Rare Tumors and Tumor-like Conditions in Urological Pathology

447 Pages·2015·58.165 MB·English

by  Antonio Lopez-Beltran, Carmen L. Menendez, Rodolfo Montironi, Liang Cheng (auth.)

Rare Tumors and
Tumor-like Conditions
in Urological Pathology
Antonio Lopez-Beltran
Carmen L. Menendez
Rodolfo Montironi
Liang Cheng
123
Rare Tumors and Tumor-like Conditions
in Urological Pathology

Antonio Lopez-Beltran
Carmen L. M enendez
Rodolfo Montironi
Liang Cheng
Rare Tumors and
Tumor- like Conditions
in Urological Pathology
Antonio Lopez-Beltran, MD, PhD Rodolfo Montironi, MD
Department of Surgery and Pathology Department of Biomedical
University of Cordoba Faculty Sciences and Public Health
of Medicine Polytechnic University of the Marche
Cordoba Region (Ancona)
Spain Torrette
Italy
Carmen L. Menendez, MD
Pathology Department Liang Cheng, MD
Hospital de Cabueñes Department of Pathology
Gijón Indiana University School of Medicine
Spain Indianapolis , Indiana
USA
ISBN 978-3-319-10252-8 ISBN 978-3-319-10253-5 (eBook)
DOI 10.1007/978-3-319-10253-5
Springer Cham Heidelberg New York Dordrecht London
Library of Congress Control Number: 2014953767
© Springer International Publishing Switzerland 2015
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or
part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of
illustrations, recitation, broadcasting, reproduction on microfi lms 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. Exempted from this
legal reservation are brief excerpts in connection with reviews or scholarly analysis or material
supplied specifi cally for the purpose of being entered and executed on a computer system, for
exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is
permitted only under the provisions of the Copyright Law of the Publisher's location, in its
current version, and permission for use must always be obtained from Springer. Permissions for
use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable
to prosecution under the respective Copyright Law.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specifi c statement, that such names are
exempt from the relevant protective laws and regulations and therefore free for general use.
While the advice and information in this book are believed to be true and accurate at the date of
publication, 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)
Contents
1 Renal Tumors and Tumor-Like Conditions . . . . . . . . . . . . . . . . 1
1.1 Basic Anatomy and Histology . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.3 Familial Renal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3.1 Von Hippel-Lindau (VHL) Clear
Cell Renal Cell Carcinoma (RCC) . . . . . . . . . . . . . . 4
1.3.2 Hereditary Papillary RCC. . . . . . . . . . . . . . . . . . . . . 4
1.3.3 Hereditary Leiomyomatosis RCC. . . . . . . . . . . . . . . 4
1.3.4 Birt-Hogg-Dube Syndrome. . . . . . . . . . . . . . . . . . . . 5
1.4 Renal Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.4.1 Clear Cell RCC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.4.2 Multilocular Cystic Clear Cell Renal Cell
Neoplasm of Low Malignant Potential. . . . . . . . . . . 6
1.4.3 Papillary RCC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
1.4.4 Chromophobe RCC . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.4.5 Hybrid Oncocytic Chromophobe Tumor (HOCT). . . 12
1.4.6 Collecting Duct Carcinoma . . . . . . . . . . . . . . . . . . . 14
1.4.7 Renal Medullary Carcinoma. . . . . . . . . . . . . . . . . . . 16
