Frozen Section Library: Pleura

For other titles published in this series, go to www.springer.com/series/7869

Frozen Section Library: Pleura

Philip T. Cagle, MD

Weill Medical College of Cornell University, NY, NY The Methodist Hospital, Houston, TX, USA

Timothy Craig Allen, MD, JD

University of Texas Health Science Center at Tyler, Tyler, TX, USA

Dr. Philip T. CagleWeill Medical College of Cornell UniversityThe Methodist HospitalHouston, TXUSApcagle@tmhs.org

Dr. Timothy Craig AllenUniversity of Texas Health Science Center at TylerTyler, TXUSAtimothy.allen@uthct.edu

ISSN 1868-4157 e-ISSN 1868-4165ISBN 978-0-387-95985-6 e-ISBN 978-0-387-95986-3DOI 10.1007/978-0-387-95986-3Springer New York Dordrecht Heidelberg London

Library of Congress Control Number: 2010921592

© Springer Science+Business Media, LLC 2010All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden.The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights.While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

To my wife, KirstenPhilip T. Cagle

To my parents, Oliver and Mildred AllenTimothy Craig Allen

vii

Series Preface

For over 100 years, the frozen section has been utilized as a tool for the rapid diagnosis of specimens while a patient is undergoing surgery, usually under general anesthesia, as a basis for making immediate treatment decisions. Frozen section diagnosis is often a challenge for the pathologist who must render a diagnosis that has crucial import for the patient in a minimal amount of time. In addition to the need for rapid recall of differential diagnoses, there are many pitfalls and artifacts that add to the risk of frozen section diagnosis that are not present with permanent sections of fully processed tissues that can be examined in a more leisurely fashion. Despite the century-long utilization of frozen sections, most standard pathology textbooks, both general and subspecialty, largely ignore the topic of frozen sections. Few textbooks have ever focused exclusively on frozen section diagnosis, and those textbooks that have done so are now out-of-date and have limited illustrations.

The Frozen Section Library series is meant to provide conven-ient, user-friendly handbooks for each organ system to expedite use in the rushed frozen section situation. These books are small and lightweight, copiously color illustrated with images of actual frozen sections, highlighting pitfalls, artifacts, and differential diagnosis. The advantages of a series of organ-specific handbooks, in addition to the ease of use and manageable size, are that (1) a series allows more comprehensive coverage of more diagnoses, both common and rare, than a single volume that tries to highlight a limited number of diagnoses for each organ and (2) a series allows more detailed insight by permitting experienced authorities to emphasize the peculiarities of frozen section for each organ system.

As a handbook for practicing pathologists, these books will be indispensable aids to diagnosis and avoiding dangers in one of the most challenging situations that pathologists encounter. Rapid consideration of differential diagnoses and how to avoid traps caused by frozen section artifacts are emphasized in these

viii SerieS Preface

handbooks. A series of concise, easy-to-use, well-illustrated handbooks alleviates the often frustrating and time-consuming, sometimes futile, process of searching through bulky textbooks that are unlikely to illustrate or discuss pathologic diagnoses from the perspective of frozen sections in the first place. Tables and charts will provide guidance for differential diagnosis of various histologic patterns. Touch preparations, which are used for some organs such as central nervous system or thyroid more often than others, are appropriately emphasized and illustrated according to the need for each specific organ.

This series is meant to benefit practicing surgical pathologists, both community and academic, and pathology residents and fel-lows and also to provide valuable perspectives to surgeons, surgery residents, and fellows who must rely on frozen section diagnosis by their pathologists. Most of all, we hope that this series contrib-utes to the improved care of patients who rely on the frozen sec-tion to help guide their treatment.

Houston, TX Philip T. Cagle Series Editor

ix

Preface

Frozen sections are diagnosed by the pathologist while a patient is undergoing surgery, often under general anesthesia, for the purpose of rapid diagnosis, which may be used to make imme-diate treatment decisions or to confirm that diagnostic tissues have been sampled for further study. As a result, frozen section diagnosis is often a highly demanding situation for the patholo-gist who must render a diagnosis quickly and is a basis for critical decisions to the surgeon. In addition to the need for rapid recall of differential diagnoses, there are many pitfalls and artifacts that add to the risk of frozen section diagnosis that are not present with permanent sections of fully processed tissues that can be examined in a more leisurely fashion. Most standard pathology textbooks, both general and subspecialty, largely ignore the topic of frozen section. Few textbooks have ever focused exclusively on frozen section diagnosis.

