and magnifying video-colonoscopy, renders almost all dysplastic lesions in ulcerative colitis visible, whether flat, sessile or raised (Kiesslich et al, 2003; Rutter et al, 2004; Hurlstone et al, 2004). Secondly, it has been shown that local excision of dysplastic lesions in ulcerative colitis patients, whatever the subtype of the lesion, may be adequate treatment with favourable long term follow up (Odze et al, 2004). This, then, places much more emphasis on endoscopic surveillance with chromoendoscopy and local treatment rather than major surgery. This should certainly make the pathologist's role easier, especially in the differentiation of sporadic adenoma from DALM. If both are to be treated by local endoscopic excision, then the differentiation, prior to that removal, becomes much less important and can await receipt of the whole specimen and biopsies from its environs. This does not diminish the pathologist's role in the diagnosis of dysplasia in UC but it does mean that we have to be less concerned with being dogmatic about the differentiation of sporadic adenoma from ulcerative colitis-associated dysplasia at the time of biopsy of such lesions. References Hurlstone DP, McAlindon ME, Sanders DS, Koegh R, Lobo AJ, Cross SS. Further validation of high-magnification chromoscopic colonoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis. G astroenterology 2004; 126: 376-8. Hyde G, Warren BF, Jewell DP. Histological changes associated with the use of intravenous cyclosporin in the treatment of severe ulcerative colitis may mimic dysplasia. Colorectal Disease 2002; 4: 455-458. Kiesslich R, Fritsch J, Holtmann M, Koehler HH, Stolte M, Kanzler S, Nafe B, Jung M, Galle PR, Neurath MF. Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis . Gastroenterology 2003; 124: 880-8. Mueller E, Vieth M, Stolte M, Mueller J. The differentiation of true adenoma from colitis associated dysplasia in ulcerative colitis: a comparative immunohistochemical study. Hum Pathol 1999; 30: 898-905. Odze RD , Farraye FA, Hecht JL, Hornick JL. Long-term follow-up after polypectomy treatment for adenoma-like dysplastic lesions in ulcerative colitis . Clin Gastroenterol Hepatol 2004; 2: 534-41. Rutter MD, Saunders BP, Wilkinson KH, Kamm MA, Williams CB, Forbes A. Most dysplasia in ulcerative colitis is visible at colonoscopy. Gastrointest Endosc 2004; 60: 334-339. Torres C, Antonioli D, Odze RD. Polypoid dysplasia and adenomas in inflammatory bowel disease: a clinical, pathologic, and follow-up study of 89 polyps from 59 patients. Am J Surg Pathol 1998; 22: 275-84.