Chondroblastoma 

Updated: Sep 25, 2020
Author: Timothy A Damron, MD; Chief Editor: Omohodion (Odion) Binitie, MD 

Overview

Background

A chondroblastoma is a rare, usually benign, tumor of bone that accounts for approximately 1% of all bone tumors. In 1931, Codman classified it as a chondromatous variant of giant cell tumors, when he described these lesions in the proximal humerus.[1] A decade later, Jaffe and Lichtenstein renamed the Codman tumor a benign chondroblastoma to emphasize the chondroblastic genesis of the lesion and to distinguish it from the classic giant cell tumor of bone.[2]

Although the exact etiology of chondroblastoma remains uncertain, the presentation, appropriate evaluation, and treatment of patients with the condition have been well described. (See Presentation, Workup, and Treatment.)

Pathophysiology

Various theories have been proposed concerning the pathogenesis of chondroblastomas. Mii et al described the results of ultrastructural examination of chondroblastomas,[3] demonstrating subcellular calcium-containing precipitates similar to those seen in chondrocytes. On the basis of these findings, the authors concluded that the tumors are of chondrogenic origin.

Aigner et al, however, noted the presence of osteoid matrix–containing type I collagen and the absence of true cartilage matrix production.[4] They considered the term chondroblastoma to be a misnomer and believed that the tumor should be reclassified as a bone-forming neoplasm.

Brien et al compared the characteristics of chondroblastoma of bone to chondroblastoma of soft tissue, giant cell tumor of the tendon sheath (GCTTS), and pigmented villonodular synovitis (PVNS).[5] On examination of about 15 examples of GCTTS and PVNS, large areas of chondroid differentiation were noted that could not be distinguished from chondroblastoma of bone by either histologic or electron microscopic features. The researchers theorized that chondroblastoma of bone stems from an intraosseous proliferation of tendon sheath cells that have a predilection for chondroid formation.

Chondroblastomas typically occur in the epiphyses of tubular long bones. The distal femoral and proximal tibial epiphyses are most frequently involved, followed by the proximal humerus, where approximately 18% of chondroblastomas appear.[6]

Etiology

Risk factors for chondroblastoma remain to be established. There have been reports of abnormalities in chromosomes 5 and 8, as well as of p53 mutations, in patients with chondroblastoma.[7] Sjögren et al performed cytogenetic analysis of benign and malignant cartilage tumors, and although no consistent karyotypic abnormalities were oberved, there were recurrent breakpoints seen at 2q35, 3q21-23, and 18q21.[8]

 

Epidemiology

In the United States, chondroblastoma accounts for approximately 1% of all bone tumors. The international incidence is not reported in the current literature.

Approximately 92% of patients presenting with chondroblastoma are younger than 30 years. However, chondroblastomas have been reported to arise in patients as young as 2 years and as old as 83 years. In several large series, most patients were diagnosed in the second decade of life. The male-to-female ratio is 2:1 in most series. No racial predilection is recognized.

Prognosis

Patients with benign chondroblastoma may limit activities because of pain. Malignant chondroblastomas, which may occur many years after the original lesion (even in the absence of radiation), are extremely rare—so rare that chondroblastomas have been reclassified from "rarely metastasizing" to "benign" by the World Health Organization[9] (WHO)—and are associated with a dismal prognosis.

Local recurrence in long-bone lesions is approximately 10% and is higher for chondroblastomas arising in flat bones, especially those lesions arising in the vicinity of the triradiate cartilage. Average time to recurrence is 34 months after initial treatment. Most authors have not reported any significant difference in recurrence rates for tumors, regardless of the age or sex of the patient, the size of the lesion, the amount of calcification or vascular invasion seen on histologic examination, the duration of follow-up, or the method of treatment.

Springfield attributed a higher recurrence rate in patients with open physeal plates to a less aggressive curettage performed in an effort to avoid future growth arrest.[10] Recurrences may be treated with repeat curettage, with or without bone graft or cementation, and with marginal excision of any soft-tissue component.[11]

Whereas most chondroblastomas are small, well-marginated lesions that are successfully treated with intralesional curettage, a small subset of chondroblastomas behave in a much more aggressive fashion. Some of these tumors retain their benign microscopic features but nonetheless become very large or have the capability of metastasizing to the lungs and soft tissues.

