Diagnosis of Endometrial Biopsies and Curettings: A Practical Approach

382 Pages·2019·76.953 MB·English

by  Tricia A. Murdock, Emanuela F.T. Veras, Robert J. Kurman, Michael T. Mazur

Diagnosis of
Endometrial Biopsies
and Curettings
A Practical Approach
Tricia A. Murdock
Emanuela F. T. Veras
Robert J. Kurman
Michael T. Mazur
Third Edition
123
Diagnosis of Endometrial Biopsies
and Curettings
Tricia A. Murdock • Emanuela F. T. Veras
Robert J. Kurman • Michael T. Mazur
Diagnosis of
Endometrial Biopsies
and Curettings
A Practical Approach
Third Edition
Tricia A. Murdock Emanuela F. T. Veras
Department of Pathology Department of Pathology
The Johns Hopkins Hospital The Johns Hopkins Hospital
Baltimore, MD Baltimore, MD
USA USA
Robert J. Kurman Michael T. Mazur
Department of Pathology Department of Pathology and
The Johns Hopkins Hospital Laboratory Medicine, State University
Baltimore, MD of New York Upstate Medical University
USA Syracuse, NY
USA
ISBN 978-3-319-98607-4 ISBN 978-3-319-98608-1 (eBook)
https://doi.org/10.1007/978-3-319-98608-1
Library of Congress Control Number: 2018960871
© Springer Nature Switzerland AG 2019
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Preface
The third edition of Diagnosis of Endometrial Biopsies and Curettings: A
Practical Approach developed from positive comments received from the
second edition and recognition that several topics have advanced since the
last publication. The emphasis of this book is to provide a foundation for a
daily, pragmatic approach for common entities found in endometrial samples.
Our understanding of endometrial pathology has evolved, and clinical termi-
nology accompanying these specimens also has changed. Therefore, the
entire text has been updated; all illustrations are now in color.
As with the first two editions, the focus of this book is to assist the patholo-
gist in the routine evaluation of endometrial tissue specimens. The book is not
intended to be an all-encompassing text of endometrial pathology but to
guide the pathologist through the more common diagnoses such as artifacts,
benign entities, precursor lesions, and neoplasia. We recognize that for cer-
tain areas, such as precursors of endometrial cancer, there is ongoing debate
and study regarding the terminology for these lesions. Different investigators
and practitioners prefer different terminologies (hyperplasia/atypical hyper-
plasia versus hyperplasia/endometrial intraepithelial neoplasia [EIN]), and
we therefore attempt to provide a balanced discussion of both so readers can
decide which they prefer. For the majority of the text, the terminology and
classification schemes mirror the most recent edition (2014) of the WHO
Classification of Tumors of Female Reproductive Organs in an effort to pro-
mote uniform and comprehensive communication with our clinical col-
leagues as ultimately this is the most important role of the diagnostic surgical
pathologist.
In the second edition, immunohistochemistry (IHC) was largely discussed
in the final chapter on methodology, but as its use in diagnosis has greatly
expanded, the current edition incorporates IHC into each of the individual
chapters. Furthermore, IHC now has an important role as a surrogate marker
of genetic aberrations, knowledge of which is becoming increasingly impor-
tant for diagnostic and therapeutic purposes. For example, the use of fumarate
hydratase staining to detect fumarate hydratase-deficient leiomyomas can
lead to the recognition of the hereditary leiomyomatosis and renal cell carci-
noma syndrome.
Although molecular diagnostics currently are infrequently used in routine
evaluation of endometrial specimens, pathologists need to be familiar with
the advances in molecular genetics as this is transforming our understanding
of many of the pathologic conditions that can be found in endometrial
v
vi Preface
samples. For example, the classification of endometrial stromal tumors has
been modified based on fluorescence in situ hybridization and targeted RNA
sequencing that have demonstrated different types of high-grade endometrial
stromal sarcomas depending on their molecular genetic features. Another
example is that through molecular genotyping, we are now able to defini-
tively diagnose partial hydatidiform moles, whereas in the past morphologi-
cal, immunohistochemical, and cytogenetic studies were insufficiently
reliable to make a definitive diagnosis.
In summary, we hope that this new edition continues to be a foundation for
the diagnosis of endometrial specimens with a strong emphasis on the impor-
tant morphologic features and that this will be useful to pathologists and
gynecologists.
Baltimore, MD, USA Tricia A. Murdock
Baltimore, MD, USA Emanuela F. T. Veras
Baltimore, MD, USA Robert J. Kurman
Syracuse, NY, USA Michael T. Mazur
Acknowledgments
We are grateful to Norman Barker, a friend and colleague, who provided his
expertise in the field of medical illustration and tirelessly assisted us with the
images depicted in this edition. We are also grateful to Dr. Lora Ellenson,
another good friend and esteemed colleague, for generously supplying
updated information that helped enrich the contents of this book.
vii
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Indications for Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Clinical History and Biopsy Interpretation . . . . . . . . . . . . . . . . . . . 2
Abnormal Uterine Bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Infertility Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Products of Conception . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Hormone Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Other Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Clinical Queries and Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
2 The Normal Endometrium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
General Considerations in Histologic Evaluation . . . . . . . . . . . . . . 10
Histologic Features of Normal Cycling Endometrium . . . . . . . . . . 13
Proliferative Phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Secretory Phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Menstrual Endometrium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Pitfalls in The Histologic Assessment
of The Normal Endometrium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Sample Adequacy and Standardized Reporting . . . . . . . . . . . . . . . 24
Artifacts and Contaminants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Irregular Secretory Endometrium . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Clinical Queries and Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
3 Pregnancy, Abortion, and Ectopic Pregnancy . . . . . . . . . . . . . . . 39
Endometrial Glands and Stroma in Pregnancy . . . . . . . . . . . . . . . . 40
