Ebook Atlas of non-gynecologic cytology: Part 1

Part 1 of ebook Atlas of non-gynecologic cytology provide readers with content about: salivary gland fine needle aspiration; thyroid fine needle aspiration cytology; breast cytology; pulmonary cytology; gastrointestinal cytology;... Please refer to the ebook for details!

Atlas of

Non-Gynecologic Cytology

123

Xin Jing Momin T Siddiqui Qing Kay Li

Editors

Atlas of Anatomic Pathology

Series Editor

Liang Cheng

Indianapolis, Indiana

USA

classification of a wide spectrum of benign, congenital, inflammatory, nonneoplastic, and neoplastic lesions in various organ systems Normal and variations of “normal” histology will also be illustrated Each atlas will focus on visual diagnostic criteria and differential diagnosis

It will be organized to provide quick access to images of lesions in specific organs or sites Each atlas will adapt the well-known and widely accepted terminology, nomenclature, classification schemes, and staging algorithms Each volume in this series will be authored by nationally and internationally recognized pathologists Each volume will follow the same organizational structure The first Section will include normal histology and normal variations The second Section will cover congenital defects and malformations The third Section will cover benign and inflammatory lesions The fourth Section will cover benign tumors and benign mimickers

of cancer The last Section will cover malignant neoplasms Special emphasis will be placed on normal histology, gross anatomy, and gross lesion appearances since these are generally lacking

or inadequately illustrated in current textbooks The detailed figure legends will concisely summarize the critical information and visual diagnostic criteria that the pathologist must recognize, understand, and accurately interpret to arrive at a correct diagnosis This book series

is intended chiefly for use by pathologists in training and practicing surgical pathologists in their daily practice The atlas series will also be a useful resource for medical students, cytotechnologists, pathologist assistants, and other medical professionals with special interest

in anatomic pathology Trainees, students, and readers at all levels of expertise will learn, understand, and gain insights into the complexities of disease processes through this comprehensive resource Macroscopic and histological images are aesthetically pleasing in many ways This new series will serve as a virtual pathology museum for the edification of our readers

More information about this series at http://www.springer.com/series/10144

Xin Jing • Momin T Siddiqui • Qing Kay Li Editors

Atlas of Non-Gynecologic Cytology

The University of Michigan-Michigan Medicine

Atlas of Anatomic Pathology

ISBN 978-3-319-89673-1 ISBN 978-3-319-89674-8 (eBook)

https://doi.org/10.1007/978-3-319-89674-8

Library of Congress Control Number: 2018945110

© Springer International Publishing AG, part of Springer Nature 2018

This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction

on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed.

The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.

The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed

to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Printed on acid-free paper

This Springer imprint is published by the registered company Springer International Publishing AG part of Springer Nature

The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Michael, for instilling in me a passion for cytopathology.

One Picture Is Worth Ten Thousand Words — Frederick Barnard, 1927

Remarkable progress has been made in anatomic and surgical pathology during the last 10 years The ability of surgical pathologists to reach a definite diagnosis is now enhanced by immunohistochemical and molecular techniques Many new clinically important histopatho-logic entities and variants have been described using these techniques Established diagnostic entities are more fully defined for virtually every organ system The emergence of personalized medicine has also created a paradigm shift in surgical pathology Both promptness and preci-sion are required of modern pathologists Newer diagnostic tests in anatomic pathology, how-ever, cannot benefit the patient unless the pathologist recognizes the lesion and requests the necessary special studies An up-to-date atlas encompassing the full spectrum of benign and malignant lesions, their variants, and evidence-based diagnostic criteria for each organ system

is needed This atlas is not intended as a comprehensive source of detailed clinical information concerning the entities shown Clinical and therapeutic guidelines are served admirably by a large number of excellent textbooks This atlas, however, is intended as a “first knowledge base” in the quest for definitive and efficient diagnosis of both usual and unusual diseases

The Atlas of Anatomic Pathology is presented to the reader as a quick reference guide for

diagnosis and classification of benign, congenital, inflammatory, nonneoplastic, and neoplastic lesions organized by organ systems Normal histology and variations are illustrated for each organ and anatomic system The atlas focuses on visual diagnostic criteria and differential diagnosis The organization is intended to provide quick access to images and confirmatory tests for each specific organ or site The atlas adopts the well-known and widely accepted ter-minology, nomenclature, classification schemes, and staging algorithms

This book series is intended chiefly for use by pathologists in training and practicing cal pathologists in their daily practice It is also a useful resource for medical students, cyto-technologists, pathologist assistants, and other medical professionals with special interest in anatomic pathology We hope that our trainees, students, and readers at all levels of expertise will learn, understand, and gain insight into the pathophysiology of disease processes through this comprehensive resource Macroscopic and histological images are aesthetically pleasing

surgi-in many ways We hope that the new series will serve as a virtual pathology museum for the edification of our readers

As we all know, cytology not only provides an accurate diagnosis at the cellular level by using minimally invasive procedures but also provides material for molecular characterization of a lesion/tumor for targeted therapy In the era of personalized medicine, cytology has continued

to grow and evolve as a critical diagnostic tool Recently, the diagnostic criteria of tumors have become more refined, and certain terminology has been changed based on current TCGA (the Cancer Genome Atlas) data and WHO classifications Therefore, it is necessary to update our knowledge and terminology in cytology

In this book, we focus on all aspects of non-gynecologic cytopathology, from key features

of benign and malignant lesions to diagnostic pearls and ancillary testing Although this book

is written by multiple authors, all chapters follow a similar format: brief introduction of the specific organ/system (including types of specimens and techniques to obtain samples), description of normal findings, and a practical approach to diagnose benign and malignant lesions The key cytomorphological features and main differential diagnoses of lesions are also summarized in concise tables Images in each chapter are instructive and represent findings It

also retains the quality and clarity of the Atlas of Anatomic Pathology series, and, like other

volumes, this volume aims to be concise and comprehensive yet clinically relevant to daily practice We also discuss important ancillary tests in each chapter, such as flow cytometry, immunohistochemistry, and molecular testing, which are crucial for an accurate diagnosis and differential diagnosis as well as for targeted therapy The updated knowledge, key cytomorpho-logical features, current terminology, and molecular diagnostic tests are the highlights of this book

Finally, we wish for our book to be a practical resource for cytotechnologists, gists, and pathologists who are practicing general surgical pathology and cytopathology The book will also be a valued text for medical students, residents, fellows, and other allied health personnel who take care and/or treat patients based on the histological diagnosis of diseases

New York, NY, USA Momin T. Siddiqui, M.D., F.I.A.C Baltimore, MD, USA Qing Kay Li, M.D., Ph.D., F.C.A.P

Preface

1 Salivary Gland Fine Needle Aspiration 1

He Wang, Aatika Malik, and Yun Gong

2 Thyroid Fine Needle Aspiration Cytology 19

Gabriela Oprea-Ilies and Momin T Siddiqui

6 Pancreaticobiliary Tract Cytology 157

Judy Pang and Andrew Sciallis

7 Liver Cytology 173

Derek B Allison, David Borzik, and Qing Kay Li

8 Kidney and Adrenal Gland Cytology 199

11 Lymph Node Cytology 259

Von G Samedi and Qian-Yun Zhang

Index 289

Contents

Yun  Gong, M.D Department of Pathology and Laboratory Medicine, The University of

