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'''For patient information, click [[Chordoma (patient information)|here]]'''
'''For patient information, click [[Chordoma (patient information)|here]]'''


{{CMG}}
{{CMG}};{{AE}} {{PSK}}


{{SK}} Notochordoma; chordocarcinoma; chordoepithelioma
{{SI}}
{{SK}} Notochordoma; Chordocarcinoma; Chordoepithelioma; Clival chordoma; Familial chordoma; Intracranial chordoma; Sacrococcygeal chordoma; Skull base chordoma; Skull-base chordoma; Spinal chordoma; Chondroid chordoma; Classical chordoma; Dedifferentiated chordoma
==Overview==
==Overview==
Chordoma is a rare bone cancer that is diagnosed in only about 300 patients in the U.S. each year. Chordoma accounts for 1% of intracranial tumors and 4% of all primary bone tumors. It develops at the base of the skull, in a vertebra, or at end of the spine (in the sacrum or the coccyx) with about equal frequency. The cells that give rise to chordoma come from the notochord. The notochord is an important structure in the early embryo that disappears before birth. However, even after birth, some cells from the notochord remain in bones at the base of the skull, in vertebrae, and in the tail bone. Rarely, one of these cells, which are called notochord remnants, undergoes changes that give rise to a chordoma. They originate from embryonic remnants of the primitive notochord (earliest fetal axial skeleton, extending from the Rathke's pouch to the coccyx). Since chordomas arise in bone, they are usually extradural and result in local bone destruction.
Chordoma is a rare bone cancer that is diagnosed in only about 300 patients in the U.S. each year. Chordoma accounts for 1% of intracranial tumors and 4% of all primary bone tumors. It occurs exclusively in the axial skeleton and has a predilection for the [[sacrum]] (50%), base of the skull (35%), and mobile [[spine]] (15%).<ref name="Aguiar JúniorAndrade2014">{{cite journal|last1=Aguiar Júnior|first1=Samuel|last2=Andrade|first2=Wesley Pereira|last3=Baiocchi|first3=Glauco|last4=Guimarães|first4=Gustavo Cardoso|last5=Cunha|first5=Isabela Werneck|last6=Estrada|first6=Daniel Alvarez|last7=Suzuki|first7=Sergio Hideki|last8=Kowalski|first8=Luiz Paulo|last9=Lopes|first9=Ademar|title=Natural history and surgical treatment of chordoma: a retrospective cohort study|journal=Sao Paulo Medical Journal|volume=132|issue=5|year=2014|pages=297–302|issn=1516-3180|doi=10.1590/1516-3180.2014.1325628}}</ref> The cells that give rise to arise from the [[notochord]]. The notochord is an important structure in the early [[embryonic]] life that degenerates before birth. However, even after birth, some cells from the notochord remain in bones at the base of the [[skull]], [[vertebrae]], and the [[coccyx]]. Rarely, one of these cells, which are called notochord remnants, undergoes changes that give rise to a chordoma. Since chordomas arise in [[bone]], they are usually extradural and result in local bone destruction. On gross pathology, gelatinous mucoid substance, [[necrosis]], [[hemorrhage]], and [[calcification]] are characteristic findings of chordoma. On microscopic histopathological analysis, vacuolated cells with eccentric [[nucleus]], physaliphorous cells, [[Atypia|cytological atypia]], and high [[mucin]] content within [[cytoplasm]] are characteristic findings of chordoma. Symptoms of chordoma include [[radicular pain]] and sensory deficit related to [[nerve root]] compression. Clival chordoma must be differentiated from [[chondrosarcoma]] of skull base, [[plasmacytoma]], [[meningioma]] of skull base, [[pituitary macroadenoma]], and ecchordosis physaliphora. Vertebral Chordoma must be differentiated from [[chondrosarcoma]], [[giant cell tumor of bone]], spinal metastases, [[plasmacytoma]], and [[Lymphoma|spinal lymphoma]]. The [[incidence]] of chordoma is approximately 0.1 per 100,000 individuals in the United States.<ref name="NibuJosé-Edwards2013">{{cite journal|last1=Nibu|first1=Yutaka|last2=José-Edwards|first2=Diana S.|last3=Di Gregorio|first3=Anna|title=From Notochord Formation to Hereditary Chordoma: The Many Roles of Brachyury|journal=BioMed Research International|volume=2013|year=2013|pages=1–14|issn=2314-6133|doi=10.1155/2013/826435}}</ref> Chordomas may appear at any age, but are most commonly noticed among patients older than 30 years of age. Men are more commonly affected with chordomas than females.<ref name="CarrauFilho2014">{{cite journal|last1=Carrau|first1=Ricardo|last2=Filho|first2=Leo|last3=Jamshidi|first3=Ali|last4=Mohyeldin|first4=Ahmed|last5=Prevedello|first5=Daniel|title=Nuances in the Treatment of Malignant Tumors of the Clival and Petroclival Region|journal=International Archives of Otorhinolaryngology|volume=18|issue=S 02|year=2014|pages=S157–S172|issn=1809-9777|doi=10.1055/s-0034-1395267}}</ref> Chordoma does not usually spread to other bones but can recur after treatment. [[Prognosis]] is generally poor, and the 10-year survival rate of patients with chordoma is approximately 40%. CT scan may be diagnostic of chordoma. Findings on CT scan suggestive of chordoma include expansile soft-tissue mass with a centrally located well-circumscribed destructive lytic lesion, marginal [[sclerosis]], and irregular intratumoral [[Calcification|calcifications]]. On MRI, chordoma is characterized by [[Calcification|calcifications]] and bony expansion.<ref name="CarrauFilho2014">{{cite journal|last1=Carrau|first1=Ricardo|last2=Filho|first2=Leo|last3=Jamshidi|first3=Ali|last4=Mohyeldin|first4=Ahmed|last5=Prevedello|first5=Daniel|title=Nuances in the Treatment of Malignant Tumors of the Clival and Petroclival Region|journal=International Archives of Otorhinolaryngology|volume=18|issue=S 02|year=2014|pages=S157–S172|issn=1809-9777|doi=10.1055/s-0034-1395267}}</ref> [[Chemotherapy]] for chordomas usually results in low response rates.<ref name="Aguiar JúniorAndrade2014">{{cite journal|last1=Aguiar Júnior|first1=Samuel|last2=Andrade|first2=Wesley Pereira|last3=Baiocchi|first3=Glauco|last4=Guimarães|first4=Gustavo Cardoso|last5=Cunha|first5=Isabela Werneck|last6=Estrada|first6=Daniel Alvarez|last7=Suzuki|first7=Sergio Hideki|last8=Kowalski|first8=Luiz Paulo|last9=Lopes|first9=Ademar|title=Natural history and surgical treatment of chordoma: a retrospective cohort study|journal=Sao Paulo Medical Journal|volume=132|issue=5|year=2014|pages=297–302|issn=1516-3180|doi=10.1590/1516-3180.2014.1325628}}</ref> The predominant therapy for chordoma is surgical resection. Adjunctive [[radiation]] may be required.
 
