Опухоли легких, плевры, тимуса и сердца ВОЗ

Tumours oftheLung,ClasificationPleura,WHO Thymus

IARC

World Health Organization Classification of Tumours

Pathology & Genetics

Tumours of the Lung, Pleura,

Thymus and Heart

Edited by William D. Travis, Elizabeth Brambilla,

H. Konrad Müller-Hermelink and Curtis C. Harris

Previous volumes in this series

Kleihues P., Cavenee W.K. (Eds.):	Hamilton S.R., Aaltonen L.A. (Eds.):	Jaffe E.S., Harris N.L., Stein H.,
World Health Organization	World Health Organization	Vardiman J.V. (Eds.): World Health
Classification of Tumours.	Classification of Tumours.	Organization Classification ofTumours.
Pathology and Genetics of	Pathology and Genetics of Tumours	Pathology and Genetics ofTumours of
Tumours of the Nervous System.	of the Digestive System.	Haematopoietic and LymphoidTissues.
IARC Press: Lyon 2000	IARC Press: Lyon 2000	IARC Press: Lyon 2001
ISBN 92 83 22409 4	ISBN 92 83 22410 8	ISBN 92 83 22411 6
Fletcher C.D., Unni K.K.,	Tavassoli F.A., Devilee P. (Eds.):	Eble J.N., Sauter G., Epstein J.E.,
Mertens F. (Eds.): World Health	World Health Organization	Sesterhenn I.A. (Eds.): World Health
Organization Classification of Tumours.	Classification of Tumours.	Organization Classification of Tumours.
Pathology and Genetics of Tumours of	Pathology and Genetics of Tumours of	Pathology and Genetics of Tumours of
Soft Tissue and Bone.	the Breast and Female Genital Organs	the Urinary System and Male Genital
IARC Press: Lyon 2002	IARC Press: Lyon 2003	Organs.
ISBN 92 832 2413 2	ISBN 92 832 2412 4	IARC Press: Lyon 2004
		ISBN 92 832 2415 9

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World Health Organization Classification of Tumours

WHO

OMS

International Agency for Research on Cancer (IARC)

Pathology and Genetics of

Tumours of the Lung, Pleura,

Thymus and Heart

Edited by

William D. Travis

Elisabeth Brambilla

H. Konrad Müller-Hermelink

Curtis C. Harris

IARCPress

Lyon, 2004

World Health Organization Classification of Tumours

Series Editors Paul Kleihues, M.D.

Leslie H. Sobin, M.D.

Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart

Editors	William D. Travis, M.D.
	Elisabeth Brambilla, M.D.
	H. Konrad Müller-Hermelink, M.D.
	Curtis C. Harris, M.D.
Coordinating Editors	Wojciech Biernat, M.D.
	Janice Sych, Ph.D.
Editorial Assistants	Stéphane Sivadier
	Agnès Meneghel
	Voichita Meyronein
Layout	Vanessa Meister
	Marlen Grassinger
	Sibylle Söring
Illustrations	Thomas Odin
Printed by	Team Rush
	69603 Villeurbanne, France
Publisher	IARCPress
	International Agency for
	Research on Cancer (IARC)
	69008 Lyon, France

This volume was produced in collaboration with the

International Academy of Pathology (IAP)

and the

International Association for the Study of Lung Cancer (IASLC)

The WHO Classification of Tumours of Lung, Thymus and Heart presented in this book reflects the views of a Working Group that convened for an Editorial and Consensus Conference in Lyon, France, March 12-16, 2003.

Members of the Working Group are indicated in the List of Contributors on page 289.

Published by IARC Press, International Agency for Research on Cancer, 150 cours Albert Thomas, F-69008 Lyon, France

© International Agency for Research on Cancer, 2004. Reprinted 2007.

Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved.

The International Agency for Research on Cancer welcomes

requests for permission to reproduce or translate its publications, in part or in full. Requests for permission to reproduce figures or charts from this publication should be directed to

the respective contributor (see section Source of Charts and Photographs).

The designations used and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the

World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.

The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others

of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.

The authors alone are responsible for the views expressed in this publication.

