Rare and Uncommon Gynecological Cancers (eBook)

Dr. Nicholas Reed is a consultant Clinical Oncologist based at the Beatson Oncology Centre in Glasgow, Scotland. He has been a consultant oncologist for more than 25 years and is involved in the delivery of both chemotherapy and radiation treatment for patients with gynaecological, thyroid and neuroendocrine cancers. He has also been committed to the management of rare gynaecological cancers: he was a facilitator for the Gynaecological Cancer InterGroup Rare Tumour sub-group and is currently active in the UK in establishing database, registry and guidelines for these tumours. Dr. Nadeem Siddiqui is a consultant Gynaecological Oncologist and Surgeon based at the Glasgow Royal Infirmary, Scotland, where he leads the team responsible for the surgical care of patients with gynaecological cancers. He is currently the chairman of the Scottish Gynaecological Cancer Trials Group and Chairman of the Cervix committee of the EOIRTC Gynaecological Cancer Group. Dr. John Green is a Senior Lecturer in Cancer Studies at the University of Liverpool, England. He has been involved in the management of gynaecological cancers for 30 years and has been a principal investigator for numerous trials. He has also had a strong commitment to support translational research studies in gynaecological tumours. He has been actively involved in the UK National Cancer Research Institute Gynaecological Cancer Study Group, the EORTC Gynaecological Cancer Group and the Gynaecological Cancer InterGroup. Professor David Gershenson from the MD Anderson Hospital in Texas is one of North America’s most distinguished Gynaecological Oncologists and has published very extensively on gynaecological cancers. His many publications include expert papers on granulosa and sex cord tumours, germ cell tumours, borderline ovarian tumours and other rarer gynaecological cancers. He is a former editor of Gynaecological Oncology and a very senior and active member of the Gynaecological Oncology Group. Dr Rachel Connor is a consultant Radiologist at the Southern General Hospital Glasgow and Lead Radiologist supporting the Gynaecological Cancer Managed Clinical Network for the West of Scotland. She has been a consultant radiologist for over 20 years and was Lead Clinician for Imaging for South Glasgow. She has been an integral member of the West of Scotland Network for Gynaecological cancers since its inception. She has written Imaging guidelines to support the Network, and has been involved in introducing many new techniques to support and develop imaging in Gynaecological cancers locally where she is recognised as a champion. This has all been achieved whilst supporting a full clinical load of routine imaging

Contents 5
Part I:General Principles 7
1: Introduction 8
1.1 Rationale for the Textbook 8
1.2 Multidisciplinary Team Management 9
1.3 Structure of the Book 9
1.4 Databases, Registries and Tumour Banks 9
1.5 Clinical Trials 10
1.6 Tumour Sub-Types 10
1.7 Guidelines vs. Protocols 10
2: Epidemiology and Databases 11
2.1 Rare and Uncommon Gynaecological Cancers 12
2.2 Definition: What is Rare? 12
2.3 Examples of Rare and Uncommon Cancers 13
3: Rare and Uncommon Gynaecological Cancers: A Clinical Guide 14
3.1 Pathology 14
References 16
4: The Contribution of Diagnostic Imaging in Rare Gynaecological Malignancies 18
4.1 Introduction 18
4.2 Imaging Techniques for Evaluating the Primary Gynaecological Malignancy 18
4.2.1 Ultrasound 18
4.2.2 CT 19
4.2.3 CT/PET 19
4.2.4 MRI 20
4.3 Lymph Node Imaging in Gynaecological Malignancy 23
4.4 Staging Considerations 24
4.4.1 Uterus 24
4.4.2 Cervix 26
4.4.3 Vagina 28
4.4.4 Vulva 28
4.4.5 Ovary 29
4.5 Imaging Characteristics of Specific Tumours 30
4.5.1 Uterus 30
4.5.1.1 Clear Cell and Serous Endometrial Tumours 30
4.5.1.2 Carcinosarcoma 31
4.5.1.3 Leiomyosarcoma and Endometrial Stromal Sarcoma 33
4.5.1.4 Leiomyosarcoma 37
4.5.1.5 Adenosarcoma 41
4.5.2 Cervical Cancers 41
4.5.2.1 Small Cell Carcinoma 43
4.5.3 Uterine and Cervical lymphoma 44
4.5.4 Cervical Sarcomas 45
4.5.5 Vaginal Tumours 45
4.5.6 Rare Ovarian Tumours 47
