Soft Tissue Tumors

Soft Tissue TumorsA Multidisciplinary, Decisional

Diagnostic Approach

Edited by

Jerzy KlijanienkoInstitut Curie

Real LagaceCentre Hospitalier Universitaire de Quebec

Quebec, Canada

Copyright r 2011 by John Wiley & Sons, Inc. All rights reserved.

Published by John Wiley & Sons, Inc., Hoboken, New Jersey

Published simultaneously in Canada

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Library of Congress Cataloging-in-Publication Data:

Soft tissue tumors : a multidisciplinary, decisional, diagnostic approach / edited by Jerzy Klijanienko,

Real Lagace.

p. ; cm.

Includes bibliographical references.

ISBN 978-0-470-50571-7 (cloth)

1. Soft tissue neoplasms. I. Klijanienko, Jerzy. II. Lagace, Real.

[DNLM: 1. Soft Tissue Neoplasms. WD 375]

RC280.S66S72 2010

616.99u4075—dc22 2010036846

Printed in the United States of America

10 9 8 7 6 5 4 3 2 1

Contents

Foreword ix

Alain Verhest

Preface xiii

Acknowledgments xv

Contributors xvii

1 Clinical approach in soft tissue tumors 1

Fran�cois Goldwasser

1.1 Epidemiology / 1

1.2 Clinics and clinical profiles / 5

1.3 Clinical differential diagnosis / 13

1.4 The importance of molecular diagnosis and its perspectives / 14

1.5 Treatment strategies / 14

2 Radiological diagnostic approach in soft tissue tumors 21

Herve Brisse

2.1 Introduction / 21

2.2 Patient management / 22

2.3 Imaging techniques / 22

2.4 Radiologic characterization / 24

2.5 Tumor biopsy / 29

3 Sampling procedure, fine needle aspiration (FNA), and coreneedle biopsy (CNB) 37

Henryk A. Domanski

3.1 Advantages and limitations of FNA and CNB in soft tissue lesions / 37

v

3.2 Techniques of FNA and CNB as applied to soft tissue lesions / 43

3.3 Processing the FNA and CNB samples and preparation of the FNA speci-men for ancillary techniques / 45

3.4 Challenges in the FNA and CNB of soft tissue / 51

3.5 Complications of FNA and CNB of soft tissue / 56

4 Ancillary techniques 61

4.1 Immunocytochemistry / 61Carlos Bedrossian

4.2 Immunohistochemistry / 66Real Lagace

4.3 Genetic Techniques / 70Jerome Couturier

4.4 Grading of soft tissue tumors / 76Real Lagace

4.5 Future investigations of ancillary techniques / 79Stamatios Theocharis

5 Principal aspects in fine needle aspiration and core needle biopsies 87

Jerzy Klijanienko and Real Lagace

5.1 Normal tissue / 87

5.2 Cytologic classification of soft tissue tumors based on the principal pat-terns / 89

5.3 Diagnostic accuracy of FNA in soft tissue tumors / 107

5.4 Smear composition and the differential diagnosis of soft tissue tumors / 110

6 Particular aspects 121

Jerzy Klijanienko and Real Lagace

6.1 Low-grade spindle cell tumors / 121

6.1.1 Fibromatoses and Desmoids / 122

6.1.2 Nodular Fasciitis / 130

6.1.3 Dermatofibrosarcoma Protuberans / 137

6.1.4 Benign Fibrous Histiocytoma (Cellular and Atypical Variants) / 145

6.1.5 Solitary Fibrous Tumor / 153

6.2 Tumors with fibrillary stroma / 158

6.2.1 Benign Peripheral Nerve Sheath Tumors(Schwannoma, Ancient Schwannoma and Neurofibroma) / 158

6.2.2 Low-Grade Malignant Peripheral Nerve Sheath Tumor / 171

6.3 Malignant spindle cell tumors / 177

6.3.1 Leiomyosarcoma / 178

6.3.2 Synovial Sarcoma / 187

6.3.3 Fibrosarcoma / 197

6.3.4 Malignant Fibrous Histiocytoma � Storiform Pattern / 207

vi CONTENTS

6.3.5 Malignant Peripheral Nerve Sheath Tumor / 212

6.3.6 Spindle Cell Angiosarcoma / 214

6.3.7 Kaposi Sarcoma / 225

6.4 Myxoid tumors / 229

6.4.1 Myxoid Liposarcoma (With or Without Round orSpindle Cells) / 229

6.4.2 Myxofibrosarcoma / 238

6.4.3 Myxoid Leiomyosarcoma / 246

6.4.4 Myxoma and Cellular Myxoma / 247

6.4.5 Chordoma / 254

6.4.6 Extraskeletal Myxoid Chondrosarcoma / 257

6.5 Atypical lipomatous tumors / 263

6.5.1 Well-Differentiated liposarcoma / Atypical Lipoma / 263

6.5.2 Spindle Cell and Pleomorphic Lipoma / 270

6.6 Epithelioid tumors / 275

6.6.1 Epithelioid Sarcoma / 276

6.6.2 Gastrointestinal Stromal Tumor (GIST)/EpithelioidLeiomyosarcoma / 282

6.6.3 Epithelioid Angiosarcoma / 287

6.6.4 Granular Cell Tumor / 294

6.6.5 Rhabdoid Tumor / 297

6.6.6 Alveolar Soft Part Sarcoma / 305

6.6.7 Clear Cell Sarcoma / 310

6.6.8 Malignant Melanoma and Metastases / 317

6.7 Pleomorphic sarcomas / 319

6.7.1 Pleomorphic Malignant Fibrous Histiocytoma / 319

6.7.2 Pleomorphic Liposarcoma / 326

6.7.3 Pleomorphic Leiomyosarcoma and Rhabdomyosarcoma / 331

6.7.4 Extraskeletal Osteosarcoma / 341

6.7.5 Pleomorphic Malignant Peripheral Nerve Sheath Tumor / 350