Texas MD Anderson Cancer Center, Houston, TX, USA

Xin Jing, M.D Department of Pathology, The University of-Michigan Medicine, Ann Arbor,

MI, USA

Madelyn Lew, M.D Department of Pathology, University of Michigan, Ann Arbor, MI, USA Qing  Kay  Li, M.D., Ph.D., F.C.A.P Department of Pathology and Oncology, The Johns

Hopkins Medical Institutions, Baltimore, MD, USA

Aatika Malik, M.D Department of Pathology and Laboratory Medicine, Temple University

Lewis Katz School of Medicine, Philadelphia, PA, USA

Gabriela Oprea-Ilies, M.D Department of Pathology, Emory University School of Medicine,

Atlanta, GA, USA

Judy  Pang, M.D Department of Pathology, The University of Michigan, Ann Arbor,

Momin  T.  Siddiqui, M.D., F.I.A.C Department of Pathology and Laboratory Medicine,

Weill Cornell Medicine, New York, NY, USA

He Wang, M.D., Ph.D Department of Pathology and Laboratory Medicine, Robert Wood

Johnson Medical School of Rutgers University, New Brunswick, NJ, USA

Qian-Yun  Zhang, M.D., Ph.D Department of Pathology, University of New Mexico

Hospital, Albuquerque, NM, USA

© Springer International Publishing AG, part of Springer Nature 2018

X Jing et al (eds.), Atlas of Non-Gynecologic Cytology, Atlas of Anatomic Pathology,

https://doi.org/10.1007/978-3-319-89674-8_1

Salivary Gland Fine Needle Aspiration

He Wang, Aatika Malik, and Yun Gong

Introduction

Salivary glands comprise three paired major glands—the

parotid, submandibular, and sublingual—and numerous

minor glands Most salivary gland fine needle aspiration

(FNA) targets parotid and submandibular glands The masses

or cystic lesions of salivary glands have a wide range of

dif-ferential diagnoses, from inflammatory response to

neo-plasm to less common causes of infection [1] The World

Health Organization has included at least 37 morphologic

types of primary salivary gland tumors, many of which show

remarkable overlapping of morphologic features (Table 1.1)

[2] The application of needle aspiration to diagnose salivary

gland lesions was documented by the 1930s [3 4] Over the

past few decades, FNA has developed into a widely accepted

diagnostic procedure and is often the first step in the

evalua-tion of salivary gland lesions, with reported 79% accuracy,

74% sensitivity, and 88% specificity rates [5 7] FNA has

the potential to change the clinical approach in up to one

third of patients [8] The high accuracy of salivary gland

FNA benefits from high frequencies of certain tumors with

relatively unique cytologic features, including matrix

com-ponent in the smears The main purpose of this chapter is to

highlight these characteristic findings It cannot be

overem-phasized that these morphologic features must be interpreted

in the appropriate clinical and radiologic settings, including

lesion site and size, speed of growth, clinical symptoms, and the patient’s age, gender, and ethnicity Like any cytologic samples, accurate salivary gland FNA diagnosis depends on adequate tissue sampling Procedures including rapid on-site

H Wang, M.D., Ph.D ( * )

Department of Pathology and Laboratory Medicine,

Robert Wood Johnson Medical School of Rutgers University,

New Brunswick, NJ, USA

e-mail: hw423@rwjms.rutgers.edu

A Malik, M.D

Department of Pathology and Laboratory Medicine, Temple

University Lewis Katz School of Medicine, Philadelphia, PA, USA

e-mail: aatika.malik@tuhs.temple.edu

Y Gong, M.D

Department of Pathology and Laboratory Medicine, The University

of Texas MD Anderson Cancer Center, Houston, TX, USA

e-mail: yungong@mdanderson.org

1

Table 1.1 World Health Organization histologic classifications of

salivary gland neoplasms [ 2 ] Classification Entities Malignant tumors Mucoepidermoid carcinoma

Adenoid cystic carcinoma Acinic cell carcinoma Polymorphous adenocarcinoma Clear cell carcinoma

Basal cell adenocarcinoma Intraductal carcinoma Adenocarcinoma, not otherwise specified Salivary duct carcinoma

Myoepithelial carcinoma Epithelial-myoepithelial carcinoma Carcinoma ex pleomorphic adenoma Secretory carcinoma

Sebaceous adenocarcinoma Carcinosarcoma

Poorly differentiated carcinoma Lymphoepithelial carcinoma Small-cell carcinoma Oncocytic carcinoma Sialoblastoma Benign tumors Pleomorphic adenoma

Myoepithelioma Basal cell adenoma Warthin tumor Oncocytoma Lymphadenoma Cystadenoma Sialadenoma papilliferum Ductal papilloma Sebaceous adenoma Canalicular adenoma Other ductal adenomas Benign soft tissue

lesions

Hemangioma Lipoma/sialolipoma Hematolymphoid

tumors

MALT lymphoma Follicular lymphoma Diffuse large B-cell lymphoma (DLBCL)

evaluation (ROSE) are critical to ensure sufficient diagnostic

material

For a long time, there has been no consensus on how to

report salivary gland cytopathology The result has been

inconsistent use of terminologies among institutions and

individual cytopathologists, causing confusion in

communi-cation between cytopathologists and clinicians [9] An

inter-national group of cytopathologists, surgical pathologists,

and head and neck surgeons have recently drafted The Milan

System for Reporting Salivary Gland Cytopathology

(Table 1.2) This practical, user-friendly classification

sys-tem is sponsored by the American Society of Cytopathology

and the International Academy of Cytopathology [10]

Impressive advances have been made in recent years in

the understanding of the molecular pathogenesis of salivary

gland tumors These molecular changes, including several

recurrent chromosome translocations, have been identified

in several common subtypes of salivary gland tumors [1 9

11] Though validation of these newly identified genetic

changes and development of targeted therapies is still

ongo-ing, ancillary tests based on these genetic changes have been

introduced into daily practice (Table 1.3) [12, 13] Other

technologies, including tissue microarray of antibody,

pro-vide another set of diagnostic markers for more accurate

classification of salivary gland tumors (Table 1.4) [14]

Table 1.3 Molecular biomarkers for salivary gland tumors

Pleomorphic adenoma PLAG1 fusions

CRTC3-MAML2

30–80%

~5%

Del(1p) Adenoid cystic carcinoma (ACC) MYB-NF1B >80% Del(1p), del(6q)

Mammary analogue secretory carcinoma (MASC) ETV6-NTRK3 Translocation >80%

Hyalinizing clear cell carcinoma (HCCC) EWSR1-ATF1 ~80%

PLAG1 pleomorphic adenoma gene 1, HMG2 high mobility group AT-hook 2, HER2 human epidermal growth factor receptor 2, TP53 tumor protein p53, CRTC1 cAMP response element-binding protein-regulated transcription coactivator 1, MAML2 mastermind-like 2, CRTC3 cAMP response element-binding protein-regulated transcription coactivator 3, Del deletion, MYB v-myb avian myeloblastosis viral oncogene homolog,

