Incidence of Pancreatic Intraepithelial Neoplasia in an Autopsy Series

Abstract

ObjectivesPancreatic intraepithelial neoplasia (PanIN) is the currently preferred designation for putative preneoplastic changes in the pancreas. There are few data for the incidence of PanIN in the general population. Our goal was to determine the incidence of PanIN in a large group of pancreases obtained at autopsy.MethodsSlides stained with hematoxylin and eosin were scanned to count PanIN.ResultsWe found multiple PanINs in most pancreases and at least 1 in 86.4% of 154 pancreases when multiple slides (8–12) from each were examined. The average age at autopsy was 62 years, and 90% of the patients were 40 years or older. Several questions were raised by our observations. Should a minimum size be defined for classification as PanIN? Do PanINs occur in lesions that apparently arise from acinar to ductal metaplasia? Does squamous metaplasia in PanIN have any special significance, and do purely squamous lesions have preneoplastic significance?ConclusionsWe conclude that the incidence of PanIN is higher than previously reported.

Chronic Jetlag Accelerates Pancreatic Neoplasia in ConditionalKras-Mutant Mice

“…Consistent with our KC model, PanIN-1s were always present in the pancreas when PanIN-2 or -3 were identified. These autopsy findings were also confirmed in a separate study (Longnecker and Suriawinata 2022). Thus, our model is concordant with the neoplastic process that occurs in humans and relevant for studying PanIN progression.…”

“…The majority of the lesions were PanIN-1, with fewer PanIN-2 and PanIN-3 lesions identified (Shi et al 2009); again mirroring the findings in our KC model where there is multifocal lesion formation, and the majority of the lesions at 9 months were PanIN-1 with fewer PanIN-2 and PanIN-3. Moreover, in the study by Shi et al (Shi et al 2009), PanIN lesions were found in the pancreas remote from invasive cancer, which supports the findings from autopsy studies (Matsuda et al 2017; Longnecker and Suriawinata 2022) that not all PanINs progress to cancer. Similar to the etiology of PanINs in our model, greater than 95% of human PanINs harbor a Kras mutation (including 92% of PanIN-1) (Kanda et al 2012), and it is generally accepted that the fraction of Kras -mutant cells in PanINs increases with PanIN grade, indicating clonal expansion of the Kras -mutant cells that have been ‘transformed’ (Kanda et al 2012).…”

Three-dimensional genomic mapping of human pancreatic tissue reveals striking multifocality and genetic heterogeneity in precancerous lesions

“…Although previous studies have postulated that multifocal PanIN lesions arise separately, our work definitively demonstrates their independent nature through the development of a technique for integrated 3D modeling and genomic analyses. 6,[37][38][39][40] We found that spatially distinct PanINs most often arise from independent genetic events, exemplified by discordant somatic mutations between spatially discrete lesions. Furthermore, we demonstrate that the proximity of LG or HG PanIN to PDAC does not guarantee shared genetic origins -our cohort included 2 examples of PanINs containing HG dysplasia that were genetically distinct from adjacent PDACs, further emphasizing the importance of 3D genomic analyses to ascertain genetic origins.…”

Analysis of donor pancreata defines the transcriptomic signature and microenvironment of early pre-neoplastic pancreatic lesions

“…In contrast, pancreatic intraepithelial neoplasia (PanIN) is microscopic and typically only encountered following resection of other pancreatic pathologies, including overt cancer (11)(12)(13). Autopsy studies -mostly in an older patient population-indicate that PanIN is common in older individuals, however poor preservation of the pancreas due to prolonged warm ischemic time severely limits molecular analysis of autopsy samples (14)(15)(16)(17)(18). The prevalence of PanIN in the general healthy population remains unknown.…”