==Classification==
Chordoma may be classified into three subtypes based on the tumors location along the spine: sacrococcygeal lesions, skull-base lesions, and vertebral body lesions .<ref name="NibuJosé-Edwards2013">{{cite journal|last1=Nibu|first1=Yutaka|last2=José-Edwards|first2=Diana S.|last3=Di Gregorio|first3=Anna|title=From Notochord Formation to Hereditary Chordoma: The Many Roles of Brachyury|journal=BioMed Research International|volume=2013|year=2013|pages=1–14|issn=2314-6133|doi=10.1155/2013/826435}}</ref> Chordomas are relatively evenly distributed among three locations:<ref name="Di MaioAl Zhrani2015">{{cite journal|last1=Di Maio|first1=Salvatore|last2=Al Zhrani|first2=Gmaan A.|last3=Al Otaibi|first3=Fahad E.|last4=Alturki|first4=Abdulrahman|last5=Kong|first5=Esther|last6=Yip|first6=Stephen|last7=Rostomily|first7=Robert|title=Novel targeted therapies in chordoma: an update|journal=Therapeutics and Clinical Risk Management|year=2015|pages=873|issn=1178-203X|doi=10.2147/TCRM.S50526}}</ref> 
 
===Sacrococcygeal===
This is the most common location, accounting for approximately 30-50% of all chordomas and involving particularly the fourth and fifth sacral segments. The [[tumor]] may be particularly large at presentation.
===Skull-base===
The clival region is the next most common, accounting for 30-35% of cases. Typically the mass projects in the midline posteriorly indenting the [[pons]]. This characteristic appearance has been termed the "thumb sign".
===Vertebral Bodies===
Chordomas of the [[vertebral bodies]] are rare but after lymphoproliferative tumors are nonetheless the most common primary [[malignancy]] of the [[spine]] in adults. Chordomas most commonly involve the cervical [[spine]] (particularly C2), followed by the lumbar spine then the thoracic spine. They often extend across the [[intervertebral disc space]], involving more than one vertebral segment. Chordomas may extend into the epidural space, compressing the spinal cord, or along the [[Nerve root|nerve roots]], enlarging the neural exit foramen.


==Pathophysiology==
==Pathophysiology==
*Fluid and gelatinous mucoid substance (associated with recent and old haemorrhage) and necrotic areas are found within the tumor.
On gross pathology, gelatinous mucoid substance, [[necrosis]], [[hemorrhage]], and [[calcification]] are characteristic findings of chordoma. On microscopic histopathological analysis, vacuolated cells with eccentric [[nucleus]], physaliphorous cells, cytological [[atypia]], and high [[mucin]] content within [[cytoplasm]] are characteristic findings of chordoma.
*In some patients, calcification and sequestered bone fragments are found as well.
===Gross Pathology===
*The variety of these components may explain the signal heterogeneity observed on MRI.
*On gross examination, chordomas are generally soft and appear to be well encapsulated.
*Incomplete delineation of the tumor and microscopic distal extension of tumor cells may explain the frequency of recurrences.
*Lobulations are apparent on cut section, and the tumor usually has a bluish gray color with extensive gelatinous translucent areas that are focally cystic and hemorrhagic.<ref name=humpath>Chordoma. Human Pathology. http://www.humpath.com/spip.php?article10840</ref>
*Physaliphorous cells are classically seen on microscopy.
*In some patients, [[calcification]] and sequestered bone fragments are found as well.
*Metastatic spread of chordomas is observed in 7-14% of patients and includes nodal, pulmonary, bone, cerebral or abdominal visceral involvement, predominantly from massive tumors.
*True malignant forms of chordomas occasionally have areas of typical chordoma and undifferentiated areas, most often suggestive of fibrosarcoma.


===Microscopic Pathology===
===Microscopic Pathology===
*Photomicrograph demonstrating the typical chordoma cells with large, pleomorphic nuclei and vacuolated cytoplasm (hematoxylin and eosin stain) forming sheets or lobular structures that are embedded in a mucoid stroma.
*Cells are often vacuolated, displacing the [[nucleus]] eccentrically.
*Ultrastructural studies have indicated that the vacuoles can be divided into two subtypes, smooth-walled and villous, based upon the absence or presence of microvilli, respectively.<ref name="NibuJosé-Edwards2013">{{cite journal|last1=Nibu|first1=Yutaka|last2=José-Edwards|first2=Diana S.|last3=Di Gregorio|first3=Anna|title=From Notochord Formation to Hereditary Chordoma: The Many Roles of Brachyury|journal=BioMed Research International|volume=2013|year=2013|pages=1–14|issn=2314-6133|doi=10.1155/2013/826435}}</ref>
*Physaliphorous cells may be present.
*Characteristic of chordomas chondroids are the formation of lobules of neoplastic tissue separated by fibrous stroma and areas of chondroid tissue and vacuolated cell and lymphocytic infiltration.
*Cytological [[atypia]] may be present.
*The tumor displays remarkable morphological variation, mainly based on the amount of interstitial matrix and vacuolated cells; these physaliphorous cells (arrow) with multivacuolated cytoplasm and sometimes pleomorphic nuclei are surrounded by mucinous extracellular matrix, some with chondroid aspect. Physaliphorous comes from the Greek word physalis (bubble).
*High mucin content within cytoplasm and in matrix renders a deep, eosinophilic appearance on H&E stained sections.
*PAS stain: the cytoplasm of many tumor cells is strongly PAS positive (arrows), highlighting them against mucoid matrix. The vacuoles, however, are usually negative. To define the nature of PAS positive material (glycogen), the technique was repeated in cuts, one of which was previously handled by diastase. (c) Neoplastic physaliphorous cells with arrows.
*Characterized immunohistochemically by S-100 and epithelial membrane antigen positivity.
*AE1/AE3: antibodies against keratins clearly show the ratio of neoplastic cells (dark brown) and interstitial tissue (in blue). The lobules of tumor tissue stand out, surrounded by strands of fibrous tissue
*Histologically, chordomas are categorized as classical (or conventional), chondroid, and dedifferentiated chordomas.<ref name="NibuJosé-Edwards2013">{{cite journal|last1=Nibu|first1=Yutaka|last2=José-Edwards|first2=Diana S.|last3=Di Gregorio|first3=Anna|title=From Notochord Formation to Hereditary Chordoma: The Many Roles of Brachyury|journal=BioMed Research International|volume=2013|year=2013|pages=1–14|issn=2314-6133|doi=10.1155/2013/826435}}</ref>
*Physaliphorous cells are typical of classical chordomas, appearing as groups of gray-white large cells separated by fibrous septa into lobules and surrounded by a basophilic extracellular matrix rich in mucin and [[glycogen]].
*Chondroid chordomas show histological features resembling both chordoma and [[chondrosarcoma]], a malignant tumor of the [[bone]] and soft tissue.
*Chondroid chordomas account for 5%–15% of all chordomas and up to 33% of all cranial chordomas, being preferentially found on the spheno-occipital side of the skull base.
*Despite an appearance that resembles [[hyaline cartilage]], these tumors retain an epithelial phenotype and express specific chordoma markers, including [[cytokeratin]] and S-100, which are not found in cartilaginous tissue; this has suggested their alternative, more appropriate classification as “hyalinized chordomas”.
*Dedifferentiated chordomas are also rare, 10% of chordomas, and characterized by sarcomatous regions that are comprised of spindle-shaped polygonal cells.


