Chondroblastoma

Chondroblastoma is a benign bone tumor that produces chondroid matrix. Although it is benign, it can be locally aggressive, causing destruction (lysis) of the involved bone. Chondroblastoma typically arises in the epiphysis or apophysis of the long bones in skeletally immature patients.

Epidemiology

Chondroblastoma accounts for 1 to 2% of all bone tumors and 5% of benign bone tumors. It commonly presents in patients 10 to 25 years old and has a 2:1 male-predominance. A majority of cases involve the distal femur, proximal tibia and proximal humerus. Other less common sites include the proximal femur, calcaneus, talus, and patella. Chondroblastoma can also be found rarely in the flat bones (e.g., scapula, sternum, skull), the patella (a sesamoid bone) or the growing acetabulum. When it occurs in the skull, the patient is typically older than patients who present with long bone lesions.

Clinical Features

Symptoms of chondroblastoma can vary, but localized pain and swelling in the affected bone, especially during activity, are common. As the tumor grows, it can also cause joint stiffness, limited mobility, and difficulty walking. The delay between onset of symptoms and diagnosis can range from less than 1 month to many years. Some patients may present with a joint effusion or rarely, a pathologic fracture. If the skull is involved, patients may present with hearing loss, tinnitus, or vertigo.

Radiologic Features

On radiographs, chondroblastomas are typically lytic, central or eccentric lesions found in the epiphysis. Most chondroblastomas are relatively small, measuring 3-6 cm. The lesion has a sharply demarcated, geographic margin and does not expand the cortex. The tumor may cross the physis, but is usually confined to the epiphysis, with or without a sclerotic border (Figure 1).

Figure 1: AP X-ray of the knee demonstrating an 16-year-old with chondroblastoma of the epiphysis in the distal femur. (Image courtesy of “Epidemological, radiographic and prognostic evaluation of chondroblastoma.” Acta Ortopédica Brasileira 33.spe1 (2025): e283605.)

On T1-weighted MRI images, chondroblastomas appear as an intermediate signal intensity lesion. Abundant surrounding bone marrow edema is frequently seen on fluid-sensitive MRI sequences. Chondroblastomas can have a cystic component, with so-called fluid-fluid levels seen on T2 MRI sequences, as well (Figure 2 ). Matrix calcifications can be seen in about 33% of cases. On computed tomography (CT), stippled calcification of a cartilaginous matrix can be observed. CT can provide more detailed information on the size and shape of the tumor.

Figure 2: Coronal T2 coronal MRI of the distal femoral chondroblastoma shown in figure 1 as well, demonstrating hyperintensity of the partly cystic lesion as well as surrounding bone marrow edema. (Image courtesy of “Epidemological, radiographic and prognostic evaluation of chondroblastoma.” Acta Ortopédica Brasileira 33.spe1 (2025): e283605.)

Chondroblastoma is a rare bone tumor, and other bone tumors as well as infection can have similar radiographic features. Therefore, as with most lesions, a biopsy is necessary to confirm the diagnosis of chondroblastoma.

Pathology

Grossly, chondroblastomas may have calcified, hemorrhagic, and/or cystic components. Histologically, the tumor is composed of sheets of chondroblasts with oval nuclei featuring a prominent longitudinal groove. (The are said to resemble a coffee bean, hence the name, “coffee bean nuclei.”) The chondroblasts are arranged in a “cobblestone”-like pattern, with randomly interspersed, osteoclast-like giant cells. A fine network of calcification known as “chicken wire” calcification is characteristic but not seen in all tumors (Figure 3).

Figure 3: H&E stain of chondroblastoma, demonstrating mononuclear chondroblasts with sharp margins and coffee bean nuclei, fitted together in a “cobblestone”-like pattern with interspersed, multinucleated, osteoclast-like giant cells. The chondroid matrix can be eosinophilic or basophilic and can sometimes resemble woven bone. The “chicken wire” calcification is due to the mineralization of matrix surrounding single cells, and is seen here as the thin network of deep purple-stained calcification. (Images courtesy of Dr. Gord Zhu)

Secondary aneurysmal bone cyst is present in up to one-third of cases.

The expression of S100 and SOX9 proteins, as well as heterogeneous arrangements on chromosomes 5 and 8, are all commonly associated with chondroblastoma. S100 is a protein that is normally produced by chondrocytes. SOX9 is a transcription factor that plays a critical role in chondrogenesis. Both S100 and SOX9 can be detected using immunohistochemistry staining.

Over 90% of chondroblastomas harbor the H3.3 K36M mutation (a lysine-to-methionine substitution at position 36 of histone H3.3, encoded by H3F3B). This is now considered the defining molecular event and has a mutation-specific antibody (H3K36M IHC) that is highly specific for chondroblastoma.

Heterogeneous chromosomal arrangements on chromosomes 5 and 8 have also been observed in chondroblastoma, although the significance of these findings is not fully understood. These chromosomal abnormalities may play a role in the development or progression of the tumor, or they may simply be incidental findings.

Differential Diagnosis

The differential diagnosis of chondroblastoma includes the following: chondromyxoid fibroma, giant cell tumor, osteosarcoma, chondrosarcoma, fibrous dysplasia, and infection. A biopsy of the affected bone is usually necessary to confirm the diagnosis and rule out other bone-related conditions.

Disease Course: Treatment and Prognosis

Surgical removal of the tumor is the mainstay of treatment for chondroblastoma. The goal of surgery is to completely remove the tumor while preserving as much healthy bone and joint function as possible. Standard treatment includes intralesional curettage with or without adjuvant (such as phenol, cryotherapy, argon beam, or burring) and bone grafting of the defect. Gaining access to the lesion during surgery without damaging the nearby physis and articular surface can be challenging.

Radiographic surveillance is typically performed for at least 3-5 years postoperatively to monitor local recurrence, the rate of which is up to 25% in some series. In the case of local recurrence, wide resection may be considered.

Pulmonary metastases have been reported in less than 1% of benign chondroblastomas. These lung lesions are typically indolent and can be treated definitively with surgical resection. Chest radiographs may be performed annually as part of surveillance imaging.

Key Test Topics

Epiphyseal lytic lesion in a pediatric patient.
Chicken wire calcification in between cobble-stone chondroblasts and the presence of chondroid matrix on histology.

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