Modern Techniques in Cytopathology

Modern Techniques in Cytopathology

Monographs in Clinical Cytology

Vol. 25

Series Editor

Philippe Vielh Paris

Modern Techniques in Cytopathology

Volume Editors

Marilyn M. Bui Tampa, FL

Liron Pantanowitz Pittsburgh, PA

60 figures in color, and 9 tables, 2020

Monographs in Clinical Cytology

Founded 1965 by Georg L. Wied, Chicago, IL

_______________________

Dr. Marilyn M. Bui

Department of Pathology

Moffitt Cancer Center

12902 USF Magnolia Drive

Tampa, FL 33612 (USA)

E-Mail Marilyn.Bui@moffitt.org

_______________________

Dr. Liron Pantanowitz

Department of Pathology

UPMC Cancer Pavilion Suite 201

5150 Centre Avenue

Pittsburgh, PA 15232 (USA)

E-Mail pantanowitzl@upmc.edu

Library of Congress Cataloging-in-Publication Data

Names: Bui, Marilyn M., editor. | Pantanowitz, Liron, editor.

Title: Modern techniques in cytopathology / volume editors, Marilyn M. Bui, Liron Pantanowitz.

Other titles: Monographs in clinical cytology ; v. 25. 0077-0809

Description: Basel ; Hartford : Karger, 2020. | Series: Monographs in clinical cytology, 0077-0809 ; vol. 25 | Includes bibliographical references and index. | Summary: The purpose of this book is to describe, illustrate, and review many of the most recent developments regarding modern techniques employed in cytopathology. It is intended for all cytologists, including cytopathologists, cytotechnologists, cytology lab assistants, trainees, research scientists, and anyone who is interested in the field of cytopathology-- Provided by publisher.

Identifiers: LCCN 2019055020 (print) | LCCN 2019055021 (ebook) | ISBN 9783318065756 hardcover ; alk. paper | ISBN 9783318065763 ebook

Subjects: MESH: Cytodiagnosis--methods | Cells--pathology

Classification: LCC RB43 (print) | LCC RB43 (ebook) | NLM W1 MO567KF v.25 2020 | DDC 616.07/582--dc23

LC record available at https://lccn.loc.gov/2019055020

LC ebook record available at https://lccn.loc.gov/2019055021

Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents®.

Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.

All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.

© Copyright 2020 by S. Karger AG, P.O. Box, CH-4009 Basel (Switzerland)

www.karger.com

Printed on acid-free and non-aging paper (ISO 9706)

ISSN 0077–0809

ISBN 978–3–318–06575–6

e-ISBN 978–3–318–06576–3

Contents

Bui MM, Pantanowitz L (eds): Modern Techniques in Cytopathology.

Monogr Clin Cytol. Basel, Karger, 2020, vol 25, pp V–VI (DOI: 10.1159/000455771)

Preface

In the era of precision medicine, physicians are increasingly in need of more definitive diagnostic, prognostic, and predictive information derived from small biopsy specimens such as cytology samples to guide effective patient care. Cytopathology is well poised to meet this challenge. Whilst the traditional cytomorphologic component of cytology practice is still valid, there have been enormous advances made in the field of cytopathology thanks to transformative technology and innovative individuals that have augmented the cytologists’ ability to meet the demands of modern medicine. The purpose of this book is to describe, illustrate, and review many of the most recent developments regarding modern techniques employed in cytopathology.

This contemporary monograph is intended for all cytologists, including cytopathologists, cytotechnologists, cytology lab assistants, trainees, research scientists, and anyone who is interested in the field of cytopathology. We have invited pioneering experts in their respective fields to author these chapters. This book is not only the culmination of their groundbreaking work and effort, but also represents a critical review of the current literature. We have attempted to provide readers with an informative and comprehensive aid so that they may better appreciate how emerging technology has been applied to cytology.

