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CHORDOMAS AND CHONDROSARCOMAS OF THE SKULL BASE AND SPINE

CHORDOMAS AND CHONDROSARCOMAS OF THE SKULL BASE AND SPINE

Copyright

Dedication

Contents

List of Contributors

Foreword

Preface

I - EMBRYOLOGY, PATHOLOGY,AND MOLECULAR BIOLOGY

1 - Embryology of the Skull Base and Vertebral Column

INTRODUCTION

THE SKULL BASE

Genetic Control of Skull Base Development

Embryology of the Skull Base

EMBRYOLOGICAL DEVELOPMENT OF THE NOTOCHORD AND VERTEBRAL COLUMN

References

2 - Pathology of Chordoma and Chondrosarcoma of the Axial Skeleton

CHORDOMA

INTRODUCTION

EPIDEMIOLOGY

CLASSIFICATION AND PATHOLOGY

Conventional Chordoma

Chondroid Chordoma

Dedifferentiated Chordoma

CYTOGENETICS

PROGNOSTICALLY AND THERAPEUTICALLY SIGNIFICANT PATHOLOGICAL FEATURES

CHONDROSARCOMA

INTRODUCTION

EPIDEMIOLOGY

CLASSIFICATION AND PATHOLOGY

References

Further Reading

3 - Molecular Drivers in Chordoma

PATHOGENESIS AND MOLECULAR BIOLOGY OF CHORDOMA

Histological Grading

Cytogenetic Abnormalities

Epigenetic Deregulations

Receptor Tyrosine Kinase Signaling Pathways

HYPOXIA AND ANGIOGENESIS IN CHORDOMA

APOPTOSIS IN CHORDOMA

CANCER STEM CELLS

ANIMAL MODELS OF CHORDOMA

MOLECULAR DRIVERS IN CHORDOMA INVASION AND METASTASIS

SUMMARY/CONCLUSIONS

References

4 - Molecular Drivers in Chondrosarcoma

INTRODUCTION

CLINICOPATHOLOGICAL CLASSIFICATION OF CHONDROSARCOMA

Conventional Chondrosarcoma

Rare Chondrosarcoma Subtypes

MOLECULAR DRIVERS IN CHONDROSARCOMA

Central, Dedifferentiated, and Periosteal Chondrosarcoma

IDH1 and IDH2 Mutations

CELLULAR CONSEQUENCES OF AN IDH1 OR IDH2 MUTATION

IDH1 AND IDH2 MUTATIONS IN ENCHONDROMA AND CHONDROSARCOMA

COL2A1 Mutations

Dysregulation of the Hedgehog Pathway

P53 and pRb Pathway Alterations in the Progression From Low to High-Grade Chondrosarcoma

