Abstract
Definition: Malignant cartilaginous-matrix producing tumors.
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Keywords
- Central chondrosarcoma
- Peripheral (Secondary) chondrosarcoma
- Dedifferentiated chondrosarcoma
- Periosteal chondrosarcoma
- Clear cell chondrosarcoma
- Mesenchymal chondrosarcoma
- Extraskeletal myxoid chondrosarcoma
Definition: Malignant cartilaginous-matrix producing tumors.
CHS varieties and their incidence on 100 cases
Chondrosarcomas varieties | % |
---|---|
• Central | 55–60 |
• Peripheral | 15–20 |
• Dedifferentiated central | 15 |
• Soft tissues | 5–6 |
• Clear cells | 2 |
• Periosteal | 2 |
• Mesenchymal | 1–2 |
• Dedifferentiated peripheral | 1 |
1 Central Chondrosarcoma
Epidemiology: Males. Adult age. Extremely rare in children.
Localization: Proximal femur, pelvis, proximal humerus, scapula, proximal tibia. In long bones, it starts at the metaphyseal extending as far as half or more of the entire bone.
Clinical: Deep, discontinuous, mild pain with small swelling. In the pelvis and at more advanced phases large soft tissue mass is present. Pathologic fractures are rare.
Imaging: On X-ray—intraosseous, osteolytic, geographic lesion with diffused, irregular, granules, nodules, radiopaque rings of calcifications. Sometimes, a bubbling or “honeycomb” feature, metallic or compact opacity. Cortex is scalloped, thinned, and destroyed. Often, it is thickened because the cortical bone reacts to the slow neoplastic infiltration with hyperostosis. Periosteal reaction is faint, with short perpendicular spiculae as a velvet or “beard” appearance. Margins may be sharp, with partial sclerotic rim or ill-defined, faded. It grows where there is less resistance (along the medullary canal). Soft tissue mass are not calcified. On bone scan—increased uptake more than radiographic extension. On angiography—avascular, but there may be a peripheral vascularization around the mass. On CT—typical calcified radiolucency, endosteal scalloping, buttressing, no enhancement, often well contained. May show remnants of prior enchondroma. On MRI—gray homogeneous signal contrasts clearly with white marrow signal on T1, typical bright lesion on T2, unexpected medullary extension on coronal projection.
Histopathology: Lobular, faceted mass of grayer, softer, juicer, more transparent than normal cartilage. Frequent gelatinous, grayish-white, mucoid, hemorrhagic, and necrotic areas. Spots or calcified rings to the periphery of the lobules, hard and gritty, with a chalky yellowish aspect. Grade 1 (20% of the cases): well-differentiated cartilage with increased cellularity compared to enchondroma; chondrocytes are organized in sheets and show slightly nuclear atypia with frequent binucleation; infiltration of the surrounding bony trabeculae is the most important feature in the differential diagnosis with enchondroma. Grade 2 (60% of the cases), hypercellular lesion with hyperchromatic nuclei, frequent binucleate cells, generally in a myxoid matrix; extensive infiltration of the medullary spaces and infiltration of the soft tissues can be present. Grade 3 (20% of the cases): high cellularity with pleomorphic, hyperchromic, gigantic, bizarre cells. Mitotic figures can be found. Diffusely infiltrating the bone marrow spaces with destruction of bony trabeculae and the soft tissue. Point mutations of IDH1/IDH 2 gene are present in about 50% of central chondrosarcomas.
Course and Staging: Very slow growth. Typical progression in malignancy: transformation from a low to high grade or to another malignant tumor. Grade 1: very rare metastases, recurrence even after 10 years. Grade 2: frequent early or late metastases, recurrence within 5 years. Grade 3: higher rate of early metastases, recurrence often within 1 year, usually stage IIB.
Treatment and Prognosis: Wide or radical resections are curative. High risk of recurrence with inadequate margins and when incisional biopsy is not performed carefully because tumoral cells may be implanted in the soft tissue. Lung metastases must be excised. Radio- and chemotherapy are not used because they are poorly effective. Death is rare in grade 1 lesions, but it occurs in 30 and 60% respectively, of grade 2 and 3 lesions.