==Classification==
<gallery>
Chordomas are classified on the basis of their location along the spine. Depending on their location, chordomas are predominantly subdivided into clival (or skull-base), sacrococcygeal, cervical, thoracic, and lumbar.<ref name="NibuJosé-Edwards2013">{{cite journal|last1=Nibu|first1=Yutaka|last2=José-Edwards|first2=Diana S.|last3=Di Gregorio|first3=Anna|title=From Notochord Formation to Hereditary Chordoma: The Many Roles of Brachyury|journal=BioMed Research International|volume=2013|year=2013|pages=1–14|issn=2314-6133|doi=10.1155/2013/826435}}</ref> Chordomas are relatively evenly distributed among three locations:<ref name="Di MaioAl Zhrani2015">{{cite journal|last1=Di Maio|first1=Salvatore|last2=Al Zhrani|first2=Gmaan A.|last3=Al Otaibi|first3=Fahad E.|last4=Alturki|first4=Abdulrahman|last5=Kong|first5=Esther|last6=Yip|first6=Stephen|last7=Rostomily|first7=Robert|title=Novel targeted therapies in chordoma: an update|journal=Therapeutics and Clinical Risk Management|year=2015|pages=873|issn=1178-203X|doi=10.2147/TCRM.S50526}}</ref>
Sacrococcygeal: 30-50%
Spheno-occipital: 30-35%
Vertebral body: 15-30%


===Sacrococcygeal===
Chordoma histology.jpg|Micrograph showing a chordoma. HPS stain.<ref name=wikipedia>Chordoma. Wikipedia. https://en.wikipedia.org/wiki/Chordoma</ref>
This is the most common location, accounting for approximately 30-50% of all chordomas and involving particularly the fourth and fifth sacral segments. In this location a male predilection has been reported (M:F ratio of 2:1) and the tumor may be particularly large at presentation.
Low magnification chordoma.jpg|Low power view. Somewhat lobulated tumor with loose areas, cellular areas, and fibrous septa.<ref name=LP>Chordoma. Libre Pathology. http://librepathology.org/wiki/index.php/Chordoma</ref>
Chordoma is the most common primary malignant sacral tumor.
Physaliferous cells.jpg|Physaliphorous cells.<ref name=LP>Chordoma. Libre Pathology. http://librepathology.org/wiki/index.php/Chordoma</ref>


===Spheno-occipital===
</gallery>
The clival region is the next most common, accounting for 30-35% 2-3 of cases. Typically the mass projects in the midline posteriorly indenting the pons. This characteristic appearance has been termed the 'thumb sign". In contrast to sacrococcygeal tumours, there is currently no recognised gender difference.


===Vertebral bodies===
===Genetics===
Chordomas of the vertebral bodies are rare but after lymphoproliferative tumours are nonetheless the most common primary malignancy of the spine in adults. They most commonly involve the cervical spine (particularly C2), followed by the lumbar spine then the thoracic spine. They often extend across the intervertebral disc space, involving more than one vertebral segment. They may extend into the epidural space, compressing the spinal cord, or along the nerve roots, enlarging the neural exit foramen.
*Recent genetic analysis of chordoma using high-resolution array [[comparative genomic hybridization]] among patients with familial chordoma revealed unique [[Chromosomal duplication|duplications]] in the 6q27 chromosomal region.<ref name="CarrauFilho2014">{{cite journal|last1=Carrau|first1=Ricardo|last2=Filho|first2=Leo|last3=Jamshidi|first3=Ali|last4=Mohyeldin|first4=Ahmed|last5=Prevedello|first5=Daniel|title=Nuances in the Treatment of Malignant Tumors of the Clival and Petroclival Region|journal=International Archives of Otorhinolaryngology|volume=18|issue=S 02|year=2014|pages=S157–S172|issn=1809-9777|doi=10.1055/s-0034-1395267}}</ref>
*Interestingly, the duplicated region only contained the T ([[brachyury]]) gene, which was previously found to be uniquely overexpressed in almost all sporadic chordomas compared with other bone or cartilaginous lesions.
*[[Brachyury]] regulates several compelling [[stem cell]] genes and has recently been implicated in promoting epithelial-mesenchymal transition in other human [[carcinoma|carcinomas]].  
*Although it is still not clear what role brachyury plays in the [[pathogenesis]] of chordomas, the identification of the duplication and the remarkable overexpression seen in samples suggest that it may be a critical molecular driver in the initiation and propagation of chordoma.


==Differential Diagnosis==
==Differentiating Chordoma from other Diseases==
For clival/spheno-occipitial lesions differentials to consider include:  
'''Clival chordoma''' must be differentiated from other diseases such as:
Chondrosarcoma of skull base
*[[Chondrosarcoma]] of skull base
Plasmacytoma
*[[Plasmacytoma]]
Meningioma of skull base
*[[Meningioma]] of skull base
Pituitary macroadenoma
*[[Pituitary macroadenoma]]
Ecchordosis physaliphora
*Ecchordosis physaliphora


For vertebral lesions, consider:
'''Vertebral chordoma''' must be differentiated from other diseases such as:
Chondrosarcoma ◦neural arch > vertebral body
*[[Chondrosarcoma]]
Thoracic spine is the most commonly involved spinal region
**Neural arch > vertebral body
Chondroid matrix (rings & arcs)
**Thoracic spine is the most commonly involved spinal region
Similar MRI appearance to chordomas (low to intermediate signal intensity on T1, hyperintense on T2, enhances)
**Chondroid matrix (rings & arcs)
**Similar MRI appearance to chordomas (low to intermediate signal intensity on T1, hyperintense on T2, enhances)


*Giant cell tumour
*[[Giant cell tumor of bone]]
**F>M
**Location: sacrum > thoracic spine > cervical spine > lumbar spine
**Location: sacrum > thoracic spine > cervical spine > lumbar spine
**No mineralised matrix
**No mineralised matrix
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*Spinal metastases  
*Spinal metastases  
**Hypointense on T1; variably hyperintense on T2
**Hypointense on T1; variably hyperintense on T2
*Often multiple, involving vertebral bodies and posterior elements
**Often multiple, involving vertebral bodies and posterior elements


*Plasmacytoma
*[[Plasmacytoma]]
**Destructive vertebral body lesion (similar appearance to lytic metastases)
**Destructive vertebral body lesion (similar appearance to lytic metastases)


Spinal lymphoma  
*Spinal [[lymphoma]]
*Multifocal disease
**Multifocal disease
*Heterogenous T2 signal
**Heterogenous T2 signal