Apoptosis and Prosurvival Pathways Implicated in Chondrosarcoma

Peripheral Chondrosarcoma

EXT1 and EXT2 Mutations in Osteochondroma and Peripheral Chondrosarcoma

p53 and pRb Pathway Alterations

Mesenchymal Chondrosarcoma: HEY1-NCOA2 Fusion

Clear-Cell Chondrosarcoma

SUMMARY/CONCLUSION

References

II - DEMOGRAPHICS, PRESENTATION,AND DIAGNOSIS

5 - Demographics, Presentation, and Diagnosis

INTRODUCTION

DEMOGRAPHICS

Chordomas

Chondrosarcomas

PRESENTATION

Skull Base Tumors

Spinal Tumors

Pediatric Cases

DIAGNOSIS

Diagnostic Approach to Skull Base Tumors

Diagnostic Approach to Spinal Tumors

CONCLUSIONS

References

6 - Differential Diagnosis of Clival and Spinal Tumors

INTRODUCTION

CONGENITAL TUMORS

Ecchordosis Physaliphora

Benign Notochordal Cell Tumor

PRIMARY CARTILAGINOUS TUMORS

Chondroma

Chondroblastoma

PRIMARY OSSEOUS TUMORS

Osteoma and Osteoblastoma

Osteosarcoma

Giant Cell Tumor

Intraosseous Hemangioma

CENTRAL NERVOUS SYSTEM TUMORS

Schwannoma

Pituitary Macroadenoma

SECONDARY NEOPLASTIC TUMORS

Metastatic Carcinoma

Hematological Malignancies

Plasma Cell Neoplasms

Langerhans Cell Histiocytosis

Adult T-cell Leukemia/Lymphoma

Hodgkin and Non-Hodgkin Lymphomas

Nasopharyngeal Carcinoma

NONNEOPLASTIC TUMORS

Aneurysmal Bone Cyst

Fibrous Dysplasia

OTHER TUMORS

References

7 - Imaging Cranial Base Chordoma and Chondrosarcoma

IMAGING TECHNIQUE

PART I: CHORDOMA

PART II: CHONDROSARCOMA

PART III: POTENTIALLY CONFOUNDING LESIONS

References

Further Reading

8 - Imaging Chordoma and Chondrosarcoma of the Vertebrae and Sacrum

PART I: CHORDOMA

PART II: CHONDROSARCOMA

PART III: POTENTIALLY CONFOUNDING LESIONS

References

Additional Reading

III - SURGERY OF SKULL BASE TUMORS

9 - Surgical Anatomy of the Skull Base

INTRODUCTION

GENERAL SKULL BASE ANATOMY2

Anterior Skull Base (Fig. 9.1)

Middle Skull Base (Fig. 9.2)

Posterior Skull Base (Fig. 9.3)

ESSENTIAL ENDOSCOPIC ENDONASAL ANATOMY: THE SPHENOID BONE, SPHENOID SINUS, AND PITUITARY GLAND (FIG. 9.4)

Sphenoid Bone

The Sphenoid Sinus

The Pituitary Gland and Suprasellar Space

ANATOMY OF THE CLIVUS AND ENVIRONS

General

Surgical Subdivision of the Clivus (Fig. 9.5)

Upper Clivus (Fig. 9.6)

Middle Clivus (Fig. 9.7)

Lower Clivus (Fig. 9.8)

References

10 - Skull Base Tumors: Surgical Considerations

INTRODUCTION

TREATMENT STRATEGIES

SKULL BASE SURGICAL PRINCIPLES

PREOPERATIVE ASSESSMENT

CHOICE OF APPROACH: ANATOMIC CONSIDERATIONS

SURGICAL CORRIDORS TO ANATOMICALLY DISTINCT MODULES OF THE SKULL BASE

ANTERIOR APPROACHES TO CLIVAL TUMORS

Subfrontal Approaches

Transfacial Approaches

Transfacial–Transnasal Approaches

Transfacial–Transoral Approaches

Endoscopic Endonasal Approaches

LATERAL APPROACHES TO CLIVAL AND PETROUS TUMORS

Anterolateral Corridor

Lateral Corridor

Lateral–Inferior Corridor

Posterolateral Corridor

Inferior–Posterolateral Corridor

CONCLUSIONS

References

11 - Midline Subfrontal Approaches: The Transbasal Approach and Extended Modifications to Access the Clivus

INTRODUCTION

SURGICAL CONSIDERATIONS: SELECTION OF APPROACH

PREOPERATIVE CONSIDERATIONS

SURGICAL POSITIONING

SKIN INCISION

STANDARD BIFRONTAL TRANSBASAL APPROACH

EXTENDED TRANSBASAL APPROACHES

Level 1 Transbasal Approach

Level 2 Transbasal Approach

Level 3 Transbasal Approach

MODIFIED ONE-PIECE EXTENDED TRANSBASAL APPROACH

SUBCRANIAL APPROACH

COMBINED TRANSBASAL AND ENDOSCOPIC ENDONASAL APPROACH

RECONSTRUCTION

POSTOPERATIVE MANAGEMENT

CONCLUSION

References

12 - The Endoscopic Endonasal Approach to Chordomas and Chondrosarcomas

INTRODUCTION

ANATOMY—ENDONASAL PERSPECTIVE

INDICATIONS AND PREOPERATIVE PLANNING

APPROACH

SINUS/NASAL PHASE

TRANSMAXILLARY APPROACHES

UPPER CLIVUS

MID-CLIVUS

LOWER CLIVUS/CRANIOCERVICAL JUNCTION

PETROUS APEX/PETROCLIVAL JUNCTION/CAVERNOUS SINUS/OCCIPITAL CONDYLE (CORONAL PLANE)

