Frozen Section Library: Pleura

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2 Frozen Section Library: Pleura For other titles published in this series, go to

3 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

4 Dr. Philip T. Cagle Weill Medical College of Cornell University The Methodist Hospital Houston, TX USA Dr. Timothy Craig Allen University of Texas Health Science Center at Tyler Tyler, TX USA ISSN e-issn ISBN e-isbn DOI / Springer New York Dordrecht Heidelberg London Library of Congress Control Number: Springer Science+Business Media, LLC 2010 All 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 (

5 To my wife, Kirsten Philip T. Cagle To my parents, Oliver and Mildred Allen Timothy Craig Allen

6 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 convenient, 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 vii

7 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 fellows 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 contributes to the improved care of patients who rely on the frozen section to help guide their treatment. Houston, TX Philip T. Cagle Series Editor

8 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 immediate 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 pathologist 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, userfriendly handbook to expedite use when performing intraoperative 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 associated with those specific diagnoses. The diagnostic issues impacting 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 histologic 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 ix

9 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 pathologists, 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 Houston, TX Timothy Craig Allen Philip T. Cagle

10 Contents Preface... ix 1. Diffuse Malignant Mesothelioma... 1 Introduction... 1 Diffuse Malignant Mesothelioma Metastatic Cancers Other Primary Neoplasms of the Pleura Pleuritis and Pleural Plaque Uncommon Nonneoplastic Lesions of the Pleura Benign Reactive Proliferations vs. Malignancy Suggested Reading Index xi

11 Chapter 1 Diffuse Malignant Mesothelioma INTRODUCTION Frozen section of pleural tissue is performed during surgery to confirm that diagnostic tissue has been obtained for permanent section examination and to decide on intraoperative therapy. Benign reactive/inflammatory conditions (infections, plaques, pleuritis of various etiologies), benign neoplasms, primary pleural malignancies, 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 limitations. 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 necessary 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 abnormality, 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 P.T. Cagle and T.C. Allen, Frozen Section Library: Pleura, Frozen Section Library 3, DOI / _1, Springer Science + Business Media, LLC 2010

12 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 reactive/inflammatory conditions (samples may be taken for additional studies such as permanent sections, microbiologic cultures, etc), (2) complete resection for benign neoplasms, localized malignant neoplasms, 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 MESOTHELIOMA Although it is the most common primary neoplasm of the pleura, diffuse malignant mesothelioma (DMM) is relatively rare compared 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 differential 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 distinguishing 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 underlying or neighboring tissues and sometimes form bulky masses, but their gross distribution along serosal membrane surfaces is an essential feature of their diagnosis. The gross description of the surgeon and the radiologic findings to confirm the characteristic growth patterns 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