==Epidemiology==
==Epidemiology and Demographics==
Chordomas are rare neoplasms, occurring with an annual age-adjusted incidence of 0.02 per 100,000 person-years, and account for 1%–4% of all primary malignant bone tumors.<ref name="Di MaioAl Zhrani2015">{{cite journal|last1=Di Maio|first1=Salvatore|last2=Al Zhrani|first2=Gmaan A.|last3=Al Otaibi|first3=Fahad E.|last4=Alturki|first4=Abdulrahman|last5=Kong|first5=Esther|last6=Yip|first6=Stephen|last7=Rostomily|first7=Robert|title=Novel targeted therapies in chordoma: an update|journal=Therapeutics and Clinical Risk Management|year=2015|pages=873|issn=1178-203X|doi=10.2147/TCRM.S50526}}</ref>
Chordomas are rare tumors that affect approximately one in a million individuals. Chordoma represents up to 4% of primary malignant bone tumors and 20% of primary spine tumors.<ref name="NibuJosé-Edwards2013">{{cite journal|last1=Nibu|first1=Yutaka|last2=José-Edwards|first2=Diana S.|last3=Di Gregorio|first3=Anna|title=From Notochord Formation to Hereditary Chordoma: The Many Roles of Brachyury|journal=BioMed Research International|volume=2013|year=2013|pages=1–14|issn=2314-6133|doi=10.1155/2013/826435}}</ref>
 
===Incidence===
*Chordomas occur at any age but are usually seen in adults (30-70 years).
*The [[incidence]] of chordoma is approximately 0.1 per 100,000 individuals in the United States.<ref name="NibuJosé-Edwards2013">{{cite journal|last1=Nibu|first1=Yutaka|last2=José-Edwards|first2=Diana S.|last3=Di Gregorio|first3=Anna|title=From Notochord Formation to Hereditary Chordoma: The Many Roles of Brachyury|journal=BioMed Research International|volume=2013|year=2013|pages=1–14|issn=2314-6133|doi=10.1155/2013/826435}}</ref>
*Those located in the spheno-occipital region most commonly occur in patients 20-40 years of age.
===Age===
*Sacrococcygeal chordomas are typically seen in a slightly older age group (peak around 50 years).
*Chordomas may appear at any age, but are most commonly noticed among patients older than 30 years of age.
*The median age at presentation for cranial chordomas is in the sixth decade, slightly younger for sacral chordomas, and with rare occurrences in the pediatric population.<ref name="Di MaioAl Zhrani2015">{{cite journal|last1=Di Maio|first1=Salvatore|last2=Al Zhrani|first2=Gmaan A.|last3=Al Otaibi|first3=Fahad E.|last4=Alturki|first4=Abdulrahman|last5=Kong|first5=Esther|last6=Yip|first6=Stephen|last7=Rostomily|first7=Robert|title=Novel targeted therapies in chordoma: an update|journal=Therapeutics and Clinical Risk Management|year=2015|pages=873|issn=1178-203X|doi=10.2147/TCRM.S50526}}</ref>
*The median age at presentation for cranial chordomas is in the sixth decade, slightly younger for sacral chordomas, and with rare occurrences in the pediatric population.<ref name="Di MaioAl Zhrani2015">{{cite journal|last1=Di Maio|first1=Salvatore|last2=Al Zhrani|first2=Gmaan A.|last3=Al Otaibi|first3=Fahad E.|last4=Alturki|first4=Abdulrahman|last5=Kong|first5=Esther|last6=Yip|first6=Stephen|last7=Rostomily|first7=Robert|title=Novel targeted therapies in chordoma: an update|journal=Therapeutics and Clinical Risk Management|year=2015|pages=873|issn=1178-203X|doi=10.2147/TCRM.S50526}}</ref>
*They are commonly found in Caucasians.
*Chordomas in children and adolescents account for <5% of all chordoma cases.<ref name="CarrauFilho2014">{{cite journal|last1=Carrau|first1=Ricardo|last2=Filho|first2=Leo|last3=Jamshidi|first3=Ali|last4=Mohyeldin|first4=Ahmed|last5=Prevedello|first5=Daniel|title=Nuances in the Treatment of Malignant Tumors of the Clival and Petroclival Region|journal=International Archives of Otorhinolaryngology|volume=18|issue=S 02|year=2014|pages=S157–S172|issn=1809-9777|doi=10.1055/s-0034-1395267}}</ref>
===Gender===
*Males are more commonly affected with chordomas than females.<ref name="CarrauFilho2014">{{cite journal|last1=Carrau|first1=Ricardo|last2=Filho|first2=Leo|last3=Jamshidi|first3=Ali|last4=Mohyeldin|first4=Ahmed|last5=Prevedello|first5=Daniel|title=Nuances in the Treatment of Malignant Tumors of the Clival and Petroclival Region|journal=International Archives of Otorhinolaryngology|volume=18|issue=S 02|year=2014|pages=S157–S172|issn=1809-9777|doi=10.1055/s-0034-1395267}}</ref>


==Prognosis==
==Natural History, Complications, Prognosis==
*Prognosis is typically poor, due to the locally aggressive nature of these tumors, with the 10-year survival approximately 40%.
===Prognosis===
*Prognosis is generally poor, and the 10-year survival rate of patients with chordoma is approximately 40%.
*The median survival of cranial base chordomas is estimated at 6.29 years, with 5-year overall survival and progression-free survival rates of 78.4% and 50.8%, respectively.<ref name="Di MaioAl Zhrani2015">{{cite journal|last1=Di Maio|first1=Salvatore|last2=Al Zhrani|first2=Gmaan A.|last3=Al Otaibi|first3=Fahad E.|last4=Alturki|first4=Abdulrahman|last5=Kong|first5=Esther|last6=Yip|first6=Stephen|last7=Rostomily|first7=Robert|title=Novel targeted therapies in chordoma: an update|journal=Therapeutics and Clinical Risk Management|year=2015|pages=873|issn=1178-203X|doi=10.2147/TCRM.S50526}}</ref>
*The median survival of cranial base chordomas is estimated at 6.29 years, with 5-year overall survival and progression-free survival rates of 78.4% and 50.8%, respectively.<ref name="Di MaioAl Zhrani2015">{{cite journal|last1=Di Maio|first1=Salvatore|last2=Al Zhrani|first2=Gmaan A.|last3=Al Otaibi|first3=Fahad E.|last4=Alturki|first4=Abdulrahman|last5=Kong|first5=Esther|last6=Yip|first6=Stephen|last7=Rostomily|first7=Robert|title=Novel targeted therapies in chordoma: an update|journal=Therapeutics and Clinical Risk Management|year=2015|pages=873|issn=1178-203X|doi=10.2147/TCRM.S50526}}</ref>
*The lethality of skull-base chordoma is largely due to local progression, although systemic metastasis has been reported in 12.5% of skull base/craniocervical tumors.<ref name="Di MaioAl Zhrani2015">{{cite journal|last1=Di Maio|first1=Salvatore|last2=Al Zhrani|first2=Gmaan A.|last3=Al Otaibi|first3=Fahad E.|last4=Alturki|first4=Abdulrahman|last5=Kong|first5=Esther|last6=Yip|first6=Stephen|last7=Rostomily|first7=Robert|title=Novel targeted therapies in chordoma: an update|journal=Therapeutics and Clinical Risk Management|year=2015|pages=873|issn=1178-203X|doi=10.2147/TCRM.S50526}}</ref>
*The lethality of skull-base chordoma is largely due to local progression, although systemic [[metastasis]] has been reported in 12.5% of skull base tumors.<ref name="Di MaioAl Zhrani2015">{{cite journal|last1=Di Maio|first1=Salvatore|last2=Al Zhrani|first2=Gmaan A.|last3=Al Otaibi|first3=Fahad E.|last4=Alturki|first4=Abdulrahman|last5=Kong|first5=Esther|last6=Yip|first6=Stephen|last7=Rostomily|first7=Robert|title=Novel targeted therapies in chordoma: an update|journal=Therapeutics and Clinical Risk Management|year=2015|pages=873|issn=1178-203X|doi=10.2147/TCRM.S50526}}</ref>
==Complications==
 