Metastases may be synchronous or metachronous, occurring concurrently with the primary bone tumor or up to 33 years later. Metastases can occur even without surgical manipulation or local recurrence of the primary tumor. These more aggressive lesions may be treated with en-bloc resection and reconstruction where intralesional curettage would leave a large, bony defect. Pulmonary implants or soft-tissue metastases should be resected, especially if they are progressive.

Another rare subset of chondroblastomas may become frankly malignant even though no prior radiation therapy was used. Kyriakos et al used the term malignant chondroblastoma to describe tumors that continue to grow or disseminate, not just those that metastasize.[12] Malignant transformation typically occurs many (usually >10) years after treatment of the initial benign lesion. Pulmonary metastases may develop along with the malignant bony lesion.

Microscopic examination of the malignant bone lesion shows features similar to the original lesion (along with other areas with nuclear pleomorphism), abundant and abnormal mitotic figures, tumor necrosis, and intravascular thrombi. Ostrowski et al reported a patient with malignant transformation of a recurrent pelvic chondroblastoma with a p53 mutation.[13] Frankly malignant chondroblastoma tends to be resistant to surgery, radiation, and chemotherapy, and patients with these tumors have had dismal prognoses.

A retrospective study by Farfalli et al focused primarily on long-term joint status and functional outcomes (rather than oncologic outcomes) after curettage for epiphyseal chondroblastoma.[14]  The investigators found that aggressive curettage of epiphyseal chondroblastoma frequently led to osteoarthritis and that tumors in the proximal femur appeared particularly likely to be associated with secondary osteoarthritis and prosthetic replacement.

 

Presentation

History

Pain is the most common presenting symptom of a chondroblastoma. It typically is mild and gradually progressive and initially may be attributed to a minor injury. If the lesion is juxta-articular, the patient may complain of joint swelling or diminished range of motion. Usually, constitutional symptoms are lacking. In their series of 70 patients, Turcotte et al found the average duration of symptoms in patients with chondroblastoma to be 20 months.[15]

Physical Examination

The physical examination is remarkable for localized tenderness in most patients. Soft-tissue swelling, mass, or joint effusion is present in about 20% of cases. Muscular atrophy or decreased joint motion is less common.

 

DDx

Diagnostic Considerations

Chondromyxoid fibromas, which are found in patients in the same age group in which chondroblastomas are found, may mimic the latter radiographically and microscopically. Both types of lesions tend to have well-circumscribed lytic areas on radiographs, microscopically seen areas of immature cartilage and giant cells, and perilesional marrow edema on magnetic resonance imaging (MRI). However, chondromyxoid fibromas most often arise from the metaphysis or metadiaphysis rather than from the epiphysis (where 90% of chondroblastomas are located), are devoid of calcification, and have a characteristic myxoid, pseudolobular pattern of organization, as well as more pleomorphic stellate cells.

Giant cell tumors of bone also may mimic chondroblastomas; the epiphyseal location and histologic characteristics can be quite similar. However, the former are almost exclusively seen in patients who are skeletally mature, whereas chondroblastomas tend to arise in skeletally immature patients. Furthermore, the epicenter of a giant cell tumor lies within the metaphysis. On histologic examination, giant cell tumors have elongated cells that are clustered together, in contrast to the round or polygonal cells of chondroblastoma. Calcifications and chondroid matrix also are absent in giant cell tumors. 

Eosinophilic granuloma is a lesion found in young patients that may appear in rare instances as a radiolucent epiphyseal lesion similar to chondroblastoma. However, microscopic examination reveals a more heterogeneous collection of cells, including histiocytes, granulocytes, and eosinophils.

Chondroblastomalike osteosarcoma may be confused with chondroblastoma.[16]

Finally, clear cell chondrosarcoma may have features that overlap those of chondroblastoma, but the presence of large cells with abundant clear cytoplasm and vesicular nuclei, as well as type II collagen and malignant chondrocytes, should distinguish this tumor. Typically, clear cell chondrosarcoma is an epiphyseal tumor of adulthood. 