Key points | |
---|---|
• Clinical | Pain, adults, no children |
• Radiological | Lytic lesion with granular calcifications. Expanded and invaded cortex |
• Histological | Lobules of cartilage infiltrating host trabeculae |
• Differential diagnosis | Chondroma, dedifferentiated chondrosarcoma |
2 Peripheral (Secondary) Chondrosarcoma
Definition: It originates from an osteochondroma on the bone surface.
Epidemiology: Males. Less frequent than central but at a younger age. Adults.
Clinical: Slow growing, hard, painful swelling, adherent to bone. At times, asymptomatic and no history of previous osteochondroma. Invading vertebral canal radicular pain and paraplegia may be present. Patients with multiple exostoses, with germiline mutations in EXT1 and EXT2 genes are at increased risk to develop a peripheral (secondary) chondrosarcoma (up to 5%, as compared to <1% in solitary osteochondroma).
Location: Pelvis (iliac wing), proximal femur (metaphyseal region), vertebral column (posterior arch), proximal humerus, ribs.
Imaging: On X-ray—typical aspect of an osteochondroma with more abundant calcifications or ossifications, intense and diffused radiopacities, with thicker superficial uncalcified layer, with fuzzy margins toward the soft tissue. At times, the implant base of the osteochondroma is still visible or the tumor invades the medullary canal. On bone scan—Intense uptake. On CT—Many, large, non-calcified tumoral lobules, ring-like, popcorn-like radiopacities, higher thickness of the cap of cartilaginous tissue. On MRI—lobulated, ill-defined, inhomogeneous muscular signal intensity on T1, extremely heterogeneous signal intensity on T2 with large foci of signal void due to the calcified areas and with a thick peripheral layer of white signal due to the cap of the lesion.
Histopathology: Large, bumpy, cauliflower-like, with a thin pseudocapsule and thick cap of cartilage, generally more than 2 cm in thickness, chalky and gritty, with hard consistency. Histologically, lobules of well-differentiated cartilage with loss of the architecture of an osteochondroma. Hypercellular areas, nuclear atypia, binucleation, and myxoid matrix can be observed. Cartilage can infiltrate the marrow spaces of the underlining cancellous bone. Infiltration of the surrounding soft tissues, sometimes with satellite nodules, is a sign of malignancy, absent in osteochondroma. Cytogenetic aberration (biallelic inactivation, deletions +/− mutations) of EXT1/EXT2 genes are present in about 90% of cases in multiple osteochondromatosis.
Course and Staging: It grows more slowly than central C, recurrence is observed from a few months to 10 years, <20% of cases have lung and late metastases. Dedifferentiated peripheral C is rare (4%). Usually, stage IB.
Treatment: Wide resection. Inadequate surgery may cause scattered neoplastic nodules in scarring tissue. Radio- and chemotherapy are not effective. Amputation is necessary when it is too large and otherwise inoperable. Peripheral C is less malignant than central because grade 1 forms are frequent and grade 3 rare.
Key points | |
---|---|
• Clinical | Slow increasing swelling |
• Radiological | Osteochondroma with lytic areas |
• Histological | Thicker cap than osteochondroma with loss of the architecture of the osteochondroma |
• Differential diagnosis | Osteochondroma, dedifferentiated peripheral chondrosarcoma |
3 Dedifferentiated Chondrosarcoma
Definition: Cartilaginous malignant tumor in which a high-grade non-cartilaginous sarcoma occurs.
Epidemiology: 15%. >50 years old. Males.
Location: Proximal femur, pelvis, proximal humerus.
Clinical: On a history of long duration with moderate symptoms, a rapid progression of pain and swelling occurs. Pathologic fractures are frequent.
