Diagnostic Value of Cytology in Pancreatic Endoscopic Ultrasound-Guided Fine Needle Aspiration: Accuracy in Common Epithelial Pancreatobiliary Tumors and the Role of Cell Block Analysis

Document Type : Original Research

Authors

1 Department of Pathology, Gastrointestinal and liver disease Research center, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran

2 Department of Pathology, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Pathology, Iran Medical School, Iran University of Medical Sciences, Tehran, Iran

4 Department of Biostatistics, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract
Background & Objective: Limited literature describes the accuracy of endoscopic ultrasonography–fine needle aspiration (EUS-FNA) cytology in various types of pancreatic epithelial tumors, and this underscores the usefulness of cell blocks, and highlights potential diagnostic pitfalls.  
Methods: This study included 108 patients who underwent EUS-FNA pancreatobiliary cytology followed by surgery. Age, gender, tumor location, tumor size, presence or absence of a cell block, cytologic and pathologic diagnoses, and histologic tumor grade were recorded. Cytologic and pathologic slides were examined, and the cytologic accuracy was determined by comparing cytologic with the histopathologic results as the gold standard. Additionally, the impact of cell block on the cytologic accuracy was assessed.
Results: EUS-FNA cytology showed an overall accuracy of 80%, a sensitivity of 90%, and a false-positive rate below 1%. Pancreatic ductal adenocarcinomas (PDAs) accounted for 65% of cases, followed by neuroendocrine tumors (NETs), solid pseudopapillary neoplasms (SPNs), mucinous cystic neoplasms (MCNs), and chronic pancreatitis. Diagnostic accuracy was higher for PDA and SPN than for NET and MCN and significantly improved to 100% in cases with a cell block.
Conclusion: Combining pancreatobiliary cytology with a cell block significantly enhances diagnostic accuracy, reaching 100%. Moreover, poorly differentiated PDAs and well-differentiated organoid-type tumors, such as NETs and SPNs, demonstrate higher diagnostic accuracy. 

Highlights

  • The diagnostic accuracy of cytology was higher with PDA and SPN than with NET and MCN and rose significantly in cases with cell block.
  • FNA cytology detected PDA more accurately as the tumor grade decreased; however, for NETs, accuracy declined with poor tumor differentiation.
  • In cases where cytology and pathology disagreed, missing tumor locations, small tumor size, tumor necrosis, and very good differentiation in PDA and cystic degeneration, papillary architecture, pleomorphism, and ganglion cells in NETs were the most frequent causes of pitfalls.