Although an epiphyseal or apophyseal location is classic for chondroblastoma and extension into the metaphysis may be seen, purely metaphyseal or diaphyseal chondroblastomas have been reported. A series of seven such cases suggests that they follow the same pediatric age distribution as their classic counterparts and, apart from their unusual location, have similar radiographic features, including extensive perilesional edema on MRI.[17]  Biopsy is still required to confirm the diagnosis, and treatment remains the same.

Differential Diagnoses

 

Workup

Imaging Studies

On radiographic images, chondroblastoma is characterized by a well-defined osteolytic lesion involving an epiphysis or secondary ossification center (see the following image).[18] In 30-50% of cases, internal calcifications will be seen within the lesion. The tumor may make the bone seem somewhat expanded with a sclerotic margin. The average size of the tumor (along its longest diameter) is 4.5 cm.

Plain film of the hip shows a femoral head with a Plain film of the hip shows a femoral head with a lytic lesion with surrounding sclerosis in the epiphysis of the proximal femur. Internal matrix formation is not present, but that finding can be a feature of this tumor.

Adequate regional radiographs should be obtained in patients with suspected chondroblastoma. (See the images below.)

Radiograph of epiphyseal lesion (hip). Radiograph of epiphyseal lesion (hip).
Radiograph demonstrating tumor on both sides of ph Radiograph demonstrating tumor on both sides of physis (humerus).

A bone scan (see the image below) may be helpful in assessing a lesion's biologic activity; it can also aid in locating other regions of disease involvement that may result from entities other than a chondroblastoma or from the rare occurrence of multifocal chondroblastomas.

Bone scan. Bone scan.

Magnetic resonance imaging (MRI; see the image below) should be conducted if any question exists about the diagnosis or lesion boundaries, including perilesional soft-tissue extension or edema.

Magnetic resonance image of a hip showing lobular Magnetic resonance image of a hip showing lobular pattern of chondroblastoma.

On T1-weighted MRI, the tumor can show up as hypointense to intense (see the image below).[19] T2-weighted images show up as isointense to hyperintense.[20] On these images, the chondroblastoma may mimic aneurysmal bone cysts, which are also expansile and osteolytic. The observation of fluid levels and septations will distinguish the cyst.

Coronal T1-weighted sequence shows a lesion of the Coronal T1-weighted sequence shows a lesion of the epiphysis with medium signal intensity. Small islands of matrix are noted.

Computed tomography (CT) may be helpful in defining the extent of the lesion within the bone, especially if the bone is in a more anatomically complex area, such as the hand, foot, or spine.

Benign pulmonary metastases occasionally may occur with chondroblastoma; therefore, a chest radiograph should be obtained. A CT scan of the chest may be used to further evaluate any suspicious areas. These pulmonary lesions are resectable and curable.

Tissue Diagnosis

If malignancy is not suspected on the basis of clinical and radiographic features, tissue may be obtained for diagnosis at the time of surgical treatment of the lesion, and no preceding biopsy is needed. However, histologic confirmation by frozen section should be sought before definitive treatment is initiated. If the lesion appears atypical on appropriate imaging studies, a needle or incisional biopsy should be performed before definitive treatment is undertaken.

Gross findings

In rare instances, the sclerotic border of the chondroblastoma will be scalloped. Curettings are characteristically soft, friable, red to gray, or brown and resemble granulation tissue.[21] Flecks of gritty, calcific material may be observed.[22] When present, cysts usually comprise a small portion of the tumor. Rarely, the cysts are large, such that the tumor grossly resembles a simple cyst.[23]

Histologic Findings

Chondroblastomas are lobulated tumors that consist of grayish-pink soft tissue intermixed with bluish chondroid tissue and calcifications. The lesions may have many hemorrhagic cystic areas.[24]

The tumors are composed of sheets of neoplastic mononuclear chondroblasts with eosinophilic cytoplasm and grooved nuclei (see the image below). Interspersed among the mononuclear cells are osteoclastlike giant cells. The chondroid matrix typically is pink; on rare occasions, the basophilic matrix seen in hyaline cartilage is present. Some chondroblastomas may have a spindle-cell component, which represents either spindle-shaped mononuclear cells or reparative cells of fibroblastic origin.