NF1B nuclear factor 1/B, ETV6 Ets variant gene 6, NTRK3 neurotrophic tyrosine receptor kinase type 3, EWSR1 Ewing sarcoma breakpoint region

1, ATF1 activating transcription factor 1, AR androgen receptor

Table 1.2 The Milan System for Reporting Salivary Gland

Cytopathology Diagnostic category

Risk of malignancy Management Nondiagnostic 25% Clinical and

radiologic correlation; repeat FNA

Nonneoplastic 10% Clinical follow-up

and radiologic correlation Atypia of undetermined

significance (AUS)

20% Repeat FNA or

surgery Neoplasm

• Benign <5% Surgery or clinical

follow-up

• Salivary gland neoplasm of uncertain malignant potential

(SUMP)

35% Surgery

Suspicious for malignancy (low-grade versus high-grade)

60% Surgery

Malignant (low-grade versus high-grade)

90% Surgery

Adapted from Faquin et al [ 10 ]; with permission

Table 1.4 Immunohistochemical markers for salivary gland tumors

Pleomorphic adenoma Positive: PLAG1, GFAP, Sox-10

Carcinoma ex pleomorphic adenoma Positive: PLAG1

Mucoepidermoid carcinoma (MEC) Positive: cytokeratin-7, cytokeratin-8, and cytokeratin-19

Negative: SMA; Sox-10; S100 Myoepithelial carcinoma (MC) Positive: vimentin; calponin; AE1/AE3; S100

Acinic cell carcinoma Positive: DOG-1, Sox-10, alpha-1- antichymotrypsin, S-100

Adenoid cystic carcinoma (ACC) Positive: CD117, MyB, CK7, p63, Sox-10

Mammary analogue secretory carcinoma

Nonneoplastic Lesions of the Salivary Gland

Nonneoplastic salivary gland lesions can be cystic or can

form discrete masses The underlying causes range from

congenital, obstructive, infective, and reactive causes

to  autoimmune conditions Aspirates with abundant

lymphocytes may need to be differentiated from

lym-phoma, whereas cystic lesions with degenerative

squa-mous cells showing minimal nuclear atypia need to be

differentiated from cystic metastatic squamous cell

carci-noma (Figs. 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.10,

and 1.11)

Fig 1.1 Low-power view of acinar cells in a normal salivary gland

The serous-type acinar cells are large, with eccentrically placed round

to oval nuclei and abundant granular cytoplasm (Diff-Quik stain)

Fig 1.2 High-power view of acinar cells in a normal salivary gland

The normal acinar cells in parotid glands are present in grape-like

clus-ters with associated small, inconspicuous tubules (Diff-Quik stain)

Fig 1.4 Diffuse hyperplastic oncocytosis of parotid gland Cohesive

sheets of oncocytic large cells with abundant cytoplasm and round, trally placed nuclei The background is clear, without fluid or lymphoid cells Histologic examination shows no capsule surrounding the lesion (Papanicolaou stain)

cen-Fig 1.3 Non-tyrosine crystals in a parotid gland cystic lesion Many

geo-metric, multifaceted non-birefringent crystalloids varying in size Crystalloids were rectangular or rod-shaped with smooth ends and parallel sides Background degenerated inflammatory cells (Papanicolaou stain)

Fig 1.5 Reactive intraparotid gland lymph nodes, with abundant,

iso-lated, and polymorphous lymphocytes and macrophages

Lymphoglandular bodies are seen in the background (Papanicolaou stain)

Fig 1.6 Resolving acute sialadenitis Numerous neutrophils in the

background of acinar cells and admixed adipose tissue (Diff-Quik stain)

Fig 1.7 Resolving acute sialadenitis Numerous neutrophils in the

background of acinar cells and a few ductal cells (Papanicolaou stain)

Fig 1.8 Granulomatous sialadenitis Aggregates of epithelioid

histio-cytes and admixed lymphohistio-cytes No necrotic debris is identified in this case (Diff-Quik stain)

Fig 1.9 Lymphoepithelial cyst Degenerated squamous cells,

abun-dant lymphocytes, macrophages, and cellular debris (Diff-Quik stain)

Fig 1.10 Lymphoepithelial cyst Degenerated glandular epithelium,

with few ciliated cells, background macrophages, and cellular debris (Diff-Quik stain)

Fig 1.11 Atypical squamous cells in nonneoplastic cysts The

squa-mous cells show mild nuclear atypia: minimal change in nuclear size

and shape, focal crowding, minimal nuclear contour irregularities, and

prominent nucleoli in a few cells (Papanicolanu stain)

Benign Epithelial Neoplasms of the Salivary

Gland

In a population-based study, benign tumors were five

times more common than malignant tumors [15]

Pleomorphic adenoma (PA) is the most common

sali-vary gland tumor; Warthin tumor is the second most

common Fortunately, both tumors show characteristic

cytologic features More women than men are affected

by benign salivary gland tumors (Figs. 1.12, 1.13, 1.14,

1.15, 1.16, 1.17, 1.18, 1.19, 1.20, 1.21, 1.22, 1.23, 1.24,

and 1.25)

Fig 1.12 Pleomorphic adenoma Sheets of ductal epithelial cells,

indi-vidual myoepithelial cells, and pale, chondromyxoid matrix (Papanicolaou stain, low power)

Fig 1.13 Pleomorphic adenoma In the air-dried preparation, the

matrix material is prominent, with characteristic frayed edges, and the individual myoepithelial cells are embedded within the matrix Note the sheet of ductal epithelial cells in the right upper corner (Diff-Quik stain, low power)

Fig 1.15 Pleomorphic adenoma The chondromyxoid matrix is the major

component in this smear; individual myoepithelial cells are identified only

at the periphery of the matrix or in the spaces between the matrixes Rare

sheets of ductal epithelial cells are visible (Diff-Quik stain)

Fig 1.16 Pleomorphic adenoma The chondromyxoid matrix is the

major component in this smear Epithelial cells are not identifiable;

only rare myoepithelial cells are present (Diff-Quik stain, low power)

Fig 1.17 Pleomorphic adenoma Elongated mesenchymal cells are

obvious in this case The pale, chondromyxoid matrix and small sheets

of bland ductal epithelial cells are characteristic (Papanicolaou stain)

Fig 1.18 Cellular pleomorphic adenoma This highly cellular smear is

filled with bland ductal epithelial cells and individual or loosely nected myoepithelial cells Careful examination reveals small clusters

con-of matrix with characteristic frayed edges (Diff-Quik stain)

Fig 1.19 Warthin tumor A cohesive, flat sheet of oncocytes with

orderly arrangement and distinct cell borders The oncocytes show form, round nuclei with even chromatin distribution; the cytoplasm is rich and granular A few inflammatory cells are seen in the background (Diff-Quik stain)

uni-Fig 1.14 Pleomorphic adenoma Groups of bland epithelial cells and rare

myoepithelial cells are clearly visible The chondromyxoid matrix is less

obvious compared to that in Diff-Quik preparation (Papanicolaou stain)

