Table Of Contentc.
J. E. Underwood
Introduction to
Biopsy Interpretation
and Surgical Pathology
With 71 Figures
Springer-Verlag
Berlin Heidelberg New 1981
York~
J. C. E. Underwood, MD, MRCPath.
Senior Lecturer in Pathology, University of Sheffield Medical School, and Honorary
Consultant Histopathologist, Royal Hallamshire Hospital, Sheffield, SlO 2RX, England.
ISBN-13: 978-1-4471-3303-2 e-ISBN-13: 978-1-4471-3301-8
DOl: 10.1007/978-1-4471-3301-8
Bibliography: p. Includes index. 1. Pathology, Surgical. 2. Biopsy. I. Title. [DNLM:
1. Biopsy. 2. Diagnosis, Surgical. WO 142 U55i] RD57.U52 616.07'5880-25572 AACRI
ISBN-13: 978-1-4471-3303-2
This work is subject to copyright. All rights are reserved, whether the whole or part of the
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© Springer-Verlag Berlin Heidelberg 1981
Softcover reprint of the hardcover 1st edition 1981
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2128/3916-543210
To Ina, Justin, and Claire
Contents
Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Xl
Acknowledgements Xlll
Explanatory Note XV
1 Diagnostic Histopathology ...................................... I
A. Origins of Histopathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I
B. The Objectives of Histopathology ................................ 4
1. Clinical Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
II. Epidemiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
III. Treatment Selection and Monitoring. . . . . . . . . . . . . . . . . . . . . . . . . 5
IV. Clinical Research. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
V. Autopsies and Clinico-pathological Correlation. . . . . . . . . . . . . . . . 6
C. The Histopathological Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
I. Diagnosis and Disease ..................................... 7
II. Diagnostic Processes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
III. Diagnostic Fallibility ...................................... 8
IV. Quality Assessment and Control. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
2 Macroscopy, Microscopy, and Sampling .......................... 15
A. Sampling Error. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
B. Sampling Biopsies and Surgical Resections. . . . . . . . . . . . . . . . . . . . . . . . . 16
I. Suspected or Proven Neoplasia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
II. Ischaemic and Vascular Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
III. Infections and Inflammatory Lesions. . . . . . . . . . . . . . . . . . . . . . . . . 21
IV. Metabolic and Degenerative Diseases. . . . . . . . . . . . . . . . . . . . . . . . . 22
C. Specific Types of Biopsy ........................................ 22
I. Needle Biopsies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
II. Mucosal Biopsies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
III. Currettings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
IV. Cone Biopsies ............................................ 25
D. Imprints, Smears, and Squashes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
E. Living Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
F. Specimen Radiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
G. Section Thickness. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Vlll Contents
I. Thick Sections 28
II. Thin Sections ........................................... . 30
H. Information and Magnification .................................. . 30
3 The Use of Stains ............. ............................... . 35
A. Principles of Staining .......................................... . 35
B. Indications for Special Stains ................................... . 37
C. Immunofluorescence and Immunohistochemistry .................. . 37
D. Identification of Specific Substances and Cells ..................... . 39
I. Connective Tissues ....................................... . 39
II. Carbohydrates .......................................... . 42
III. Nucleic Acids ........................................... . 44
IV. Fats ................................................. . 44
V. Minerals and Pigments ................................... . 45
VI. Organisms .............................................. . 46
VII. Specific Cells ............................................ . 47
E. Autoradiography ............................................ . 50
4 Interpretation of Histological Appearances ........................ . 51
A. Artifact of Sections ............................................ . 51
B. Basic Microscopy ............................................. . 53
C. Methods of Interpretation ...................................... . 54
I. Heuristic Analysis ........................................ . 54
II. Pattern Recognition ...................................... . 55
III. Clinico-pathological Integration ............................ . 58
D. Morphology of Disease Processes ................................ . 58
I. Evolution of Lesions ...................................... . 58
II. Modification by Treatment ................................ . 59
III. Significance of Specific Morphological Features ............... . 59
IV. Morphological Overlap Between Diseases .................... . 73
75
5 Borderline Lesions, Pseudomalignancy, and Mimicry . . . . . . . . ........ .
A. Borderline Lesions ............................................ . 75
I. Discrete Versus Continuous Diagnostic Categories ............ . 75
II. Use of Criteria .......................................... . 75
B. Mimicry of Histological Features ................................ . 78
C. Pseudomalignancy and Related Diagnostic Problems ............... . 78
I. Skin .................................................. . 80
II. Soft Tissues ............................................ . 84
III. Lymphoid Tissues ........................................ . 86
IV. Bone .................................................. . 87
V. Breasts ................................................ . 87
VI. Urinary Tract .......................................... . 88
VII. Thyroid ................................................ . 90
VIII. Male Genitalia .......................................... . 91
IX. Female Genital Tract .................................... . 93
X. Gastrointestinal Tract .................................... . 93
Xl. Respiratory Tract ........................................ . 94
XII. Serosal Surfaces ........................................ . 95
Contents ix
XIII. Central Nervous System 95
6 Rapid Frozen Section Diagnosis ................................. 99
A. Clinical Indications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
B. Methods...................................................... 100
C. Interpretation................................................. 101
D. Common Applications.......................................... 102
I. Breast Lesions .......................................... 102
