Chondrosarcoma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rohan A. Bhimani, M.B.B.S., D.N.B., M.Ch.[2]


The exact pathogenesis of chondrosarcoama is not fully understood. Multiple genes have been implicated in pathogenesis of chondrosarcoma. Cytogenetic analysis of chondrosarcomas revealed that structural abnormalities of chromosomes 1, 6, 9, 12 and 15 and numerical abnormalities of chromosomes 5, 7, 8 and 18 are most frequent associated. Anomalies associated with chromosome 9(9p12-22) are more commonly seen in central chondrosarcomas. Germline mutations in the exostosin (EXT1 or EXT2) genes, TP53 or pRb pathway, isocitrate dehydrogenase-1 and isocitrate dehydrogenase- 2 genes and gene encoding the receptor for parathyroid have been implicated. On gross pathology, greyish-white lobulated mass, necrosis, calcification, and mucoid degeneration are characteristic findings of chondrosarcoma. On microscopic histopathological analysis abnormal cartilage, increased cellularity, and nuclear atypia are characteristic findings of chondrosarcoma. Chondrosarcoma may be divided into three grades based on cancer cells morphology under microscope and growth rate of tumor.





Gross Pathology

Characteristic features of chondrosarcoma on gross pathology are:[22][23]

Microscopic Pathology

In general chondrosarcomas are multi-lobulated (due to hyaline cartilage nodules) with central high water content and peripheral enchondral ossification. Characteristic features on microscopic analysis are variable depending on the chondrosarcoma subtype:

Clear cell chondrosarcoma

High grade round cells with cytoplasmic clearing. Source Wikimedia common.
The lesion also had areas of more conventional chondrosarcoma. Source Wikimedia common.

Mesenchymal chondrosarcoma

Mesenchymal chondrosarcoma is a malignant tumor with a characteristic biphasic pattern:[27][28][29]

Myxoid chondrosarcoma

Anastomizing chords of small neoplastic cells surround mucin pools. Source Wikimedia common.
Chords of neoplastic cells surround mucin pools. Source Wikimedia common.

Dedifferentiated chondrosarcoma

Histological Grading

Grade 1

  • Chondrosarcoma grows relatively slowly, has cells whose histological appearance is quite similar to cells of normal cartilage.
  • Mostly chondroid matrix, little if any myxoid.
  • Mild-to-moderate increase of cellularity +/- binucleated cells.
  • Have much less aggressive invasive and metastatic properties.
Grade 1 - Somewhat cellular cartilage with binucleation. Source Wikimedia common.

Grade 2

  • Intermediate grade chondrosarcoma
  • Little chondroid matrix, necrosis and more common prominent myxoid.
Grade 2 - Very cellular cartilage with obvious hyperchromasia and nuclear atypia. Source Wikimedia common.

Grade 3

  • Grade 3 chondrosarcoma is increasingly faster-growing cancer, with more varied and abnormal-looking cells.
  • Characterized by myxoid stroma, nuclear pleomorphism and mitoses.
  • Absent chondroid matrix.
  • These are much more likely to infiltrate surrounding tissues, lymph nodes, and organs.
Grade 3 - Even more cellular neoplastic cartilage with high grade nuclear atypia. Source Wikimedia common.


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