Chordoma—Current Understanding and Modern Treatment Paradigms

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.

Cervical Paraspinal Chordoma: A Literature Review with a Novel Case Report

“…The majority of spinal chordomas occur on the midline and manifest themselves as a soft tissue mass with variable biological behaviors. There are four common types of chordoma: the classic and the chondroid forms, which are usually low-grade and locally aggressive tumors, the poorly differentiated form, and the dedifferentiated forms, which are more aggressive [ 18 ]. Typical radiological findings, which are characteristic of chordoma, comprise the presence of destructive and lytic bone lesions with sclerotic changes extending into the spinal canal [ 19 , 20 ].…”

“…Consequently, chordomas with significant bone destruction may also be misdiagnosed as other spinal tumors, causing destructive bone changes, such as: metastatic carcinoma, chondrosarcoma, chordoid meningioma, myoepithelial tumor of bone [ 29 ], but also myeloma and lymphoma [ 21 ]. Although chondrosarcoma shares similar characteristic features with chordoma in MRIs, it affects the neural arch rather than the vertebral body [ 18 ]. The presence of intralesional calcifications is highly indictive of chordoma, but the multifocal changes within the spine localizations rule out a definitive diagnosis of chordoma [ 30 ].…”

“…These tumors occur mostly on the midline and tend to invade, adjusting critical nerve and vascular structure, limiting the ability to perform en bloc resection. The description of margins by the pathologist is important to distinguish between margins that contain tumorous cells or tissues and those that do not to perform en bloc resection precisely [ 6 , 18 ]. A multitude of patient- and tumor-specific factors, including tumor location, the neurovascular anatomy, as well as patient functional status, contribute to decision-making regarding surgical approach and extent of resection, with the aim of achieving as radical a resection as possible.…”

A practical overview of CT and MRI features of developmental, inflammatory, and neoplastic lesions of the sphenoid body and clivus

“…F female. CN cranial nerve Sphenoid malignant tumour Prevalence Age (decade) of peak incidence of onset Gender predilection Clinical manifestations Chordoma [ 77 , 78 ] 6% of all primary bone tumours. Incidence: 0.08 per 100,000 III–V decade M = F CN VI palsy-related.…”

“…According to the 2021 WHO classification of central nervous system tumours, chordoma is classified as the only subtype of “notochordal tumours”, which belong to “chondro-osseous tumours” among other mesenchymal, non-meningothelial tumours [ 76 ]. It derives from undifferentiated, extradural remnants of the notochord, and four histological subtypes are recognised: conventional (most common, tumour cells embedded in hyaline cartilage-like stroma), chondroid (islands of cartilage formation), poorly differentiated, and dedifferentiated or sarcomatoid chordoma (chordoma associated with a high-grade sarcoma) [ 77 ] (Fig. 13 ).…”