Immunohistochemistry in Tumor Diagnostics

257 Pages·2017·25.45 MB·English

by  Guski

Immuno histo-
chemistry in
Tumor Diagnostics
Muin S.A. Tuff aha
Hans Guski
Glen Kristiansen
123
Immunohistochemistry in Tumor
Diagnostics
Muin S.A. Tuffaha • Hans Guski
Glen Kristiansen
Immunohistochemistry
in Tumor Diagnostics
Muin S.A. Tuffaha Glen Kristiansen
Carl-Thiem-Klinikum Universität Bonn, UKB
Institut für Pathologie Institut für Pathologie
Cottbus Bonn
Germany Germany
Hans Guski
Vivantes Klinikum Neukölln
Institut für Pathologie
Berlin
Germany
ISBN 978-3-319-53576-0 ISBN 978-3-319-53577-7 (eBook)
DOI 10.1007/978-3-319-53577-7
Library of Congress Control Number: 2017941713
© Springer International Publishing AG 2018
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This book is dedicated to the memory of my father Sami and to
the two great women in my life, my mother Haya and my wife
Ayah.
Muin S.A. Tuffaha
Dedicated to my wife Maren, and daughters Maren and Silja
who all are involved in human medicine.
Hans Guski
Dedicated to my wife Ilka and to our children Charlotte, Clara
and Karl for their support and patience.
Glen Kristiansen
Contents
1 Immunohistochemistry in Tumor Diagnostics ............... 1
1.1 E xpression Pattern and Diagnostic Pitfalls . . . . . . . . . . . . . . . 1
1.2 Immunohistochemical Pathways for the Diagnosis
Primary Tumors and of Metastasis of Unknown
Primary Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Common Immunohistochemical Markers, Diagnostic approach, Pitfalls
and Immunoprofiles of Most Common Tumors
2 Immunohistochemical Markers for the Diagnosis
of Epithelial Tumors ................................... 13
2.1 Cytokeratins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
2.2 Mucins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2.3 Claudins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2.4 M iscellaneous Epithelial Markers . . . . . . . . . . . . . . . . . . . . . 23
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
3 Markers and Immunoprofile of the Upper Respiratory
Tract and Pulmonary Tumors ........................... 29
3.1 D iagnostic Antibody Panel for Tumors of the Upper
Respiratory Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.2 D iagnostic Antibody Panel for Epithelial
Pulmonary Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.3 D iagnostic Antibody Panel for Mesenchymal
Pulmonary Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
4 Markers and Immunoprofile of Thymic Epithelial Tumors ... 37
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
5 Markers and Immunoprofile of Heart
and Pericardial Tumors ................................ 41
6 Markers and Immunoprofile of Tumors of the Oral Cavity
and Salivary Gland Tumors ............................. 43
6.1 O dontogenic Tumors and Tumors of the Oral Cavity . . . . . . 43
6.2 S alivary Gland Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
vii
viii Contents
7 Markers and Immunoprofile of Tumors
of the Gastrointestinal Tract ............................ 49
7.1 Gastrointestinal Epithelial Tumors . . . . . . . . . . . . . . . . . . . . 49
7.2 Gastrointestinal Mesenchymal Tumors . . . . . . . . . . . . . . . . . 54
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
8 M arkers and Immunoprofile of Exocrine
and Endocrine Pancreatic Tumors ....................... 59
8.1 D iagnostic Antibody Panel for Exocrine
Pancreatic Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
8.2 D iagnostic Antibody Panel for Endocrine
Pancreatic Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
9 M arkers and Immunoprofile of Hepatobiliary Tumors ...... 65
9.1 H epatocellular Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
9.2 C holangiocarcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
10 M arkers and Immunoprofile of Breast Tumors ............. 71
10.1 D iagnostic Antibody Panel for Breast Carcinoma . . . . . . . . 71
10.2 Diagnostic Antibody Panel for Fibroepithelial Tumors . . . . 71
10.3 Diagnostic Antibody Panel for Mesenchymal Tumors. . . . . 71
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
11 Markers and Immunoprofile of Tumors of Female
Reproductive Organs .................................. 83
11.1 Diagnostic Antibody Panel for Tumors of the Vulva
and Vagina . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
11.2 Diagnostic Antibody Panel for Tumors
of the Uterine Cervix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
11.3 D iagnostic Antibody Panel for Epithelial Tumors
of the Uterine Corpus, Fallopian Tube,
and Uterine Ligament . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
11.4 D iagnostic Antibody Panel for Uterine
Mesenchymal Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
11.5 T umors of the Ovary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
12 Markers and Immunoprofile of Renal and Urinary
Tract Tumors ......................................... 95
12.1 Renal Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
12.2 Urinary Tract Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
13 Markers and Immunoprofile of Male Genital
Tract Tumors ........................................ 107
13.1 Prostatic Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
13.2 Testicular and Paratesticular Tumors . . . . . . . . . . . . . . . . . 113
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Contents ix
14 Markers and Immunoprofile of Endocrine
and Neuroendocrine Tumors ........................... 121
14.1 General Endocrine and Neuroendocrine Markers . . . . . . . 121
14.2 Pituitary Gland Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
14.3 T umors of the Thyroid Gland . . . . . . . . . . . . . . . . . . . . . . . 126
14.4 T umors of the Parathyroid Gland . . . . . . . . . . . . . . . . . . . . 130
14.5 Pancreatic Endocrine Tumors . . . . . . . . . . . . . . . . . . . . . . . 132
14.6 Tumors of the Adrenal Gland . . . . . . . . . . . . . . . . . . . . . . . 132
14.7 Diagnostic Antibody Panel for Neuroendocrine
Carcinomas (Small and Large Cell Types) . . . . . . . . . . . . . 137
