Indefinite for Dysplasia in Inflammatory Bowel Disease: Subtypes and Clinical Outcomes
Victoria L Owens, John E Eaton, Thomas C Smyrk. Mayo Clinic, Rochester, MN
Background: Interpreting surveillance biopsies in inflammatory bowel disease (IBD) is not always straightforward, thus the option for a diagnosis of “indefinite for dysplasia” (IND). The original description of IND included the category “IND, unknown,” for “unexplained enlargement of nuclei that lack other characteristics of dysplasia.” We have encountered many biopsies with enlarged, round nuclei, irregular nuclear membranes and macronuclei worrisome for dysplasia. Our descriptive term is “large cell change” and we categorize it as IND, even when the cytologic atypia is marked. We reviewed biopsies diagnosed as IND to better understand “large cell change.”
Design: We reviewed all IBD surveillance biopsies called IND between 2000 and 2010 and retrospectively reclassified them as IND favor reactive, IND favor dysplasia and IND unknown, with the latter category used exclusively for biopsies with large cell change. Multiple clinical parameters were recorded from the medical record. Immunohistochemistry for p53 was performed on representative biopsies.
Results: 194 patients had biopsies called IND. 64 patients were excluded (11 with slides unavailable for review; 53 with prior or synchronous biopsy called low grade dysplasia, high grade dysplasia (HGD) or carcinoma (CA)). Of the remaining 130 patients (89M:41F), 112 had ulcerative colitis, 15 Crohn's, and 3 were unclassified. 53 patients had primary sclerosing cholangitis (PSC). Overall, 24 patients (18%) progressed to dysplasia, with 9 (7%) developing HGD/CA. We reclassified 46 patients as “reactive,” 67 as “large cell,” and 17 as “dysplasia.” Many of the large cell patients had PSC (42/67), compared to 7 reactive and 4 dysplasia patients. Progression rates to dysplasia for these groups were 13%, 15% and 47%, respectively, with progression to HGD/CA occurring in 2% of reactive, 4% of large cell and 29% of dysplasia. 214 patient biopsies were stained for p53. Strong nuclear staining for p53 was seen in 13/60 (22%) biopsies classified as reactive, 40/126 (32%) called large cell, and 16/28 (57%) called dysplasia. Of the patients who progressed to HGD/CA, 6/9 (67%) had strong p53 in their IND biopsy. We did not identify a specific medication associated with large cell change.
Conclusions: The large cell change described here can be worrisome for dysplasia, but we believe the data justifies designating this lesion as IND. Strong p53 expression in areas of large cell change may indicate increased risk for progression, but we do not advocate routine use immunohistochemistry at this time. There seems to be an association with PSC, but the explanation for that association is not known.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 108, Monday Morning