===Complications===
*Chordoma does not usually spread to other bones but can recur after treatment.
*Chordoma does not usually spread to other bones but can recur after treatment.
*Metastatic spread of chordoma is observed in 7-14% of patients and includes nodal, pulmonary, bone, cerebral or abdominal visceral involvement, predominantly from massive tumors.
*Incomplete delineation of the tumor and microscopic distal extension of tumor cells may explain the frequency of recurrences.
==History and Symptoms==
===History===
When evaluating a patient for chordoma, you should take a detailed history of the presenting symptom (duration, onset, progression), other associated symptoms, and a thorough past medical history review. Other specific areas of focus when obtaining the history are:
*Obtain a history of any previous treatment for degenerative disc disease or [[coccydynia]].
*Obtain a history of any [[bowel]], [[bladder]], and sexual function.
===Symptoms===
The indolent and slow-growing features that commonly characterize chordomas contribute to their frequently asymptomatic clinical presentation.<ref name="CarrauFilho2014">{{cite journal|last1=Carrau|first1=Ricardo|last2=Filho|first2=Leo|last3=Jamshidi|first3=Ali|last4=Mohyeldin|first4=Ahmed|last5=Prevedello|first5=Daniel|title=Nuances in the Treatment of Malignant Tumors of the Clival and Petroclival Region|journal=International Archives of Otorhinolaryngology|volume=18|issue=S 02|year=2014|pages=S157–S172|issn=1809-9777|doi=10.1055/s-0034-1395267}}</ref> When patients present with symptoms, they usually have radicular pain and sensory deficit related to nerve root compression.<ref name="Aguiar JúniorAndrade2014">{{cite journal|last1=Aguiar Júnior|first1=Samuel|last2=Andrade|first2=Wesley Pereira|last3=Baiocchi|first3=Glauco|last4=Guimarães|first4=Gustavo Cardoso|last5=Cunha|first5=Isabela Werneck|last6=Estrada|first6=Daniel Alvarez|last7=Suzuki|first7=Sergio Hideki|last8=Kowalski|first8=Luiz Paulo|last9=Lopes|first9=Ademar|title=Natural history and surgical treatment of chordoma: a retrospective cohort study|journal=Sao Paulo Medical Journal|volume=132|issue=5|year=2014|pages=297–302|issn=1516-3180|doi=10.1590/1516-3180.2014.1325628}}</ref>
The specific clinical presentation of chordoma is determined by the exact anatomical location of the tumor:
'''Symptoms observed in skull-base chordoma include''':
*[[Double vision]]
*[[Headache]]
*[[Facial pain]]
*Swallowing difficulties
'''Symptoms observed in cervical spine chordoma include''':
*[[Neck pain]]
*[[Hoarseness]]
*[[Dysphagia]]
*[[Bleeding|Laryngeal bleeding]]
'''Symptoms observed in sacral chordoma include''':
*Vague low back pain
*Lower extremity radiculopathy
*Palpable mass
*[[Bowel]] and bladder dysfunction (from local organ mass effect)
==Diagnosis==
==Diagnosis==
===X Ray===
*On X ray, chordoma appears as a solitary midline lesion with bony destruction.
===CT===
===CT===
CT
CT scan may be diagnostic of chordoma. Findings on CT scan suggestive of chordoma include:
centrally located
*Expansile soft-tissue mass that usually hyper-attenuating relative to the adjacent brain.
well-circumscribed
*Centrally located well-circumscribed destructive lytic lesion
destructive lytic lesion, sometimes with marginal sclerosis
*Marginal [[sclerosis]]
expansile soft-tissue mass (usually hyper-attenuating relative to the adjacent brain; however, inhomogenous areas may be seen due to cystic necrosis or haemorrhage; the soft-tissue mass is often disproportionately large relative to the bony destruction)
* Nonhomogenous areas may be observed due to the presence of cystic necrosis or [[hemorrhage]].
irregular intratumoral calcifications (thought to represent sequestra of normal bone rather than dystrophic calcifications)
* The soft-tissue mass is often disproportionately large relative to the bony destruction.
moderate to marked enhancement  
*Irregular intratumoral [[Calcification|calcifications]] (thought to represent sequestration of normal bone rather than dystrophic calcifications)
*Moderate to marked contrast enhancement


===MRI===
===MRI===
'''T1''': Intermediate to low signal intensity
On MRI, chordoma is characterized by [[Calcification|calcifications]] and bony expansion.<ref name="CarrauFilho2014">{{cite journal|last1=Carrau|first1=Ricardo|last2=Filho|first2=Leo|last3=Jamshidi|first3=Ali|last4=Mohyeldin|first4=Ahmed|last5=Prevedello|first5=Daniel|title=Nuances in the Treatment of Malignant Tumors of the Clival and Petroclival Region|journal=International Archives of Otorhinolaryngology|volume=18|issue=S 02|year=2014|pages=S157–S172|issn=1809-9777|doi=10.1055/s-0034-1395267}}</ref> MRI image characteristics observed among chordoma patients include:
small foci of hyperintensity (intratumoral haemorrhage or a mucus pool)
*'''T1 weighted image''':
**Intermediate to low signal intensity
**Small foci of hyperintensity (intratumoral [[hemorrhage]] or a [[mucus]] pool)
 
<gallery perRow="3">
Image:Chordoma Axial T1.jpg|Chordoma Axial T1<ref name=radio>Image courtesy of A.Prof Frank Gaillard. [http://www.radiopaedia.org Radiopaedia] (original file [http://radiopaedia.org/cases/chordoma-thumb-sign-1]). http://radiopaedia.org/licence Creative Commons BY-SA-NC</ref>
Image:Chordoma sagittal T1.jpg|Clival chordoma sagittal T1<ref name=radio>Image courtesy of A.Prof Frank Gaillard. [http://www.radiopaedia.org Radiopaedia] (original file [http://radiopaedia.org/cases/chordoma-thumb-sign-1]). http://radiopaedia.org/licence Creative Commons BY-SA-NC</ref>
</gallery>


'''T2''': most exhibit very high signal
 
*'''T2 weighted image''':
**Most exhibit very high signal
 
<gallery perRow="3">
Image:Chordoma Axial T2.jpg|Clival chordoma Axial T2<ref name=radio>Image courtesy of A.Prof Frank Gaillard. [http://www.radiopaedia.org Radiopaedia] (original file [http://radiopaedia.org/cases/chordoma-thumb-sign-1]). http://radiopaedia.org/licence Creative Commons BY-SA-NC</ref>
Image:Chordoma cornal T2.jpg|Clival chordoma coronal T2<ref name=radio>Image courtesy of A.Prof Frank Gaillard. [http://www.radiopaedia.org Radiopaedia] (original file [http://radiopaedia.org/cases/chordoma-thumb-sign-1]). http://radiopaedia.org/licence Creative Commons BY-SA-NC</ref>
</gallery>
   