1.4.8 Mucinous, Tubular and Spindle Cell Carcinoma . . . 16
1.4.9 Renal Cell Carcinoma After Neuroblastoma . . . . . . 20
1.4.10 RCC with Sarcomatoid or Rhabdoid
Differentiation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
1.4.11 Renal Cell Carcinoma, Unclassifi ed. . . . . . . . . . . . . 21
1.5 Proposed New and Emerging Epithelial Renal Tumors. . . . . 22
1.5.1 Tubulocystic Renal Cell Carcinoma. . . . . . . . . . . . . 22
1.5.2 Acquired Cystic Disease- Associated RCC. . . . . . . . 22
1.5.3 Clear Cell Papillary (Tubulo- Papillary) RCC. . . . . . 23
1.5.4 MiT Family Translocation RCC. . . . . . . . . . . . . . . . 25
1.5.5 Thyroid-Like Follicular Renal Cell Carcinoma . . . . 27
1.5.6 Succinic Dehydrogenase B Defi ciency
Associated Renal Cell Carcinoma . . . . . . . . . . . . . . 27
1.5.7 ALK-Translocation Renal Cell Carcinoma . . . . . . . 28
1.5.8 Renal Cell Carcinoma with Smooth
Muscle Stroma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
v
vi Contents
1.5.9 Tuberous Sclerosis-Associated Renal
Cell Carcinoma. . . . . . . . . . . . . . . . . . . . . . . . . . . 29
1.6 Benign Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
1.6.1 Papillary Adenoma. . . . . . . . . . . . . . . . . . . . . . . . 30
1.6.2 Metanephric Tumors. . . . . . . . . . . . . . . . . . . . . . . 30
1.6.3 Renal Oncocytoma . . . . . . . . . . . . . . . . . . . . . . . . 30
1.7 Percutaneous Biopsy of Renal Tumours . . . . . . . . . . . . . . . 33
1.8 Cystic Nephroma and Mixed Epithelial
and Stromal Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
1.9 Soft Tissue Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
1.9.1 Medullary Fibroma. . . . . . . . . . . . . . . . . . . . . . . . 37
1.9.2 Juxtaglomerular Cell Tumor. . . . . . . . . . . . . . . . . 38
1.9.3 Glomus Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
1.9.4 Angiomyolipoma . . . . . . . . . . . . . . . . . . . . . . . . . 39
1.9.5 Epithelioid Angiomyolipoma. . . . . . . . . . . . . . . . 40
1.9.6 Leiomyoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
1.9.7 Lipoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
1.9.8 Hemangioma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
1.9.9 Lymphangioma. . . . . . . . . . . . . . . . . . . . . . . . . . . 42
1.9.10 Schwannoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
1.9.11 Solitary Fibrous Tumor. . . . . . . . . . . . . . . . . . . . . 43
1.9.12 Leiomyosarcoma. . . . . . . . . . . . . . . . . . . . . . . . . . 43
1.9.13 Angiosarcoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
1.9.14 Liposarcoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
1.9.15 Rhabdomyosarcoma. . . . . . . . . . . . . . . . . . . . . . . 45
1.9.16 Malignant Fibrous Histiocytoma . . . . . . . . . . . . . 45
1.9.17 Hemangiopericytoma . . . . . . . . . . . . . . . . . . . . . . 45
1.9.18 Hemangioblastoma. . . . . . . . . . . . . . . . . . . . . . . . 46
1.9.19 Osteosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
1.9.20 Other Soft Tissue Tumors. . . . . . . . . . . . . . . . . . . 47
1.10 Wilms’ Tumor and Other Renal Neoplasms in Children. . . 48
1.10.1 Nephrogenic Rests and Nephroblastomatosis . . . 48
1.10.2 Nephroblastoma (Wilms’ Tumor). . . . . . . . . . . . . 48
1.10.3 Cystic Partially Differentiated Nephroblastoma. . . 49
1.10.4 Congenital Mesoblastic Nephroma (CMN) . . . . . 50
1.10.5 Clear Cell Sarcoma of Kidney . . . . . . . . . . . . . . . 52
1.10.6 Rhabdoid Tumor of Kidney . . . . . . . . . . . . . . . . . 52
1.10.7 Neuroblastoma . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