Imaging: On X-ray—(1) old cartilaginous lesion: moderate expansion of the bone with thickened, scalloped cortex, with many calcifications; (2) new lesion: destroying the cortex, involving the soft tissues, dissolving the calcifications, with ill-defined margins. Three different features: (a) pathologic fracture in a new aggressive lytic lesion canceling pre-existing calcifications of an intensely radiopaque old cartilaginous lesion; (b) usual chondrosarcoma aspect with a small high-grade lytic lesion; (c) typical high-grade sarcoma feature with small remnants of chondrosarcoma. On CT—two lesions of different density, matrix, enhancement. On MRI—two different signal intensities on T1 and T2.
Histopathology: Two types of tissue: (1) low-grade cartilaginous tumor; (2) high-grade malignancy, usually an osteosarcoma, an undifferentiated pleomorphic sarcoma, or an undifferentiated spindle cell sarcoma. The transition is sharp. Point mutations of IDH1/IDH2 gene are present in about 50–87% of central dedifferentiated chondrosarcomas.
Course and staging: Fast growth, high risk of recurrence with inadequate surgery, and high rate of metastases, often observed at diagnosis. Usually, stage IIB or III.
Treatment: Wide or radical resection. Chemotherapy protocols of OS have been used with effectiveness. Often, an amputation is necessary to obtain adequate margins. Poor prognosis.
Key points | |
---|---|
• Clinical | Symptoms rapidly increasing. Pathologic fracture possible |
• Radiological | Very aggressive aspects on a low-grade cartilaginous lesion |
• Histological | Two different aspects: low-grade cartilage and high-grade sarcoma |
• Differential diagnosis | Central or peripheral high-grade chondrosarcoma |
4 Periosteal Chondrosarcoma
Definition: Chondrosarcoma originating on the bone surface. The lesion is generally bigger than 5 cm in major diameter.
Epidemiology: Rare, males, adults.
Location: Mainly in the limbs: distal femur, proximal tibia, proximal humerus.
Clinical: Swelling with little or no pain.
Imaging: On X-ray—globose mass lying on the outer surface of the cortex, very radiolucent or with granules, rings, spots of cartilage, rarely bunches of faded ossifications. Outer cortical erosion, saucer-like cortex, thickness of the adjacent cortex, buttress of periosteal reaction, internal sclerotic rim, sharp margins. On CT—confirms periosteal site of the tumor without involvement of the medullary canal.
Histopathology: The lesion is composed of large lobules of cartilage, with variably hypercellularity and atypical cytological features. Intercellular matrix can be myxoid. Permeation in between the underlining bony trabeculae can be seen. Infiltration of the surrounding soft tissues is a sign of malignancy; absent in periosteal chondroma. Point mutations of IDH1/IDH2 gene are present in a subset of periosteal chondrosarcomas.
Course and staging: Rare recurrence if surgery is adequate; late, very rare mets. Usually stage IA.
Treatment: Wide resection. Prognosis is good.
Key points | |
---|---|
• Clinical | Adults, swelling |
• Radiological | Subperiosteal, metaphyseal, with erosion of the cortex, granular calcifications, periosteal reaction |
• Histological | Lobules of cartilage, generally low grade |
• Differential diagnosis | Periosteal chondroma, periosteal osteosarcoma |
5 Clear Cell Chondrosarcoma
Definition: Chondrosarcoma with large amounts of clear cells.
Epidemiology: Rare, males, adults.
Location: Epiphysis or apophysis of long bones (proximal femur and humerus), flat, short bones.
Clinical: Modest, long lasting pain. Femural pathologic neck fracture may occur at presentation.
Imaging: On X-ray—like a chondroblastoma. Osteolytic lesion with small calcifications, sharp margins, irregular and ill-defined sclerotic rim. On CT—spots or small granules typical of the cartilaginous tumors.
Histopathology: Lobular tissue with clear cells: central nucleus, extremely vacuolated cytoplasm, strongly P.A.S. positive. Rare mitotic figures. Peripheral reactive giant cells, possible areas of well-differentiated chondrosarcoma, intercellular calcification like chondroblastoma, cystic spaces, osteoid.
Course and staging: Slow growth, recurrence is possible when intralesional margins are obtained, metastases are exceptional. Usually, stage IA.
Treatment: Wide resection. Prognosis is good.
