Bone & joints
Notochordal lesions

Editorial Board Member: Michael R. Clay, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Jesse Hart, D.O.

Topic Completed: 1 June 2018

Minor changes: 5 March 2021

Copyright: 2003-2021,, Inc.

PubMed Search: Chordoma bone [title]

Jesse Hart, D.O.
Page views in 2020: 25,769
Page views in 2021 to date: 5,929
Cite this page: Hart J. Chordoma. website. 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
  • C41.2: Malignant neoplasm of the vertebral column
  • C41.4: Malignant neoplasm of pelvic bones, sacrum and coccyx
  • 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
  • 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
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)
Microscopic (histologic) images

Contributed by Jesse Hart, D.O.

Low power

High power

Abundant myxoid stroma

Epithelioid cells with eosinophilic chords

Tumor necrosis


Cytokeratin cocktail


S100 protein

Positive stains
  • Cytokeratin cocktail, EMA, S100 protein, brachyury (a nuclear stain, highly specific)
  • Decalcification may result in a loss / decrease in brachyury immunoreactivity
  • Dedifferentiated component may lose brachyury, EMA or S100 protein immunoreactivity
Negative stains
  • PTEN loss is common
  • INI1 is occasionally lost
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:
    1. EGFR
    2. PDGFβ
    3. IGFR1
    4. IGF1
    5. mTOR

  • Somatic mutation in the following genes are not present:
    1. Brachyury
    2. IDH1 or IDH2
    3. EGFR
    4. KRAS
    5. NRAS
    6. HRAS
    7. BRAF
    8. 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
    • Not usually lobulated with myxoid stroma
    • Usually positive for "origin specific markers" (PAX8 in renal cell carcinoma, TTF1 in metastatic pulmonary adenocarcinoma, etc)
    • Correlate with chest, abdomen and pelvic imaging
  • 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
  • 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?

  1. The tumor has a very low metastatic rate.
  2. The tumor has the capacity to dedifferentiate.
  3. The tumor is probably negative for EMA.
  4. These tumors are very responsive to chemotherapy.
  5. 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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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?

  1. The patient is very unlikely to die of disease in the next 9 years.
  2. The patient probably has hepatitis C.
  3. The tumor has a duplication in the brachyury gene.
  4. The tumor is positive for brachyury.
  5. These tumors are benign and adjuvant radiation therapy was unnecessary.
Board review style answer #2
D. This is a chordoma. The tumor is positive for brachyury.

Reference: Chordoma

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