Fig 1.20 Warthin tumor A cohesive, flat sheet of oncocytes with

orderly arrangement and distinct cell borders The background cystic

content is greenish brown and granular The lymphocytes are small,

with reactive pattern (Diff-Quik stain)

Fig 1.21 Warthin tumor The lymphocytes are abundant and small,

with reactive pattern A few macrophages and rare clusters of cohesive,

flat sheets of oncocytes with admixed lymphocytes are also visible The

background cystic content is greenish brown and granular (Papanicolaou

stain)

Fig 1.22 Basal cell adenoma Small- and intermediate-sized

mono-morphic, basaloid epithelial cells in cohesive groups The basaloid cells show scant cytoplasm and high nuclear/cytoplasmic ratios Dense, metachromatic, basement membrane-like stromal material in hyaline globules is characteristic (Diff-Quik stain)

Fig 1.23 Basaloid neoplasm Small- and intermediate-sized basaloid

epithelial cells with mild variability in cellular size The basaloid cells show scant cytoplasm and high nuclear/cytoplasmic ratios, no obvious nucleoli identified, but mild nuclear contour irregularities are obvious Basement membrane-like stromal material is obvious in one side of the group (Papanicolaou stain)

Fig 1.24 Oncocytoma Sheets of large, polygonal cells with centrally

placed round to oval nuclei and abundant granular cytoplasm The

background cystic content is clean and contains no lymphocytes

Oncocytomas are usually noncystic (Diff-Quik stain)

Fig 1.25 Oncocytoma Tightly clustered large bland polygonal cells

with centrally placed round nuclei without prominent nucleoli;

abun-dant cytoplasm with pink fine granules The background contains no

matrix or lymphocytes (Papanicolaou stain)

Fig 1.26 Mucoepidermoid carcinoma The smear shows mixed tumor

cell types including mucus cells, epidermoid cells, and intermediate cells, as well as mucinous background The mucus cells have a colum- nar appearance with intracytoplasmic mucin; the epidermoid cells are polygonal, with dense, cyanophilic cytoplasm; the intermediate cells are smaller, with immature squamous metaplasia-like appearance (Diff- Quik stain)

Primary Salivary Gland Carcinomas

In well-sampled and well-prepared FNA samples, high- grade malignant salivary gland tumors like salivary duct carcino-mas have cytomorphologic features that are distinctive enough to allow them to be categorized in the “malignant” category [16–18] However, some low-grade tumors like acinic cell carcinoma, epithelial myoepithelial carcinoma, and low-grade mucoepidermoid carcinoma show a cytomor-phologic overlap with their benign counterparts that precludes

a definitive diagnosis of malignancy by morphological ation alone In these situations, ancillary studies, including molecular and histochemical tests, are critically important in the differentiation between “benign” and “malignant” tumors [9] Clinically, adequate resection of low-grade malignant tumors is frequently sufficient, but high-grade malignant tumors usually require additional intervention with lymph node dissection and possible sacrifice of the facial nerve (Figs. 1.26, 1.27, 1.28, 1.29, 1.30, 1.31, 1.32, 1.33, 1.34, 1.35,

evalu-1.36, 1.37, 1.38, 1.39, 1.40, 1.41, 1.42, and 1.43)

Fig 1.27 Mucoepidermoid carcinoma Only a few mucus cells are

identified in this case Most tumor cells show prominent nucleoli with

mild variability in nuclear size and shape Few tumor cells illustrate

mild nuclear contour irregularities (Papanicolaou stain)

Fig 1.28 Mucoepidermoid carcinoma The mixed-type tumor cells are

clearly malignant with hyperchromasia, irregular nuclear contour, high nuclear to cytoplasmic ratio, and significant variability in cell size and shape Mucinous tumor cells with clear intracytoplasmic mucin are clearly visible, with surrounding epidermoid tumor cells Abundant background mucin is also noted (Papanicolaou stain)

Fig 1.29 (a) Carcinoma ex pleomorphic adenoma Sheets of bland

ductal epithelial cells, individual myoepithelial cells, and

chondromyx-oid matrix This portion of tumor shows the typical features of

pleomor-phic adenoma (Diff-Quik stain) (b) Carcinoma ex pleomorpleomor-phic

adenoma Sheets of large polygonal neoplastic cells with abundant

finely vacuolated and granular cytoplasm, as well as cytologically bland

round nuclei No distinct cell border This portion of tumor shows the

typical features of acinic cell carcinoma (Diff-Quik stain) (c)

Carcinoma ex pleomorphic adenoma A cluster of high-grade noma cells with hyperchromasia, irregular nuclear contour, high nuclear

carci-to cycarci-toplasmic ratio, and significant variability in cell size and shape

Note the matrix in the center with frayed edges (Diff-Quik stain) (d)

Carcinoma ex pleomorphic adenoma Another cluster of high-grade carcinoma cells with hyperchromasia, irregular nuclear contour, and high nuclear to cytoplasmic ratio Prominent and pleomorphic nucleoli are noted (Papanicolaou stain) Images courtesy of Dr Xin Jing

Fig 1.30 High-grade carcinoma ex pleomorphic adenoma

Corres-ponding histological examination of above case A variety of histologic

patterns are present, including salivary duct carcinoma and acinic cell

carcinoma Foci of tumor necrosis are also noted (H&E stain) Image

courtesy of Dr Xin Jing

Fig 1.31 Adenoid cystic carcinoma The tumor cells are small,

uni-form, and basaloid, with scant cytoplasm and usually bland nuclei The tumor cells form cohesive clusters Variable-sized, metachromatic base- ment membrane-like hyaline globules are sharply bordered (Diff-Quik stain)

Fig 1.29 (continued)

Fig 1.32 Adenoid cystic carcinoma The matrix component is scant

and pale in this solid variant of adenoid cystic carcinoma The basaloid

cells are uniform, with scant cytoplasm and usually bland nuclei

(Papanicolaou stain)

Fig 1.33 Acinic cell carcinoma Sheets of large, polygonal epithelial

cells with rich granular cytoplasm and indistinct cell borders No well-

formed, “grape-like” structures are identified The nuclei are round to

oval, fairly bland, and uniform Naked nuclei are also easily identified

(Diff-Quik stain)

Fig 1.34 Acinic cell carcinoma The nuclei are round to oval, with

easily identifiable nucleoli and evenly distributed chromatin Mild nuclear size variability is identified The cytoplasm in this case is degranulated and appears foamy (Papanicolaou stain)

Fig 1.35 Low-grade myoepithelial carcinoma The aspirate shows a

three-dimensional tumor fragment with high cellularity, nuclear ing, and overlapping The tumor cells are epithelioid, with a moderate amount of dense, nongranular cytoplasm The nuclei are round to oval and at places are eccentrically located with mild nuclear pleomorphism The background shows numerous naked nuclei and pale stromal frag- ments (Papanicolaou stain)

crowd-Fig 1.36 Myoepithelial carcinoma The tumor cells form small, flat

sheets or three-dimensional clusters or are singly placed The tumor

cells are epithelioid, with a moderate amount of dense cytoplasm The

background shows metachromatic stromal fragments (Diff-Quik stain)

