Abstract
Diagnosis of fine-needle aspirations of pancreatic solid masses is complicated by many factors that keep its false-negative rate high. Our novel approach analyzes cell-free cytocentrifugation supernatant, currently a discarded portion of the specimen. Supernatant and cytology slides were collected from 25 patients: 11 cases with confirmed outcome [five positive (adenocarcinoma) and six negative (inflammatory states)], plus 14 without confirmed outcomes. Slides were microdissected, DNA was extracted from microdissections and corresponding supernatants, and all were analyzed for KRAS point mutation and loss of heterozygosity. Notably, higher levels of free DNA were found in supernatants than in corresponding microdissected cells. Supernatants contained sufficient DNA for mutational profiling even when samples contained few to no cells. Mutations were present in 5/5 malignancies and no mutations were present in inflammatory states. In conclusion, these findings support using supernatant for mutational genotyping when diagnostic confirmation is required for pancreatic solid masses. Diagn. Cytopathol. 2014;42:719–725. © 2013 Wiley Periodicals, Inc.
Highlights
In particular the clinical utility of microdissection-based molecular analysis for loss of heterozygosity (LOH) and KRAS has been demonstrated in pancreaticobiliary disease, with LOH and KRAS point mutations universally recognized as hallmarks of pancreatic cancer.[23,24,25,26,27,28]
A total of 25 cytocentrifugation supernatant and microdissected cytology pancreatic fine-needle aspiration specimens were analyzed for DNA content and mutational profiling and were compared to their respective cytology findings (Tables I and II)
Eleven of these cases were from direct fine-needle aspirations of solid pancreatic mass lesions with confirmed outcome
Summary
Advances in cross-sectional and endoscopic imaging, coupled with improvements in fine-needle aspiration (FNA) sampling technology, have led to an increase in the number of specimens for cytology evaluation.[1,2,3,4,5,6,7,8,9] This is true for many organ systems and can be exemplified by the pancreas where the number of solid masses, cysts, and ductal brushing specimens for cytology examination continues to rise.[10,11] These advances have allowed for smaller lesion sizes to be detected at first diagnosis, resulting in earlier detection and treatment of cancer and precancerous processes. Besides limitations in sample quantity, another hurdle in cytology practice is sampling variation, given that neoplastic processes often are topographically heterogeneous across a particular organ or tissue This heterogeneity operates at both a cellular and a molecular level of analysis and must be considered whenever sampling from within a larger sized lesion is undertaken.[17] Recently, directed cyst wall biopsy has become available for the work up of cystic lesions of the pancreas.[18] Pancreatic cysts are especially challenging since the aspirated fluid. The ability to evaluate cellular and molecular markers of neoplastic change over a wider distance than what is confined to the sampling site would be beneficial because the impact of sampling variation could be reduced In this way, ancillary tools that utilize markers to detect cancer-associated change could significantly improve the detection and characterization of neoplasia. When specimen cellularity is low, there can be a reluctance to utilize limited numbers of stained cytology cells for molecular analysis, especially when the most representative cells are confined to a single glass slide
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