LIMITATIONS

RECONSTRUCTION

POSTOPERATIVE CARE

RESULTS

CONCLUSION

References

13 - Transoral Approaches to Midline Skull Base Tumors

SUMMARY

References

14 - Chordomas and Chondrosarcomas of the Skull Base: Anterolateral Approaches

INTRODUCTION

INDICATIONS AND PREOPERATIVE PLANNING

Endoscopic Versus Open Approaches

Radiographic Evaluation

Surgical Goals

SURGICAL TECHNIQUE AND COMPLICATION AVOIDANCE

Parasellar Region Anatomy

Frontotemporal-Orbitozygomatic Approach

Bony Cuts

Cavernous Sinus Access

Anterior Petrosectomy

Principles of Tumor Resection

POSTOPERATIVE CARE

RESULTS

Anterolateral Approach–Related Complications

CONCLUSIONS

References

Further Reading

15 - Lateral Approaches

MIDDLE CRANIAL FOSSA APPROACH

EXTENDED MIDDLE CRANIAL FOSSA APPROACH

PREOPERATIVE CONSIDERATIONS

PATIENT POSITION AND MONITORING

EXTRADURAL EXPOSURE

INTRADURAL PETROUS APICECTOMY

EXTRADURAL PETROUS APICECTOMY

TUMOR REMOVAL

RECONSTRUCTION

POTENTIAL COMPLICATIONS

COMBINATION WITH OTHER APPROACHES

BENEFITS OF THE INTRADURAL OPTION

CASE GROUP (INTRADURAL OPTION)

BENEFITS OF THE EXTRADURAL OPTION

CASE EXAMPLE (EXTRADURAL OPTION)

References

16 - Subtemporal–Preauricular Approach to the Infratemporal Fossa

BACKGROUND

APPLICATION OF THE APPROACH

Indications

Limitations

Advantages

Disadvantages

PREOPERATIVE EVALUATION AND PLANNING

OPERATIVE APPROACH

Pitfalls

CLOSURE AND RECONSTRUCTION

CASE 1

CASE 2

CASE 3

References

17 - Chordomas and Chondrosarcomas of the Skull Base: Transpetrosal Approaches

INDICATIONS AND PREOPERATIVE PLANNING

SURGICAL TECHNIQUES COMMON TO ALL TRANSPETROSAL APPROACHES

Transpetrosal (Retrolabyrinthine, Translabyrinthine, Transcochlear)

Retrolabyrinthine

Translabyrinthine

Transcochlear

Transjugular

Combined (Middle Fossa and Transpetrosal, Transpetrosal and Far Lateral, Subtemporal Transpetrous Apex)

Middle Fossa and Transpetrosal

Transpetrosal and Far Lateral Approach to Foramen Magnum

Subtemporal Transpetrous Apex

POSTOPERATIVE CARE

RESULTS

ILLUSTRATIVE CASES

CONCLUSIONS

References

18 - Chordomas and Chondrosarcomas of the Skull Base: Retrosigmoid Approaches

INTRODUCTION

INDICATIONS AND PREOPERATIVE PLANNING

SURGICAL TECHNIQUES AND COMPLICATION AVOIDANCE

POSTOPERATIVE CARE

RESULTS

CONCLUSIONS

References

19 - The Extreme Lateral Approach for Chordomas and Chondrosarcomas of the Craniovertebral Junction

INTRODUCTION

PATHOPHYSIOLOGY

SURGICAL ANATOMY

INDICATIONS

PREOPERATIVE EVALUATION

OPERATIVE PROCEDURE

Intraoperative Monitoring

Positioning

Skin Incision and Soft Tissue Dissection

Exposure and Isolation of the Vertebral Artery

Bone Removal

Tumor Resection

Closure

Stability of the Craniovertebral Junction

DISCUSSION

Case Example 1

Case Example 2

CONCLUSION

References

20 - Staged Approaches for Large Skull Base Chordomas and Chondrosarcomas

INTRODUCTION

PREOPERATIVE PLANNING

Surgical Strategies

Anterior Approaches for Midline Tumors

Endoscopic-Assisted Techniques

Transsphenoidal and Extended Transsphenoidal Approach

Transmaxillary Approach

Lateral Approaches for Paramedian Tumors

Cranioorbital Zygomatic Approach (see Chapter 14)

