Is Autoimmune Pancreatitis Associated with an Increased Risk of Malignancy? A Retrospective and Comparative Study
RK Gupta, M Genevay, NB Johnson, GY Lauwers, V Deshpande. Massachusetts General Hospital, Boston; University of Geneva, Geneva, Switzerland; Beth Israel Deconess Hospital, Boston
Background: Autoimmune pancreatitis (AIP) is a recently recognized form of chronic pancreatitis. Chronic pancreatitis-not otherwise specified (CP-NOS) is a well recognized risk factor for pancreatic carcinoma (PCA). Thus, theoretically, AIP may represent a risk factor for PCA. Furthermore, PCAs in patients with AIP have been reported. However, there has been no systematic study to explore this link. In this study we used PanINs as a surrogate marker for PCA, and compared the number, grade, and mutation profile of PanIN lesions in pancreatectomy specimens from well characterized cases with AIP, CP-NOS and serous cystadenoma (SCA).
Design: Pancreatic resection specimens with histological diagnoses of AIP, CP-NOS and SCA were reviewed. We chose 32 cases each from the cohorts of AIP, CP-NOS and SCA . We counted the number of PanIN lesions, and graded these lesions in all the three patient groups. A tissue microarray composed of high grade PanIN lesions was constructed and these arrays were stained for p16, p53, SMAD4 and Ki-67.
Results: Patients with AIP were older than those with CP-NOS (AIP 54 yr, CP-NOS 48 yr, SCA - 64yr) (p=NS). The AIP and CP-NOS cases showed both PanIN1 and 2 lesions, while individuals with SCA showed only PanIN1 lesions. On follow-up one patient each in the AIP and CP-NOS cohort developed PCA in the unresected pancreas. There were no PanIN3 lesions identified. Patients with AIP (mean =1.19) showed significantly more PanIN2 lesions than patients with CP-NOS (mean = 0.22) and serous cystadenomas (mean =0.12) (p = 0.04 and 0.03, respectively). Significantly, there were no statistically significant differences in the number of slides examined between the 3 groups. On immunohistochemistry, the majority of PanIN2 lesions in the AIP cohort (7 of the 8) and all 3 CP associated PanIN2 lesions showed loss of p16 protein expression . Two of the 7 PanIN 2 lesions in AIP expressed p53, while none of the 3 CP associated PanIN 2 lesions expressed this protein. AIP associated PanIN2 lesions showed a higher Ki67 labeling index (mean 4.92%) than similar grade lesions in CP-NOS (mean 0.52) (p=0.06).
Conclusions: The risk of PCA in AIP is at least similar to that posed by CP-NOS. A prospective longitudinal study is required to more definitively estimate the risk of malignancy in PCA. In the interim, long-term follow-up of cases with AIP may be required.
Category: Liver & Pancreas
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 198, Tuesday Afternoon