Chordoma Histopathology – Conventional, Poorly Differentiated and Dedifferentiated Types, Brachyury, Mimics and MCQs

Chordoma: subtypes, brachyury and mimics, case, IHC and MCQs, Pathology MCQ

Author: PathologyMCQ Editorial Team
Category: Bone and Soft Tissue Pathology
Last Updated: October 2026 (WHO Classification of Bone Tumours, 5th edition)
Read Time: 10 minutes
Difficulty: Moderate (MD/DNB, FRCPath, NEET-SS)

At a glance

What: malignant tumour with notochordal differentiation, arising in the sacrum, skull base (clivus) and mobile spine.
Histology: lobules separated by fibrous septa; cords and nests of physaliphorous cells in a myxoid matrix.
Key stain: nuclear brachyury, with keratin and EMA; S100 variable.
WHO 5th edition subtypes: conventional (including chondroid), poorly differentiated (SMARCB1-deficient) and dedifferentiated.
In this post: the case with gross and microscopy images, subtype and differential diagnosis tables, an IHC panel and 10 interactive MCQs.

The case

Clinical summary

A 46-year-old man presented with dull, progressive low back pain and mild difficulty walking. MRI showed a lobulated sacrococcygeal mass with bone erosion and extension into the adjacent soft tissue.

Final diagnosis: conventional chordoma of the sacrococcygeal region.

Gross findings

Lobulated, gelatinous, grey-white chordoma involving bone and soft tissue — Lobulated, gelatinous, grey-white tumour. Image: webpathology.com

The tumour is lobulated, soft and gelatinous, with a translucent grey-white, mucoid cut surface. It destroys bone and extends into the adjacent soft tissue, often with areas of haemorrhage.

Microscopy: low to high power

Low power: chordoma lobules separated by fibrous septa — Low power: lobules separated by fibrous septa

Chordoma cells in cords, epithelioid sheets and single cells in a myxoid background — Cords, epithelioid sheets and single cells

Extracellular myxoid matrix with scattered chordoma cells — Abundant extracellular myxoid matrix

Physaliphorous cells with bubbly vacuolated cytoplasm — High power: physaliphorous cells

Mild nuclear pleomorphism and vacuolated cells in a myxoid stroma — Mild nuclear pleomorphism in a myxoid stroma

Magnification	What to look for
Low power	Lobular architecture with fibrous septa; infiltration of bone and soft tissue
Intermediate power	Cords, nests, trabeculae and single cells floating in a pale blue myxoid matrix
High power	Physaliphorous cells with multiple clear cytoplasmic vacuoles; eosinophilic epithelioid cells; round to oval nuclei with mild to moderate atypia; mitoses usually few

Immunohistochemistry and genetics

Marker	Result in chordoma	Why it matters
Brachyury (TBXT)	Nuclear positive	Most specific marker of notochordal differentiation
Cytokeratin (AE1/AE3, CAM5.2)	Positive	Separates chordoma from chondrosarcoma
EMA	Positive	Shared with meningioma and carcinoma
S100	Variable, often positive	Not helpful against chondrosarcoma
SMARCB1 (INI1)	Retained (lost in poorly differentiated chordoma)	Defines the poorly differentiated subtype

Genetics: germline duplication of TBXT underlies many familial chordomas, and a common TBXT variant increases sporadic risk. Chordomas lack IDH1/2 mutations, which helps separate them from chondrosarcoma.

WHO subtypes of chordoma

Subtype	Patients and site	Histology	Key IHC	Behaviour
Conventional (including chondroid)	Adults 40–60 years; sacrum, skull base, spine	Lobules, physaliphorous cells, myxoid matrix; chondroid variant has hyaline cartilage-like matrix	Brachyury, keratin, EMA positive	Locally aggressive, frequent recurrence, late metastases
Poorly differentiated	Children and young adults; skull base and cervical spine	Sheets of epithelioid cells, few physaliphorous cells, little matrix	Brachyury positive, SMARCB1 (INI1) lost	Aggressive
Dedifferentiated	Adults; de novo, at recurrence or after radiotherapy	Conventional chordoma next to a high-grade sarcoma	Brachyury and keratin lost in the sarcomatous part	Poor prognosis

Correction to older teachingChondroid chordoma is no longer treated as a separate subtype. In WHO 5th edition it is a variant of conventional chordoma, and poorly differentiated chordoma is the newly recognised subtype.

Differential diagnosis

Mimic	Distinguishing features
Chondrosarcoma (skull base)	Lacunar chondrocytes in hyaline or myxoid matrix; brachyury and keratin negative; IDH1/2 mutation in conventional types
Chordoid meningioma	Dural-based; EMA, PR and SSTR2A positive; brachyury negative
Myxopapillary ependymoma	Filum terminale or sacral soft tissue; perivascular myxoid cuffs; GFAP positive, keratin and brachyury negative
Extraskeletal myxoid chondrosarcoma	Soft tissue; cords of eosinophilic cells; NR4A3 rearrangement; brachyury negative
Metastatic carcinoma (renal cell, signet ring)	Keratin positive but brachyury negative; organ-specific markers (PAX8, CK7/CK20)
Benign notochordal cell tumour	Intraosseous, sclerotic bone; adipocyte-like cells; no lobules, matrix or destruction; brachyury positive

Treatment and prognosis

En bloc resection with wide margins gives the best local control.
High-dose radiotherapy, usually proton or carbon ion, is used as an adjunct or when resection is not possible.
Conventional chemotherapy is ineffective.
Local recurrence is the main problem; metastases (lung, bone, lymph nodes, skin) occur late.
Poorly differentiated and dedifferentiated chordomas behave more aggressively.

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Test yourself: 10 chordoma MCQs

Case-based questions on histology, brachyury, WHO subtypes, mimics, genetics and treatment. Tap an answer for the explanation.

Score: 0 / 10

More practice: the soft tissue and bone tumour MCQ bank →

Exam pearls and key takeaway

Origin: notochordal differentiation; sacrum, skull base (clivus) and mobile spine.
Histology: lobules with fibrous septa, physaliphorous cells, myxoid matrix.
IHC: brachyury (nuclear), keratin and EMA positive; S100 variable.
WHO subtypes: conventional (chondroid is a variant), poorly differentiated (SMARCB1 loss, children) and dedifferentiated (brachyury lost in the sarcoma).
Main mimic: chondrosarcoma, which is brachyury and keratin negative and often IDH-mutant.
Key takeaway: any lobulated myxoid tumour of the axial skeleton with vacuolated epithelioid cells needs brachyury before you call it chondrosarcoma.

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