The Yokohama System for Reporting Endometrial Cytology: Definitions, Criteria, and Explanatory Notes

Foreword
Foreword
Preface
Preface: The Quest to Develop a Standardized Terminology for Endometrial Cytology
	References
Introduction
Reference
Contents
Contributors
1: Endometrial Cytology in Historical Perspective
	1.1	 General Concepts
	1.2	 Dawning of the Endometrial Cytology
	1.3	 Endometrial Cytology Based on Cyto-Architecture of Tissue Fragments
	1.4	 Endometrial Sampling by Cervical Cytology
	1.5	 Development and Evaluation of Endometrial Cell Sampling Device
	1.6	 Endometrial Cytopathology and Cell Block Preparation
	1.7	 Endometrial Cytology by Means of Liquid-Based Cytology and Its Reporting System
	1.8	 Molecular-Based Approach with LBC Samples
	References
2: Overview of the Yokohama System for Reporting Endometrial Cytology
	2.1	 Background
	2.2	 The Reproducibility Assessment of the Yokohama System
	2.3	 Clinical Handling in the Yokohama System for Reporting Endometrial Cytology
	References
3: Pathogenetic Bases of the Yokohama System for Reporting Endometrial Cytology
	References
4: Endometrial Cell Sampling Procedure to Obtain Cytologic Specimens
	4.1	 Significance of Endometrial Cytology for Women with Abnormal Uterine Bleeding at the Outpatient Clinic
	4.2	 Indications for the Use of Directly Sampled Endometrial Cytology (Table 4.1)
	4.3	 Collection Instruments and Evaluation of Endometrial Lesions by Endometrial Cytology
	4.4	 Techniques of Endometrial Sampling and Processing
	4.5	 Benefits and Harm of Directly Sampled Endometrial Cytology
	References
5: Algorithmic Interpretational and Diagnostic Approach to Endometrial Cytology for the Yokohama System
	5.1	 Definition and Criteria
		5.1.1	 Inadequate Sample for Evaluation (TYS 0)
		5.1.2	 Negative for Malignant Tumors and Precursors (TYS1)
		5.1.3	 Atypical Endometrial Cells, Cannot Exclude EAH/EIN or Malignant Condition (ATEC-AE) (TYS4)
		5.1.4	 Malignant Neoplasms (Endometrial Carcinomas) (TYS6) or Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia (EAH/EIN) (TYS5)
		5.1.5	 Endometrial Hyperplasia Without Atypia (TYS3)
		5.1.6	 Atypical Endometrial Cells of Undetermined Significance (ATEC-US) (TYS2)
	5.2	 Management
		5.2.1	 The Evaluation of the Reproducibility of the Cytological Diagnosis of Endometrial Lesions by the TYS
	References
6: Evaluation of Sample Adequacy: Cytologic Criteria
	6.1	 Background
	6.2	 Definition
	6.3	 Explanatory Note
	Reference
7: Processing Methodology of Endometrial Cytology Samples
	7.1	 Background
		7.1.1	 Processing Methodology of Endometrial Conventional Cytology Samples
		7.1.2	 Processing Methodology of Endometrial Liquid-Based Cytology (LBC) Samples
	References
8: Negative for Malignant Tumors and Precursors: TYS1
	8.1	 Normal Endometrium [1]
	8.2	 Proliferative Endometrium (PE) [1]
		8.2.1	 Background
		8.2.2	 Definition
		8.2.3	 Criteria
	8.3	 Secretory Endometrium (SE) [1]
		8.3.1	 Background
		8.3.2	 Definition
		8.3.3	 Criteria
	8.4	 Menstrual Endometrium [1]
		8.4.1	 Background
		8.4.2	 Definition
		8.4.3	 Criteria
		8.4.4	 Differential Diagnosis
	8.5	 Atrophic Endometrium [1]
		8.5.1	 Background
		8.5.2	 Definition
		8.5.3	 Criteria
	8.6	 Benign Reactive Changes: IUD (Intrauterine Contraceptive Devices)
		8.6.1	 Background
		8.6.2	 Mechanism of Action of IUD
		8.6.3	 Occurrence of IUD Associated Cellular Change
	8.7	 Benign Reactive Change: MPA (Medroxyprogesterone Acetate)
		8.7.1	 Background
		8.7.2	 Adaptation Criteria of Fertility-Sparing Treatment [29]
		8.7.3	 Physiopathological Changes and Effects of MPA Therapy
		8.7.4	 Assessing the Efficacy of MPA Therapy: Cytological Criteria
	8.8	 Benign Reactive Changes: TAM(Tamoxifen)
		8.8.1	 Background
		8.8.2	 Cytological Findings in Endometrial Mucosa after TAM Therapy
		8.8.3	 Cytological Endometrial Findings after TAM Therapy
	8.9	 Arias-Stella Reaction (ASR)
		8.9.1	 Background
		8.9.2	 Cellular Changes of Arias-Stella Reaction (ASR)
	References
9: Endometrial Hyperplasia without Atypia
	9.1	 Background
	9.2	 Definition
	9.3	 Diagnostic Criteria [7–12] (Figs. 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8 and 9.9)
	9.4	 Explanatory Note
	References
10: Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia
	10.1	 Background
	10.2	 Definition
