Contents Part I Introduction 1 General Description 2 Natural History: Importance of Size, Site, Histopathology

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1 Contents Part I Introduction 1 General Description Introduction Incidence and Prevalence Predisposing and Genetic Factors... 8 References Natural History: Importance of Size, Site, Histopathology Natural History Influence of Site Staging Staging of Retroperitoneal and Visceral Sarcoma Prognostic Factors for Extremity and Superficial Soft Tissue Sarcoma Disease-Specific Survival Prognostic Factors for Survival Following Local Recurrence of Extremity Sarcoma AJCC Staging Prognostic Factors Nomograms References General Statement as to Efficacy of Surgery, Chemotherapy, Radiation Therapy, and Immunotherapy Extent of Primary Surgery Surgical Treatment of Local Recurrence Diagnostic Imaging Surgery for Metastatic Disease Pulmonary Metastasis Surgery and Management of Sarcoma Liver Metastasis ix

2 x Contents 3.5 Radiation Therapy Adjuvant Radiation Therapy Types of Radiation Therapy Dose/Volume of Radiation Therapy Morbidity of Adjuvant Radiation Therapy Definitive Radiation Therapy Adjuvant and Neoadjuvant Chemotherapy for Soft Tissue Sarcomas Sarcomas More Common in Adults Larger Randomized Studies Selected Meta-analyses of Randomized Trials of Adjuvant Chemotherapy Adjuvant Therapy for GIST Sarcomas More Common in the Pediatric Setting Brief Comments Regarding Chemotherapy for Metastatic Soft Tissue Sarcoma Special Techniques for Primary and Locally Recurrent Disease Intra-arterial Chemotherapy Limb Perfusion and Hyperthermia Immunotherapy for Sarcomas References Part II Management by Histopathology 4 Gastrointestinal Stromal Tumors Imaging Familial GIST Natural History Diagnosis, Molecular Pathology Treatment Adjuvant Imatinib for Primary GIST Neoadjuvant Therapy for Primary Disease Not Amenable to Surgery Treatment of Recurrence First Line Imatinib: For Metastatic GIST Dose Intensity Over Time Imatinib Pharmacokinetics Second Line Sunitinib for Imatinib-Resistant Metastatic GIST Regorafenib in Third Line for Metastatic GIST Other Tyrosine Kinase Inhibitors for Metastatic GIST Failing Imatinib and Sunitinib Newer Agents for GIST... 98

3 Contents xi References Liposarcoma Imaging Diagnosis Treatment Radiation Therapy for Liposarcoma Systemic Therapy: General Considerations Adjuvant Therapy Treatment of Metastatic Disease Outcomes Outcome Following Metastasis References Leiomyosarcoma Imaging Diagnosis, Molecular Pathology Primary Treatment Radiation Therapy Systemic Therapy Adjuvant Chemotherapy for Leiomyosarcoma Outcomes After Primary Therapy Patterns of Recurrence Treatment of Recurrence Metastatic Disease References Undifferentiated Pleomorphic Sarcoma (UPS) (Malignant Fibrous Histiocytoma (MFH) and Myxofibrosarcoma) Imaging Diagnosis, Molecular Pathology Natural History Treatment Radiation Therapy Metastatic Disease Adjuvant Chemotherapy Outcome References Synovial Sarcoma Imaging Diagnosis, Molecular Pathology Treatment Radiation Therapy Chemotherapy Treatment of Recurrence

4 xii Contents Local Recurrence Systemic Treatment Outcome References Malignant Peripheral Nerve Sheath Tumor (MPNST) and Triton Tumor Presentation Imaging Diagnosis, Pathology Neurofibromatosis Type 1 and Outcome Treatment Radiation Therapy Chemotherapy for MPNST Outcome References Desmoid Tumor/Deep-Seated Fibromatosis (Desmoid-Type Fibromatosis) Clinical Presentation Imaging Diagnosis, Molecular Pathology Natural History Treatment Treatment of Recurrence Systemic Therapy Treatment by Observation Radiation Therapy Patterns of Failure Outcome References Solitary Fibrous Tumor/Hemangiopericytoma Doege Potter Syndrome Primary Therapy Systemic Therapy for Metastatic Disease Outcome References Fibrosarcoma and Its Variants Outcome Dermatofibrosarcoma Protuberans Outcome Low-Grade Fibromyxoid Sarcoma (Also Termed Evans Tumor) Outcome Sclerosing Epithelioid Fibrosarcoma