   
'''T1 C+ (Gd)''': heterogeneous enhancement with a honeycomb appearance corresponding to low T1 signal areas within the tumour
*'''T1 weighted image with gadolinium contrast''':  
GE (gradient echo): confirms haemorrhage if present with blooming.
**Heterogeneous enhancement with a honeycomb appearance corresponding to low T1 signal areas within the tumor
**Gradient echo confirms hemorrhage if present with blooming


==Treatment==
==Treatment==
*Traditionally surgical resection has been the first line of treatment in feasible scenarios, with radiotherapy offered for recurrent cases.
The predominant therapy for chordoma is surgical resection. Adjunctive [[radiation]] may be required.
*The principal goals of surgery beyond histologic confirmation of the lesion are to achieve a maximal safe resection, provide symptomatic improvement, and to facilitate adjuvant treatment, such as radiotherapy, by minimizing the treatment volume and maximizing the distance between the target volume and critical surrounding neurovascular structures.<ref name="Di MaioAl Zhrani2015">{{cite journal|last1=Di Maio|first1=Salvatore|last2=Al Zhrani|first2=Gmaan A.|last3=Al Otaibi|first3=Fahad E.|last4=Alturki|first4=Abdulrahman|last5=Kong|first5=Esther|last6=Yip|first6=Stephen|last7=Rostomily|first7=Robert|title=Novel targeted therapies in chordoma: an update|journal=Therapeutics and Clinical Risk Management|year=2015|pages=873|issn=1178-203X|doi=10.2147/TCRM.S50526}}</ref>
===Medical Therapy===
*Some advocate the combination of radiation therapy and complete or subtotal surgical resection for selected patients.
====Chemotherapy====
*Percutaneous radiofrequency ablation has been trialled as an adjunct.  
*[[Chemotherapy]] for chordomas usually results in low response rates.<ref name="Aguiar JúniorAndrade2014">{{cite journal|last1=Aguiar Júnior|first1=Samuel|last2=Andrade|first2=Wesley Pereira|last3=Baiocchi|first3=Glauco|last4=Guimarães|first4=Gustavo Cardoso|last5=Cunha|first5=Isabela Werneck|last6=Estrada|first6=Daniel Alvarez|last7=Suzuki|first7=Sergio Hideki|last8=Kowalski|first8=Luiz Paulo|last9=Lopes|first9=Ademar|title=Natural history and surgical treatment of chordoma: a retrospective cohort study|journal=Sao Paulo Medical Journal|volume=132|issue=5|year=2014|pages=297–302|issn=1516-3180|doi=10.1590/1516-3180.2014.1325628}}</ref>
*Recurrence, including seeding along the operative tract, is common.
* Only a few clinical series have reported the use of chemotherapy for managing chordoma, which is generally used in the later course of the disease and only as palliative treatment.
 
====Radiotherapy====
*The use of [[radiotherapy]] as a primary or [[adjuvant treatment]] in various treatment paradigms for chordoma has been a subject of intense debate.<ref name="CarrauFilho2014">{{cite journal|last1=Carrau|first1=Ricardo|last2=Filho|first2=Leo|last3=Jamshidi|first3=Ali|last4=Mohyeldin|first4=Ahmed|last5=Prevedello|first5=Daniel|title=Nuances in the Treatment of Malignant Tumors of the Clival and Petroclival Region|journal=International Archives of Otorhinolaryngology|volume=18|issue=S 02|year=2014|pages=S157–S172|issn=1809-9777|doi=10.1055/s-0034-1395267}}</ref>
*Unfortunately, stand-alone radiotherapy has been ineffective, even when coupled with debulking or palliative decompression.
*The proximity of chordomas to vital neurological structures such as the [[brain stem]] and nerves limits the dose of radiation that can safely be delivered.
*Therefore, highly focused radiation such as [[proton therapy]] and carbon ion therapy are more effective than conventional x-ray radiation.
*Adjuvant proton beam therapy (PBT) after gross total resection is currently the accepted treatment standard in the management of chordoma, and it is the strategy currently favored by the authors.<ref name="CarrauFilho2014">{{cite journal|last1=Carrau|first1=Ricardo|last2=Filho|first2=Leo|last3=Jamshidi|first3=Ali|last4=Mohyeldin|first4=Ahmed|last5=Prevedello|first5=Daniel|title=Nuances in the Treatment of Malignant Tumors of the Clival and Petroclival Region|journal=International Archives of Otorhinolaryngology|volume=18|issue=S 02|year=2014|pages=S157–S172|issn=1809-9777|doi=10.1055/s-0034-1395267}}</ref>
 
===Surgery===
*The principal goals of surgery include:
**Histologic confirmation of the lesion
**Achieve a maximal safe [[resection]]
**Provide symptomatic improvement
**Facilitate adjuvant treatment such as [[radiotherapy]], by minimizing the treatment volume and maximizing the distance between the target volume and critical surrounding neurovascular structures.<ref name="Di MaioAl Zhrani2015">{{cite journal|last1=Di Maio|first1=Salvatore|last2=Al Zhrani|first2=Gmaan A.|last3=Al Otaibi|first3=Fahad E.|last4=Alturki|first4=Abdulrahman|last5=Kong|first5=Esther|last6=Yip|first6=Stephen|last7=Rostomily|first7=Robert|title=Novel targeted therapies in chordoma: an update|journal=Therapeutics and Clinical Risk Management|year=2015|pages=873|issn=1178-203X|doi=10.2147/TCRM.S50526}}</ref>
*Wide en bloc resection with adequate bone and soft tissue margins is the primary surgical goal.<ref name="Aguiar JúniorAndrade2014">{{cite journal|last1=Aguiar Júnior|first1=Samuel|last2=Andrade|first2=Wesley Pereira|last3=Baiocchi|first3=Glauco|last4=Guimarães|first4=Gustavo Cardoso|last5=Cunha|first5=Isabela Werneck|last6=Estrada|first6=Daniel Alvarez|last7=Suzuki|first7=Sergio Hideki|last8=Kowalski|first8=Luiz Paulo|last9=Lopes|first9=Ademar|title=Natural history and surgical treatment of chordoma: a retrospective cohort study|journal=Sao Paulo Medical Journal|volume=132|issue=5|year=2014|pages=297–302|issn=1516-3180|doi=10.1590/1516-3180.2014.1325628}}</ref>
*However, sometimes, wide margins are very difficult to attain because these tumors are located at sites that are difficult to access, with high rates of complications and sequelae.