Readers will note that the book begins with a chapter by Rollins [1] about cytopathologists performing their own ultrasound-guided fine needle aspirations (USFNA). This chapter explains how the scope of practice for clinical cytologists has expanded by adding USFNA to their repertoire. The next chapter, by Saqi and Balassanian [2], covers cell blocks, addressing up-and-coming techniques and their practical applications. Cytology material has proven to be increasingly suitable for many new ancillary studies, often averting the need to procure large tissue samples with invasive methods. This premise is highlighted in the chapter on fluorescence in situ hybridization by Monaco and Dacic [3] as well as the chapter by Roy-Chowdhuri et al. [4] on next-generation sequencing in cytopathology. Cytopathologists have also been leading the charge with liquid biopsy, an even lesser invasive procedure than FNA. The field of liquid biopsy is methodically reviewed in the well-illustrated chapter by Katz et al. [5] about recent advances in the detection of circulating tumor cells and their clinical application. The adoption of digital imaging in cytology is another area that has grown significantly for both clinical and non-clinical applications. This book accordingly incorporates several relevant chapters including computer-assisted Pap test screening by Pantanowitz and Bui [6], telecytology for rapid on-site evaluation by Hanna et al. [7], whole-slide imaging by Li et al. [8], and image analysis by Pantanowitz and Bui [9]. The final chapter by Pantanowitz et al. [10] encompasses a potpourri of exciting topics, including clinical trials in cytology and cytobanking. However, it does not matter in which order the chapters of this book are read as each chapter represents a stand-alone contemporary review of emerging topics in cytopathology. We hope that you will find this monograph to be thought-provoking and a valuable reference for your practice.

Acknowledgements

The editors are thankful to all of the contributors for their expertise and effort. Special thanks are extended to Dr. Philippe Vielh, who envisioned and propelled this project. We also express our gratitude to our family for their unwavering support of our academic work.

Disclosure Statement

The editors have no conflicts of interest to declare.

Marilyn M. Bui, Tampa, FL, USA

Liron Pantanowitz, Pittsburgh, PA, USA

References

1Rollins SD: The interventional cytopathologist and ultrasound-guided fine-needle aspiration; in Bui MM, Pantanowitz L (eds): Modern Techniques in Cytopathology. Monogr Clin Cytol. Basel, Karger, 2020, vol 25. DOI: 10.1159/000455781.

2Saqi A, Balassanian R: Cell Blocks: Evolution, modernization, and assimilation into emerging technologies; in Bui MM, Pantanowitz L (eds): Modern Techniques in Cytopathology. Monogr Clin Cytol. Basel, Karger, 2020, vol 25. DOI: 10.1159/000455772.

3Monaco SE, Dacic S: Fluorescence in situ hybridization in cytopathology; in Bui MM, Pantanowitz L (eds): Modern Techniques in Cytopathology. Monogr Clin Cytol. Basel, Karger, 2020, vol 25. DOI: 10.1159/000455777.

4Roy-Chowdhuri S, Somak R, Pantanowitz L: Next-generation sequencing in cytopathology; in Bui MM, Pantanowitz L (eds): Modern Techniques in Cytopathology. Monogr Clin Cytol. Basel, Karger, 2020, vol 25. DOI: 10.1159/000455779.

5Katz RL, Zaidi TM, Xiaohui N: Liquid biopsy: recent advances in the detection of circulating tumor cells and their clinical application; in Bui MM, Pantanowitz L (eds): Modern Techniques in Cytopathology. Monogr Clin Cytol. Basel, Karger, 2020, vol 25. DOI: 10.1159/000455780.

6Pantanowitz L, Bui MM: Computer-assisted Pap test screening; in Bui MM, Pantanowitz L (eds): Modern Techniques in Cytopathology. Monogr Clin Cytol. Basel, Karger, 2020, vol 25. DOI: 10.1159/000455774.

7Hanna MG, Lin O, Sirintrapun SJ, Pantanowitz L: Telecytology for rapid on-site evaluation; in Bui MM, Pantanowitz L (eds): Modern Techniques in Cytopathology. Monogr Clin Cytol. Basel, Karger, 2020, vol 25. DOI: 10.1159/000496525.

8Li Z, Quick M, Pantanowitz L: Whole-slide imaging in cytopathology; in Bui MM, Pantanowitz L (eds): Modern techniques in cytopathology. Monogr Clin Cytol. Basel, Karger, 2020, vol 25. DOI: 10.1159/000455775.