6.8 Round cell sarcomas / 355

6.8.1 Embryonnal and Alveolar Rhabdomyosarcoma / 355

6.8.2 Ewing Sarcoma/Peripheral Neuroectodermal Tumor / 367

6.8.3 Desmoplastic Small Round Cell Tumor / 375

6.8.4 Extraskeletal Mesenchymal Chondrosarcoma / 379

6.8.5 Poorly Differentiated Synovial Sarcoma / 384

Index 411

CONTENTS vii

Foreword

Cytology began with vaginal sampling, and cervical cancer screening programsgradually made the method adopted worldwide.

Diagnostic cytology gained recognition much later, and fine needle aspiration(FNA) cytology initially raised many controversies, hallmarking the disadvantagescompared with the open or core biopsy, which was the considered “gold standard.”

Sweden, and the Karolinska Institute in particular, can be considered the cradle ofFNA clinical cytology.

Many cytologists, including myself, were trained there and initiated into themanagement of the sampling in the one-day clinic, examining the patient, readingthe clinical chart, and dialoguing with the radiologist.

Nowadays the diagnostic needs of the clinician, and moreover the oncologist, havedramatically increased. There is no more room for just prototypic diagnoses.

Benign versus malignant is no longer enough. Suspicion is banned.We moved from a contemplative era of morphology to an interpretive era of

diagnosis incorporating clinical, epidemiological, and radiological aspects for andagainst the cytologic criteria.

Medical oncologists ask more information than just morphology for cancer-targeted therapy planning. We enter now into the new era of molecular diagnosiswith the detection of recurrent chromosome translocations, imbalances, losses, gain,or amplifications specific to histologic types or clues of individual response toadjuvant therapy and outcome, which are even “stronger” than histological typing.

Molecular methods applied on cytological sampling or microbiopsy are becomingincreasingly important for initial diagnosis prior to neoadjuvant, nonsurgicaltherapy, and the combination of molecular biology with metaphase or interphasecytogenetics is imperative in the integrated diagnosis. Therefore, cytology cancontribute to individualizing diagnosis through these molecular analyses.

Fine needle aspiration cytology of mesenchymal lesions is not yet as widelyaccepted for epithelial lesions, and debate persists on its predictive value and

ix

accuracy in subtyping and grading sarcomas. One major drawback is the inexperi-ence of most cytopathologists in the field of soft tissue tumors.

This monograph is addressed to a wide readership of medical specialists (radi-ologists, medical oncologists, surgeons, biologists, young doctors in training, and ofcourse cytopathologists). Because of the rarity and the apparent complexity of thetopic, many surgical pathologists are reluctant to be concerned by this issue. Most oftheir adverse judgments may be avoided while reading this monograph, which makesFNA patterns in soft tissue seem not that difficult.

This monograph does not compete with well-known and largely recognized classictextbooks dealing with soft tissue tumors (Enzinger and Weiss, WHO fascicule, andothers); this book rather must be perceived as a useful original supply in thispathology providing information otherwise unavailable or difficult to locate in auser-friendly format.

The authors with North American or European background (France, Greece,Sweden, USA, and Canada) reflect widely accepted international viewpoints; theyfounded their expertise on their published research data on new entities and emergingmethodologies. They based their long-lasting practice on material collected for half acentury in dedicated reference centers such as the Institut Curie in Paris and l’Hotel-Dieu in Quebec City.

The authors aim to cover the diagnostic areas where FNA is feasible today in softtissue lesions. This includes palpable lesions and lesions sampled using variousradiological methods. Correlations with mandatory ancillary techniques are detailed.

This book proposes a new horizon in the diagnosis of soft tissue tumors, puttingforward how to obtain an optimal approach for diagnosis in the multidisciplinaryteam.

The contents are logically organized with the first chapters addressing the utility ofclinical history, patient’s age, site, and size of the tumor, which are essential in thedifferential diagnoses; the advantages of an organized multidisciplinary team areemphasized by integrating the clinical data, the radiological features, and the morpho-logical pattern.