The Frozen Section of the Pleura provides a convenient, user-friendly handbook to expedite use when performing intraopera-tive consultations on pleural specimens. This book is divided into chapters that emphasize the common questions that a pathologist must answer on frozen section examination and the pitfalls associ-ated with those specific diagnoses. The diagnostic issues impact-ing immediate surgical decision-making are color illustrated and discussed succinctly, including a complex array of primary and secondary neoplasms of the pleura that have overlapping histo-logic features and the well-known problems of reactive atypia vs. cancer in pleural tissue.

As a handbook for practicing pathologists, this book is an indispensible aid to diagnosis and avoiding dangers in one of the most challenging situations that pathologists encounter. Rapid consideration of differential diagnoses and how to avoid traps caused by frozen section artifacts will be readily accessible to the users of this handbook. Tables provide guidance for various categories of differential diagnoses. Currently, there is no other

x Preface

up-to-date single-source reference specifically focused on frozen sections of the pleura.

This book will be highly valuable to practicing surgical pathol-ogists, both community and academic, and to pathology residents and fellows. The perspectives provided will also be valuable to thoracic surgeons and especially to surgery residents and thoracic surgery fellows who must answer questions about pathology and frozen section on their board examinations.

Tyler, TX Timothy Craig AllenHouston, TX Philip T. Cagle

xi

Contents

Preface ...................................................................................... ix

1. Diffuse Malignant Mesothelioma .................................. 1Introduction ....................................................................... 1Diffuse Malignant Mesothelioma ...................................... 2

2. Metastatic Cancers ........................................................... 23

3. Other Primary Neoplasms of the Pleura ...................... 35

4. Pleuritis and Pleural Plaque .......................................... 57

5. Uncommon Nonneoplastic Lesions of the Pleura ...... 75

6. Benign Reactive Proliferations vs. Malignancy ........... 79

Suggested Reading ................................................................. 109

Index ......................................................................................... 111

P.T. Cagle and T.C. Allen, Frozen Section Library: Pleura, Frozen Section Library 3, DOI 10.1007/978-0-387-95986-3_1, © Springer Science + Business Media, LLC 2010

Chapter 1

Diffuse Malignant Mesothelioma

INTRODUCTIONFrozen section of pleural tissue is performed during surgery to confirm that diagnostic tissue has been obtained for permanent sec-tion examination and to decide on intraoperative therapy. Benign reactive/inflammatory conditions (infections, plaques, pleuritis of various etiologies), benign neoplasms, primary pleural malignan-cies, and metastatic cancers may produce overlapping radiologic, clinical, or gross findings. These diverse pleural diseases (1) may cause pleural thickening, nodules or masses observed on imaging studies or grossly by the surgeon, (2) are often accompanied by pleural effusions, and (3) may be asymptomatic or cause difficulty in breathing, chest pain, or other thoracic symptoms, regardless of the etiology. The suspected diagnosis based on clinical context and current imaging modalities often proves correct. However, even the most recent advances in noninvasive diagnosis have limita-tions. For example, a few cases of malignancy will be negative on positron emission tomography (PET) using 18-fluorodeoxyglucose (FDG), and some benign reactive/inflammatory conditions will be positive. Even when a diagnosis of cancer is correctly rendered on a clinical and radiologic basis, histologic examination may be nec-essary to determine the type of malignancy involving the pleura. Therefore, even with modern imaging techniques, t he definitive diagnosis of a pleural abnormality often requires tissue samples.

Although pleural effusion cytology and transthoracic needle biopsy may provide an accurate diagnosis of a pleural abnormal-ity, larger or more representative tissue samples may be necessary to render a diagnosis in some cases. Frozen section allows the pathologist to guide the surgeon in obtaining adequate samples

1

2 FrOzen SeCTIOn LIbrAry: PLeUrA

for diagnosis on permanent section and also provides the surgeon with immediate feedback for intraoperative therapeutic decisions. Therapy at the time of surgery depends in large part on the diagnosis rendered at frozen section: (1) often no additional therapy for reac-tive/inflammatory conditions (samples may be taken for additional studies such as permanent sections, microbiologic cultures, etc), (2) complete resection for benign neoplasms, localized malignant neo-plasms, and solitary metastases, and (3) pleurodesis, pleurectomy, decortication, or possibly more extensive resection for cancer. On occasion, frozen section of the pleura may also be performed for margins of a pleuropneumonectomy/extrapleural pneumonectomy.

DIFFUSE MALIGNANT MESOTHELIOMAAlthough it is the most common primary neoplasm of the pleura, diffuse malignant mesothelioma (DMM) is relatively rare com-pared with most cancers with about 2,000 new cases in the USA each year. Because of its extremely bleak prognosis with limited treatment options and the potential for compensation to the patient in toxic tort litigation, accurate diagnosis of DMM has great importance despite its comparative uncommonness.