Fig 1.37 Myoepithelial carcinoma Higher-power view of Fig. 1.36

The tumor cells have epithelioid and plasmacytoid appearance with a

moderate amount of dense, nongranular cytoplasm The nuclei are

round to oval and centrally located, with mild nuclear pleomorphism

Histologic examination shows infiltrative borders of this tumor (Diff-

Quik stain)

Fig 1.38 Secretory carcinoma Highly cellular smears with irregular,

three-dimensional clusters The tumor cells are medium in size and polygonal, with a moderate amount of cytoplasm The nuclei are round

to oval, with smooth contour and fine chromatin (Diff-Quik stain)

Fig 1.39 Secretory carcinoma Higher-power view shows granular

and vacuolated cytoplasm The nuclei are round to oval, with smooth contour and fine chromatin Background mucin and lymphocytes are identified (Diff-Quik stain)

Fig 1.40 Secretory carcinoma At higher power, cytoplasmic granules

and occasional cytoplasmic mucin are identified Mild nuclear size

vari-ability and occasional nucleoli are also noted (Diff-Quik stain)

Fig 1.41 Adenocarcinoma, not otherwise specified High-grade tumor

cells are easily recognizable The tumor cells show high

nuclear/cyto-plasmic ratios, significant nuclear pleomorphism, and uneven

chroma-tin distribution (Diff-Quik stain)

Fig 1.42 Adenocarcinoma, not otherwise specified High-grade tumor

cells form sheets and three-dimensional clusters Elongated nuclei and prominent nucleoli are also common findings (Papanicolaou stain)

Fig 1.43 Lymphoepithelial carcinoma Mixture of lymphocytes,

plasma cells, and syncytial sheets of large, polygonal epithelial tumor cells The epithelial tumor cells show classic malignant features: marked pleomorphic, vesicular nuclei with prominent, irregular nucle- oli (Papanicolaou stain)

Mesenchymal Tumors

Primary salivary gland soft tissue tumors are rare, with

benign tumors being more common than malignant ones

Most soft tissue tumors involve the parotid glands

Hemangiomas are the most frequent, but almost all soft

tis-sue tumors can involve the salivary glands (Figs. 1.44, 1.45,

1.46, 1.47, and 1.48) [19, 20]

Fig 1.44 Lipoma Encapsulated mature adipose tissue (core biopsy)

Fig 1.45 Granular cell tumor Small sheets of round to oval tumor

cells with rich, highly granular cytoplasm Oval nuclei with even

chro-matin distribution and smooth nuclear contour Nucleoli are not

promi-nent (Papanicolaou stain)

Fig 1.46 Leiomyoma Cluster of elongated tumor cells with even chromatin

distribution Most tumor cells are cigar-shaped at the endings (Diff-Quik stain)

Fig 1.47 Rhabdomyosarcoma Highly malignant round to oval tumor

cells with marked pleomorphic nuclei and irregular nuclear contour The tumor cells may be multinucleated (Diff-Quik stain)

Fig 1.48 Rhabdomyosarcoma Immunocytochemical stain shows that

the tumor cells are positive for desmin (cytospin)

Hematolymphoid Tumors

Primary salivary non-Hodgkin’s lymphomas constitute 2–5%

of salivary gland neoplasms and 11% of all malignant tumors

of major salivary glands [21] The distinction between

lym-phoma primarily involving the salivary gland and secondary

involvement from an intraparotid lymph node is often blurred

Extranodal marginal zone B-cell lymphoma of the MALT

type is the most common subtype (80%) and frequently is

associated with Sjögren syndrome [2] Diffuse large B-cell

lymphoma (DLBCL) accounts for 15% of all non-Hodgkin’s

lymphomas of salivary origin The parotid gland is most

com-monly affected (75%), followed by the submandibular gland

(20%) Up to 10% of cases show bilateral involvement at

pre-sentation [19] The involvement of salivary glands by

Hodgkin’s lymphoma is rare (Figs. 1.49 and 1.50)

Fig 1.49 Follicular lymphoma Highly cellular aspirate with isolated,

monotonous, round lymphoid cells, a few with nuclear clefting and

indenta-tion Flow cytometry and biopsy confirm the diagnosis (Papanicolaou stain)

Fig 1.50 Diffuse large B-cell lymphoma A cellular smear showing a

uniform population of lymphoid cells with large, vesicular nuclei with

clumped chromatin and irregular nuclear contour (Papanicolaou stain)

Fig 1.51 Metastatic, keratinizing squamous cell carcinoma The tumor

cells show bizarrely shaped, hyperchromatic nuclei and irregular nuclear contours with sharp angles Cytoplasm stains pink (Papanicolaou stain) The patient has a history of squamous cell carcinoma in the forehead

Fig 1.52 Metastatic melanoma The moderately cellular smear

con-tains singly dispersed and small aggregates of epithelioid tumor cells The tumor nuclei show a fine chromatin pattern and macronucleoli, with intranuclear inclusions Binucleated tumor cells are also identified The cytoplasm is granular with focal brown-black pigments (Papanicolaou stain) The patient has a history of melanoma in the right arm

Secondary Malignant Tumors

Metastatic tumors constituted about 7.5% of all non- hematolymphoid malignant salivary gland neoplasms in a series from the Armed Forces Institute of Pathology (AFIP) [22] Parotid glands are involved 20 times more often than subman-dibular glands [20] The peak incidence is in the seventh to eighth decade, with almost 70% of cases seen in men Of the metastatic tumors involving the parotid gland, 80% are from head and neck sites, whereas 85% of metastatic tumors in the submandibular gland are from distant sites Squamous cell car-cinoma is the most commonly diagnosed secondary tumor, fol-lowed by melanoma (Figs. 1.51, 1.52, 1.53, 1.54, and 1.55) [23]

Fig 1.53 Metastatic renal cell carcinoma Tumor cells form large,

cohesive groups, with large, round, eccentrically placed nuclei and

prominent nucleoli The cytoplasm is abundant, clear, and granular

(Papanicolaou stain) The patient has a history of clear cell renal cell

carcinoma 5 years ago

Fig 1.54 Metastatic hepatocellular carcinoma The metastatic tumor

cells have increased nuclear/cytoplasmic ratios, large round nuclei with

prominent nucleoli, and somewhat pale chromatin; the cytoplasm is

granular Spindle-shaped endothelial cells are also obvious

(Papanicolaou stain) The patient has a history of hepatocellular

carci-noma 0.5 years ago

References

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2 El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg

PJ. WHO classification of head and neck tumours 4th ed Lyon: IARC Press; 2017.

3 Martin HE, Ellis EB.  Biopsy by needle puncture and aspiration Ann Surg 1930;92:169–81.

4 Dudgeon LS, Patrick CV. A new method for the rapid cal diagnosis of tumours: with an account of 200 cases so exam- ined Br J Surg 1927;15:250–61.