Early Gestational Endometrium (1–3 Weeks
Postfertilization) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
Endometrium in Later Pregnancy (4 or More Weeks
Postfertilization) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Arias-Stella Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Other Glandular Changes in Pregnancy . . . . . . . . . . . . . . . . . . . . . 47
Trophoblast and Villi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Trophoblastic Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Immunohistochemistry of Trophoblastic Cells . . . . . . . . . . . . . . 51
Placental Implantation Site . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Chorionic Villi and Villous Trophoblast in the First Trimester . . . . 57
ix
x Contents
Hydropic Change and Other Pathologic Changes
in Abortions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Chorionic Villi and Villous Trophoblast After
the First Trimester . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Placental Polyps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Placenta Accreta . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Endometrium Associated with Ectopic Pregnancy . . . . . . . . . . . . . 64
Clinical Queries and Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
4 Gestational Trophoblastic Disease . . . . . . . . . . . . . . . . . . . . . . . . . 75
Hydatidiform Mole . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
General Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
Complete Hydatidiform Mole . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
Partial Hydatidiform Mole . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Cytogenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Abnormal (Non-molar) Villous Lesions . . . . . . . . . . . . . . . . . . . 90
Other Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Persistent Postmolar Gestational Trophoblastic Disease
and Invasive Hydatidiform Mole . . . . . . . . . . . . . . . . . . . . . . . . 91
Clinical Queries and Reporting of Hydatidiform Mole . . . . . . . 93
Gestational Trophoblastic Neoplasms. . . . . . . . . . . . . . . . . . . . . . . 94
Choriocarcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Placental Site Trophoblastic Tumor . . . . . . . . . . . . . . . . . . . . . . 100
Epithelioid Trophoblastic Tumor . . . . . . . . . . . . . . . . . . . . . . . . 107
Nonneoplastic Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
Exaggerated Placental Site . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
Placental Site Nodule and Plaque . . . . . . . . . . . . . . . . . . . . . . . . 111
Clinical Queries and Reporting of Trophoblastic Neoplasms . . . . . 112
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
5 Abnormal Uterine Bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Morphologic Features of Glandular and Stromal Breakdown
in Menstrual and Abnormal Bleeding . . . . . . . . . . . . . . . . . . . . . . . 122
Abnormal Uterine Bleeding: Nonstructural Causes . . . . . . . . . . . . 126
Estrogen-Related Bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Proliferative Endometrium with Glandular
and Stromal Breakdown . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Disordered Proliferative Endometrium
and Persistent Proliferative Phase . . . . . . . . . . . . . . . . . . . . . . . . 132
Atrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
Progesterone-Related Bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Irregular Secretory Endometrium . . . . . . . . . . . . . . . . . . . . . . . . 136
Irregular Shedding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Abnormal Secretory Endometrium with Breakdown
of Unknown Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
Clinical Queries and Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Contents xi
6 Effects of Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
Estrogenic Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
Progestins, Oral Contraceptives, and Selective
Progesterone Receptor Modulators . . . . . . . . . . . . . . . . . . . . . . . . . 146
Patterns of Response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
Decidual Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
Secretory Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Inactive Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
Other Stromal Changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
Combined Estrogen and Progestin as Replacement Therapy
for Menopausal Women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Progestin-Like Effects with No Hormone Use . . . . . . . . . . . . . . 154
Effects of Other Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
Selective Progesterone Receptor Modulators . . . . . . . . . . . . . . . 155
Tamoxifen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
Raloxifene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
Clomiphene Citrate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
Danazol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Human Menopausal Gonadotropins/Human
Chorionic Gonadotropin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
Gonadotropin-Releasing Hormone Agonists . . . . . . . . . . . . . . . 162
Antiprogestin RU486 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
Clinical Queries and Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
Postmenopausal Hormone Replacement . . . . . . . . . . . . . . . . . . . 163
Abnormal Uterine Bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
Treatment of Hyperplasia and Endometrioid Carcinoma . . . . . . 164
Infertility Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
7 Endometritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
Nonspecific Endometritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174
Inflammatory Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174
Stromal Changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Abnormal Glandular Development . . . . . . . . . . . . . . . . . . . . . . . 178
Epithelial Changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
Glandular and Stromal Breakdown . . . . . . . . . . . . . . . . . . . . . . . 179
Specific Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
Granulomatous Inflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
Actinomycosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
Cytomegalovirus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Herpesvirus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184
Mycoplasma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
Clinical Queries and Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196
8 Polyps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Classification and Histologic Features . . . . . . . . . . . . . . . . . . . . . . 200
Common Polyps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205