5 Contents xiii 12.5 Inflammatory Myofibroblastic Tumor Infantile Fibrosarcoma Myxoinflammatory Fibroblastic Sarcoma/Inflammatory Myxohyaline Tumor of Distal Extremities Adult-Type Fibrosarcoma References Vascular Sarcomas Epithelioid Hemangioendothelioma Angiosarcoma/Lymphangiosarcoma Outcome Kaposi Sarcoma References Epithelioid Sarcoma Outcome References Sarcomas More Common in Children Soft Tissue Sarcomas More Commonly Observed in Pediatric Patients Ewing Sarcoma Family of Tumors Demographics Primary Therapy Adjuvant Chemotherapy High-Dose Systemic Therapy for Metastatic Disease Standard Cytotoxic Chemotherapy After Disease Relapse Investigational Approaches Ewing Sarcoma-Like Small Blue Round Cell Tumors Rhabdomyosarcoma Demographics Molecular Biology Risk Stratification Staging Imaging Primary Therapy Chemotherapy for Metastatic Disease Mesenchymal Chondrosarcoma Embryonal Sarcoma References Radiation-Induced Sarcoma References Alveolar Soft Part Sarcoma Imaging Diagnosis, Molecular Pathology

6 xiv Contents 17.3 Primary Treatment Treatment of Metastatic Disease Outcome References Clear Cell Sarcoma/Melanoma of Soft Parts Imaging Diagnosis, Molecular Pathology Treatment Outcome References Desmoplastic Small Round Cell Tumor Imaging Diagnosis Treatment Outcome References Extraskeletal Myxoid Chondrosarcoma Imaging Diagnosis Treatment Outcome References Other Uterine Sarcomas Low Grade Endometrial Stromal Sarcoma Diagnosis Treatment Outcome High Grade Endometrial Stromal Sarcoma Outcome Undifferentiated Uterine Sarcoma (UUS) PEComas Uterine Carcinosarcomas and Other Malignant Mixed Müllerian Tumors Outcome References Extraskeletal Osteogenic Sarcoma Imaging Diagnosis Treatment Outcome References

7 Contents xv 23 Sustentacular Tumors of Lymph Tissue Follicular Dendritic Cell Tumor and Interdigitating Reticulum Cell Tumor True Histiocytic Sarcoma Langerhans Cell Tumors Outcome References Uncommon/Unique Sites Heart and Great Vessels Primary Sarcomas of the Breast Phyllodes Tumor Head and Neck Treatment Primary Sarcomas of the Mediastinum Liver References Part III Benign and Less Aggressive Lesions 25 Mostly Benign/Rarely Metastasizing Ossifying Fibromyxoid Tumor Perivascular Epithelioid Cell Tumor (PEComa) and Related Entities, Lymphangioleiomyomatosis, Angiomyolipoma, Sugar Cell Tumor Therapy Giant Cell Tumor of Tendon Sheath/Pigmented Villonodular Synovitis Myoepithelial Tumors of Soft Tissue Glomus Tumor References Selected Benign Tumors Lipoma Lipomatosis Lipoblastoma/Lipoblastomatosis Angiolipomas Angiomyolipoma Angiomyelolipoma Hibernoma Elastofibroma Granular Cell Tumors Hemangioma Leiomyoma Schwannoma Neurofibroma

8 xvi Contents Myxoma Angiomyxoma Angiofibroma References Reactive Lesions Myositis Ossificans Nodular Fasciitis Sarcoma Masquerade References Index

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