5 Mairembam P, Jay A, Beale T, Morley S, Vaz F, Kakavrezos N, et al Salivary gland FNA cytology: role as a triage tool and an approach

to pitfalls in cytomorphology Cytopathology 2016;27:91–6.

6 Zbären P, Schär C, Hotz MA, Loosli H.  Value of fine-needle aspiration cytology of parotid gland masses Laryngoscope 2001;111:1989–92.

7 Zhang C, Cohen JM, Cangiarella JF, Waisman J, McKenna BJ, Chhieng DC.  Fine-needle aspiration of secondary neoplasms involving the salivary glands A report of 36 cases Am J Clin Pathol 2000;113:21–8.

Fig 1.55 Metastatic Merkel cell carcinoma A highly cellular smear

with malignant cells arranged in a dispersed pattern with variable bers of disorganized groups of cells Cytoplasm was scant, and nuclei showed mild to moderate anisokaryosis, stippled chromatin, inconspic- uous nucleoli, and rare nuclear molding (Papanicolaou stain) The patient has a history of Merkel cell carcinoma 1 year ago

8 Shao A, Wong DK, McIvor NP, Mylnarek AM, Chaplin JM, Izzard

ME, et al Parotid metastatic disease from cutaneous squamous cell

car-cinoma: prognostic role of facial nerve sacrifice, lateral temporal bone

resection, immune status and P-stage Head Neck 2014;36:545–50.

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aspira-tion biopsy of salivary gland lesions: novel markers and proposed

new cytopathologic classification system Arch Pathol Lab Med

2015;139:1491–7.

10 Faquin WC, Rossi ED, Baloch Z, Barkan GA, Foschini M, Kurtycz

DF, et al., editors The Milan system for reporting salivary gland

cytopathology New York, NY: Springer; 2018 In Press

11 Stenman G, Persson F, Andersson MK. Diagnostic and therapeutic

implications of new molecular biomarkers in salivary gland

can-cers Oral Oncol 2014;50:683–90.

12 Skálová A, Vanecek T, Majewska H, Laco J, Grossmann P, Simpson

RH, et  al Mammary analogue secretory carcinoma of salivary

glands with high-grade transformation: report of 3 cases with the

ETV6-NTRK3 gene fusion and analysis of TP53, β-catenin, EGFR,

and CCND1 genes Am J Surg Pathol 2014;38:23–33.

13 Hudson JB, Collins BT. MYB gene abnormalities t(6;9) in adenoid

cystic carcinoma fine-needle aspiration biopsy using fluorescence

in situ hybridization Arch Pathol Lab Med 2014;138:403–9.

14 Zhu S, Schuerch C, Hunt J.  Review and updates of

immunohis-tochemistry in selected salivary gland and head and neck tumors

Arch Pathol Lab Med 2015;139:55–66.

15 Pinkston JA, Cole P.  Incidence rates of salivary gland tumors: results from a population-based study Otolaryngol Head Neck Surg 1999;120:834–40.

16 Al-Abbadi MA. Salivary gland cytology: a color atlas Hoboken, NJ: Wiley; 2011.

17 Faquin WC, Sidaway MK, Powers C.  Salivary gland ogy New York: Springer; 2008.

18 Klijanienko J, Vielh P, Batsakis JG. Salivary gland Tumours Basel: Karger; 2000.

19 Khalbuss WE, Parwani AV. Cytopathology of soft tissue and bone lesions New York: Springer; 2011.

20 Liu S, Parajul S, Hotchandani N, Jhala N, Wang JD, Khurana

JS, et  al Fine needle aspiration diagnosis of non-epithelial lesions of the major salivary glands Int J Clin Exp Pathol 2016;9:7164–71.

21 Chhieng DC, Cangiarella JF, Cohen JM.  Fine-needle aspiration cytology of lymphoproliferative lesions involving the major sali- vary glands Am J Clin Pathol 2000;113:563–71.

22 Ellis GL, Auclair PL. Tumors of the salivary glands (AFIP atlas of tumor pathology, series 4) Silver Spring, MD: American Registry

of Pathology Press; 2008.

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© Springer International Publishing AG, part of Springer Nature 2018

X Jing et al (eds.), Atlas of Non-Gynecologic Cytology, Atlas of Anatomic Pathology,

https://doi.org/10.1007/978-3-319-89674-8_2

Aspiration Cytology

Xin Jing

Introduction

Fine needle aspiration (FNA) is a simple, cost-effective, and

minimally invasive triage procedure utilized for sampling

mass lesions of various body sites and organs FNA has been

commonly used in the management of thyroid nodules, with

the aim of distinguishing thyroid nodules that require surgical

treatment (i.e., neoplastic and malignant nodules) from those

that may be managed conservatively with clinical and

imag-ing follow-up (i.e., benign and nonneoplastic nodules) [1 4]

Both palpation-guided and ultrasound (US)-guided FNAs are

options for the work-up of thyroid nodules, but US-guided

FNA has become the preferred procedure, as studies have

demonstrated that it results in more precise and adequate

sam-pling, a lower rate of false negatives, an increased diagnostic

yield, and high sensitivity and specificity in the diagnosis of

thyroid cancer [5 8] US-guided FNA may help to obtain a

better sample from nodules that have a notable cystic

compo-nent or nodules located in the posterior aspect of the thyroid

Two methods may be employed for the preparation and

processing of thyroid aspirates For FNAs with on-site

ade-quacy assessment, two direct smears are made for each pass

One smear is air-dried, stained with Diff-Quik stain, and then

evaluated immediately for specimen adequacy The other

smear is quickly fixed with alcohol-based fixatives and later

stained with Papanicolaou stain before examination The

aspiration needle is then rinsed in Cytolyt® solution for a

ThinPrep® and/or cell block preparation For FNAs without

on-site adequacy assessment, each specimen is submitted in

Cytolyt® solution, from which a ThinPrep® slide and/or a cell

block slide is prepared

Based on the 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer, FNA is the pro-cedure of choice in the evaluation of thyroid nodules in an appropriate clinical setting Accordingly, diagnostic FNA is recommended for nodules ≥1 cm in greatest dimension with

an intermediate- or high-suspicion sonographic pattern, ules ≥1.5  cm in greatest dimension with a low-suspicion sonographic pattern, and nodules ≥2 cm in greatest dimen-sion with a very low-suspicion sonographic pattern [9] The guidelines further indicate that FNA cytology of a thyroid nodule should be reported using diagnostic groups outlined

nod-in The Bethesda System for Reportnod-ing Thyroid Cytopathology

of each category [10] After publication of the World Health Organization (WHO) classification of thyroid tumors in 2004, a major modification was proposed in

2016 Accordingly, noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC) has been reclassified as noninvasive follicular thyroid neoplasm

X Jing, M.D.

