A 13-Year-Old Boy With Recurrent Lower Leg Pain

Prasenjit Das, MD, MBBS; Elanthenral Sigamani, MD


June 13, 2017

Plain radiography is useful when CMF is suspected; however, histopathologic examination is mandatory for confirmation of the diagnosis. Bubbly lesions are typical in the metaphysis, and when seen, a differential diagnosis of giant cell tumor, aneurysmal bone cyst, and CMF should always be kept in mind. The possibility of osteosarcoma should also be considered. The bubbly pattern is usually caused by ridging or endosteal scalloping of the surrounding host bone.

Histologically, the possibility of a low-grade chondrosarcoma should also be carefully ruled out. Because of the nodular growth pattern of any cartilaginous tumor, the histologic diagnosis is primarily based on the extent of cellularity and the cytologic atypia of the tumor cells. However, mild to moderate cytologic atypia has also been described in CMF; therefore, the extent of cellularity, multinucleation within the lacunae, and the presence of atypical mitotic activity in the tumor should be relied on as features to rule out chondrosarcoma.

In this context, remembering that the periphery of the nodules in CMF show marked cellularity should prompt histopathologists to concentrate on the center of the lobules when assessing the criteria of cellularity. CMF, like osteosarcoma, shows erosion of cortical bone with soft-tissue infiltration. Osteoid production by the tumor cells is also characteristic of this lesion. Radiologic correlation is mandatory because CMFs are typically bubbly and oval, and have a long axis parallel to that of the long bone. Extension into diaphysis or epiphysis is not uncommon.[5,7] Unlike other cartilaginous tumors, calcification is less frequent and the margins are typically scalloped.

MRI may help to resolve minute details, such as soft-tissue extension. T2-weighted MRI reveals a hyperintense, homogeneous lesion (Figure 3). CT may help to identify any calcifications within the lesion, which are uncommon and occur in about 2% of cases.[5,7]

Figure 3.

The histogenesis of CMF is uncertain and is a matter of continuing speculation. The cartilaginous origin, as apparent on the morphologic features, has been supported by ultrastructural studies and by immunohistochemical staining for S100 protein. Because of their occasional immunopositivity for smooth-muscle actin and S100 proteins, possible myofibroblastic, myochondroblastic, and chondrocytic differentiation was suggested.[7] For the same reasons, a possible resemblance with chondroblastoma was cited; however, this finding was not substantiated by other studies. Studies have indicated osteocalcin reactivity, which is seen in more than 50% of CMFs, as a cause to support its link with other bone and cartilage tumors, especially chondroblastomas.[7]

A study by Romeo and colleagues[8] examined the DNA microarray of CMF and found that the differential expression of adhesion and extracellular matrix molecules, including CD166, versican, perlecan, and Col4A2, may interfere with normal cartilaginous differentiation and lead to the development of CMF. Some studies indicate a possible cartilaginous derivation by examining the expression of transcription factor SOX9 in the tumor cell nuclei, along with high expression of collagen type II in the cell cytoplasm. A low (< 5%) MIB-1 proliferation index also supports its indolent character.

Although many cytogenetic abnormalities have been reported in CMF, t(1;5)(p13;p13) is a novel clonal cytogenetic abnormality in CMF and has diagnostic significance. Other frequent chromosomal abnormalities described are aberrations in chromosomes 2 and 5.[7]


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