Comparative Musculoskeletal Histology

Giant Cell–Containing Tumors

Giant Cell Tumor, Chondroblastoma, Nonossifying Fibroma, and Chondromyxoid Fibroma


All of these lesions contain giant cells. The distinction is often made by observing the background cells, which are different in each and provide clues to the diagnosis. Note that the majority of the features that will separate most of these lesions will be on the imaging studies, and remember that the diagnosis should not be made without imaging review.

Giant Cell Tumor ( Chapter 15 )

  • The prototypic giant cell–containing lesion is giant cell tumor of bone. In contrast to other giant cell–containing lesions, giant cell tumor does not produce extracellular matrix, and the nuclei of the mononuclear cells are identical to the nuclei of the giant cells. Hemorrhage may be present in giant cell tumor, whereas nonossifying fibromas will typically demonstrate hemosiderin.

Chondroblastoma ( Chapter 9 )

  • In contrast to giant cell tumor, the number of giant cells in chondroblastoma that are seen is distinctly fewer, and islands of chondroid matrix are present. At higher power, the mononuclear cells have nuclear grooves, which are not seen in giant cell tumors. Immunohistochemistry for S100 is positive, which is not seen in giant cell tumors or nonossifying fibromas.

Nonossifying Fibroma ( Chapter 4 )

  • Note the background of spindle cells and foamy xanthoma cells, among which are scattered giant cells. This background is distinctly different from giant cell tumor and often has a storiform pattern (not seen here). Hemosiderin is also often seen.

Chondromyxoid Fibroma ( Chapter 11 )

  • The background consists of lobules of chondroid matrix ( upper right-hand corner ) and myxoid and fibrous-like stroma. Giant cells are interspersed and are fewer in number than in giant cell tumor of bone. There can sometimes be histologic overlap with chondroblastoma on limited samples. As in chondroblastoma, S100 staining is positive.

Benign Versus Low-Grade Malignant Chondroid Tumors

Enchondroma Versus Low-Grade Chondrosarcoma


Both enchondroma and low-grade chondrosarcoma contain hyaline-type cartilage matrix and can often be difficult to distinguish histologically. However, it is the relationship between the tumor and surrounding bone that helps to differentiate benign from malignant chondroid tumors. Note that the majority of the features that will separate most of these lesions will be on the radiology, and remember that diagnosis should not be made without review of the imaging studies.

Enchondroma ( Chapter 6 )

  • The encasement of cartilage by bone reflects the indolent, benign nature of this enchondroma. Note the bluish lobules of cartilage surrounded by mature bone. Cellularity of the cartilage portion by itself is not a reliable indicator of malignancy.

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