Chordoma, a slow-growing malignancy originating from notochord remnants, typically presents in middle-aged adults with characteristic physaliphorous cells histologically and demonstrates bone destruction and heterogeneous enhancement in sacrococcygeal or clival regions on imaging.
Description
Chordoma is a rare malignant neoplasm that arises from notochordal remnants. These are slow-growing but locally aggressive tumours which have a tendency to recur after surgical resection. They predominantly occur in adults, with a peak incidence in the fifth and sixth decades of life. Most common locations are the sacrococcygeal and spheno-occipital regions.
Pathogenesis
The exact pathogenesis of chordoma is not entirely understood. It is believed to originate from remnants of the notochord, a structure in embryonic development that contributes to the formation of the vertebral column. Genetic alterations, such as duplications of the T (Brachyury) gene on chromosome 6, have been identified in familial and sporadic cases.
Epidemiology, Risk Factors & Associations
Chordomas are rare, accounting for about 1-4% of all malignant bone tumours. Commonly affects adults in their 60s. Males are slightly more affected than females. Risk factors have not been clearly defined due to the rare nature of the disease. There’s no established link with environmental or occupational exposure.
Clinical Features
The clinical presentation of chordoma is often related to the location of the tumour. Sacrococcygeal chordomas often present with pain, bowel and bladder disturbances. Spheno-occipital chordomas can present with headaches, visual disturbances, and cranial nerve palsies.
Complications
Complications are mainly due to local invasion of the tumour causing neurological deficits. Recurrence is common after surgical resection, and metastasis, though rare, can occur and is associated with poor prognosis.
Subtypes
Chordoma has three main histological subtypes:
- Classical or Conventional Chordoma (~85% of cases): Characterised by physaliferous cells arranged in cords or nests within a myxoid stroma.
- Chondroid Chordoma (10-15% of cases): Resembles a cartilaginous neoplasm, with areas of conventional chordoma. Typically found in spheno-occpital/nasal/clivus regions.
- Dedifferentiated Chordoma (<5% of cases): An aggressive variant, typically resistant to treatment.
Pathological Features
Histopathology
- On gross examination, chordomas are lobulated masses, often with areas of haemorrhage and necrosis.
- Histologically characterised by cells with abundant eosinophilic cytoplasm (physaliferous cells) within a myxoid stroma.
Immunohistochemistry
- Positive for epithelial markers (such as cytokeratins), S100 protein, and brachyury.
Radiological Features
General Features
- A solitary midline mass found predominantly in the lower sacral elements (60%), spheno-occipital/nasal regions (25%), cervical spine (10%) and thoracolumbar spine (5%).
- Clivus is a typical location of spheno-occpital chordomas, usually chondroid chordoma subtype.
- In the cervical region, C2 is most commonly involved.
- In the sacrococcygeal region, S4–5 is most commonly involved. The tumour may cross the sacroiliac joint.
- Locally aggressive with a propensity to invade the adjacent structures.
- Typically displaces the rectum anteriorly and usually does not invade the pelvic structures due to limitation by the presacral fascia
- Slow growing – Narrow zone of transition, possibly partially sclerotic margin, no periosteal reaction.
- Calcification (nodular or scattered) is seen in 90%
MRI
- Typically appear as lobulated, heterogeneously enhancing masses.
- Vertebral chordomas may extend to involve posterior elements, displaying spinal cord and nerve roots. Sacrum chordomas may involve surrounding gluteal or posterior paraspinal musclature, or extend to retrorectal region.
- T1: Low to intermediate signal intensity relative to muscle. Heterogeneity may be due to dense haemorrhage or mucinous material.
- T2: Heterogenous high signal intensity. Can have a hypointense rim and multiple internal septae.
- Gd+: Heterogenous mild to moderate enhancement
- GRE: May demonstrate intratumoural calcification
CT
- Lytic and destructive lesions, often with soft tissue mass.
- Areas of low attenuation within the mass reflect the myxoid properties (high water content) of the tissue.
- In contrast to most other bone tumours of the spine, chordomas infiltrate the disc spaces to involve other vertebral bodies.
- No true matrix but internal calcification typically present
- The presence of bone expansion, remodelling, and a ‘honeycomb’ appearance are suggestive features.
Grading and Staging
Chordomas are typically graded based on histological subtype and degree of differentiation, with dedifferentiated subtype and higher mitotic activity indicating a worse prognosis. There is no specific staging system for chordoma; the tumour size, local invasion, and presence of metastasis are key factors that influence prognosis and management.
Differential Diagnosis
- Chondrosarcoma: Can be differentiated by the absence of notochordal differentiation and brachyury expression.
- Metastatic carcinoma: Can be differentiated based on clinical history and immunohistochemistry.
- Myxopapillary ependymoma (when located in the spine): Can be distinguished by its characteristic histologic appearance and GFAP positivity.
- Plasmacytoma
- Solitary metastatic deposit
- Giant Cell Tumour
Management
The mainstay of treatment for chordoma is surgical resection, aiming at maximal tumour removal while preserving neurological function. This is often followed by high-dose radiation therapy. Given their relative resistance to conventional chemotherapy, new therapeutic approaches, such as molecular targeted therapies and immunotherapy, are under investigation.