Department of Pathology, The University of Michigan-Michigan

Medicine, Ann Arbor, MI, USA

e-mail: xinjing@med.umich.edu

2

with papillary-like nuclear features (NIFTP) Because of

its highly indolent clinical behavior, NIFTP would not be

treated as conventional or other variants of PTC [11] The

implementation of a histologic diagnosis of NIFTP may

potentially alter the risk of malignancy (ROM) across the

TBSRTC diagnostic categories [12–15]

The majority of thyroid nodules fall into either a

benign or malignant category Table 2.1 summarizes the

cytologic features of nonneoplastic, neoplastic, and

malignant lesions of the thyroid Some thyroid lesions are

the so-called gray zone nodules, with an indeterminate

diagnostic interpretation (atypia or suspicious) In this

category, ancillary tests play an important role in

estab-lishing a definitive diagnosis in patients with an initial

indeterminate diagnosis In this regard, an elevated serum

calcitonin level, positive special stain for Congo red, and/

or immunocytochemical study showing positive

expres-sion of calcitonin, chromogranin, synaptophysin, CD56,

and CEA will support the diagnosis of medullary thyroid

carcinoma Flow cytometry demonstrating a monoclonal

population of lymphocytes may provide a definitive

diag-nosis and subclassification of lymphomas There has

been a gradually increased trend in the use of

commer-cially available molecular testing as an adjunct to FNA

cytology in order to stratify the indeterminate thyroid

nodules This testing uses either a rule-in or rule-out approach for the stratification of indeterminate thyroid nodules, and each of these tests carries its own strengths and limitations The selection of an appropriate test and interpretation of the testing result are crucial to achieve the goal of minimizing undertreatment or overtreatment

of patients [14]

Nondiagnostic/Unsatisfactory Specimens

An adequate specimen should contain at least six groups

of follicular cells, with each group having a minimum of ten well-preserved and well-visualized follicular cells Regardless of the number of follicular cells, a specimen with atypical follicular cells or atypical cells of other ori-gins, a moderate to abundant amount of inflammatory cells (polymorphous lymphocytes, neutrophils, and aggregates of histiocytes), or abundant colloid material is also considered adequate Any specimen that does not ful-fill these criteria is classified as nondiagnostic/unsatisfac-tory It is not uncommon for a nondiagnostic specimen (cystic fluid only) to contain abundant macrophages and rare cyst-lining cells The cyst-lining cells may have round, oval, or spindle-shaped nuclei, occasional intra-

Table 2.1 Key features for the cytologic diagnosis of benign and malignant thyroid lesions

Cytologic diagnosis Key features

Nodular hyperplasia Various proportions of follicular cells and Hürthle cells which are arranged as sheets, intact

follicles, and/or papillae with monolayer, honeycombing pattern No marked nuclear overlapping/ crowding No marked cytologic/nuclear atypia Colloid and/or histiocytes may be present in the background

Lymphocytic thyroiditis Mixture of polymorphous lymphocytes, follicular cells, and Hürthle cells Predominantly

lymphocytes without or with rare follicular/Hürthle cells may be seen Hürthle cells may show a spectrum of cytologic/nuclear atypia Various amounts of colloid may be present in the background

Follicular neoplasm Hypercellular The cells are arranged as microfollicles and/or trabeculae with nuclear overlapping/

crowding Various degrees of cytologic/nuclear atypia may be present No or rare amount of colloid is present

Papillary thyroid

carcinoma (PTC)

Cellular aspirate with cells arranged as sheets and/or papillae The cells show a syncytial pattern with nuclear crowding/molding Elongated nuclei, nuclear enlargement, irregular nuclear membrane, powdery chromatin, intranuclear grooves, and pseudoinclusions are evident

Single cells, histiocytoid cells, squamoid cells, bubble-gum colloid, and/or psammoma bodies may be seen

Medullary thyroid carcinoma

(MTC)

Classic findings include the presence of plasmacytoid and/or spindled cells with or without amyloid The nuclei contain salt-and- pepper chromatin and inconspicuous nucleoli Ancillary tests must be performed to confirm the cytologic diagnosis because of the wide spectrum of cytomorphologic features

Poorly differentiated thyroid

carcinoma (PDTC)

Cellular aspirate with single or clusters of monotonous follicular cells The cells have a scant amount

of cytoplasm, high nuclear/cytoplasmic ratio, and variable nuclear atypia Apoptosis, mitosis, and necrosis may be present Ancillary tests are suggested to distinguish it from medullary thyroid carcinoma and other entities with a small, blue cell appearance

Anaplastic thyroid carcinoma

(ATC)

Various cellularities with isolated or groups of neoplastic cells The cells show marked pleomorphism

in nuclear size and shape Nuclear enlargement, irregular nuclear contours, coarse chromatin, prominent nucleoli, and multinucleation may be present

nuclear grooves, and ill-defined nuclear holes These

cyst-lining cells may be misinterpreted as neoplastic/

malignant cells, such as papillary thyroid carcinoma

TBSRTC recommends repeat FNA under US guidance

[10] (Fig. 2.1)

Benign Entities

Nonneoplastic entities such as colloid nodule, nodular

hyperplasia, and thyroiditis belong to this category; the

implied risk of malignancy is 0–3% TBSRTC suggests

clin-ical follow- up at intervals of 6–18  months for at least

3–5 years after the initial diagnosis A repeat FNA is

recom-mended for nodules with marked growth or suspicious US

abnormalities Surgical intervention is recommended for

large and symptomatic nodules, nodules showing

worri-some clinical and US features, or nodules that are associated

with malignancy [10]

Colloid Nodule

FNA specimens of colloid nodules contain abundant thick and/or thin (watery) colloid, with no follicular cells or only rare follicular cells (Fig. 2.2)

Nodular Hyperplasia

Aspirates of nodular hyperplasia contain a mixture of lar/Hürthle cells, colloid, and macrophages in various propor-tions Most of the follicular/Hürthle cells are arranged as monolayered, honeycomb-like sheets and/or three- dimensional spheres (intact follicles) with evenly distributed nuclei The follicular cells have a scant to moderate amount of delicate cytoplasm, round to oval nuclei, granular chromatin, and inconspicuous nucleoli Hürthle cells may show moderate to abundant granular cytoplasm and prominent nucleoli Rare microfollicles may also be appreciated (Figs. 2.3 and 2.4)

follicu-a

b

Fig 2.1 Nondiagnostic specimen (a, b) Abundant macrophages with

heavy hemosiderin deposits (Diff-Quik and Papanicolaou stains)

a

b

Fig 2.2 Colloid nodule (a, b) Abundant thick and thin, homogeneous-

looking colloid material, respectively The thin colloid shows a mosaic pattern, with a folded tissue paper appearance No follicular cells are present (Diff-Quik stain)

a b

Fig 2.3 Nodular hyperplasia (a, b) Follicular cells are arranged as

monolayered, honeycombing sheets (Diff-Quik and Papanicolaou

stains) (c, d) Follicular cells are forming three-dimensional spheres

(intact follicles) Nuclei are evenly distributed without overlapping or crowding (Diff-Quik and Papanicolaou stains)

Fig 2.4 Nodular hyperplasia in Graves’ disease (a, b) Large monolayer sheets of cells with abundant cytoplasm, marginal cytoplasmic vacuoles,

and frayed edges (Diff-Quik stain)

a b

c

Fig 2.5 Lymphocytic thyroiditis (a) Only polymorphous lymphocytes and rare multinucleated histiocytes are present (Diff-Quik stain)