==References==
==References==

Latest revision as of 16:18, 27 March 2019

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Synonyms and keywords: Notochordoma; Chordocarcinoma; Chordoepithelioma; Clival chordoma; Familial chordoma; Intracranial chordoma; Sacrococcygeal chordoma; Skull base chordoma; Skull-base chordoma; Spinal chordoma; Chondroid chordoma; Classical chordoma; Dedifferentiated chordoma

Overview

Chordoma is a rare bone cancer that is diagnosed in only about 300 patients in the U.S. each year. Chordoma accounts for 1% of intracranial tumors and 4% of all primary bone tumors. It occurs exclusively in the axial skeleton and has a predilection for the sacrum (50%), base of the skull (35%), and mobile spine (15%).[1] The cells that give rise to arise from the notochord. The notochord is an important structure in the early embryonic life that degenerates before birth. However, even after birth, some cells from the notochord remain in bones at the base of the skull, vertebrae, and the coccyx. Rarely, one of these cells, which are called notochord remnants, undergoes changes that give rise to a chordoma. Since chordomas arise in bone, they are usually extradural and result in local bone destruction. On gross pathology, gelatinous mucoid substance, necrosis, hemorrhage, and calcification are characteristic findings of chordoma. On microscopic histopathological analysis, vacuolated cells with eccentric nucleus, physaliphorous cells, cytological atypia, and high mucin content within cytoplasm are characteristic findings of chordoma. Symptoms of chordoma include radicular pain and sensory deficit related to nerve root compression. Clival chordoma must be differentiated from chondrosarcoma of skull base, plasmacytoma, meningioma of skull base, pituitary macroadenoma, and ecchordosis physaliphora. Vertebral Chordoma must be differentiated from chondrosarcoma, giant cell tumor of bone, spinal metastases, plasmacytoma, and spinal lymphoma. The incidence of chordoma is approximately 0.1 per 100,000 individuals in the United States.[2] Chordomas may appear at any age, but are most commonly noticed among patients older than 30 years of age. Men are more commonly affected with chordomas than females.[3] Chordoma does not usually spread to other bones but can recur after treatment. Prognosis is generally poor, and the 10-year survival rate of patients with chordoma is approximately 40%. CT scan may be diagnostic of chordoma. Findings on CT scan suggestive of chordoma include expansile soft-tissue mass with a centrally located well-circumscribed destructive lytic lesion, marginal sclerosis, and irregular intratumoral calcifications. On MRI, chordoma is characterized by calcifications and bony expansion.[3] Chemotherapy for chordomas usually results in low response rates.[1] The predominant therapy for chordoma is surgical resection. Adjunctive radiation may be required.

Classification

Chordoma may be classified into three subtypes based on the tumors location along the spine: sacrococcygeal lesions, skull-base lesions, and vertebral body lesions .[2] Chordomas are relatively evenly distributed among three locations:[4]

Sacrococcygeal

This is the most common location, accounting for approximately 30-50% of all chordomas and involving particularly the fourth and fifth sacral segments. The tumor may be particularly large at presentation.

Skull-base

The clival region is the next most common, accounting for 30-35% of cases. Typically the mass projects in the midline posteriorly indenting the pons. This characteristic appearance has been termed the "thumb sign".

Vertebral Bodies

Chordomas of the vertebral bodies are rare but after lymphoproliferative tumors are nonetheless the most common primary malignancy of the spine in adults. Chordomas most commonly involve the cervical spine (particularly C2), followed by the lumbar spine then the thoracic spine. They often extend across the intervertebral disc space, involving more than one vertebral segment. Chordomas may extend into the epidural space, compressing the spinal cord, or along the nerve roots, enlarging the neural exit foramen.

Pathophysiology

On gross pathology, gelatinous mucoid substance, necrosis, hemorrhage, and calcification are characteristic findings of chordoma. On microscopic histopathological analysis, vacuolated cells with eccentric nucleus, physaliphorous cells, cytological atypia, and high mucin content within cytoplasm are characteristic findings of chordoma.

Gross Pathology

  • On gross examination, chordomas are generally soft and appear to be well encapsulated.
  • Lobulations are apparent on cut section, and the tumor usually has a bluish gray color with extensive gelatinous translucent areas that are focally cystic and hemorrhagic.[5]
  • In some patients, calcification and sequestered bone fragments are found as well.

Microscopic Pathology

  • Cells are often vacuolated, displacing the nucleus eccentrically.
  • Physaliphorous cells may be present.
  • Cytological atypia may be present.
  • High mucin content within cytoplasm and in matrix renders a deep, eosinophilic appearance on H&E stained sections.
  • Characterized immunohistochemically by S-100 and epithelial membrane antigen positivity.
  • Histologically, chordomas are categorized as classical (or conventional), chondroid, and dedifferentiated chordomas.[2]
  • Physaliphorous cells are typical of classical chordomas, appearing as groups of gray-white large cells separated by fibrous septa into lobules and surrounded by a basophilic extracellular matrix rich in mucin and glycogen.
  • Chondroid chordomas show histological features resembling both chordoma and chondrosarcoma, a malignant tumor of the bone and soft tissue.
  • Chondroid chordomas account for 5%–15% of all chordomas and up to 33% of all cranial chordomas, being preferentially found on the spheno-occipital side of the skull base.
  • Despite an appearance that resembles hyaline cartilage, these tumors retain an epithelial phenotype and express specific chordoma markers, including cytokeratin and S-100, which are not found in cartilaginous tissue; this has suggested their alternative, more appropriate classification as “hyalinized chordomas”.
  • Dedifferentiated chordomas are also rare, 10% of chordomas, and characterized by sarcomatous regions that are comprised of spindle-shaped polygonal cells.

Genetics

  • Recent genetic analysis of chordoma using high-resolution array comparative genomic hybridization among patients with familial chordoma revealed unique duplications in the 6q27 chromosomal region.[3]
  • Interestingly, the duplicated region only contained the T (brachyury) gene, which was previously found to be uniquely overexpressed in almost all sporadic chordomas compared with other bone or cartilaginous lesions.
  • Brachyury regulates several compelling stem cell genes and has recently been implicated in promoting epithelial-mesenchymal transition in other human carcinomas.
  • Although it is still not clear what role brachyury plays in the pathogenesis of chordomas, the identification of the duplication and the remarkable overexpression seen in samples suggest that it may be a critical molecular driver in the initiation and propagation of chordoma.

Differentiating Chordoma from other Diseases

Clival chordoma must be differentiated from other diseases such as:

Vertebral chordoma must be differentiated from other diseases such as:

  • Chondrosarcoma
    • Neural arch > vertebral body
    • Thoracic spine is the most commonly involved spinal region
    • Chondroid matrix (rings & arcs)
    • Similar MRI appearance to chordomas (low to intermediate signal intensity on T1, hyperintense on T2, enhances)
  • Giant cell tumor of bone
    • Location: sacrum > thoracic spine > cervical spine > lumbar spine
    • No mineralised matrix
    • Heterogeneous intermediate to hyperintense T2 signal
  • Spinal metastases
    • Hypointense on T1; variably hyperintense on T2
    • Often multiple, involving vertebral bodies and posterior elements
  • Plasmacytoma
    • Destructive vertebral body lesion (similar appearance to lytic metastases)
  • Spinal lymphoma
    • Multifocal disease
    • Heterogenous T2 signal

Epidemiology and Demographics

Chordomas are rare tumors that affect approximately one in a million individuals. Chordoma represents up to 4% of primary malignant bone tumors and 20% of primary spine tumors.[2]

Incidence

  • The incidence of chordoma is approximately 0.1 per 100,000 individuals in the United States.[2]