There are two primary categories of differential diagnoses for DMM. The first category of differential diagnoses is DMM vs. other types of cancer involving the pleura. The latter includes primary pleural cancers other than DMM and, more commonly, cancers metastatic to the pleura. The histologic features of these differen-tial diagnoses are further discussed in Chaps. 2 and 3. The second category of differential diagnoses is DMM vs. benign reactive/inflammatory processes that produce mesothelial hyperplasia or granulation tissue that mimics DMM. The problem of distinguish-ing benign reactive proliferations from malignancy, particularly DMM, is discussed in detail in Chap. 6.

DMM arises from mesothelial cells and often spreads as diffuse nodules over serosal membrane surfaces, classically encasing the lung along the pleural surface. DMM may invade or metastasize into under-lying or neighboring tissues and sometimes form bulky masses, but their gross distribution along serosal membrane surfaces is an essen-tial feature of their diagnosis. The gross description of the surgeon and the radiologic findings to confirm the characteristic growth pat-terns of DMM are very important to the diagnosis of DMM. However, metastatic cancers and other primary cancers of the pleura may grow in patterns that mimic the growth pattern of DMM and, therefore, serosal surface distribution by itself is not diagnostic of DMM.

Essentially always, the definitive diagnosis of DMM depends on examination of permanent tissue sections, often accompanied

DIFFUSe MALIgnAnT MeSOTheLIOMA 3

by confirmatory special studies. DMM has a wide range of histologic patterns that may potentially overlap with the histologic patterns of many other types of cancer. Knowledge of the diverse histologic patterns of DMM at frozen section allows the pathologist to sus-pect a diagnosis of DMM and better guide the surgeon in obtaining tissue that is satisfactory for confirmatory study on permanent sections and in making immediate decisions regarding pleurod-esis, pleurectomy, decortication, or other treatments at the time of surgery.

DMM is divided into three major histologic types: epithelioid, sarcomatoid, and mixed (biphasic). The differential diagnosis varies with the histologic type. Epithelioid DMMs are composed of cuboidal, polygonal, or oval cells and include reactive nonneo-plastic mesothelial hyperplasia, carcinomas, and other epithelioid malignancies (metastatic or primary to the pleura) in their his-tologic differential diagnosis. Sarcomatoid DMMs are composed of spindle cells and have as their histologic differential diagnosis fibrous pleuritis and granulation tissue in addition to sarcomas and other spindle cell neoplasms metastatic or primary to the pleura. Mixed or biphasic DMM has both epithelioid and sarco-matoid components and includes reactive pleuritis and biphasic neoplasms in its differential diagnosis. The major histologic types of DMM are further subdivided into histologic variants, which are listed in Table 1.1. These histologic variants have their own specific considerations in their differential diagnoses. Table 1.2 summarizes the DMM histologic patterns that enter into the dif-ferential diagnosis of various pleural proliferative lesions, both malignant and benign.

In many cases, particularly with certain histologic patterns such as the well-differentiated epithelioid types that resemble mes-othelial cells, DMMs are correctly identified or strongly suspected based on their routine histology at frozen section. However, due to the overlap of radiologic, clinical, gross, and histologic features, differentiation of DMM from metastatic cancers often requires evaluation of the permanent sections usually with confirmation by immunostains. Therefore, during procedures to obtain tissue for diagnosis, the pathologist may suggest DMM or a suspicion of DMM, depending on the level of certainty at the frozen section, and advise the surgeon that confirmation of the diagnosis will occur after permanent sections and ancillary studies are reviewed. Pleurodesis or other procedure for malignancy may be performed by the surgeon even if there is a need for the pathologist to confirm the type of malignancy at a later time, provided that a diagnosis of cancer has been made at frozen section (Figs. 1.1–1.26).

4 FrOzen SeCTIOn LIbrAry: PLeUrA

Table 1.1 Histologic variants of diffuse malignant mesothelioma.

Epithelioid histologic patternsSolid Well-differentiated (mesothelial cell-like) Poorly differentiatedTubulopapillaryAcinar (glandular)Adenomatoid (microglandular)/microcysticClear cellDeciduoidAdenoid cysticSignet ringSmall cellDesmoplasticSarcomatoid histologic patternsSarcomatous Fibrous histiocytoma-like Osteosarcomatous ChondrosarcomatousLymphohistiocytoidDesmoplasticMixed (biphasic) histologic patternsMiscellaneous histologic patternsPleomorphicTransitional