Bone & joints
Notochordal lesions
Chordoma
Author: Jesse Hart, D.O.
Editorial Board Member: Michael R. Clay, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 1 June 2018
Minor changes: 5 March 2021
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: Chordoma bone [title]
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Pathophysiology | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Hart J. Chordoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonechordoma.html. Accessed March 7th, 2021.
Definition / general
- A malignant tumor with notochordal differentiation
- 3 types:
- Chordoma, not otherwise specified (NOS): ~ 95% of cases (World Neurosurg 2017;104:346)
- Chondroid chordoma (considered prognostically equivalent to chordoma, NOS): ~ 4% of cases
- Dedifferentiated chordoma (< 1% of chordomas): a biphasic tumor composed of a chordoma, NOS + high grade sarcomatous transformation (usually high grade undifferentiated pleomorphic sarcoma or osteosarcoma); poor prognosis
- Chordoma periphericum is a primary soft tissue chordoma and is very rare
Essential features
- Typically involves the clivus, sacrococcygeal bones or vertebrae
- Chords, sheets and individual cells, including cells with bubbly cytoplasm (physaliphorous cells), arranged in lobules set in a myxoid matrix
- Positive for cytokeratin, EMA, S100 protein and brachyury
ICD coding
Epidemiology
- 1 - 5% of primary malignant bone tumors (Orthop Clin North Am 1989;20:417)
- Most commonly arises in the 40 - 60 year old age group (may occur at any age) (Cancer Causes Control 2001;12:1)
- Male predominance (~ 2:1)
Sites
- Intraosseous: > 95% of cases (usually axial skeleton) (Cancer Causes Control 2001;12:1)
- Base of skull / clivus of occipital bone
- Vertebral bodies
- Sacrococcygeal bones
- Extra-axial skeleton (rare)
- Soft tissue (chordoma periphericum): rare (Skeletal Radiol 2013;42:1451)
- Children and young adults: usually cranial chordoma
Pathophysiology
- Most cases are sporadic, but rare cases may arise from a benign notochordal tumor (Br J Radiol 2010;83:e49)
- T gene (brachyury) duplication (6q27)
- T-box transcription factor involved in mesodermal differentiation during gastrulation (formation of 3 germ layers), including notochordal development (Development 2014;141:3819)
- 7% of sporadic chordomas
- Familial associated tumors (autosomal dominant) are rare; they are associated with T gene duplication
- Rare cases associated with tuberous sclerosis (Neurosurg Clin N Am 2015;26:437, Nat Rev Mol Cell Biol 2009;10:307)
Radiology description
- Lytic bone tumor with osseous destruction and soft tissue invasion
- T2 - weighted MRI demonstrates high signal intensity
Radiology images
Contributed by Jesse Hart, D.O.
High signal intensity
Destruction of cervical vertebrae
Case #110
MRI with sacral mass
Prognostic factors
- Median survival is 7 years
- Five year overall and disease free survival are 61% and 71%; 10 year overall and disease free survival are 41% and 57% (World Neurosurg 2017;104:346)
- Worse prognosis in cranial cases
- Approximately 40% of non cranial tumors metastasize (lung, bone, lymph nodes, subcutaneous tissue)
- Chordoma, NOS and chondroid chordoma are prognostically equivalent but dedifferentiated chordoma has a worse prognosis
Case reports
- 47 year old Caucasian man with persistent pain in the low back area (Case #110)
- 58 year old man with clival dedifferentiated chordoma (Anal Quant Cytopathol Histpathol 2014;36:330)
- 71 year old man with lumbosacral tumor with high grade malignant cartilaginous and spindle cell components (Am J Surg Pathol 1990;14:384)
- 72 year old man with giant lumbar chordoma (Medicine (Baltimore) 2018;97:e11128)
- 77 year old woman with clival chordoma (Pol J Radiol 2017;82:670)
- Patient with chordoma of distal ulna (chordoma periphericum) (Am J Surg Pathol 2001;25:263)
- Patient with spheno-occipital tumor evolving to an acute pontocerebellar hemorrhage (Arch Pathol Lab Med 1989;113:1075)
Treatment
- Usually surgery followed by radiation or radiation alone in poor surgical candidates (J Orthop 2018;15:679, Int J Radiat Oncol Biol Phys 2006;65:1514)
- Poor response to chemotherapy
- Tyrosine kinase inhibitors have been used in advanced cases (Eur J Cancer 2017;79:119)
Gross description
- Expansile lobulated mass that usually permeates the cortex and invades adjacent soft tissue
- 5 - 15 cm in greatest dimension
- Cut surface is gelatinous to chondroid
Gross images
Contributed by Jesse Hart, D.O.