(b, c) Hürthle cells and background lymphocytes (Diff-Quik and Papanicolaou stains)

Lymphocytic (Hashimoto’s) Thyroiditis

FNA specimens of lymphocytic (Hashimoto’s) thyroiditis

contain various proportions of polymorphous lymphocytes,

follicular cells, and Hürthle cells Follicular/Hürthle cells are

arranged as single cells and/or sheets and show a spectrum of

cytologic changes Nuclei with various degrees of atypia and prominent nucleoli may present Sometimes the specimen may reveal solely lymphocytes If lymphocytes show any atypical features (such as monotonous appearance) and non- Hodgkin’s lymphoma is suspected, collecting additional mate-rial for flow cytometry analysis is recommended (Fig. 2.5)

Subacute thyroiditis (De Quervain’s thyroiditis) presents as a

painful lesion and is rarely aspirated due to its typical

clini-cal presentation Aspiration may be performed to rule out

possible neoplasm or malignancy Depending on the stage of

disease, the aspirates may reveal various proportions of licular cells, mixed inflammatory cells (neutrophils, lympho-cytes, eosinophils, macrophages), and aggregates of histiocytes (granulomas) Without aggregates of histiocytes (granulomas), the mere presence of follicular cells mixed with inflammatory cells is a nonspecific finding (Fig. 2.6)

Infectious Thyroiditis

Infectious thyroiditis is rare because of the unique anatomic

location, rich blood supply and lymphatic drainage, and high

iodine content of the thyroid gland Infection may be caused

by bacteria, viruses, fungi, or parasites Immunocompromised individuals are susceptible to opportunistic infections The aspirate may reveal follicular cells, mixed inflammatory cells, and debris Pathogens may be identified with or with-out special stains (e.g., GMS stain) (Figs. 2.7 and 2.8)

a

b

Fig 2.8 Cryptococcal thyroiditis (a, b) Mixture of follicular cells,

lymphocytes, and histiocytes The histiocytes contain cryptococci with

a thick capsule (Diff-Quik stain) (Image courtesy of Dr Claire Michael)

a

b

c

Fig 2.7 Granulomatous aspergillosis (a) Necrotic debris and

histio-cytes; some histiocytes have multinucleation (Diff-Quik) (b, c)

Aspergillus showing septate hyphae and branching at a 45° angle

( Diff- Quik and GMS stains) (Image courtesy of Dr Claire Michael)

Fig 2.9 Amyloid nodule Amyloid is interspersed with fibroblast

nuclei (Papanicolaou stain)

Fig 2.10 Black thyroid Follicular cells contain cytoplasmic

pig-ments, which are coarse and brown (Papanicolaou stain)

Amyloid Nodule

Systemic amyloidosis may cause amyloid deposits in the

thy-roid gland, resulting in focal or diffuse enlargement The

appear-ance of amyloid material in FNA specimens often resembles

colloid, but amyloid is often interspersed with fibroblast nuclei

(Fig. 2.9) Amyloid stained by Congo red shows apple-green

birefringence under polarized light microscopy Immunostain

for amyloid may also help in establishing the diagnosis

Black Thyroid

Black thyroid is a benign condition that may be seen in patients taking antibiotics of the tetracycline group for long periods of time FNA specimens reveal coarse, brown pig-ment granules in the cytoplasm of follicular cells The pig-ment granules are thought to be a type of melanin, as they are positive for Fontana stain If in doubt, an immunostaining panel consisting of more than one melanoma marker may be performed to differentiate it from melanoma (Fig. 2.10)

b

c

Fig 2.11 Papillary thyroid carcinoma (PTC) (a) Hypercellular

specimen with papillary-like fragments (b, c) The cells show

syncy-tial, swirling arrangement with unevenly distributed nuclei Quik stain)

Malignant Entities

The diagnosis of malignancy is rendered when specimens

reveal definitive cytomorphologic features of malignancy

Papillary thyroid carcinoma (PTC) is the most common

malignant tumor, accounting for approximately 80% of all

thyroid cancers Other malignant entities include medullary

thyroid carcinoma (MTC, 7%), poorly differentiated thyroid

carcinoma (PDTC, 4–7%), anaplastic thyroid carcinoma

(ATC, <5%), squamous cell carcinoma (≤1%), lymphoma

(5%), and metastatic malignancy (2.7–4.0%) The most

com-mon origins of metastatic malignancy in the thyroid are the

lung, breast, skin, colon, and kidney

Papillary Thyroid Carcinoma (PTC)

The cytologic features seen in conventional PTC and its

variants include hypercellularity; papillae or syncytial

tis-sue fragments with nuclear overlapping; oval, elongated,

or irregularly shaped nuclei with nuclear enlargement,

intranuclear longitudinal grooves, and cytoplasmic

pseu-doinclusions; powdery chromatin; and marginally located

micronucleoli Cells with histiocytoid or squamoid

cytoplasm, bubble-gum colloid, psammoma bodies, and

multinucleated giant cells may be present Variants of

PTC show the characteristic nuclear features to various

extents (obvious to subtle) while exhibiting different

architectural patterns, unusual cytoplasmic features, or

different backgrounds The variants of PTC include

fol-licular, macrofolfol-licular, cystic, oncocytic, Warthin-like,

tall-cell, and columnar-cell variants, as well as

hyaliniz-ing trabecular tumor It may be a challenge to further

cat-egorize these variants, but subcategorization based on

cytologic findings is not necessary, as total thyroidectomy

is commonly the first-line treatment for conventional PTC

and its variants (Figs. 2.11, 2.12, 2.13, 2.14, 2.15, 2.16,

2.17, 2.18, 2.19, and 2.20)

b

Fig 2.13 PTC (a, b) Multiple intranuclear pseudoinclusions are

pres-ent (Diff-Quik and Papanicolaou stains)

Fig 2.14 PTC Intranuclear grooves, powdery chromatin, and

margin-ally located micronucleoli are present (Papanicolaou stain)

Fig 2.12 PTC (a, b) Hypercellular specimen with monolayer,

syn-cytial sheets showing nuclear overlapping and crowding Round,

oval, or elongated nuclei, nuclear enlargement, irregular nuclear

membrane, and occasional intranuclear inclusions and grooves are seen (Papanicolaou stain)

Fig 2.15 PTC Bubble gum-like colloid interspersed with malignant

cells (Diff-Quik stain)

a

b

c

Fig 2.16 PTC (a) Psammoma bodies are surrounded by malignant

cells (Diff-Quik stain) (b) Psammoma body is adjacent to a papillary cluster of malignant cells (Papanicolaou stain) (c) Psammoma body

and multinucleated giant cell (Papanicolaou stain)

a b

c

Fig 2.17 PTC (a–c) Papillary clusters containing malignant cells and

psammoma bodies The histiocytoid-looking malignant cells have

vac-uolated cytoplasm and enlarged nuclei Intranuclear grooves and

inclu-sions, marginally located nuclei, and powdery chromatin are present (Papanicolaou stain)