Key points | |
---|---|
• Clinical | Epiphysis and apophysis in adults |
• Radiological | Osteolytic, like a chondroblastoma |
• Histological | Lobules of clear cells, possible areas of hyaline cartilage, giant cells, calcifications, osteoid |
• Differential diagnosis | Chondroblastoma |
6 Mesenchymal Chondrosarcoma
Definition: Malignant neoplasm composed of small round cells and islands of well-differentiated hyaline cartilage.
Epidemiology: Very rare, no sex predilection, young adults and elderly patients.
Location: Trunk and craniofacial bones. Rare in the limbs.
Clinical: Pain and swelling.
Imaging: On X-ray—osteolytic lesion with permeative destruction of bone, ill-defined margins, breaking the cortex, with soft tissue mass, with faded typical calcifications.
Histopathology: Dense round cells proliferation with hemangiopericytoma-like architecture. Within the tissue there are small foci or larger islands of well-differentiated hyaline cartilage. Osteoid-like matrix can be present.
Course and staging: Fast growth, high rate of recurrence with inadequate surgery and frequent metastases. Usually, IIB.
Treatment: Wide or radical resection. Chemotherapy is used but its real effectiveness is not yet known. Prognosis is poor.
Key points | |
---|---|
• Clinical | Very rare in bone, adults, pain and swelling |
• Radiological | Aggressive osteolysis, with possible calcification |
• Histological | Mixed population with isles of cartilage and undifferentiated round cells |
• Differential diagnosis | None |
Chromosomal translocations | ||
---|---|---|
• t(8;8)(q21.1;q13.3) | HEY1-NCOA2 | >90% |
• t(1;5)(q42;q32) | IRF2BP2-CDX1 | Rare |
7 Extraskeletal Myxoid Chondrosarcoma
Definition: Soft tissue sarcoma composed of spindle and epithelioid tumor cells associated with extracellular myxoid matrix. Extraskeletal myxoid chondrosarcomas are genetically distinct from osseous chondrosarcoma.
Epidemiology: Rare, male/female ratio 2:1, adults (40–70 years).
Location: Deep-seated, proximal extremities and trunk.
Clinical: Enlarging painless soft tissue mass.
Imaging: Although imaging characteristics are nonspecific, most tumors appear lobulated, and highly myxoid tumors have a homogeneous high intensity signal on T2-weighted MRI images. Tumors with necrosis or hemorrhage have a more heterogeneous appearance.
Histopathology: The tumor is composed of cytologically uniform oval to spindle cells embedded in flocculent myxoid ground substance, with fibrous bands dividing individual lobules of tumor. Cells may be arranged as cords, strands, nests, and sheets and typically show uniform dark staining nuclei with indistinct nucleoli. In hypervascular matrix-poor regions, tumor cells often display larger, more vesicular nuclei with visible nucleoli; some tumor cells may have distinctly rhabdoid morphology. Tumor is hypovascular and the matrix stains alcian-blue positive at pH 4.0 and 1.0 (chondroitin sulfate positive). At the genetic level, the majority of tumors exhibit the t(9,22)(q22;q12) translocation involving EWS and CHN genes.
Course and Staging: Five-year survival rates are high (>80%); however, late lung metastases occur, and 10- and 15-year disease free survival rates are considerably lower.
Treatment: Wide surgical excision. Kinase inhibitors’ efficacy (pazopanib) in advanced and non-operable disease is under investigation.
Chromosomal translocations | ||
---|---|---|
• t(9;22)(q22;q12) | EWS-NR4A3 (CHN, TEC, NOR1) | 72% |
• t(9;17)(q22;q11) | TAF2N-NR4A3 (CHN, TEC, NOR1) | 16% |
• t(9;15)(q22;q21) | TCF12-NR4A3 (CHN, TEC, NOR1) | <1% |
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Donati, D.M., Bianchi, G. (2020). Chondrosarcomas (CHS). In: Picci, P., et al. Diagnosis of Musculoskeletal Tumors and Tumor-like Conditions. Springer, Cham. https://doi.org/10.1007/978-3-030-29676-6_34
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