II. Thyroid ................................................ 103
III. Parathyroid Glands ...................................... 103
IV. Gastrointestinal Tract .................................... 104
V. Respiratory Tract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
VI. Urinary Tract .......................................... 104
VII. Bone and Soft Tissues .................................... 105
VIII. Skin .................................................. 105
E. Reliability ................................................... 105
7 Diagnostic Electron Microscopy ................................ 109
A. Principles of Transmission Electron Microscopy. . . . . . . . . . . . . . . . . . . 109
I. The Electron Microscope ................................ 109
II. Specimen Processing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
B. Diagnostic Value of Transmission Electron Microscopy. . . . . . . . . . . . . 112
I. Renal Disease ........................................... 112
II. Tumour Histogenesis ..................................... 113
III. Virus Identification. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
IV. Miscellaneous Applications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
C. Scanning Electron Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
D. X-ray Microanalysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
8 Quantitative Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
A. Stereological Principles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
B. Stereological Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
I. Volumetric Analysis .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
II. Surface Area ............................................ 124
III. Surface-to-Volume Ratios. . . ... .. . .. . . .. .. ..... .. . .. . . . .. . 124
IV. Particle Size and Density. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
C. Automatic and Semi-Automatic Image Analysis ................... 125
D. Microspectrophotometry and Flow Microfluorimetry. ... .. . .. . . . .. . 125
E. Practical Applications ........................... ............. 126
I. Metabolic Bone Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
II. Jejunal Biopsies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
III. Respiratory Tract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
IV. Tumours.... . . . . ... . . .. . . . ... .. . . . . . .. . . ..... .. . . . .. . .. . 128
9 Reporting and Classification of Biopsy Diagnoses .................. 131
A. The Biopsy Report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
I. Gross Description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
II. Histology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
III. Other Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
X Contents
IV. Summary............................................... 132
B. Disease Classifications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
I. "Lumping" and "Splitting" . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
II. Nomenclature and Codes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
III. Problems in Tumour Classification and Grading ..... . . . . . . . . . 135
C. Data Storage and Retrieval . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
D. Clinical Assimilation .......................................... 137
Subject Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Preface
This book is primarily addressed to the needs of the trainee histopathologist. It is
intended to bridge that gap between the descriptive histopathology taught as part of
the undergraduate medical curriculum and the interpretative skills required of the
diagnostician. My object is to convey the basic general principles, in theory and
practice. Books are, however, only adjuncts to practical experience and not
substitutes for it. Indeed, to obtain the maximum benefit from this book it is essential
that the reader is actively involved in the work ofa diagnostic laboratory. Only in this
way can the trainee become thoroughly conversant with the rudiments of biopsy
interpretation.
To retain detailed knowledge of the histological appearances of the plethora of
diseases and their permutations to which humans are subject is beyond the mental
resources of most individuals. For this reason, histopathologists probably refer to
books more often than do most other specialists. This book aims to provide a core of
knowledge sufficient to master the fundamental aspects, while still encouraging the
intelligent use of all those indispensable atlases, monographs, and fascicles for which
there is no substitute.
I make no apologies for beginning the text with a brief account of the history of the
biopsy. The origins ofb iopsy diagnosis might be dismissed as having little relevance to
current practice, but it is often easier to understand a subject if one can see how it has
evolved and recognise the various ways in which it may continue to develop. Also, it
would have been easy to evade the need for a systematic consideration of the actual
processes of interpretation. Having decided that the reader should be introduced to
heuristics and pattern recognition, I was anxious to avoid giving an idiosyncratic
account of something so personal and subjective. I hope I have succeeded in showing
that there is nothing particularly arcane about the methods we use to interpret
histological images.
The histopathological diagnosis does not begin and end with the inert, two
dimensional, brightly coloured artifact of the stained histological section. It begins
with a living patient and ends with a credible report embodying a diagnosis or any
other infonnation that may guide the treatment ofthe patient. Modern investigative
techniques may be needed to solve some diagnostic problems and for that reason I
have included a general introduction to newer methods of histopathological analysis
ofp roven clinical value. These include electron microscopy, immunological methods,
and stereology. Those who work in laboratories without such resources will, I hope,
find guidance to the potential usefulness of these relatively sophisticated techniques.
Perhaps they will be prompted to seek appropriate help and advice from colleagues
who have access to the materials and skills that are necessary to solve some ofthe more
difficult problems that may come th~ir way.
xii Preface
I have referred to published work liberally but not uncritically. I hope that the text
will whet the reader's appetite for more information and give directions as to where it
may be satiated.
For the trainee, this will be an introduction to biopsy interpretation and surgical
pathology in the context of contemporary clinical medicine. The text is an overview
and commentary on current theory and practice in histopathology; I would therefore
be well pleased ifsenior pathologists or clinicians also found somethi ng ofi nterest and
value in these pages.
Sheffield, January 1981 J. C. E. Underwood
