Abstract
Chordoma is a low-grade notochordal tumor of the skull base, mobile spine and sacrum which behaves malignantly and confers a poor prognosis despite indolent growth patterns. These tumors often present late in the disease course, tend to encapsulate adjacent neurovascular anatomy, seed resection cavities, recur locally and respond poorly to radiotherapy and conventional chemotherapy, all of which make chordomas challenging to treat. Extent of surgical resection and adequacy of surgical margins are the most important prognostic factors and thus patients with chordoma should be cared for by a highly experienced, multi-disciplinary surgical team in a quaternary center. Ongoing research into the molecular pathophysiology of chordoma has led to the discovery of several pathways that may serve as potential targets for molecular therapy, including a multitude of receptor tyrosine kinases (e.g., platelet-derived growth factor receptor [PDGFR], epidermal growth factor receptor [EGFR]), downstream cascades (e.g., phosphoinositide 3-kinase [PI3K]/protein kinase B [Akt]/mechanistic target of rapamycin [mTOR]), brachyury—a transcription factor expressed ubiquitously in chordoma but not in other tissues—and the fibroblast growth factor [FGF]/mitogen-activated protein kinase kinase [MEK]/extracellular signal-regulated kinase [ERK] pathway. In this review article, the pathophysiology, diagnosis and modern treatment paradigms of chordoma will be discussed with an emphasis on the ongoing research and advances in the field that may lead to improved outcomes for patients with this challenging disease.
Highlights
Introduction published maps and institutional affilChordoma is a notochordal tumor of the skull base, mobile spine and sacrum which remains a considerable treatment challenge despite over 150 years of surgical and chemoradiotherapeutic advances since the first description of the entity by Virchow in 1857 [1].While histologically considered low-to-intermediate grade, these tumors behave in a malignant manner [2], inevitably recur despite aggressive therapy and confer considerable morbidity and mortality [3,4,5,6,7]
Patients with skull base chordomas often present with headaches, cranial neuropathies and endocrinopathies, whereas patients with chordomas of the mobile spine and sacrum may present with localized pain, radiculopathies, myelopathy and/or bowel/bladder dysfunction
computed tomography (CT)-guided needle biopsy is recommended rather than open biopsy for suspected chordomas of the mobile spine and sacrum, as seeding is likely to occur as a result of open biopsy, but when a needle is used, the tract may be resected at the time of definitive tumor resection
Summary
Chordomas are presumed to derive from undifferentiated, extradural, vestigial remnants of the notochord, an embryonic structure that coordinates cell fate and development. In humans and other higher vertebrates, the notochord ossifies to form the vertebral bodies and completely regresses within the first few years of life. Following this process only a small remnant of the notochord remaining as the nucleus pulposis of intervertebral discs [11,26,29]. Though BNCT and other ectopic notochordal remnants have been hypothesized to serve as the precursors for chordoma [31], the incidence of vestigial notochordal remnants such as BNCT is much higher than that of chordoma and the large majority of these notochordal remnants are presumed to lie dormant indefinitely, unless spurred by some stimulus—whether exogenous or endogenous—to mutate and become malignant [32]
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