1.10.8 Primitive Neuroectodermal Tumor (PNET). . . . . 52
1.10.9 Desmoplastic Small Round Cell Tumor. . . . . . . . 52
1.10.10 Synovial Sarcoma. . . . . . . . . . . . . . . . . . . . . . . . . 53
1.10.11 Ossifying Renal Tumor of Infancy. . . . . . . . . . . . 54
1.11 Other Rare Tumors and Tumor-Like Conditions. . . . . . . . . 54
1.11.1 Neuroendocrine Tumors. . . . . . . . . . . . . . . . . . . . 54
1.11.2 Hematopoietic and Lymphoid Tumors. . . . . . . . . 54
1.11.3 Germ Cell Tumors . . . . . . . . . . . . . . . . . . . . . . . . 54
1.11.4 Other Rare Epithelial Tumors and Renal
Cell Carcinoma in Children . . . . . . . . . . . . . . . . . 55
1.11.5 Tumor-Like Conditions. . . . . . . . . . . . . . . . . . . . . 55
Contents vii
1.12 Secondary Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
2 Tumors and Tumor-Like Conditions of Urinary Bladder,
Renal Pelvis, Ureter and Urethra. . . . . . . . . . . . . . . . . . . . . . . . . 63
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
2.1.1 Basic Anatomy and Histology. . . . . . . . . . . . . . . . 63
2.2 Urinary Bladder. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
2.2.1 Urothelial Carcinoma . . . . . . . . . . . . . . . . . . . . . . 68
2.2.2 Flat Intraepithelial Lesions . . . . . . . . . . . . . . . . . . 68
2.2.3 Urothelial Carcinoma . . . . . . . . . . . . . . . . . . . . . . 84
2.2.4 Benign Urothelial Neoplasms . . . . . . . . . . . . . . . . 122
2.2.5 Glandular Neoplasms . . . . . . . . . . . . . . . . . . . . . . 128
2.2.6 Squamous Cell Neoplasms . . . . . . . . . . . . . . . . . . 135
2.2.7 Neuroendocrine Tumors . . . . . . . . . . . . . . . . . . . . 139
2.2.8 Soft Tissue Tumors . . . . . . . . . . . . . . . . . . . . . . . . 148
2.2.9 Malignant Melanoma. . . . . . . . . . . . . . . . . . . . . . . 166
2.2.10 Germ Cell Tumors. . . . . . . . . . . . . . . . . . . . . . . . . 167
2.2.11 Hematologic Malignancies . . . . . . . . . . . . . . . . . . 167
2.2.12 Tumor-Like Conditions. . . . . . . . . . . . . . . . . . . . . 168
2.2.13 Metastatic Tumors and Secondary Extension . . . . 176
2.2.14 Metastatic Urothelial Carcinoma. . . . . . . . . . . . . . 176
2.3 The Renal Pelvis and Ureter . . . . . . . . . . . . . . . . . . . . . . . . 177
2.4 The Urethra . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
3 The Prostate and Seminal Vesicles. . . . . . . . . . . . . . . . . . . . . . . . 195
3.1 Basic Anatomy and Histology. . . . . . . . . . . . . . . . . . . . . . . 196
3.1.1 The Prostate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196
3.1.2 The Seminal Vesicles and Ejaculatory Ducts . . . . 201
3.2 Adenocarcinoma of the Prostate . . . . . . . . . . . . . . . . . . . . . 202
3.2.1 Preneoplastic Lesions and Conditions. . . . . . . . . . 202
3.3 Diagnostic Criteria for Prostate Adenocarcinoma . . . . . . . . . 214
3.3.1 Histologic Features of Prostate Cancer. . . . . . . . . 215
3.4 Rare Histologic Subtypes of Prostatic Carcinoma. . . . . . . . 224
3.4.1 Pseudohyperplastic Adenocarcinoma . . . . . . . . . . 224
3.4.2 Foamy Gland Adenocarcinoma. . . . . . . . . . . . . . . 225
3.4.3 Atrophic Adenocarcinoma. . . . . . . . . . . . . . . . . . . 226
3.4.4 Adenocarcinoma with Glomeruloid Features . . . . 228
3.4.5 Mucinous and Signet Ring
Cell Adenocarcinoma . . . . . . . . . . . . . . . . . . . . . . 228
3.4.6 Oncocytic Adenocarcinoma . . . . . . . . . . . . . . . . . 229
3.4.7 Lymphoepithelioma-Like Carcinoma
of the Prostate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230