4.5.7 Germ Cell Tumours 48
4.5.8 Teratoma 48
4.5.9 Carcinoid Tumours 49
4.5.10 Immature Teratomas 50
4.5.11 Yolk Sac Tumours 53
4.5.12 Sex Cord Stromal Tumours 53
4.5.13 Granulosa Tumours 53
4.5.14 Steroid Cell Tumours 56
4.5.15 Stromal Tumours 57
4.5.16 Rare Epithelial Tumours 58
4.5.16.1 Clear Cell Carcinoma 58
4.5.17 Brenner Tumours 59
4.5.18 Small Cell Ovarian Cancer 61
4.5.19 Fallopian Tube Carcinoma 63
References 65
Part II:Ovarian Rare Cancers 68
5: Mucinous Cancers: Ovary 69
5.1 Introduction and Epidemiology 69
5.2 Pathology 69
5.3 Biomarkers and Immunophenotyping 70
5.4 Clinical Features: Primary vs. Secondary Cancer 70
5.5 Clinical Management 71
5.5.1 Imaging 71
5.6 Tumour Markers 71
5.7 Endoscopy/Colonoscopy 71
5.8 Treatment of Mucinous Epithelial Ovarian Cancer 71
5.9 Treatment of Advanced Mucinous Ovarian Cancer 72
5.10 New Studies for Mucinous Ovarian Cancer 73
References 74
6: Pseudomyxoma Peritonei 76
6.1 Introduction 76
6.2 Origin of PMP 76
6.3 Pathophysiology of PMP 77
6.3.1 The Redistribution Phenomenon 77
6.4 Pathological Classification 78
6.5 Diagnosis 78
6.5.1 Preop Assessment: Tumour Markers – CEA, CA125, CA19.9 and Laparoscopy 79
6.5.2 Operative Strategy in Unexpected Case 79
6.6 Treatment 79
6.6.1 Surgical Treatment of PMP 79
6.6.2 Rationale for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) 79
6.6.3 Survival Following CRS and HIPEC 80
6.6.4 Morbidity and Mortality of CRS with HIPEC 80
6.7 Conclusion 80
References 80
7: Ovarian Clear Cell Carcinoma 83
7.1 Introduction 83
7.2 Management 84
7.3 Histopathology and Molecular Characterisation 85
7.4 Biomarkers 86
7.5 Therapeutic Targets 86
References 88
8: Clear Cell Carcinoma of the Ovary 91
8.1 Incidence and Clinical Behavior 91
8.2 Histopathological Issues 91
8.2.1 Histopathological Characteristics 91
8.2.2 Origin of CCC 92
8.3 Molecular Biology 93
8.4 Surgery and Surgical Staging 94
8.4.1 Cytoreductive Surgery 94
8.4.2 Lymph-Node Metastasis 94
8.4.3 Stage Distribution 95
8.5 Adjuvant Treatment 95
8.5.1 Response Rate in Postoperative Chemotherapy (Table 8.2) 95
8.5.1.1 Conventional Platinum-Based Chemotherapy 95
8.5.1.2 Combination Therapy of Paclitaxel and Platinum 95
8.5.2 Survival Rate and Time 95
8.5.2.1 Conventional Platinum-Based Chemotherapy 95
8.5.2.2 Combination Therapy of Paclitaxel and Platinum 96
8.5.2.3 Combination Therapy with Irinotecan 97
8.6 Mechanisms of Chemotherapy Resistance (Table 8.3) 98
8.6.1 ABC Transporter 98
8.6.2 Drug Inactivation 98
8.6.3 Low Cell Proliferation 98
8.6.4 Stress Response, Glycogenesis and Glycolysis 98
8.6.5 Other 99
8.7 Future Therapy 99
References 100
9: The Continuum of Serous Ovarian Tumors of Low Malignant Potential and Low-Grade Serous Carcinoma of the Ovary 104
9.1 Introduction 104
9.2 Serous Tumors of Low Malignant Potential 104
9.3 Low-Grade Serous Carcinoma 105
9.3.1 Pathology 106
9.3.2 Clinical Behavior and Management 107
9.3.3 Molecular Biology 108
9.3.3.1 Mutational Analyses 108
9.3.3.2 Expression Profiling Studies 108
9.3.3.3 Other Biomarkers 109
9.4 Summary 109
References 109
10: Sex Cord-Stromal Tumors 111
10.1 Ovarian Sex Cord-Stromal Tumors 111
10.1.1 Overview and Epidemiology 111
10.1.2 Pathology, Molecular Characteristics, and Associated Biomarkers 113
10.1.2.1 Pathology 113
10.1.2.2 Molecular Characteristics 115
10.1.2.3 Associated Biomarkers 116
10.1.3 Diagnosis 116
10.1.4 Imaging 117
10.1.5 Surgical Therapy and Staging 118
10.1.5.1 General Treatment Guidelines: Surgical Therapy 118
10.1.6 Adjuvant Therapy 120
10.1.7 Treatment for Recurrent Disease 122
10.2 Uterine Tumors Resembling Ovarian Sex Cord-Stromal Tumors 123
References 124
11: Squamous Cell Carcinomas Arising From Dermoids 129
References 131
12: Ovarian Carcinosarcomas 132
12.1 Incidence and Epidemiology 132
12.2 Pathology 133
12.3 Investigations and Initial Management 133
12.4 Surgical Management 133
12.5 Post-Operative Management 134
12.6 Modern Approach to Management 135
12.7 The Future 136
12.8 Conclusions 137
References 137
13: Small Cell and Neuroendocrine Cancers of the Ovary 140
13.1 Introduction 140