Histology of chondroblastoma. Histology of chondroblastoma.
Medium-power photomicrograph with lobules of chond Medium-power photomicrograph with lobules of chondroid matrix. In these lesions, the cartilage can be eosinophilic, with superficial resemblance to osseous matrix. Correlation with the radiologic studies is often helpful when in doubt.
Low-power photomicrograph demonstrates islands of Low-power photomicrograph demonstrates islands of hyaline-type cartilage, which can often be seen in chondroblastomas.

One of the most characteristic findings in the histologic examination of chondroblastomas is linear deposition of calcification surrounding individual chondroblasts, creating a chicken-wire pattern (see the image below). Calcification may be so extensive that the chondrocytes in the area are not viable. In sections with well-preserved chondroblasts, mitoses may be seen, but atypical mitoses are not present in benign chondroblastoma.

Chondroblastoma histology demonstrating chicken-wi Chondroblastoma histology demonstrating chicken-wire calcifications.

Cystic changes within chondroblastomas are common. Some represent secondary aneurysmal bone cysts, which are found in 20-25% of all patients with chondroblastomas. Other cysts are filled with serous fluid and are divided into unilocular or multilocular spaces. When these other cysts are present, the tumors are termed cystic chondroblastomas. Initially, there was concern that cystic chondroblastomas had a much higher recurrence rate than typical chondroblastomas, but later reports did not confirm this theory.

Medium-power photomicrograph demonstrates secondar Medium-power photomicrograph demonstrates secondary cystic changes, which can often accompany chondroblastomas. Careful sampling of the tumor will show the correct etiology for the changes noted here.

Less frequently seen histologic findings are cellular atypia with enlargement and irregularity of chondroblast nuclei (occurring in 30% of cases); hemosiderin (in 25% of cases); surrounding cortical and soft-tissue permeation (in 5% of cases); myxoid areas (in 2% of cases); and vascular invasion (in 1% of cases).

Immunostaining occasionally can be helpful in confirming the diagnosis of chondroblastoma.[19] S-100 protein is strongly positive in the mononuclear cells, though it is absent in multinucleated giant cells and is present only focally in tumors with a large cystic component. Chondroblastomas are also positive for vimentin. Reticulin stain reveals a honeycomb pattern.

Immunohistochemistry for S100 is positive in chond Immunohistochemistry for S100 is positive in chondroblastomas and is often helpful, especially when the tissue sample is small.
 

Treatment

Approach Considerations

No evidence suggests that chondroblastoma resolves spontaneously; accordingly, surgical treatment is generally indicated.

Percutaneous radiofrequency ablation (RFA) may be an alternative to surgery for the treatment of certain chondroblastomas,[25] but according to Rybak et al, larger lesions that are under weightbearing surfaces should be approached with caution because of an increased risk of articular collapse and recurrence.[26]

Medical Therapy

Radiation therapy has been employed in the treatment of chondroblastoma but has essentially no current role in its treatment.[27, 25]

Chemotherapy has not been reported in the condition's treatment.

In search of a targeted therapy for patients with disseminated chondroblastoma or those in need of medical management, Yang et al reported positive effects of targeted inhibition of mTOR (mammalian target of rapamycin) and HIF (hypoxia-inducible factor) pathways in benchtop work with chondroblastoma. Combination treatment of low-dose rapamycin, FM19G11, and leucine deprivation were inhibitory on the chondroblastoma cell line examined.[28]

A study by Suster et al demonstrated that chondroblastomas, along with other giant cell–rich bone lesions, expressed receptor activator of nuclear factor-κB ligand (RANKL).[29]  This finding suggested that chondroblastomas might potentially be treatable with RANKL inhibitors such as denosumab, which has previously shown success with giant cell tumors of bone. 

Pain medications should be administered as needed.

Surgical Therapy

The most common surgical procedure used for chondroblastoma is curettage, with or without autograft or allograft bone grafting.[30, 31, 32] Other options, used less frequently, include the following:

  • Substitution of polymethylmethacrylate (PMMA) or fat implantation for bone graft
  • Chemical cauterization (with phenol) of the curetted lesion
  • Liquid nitrogen cryotherapy
  • Marginal resection
  • Wide resection

Large or recurrent chondroblastomas should be managed by an orthopedic oncologist.