3.4.8 Prostatic Ductal Adenocarcinoma. . . . . . . . . . . . . 232
3.4.9 Intraductal Carcinoma. . . . . . . . . . . . . . . . . . . . . . 237
3.4.10 Small Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . 239
3.4.11 Sarcomatoid Carcinoma (Carcinosarcoma). . . . . . 241
3.4.12 PIN-Like Carcinoma . . . . . . . . . . . . . . . . . . . . . . . 243
3.4.13 Pleomorphic Giant Cell Carcinoma. . . . . . . . . . . . 244
viii Contents
3.5 Gleason Grading of Prostate Cancer . . . . . . . . . . . . . . . . . . 247
3.5.1 Gleason Patterns. . . . . . . . . . . . . . . . . . . . . . . . . . . . 248
3.5.2 Reporting Gleason Scores in Prostate Needle
Biopsies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
3.5.3 Reporting Gleason Scores in Radical
Prostatectomies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
3.5.4 Grading Variants and Variations
of Adenocarcinoma of the Prostate . . . . . . . . . . . . . 252
3.5.5 Correlation Between Needle Biopsy
and RP Gleason Scores . . . . . . . . . . . . . . . . . . . . . . 252
3.5.6 Pathology of the Prostate After Treatment. . . . . . . . 254
3.6 Pathologic Prognosis of Prostate Cancer. . . . . . . . . . . . . . . 261
3.6.1 Prostate Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
3.6.2 Prognostic Factors After Radical Prostatectomy. . . 266
3.7 Basic Molecular Pathology of Prostate Cancer . . . . . . . . . . 271
3.8 Rare Forms of Prostatic Tumours . . . . . . . . . . . . . . . . . . . . 274
3.9 Tumors and Tumor-Like Conditions
of the Prostate Stroma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
3.10 Miscellaneous Primary Tumours of the Prostate. . . . . . . . . 298
3.11 Secondary Tumours Involving the Prostate. . . . . . . . . . . . . 298
3.12 Seminal Vesicles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
4 Testis and Paratesticular Structures . . . . . . . . . . . . . . . . . . . . . . 311
4.1 Basic Anatomy and Histology. . . . . . . . . . . . . . . . . . . . . . . 312
4.2 C lassifi cation of Tumors and Tumor-Like Conditions. . . . . 313
4.2.1 Germ Cell Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . 314
4.2.2 Intratubular Germ Cell Neoplasia,
Unclassifi ed (IGCNU). . . . . . . . . . . . . . . . . . . . . . . 315
4.2.3 Germ Cell Tumors of One Histologic Type. . . . . . . 316
4.2.4 Seminoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
4.2.5 Spermatocytic Seminoma . . . . . . . . . . . . . . . . . . . . 320
4.3 Non-seminomatous Germ Cell Tumors (NSGCTs). . . . . . . 322
4.3.1 Embryonal Carcinoma. . . . . . . . . . . . . . . . . . . . . . . 322
4.4 Yolk Sac Tumor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
4.4.1 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
4.4.2 Immunohistochemistry . . . . . . . . . . . . . . . . . . . . . . 327
4.4.3 Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330
4.5 Polyembryoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
4.6 Choriocarcinoma and Other Types of Throphoblastic
Neoplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
4.6.1 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
4.6.2 Morphologic Variants. . . . . . . . . . . . . . . . . . . . . . . . 332
4.6.3 Immunohistochemistry . . . . . . . . . . . . . . . . . . . . . . 333
4.6.4 Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334
4.7 Teratoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334
4.7.1 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334
4.7.2 Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334
4.7.3 Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
