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Chapter 1 – Pathology and Classification

WHO classification of bone sarcomas (2)

Osteosarcoma is the most common primary bone sarcoma. Ewing sarcoma is relatively uncommon, but the second most common bone sarcoma in children.

The figure shows permeative growth pattern in high-grade osteosarcoma (A) with pleomorphic tumour cells producing osteoid (B). The diagnosis is based on morphology.

The figure shows typical undifferentiated small blue round cell morphology of Ewing sarcoma (A) with strong diffuse CD99 expression (B). The diagnosis is confirmed by molecular analysis demonstrating an EWSR1-ETS fusion.

After neoadjuvant chemotherapy (ChT) in Ewing sarcoma and osteosarcoma, response should be evaluated morphologically.

In osteosarcoma, response to ChT is one of the most important prognostic factors for OS and disease-free survival; <10% viable tumour cells is considered a good response.

In Ewing sarcoma, histopathological assessment of tumour response also has prognostic value, though it is more difficult to evaluate due to volume changes.


Giant cell tumour of bone (GCTB) is locally aggressive. The peak incidence is between 20 and 45 years of age.

GCTB is characterised by the presence of neoplastic mononuclear stromal cells admixed with reactive multinucleated osteoclast-type giant cells. It has a mutation in H3F3A at the G34 position, which can be demonstrated using IHC.

GCTB can be treated with denosumab (a RANKL antibody) that targets and binds with high affinity and specificity to RANKL, preventing activation of the osteoclast-type giant cells. At histology, no more giant cells are seen.


1. What is the function of denosumab?
2. What is the most common bone sarcoma?
3. What is the morphological hallmark of osteosarcoma?

WHO classification of bone sarcomas - 1 Summary and further reading

Chapter 1 – Pathology and Classification

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