13.2 Pathology 140
13.3 Clinical Presentation 141
13.4 Post-Operative Management 142
13.5 Recent Literature 142
References 143
14: Primary Ovarian Carcinoids and Neuro-Endocrine Tumours Including Struma Ovarii 145
14.1 Primary Insular Carcinoids of the Ovary 145
14.2 Primary Trabecular Carcinoids of the Ovary 145
14.3 Primary Mucinous Ovarian Carcinoids 146
14.4 Strumal Carcinoids 146
14.5 Metastases 146
14.6 Pathology 146
14.7 Carcinoid Syndrome 146
14.8 Imaging 147
14.9 Biochemical and Tumour Markers 147
14.10 Management and Clinical Course 147
14.11 Treatment of Relapsed Disease 148
14.12 Treatment of Ovarian Strumal Carcinoids 149
References 149
Part III:Uterine Rare Cancers 151
15: Reed Uterine Carcinosarcomas 152
15.1 Introduction 152
15.2 Presentation 152
15.3 Staging Investigations 153
15.4 Pathology 154
15.5 Surgical Management 154
15.6 Postoperative Adjuvant Therapies 155
15.6.1 To Irradiate or Not? 155
15.6.2 Adjuvant Hormonal Therapy 156
15.6.3 Adjuvant Chemotherapy 156
15.7 Recommendations of Care 157
15.8 Recurrent and Advanced Disease 157
15.9 Conclusions 160
References 160
16: Leiomyosarcomas of Uterus 163
16.1 Introduction 163
16.2 Incidence and Epidemiology 163
16.3 Presentation 164
16.4 Pathology 165
16.5 Surgical Management 165
16.6 Post-Operative Care 166
16.6.1 Adjuvant Treatments 166
16.6.2 Radiation Therapy 166
16.6.3 Adjuvant Chemotherapy 167
16.7 Recurrent and Advanced Disease 168
16.8 Recurrent or Locally Advanced Leiomyosarcomas 168
16.8.1 Hormonal Therapies 169
16.8.2 Chemotherapy 169
16.8.3 Combination Therapy 170
16.8.4 Targeted Agents 170
16.9 Lung Metastases 171
16.10 Clinical Trials 171
16.11 Conclusions 171
References 171
17: Mucinous Tumours of the Uterine Corpus 174
17.1 Presentation 174
17.2 Surgical Management 174
17.3 Post-Operative Management 174
References 175
18: Clear Cell Cancers of Uterus 176
18.1 Incidence and Epidemiology 176
18.2 Clinical Presentation 176
18.3 Imaging and Diagnostic Work Up 176
18.4 Pathology 176
18.5 Surgical Assessment and Management 177
18.6 Adjuvant Post-Operative Treatments 178
18.6.1 External Beam Radiation Therapy 179
18.6.2 Brachytherapy 179
18.6.3 Chemo-Radiotherapy 180
18.7 Adjuvant Chemotherapy 180
18.7.1 Relapsed/Advanced Local Disease 180
18.8 Follow-Up Protocols 181
18.9 Relapsed Disease 181
References 181
Part IV:Cervix and Vulval Cancers 185
19: Small Cell and Neuroendocrine Cancers of the Cervix 186
19.1 Introduction 186
19.2 Presentation 187
19.3 Pathology 187
19.4 Staging 188
19.5 Treatment Options 188
19.6 Localised Disease 188
19.6.1 The Role of Surgery 188
19.6.2 Adjuvant Therapy 189
19.6.3 Primary Chemo-Radiation 189
19.6.4 Multi-Modality Therapy 189
19.7 Extensive Disease 190
19.8 Large Cell Variant of Small Cell Cancer 190
19.9 Conclusions 190
References 191
20: Primary Malignant Melanoma of the Vulva and Vagina 193
20.1 Introduction 193
20.2 Demographics and Aetiology 193
20.3 Clinical Presentation 193
20.4 Histopathological Subtypes 193
20.5 Staging and Prognosis 194
20.6 Role of Primary Surgery 195
20.7 Assessment of Lymph Node Status 195
20.8 Role of Adjuvant Therapy 196
20.9 Conclusion 196
References 196
21: Gynecologic Cancers in Pregnancy: Guidelines of an International Consensus Meeting 198
21.1 Introduction 198
21.2 Imaging and Oncological Treatment Modalities During Pregnancy 199
21.2.1 Imaging and Diagnosis During Pregnancy 200
21.2.2 Surgery During Pregnancy 201
21.2.3 Systemic Anticancer Treatment During Pregnancy 201
21.2.4 Radiotherapy During Pregnancy 203
21.2.5 Supportive Therapy and Symptom Control in the Pregnant Patient 204
21.3 Monitoring Pregnancy and Neonatal Outcome 204
21.3.1 Monitoring of the Pregnancy, Complicated with a Gynecologic Cancer 204
21.3.2 Neonatal and Long-Term Outcome After In Utero Exposure to Chemotherapy 205
21.4 Organ Pathology 206
21.4.1 Pre-Invasive Cervical Cancer 206
21.4.2 Invasive Cervical Cancer 206
21.4.3 Vulvar Cancer 208
21.4.4 Endometrial Cancer 209
21.4.5 Ovarian Neoplasm 209
21.4.6 Psychosocial and Ethical Concerns of Cancer Diagnosis During Pregnancy 210
21.5 Conclusion 211
References 211
Index 217