Precious advice for obtaining optimal material is developed in the technicalchapters. The authors offer to teach a diagnostic method of approach that optimizeshealth care. Complete decisional trees concerning radiology, FNA, core needle, andimmunocyto/histochemistry are proposed; weak points are stressed, errors areanalyzed, and troubleshooting is proposed.

The basics of morphologic patterns are then reviewed focusing on the results ofoptimal nonsurgical sampling in offering opportunities for conventional cytologyand histology as well for immunostaining and molecular techniques.

Sampling by FNA or core biopsy is less invasive than open biopsy (violation ofanatomical compartments, tissue displacements, and vascular emboli). First linemutilating surgery or open biopsy imperatively submits the patient to delayed healingand histological diagnosis.

Risk of tumor seeding within the needle track is a scarecrow.FNA cell-rich material (usually l0�20 millions cells through one needle pass) is in

many cases much better than microbiopsy for molecular techniques: “cell by cell”analysis for fluorescent in situ hybridization (FISH) and “sorted” tumor cells byfluorescence immunophenotyping (FICTION).

x FOREWORD

The future is definitely in “small sampling” through both FNA and core formicrobiology and molecular genetics.

Obtaining FNA one-day diagnosis allows initial fast treatment while waiting fordefinitive pathological and genomic results, which is extremely important in pediatricround cell sarcomas/blastematous tumors.

Even if some entities may have a surprisingly characteristic morphology allowingan accurate cytologic typing (like myxoid liposarcoma and synovial sarcoma),identification of translocations and oncogene mutations are requested in severaltumor types. Specific molecular findings are detected by reverse transcriptase PCR orISH. In situ hybridization (ISH) is based on morphology by direct microscopicvisualization of probe-specific intranuclear signals. The method allows a targeteddetection of genetic aberrations in the nondividing nucleus. The FISH can be appliedto isolated cells from aspirated fluids, intraoperative smears, cell cultures, or paraffin-embedded and frozen tissue blocks. PCR and ISH are complementary methods, andoptimal diagnostic accuracy can be reached when both are available.

In the two last chapters, all differential diagnoses and pitfalls of a wrong orunlikely diagnosis are reviewed entity by entity.

For a practical point on the benchmark, the chapters of entities were groupedfollowing a predominant cell pattern and not an academic classification, which is basedon the putative tissue origin; all these facilitate the diagnosis on small tissue volume.For these reasons, some entities, like MPNST or leiomyosarcoma, may be shown inboth low-grade and high-grade chapters. All groups of tumors are supported by acomplete bibliography hallmarking, for example, that low-grade tumors (like schwan-noma, fibromyxosarcoma, and leiomyosarcoma) being benign or malignant may haveidentical surgical management—the diagnosis of low-grade tumor allows for “pre-pared” surgery in good conditions.

This monograph supplemented by numerous high-quality morphology illustra-tions of both FNA and core needle, will become a precious guide to the cytopathol-ogist in eliminating all the incompatible, improbable, possible diagnoses and inretaining only the likely one.

Alain Verhest, MD, PhD, FIAC

Past President of the International Academy of CytologyFormer Head of the Department of Pathology, Cytology & Cytogenetics

Institut Jules Bordet, Cancer Center of the Untversite Libre de Bruxelles, Belgium

FOREWORD xi

Preface

The purpose of this monograph is to highlight a multidisciplinary approach to softtissue tumors, based on the combined experience of European and North Americanclinicians, radiologists, biologists, surgical pathologists, and cytopathologists. Itdoes not have the pretention to cover the wide field of mesenchymal neoplasms andpseudotumors, which is very adequately provided in the well-known classic text-books. Clinical presentation as well as epidemiology and the importance of aprecise diagnosis are presented from the clinician point of view. A chapter isdevoted to the radiologic evaluation, which has evolved during the past half-century, particularly the techniques of computed tomography and magneticresonance imaging that are essential in the diagnosis/decisional trees for patholo-gical sampling and the staging of malignant neoplasms. Special emphasis is given tocytological study of specimens of both fine needle aspiration (FNA) biopsy andcore needle biopsy (CNB) because the material that forms the basis of the presentbook has been collected from the cytopathology files of Curie Institute, Paris. In thelast decades, FNA and CNB have been recognized as useful tools in the primarydiagnosis of soft tissue tumors. Accordingly, a chapter deals with the optimalmethodologies to obtain representative diagnostic material, as well as the advan-tages and disadvantages of FNA versus CNB.

Ancillary studies such as immunohistochemistry, cytogenetics, and molecularbiology are discussed in general chapters, because they are essential to diagnosis inseveral malignant entities. Given the limitations and the pitfalls of grading malignantsoft tissue tumors, the rules for obtaining the highest performance and thereproducibility of the systems are discussed as are the controversies in the literatureregarding the grading with aspirates and core needle biopsy specimens. The secondpart of the monograph deals with different tumors entities that have been groupedaccording to their principal morphological pattern of presentation, namely low-gradespindle cell, tumors with fibrillary stroma, malignant spindle cell, myxoid, lipoma-tous, epithelioid, pleomorphic, and round cell.

xiii