Chondrosarcoma

Chondrosarcoma is a malignant tumour whose cells produce cartilaginous matrix. It is the second most common primary malignant bone tumour after osteosarcoma, about 20% of primary bone malignancies, with an annual incidence of roughly 1 per million. Two things make it a different problem from the other bone sarcomas: the conventional form does not respond to chemotherapy or standard-dose radiotherapy, so surgery has to cure it, and at the low-grade end it is hard to tell from a benign enchondroma.

Who. The conventional type peaks at 50-70 years with a male predominance of 2:1. The clear cell and mesenchymal variants arise in younger patients, 20-40 years. Children are rarely affected, under 1% of cases.

Where. The pelvis and the upper femur (proximal femur and femoral shaft) dominate; the flat bones (the ribs, especially the costal cartilage, and the scapula) and the proximal humerus follow. Hands and feet are rare sites, the reverse of enchondroma.

Cartilage biology and treatment resistance. Chondrosarcoma arises from malignant transformation of chondrocytes, and the tissue those cells make explains the treatments that fail. Cartilage matrix is avascular: no blood vessels penetrate it, so drugs reach the tumour cells poorly, the environment is hypoxic, which reduces the efficacy of radiotherapy, and drug-resistance proteins are highly expressed. The cells themselves have a low mitotic rate, especially in grade I lesions, and low metabolic activity, which contributes to the imaging patterns; they produce abundant matrix, proteoglycans and type II collagen, and grow as lobules separated by fibrous septa.

Primary and secondary tumours. Central chondrosarcoma arises de novo in previously normal bone in 75% of cases and by malignant transformation of an enchondroma in 25%; transformation of an osteochondroma is rare. Suspect a secondary tumour when a long-standing, asymptomatic cartilage lesion becomes painful or enlarges. Two premalignant settings, one central and one peripheral, must be known.

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Histological grading. Grade is the most important prognostic factor for chondrosarcoma, correlating directly with survival, metastatic potential and local recurrence. It rests on cellularity, nuclear features and mitotic activity, and it needs adequate tissue and expert pathology: a needle biopsy can sample only the low-grade areas of a heterogeneous tumour, and up to 10% of tumours show grade progression in different areas, which is why the biopsy is aimed at the most aggressive-looking part of the lesion (Investigations).

Nomenclature. WHO now calls a grade I lesion in a long bone an atypical cartilaginous tumour (ACT), deliberately reserving "chondrosarcoma grade 1" for the axial skeleton and pelvis, because behaviour differs by site. The treatment consequence of that split is set out under Management.

Subtypes. Central (conventional) chondrosarcoma accounts for 85% of cases; the four variants that follow are rare, and each breaks one of the conventional tumour's rules, of site, age, grade or treatment.

Central (Conventional)Clear CellPeriostealMesenchymalDedifferentiated

Central (conventional) chondrosarcoma arises in the medullary cavity, peaks at 50-70 years and favours the pelvis and proximal long bones. Histologically it is lobulated hyaline cartilage. On imaging it is a central medullary lesion with rings-and-arcs calcification and endosteal scalloping; a soft-tissue mass appears in the higher grades.

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Clear cell chondrosarcoma is a rare low-grade variant, under 2% of cases, and it breaks the usual rules of site and age: it sits in the epiphysis and presents at 20-40 years. The cells have clear, glycogen-rich cytoplasm, and the lesion can mimic chondroblastoma. It recurs locally in 15-20%, metastasises rarely (under 5%) and has an excellent prognosis after adequate resection, with one caveat: late recurrence is characteristic, so surveillance must run well beyond five years.

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'Low grade' here does NOT mean curettage - this is the exception to the atypical cartilaginous tumour rule

Elsewhere on this page a grade I lesion in a long bone is an atypical cartilaginous tumour, and intralesional curettage is an appropriate, evidence-supported option. Do not carry that rule across to clear cell chondrosarcoma. It is a distinct entity, not conventional grade 1, and it requires wide en-bloc resection.

The two are easy to conflate because both are called low grade and both sit in a long bone - but clear cell is epiphyseal, occurs in the skeletally MATURE (20-40 years), and behaves as a malignancy: intralesional curettage contaminates the joint and soft tissues and produces local recurrence rates several-fold higher, with recurrences that can return at higher grade. The characteristic clinical story is a lesion curetted elsewhere as a presumed chondroblastoma or bone cyst, returning years later.