9Pantanowitz L, Bui MM: Image analysis in cytopathology; in Bui MM, Pantanowitz L (eds): Modern Techniques in Cytopathology. Monogr Clin Cytol. Basel, Karger, 2020, vol 25. DOI: 10.1159/000455776.

10Pantanowitz L, Monaco SE, da Cunha Santos G: Other cytology applications: clinical trials, checkpoint inhibitors, and cytobanking; in Bui MM, Pantanowitz L (eds): Modern Techniques in Cytopathology. Monogr Clin Cytol. Basel, Karger, 2020, vol 25. DOI: 10.1159/000455773.

Chapter 1

Bui MM, Pantanowitz L (eds): Modern Techniques in Cytopathology.

Monogr Clin Cytol. Basel, Karger, 2020, vol 25, pp 1–5 (DOI: 10.1159/000455781)

______________________

The Interventional Cytopathologist and Ultrasound-Guided Fine-Needle Aspiration

Susan D. Rollins

ETSU Department of Pathology, Outpatient Cytopathology Center, Johnson City, TN, USA

______________________

Abstract

Ultrasound-guided fine-needle aspiration (FNA) biopsy allows for accurate sampling of mass lesions. The diagnostic information from this procedure is maximized when the pathologist is intimately involved with specimen procurement, specimen triage, and interpretation. This chapter discusses the role of the interventional cytopathologist, training opportunities, and basic information for starting a pathologist ultrasound-guided FNA clinic.

© 2020 S. Karger AG, Basel

In 2009, the College of American Pathologists began offering a course to cytologists in ultrasound-guided fine-needle aspiration (USFNA) biopsy entitled Ultrasound-Guided Fine-Needle Aspiration Advanced Practical Pathology Program (USFNA AP3). Prior to this, only a handful of cytopathologists were performing their own USFNA biopsies. In less than a decade, cytopathologists have realized the utility of learning and practicing USFNA. The technique is now taught in residency and fellowship programs. Highlighting the importance of USFNA in cytopathology training programs, the July 2015 ACGME and ABP Cytopathology Milestone Project (PC2) cited this skill as a level 4 milestone in cytopathology training. According to this milestone the cytology trainee should have the following competency: Describes and discusses indications and/or performs ultrasound-guided FNAB and core-needle biopsy [1].

The scope of practice for clinical cytologists is markedly expanded when USFNA is added to their repertoire. In addition to palpable masses, cytologists have the opportunity to sample non-palpable superficial targets. Sampling of palpable masses is also improved. The cytologist has control over needle gauge, number of passes, area of lesion sampled, and, based on rapid on-site cytologic evaluation (ROSE), specimens can be appropriately triaged for ancillary studies such as cell block, immunocytochemical stains, cultures, flow cytometry, molecular studies, and/or core-needle biopsy. With experience, the cytologist can learn how to correlate ultrasound (US) features of a mass with the cytologic findings and can integrate this information into the cytology report to better guide clinicians in appropriate follow-up care and specialist referral. The ability to link the cytology procedure and report to patient management algorithms is immensely valuable for the patient and can be personally gratifying for the clinical cytopathologist. Cytologist-centered USFNA offers patients streamlined, cost-effective, and personalized care.

ROSE of FNA biopsy specimens helps ensure adequate samples for cytologic interpretation. A downside of ROSE is that either a cytotechnologist or pathologist must be on site in radiology or a clinic where the biopsy is performed, which can be a time-intensive endeavor [2]. Even though reimbursement for ROSE is offered, the reimbursement is low and valuable pathologist time is lost [3]. Additionally, if ROSE is undertaken by a cytotechnologist, critical decisions about triage of the specimen may not be possible. Cytopathologist USFNA is preferred over traditional paradigms in which the biopsy is performed by a non-pathologist because the imaging physician assigned to do the biopsy may not be skilled in USFNA. The physician may not understand the importance of sampling masses in specific areas to optimize the sample and could be resistant to suggestions about where to biopsy for optimum sampling. When not under the purview of a cytopathologist, slide smearing and specimen preparation can be poor when it is done by a person not acutely aware of the fragility of cells. A poor smear can sabotage all other aspects of the FNA procedure; therefore, this seemingly simple part of the process is often undervalued by those not intimately involved with specimen interpretation [4].