Age

  • Chordomas may appear at any age, but are most commonly noticed among patients older than 30 years of age.
  • The median age at presentation for cranial chordomas is in the sixth decade, slightly younger for sacral chordomas, and with rare occurrences in the pediatric population.[4]
  • Chordomas in children and adolescents account for <5% of all chordoma cases.[3]

Gender

  • Males are more commonly affected with chordomas than females.[3]

Natural History, Complications, Prognosis

Prognosis

  • Prognosis is generally poor, and the 10-year survival rate of patients with chordoma is approximately 40%.
  • The median survival of cranial base chordomas is estimated at 6.29 years, with 5-year overall survival and progression-free survival rates of 78.4% and 50.8%, respectively.[4]
  • The lethality of skull-base chordoma is largely due to local progression, although systemic metastasis has been reported in 12.5% of skull base tumors.[4]

Complications

  • Chordoma does not usually spread to other bones but can recur after treatment.
  • Metastatic spread of chordoma is observed in 7-14% of patients and includes nodal, pulmonary, bone, cerebral or abdominal visceral involvement, predominantly from massive tumors.
  • Incomplete delineation of the tumor and microscopic distal extension of tumor cells may explain the frequency of recurrences.

History and Symptoms

History

When evaluating a patient for chordoma, you should take a detailed history of the presenting symptom (duration, onset, progression), other associated symptoms, and a thorough past medical history review. Other specific areas of focus when obtaining the history are:

  • Obtain a history of any previous treatment for degenerative disc disease or coccydynia.
  • Obtain a history of any bowel, bladder, and sexual function.

Symptoms

The indolent and slow-growing features that commonly characterize chordomas contribute to their frequently asymptomatic clinical presentation.[3] When patients present with symptoms, they usually have radicular pain and sensory deficit related to nerve root compression.[1] The specific clinical presentation of chordoma is determined by the exact anatomical location of the tumor:

Symptoms observed in skull-base chordoma include:

Symptoms observed in cervical spine chordoma include:

Symptoms observed in sacral chordoma include:

  • Vague low back pain
  • Lower extremity radiculopathy
  • Palpable mass
  • Bowel and bladder dysfunction (from local organ mass effect)

Diagnosis

X Ray

  • On X ray, chordoma appears as a solitary midline lesion with bony destruction.

CT

CT scan may be diagnostic of chordoma. Findings on CT scan suggestive of chordoma include:

  • Expansile soft-tissue mass that usually hyper-attenuating relative to the adjacent brain.
  • Centrally located well-circumscribed destructive lytic lesion
  • Marginal sclerosis
  • Nonhomogenous areas may be observed due to the presence of cystic necrosis or hemorrhage.
  • The soft-tissue mass is often disproportionately large relative to the bony destruction.
  • Irregular intratumoral calcifications (thought to represent sequestration of normal bone rather than dystrophic calcifications)
  • Moderate to marked contrast enhancement

MRI

On MRI, chordoma is characterized by calcifications and bony expansion.[3] MRI image characteristics observed among chordoma patients include:

  • T1 weighted image:
    • Intermediate to low signal intensity
    • Small foci of hyperintensity (intratumoral hemorrhage or a mucus pool)


  • T2 weighted image:
    • Most exhibit very high signal
  • T1 weighted image with gadolinium contrast:
    • Heterogeneous enhancement with a honeycomb appearance corresponding to low T1 signal areas within the tumor
    • Gradient echo confirms hemorrhage if present with blooming

Treatment

The predominant therapy for chordoma is surgical resection. Adjunctive radiation may be required.

Medical Therapy

Chemotherapy

  • Chemotherapy for chordomas usually results in low response rates.[1]
  • Only a few clinical series have reported the use of chemotherapy for managing chordoma, which is generally used in the later course of the disease and only as palliative treatment.

Radiotherapy

  • The use of radiotherapy as a primary or adjuvant treatment in various treatment paradigms for chordoma has been a subject of intense debate.[3]
  • Unfortunately, stand-alone radiotherapy has been ineffective, even when coupled with debulking or palliative decompression.
  • The proximity of chordomas to vital neurological structures such as the brain stem and nerves limits the dose of radiation that can safely be delivered.
  • Therefore, highly focused radiation such as proton therapy and carbon ion therapy are more effective than conventional x-ray radiation.
  • Adjuvant proton beam therapy (PBT) after gross total resection is currently the accepted treatment standard in the management of chordoma, and it is the strategy currently favored by the authors.[3]

Surgery

  • The principal goals of surgery include:
    • Histologic confirmation of the lesion
    • Achieve a maximal safe resection
    • Provide symptomatic improvement
    • Facilitate adjuvant treatment such as radiotherapy, by minimizing the treatment volume and maximizing the distance between the target volume and critical surrounding neurovascular structures.[4]
  • Wide en bloc resection with adequate bone and soft tissue margins is the primary surgical goal.[1]
  • However, sometimes, wide margins are very difficult to attain because these tumors are located at sites that are difficult to access, with high rates of complications and sequelae.

References

  1. 1.0 1.1 1.2 1.3 1.4 Aguiar Júnior, Samuel; Andrade, Wesley Pereira; Baiocchi, Glauco; Guimarães, Gustavo Cardoso; Cunha, Isabela Werneck; Estrada, Daniel Alvarez; Suzuki, Sergio Hideki; Kowalski, Luiz Paulo; Lopes, Ademar (2014). "Natural history and surgical treatment of chordoma: a retrospective cohort study". Sao Paulo Medical Journal. 132 (5): 297–302. doi:10.1590/1516-3180.2014.1325628. ISSN 1516-3180.
  2. 2.0 2.1 2.2 2.3 2.4 Nibu, Yutaka; José-Edwards, Diana S.; Di Gregorio, Anna (2013). "From Notochord Formation to Hereditary Chordoma: The Many Roles of Brachyury". BioMed Research International. 2013: 1–14. doi:10.1155/2013/826435. ISSN 2314-6133.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Carrau, Ricardo; Filho, Leo; Jamshidi, Ali; Mohyeldin, Ahmed; Prevedello, Daniel (2014). "Nuances in the Treatment of Malignant Tumors of the Clival and Petroclival Region". International Archives of Otorhinolaryngology. 18 (S 02): S157–S172. doi:10.1055/s-0034-1395267. ISSN 1809-9777.
  4. 4.0 4.1 4.2 4.3 4.4 Di Maio, Salvatore; Al Zhrani, Gmaan A.; Al Otaibi, Fahad E.; Alturki, Abdulrahman; Kong, Esther; Yip, Stephen; Rostomily, Robert (2015). "Novel targeted therapies in chordoma: an update". Therapeutics and Clinical Risk Management: 873. doi:10.2147/TCRM.S50526. ISSN 1178-203X.
  5. Chordoma. Human Pathology. http://www.humpath.com/spip.php?article10840
  6. Chordoma. Wikipedia. https://en.wikipedia.org/wiki/Chordoma
  7. 7.0 7.1 Chordoma. Libre Pathology. http://librepathology.org/wiki/index.php/Chordoma
  8. 8.0 8.1 8.2 8.3 Image courtesy of A.Prof Frank Gaillard. Radiopaedia (original file [1]). http://radiopaedia.org/licence Creative Commons BY-SA-NC


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