Enquiries should be addressed to the

Communications Unit, International Agency for Research on Cancer, 69008 Lyon, France, which will provide the latest information on any changes made to the text and plans for new editions.

Format for bibliographic citations:

Travis W.D., Brambilla E., Muller-Hermelink H.K., Harris C.C. (Eds.): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. IARC Press: Lyon 2004

IARC Library Cataloguing in Publication Data

Pathology and genetics of tumours of the lung, pleura, thymus and heart / editors W.D. Travis… [et al.]

(World Health Organization classification of tumours ; 7)

1. Lung neoplasms - genetics 2. Lung neoplasms - pathology

3. Pleura neoplasms - genetics 4. Pleura neoplasms, - pathology 5. Thymus neoplasms - genetics 6. Thymus neoplasms - pathology 7. Heart neoplasms – genetics 8. Heart neoplasms - pathology

I. Travis William D. II. Series

ISBN 92 832 2418 3 (NLM Classification: WJ 160)

Contents

1 Tumours of the lung	9
WHO and TNM classifications	10
Introduction	12
Epidemiology and etiology	12
Clinical features and staging	16
Concept of pulmonary neuroendocrine tumours	19
Genetic and molecular alterations	21
Genetic susceptibility	24
Malignat epithelial tumours	26
Squamous cell carcinoma	26
Small cell carcinoma	31
Adenocarcinoma	35
Mixed subtype	37
Acinar adenocarcinoma	37
Papillary adenocarcinoma	38
Bronchioloalveolar adenocarcinoma	38
Solid adenocarcinoma	38
Fetal adenocarcinoma	40
Mucinous (colloid) adenocarcinoma	40
Mucinous cystadenocarcinoma	40
Signet ring adenocarcinoma	40
Clear cell adenocarcinoma	40
Large cell carcinoma	45
Large cell neuroendocrine carcinoma	47
Basaloid carcinoma	48
Lymphoepithelioma-like carcinoma	48
Clear cell carcinoma	48
Rhabdoid phenotype	48
Adenosquamous carcinoma	51
Sarcomatoid carcinoma	53
Pleomorphic carcinoma	55
Spindle cell carcinoma	55
Giant cell carcinoma	55
Carcinosarcoma	56
Pulmonary blastoma	56
Carcinoid tumour	59
Typical carcinoid	59
Atypical carcinoid	59
Salivary gland tumours	63
Mucoepidermoid carcinoma	63
Adenoid cystic carcinoma	65
Epithelial-myoepithelial carcinoma	67
Preinvasive epithelial lesions	68
Squamous dysplasia and carcinoma in situ	68
Atypical adenomatous hyperplasia	73
Diffuse idiopathic pulmonary neuroendocrine	76
cell hyperplasia
Benign epithelial lesions	78
Papilloma	78
Squamous cell papilloma	78
Glandular papilloma	80
Mixed papilloma	81
Alveolar adenoma	82

Papillary adenoma	84
Adenomas of salivary gland type	85
Mucous gland adenoma	85
Pleomorphic adenoma	86
Mucinous cystadenoma	87
Lymphoid / histiocytic tumours	88
MALT lymphoma	88
Diffuse large B-cell lymphoma	91
Lymphomatoid granulomatosis	92
Pulmonary Langerhans cell histiocytosis	95
Mesenchymal tumours	97
Epithelioid haemangioendothelioma /
angiosarcoma	97
Pleuropulmonary blastoma	99
Chondroma	101
Congenital peribronchial
myofibroblastic tumour	102
Diffuse pulmonary lymphangiomatosis	104
Inflammatory myofibroblastic tumour	105
Lymphangioleiomyomatosis	107
Pulmonary vein sarcoma	108
Pulmonary artery sarcoma	109
Synovial sarcoma	111
Miscellaneous tumours	113
Hamartoma	113
Sclerosing haemangioma	115
Clear cell tumour	118
Teratoma	119
Intrapulmonary thymoma	120
Melanoma	121
Metastases to the lung	122
2 Tumours of the pleura	125
WHO and TNM classifications	126
Mesothelioma	128
Epithelioid mesothelioma	132
Sarcomatoid mesothelioma	133
Desmoplastic mesothelioma	133
Biphasic mesothelioma	134
Well differentiated papillary mesothelioma	135
Localized malignant mesothelioma	136
Adenomatoid tumour	136
Lymphomas	137
Primary effusion lymphoma	137
Pyothorax-associated lymphoma	138
Mesenchymal tumours	141
Epithelioid haemangioendothelioma /
angiosarcoma	141
Synovial sarcoma	141
Solitary fibrous tumour	142
Calcifying tumour	143
Desmoplastic small round cell tumour	144