	10.3	 Cytological Diagnostic Criteria [14–18] (Figs. 10.4, 10.5, 10.6, 10.7, 10.8, 10.9, 10.10, 10.11, 10.12 and 10.13)
	10.4	 Explanatory Note
	References
11: Malignant Neoplasm
	11.1	 Endometrial Endometrioid Carcinoma
		11.1.1	 Background
		11.1.2	 Definition
		11.1.3	 Cytologic Diagnostic Criteria [6–10] (Figs. 11.2, 11.3, 11.4, 11.5, 11.6, 11.7, 11.8 and 11.9)
		11.1.4	 Explanatory Note
	11.2	 Serous Carcinoma, Including Serous Endometrial Intraepithelial Carcinoma (SEIC)
		11.2.1	 Background
		11.2.2	 Definition
		11.2.3	 Cytologic Diagnostic Criteria (Figs. 11.21, 11.22, 11.23, 11.24, 11.25, 11.26 and 11.27)
		11.2.4	 Explanatory Note
	11.3	 Clear Cell Carcinoma
		11.3.1	 Background
		11.3.2	 Definition
		11.3.3	 Cytologic Diagnostic Criteria (Figs. 11.37, 11.38, 11.39, 11.40 and 11.41)
		11.3.4	 Explanatory Note
	References
12: Endometrial Glandular and Stromal Breakdown (EGBD) as Benign Mimics of Malignancy
	12.1	 Background
	12.2	 Definition
		12.2.1	 Condensed Stromal Clusters (CSC)
		12.2.2	 Metaplastic Clusters with Irregular Protrusion (MCIP)
		12.2.3	 Light Green Body (LGB)
	12.3	 Criteria
		12.3.1	 Condensed Stromal Clusters (CSC)
		12.3.2	 Metaplastic Clusters with Irregular Protrusion (MCIP)
		12.3.3	 MCIP with Condensed Stromal Clusters (CSC)
		12.3.4	 Light Green Body (LGB)
	12.4	 How to Classify EGBD in the “Algorithmic Approach to the Yokohama System (TYS)”
	12.5	 Differential Diagnosis
		12.5.1	 Nuclear Findings in LBC: Discrimination Between EGBD and G1-EEC
		12.5.2	 Immunocytochemical Findings in LBC: Discrimination Between EGBD and EEC
			12.5.2.1	 CSC of EGBD versus CCC of EEC
			12.5.2.2	 SPSC (MCIP) of EGBD versus CCC of EEC/ESC
	12.6	 Explanatory Note
		12.6.1	 *1: Light Green Body (LGB)
		12.6.2	 *2: Comparison of the Frequency of Nuclear Shape
		12.6.3	 *3: IMP3 Immunocytochemical Expression in LBC Samples
	References
13: Atypical Endometrial Cells (ATEC)
	13.1	 Background
	13.2	 Definition
	13.3	 ATEC-US
	13.4	 ATEC-AE
	References
14: Cell Block Techniques for Endometrial Cytology Technical Procedures, Role of Immunocytochemistry, Advantages, Applications
	14.1	 Cell Block Preparation and Techniques
		14.1.1	 Cell Block Preparation
		14.1.2	 Cell Block Techniques
	14.2	 Immunocytochemistry
		14.2.1	 Application of Immunocytochemistry in Endometrial Cancer
			14.2.1.1	 Beta-Catenin
		14.2.2	 Distinguishing Endometrioid Carcinoma from Endocervical Carcinoma
			14.2.2.1	 NON-HPV-Related Carcinomas.
		14.2.3	 Distinguishing Endometrial Carcinoma from Colonic Adenocarcinoma
		14.2.4	 Distinguishing Endometrial Carcinoma from Ovarian Carcinoma
	References
15: Molecular Pathology of Endometrial Carcinoma: A General Appraisal
	15.1	 Introduction
		15.1.1	 Molecular Alterations in Endometrioid Carcinoma
	15.2	 Molecular Alterations in Non-endometrioid Carcinomas
	15.3	 New Perspectives after TCGA Classification
	15.4	 Technical Analyses
	15.5	 Clinical Relevance of Molecular Characterization
	References
16: Molecular Pathology of Endometrial Carcinoma on LBC Samples and Cell Blocks
	16.1	 Introduction
	16.2	 Liquid-Based Cytology and Cell Blocks in Endometrial Cancer Diagnosis
	16.3	 Molecular Tests in Liquid-Based Cytology and Cell Blocks: A New ERA
	16.4	 NGS (Next-Generation Sequencing)
	References
17: Future Challenges and Perspectives of Endometrial Cytology
	17.1	 Background
	17.2	 Current Status and Future Perspectives of Digital Cytology
	17.3	 The Morphometric Approach to Endometrial Cytology Interpretation
	17.4	 Current Status and Future Perspectives of Flow Cytometry (LC-1000)-Assisted Endometrial Cytology Interpretation
	17.5	 Value of Cell-Free DNA Samples in the Follow-Up of Endometrial Malignancies
		17.5.1	 Molecular Study of Liquid-Based Pap Samples and of cf-DNA in Uterine Lavage Fluid
	References
18: The Future Direction in Endometrial Oncology through the Liquid Biopsy
	18.1	 Introduction
	18.2	 Circulating Tumor DNA (ct-DNA) Evaluation for Monitoring Endometrial Cancer
	18.3	 Liquid-Based Pap Samples and ct-DNA in Uterine Fluid
	18.4	 Circulating Tumor Cells (CTCs) Evaluation for Monitoring Endometrial Cancer Patients
	18.5	 Circulating Tumor Cells (CTCs) Evaluation for Early Cancer Detection of Endometrial Cancer
	18.6	 Digital Imaging and Deep-learning Model and Liquid Biopsy
	References
Index