Surgical curettage vs radiofrequency ablation

Although open surgical curettage remains the most commonly used treatment, an emerging pool of literature continues to support the safety and efficacy of treatment with RFA.

Studies of longer-term follow-up after conventional curettage and grafting have generally reported excellent results with a low complication rate. At a mean 8-year follow-up of 24 patients treated by curettage and bone grafting, a recurrence rate of only 4% (1/24) was reported by Lehner et al, and 88% of patients achieved good or excellent results.[33] In a report of 14 patients using extended intralesional curettage with high-speed burring, intralesional cryotherapy, and autogenous bone grafting, Mashhour et al noted that the recurrence rate was low (1/14) after mean 4-year follow-up, but two patients experienced growth arrest.[34]

For balance, however, in a large series of 87 purely pediatric chondroblastoma cases, the recurrence rate after curettage and grafting was 32%.[35] Risk factors for recurrence included epiphyseal location (contrasted with metaphyseal, apophyseal, and combined metaphyseal-epiphyseal), proximal femoral lesions, and tarsal lesions. In 63% of the patients, treatment consisted of intralesional curettage with autogenous bone grafting; functional outcome was good for 68.5% of the patients; and 32% of the lesions recurred.[6]

The difficulty of treating femoral head lesions led two authors to publish papers examining that site in particular. In a series of 10 patients with femoral head lesions, a direct approach to the lesion through the femoral neck was favored over curettage through a drill hole within the femoral neck.[36] A trap-door technique was also reported as a successful salvage technique in that series. For a large femoral head defect, a vascularized fibular graft was successfully used to reconstruct the defect created by open surgical treatment.[37]

RFA for chondroblastoma has been described in several reports, but follow-up has been shorter than for surgery, and caution is recommended when the lesions are larger than 2.5 cm and when there is no subchondral bone support. Nevertheless, proponents favor RFA for smaller lesions with intact subchondral bone and difficult-to-access lesions.[38] However, many reports have included fewer than 10 patients, follow-up has been shorter than that for conventional curettage and grafting, and complications have been reported in as many as 20%.[39, 40] Complications of RFA for chondroblastoma have included subchondral fracture, chondrolysis, persistent pain, and need for repeat RFA.

In a study of RFA for chondroblastoma by Rybak et al,[26] 12 of 14 patients available for follow-up (median, 41 months) reported complete relief of symptoms without the need for medications, and all returned to previous activities. One patient, who had the largest lesion, required surgery because of articular collapse in the area of treatment; another required surgical treatment because of mechanical problems. The authors concluded that percutaneous RFA is an alternative to surgery for selected chondroblastomas but that larger lesions under weightbearing surfaces must be approached with caution because of an increased risk of articular collapse and recurrence.

Xie et al carried out a retrospective study of 25 consecutive patients treated with RFA over a period of approximately 7 years.[41] Patients were assessed after 1 month, then every 3-6 months, and then yearly for up to 3 years. Recovery was monitored with serial magnetic resonance imaging (MRI), and functional outcome was quantified with the Musculoskeletal Tumour Society Score (MSTS). The authors found RFA to an effective alternative to surgery in the management of chondroblastoma and suggested that it should be considered as a first-line treatment.

Complications

In addition to recurrence, many complications can occur after treatment of chondroblastomas, including the following:

  • Infection
  • Development of degenerative joint changes
  • Fracture through the lesion
  • Failure of osteoarticular allografts, if used
  • Premature physeal closure and subsequent limb-length discrepancy or angular deformity of the limb
  • Malignant transformation or development of a postradiation sarcoma as late as 18 years after diagnosis (in rare cases in which radiation therapy is used)

Activity

Unless the lesion is particularly large and creates a risk of pathologic fracture, patients may participate in activity as tolerated. If an en-bloc excision is performed, the patient's activity may be limited to protect the reconstruction.

Long-Term Monitoring

In view of the 10% risk of local recurrence, patients should be monitored for at least several years. Monitor patients with open physes at the time of treatment for premature physeal closure.

At follow-up, patients should be evaluated with a thorough history and physical examination and with appropriate radiographs.