Contents ix
4.8 Burned Out GCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
4.9 Tumors of More than One Histologic Type
(Mixed Forms). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
4.9.1 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336
4.9.2 Prognostic Factors. . . . . . . . . . . . . . . . . . . . . . . . . 337
4.10 Tumors of Sex Cord/Gonadal Stroma . . . . . . . . . . . . . . . . . 338
4.11 Benign and Malignant Leydig Cell Tumors. . . . . . . . . . . . . 339
4.11.1 Pathology of Benign Tumors. . . . . . . . . . . . . . . . . 339
4.11.2 Pathology of Malignant Tumors . . . . . . . . . . . . . . 339
4.11.3 Genetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342
4.12 Benign and Malignant Sertoli Cell Tumors. . . . . . . . . . . . . 342
4.12.1 Pathology of Benign Tumors. . . . . . . . . . . . . . . . . 342
4.12.2 Pathology of Malignant Tumors . . . . . . . . . . . . . . 346
4.12.3 Genetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346
4.13 Large Cell Calcifying Sertoli Cell Tumor (LCCST) . . . . . . 346
4.13.1 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346
4.14 Granulosa Cell Tumor of Adult Type . . . . . . . . . . . . . . . . . 347
4.15 Granulosa Cell Tumor of Juvenile Type . . . . . . . . . . . . . . . 347
4.16 Thecoma–Fibroma Type Tumors. . . . . . . . . . . . . . . . . . . . . 347
4.17 Mixed or Incompletely Differentiated (Undifferentiated)
Gonadal Stromal Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . 348
4.18 Mixed Germ Cell/Sex Cord Stromal Tumor . . . . . . . . . . . . 348
4.18.1 Gonadoblastoma . . . . . . . . . . . . . . . . . . . . . . . . . . 348
4.18.2 Germ Cell Sex Cord/Gonadal Stromal Tumor,
Unclassifi ed. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
4.19 Other Tumors of the Testis. . . . . . . . . . . . . . . . . . . . . . . . . . 350
4.19.1 Carcinoid. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
4.19.2 Nephroblastoma. . . . . . . . . . . . . . . . . . . . . . . . . . . 350
4.19.3 Lymphoma and Plasmacytoma . . . . . . . . . . . . . . . 350
4.19.4 Leukemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
4.20 Other Rare Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352
4.21 Testicular Metastases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
4.22 Tumors of the Paratesticular Region . . . . . . . . . . . . . . . . . . 355
4.23 Tumors of Ovarian (Müllerian) Epithelial Types. . . . . . . . . 355
4.24 Tumors of Collecting Ducts and Rete Testis . . . . . . . . . . . . 355
4.24.1 Adenoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
4.24.2 Adenocarcinoma of Rete Testis. . . . . . . . . . . . . . . 355
4.25 Epithelial Tumors of the Epididymis. . . . . . . . . . . . . . . . . . 356
4.25.1 Papillary Cystadenoma of the Epididymis . . . . . . 356
4.25.2 Adenocarcinoma of the Epididymis . . . . . . . . . . . 357
4.25.3 Adenomatoid Tumor . . . . . . . . . . . . . . . . . . . . . . . 358
4.26 Mesothelioma of the Tunica Vaginalis Testis . . . . . . . . . . . 358
4.26.1 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359
4.27 Melanotic Neuroectodermal Tumor of Infancy. . . . . . . . . . 360
4.28 Desmoplastic Small Round Cell Tumor . . . . . . . . . . . . . . . 360
4.29 Soft Tissue Tumors of the Spermatic Cord . . . . . . . . . . . . . 361
4.30 Tumor-Like Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362
4.30.1 Intratesticular Hemorrhage . . . . . . . . . . . . . . . . . . 362
4.30.2 Segmental Testicular Infarction. . . . . . . . . . . . . . . 362