ix
Contents
1 General Description ............................................................................... 1
Introduction ................................................................................................ 1
Incidence and Prevalence ........................................................................... 3
Predisposing and Genetic Factors .............................................................. 8
References .................................................................................................. 13
2 Natural History: Importance of Size, Site,
and Histopathology .................................................................................. 19
Natural History ........................................................................................... 19
Influence of Site ......................................................................................... 19
Staging ....................................................................................................... 19
Staging of Retroperitoneal Visceral Sarcoma ............................................ 26
Prognostic Factors for Extremity and Superficial
Soft Tissue Sarcoma ................................................................................... 30
Disease-Specific Survival .......................................................................... 31
Prognostic Factors for Survival Following Local
Recurrence of Extremity Sarcoma ............................................................. 32
Prognostic Factors: Nomograms ................................................................ 32
References .................................................................................................. 34
3 General Statement as to Efficacy of Surgery/
Chemotherapy/Radiation Therapy ........................................................ 37
Extent of Primary Surgery ......................................................................... 37
Surgical Treatment of Local Recurrence ................................................... 39
Diagnostic Imaging .................................................................................... 39
Surgery for Metastatic Disease .................................................................. 41
Pulmonary Metastasis ............................................................................ 41
Radiation Therapy ...................................................................................... 49
Adjuvant Radiation Therapy .................................................................. 49
Dose of Radiation Therapy .................................................................... 51
Adjuvant Brachytherapy ........................................................................ 51
x Contents
Radiation Therapy in the Presence of Positive
Microscopic Margins ............................................................................. 52
Definitive Radiation Therapy ................................................................. 52
Radiation to Patients with Neurovascular Involvement ......................... 52
Wound Complications of Radiation Therapy ......................................... 53
Sarcomas More Common in Adults ....................................................... 54
Larger Randomized Studies ................................................................... 54
Selected Meta-analyses of Randomized Trials
of Adjuvant Chemotherapy .................................................................... 56
Adjuvant Therapy for GIST ................................................................... 57
Sarcomas More Common in the Pediatric Setting ................................. 58
Special Techniques for Primary and Locally Recurrent Disease ............... 60
Intra-arterial Chemotherapy ................................................................... 60
Limb Perfusion and Hyperthermia ......................................................... 60
References .................................................................................................. 61
Part I Management by Histopathology: Introduction
4 Gastrointestinal Stromal Tumors (GISTs) ............................................. 67
Imaging ...................................................................................................... 67
Familial GIST ............................................................................................ 67
Natural History ........................................................................................... 72
Diagnosis, Molecular Pathology ................................................................ 73
Treatment ................................................................................................... 74
Adjuvant Imatinib for Primary GIST ..................................................... 74
Neoadjuvant Therapy for Primary Disease Not
Amenable to Surgery ............................................................................. 77
Treatment of Recurrence ........................................................................ 77
Systemic Targeted Therapy for Metastatic GIST ................................... 77
Dose Intensity over Time ....................................................................... 82
Imatinib Pharmacokinetics ..................................................................... 83
Second-Line Sunitinib for Imatinib-Resistant Metastatic GIST ................ 84
Other Tyrosine Kinase Inhibitors for Metastatic GIST
Failing Imatinib and Sunitinib ............................................................... 85
Newer Agents ............................................................................................. 85
References .................................................................................................. 87
5 Liposarcoma ............................................................................................. 93
Imaging ...................................................................................................... 97
Diagnosis .................................................................................................... 99
Treatment ................................................................................................... 99
Radiation Therapy ...................................................................................... 103
Systemic Therapy: General Considerations ............................................... 104
Adjuvant Therapy ...................................................................................... 105
Treatment of Metastatic Disease ................................................................ 105
Contents xi
Outcomes ................................................................................................... 107
Outcome Following Metastasis .................................................................. 109
References .................................................................................................. 110
6 Leiomyosarcoma .................................................................................... 113
Imaging ...................................................................................................... 113
Diagnosis, Molecular Pathology ................................................................ 115
Treatment ................................................................................................... 117
Radiation Therapy ...................................................................................... 120
Systemic Therapy ....................................................................................... 120
Adjuvant Chemotherapy ........................................................................ 120
Treatment of Recurrence ............................................................................ 121
Metastatic Disease ..................................................................................... 121
Outcome ..................................................................................................... 123
References .................................................................................................. 124
7 Undifferentiated Pleomorphic Sarcoma
(UPS; Malignant Fibrous Histiocytoma: MFH)
and Myxofi brosarcoma ............................................................................ 129
Imaging ...................................................................................................... 129
Diagnosis/Molecular Pathology ................................................................. 129
Natural History ........................................................................................... 131
Treatment ................................................................................................... 132
Radiation Therapy ...................................................................................... 132
Metastatic Disease ..................................................................................... 132
Adjuvant Chemotherapy ............................................................................ 133
Outcome ..................................................................................................... 134
References .................................................................................................. 135
8 Synovial Sarcoma ..................................................................................... 137