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
15 Markers and Immunoprofile of Mesothelioma Tumors
of the Peritoneum .................................... 139
15.1 Diagnostic Antibody Panel for Mesothelial Tumors . . . . . 139
15.2 D iagnostic Antibody Panel for Epithelial Tumors
of Müllerian Type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
15.3 D iagnostic Antibody Panel for Smooth Muscle Tumors . . 139
15.4 Diagnostic Antibody Panel for Tumors
of Uncertain Origin and Miscellaneous
Peritoneal Primary Tumors . . . . . . . . . . . . . . . . . . . . . . . . . 139
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
16 Markers and Immunoprofile of Lymphoid
Tissue Neoplasms .................................... 149
16.1 Screening Markers for Lymphoma . . . . . . . . . . . . . . . . . . . 150
16.2 Markers and Immunoprofile of B-Cell Neoplasms . . . . . . 154
16.3 M arkers and Immunoprofile of Plasma Cell Neoplasms . . 164
16.4 M arkers and Immunoprofile of T-Cell Neoplasms . . . . . . . 166
16.5 Markers and Immunoprofile of NK-Cell Neoplasms . . . . . 170
16.6 Markers and Immunoprofile of Hodgkin’s Lymphoma . . . 174
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
17 Markers and Immunoprofile of Myeloid Neoplasm ........ 181
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184
18 Markers and Immunoprofile of Mastocytosis ............. 185
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186
19 Markers and Immunoprofile of Histiocytic and Dendritic
Cell Tumors ......................................... 187
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
20 Markers and Immunoprofile of Skin Tumors ............. 191
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
21 Markers and Immunoprofile of Melanocytic Tumors ....... 197
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
22 Markers and Immunoprofile of Fibroblastic,
Myofibroblastic, and Fibrohistiocytic Tumors ............. 203
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
x Contents
23 Markers and Immunoprofile of Muscle Tumors ........... 209
23.1 Diagnostic Antibody Panel for Skeletal
Muscle Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
23.2 Diagnostic Antibody Panel for Smooth
Muscle Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216
24 Markers and Immunoprofile of Vascular
and Perivascular Tumors .............................. 217
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
25 Markers and Immunoprofile of Adipocytic Tumors ........ 225
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228
26 Markers and Immunoprofile of Peripheral Nerve
and Nerve Sheath Tumors ............................. 229
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
27 Markers and Immunoprofile of Central Nervous
System Tumors ...................................... 233
27.1 Diagnostic Antibody Panel for Tumors
of the Central Nervous System . . . . . . . . . . . . . . . . . . . . . . 233
27.2 Diagnostic Antibody Panel for Meningeal Tumors . . . . . . 234
28 Markers and Immunoprofile of Ewing’s
Sarcoma/Primitive Neuroectodermal Tumors (PNETs) ..... 241
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
29 Markers and Immunoprofile of Extraskeletal Osseous
and Cartilaginous Tumors ............................. 247
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248
30 Markers and Immunoprofile of Miscellaneous Tumors
and Tumors of Uncertain Differentiation ................. 249
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
31 Markers to Assist the Diagnosis of Dysplasia and Malignant
Transformation ...................................... 253
32 Recommendations for the Utility of Immunohistochemistry
in Tumor Diagnosis ................................... 257
Index ................................................... 259
Introduction
Immunohistochemistry in Tumor Diagnostics
In recent years, classical histopathology has rapidly developed with a num-
ber of additional high sensitive diagnostic tools including immunohisto-
chemistry, cytogenetics, and molecular pathology aside from conventional
microscopy and electron microscopy. These methods provide further
objective and reproducible criteria for diagnosis, classification, and follow-
up of tumors.
In modern diagnostic histopathology, immunohistochemistry plays a cen-
tral role as a very informative tool for tumor diagnosis and management of
oncologic patients. This method has been used since the 1940s and was pri-
marily published by Coons et al [1]. In the last 20 years, immunohistochem-
istry was dramatically developed into a highly specialized molecular
technique combining the principles of immunology, biochemistry, and histol-
ogy and became a very powerful tool in the daily diagnostic histopathology.
Nowadays, we have several thousands of monoclonal and polyclonal anti-
bodies specific of cellular and extracellular structures. Immunohistochemistry
is essential to determine the histogenetic origin of tumors required for tumor
classification by the detection of specific cellular antigens on tissue sections
prepared from frozen tissue or formalin-fixed paraffin-embedded tissue
blocks or even from cytology specimens. It is also one of the most efficient
methods to detect minimal residual tumor cells in different locations such as
surgical margins, lymph nodes, and bone marrow, which is very important for
tumor staging and the planning of therapeutic strategies.
Immunohistochemistry is also helpful to determine the sensitivity of dif-
ferent tumors to several types of therapeutic agents such as steroid-receptor-
antagonists, humanized monoclonal antibodies, and enzyme antagonists
including tyrosine-kinase inhibitors. To merge proteomics or epitomics into a
morphological context is an invaluable asset to the discerning and knowl-
edgeable pathologist. Furthermore, immunohistochemistry offers a number
of significant prognostic and etiopathological markers interesting for tumor
follow-up and research. However, it must also be said that quantitative immu-
xi