The discriminator to reach for is the physis: an epiphyseal cartilage lesion in an OPEN physis is usually chondroblastoma, benign, painful and in a younger patient; the same appearance with a CLOSED physis should raise clear cell chondrosarcoma or giant cell tumour. Under the microscope the clear cell chondrosarcoma cells are larger, with more abundant clear cytoplasm, than those of chondroblastoma, and a negative H3K36M immunostain supports the shift, though it does not exclude chondroblastoma. See Clear Cell Chondrosarcoma.

Periosteal (juxtacortical) chondrosarcoma arises from the periosteum on the surface of the bone rather than in the medullary cavity, in the hands, feet and long-bone metaphyses. It is usually low grade (I-II) and carries a better prognosis than a central tumour of the same grade, because it is detected earlier and a wide margin is easier to achieve. Treatment is wide local excision, preserving the medullary canal if possible; recurrence is low with adequate margins and metastases are very rare.

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Mesenchymal chondrosarcoma is a rare high-grade variant, under 5% of cases, seen at 20-30 years in the ribs, jaw and pelvis. It is biphasic, small round blue cells with islands of cartilage, and the HEY1-NCOA2 fusion is diagnostic. It metastasises early to lung and bone, recurs locally in 40-50%, and 5-year survival is 55%. Treatment is wide resection plus chemotherapy: unlike conventional chondrosarcoma, the mesenchymal type may respond to the regimens used for Ewing sarcoma, and radiotherapy has a role as well (Management).

Dedifferentiated chondrosarcoma, 5-10% of chondrosarcomas, carries the worst prognosis of any subtype. It is a biphasic tumour, low-grade cartilage lying beside a high-grade non-cartilaginous sarcoma (osteosarcoma, fibrosarcoma or undifferentiated), in a patient of 60-70 years, most often in the pelvis or femur. It metastasises early to the lung, recurs locally in 50%, and 5-year survival is 7-24%. It is treated as a high-grade sarcoma despite the cartilage component: wide resection plus neoadjuvant chemotherapy (Management).

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Imaging Clue

Suspect dedifferentiated chondrosarcoma when imaging shows a biphasic pattern: a typical chondroid lesion with an adjacent non-mineralised aggressive soft-tissue mass. The high-grade component shows lytic destruction and soft-tissue extension.

Chondrosarcoma is staged with the Enneking system for musculoskeletal sarcomas, which combines grade, compartment and metastasis into a stage that predicts survival. A tumour is intracompartmental (T1) while it is confined within the cortex or a single anatomic compartment, and extracompartmental (T2) once it extends beyond the cortex into the soft tissues or crosses a major fascial plane.

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Symptoms. Pain, dull and aching, is the presenting complaint in 70-80% of patients and a palpable mass in 50%. Pathological fracture is rare, 5-10%, but signals aggressive biology, and some lesions are incidental findings on imaging done for something else. Progression is slow, over months to years; rapid onset of symptoms points to a higher-grade lesion, and pelvic tumours present late because of their deep location.

When a cartilage lesion has turned. New pain in a previously asymptomatic cartilage lesion, or pain that progresses despite conservative treatment, suggests malignant transformation. Age over 40 with a new cartilage lesion, an axial or proximal long-bone site (enchondromas favour the hands) and cortical destruction or a soft-tissue mass all point the same way; the size and scalloping thresholds are under Investigations.

Examination. A mass, when present, is firm, deep and fixed to bone, with tenderness over the lesion; movement may be restricted if the lesion is juxta-articular, and deformity or crepitus mark the rare pathological fracture. The patient is usually systemically well, lymph nodes are not typically involved and metastases are rare at presentation, but examine the chest and record the neurovascular status, assessing for compression.

Algorithm

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Treatment by Grade and Location

Grade I (Low-Grade)Grade II-III (High-Grade)Dedifferentiated TypePelvic Chondrosarcoma

The goal is cure with negative margins and preserved function, and, for the long-bone lesion, no more surgery than the tumour needs. Stage with MRI of the entire bone and a CT chest, and consider PET-CT if the diagnosis is uncertain.