Extended Middle Fossa Approach (see Chapter 15)

Transcondylar Approach (see Chapter 19)

Staged Approaches for Tumors With Extracranial Extension

Illustrative Cases

Case 1

Case 2

CONCLUSIONS

References

21 - Cerebral Revascularization for Skull Base Tumors

PREOPERATIVE EVALUATION

BYPASS TYPES AND SELECTION

OPERATIVE TECHNIQUE

Anesthesia and Monitoring

Direct Reconstruction/Interposition Graft

Operative Procedure: High-Flow Bypass

Donor Vessel

Radial Artery Graft

Pressure Distention Technique

Saphenous Vein Graft

Anterior Tibial Artery

Vein Grafting Procedure

Cervical External Carotid Artery as Donor Vessel

Cervical Internal Carotid Artery (or External Carotid Artery) to Supraclinoid Internal Carotid Artery

Troubleshooting

Complications

POSTOPERATIVE CARE AND FOLLOW-UP

RESULTS AND CASE EXAMPLES

Skull Base Tumors

Case 7

Case 8

References

22 - Skull Base Reconstruction Following Resection of Skull Base Chordomas and Chondrosarcomas

INTRODUCTION

CONSIDERATION AND GOALS OF SKULL BASE RECONSTRUCTION

RECONSTRUCTION OF THE SKULL BASE

Primary Closure

Free Autografts

Free Mucoperiosteal/Mucoperichondrial Autograft

Autologous Fascia Lata Graft

Free-Fat Autograft

Free-Cartilage Autograft

Free-Bone Autograft

Use of Synthetic and Heterologous Materials

Vascularized Flaps

Nasoseptal or Hadad–Bassagaisteguy Flap

Technique

Double NSF

Posterior Pedicle Inferior Turbinate Flap

Technique

Lateral Nasal Wall Flaps—Anteriorly Pedicled Hadad–Bassagaisteguy Flap 2 and Posteriorly Pedicled or Carrau–Hadad Flap

Posterior Pedicle Middle Turbinate Flap

Extranasal Flaps

Temporoparietal Fascia Flap

Technique

Occipital Galeopericranial Flap

Palatal Flap (Oliver Pedicled Palatal Flap)

Temporalis Muscle Flap

Pericranial and Galeo-Pericranial Flap

Pedicled Buccal Fat Pad Flap

Pedicled Facial Buccinator and Facial Artery Musculomucosal Flap

The Salpingopharyngeus Flap (Dicle Flap)

Free Flaps

POSTOPERATIVE CARE

OUTCOMES

COMPLICATION

Postoperative Cerebrospinal Fluid Leak

RECOMMENDATION

CONCLUSION

CASE PRESENTATION

Case 1

Case 2

References

23 - Stabilization of the Craniocervical Junction Following Resection of Chordomas and Chondrosarcomas of the Skull Base and Spine

INTRODUCTION

SURGICAL TECHNIQUE

Preoperative Decision Making

Anesthesia Concerns

Patient Positioning

Operative Approach

Implant Options

Complications

IMPORTANT CONSIDERATIONS

Extent of Fusion

Condylar Resection

REPRESENTATIVE CASE

References

IV - SURGERY OF SPINAL AND SACRAL TUMORS

24 - Chordomas and Chondrosarcomas of the Spine: Preoperative Planning, Surgical Strategies, and Complications Avoidance

INTRODUCTION

RATIONALE FOR SURGICAL TREATMENT

Diagnosis and Staging

Indications and Surgical Planning for En Bloc Spinal Resections

Preoperative Embolization

SURGICAL TECHNIQUE FOR EN BLOC RESECTION OF SPINE TUMORS

Cervical

Thoracic

Lumbar

Sacrum

PERIOPERATIVE COMPLICATIONS

CONCLUSIONS

References

25 - Surgical Management of Chordomas and Chondrosarcomas of the Cervical Spine

INTRODUCTION

SURGICAL MANAGEMENT

ILLUSTRATIVE CASES

Case 1

Case 2

CONCLUSION

References

26 - Surgical Management of the Chordomas and Chondrosarcomas of the Thoracic Spine