Keywords

Subjects


  1. Pal R, Singh B, Bhadada SK, et al. COVID-19-associated mucormycosis: an updated systematic review of literature. Mycoses. 2021;64(12):1452-9. [DOI:10.1111/myc.13338] [PMID]
  2. Hoenigl M, Seidel D, Carvalho A, et al. The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries. Lancet Microbe. 2022;3(7):e543-52. [DOI:10.1016/S2666-5247(21)00237-8] [PMID]
  3. Patel A, Kaur H, Xess I, et al. A multicentre observational study on the epidemiology, risk factors, management and outcomes of mucormycosis in India. Clin Microbiol Infect. 2020;26(7):944.e9-944.e15. [DOI:10.1016/j.cmi.2019.11.021] [PMID]
  4. Farmakiotis D, Kontoyiannis DP. Mucormycoses. Infect Dis Clin North Am. 2016;30(1):143-63. [DOI:10.1016/j.idc.2015.10.011] [PMID]
  5. Spellberg B, Edwards J, Ibrahim A. Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev. 2005;18(3):556-69. [DOI:10.1128/CMR.18.3.556-569.2005] [PMID]
  6. Spellberg B, Ibrahim AS. Recent advances in the treatment of mucormycosis. Curr Infect Dis Rep. 2010;12(6):423-9. [DOI:10.1007/s11908-010-0129-9] [PMID]
  7. Nanotechnology and Drug Delivery, Volume One. Nanotechnology and Drug Delivery, Volume One.
  8. Kamiński DM. Recent progress in the study of the interactions of amphotericin B with cholesterol and ergosterol in lipid environments. Eur Biophys J. 2014;43(10-11):453-67. [DOI:10.1007/s00249-014-0983-8] [PMID]
  9. Sharma V, Anandhakumar S, Sasidharan M. Self-degrading niosomes for encapsulation of hydrophilic and hydrophobic drugs: an efficient carrier for cancer multi-drug delivery. Mater Sci Eng C. 2015;56:393-400. [DOI:10.1016/j.msec.2015.06.049] [PMID]
  10. Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. 2019;19(12): e405-21.
  11. Ervens J, Ghannoum M, Graf B, Schwartz S. Successful isavuconazole salvage therapy in a patient with invasive mucormycosis. Infection. 2014;42(2):429-32. [DOI:10.1007/s15010-013-0552-6] [PMID]
  12. Berkow EL, Lockhart SR, Ostrosky-Zeichner L. Antifungal susceptibility testing: current approaches. Clin Microbiol Rev. 2020;33(3):e00138-19. [DOI:10.1128/CMR.00069-19] [PMID]
  13. Badali H, Cañete-Gibas C, McCarthy D, et al. Epidemiology and antifungal susceptibilities of mucoralean fungi in clinical samples from the United States. J Clin Microbiol. 2021;59(9):e0128821. [DOI:10.1128/JCM.01230-21] [PMID]
  14. Tosti A, Vlahovic TC, Arenas R, editors. Onychomycosis. Cham: Springer International Publishing; 2017. [DOI:10.1007/978-3-319-44853-4]
  15. Hauer B, Meinzer A, Posanski U, Richter F, KK S. Pharmaceutical compositions comprising cyclosporins. Google Patents. 1994;(US 2003/0143250 A1):5,342,625.
  16. Barratt G, Bretagne S. Optimizing efficacy of amphotericin B through nanomodification. Int J Nanomedicine. 2007;2(3):301-13.
  17. Eskandari SE, Firooz A, Nassiri-Kashani M, et al. Safety evaluation of topical application of nano-liposomal form of amphotericin B (Sinaampholeish) on healthy volunteers: Phase I clinical trial. Iranian Journal of Parasitology. [Forthcoming].
  18. European Committee for Antimicrobial Susceptibility Testing (EUCAST). Method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia forming moulds. Version 9.3.2.
  19. Espinel-Ingroff A, Chakrabarti A, Chowdhary A, et al. Multicenter evaluation of MIC distributions for epidemiologic cutoff value definition to detect amphotericin B, posaconazole, and itraconazole resistance among the most clinically relevant species of Mucorales. Antimicrob Agents Chemother. 2015; 59(3):1745-50. [DOI:10.1128/AAC.04435-14] [PMID]
  20. Musuuza JS, Watson L, Parmasad V, Putman-Buehler N, Christensen L, Safdar N. Prevalence and outcomes of co-infection and superinfection with SARS-CoV-2 and other pathogens: a systematic review and meta-analysis. PLoS One. 2021;16(5):e0251170. [DOI:10.1371/journal.pone.0251170] [PMID]
  21. Garg D, Muthu V, Sehgal IS, et al. Coronavirus disease (COVID-19) associated mucormycosis (CAM): case report and systematic review of literature. Mycopathologia. 2021;186(2):289-98. [DOI:10.1007/s11046-021-00528-2] [PMID]
  22. Sen M, Honavar S, Sengupta S, et al. Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India - Collaborative OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1. Indian J Ophthalmol. 2021;69(7):1670-92. [DOI:10.4103/ijo.IJO_1565_21] [PMID]
  23. Hoenigl M, Seidel D, Carvalho A, et al. The emergence of COVID-19 associated mucormycosis: analysis of cases from 18 countries. SSRN Electron J. 2021. [DOI:10.2139/ssrn.3844587]
  24. Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. 2019;19(12): e405-21.
  25. Wadhwa S, Paliwal R, Paliwal S, Vyas S. Nanocarriers in ocular drug delivery: an update review. Curr Pharm Des. 2009;15(23):2724-50. [DOI:10.2174/138161209788923886] [PMID]
  26. Ahmad Nasrollahi S, Fattahi A, Naeimifar A, et al. The in vitro effect of nanoliposomal amphotericin B against two clinically important dermatophytes. Int J Dermatol. 2022;61(4):383-9. [DOI:10.1111/ijd.15609] [PMID]
  27. de Bastiani FWM da S, Spadari C de C, de Matos JKR, Salata GC, Lopes LB, Ishida K. Nanocarriers provide sustained antifungal activity for amphotericin B and miltefosine in the topical treatment of murine vaginal candidiasis. Front Microbiol. 2020;10:3081. [DOI:10.3389/fmicb.2019.02976] [PMID]
  28. Espinel-Ingroff A, Chakrabarti A, Chowdhary A, et al. Multicenter evaluation of MIC distributions for epidemiologic cutoff value definition to detect amphotericin B, posaconazole, and itraconazole resistance among the most clinically relevant species of Mucorales. Antimicrob Agents Chemother. 2015;59(3):1745-50. [DOI:10.1128/AAC.04435-14] [PMID]
  29. Arendrup MC, Jensen RH, Meletiadis J. In vitro activity of isavuconazole and comparators against clinical isolates of the Mucorales order. Antimicrob Agents Chemother. 2015;59(12):7735-42. [DOI:10.1128/AAC.01919-15] [PMID]
  30. Chowdhary A, Kathuria S, Singh PK, et al. Molecular characterization and in vitro antifungal susceptibility of 80 clinical isolates of mucormycetes in Delhi, India. Mycoses. 2014;57(S3):97-107. [DOI:10.1111/myc.12234] [PMID]
  31. Chowdhary A, Singh PK, Kathuria S, Hagen F, Meis JF. Comparison of the EUCAST and CLSI broth microdilution methods for testing isavuconazole, posaconazole, and amphotericin B against molecularly identified Mucorales species. Antimicrob Agents Chemother. 2015;59(12):7882-7. [DOI:10.1128/AAC.02107-15] [PMID]
  32. Pfaller MA, Rhomberg PR, Wiederhold NP, et al. In vitro activity of isavuconazole against opportunistic fungal pathogens from two mycology reference laboratories. Antimicrob Agents Chemother. 2018;62(10):e01230-18. [DOI:10.1128/AAC.01230-18] [PMID]
  33. Abdorahimi M, Pakdel F, Salehi M, et al. COVID-19-associated rhino-orbital-cerebral mucormycosis: clinical features, antifungal susceptibility, management and outcome in a tertiary hospital in Iran. Mycopathologia. 2023;188(5):783-92. [DOI:10.1007/s11046-023-00785-3] [PMID]
  34. Pfaller MA, Carvalhaes CG, Devries S, Rhomberg PR, Castanheira M. Impact of COVID-19 on the antifungal susceptibility profiles of isolates collected in a global surveillance program that monitors invasive fungal infections. Med Mycol. 2022;60(5):28-34. [DOI:10.1093/mmy/myac028] [PMID]
Volume 20, Issue 1
Winter 2025
Pages 98-107

  • Receive Date 21 July 2024
  • Revise Date 20 August 2024
  • Accept Date 07 December 2024