Chordoma has fleshy cut surface
Chordoma has invaded the soft tissue
Microscopic (histologic) description
- Chordoma, NOS:
- Infiltrative border
- Low power architecture is lobular, with fibrous bands separating lobules
- Cytoarchitecture (within the lobules) consists of cells forming short chords, dense epithelioid sheets / nest and single cells within the matrix
- Extracellular myxoid matrix
- Cells are epithelioid with abundant clear (glycogen) to eosinophilic cytoplasm that may be have a bubbly / vacuolated appearance (physaliphorous cells)
- Nuclear pleomorphism is heterogenous throughout the neoplasm, with low grade and higher grade areas; vesicular nucleus is common; nuclear pseudoinclusions may be seen
- Mitoses may be present
- Occasionally mitotically active spindle cells
- Chondroid chordoma:
- Matrix mimics hyaline cartilage (may be focal or extensive)
- De-differentiated chordoma:
- A biphasic tumor with two juxtaposed components:
- Chordoma, NOS component
- High grade sarcomatous component (high grade undifferentiated pleomorphic sarcoma or osteosarcoma)
- A biphasic tumor with two juxtaposed components:
Microscopic (histologic) images
Contributed by Jesse Hart, D.O.
Low power
High power
Abundant myxoid stroma
Epithelioid cells with eosinophilic chords
Tumor necrosis
Brachyury
Cytokeratin cocktail
EMA
S100 protein
Positive stains
Molecular / cytogenetics description
- T gene (brachyury) duplication (6q27) occurs in ~ 7% of sporadic chordomas; however, nearly all notochordal tumors over express brachyury (epigenetic mechanisms) (Surg Pathol Clinics 2017;10:637)
- Homozygous or heterozygous loss of CDKN2A (p16, p14ARF) or CDKN2B (p15) at 9p21 seen in ~ 70% of cases
- EGFR amplification is common (7p12)
- Commonly activated pathways:
- EGFR
- PDGFβ
- IGFR1
- IGF1
- mTOR
- Somatic mutation in the following genes are not present:
- Brachyury
- IDH1 or IDH2
- EGFR
- KRAS
- NRAS
- HRAS
- BRAF
- FGFR1-4
- Chromothripsis is seen in a subset of sporadic chordomas, which is a genetic mechanism in which hundreds of simultaneous gene rearrangements occur, secondary to a seminal event occurring when chromosomes are condensed in mitosis (ionizing radiation, aborted apoptosis in which chromosomes have already begun to fragment, telomere dysfunction), resulting in localized chromosomal fragmentation (involving one or a few chromosomes) and rejoining with incorrect orientations
- Poorly differentiated chordoma: molecularly different from conventional chordoma and characterized for SMARCB1 deletion and subsequent loss of INI1 expression (Genes Chromosomes Cancer 2019;58:804)
Differential diagnosis
- Chondrosarcoma: may be confused with chondroid chordoma but will be negative for epithelial markers (Cytokeratin / EMA) and brachyury; unlike chordoma, chondrosarcoma may demonstrate IDH1 or IDH2 mutations
- Metastatic carcinoma: usually negative for S100 protein and brachyury
- Myoepithelial tumors: may occur in soft tissue (the differential would be with chordoma periphericum) or bone, co-expresses epithelial markers (Cytokeratin / EMA) and S100 protein, may have epithelioid cells in a myxoid stroma
- Will be negative for brachyury
- May have an EWSR1 gene rearrangement (~ 50% of cases) (Genes Chromosomes Cancer 2010;49:1114)
- Myxopapillary ependymoma: involves the sacral region but negative for epithelial markers
Board review style question #1
- A 56 year old male had a 6.2 cm sacral mass. The microscopic image is from the resection specimen. Which of the following is true about this entity?
- The tumor has a very low metastatic rate.
- The tumor has the capacity to dedifferentiate.
- The tumor is probably negative for EMA.
- These tumors are very responsive to chemotherapy.
- These tumors usually occur in the extremities.
Board review style answer #1
B. This is a chordoma. The tumor has the capacity to dedifferentiate.
Reference: Chordoma
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Reference: Chordoma
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Board review style question #2
- A 65 year old male has a large vertebral tumor which was resected and found to express both EMA and S100 protein (image shown). His family history is negative for tumors of any type. The patient underwent adjuvant radiation therapy and is now disease free 1 year after surgery. Which of the following is most likely true?
- The patient is very unlikely to die of disease in the next 9 years.
- The patient probably has hepatitis C.
- The tumor has a duplication in the brachyury gene.
- The tumor is positive for brachyury.
- These tumors are benign and adjuvant radiation therapy was unnecessary.
Board review style answer #2