Imaging ...................................................................................................... 137
Diagnosis, Molecular Pathology ................................................................ 137
Treatment ................................................................................................... 141
Radiation Therapy ...................................................................................... 141
Chemotherapy ............................................................................................ 141
Treatment of Recurrence ............................................................................ 143
Local Recurrence ................................................................................... 143
Systemic Treatment ................................................................................ 143
Outcome ..................................................................................................... 145
References .................................................................................................. 146
9 Malignant Peripheral Nerve Sheath Tumor
(MPNST) and Triton Tumor ................................................................... 149
Presentation ................................................................................................ 149
Imaging ...................................................................................................... 149
Diagnosis/Pathology .................................................................................. 152
Neurofibromatosis Type 1 and Outcome ................................................... 154
xii Contents
Treatment ................................................................................................... 154
Radiation Therapy ...................................................................................... 154
Chemotherapy ............................................................................................ 155
Outcome ..................................................................................................... 157
References .................................................................................................. 158
10 Desmoid Tumor/Deep-Seated Fibromatosis
(Desmoid-Type Fibromatosis) ................................................................. 161
Clinical Presentation .................................................................................. 163
Imaging ...................................................................................................... 163
Diagnosis: Molecular ................................................................................. 163
Natural History ........................................................................................... 165
Treatment ................................................................................................... 166
Treatment of Recurrence ............................................................................ 166
Systemic Therapy ....................................................................................... 167
Treatment by Observation .......................................................................... 169
Radiation Therapy ...................................................................................... 169
Patterns of Failure ...................................................................................... 170
Outcome ..................................................................................................... 171
References .................................................................................................. 175
11 Solitary Fibrous Tumor/Hemangiopericytoma ..................................... 179
Outcome ..................................................................................................... 182
References .................................................................................................. 183
12 Fibrosarcoma and Its Variants ............................................................... 185
Outcome ..................................................................................................... 185
Dermatofibrosarcoma Protuberans ............................................................. 185
Outcome ..................................................................................................... 188
Low-Grade Fibromyxoid Sarcoma (Evans’ Tumor) .................................. 189
Outcome ..................................................................................................... 194
Sclerosing Epithelioid Fibrosarcoma ......................................................... 194
Inflammatory Myofibroblastic Tumor........................................................ 195
Infantile Fibrosarcoma ............................................................................... 196
Myxoinflammatory Fibroblastic Sarcoma/Inflammatory
Myxohyaline Tumor of Distal Extremities ................................................ 197
Adult-Type Fibrosarcoma .......................................................................... 197
References .................................................................................................. 198
13 Vascular Sarcomas ................................................................................... 201
Epithelioid Hemangioendothelioma .......................................................... 201
Angiosarcoma/Lymphangiosarcoma .......................................................... 204
Outcome ..................................................................................................... 209
Kaposi Sarcoma ......................................................................................... 210
References .................................................................................................. 211
Contents xiii
14 Epithelioid Sarcoma ................................................................................. 215
Outcome ..................................................................................................... 217
References .................................................................................................. 219
15 Sarcomas More Common in Children ................................................... 221
Soft Tissue Sarcomas More Commonly Observed
in Pediatric Patients .................................................................................... 221
Ewing Sarcoma Family of Tumors (EFT) ................................................. 222
Demographics ............................................................................................ 226
Primary Therapy ........................................................................................ 226
Adjuvant Chemotherapy ............................................................................ 228
High-Dose Systemic Therapy for Metastatic Disease ............................... 229
Standard Cytotoxic Chemotherapy After Disease Relapse ........................ 230
Investigational Approaches ........................................................................ 231
Ewing Sarcoma-Like Small Round Cell Tumors....................................... 232
Rhabdomyosarcoma ................................................................................... 233
Demographics ............................................................................................ 234
Molecular Biology ..................................................................................... 236
Risk Stratification....................................................................................... 238
Staging ....................................................................................................... 238
Imaging ...................................................................................................... 240
Primary Therapy ........................................................................................ 240
Chemotherapy for Metastatic Disease ....................................................... 242
Embryonal Sarcoma ................................................................................... 243
Calcifying Nested Stromal and Epithelial Tumor ...................................... 244
References .................................................................................................. 245
16 Radiation-Induced Sarcomas .................................................................. 251
References .................................................................................................. 256
17 Alveolar Soft Part Sarcoma .................................................................... 259
Imaging ...................................................................................................... 259
Diagnosis/Molecular Pathology ................................................................. 259
Primary Treatment ..................................................................................... 262
Treatment of Metastatic Disease ................................................................ 262
Outcome ..................................................................................................... 263
References .................................................................................................. 264
