Diagnostic Performance of Pancreatic Cytology with the Papanicolaou Society of Cytopathology System: A Systematic Review, before Shifting into the Upcoming WHO International System.

Ilias Nikas,Dimitrios Ntourakis,Stylianos Chatziioannou,Svenja Seide,Jordan Reynolds,Tanja Proctor

doi:10.3390/ijms23031650

Abstract

The Papanicolaou Society of Cytopathology (PSC) reporting system classifies pancreatobiliary samples into six categories (I–VI), providing guidance for personalized management. As the World Health Organization (WHO) has been preparing an updated reporting system for pancreatobiliary cytopathology, this systematic review aimed to evaluate the risk of malignancy (ROM) of each PSC category, also the sensitivity and specificity of pancreatic FNA cytology using the current PSC system. Five databases were investigated with a predefined search algorithm. Inclusion and exclusion criteria were applied to select the eligible studies for subsequent data extraction. A study quality assessment was also performed. Eight studies were included in the qualitative analysis. The ROM of the PSC categories I, II, III, IV, V, VI were in the ranges of 8–50%, 0–40%, 28–100%, 0–31%, 82–100%, and 97–100%, respectively. Notably, the ROM IVB (“neoplastic—benign”) subcategory showed a 0% ROM. Four of the included studies reported separately the ROMs for the IVO subcategory (“neoplastic—other”; its overall ROM ranged from 0 to 34%) with low (LGA) and high-grade atypia (HGA). ROM for LGA ranged from 4.3 to 19%, whereas ROM for HGA from 64 to 95.2%. When the subcategory IVO with HGA was considered as cytologically positive, together with the categories V and VI, there was a higher sensitivity of pancreatic cytology, at minimal expense of the specificity. Evidence suggests the proposed WHO international system changes—shifting the IVB entities into the “benign/negative for malignancy” category and establishing two new categories, the “pancreatic neoplasm, low-risk/grade” and “pancreatic neoplasm, high-risk/grade”—could stratify pancreatic neoplasms more effectively than the current PSC system.

Highlights

Fine-needle aspiration (FNA) of the pancreas—performed mostly with endoscopic ultrasound (EUS-FNA)—is a safe, minimally-invasive, and specific diagnostic procedure.EUS-FNA can effectively triage the aspirated material for cytomorphologic, biochemical, and molecular pathology evaluation, facilitating the diagnosis of pancreatic solid and cystic lesions and improving patient care [1,2,3]
The Papanicolaou Society of Cytopathology (PSC) reporting system was developed with the aim to improve communication among clinicians and offer guidance for personalized management, through providing risk stratification and supporting a multimodal approach that incorporates cytomorphologic, radiologic, biochemical, immunochemical, and molecular findings [4,5]
Cystic fluid levels more than 192 ng/mL and/or the presence of a KRAS mutation support the diagnosis of mucinous neoplastic cyst, while a GNAS mutation the diagnosis of intraductal papillary mucinous neoplasms (IPMNs) [5,20,21,22,23]

Summary

Introduction

EUS-FNA can effectively triage the aspirated material for cytomorphologic, biochemical, and molecular pathology evaluation, facilitating the diagnosis of pancreatic solid and cystic lesions and improving patient care [1,2,3]. The Papanicolaou Society of Cytopathology (PSC) reporting system uses a standardized approach, classifying pancreatobiliary samples into the following categories: I, nondiagnostic; II, negative; III, atypical; IV, neoplastic (consisting of two subcategories: IVB, neoplastic—benign; IVO, neoplastic—other); V, suspicious for malignancy; and IV, malignant. While the IVB category comprises mostly serous cystadenoma (SCA), the IVO is rather heterogeneous including intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) of any grade, besides solid neoplasms exhibiting malignant potential, like pancreatic neuroendocrine tumors (PanNETs) and solid pseudopapillary neoplasms (SPNs) [4,5]. Proposed changes include eliminating the “neoplastic: benign” PSC subcategory, while shifting SCA and lymphangioma interpretations into the “benign/negative for malignancy” WHO category; replacing the “neoplastic—other” PSC category with two new WHO categories, the “pancreatic neoplasm, low-risk/grade” and “pancreatic neoplasm, high-risk/grade”, encompassing the interpretations of IPMN or MCN with low-to intermediate and high-grade dysplasia, respectively; and moving the PanNETs and SPNs from the “neoplastic—other” PSC subcategory into the WHO category “positive for malignancy”, aligning with the recent WHO Classification of the Digestive System Tumors [6,7]

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Discussion

Conclusion