INTRODUCTION

Chordomas of the Thoracic Spine

Chondrosarcomas of the Thoracic Spine

PREOPERATIVE PLANNING

Oncologic Staging

Surgical Staging

SURGICAL TECHNIQUE: THORACIC SPINE EN BLOC SPONDYLECTOMY

Posteroranterior (Back–Front) Approach

Posterior-Only Thoracic Spondylectomy

COMPLICATION AVOIDANCE AND POSTOPERATIVE CARE

RESULTS

Treatment of Relapse

SUMMARY

References

27 - Surgical Management of Chordomas and Chondrosarcomas of the Lumbar Spine

INTRODUCTION

Indications and Preoperative Planning

Surgical Technique and Complication Avoidance

Combined Approach—Stage 1

Combined Approach—Stage 2

POSTOPERATIVE CARE

RESULTS

CONCLUSION

References

28 - Anatomical Considerations for Resection of Chordomas and Chondrosarcoma of the Sacrum

THE SOFT TISSUES

THE SCIATIC NOTCH

LIGAMENTS

THE SACROSPINAL CANAL

PRESACRAL DISSECTION

OSTEOTOMY

NEURECTOMY

CLOSURE

References

29 - Surgical Treatment of Sacral Chordoma

INTRODUCTION

EVIDENCE FOR SURGICAL RESECTION

Preoperative Planning

Surgical Technique

Posterior Approach

Combined Anterior–Posterior Approach

LUMBOPELVIC RECONSTRUCTION

Instrumentation Techniques

Arthrodesis Techniques

SOFT-TISSUE RECONSTRUCTION

Local Tissue Advancement

Pedicle Flaps

Free-Tissue Transfer

CONCLUSION

References

V - RADIATION THERAPY OF CHORDOMASAND CHONDROSARCOMAS

30 - Fractionated Photon Radiation Therapy forSkull Base Chordomas and Chondrosarcomas

INTRODUCTION

STRATEGIES FOR DELIVERINGFRACTIONATED PHOTON RADIATIONTHERAPY

Intensity-Modulated Radiation Therapy

Helical Tomotherapy

CyberKnife

RESULTS OF MODERN PHOTONTHERAPY

SUMMARY

References

31 - Stereotactic Radiosurgery for Skull Base Chordomas and Chondrosarcomas

BACKGROUND

RADIOBIOLOGICAL PRINCIPLES

INDICATIONS FOR RADIOTHERAPY

RADIATION TECHNIQUES

RESULTS

Conventional Fractionation (Photons or Protons)