18 Clear Cell Sarcoma/Melanoma of Soft Parts ........................................ 267
Imaging ...................................................................................................... 267
Diagnosis: Molecular Pathology ................................................................ 267
Treatment ................................................................................................... 270
Outcome ..................................................................................................... 271
References .................................................................................................. 272
xiv Contents
19 Desmoplastic Small Round Cell Tumor ................................................. 275
Imaging ...................................................................................................... 275
Diagnosis .................................................................................................... 275
Treatment ................................................................................................... 276
Outcome ..................................................................................................... 278
References .................................................................................................. 279
20 Extraskeletal Myxoid Chondrosarcoma ................................................ 281
Imaging ...................................................................................................... 281
Diagnosis .................................................................................................... 281
Treatment ................................................................................................... 285
Outcome ..................................................................................................... 285
References .................................................................................................. 286
21 Other Uterine Sarcomas .......................................................................... 289
Endometrial Stromal Sarcoma ................................................................... 289
Diagnosis ................................................................................................ 289
Treatment ............................................................................................... 290
Outcome ................................................................................................. 291
Undifferentiated Endometrial Sarcoma ..................................................... 293
Outcome ................................................................................................. 294
Uterine Carcinosarcomas and Other Malignant
Mixed Müllerian Tumors ........................................................................... 294
PEComas .................................................................................................... 296
Outcome ................................................................................................. 296
References .................................................................................................. 297
22 Extraskeletal Osteogenic Sarcoma ......................................................... 301
Imaging ...................................................................................................... 301
Diagnosis .................................................................................................... 301
Treatment ................................................................................................... 305
Outcome ..................................................................................................... 305
References .................................................................................................. 307
23 Sustentacular Tumors of Lymph Tissue ................................................. 309
Follicular Dendritic Cell Tumor (Dendritic Reticulum
Cell Tumor [FDCT]) and Interdigitating Reticulum
Cell Tumor (IDRCT).................................................................................. 312
True Histiocytic Sarcoma ........................................................................... 312
Langerhans Cell Tumors ............................................................................ 313
Outcome ..................................................................................................... 313
References .................................................................................................. 315
24 Uncommon/Unique Sites ......................................................................... 317
Heart and Great Vessels ............................................................................. 317
Primary Sarcomas of the Breast ................................................................. 318
Phyllodes Tumor .................................................................................... 321
Diagnosis ................................................................................................ 322
Outcome ................................................................................................. 323
Contents xv
Head and Neck ........................................................................................... 323
Treatment ............................................................................................... 324
Primary Sarcomas of the Mediastinum ...................................................... 324
Liver ........................................................................................................... 325
References .................................................................................................. 325
Part II Benign and Less Aggressive Lesions: Introduction
25 Mostly Benign/Rarely Metastasizing Soft Tissue Tumor ..................... 329
Ossifying Fibromyxoid Tumor .................................................................. 329
Perivascular Epithelioid Cell Tumor (PEComa)
and Related Entities: Lymphangioleiomyomatosis,
Angiomyolipoma, and Sugar Cell Tumor .................................................. 330
Therapy ...................................................................................................... 331
Giant Cell Tumor of Tendon Sheath/Pigmented
Villonodular Synovitis ............................................................................... 332
Myoepithelioma of Soft Tissue .................................................................. 334
Glomus Tumor ........................................................................................... 334
References .................................................................................................. 336
26 Benign Soft Tissue Tumors ...................................................................... 339
Lipoma ....................................................................................................... 339
Lipomatosis ................................................................................................ 340
Lipoblastoma/Lipoblastomatosis ............................................................... 340
Angiolipoma .............................................................................................. 341
Angiomyolipoma ....................................................................................... 341
Angiomyelolipoma .................................................................................... 343
Hibernoma .................................................................................................. 343
Elastofibroma ............................................................................................. 345
Granular Cell Tumor .................................................................................. 347
Hemangioma .............................................................................................. 347
Leiomyoma ................................................................................................ 350
Schwannoma .............................................................................................. 350
Neurofibroma ............................................................................................. 350
Myxoma ..................................................................................................... 351
Angiomyxoma ............................................................................................ 352
References .................................................................................................. 353
27 Reactive Lesions ....................................................................................... 355
Myositis Ossificans .................................................................................... 355
Nodular Fasciitis ........................................................................................ 355
Sarcoma Masquerade ................................................................................. 356
References .................................................................................................. 358
Suggested Keywords ........................................................................................ 359
Index .................................................................................................................. 369