molecular pathology of pancreatic FNA

 mutational profiling

• next-generation sequencing (NGS)

 mutational profiling of the cytocentrifugation supernatant fluid

• In a study, 5/23 samples cytologically confirmed as adenocarcinoma showed detectable mutations both in the microdissected slide-based cytology cells and in the cytocentrifugation supernatant. (24051700)
• While most mutations detected were present in both microdissected slides and supernatant fluid specimens, the latter showed additional mutations supporting greater sensitivity for detecting relevant DNA damage.
• Clonality for individual marker mutations was higher in the supernatant fluid than in microdissected cells.
• Cytocentrifugation supernatant fluid contains levels of amplifiable DNA suitable for mutation detection and characterization.
• The finding of additional detectable mutations at higher clonality indicates that supernatant fluid may be enriched with tumor DNA.
• Molecular analysis of the supernatant fluid could serve as an adjunct method to reduce sampling variability and increase diagnostic yield, especially in cases with a high clinical suspicion for malignancy and limited number of atypical cells in the smears.

Molecular Targets

 Cancer gene mutations

• KRAS
• GNAS
• VHL / OGG1
• PTEN / MXI1
• TP53
• SMAD4 / DCC
• CDKN2A / p16
• RNF43 / NME1
• PSEN2 / TFF1
• CMM1 / LMYC
• MCC / APC
• NF2

Tools

 PancraGEN by Interpace Diagnostics

Open references

 A combination of molecular markers and clinical features improve the classification of pancreatic cysts. Springer S, Wang Y, Dal Molin M et al. Gastroenterology. 2015 Nov;149(6):1501-10. doi : 10.1053/j.gastro.2015.07.041
PMID: 26253305 Free

 The added value of using mutational profiling in addition to cytology in diagnosing aggressive pancreaticobiliary disease: review of clinical cases at a single center. Malhotra N, Jackson SA, Freed LL, Styn MA, Sidawy MK, Haddad NG, Finkelstein SD.
BMC Gastroenterol. 2014 Aug 1;14:135. doi : 10.1186/1471-230X-14-135
PMID: 25084836 (Free)

 The value of mutational profiling of the cytocentrifugation supernatant fluid from fine-needle aspiration of pancreatic solid mass lesions. Deftereos G, Finkelstein SD, Jackson SA, Ellsworth EM, Krishnamurti U, Liu Y, Silverman JF, Binkert CR, Ujevich BA, Mohanty A. Mod Pathol. 2014 Apr;27(4):594-601. doi : 10.1038/modpathol.2013.147 PMID: 24051700 (Free)

 Molecular analysis of centrifugation supernatant fluid from pancreaticobiliary duct samples can improve cancer detection. Finkelstein SD, Bibbo M, Loren DE, Siddiqui AA, Solomides C, Kowalski TE, Ellsworth E. Acta Cytol. 2012;56(4):439-47. doi : 10.1159/000339638 PMID: 22846349 (Free)

Paywall References

 Targeted next-generation sequencing of FNA-derived DNA in pancreatic cancer
J Clin Pathol jclinpath-2016-203928 Published Online First: 26 September 2016

 EUS-guided pancreatic fluid aspiration for DNA analysis of KRAS and GNAS mutations for the evaluation of pancreatic cystic neoplasia: a pilot study. Siddiqui AA, Kowalski TE, Kedika R, Roy A, Loren DE, Ellsworth E, Adler D, Finkelstein SD.
Gastrointest Endosc. 2013 Apr;77(4):669-70. doi : 10.1016/j.gie.2012.11.009
PMID: 23498145

 Al-Haddad MA, Kowalski T, Siddiqui A, et al. Integrated molecular pathology accurately determines the malignant potential of pancreatic cysts. Endoscopy. 2015;47(2):136-146.

 V. Chernyak et al, Incidental pancreatic cystic lesions Radiology 2015 274 161-9

 BU Wu, et al, Prediction of malignancy in cystic neoplasms of the pancreas: a population based cohort study, Am J Gastro 2014 109 121-9

 Loren D, Kowalski T, Siddiqui A, et al. Influence of integrated molecular pathology test results on real-world management decisions for patients with pancreatic cysts: analysis of data from a national registry cohort. Diagnostic Pathology. 2016;11:5. doi : 10.1186/s13000-016-0462-x

 Gaujoux S., , Brennan, M., et al. Cystic Lesions of the Pancreas: Changes in the Presentation and Management of 1,424 Patients at a Single Institution over a 15-year Time Period. J Am Coll Surg. 2011 April; 212(4): doi : 10.1016/j.jamcollsurg.2011.01.016

 Kaimalkliotis, P., Riff, B., et al. Sendai and Fukuoka Consensus Guidelines Identify Advanced Neoplasia in Patients With Suspected Mucinous Cystic Neoplasms of the Pancreas. Clinical Gastroenterology and Hepatology 2015;13:1808–1815: doi : 10.1016/j.cgh.2015.03.017