Where the site decides the operation. A grade I tumour of the axial skeleton or a flat bone, and any lesion with soft-tissue extension, is treated by wide resection with a 1-2cm margin; limb salvage is usually achievable and the defect is reconstructed with an allograft, an endoprosthesis or an arthrodesis. A grade I lesion of a long bone that is confined to bone is an atypical cartilaginous tumour, and for it intralesional curettage with an adjuvant, or observation, is an evidence-supported option, as the warning below sets out. There is no adjuvant treatment: chemotherapy is ineffective, and radiotherapy is reserved for the unresectable tumour with positive margins. Surveillance follows the schedule under Postoperative Care.

Grade I / atypical cartilaginous tumour: do NOT wide-resect a long-bone lesion by reflex

The old teaching that every chondrosarcoma, including grade I, needs a wide resection is out of date for the appendicular skeleton, and following it causes real harm - a segmental defect and reconstruction instead of a curettage in a tumour that rarely metastasises. The WHO split between the atypical cartilaginous tumour of a long bone and chondrosarcoma grade 1 of the axial skeleton exists because the evidence follows the same split:

• Long bone, confined to bone (Enneking IA): intralesional curettage with an adjuvant is a safe and reasonable option - 5-year disease-free survival was 97.0% in 37 long-bone lesions treated this way, with a mean MSTS score of 27.9.
• Flat bone (pelvis, scapula, ribs), or any lesion with soft-tissue extension (Enneking IB): this is where curettage fails. Disease-free survival fell to 80.0% in flat bones (p=0.001), and every recurrence in the series had presented with soft-tissue extension. These need wide resection.

Observation is also a legitimate option, not a fringe view. Among 228 patients with radiologically aggressive long-bone cartilage lesions, 153 observed and 75 curetted, MSTS scores were essentially identical (97% versus 96%) but the observed group had significantly FEWER functional limitations - and for lesions over 4.4 cm surgery was significantly worse on both function and pain. The authors concluded that more of these lesions could simply be watched, provided follow-up is guaranteed.

The figure sometimes quoted for recurrence after intralesional treatment of low-grade disease - anything approaching 50% or more - does not match these series, where recurrence after curettage was in the low single figures for long-bone lesions confined to bone. Reserve wide resection for the axial skeleton, flat bones, soft-tissue extension, and any lesion that is not truly low grade.

The goal is wide resection with negative margins and control of metastatic disease. Staging is MRI of the entire bone and a CT chest, essential because lung metastases are present in 10-20%, with PET-CT or a bone scan for distant disease.

Resection. Wide resection with 2-3cm margins, removing the whole tumour en bloc with a cuff of normal tissue and the biopsy tract; neurovascular sacrifice may be required. The reconstruction is chosen by site and patient:

• Endoprosthesis: proximal or distal femur, allowing immediate weight-bearing
• Allograft-prosthetic composite: joint reconstruction that keeps bone stock
• Massive allograft: preserves bone stock in the young patient
• Amputation: when neurovascular sacrifice is required or limb salvage has failed

Adjuvant therapy. Chemotherapy is generally ineffective and not routinely used. Radiotherapy is reserved for the unresectable tumour or positive margins, at 60-70 Gy; for a grade II tumour, consider adjuvant treatment if the margin is close. Selected lung metastases may be resected.

Margin Status is Critical

Margin status is the most important surgical factor for local control. Positive margins raise the local recurrence risk from under 10% with negative margins to 40-60%, so re-resection should be considered whenever the margin is positive and it is anatomically feasible.

Treat it as a high-grade sarcoma despite the cartilage component, with full staging on a high-grade sarcoma protocol: CT chest, PET-CT, and MRI of the entire bone and the adjacent joint.

Chemotherapy comes before surgery, unlike conventional chondrosarcoma, because the target is the high-grade non-cartilaginous component. The regimens are doxorubicin and ifosfamide or high-dose methotrexate, with response assessed on imaging after 2-3 cycles. Surgery is then wide resection with negative margins; amputation is often required because of aggressive local spread, and limb salvage is considered if the response to chemotherapy has been good. Afterwards the chemotherapy protocol is completed, a total of 6 cycles, radiotherapy is given for positive margins, and surveillance is aggressive because the metastatic rate is high.