Training

To date, several didactic and hands-on courses are available to cytopathologists to learn USFNA. The College of American Pathologists’ AP3 multiday course covers topics including the basic physics of US, criteria for stratifying risk of malignancy of a lesion based on US criteria, techniques of needle placement using US guidance, importance and practice of specimen preparation and smearing, and medical coding. If the participant passes two practical examinations and a written exam, a certificate valid for 5 years is awarded for this accomplishment. Other learning venues include courses offered by The American Association of Clinical Endocrinologists (AACE). USFNA courses and poster presentations are now a part of meetings sponsored by the ASC, USCAP, CAP, and ASCP.

Cytologists are eligible to apply for ECNU (Endocrine Certification in Neck Ultrasound) certification. For such certification, the candidate must pass the Comprehensive Certification Examination (CCE) and successfully complete the Validation of Competency Process (VCP). Cytologists who pass this rigorous curriculum may use the ECNU designation after their names.

Taking a course in USFNA is just the beginning of learning the art of US-guided needle placement and correlating mass image characteristics resulting in an integrated cytologic diagnosis. Dedicated practice is needed since every patient can present a slightly different challenge to the aspirating physician, whether that be an anxious or non-compliant patient, body habitus, or location of the mass. Part of what makes USFNA an interesting and challenging endeavor is having to tailor each FNA procedure to the needs of the individual patient. Learning to target specific areas in a mass to within a few millimeters is an art. This takes practice, but when accomplished is very satisfying. The prescription is practice, practice, practice!

US-Cytology Correlation

The triple-test concept in breast FNA is not new to cytopathologists. Physical examination, imaging, and cytology findings all need to be taken into account for clinical guidance. Cytologist USFNA is an expansion of the triple test concept. Much can be learned about a mass to be sampled from its US characteristics: mass shape, margins, echogenicity, blood flow pattern, presence or absence of posterior acoustic shadowing, and characteristics of echogenic foci.

US features of a mass impart a degree of relative risk which can be classified as favor benign, indeterminate, or suspicious for malignancy. The categorization of a mass based on US findings closely parallels what pathologists are already very familiar with based on experience with gross and microscopic pathology. Correlation of US images and cytology findings is of utmost importance. If the US findings are suspicious for malignancy but the cytology is benign, the cytologist needs to determine whether there is a sampling problem or why the US and cytology do not correlate. In the case of benign-appearing US features and malignant cytology, the same correlation needs to be done. For example, a well circumscribed mildly hypoechoic breast mass with posterior enhancement could be classified as favor benign or indeterminate by US criteria, but is a mucinous carcinoma by cytology; the cytologist knows that the results correlate. The cytologist is in the perfect position to understand why these processes have their particular US characteristics. With experience, the cytologist can even begin to predict what cytology will show based on the US features of the lesion. Radiologists, even with the availability of ROSE, do not get to so closely correlate US findings and cytology findings.

Credentialing

At the time of writing this chapter, there is no credentialing required in order for cytopathologists to perform and bill for USFNA. However, no one can predict the whims of insurers and thus this may change.

Fig. 1. USFNA exam room setup.

Cytopathologists may have to meet certain standards by their employers or institutions for whom they work [5, 6]. Institutional requirements may vary greatly, and it is hoped that the cytopathologist will be instrumental with helping to establish credentialing requirements.

Equipment

For a cytologist with an active FNA service, very little additional equipment is required when expanding their service to USFNA. There are numerous US machines available at various price points and features. Choice of a portable or floor model depends on personal preference. For USFNA of superficial masses, a linear high-frequency transducer is required. A small transducer footprint will allow for easier sampling of masses in the head and neck region. Unless a specialized feature such as elastography is desired, almost any modern US will meet the needs for a cytologist doing USFNA. When selecting an US machine, it is important that the buyer is comfortable with the image quality and ease of the user-machine interface. It is important to not only consider the purchase price of the unit, but also the warranty, cost of service contracts, use of a loaner unit if repair