Peripheral intermediate and high-grade chondrosarcoma
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Peripheral chondrosarcomas grade 2 and 3 are malignant intermediate and high-grade chondrogenic neoplasms originating from the bony surface in the chondral cap of pre-existing osteochondromas as a result of malignant transformation, thus the name secondary peripheral chondrosarcoma 1,2. Secondary peripheral low-grade chondrosarcomas are not covered in this article.
The term ‘chondrosarcoma secondary to osteochondroma’ is discouraged 1.
Intermediate and high-grade chondrosarcomas make up for ~9-10% 3 of secondary peripheral chondrosarcomas the remainder being peripheral low-grade chondrosarcomas. Similarly to their low-grade counterparts, peripheral chondrosarcomas grades 2 and 3 are most often seen in the 3rd and 4th decades of life 1,4.
The diagnosis of secondary peripheral chondrosarcoma is made by a combination of clinical information, the location of the tumor and typical imaging features such as the size of the cartilaginous cap 1, 5,6. In addition to imaging features pointing to a high-grade tumor such as a sizable chondral cap, a diffusely thickened cap type and intraosseous extension of the chondral tumor 5 the presence of mitoses and nuclear pleomorphism on histology aid in establishing the correct diagnosis 6. However, it is important to note that tumor grade determined by preoperative biopsy seems to be inaccurate in a significant number of cases 7.
Diagnostic criteria according to the WHO classification of soft tissue and bone tumors (5th edition) 1:
cartilaginous tumor originating from a pre-existing osteochondroma or evidence of a precursor lesion stalk
cartilaginous cap with a size exceeding 2 cm, perpendicular to the bone-cartilage interface (tidemark)
presence of mitoses and/or nuclear pleomorphism
A longstanding mass lesion with recent enlargement and/or pain are typical symptoms. Tumor growth after puberty or skeletal maturity is suspicious 1. Depending on the location of the tumor limited joint motion or neurological symptoms might occur 1.
Peripheral chondrosarcomas grades 2 and 3 are malignant intermediate and high-grade cartilaginous neoplasms evolving at the surface of bone within the cartilaginous cap of pre-existing osteochondromas 1-3.
Individuals with osteochondromas in particular multiple osteochondromas at risk of tumor progression with an estimated risk of ~5%.
The most common sites involved are the pelvis, trunk and proximal femur 1,3.
Grossly, peripheral chondrosarcomas grades 2 and 3 are characterized by the following features 1:
lobular translucent blue-white tumor
focal areas with myxoid and cystic changes
lobular cartilaginous cap exceeding 2 cm
possibly recognisable osteochondroma stalk
Histomorphologically, peripheral intermediate and high-grade chondrosarcomas are identical to central intermediate and high-grade chondrosarcomas and display the following microscopical features 1,6:
cartilaginous matrix-producing tumor
coarse and irregular calcifications
presence of nuclear pleomorphism and mitoses
sometimes evidence of endochondral ossification and a pre-existing osteochondroma
cystic spaces with mucoid material
binucleated cells, areas of necrosis
Similar to central intermediate and high-grade chondrosarcomas, secondary peripheral intermediate and high-grade chondrosarcomas are associated with chromosomal instability and complex karyotypes probably due to alterations in p53 and RB1 signaling pathways. As opposed to peripheral low-grade chondrosarcomas where EXT-mutant and EXT-wildtype cells coexist, EXT-wildtype cells predominate in peripheral intermediate and high-grade chondrosarcomas 1. Mutations in IDH1 and IDH2 are absent 1.
General radiographic signs of secondary peripheral high-grade chondrosarcoma overlap with the imaging features of other peripheral cartilaginous tumors especially low-grade peripheral chondrosarcoma and periosteal chondrosarcoma.
Radiographic features of peripheral chondrosarcomas include the following 9,10:
enlargement of a previously non-growing osteochondroma after skeletal maturation
irregular or indistinct lesion surface
intralesional focal osteolytic areas
irregular lesion calcification
extensive erosion or destruction of the adjacent bone
soft tissue mass with scattered or irregular chondral calcifications
The cartilage cap of peripheral chondral tumors including osteochondromas, and peripheral low-grade and high-grade chondrosarcomas is best evaluated with fat-saturated T2 weighted images 9-12. The cut-off thickness of the chondral cap >2 cm measured from the tidemark of the subchondral bone plate has high accuracy for the differentiation towards osteochondromas 10.
Additional features indicating peripheral high-grade chondrosarcoma include the following 5:
diffuse cap type (>75% of the circumference of the cartilage cap thickened)
greater cap thickness
T1: low signal vs muscle
T2/STIR: high signal intensity with punctate or curvilinear signal voids indicating matrix mineralization 9,10
T1 C+ (Gd): peripheral and septal enhancement
Increased uptake on bone scintigraphy indicates peripheral chondrosarcoma 7.
The radiological report should include a description of the following 5,9-12:
tumor size and location (tubular bones of extremities, axial skeleton)
intralesional calcifications with irrelugalities and/or lytic zones
the thickness of the cartilaginous cap 5
measured from the tidemark of the subchondral bone plate: cut-off value >2 cm, but high-grade tumors tend to have thicker caps
estimation of the abnormally thickened cap type (focal/regional/diffuse) 5
involvement of the stalk
adjacent bone destruction
presence of metastases
Treatment and prognosis
Surgical excision with wide margins is the treatment of choice 1,13. Prognosis is significantly worse than for their low-grade counterparts with a mortality rate of slightly more than 20% 13.
Like in peripheral low-grade chondrosarcoma, recurrences are a major problem with multiple recurrences being quite common 13.
The main complication is local and distant tumor recurrences 1. Peripheral high-grade chondrosarcoma might have metastases.
History and etymology
Chondrosarcomas as well as their differentiation into central and peripheral chondrosarcomas was first described by the American bone pathologists Louis Liechtenstein and Henry Lewis Jaffe in 1942 14. The designation of secondary peripheral intermediate and high-grade chondrosarcomas as a separate entity within the WHO classification of bone tumors happened in the fourth edition 15.
The main differential diagnoses of low-grade peripheral chondrosarcomas are 5,9-11:
dedifferentiated chondrosarcoma: bi-morphic histomorphology
central intermediate and high-grade chondrosarcoma: no stalk or evidence of osteochondroma,
low-grade peripheral chondrosarcoma: smaller cap thickness, focal or regional cap type
osteochondroma: cap thickness <2 cm
periosteal chondrosarcoma: no precursor osteochondroma, association with the periosteum
periosteal chondroma: originates from periosteum or the bony surface; lesion size <3 cm 16