The most challenging location, because the tumour presents late and the resection is difficult. Planning starts with a CT with 3D reconstruction, an MRI of the pelvis for neurovascular involvement and the sacral plexus, angiography with a view to preoperative embolisation, and a judgement of resectability by the type of pelvic resection required.

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The resection types, and what each costs:

• Type I: iliac wing, the best prognosis; no reconstruction is required because the segment is non-weight-bearing
• Type II: periacetabular, the most common; reconstructed with a saddle prosthesis or custom implant, or by hip transposition of the proximal femur onto the remaining ilium
• Type III: pubic rami
• Type IV: sacral, the worst prognosis

Adequate margins are often anatomically impossible, blood loss is massive (type and crossmatch 6-10 units), and the sacral plexus may have to be sacrificed. Where life expectancy is limited, no reconstruction is a legitimate choice.

Pelvic Chondrosarcoma Prognosis

Pelvic chondrosarcoma has a worse prognosis than appendicular disease (5-year survival 30-60% versus 70-90%) because of late presentation, the difficulty of achieving wide margins, and a higher local recurrence rate (30-50%).

Role of Radiotherapy

Conventional chondrosarcoma does not respond to standard radiation doses, which is the accurate form of the "radio-resistant" claim and the reason radiotherapy is not standard treatment; conventional photon radiotherapy gives local control in under 50%. Where it is used, the dose has to be high: 60-70 Gy with conventional photons, 70-80 CGE with protons. Proton beam therapy is the technique for skull-base lesions, and carbon-ion radiotherapy is emerging.

The indications are therefore few:

• Unresectable tumours (skull base, axial spine), where high-dose proton or carbon-ion therapy achieves control that photons at conventional doses do not
• Positive margins when re-resection is not feasible
• Palliation of metastases
• Mesenchymal chondrosarcoma, the subtype routinely given Ewing-type chemotherapy and radiotherapy rather than surgery alone

State the mesenchymal evidence carefully. Xu's systematic review of 107 patients (PMID 25849226) found that neither anthracycline-based chemotherapy nor radiotherapy was associated with overall survival, and recommended radiotherapy specifically as salvage for a positive margin to improve local control. Radiotherapy for this subtype is standard practice by extrapolation from small round cell biology, not a demonstrated adjuvant survival benefit, and the negative margin remains the part with evidence behind it.

The two reconstructions rehabilitate differently for one reason: a metal implant is stable the moment it is fixed, whereas an allograft has to incorporate and remodel before it can be loaded. That difference sets the weight-bearing rule in each protocol.

Surveillance Protocol

The schedule. Every visit is a clinical examination, a chest radiograph (PA and lateral) and local imaging (radiograph or MRI), with a CT chest if there is anything concerning. The interval lengthens as the risk falls, but it never reaches zero:

• Years 1-2: every 3 months, the highest-risk period
• Years 3-5: every 6 months
• Beyond 5 years: annually, for life, because late recurrences are possible

The reconstruction is watched too. Annual radiographs look for loosening, wear and subsidence of an endoprosthesis, and for fracture, nonunion and collapse of an allograft, with earlier imaging for pain or functional decline.

Where it spreads. The lungs take 90% of metastases and bone the remaining 10%, the latter especially with the higher grades, and metastases can appear late, 5-10 years after resection. The metastatic rate rises with grade, as the table shows.

Global Epidemiology

Chondrosarcoma is the most common primary bone sarcoma in adults and the second most common primary bone malignancy overall (after osteosarcoma), with an annual incidence of roughly 1 per million population worldwide. Population-based registry data (SEER) confirm a steep prognostic gradient by subtype: median survival ranges from around 97 months for juxtacortical lesions down to only about 11 months for dedifferentiated tumours, with metastatic disease at diagnosis the dominant independent predictor of death across all subtypes (Amer et al., J Orthop Res 2020 — PMID 31498474).

Practice Variation

Multidisciplinary Team Composition

Essential members:

• Orthopaedic oncologist (surgeon)
• Medical oncologist
• Radiation oncologist
• Musculoskeletal radiologist
• Musculoskeletal pathologist
• Specialist oncology nurse
• Physiotherapist, occupational therapist
• Psychologist, social worker