3 Tumours of the thymus	145
WHO and TNM classifications	146
Tumours of the Thymus: Introduction	148
Thymomas	152
Type A	154
Type AB	157
Type B1	159
Type B2	161
Type B3	164
Micronodular thymoma	167
Metaplastic thymoma	169
Microscopic thymoma	171
Sclerosing thymoma	171
Lipofibroadenoma	171
Thymic carcinomas	172
Squamous cell carcinoma	172
Basaloid carcinoma	175
Mucoepidermoid carcinoma	176
Lymphoepithelioma-like carcinoma	177
Sarcomatoid carcinoma	179
Clear cell carcinoma	182
Papillary adenocarcinoma	183
Non-papillary adenocarcinoma	184
Carcinoma with t(15;19) translocation	185
Undifferentiated carcinoma	187
Thymic neuroendocrine tumours	188
Typical carcinoid	191
Atypical carcinoid	191
Large cell neuroendocrine carcinoma	193
Small cell neuroendocrine carcinoma	193
Combined thymic epithelial tumours	196
Germ cell tumours of the mediastinum	198
Seminoma	202
Embryonal carcinoma	205
Yolk sac tumour	207
Choriocarcinoma	209
Teratoma	210
Mixed germ cell tumours	213
GCT with somatic type malignancy	216
GCT with haematologic malignancies	219
Lymphomas of the mediastinum	221
Primary large B-cell lymphoma	222
Thymic MALT lymphoma	225
Precursor T-lymphoblastic lymphoma /
leukaemia	227
Anaplastic large T-cell lymphoma	229
Hodgkin lymphoma	230
Grey zone lymphoma Hodgkin / NHL	233
Histiocytic tumours	234
Dendritic cell tumours	236
Myeloid sarcoma and extramedullary AML	238
Soft tissue tumours of the mediastinum	239
Thymolipoma	239
Mediastinal lipoma	240
Liposarcoma	240
Solitary fibrous tumour	241
Rhabdomyosarcoma	242
Synovial sarcoma	244
Vascular neoplasms	244

Leiomyomatous tumours	244
Neurogenic tumours	245
Ectopic thyroid tumours	246
Ectopic parathyroid tumours	246
Metastases to the mediastinum	247
4 Tumours of the heart	249
WHO classification	250
Introduction	251
Benign tumours with myocyte differentiation	254
Rhabdomyoma	254
Histiocytoid cardiomyopathy	256
Hamartoma of mature cardiac myocytes	258
Adult cellular rhabdomyoma	259
Benign tumours of pluripotent mesenchyme	260
Cardiac myxoma	260
Papillary fibroelastoma	263
Haemangioma	266
Benign tumours with myofibroblastic
differentiation	268
Cardiac fibroma	268
Inflammatory myofibroblastic tumour	270
Cardiac lipoma	271
Cystic tumour of atrioventricular node	272
Cardiac sarcomas	273
Angiosarcoma	273
Epithelioid haemangioendothelioma	275
Pleomorphic malignant fibrous histiocytoma /
unidifferentiated pleomorphic sarcoma	276
Fibrosarcoma and myxosarcoma	277
Rhabdomyosarcoma	278
Leiomyosarcoma	280
Synovial sarcoma	280
Cardiac lymphomas	282
Metastatic tumours to the heart	284
Pericardial tumours	285
Solitary fibrous tumour	285
Malignant mesothelioma	286
Germ cell tumours	287
Metastatic pericardial tumours	287
Contributors	299
Source of charts and photographs	304
References	306
Subject index	353