Spine Versus Skull Base SRS

Skull Base SRS

COMPLICATIONS

Advantages and Limitations

CONCLUSION

References

Further Reading

32 - Proton Therapy for Skull Base Chordomas and Chondrosarcomas

INTRODUCTION

CHARACTERISTICS OF PROTON RADIATION THERAPY

HISTORY OF PROTON RADIATION THERAPY FOR TUMORS OF THE BASE OF THE SKULL

TREATMENT MANAGEMENT

MODERN RESULTS

Local Control

Toxicity

Reirradiation

Innovations

References

33 - Photon Irradiation for Spinal Chordomas and Chondrosarcomas

INTRODUCTION

EXTERNAL BEAM RADIOTHERAPY WITH CONVENTIONAL FRACTIONATION

STEREOTACTIC RADIOSURGERY

RADIATION TOXICITY

CONCLUSIONS

References

34 - Proton Therapy for Spinal Chordomas and Chondrosarcomas

GENERAL COMMENTS

GENERAL CONSIDERATIONS

Surgery

SPINE CHORDOMAS AND CHONDROSARCOMAS

Spine Chondrosarcoma

Spine/Sacral Chordoma

SEQUENCING OF RADIATION THERAPY AND SURGERY

CONCLUSION

Illustrative Patient Treatment Plans

References

Further Reading

35 - Heavy Ion Radiation for Chordomas and Chondrosarcomas

INTRODUCTION

RADIOBIOLOGICAL AND PHYSICAL PRINCIPLES

BIOLOGICAL CHARACTERISTICS

INDICATIONS

Skull Base Chordoma

Skull Base Chondrosarcoma

Sacrum and Mobile Spine Chordomas and Chondrosarcomas

TECHNICAL CHARACTERISTICS

RESULTS

Skull Base Chordoma

Skull Base Chondrosarcoma

Sacrum and Mobile Spine Chordoma

Sacral and Mobile Spine Chondrosarcoma

COMPLICATIONS

Skull Base Chondrosarcoma

Skull Base Chordoma

Secondary Malignancy

Sacral and Spine Chordoma and Chondrosarcoma

ADVANTAGES OF CARBON ION

LIMITATIONS OF CARBON IONS

CONCLUSIONS

References

VI - SPECIAL CONSIDERATIONS

36 - Chordomas and Chondrosarcomas in Children

INCIDENCE

PRESENTATION

RADIOLOGY

PATHOLOGY

TREATMENT

OUTCOMES AND PROGNOSIS

CONCLUSIONS

References

37 - Recurrent Skull Base Chordomas: Role of Surgery

INTRODUCTION

DIAGNOSIS OF RECURRENT TUMOR

DECISION-MAKING

MORBIDITY AND MORTALITY OF REOPERATION

CONCLUSIONS

References

38 - Systemic Therapies for Locally Recurrent or Metastatic Disease

CHORDOMA

Cytotoxic Therapy

Molecularly Targeted Therapy

Imatinib

Imatinib Combination Strategies

Sunitinib

Sorafenib

Dasatinib

Anti-EGFR Therapy

Future Directions in Systemic Therapies for Chordomas

CHONDROSARCOMA

CYTOTOXIC THERAPY

MOLECULARLY TARGETED THERAPY

FUTURE DIRECTIONS IN SYSTEMIC THERAPIES FOR CHONDROSARCOMAS

References

39 - Chordomas and Chondrosarcomas of the Axial Skeleton: Emerging Therapies and Future Directions

INTRODUCTION: BARRIERS TO TRADITIONAL THERAPIES

SURGICAL METHODS: IMPROVEMENT IN TECHNIQUES

ADVANCES IN RADIATION THERAPY: RADIATION THERAPY EMERGING AS A USEFUL ADJUVANT

SYSTEMIC THERAPY: INNOVATIVE APPROACHES TO METASTATIC AND LOCALLY RECURRENT DISEASE

Chordoma: Potential Future Strategies

Chondrosarcoma: Potential Future Strategies

References

Further Reading

40 - Prognosis, Survival, and Surveillance

CHORDOMA

Prognostic Factors

Age

Site of Origin

Tumor Molecular Features

Presence of Metastasis

Survival Rates

Surveillance

Chordoma Summary

CHONDROSARCOMA

Prognostic Factors

Impact of Resection Status, Grade, and Location

Surveillance

Chondrosarcoma Summary

References

VII - PATIENT ADVOCACY

41 - The Chordoma Foundation

INTRODUCTION

Organizational Profile

Goals

Better Treatments

Better Medical Care

Better Patient Experience

PROGRAMS AND SERVICES

Research

Uniting and Strengthening the Research Community

Investing in High-Impact Research

Resource Development

Biospecimens

Disease Models

Tools and Reagents

Target Discovery

Therapeutic Discovery

Preclinical Research

Clinical Research

Clinical Trials

Observational Research

Sharing Data and Biological Resources

Data

Biological Resources

Healthcare Improvement

Standardization

Education

Patient Services

Education

Navigation

Support

CONCLUSION

References

42 - Sarcoma Patient Advocacy: Hope and Help

SARCOMA STATISTICS

THE SARCOMA FOUNDATIONOF AMERICA

SARCOMA RESEARCH GRANTS

PATIENT EDUCATION

DISEASE AWARENESS

LEGISLATIVE ADVOCACY

SUMMARY

Index

A

B

C

D

E

F

G

H

I

J

K

L

M

N

O

P

Q

R

S

T

U

V

W

Y

Z

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