Benign Cartilage Lesions

Definition

Enchondroma is a common intramedullary benign neoplasm composed of mature cartilage. It has a limited growth potential, and a majority of enchondromas are small, asymptomatic lesions less than 3 cm in diameter.

Incidence and Location

Enchondroma is a frequently occurring benign tumor that, in different series, accounts for 12% to 24% of benign bone tumors and 3% to 10% of all bone tumors. The age of patients varies widely, and in some series, enchondromas are fairly evenly distributed throughout all decades of life. In other series, the peak age incidence seems to be during the third and fourth decades of life. More than 60% of patients are age 10 to 40 years. There is no clear sex predilection, and the male-to-female sex ratio is about 1 : 1. The small bones of the hands and feet are the most frequent anatomic sites for enchondroma, and approximately 60% of cases are located in these sites. The small bones of the hands are more frequently involved than the bones of the feet (ratio approximately 7 : 1). Involvement of the long tubular bones is next in frequency. The femur is the most frequently involved long tubular bone and makes up approximately 17% of all cases. Enchondromas of the femur are typically located near the proximal or distal ends. Midshaft involvement is very rare. The proximal humerus is involved in approximately 7% of cases. Enchondromas occur less commonly in the bones of the forearm, tibia, and fibula. They are very rare in the pelvis, ribs, scapulae, and vertebrae. Moreover, in several major series of bone tumors, there is not a single report of an enchondroma in the craniofacial bones. In general, enchondromas are extremely rare in the sites most commonly affected by chondrosarcoma: the trunk bones. To the contrary, they occur frequently in the acral skeleton, where chondrosarcomas almost never occur. The site where significant overlap between the skeletal distribution of enchondroma and chondrosarcoma occurs is in the long tubular bones, where both lesions occur with similar frequency. The peak age incidence and most common sites of enchondroma are depicted in Figure 6-1 .

Clinical Symptoms

Typically, enchondroma is an asymptomatic lesion incidentally discovered on radiographs or radioisotope scans performed for other reasons. In the small bones of the hands and feet, an enchondroma can expand the bone contour and present as a palpable mass. Pathologic fracture can be the presenting sign of enchondroma in phalanges, metacarpals, and metatarsal bones. Pain in cartilage lesions often correlates with growth activity. Therefore, if such growth cannot be explained by recent injury, pathologic fracture, or the presence of other unrelated conditions, pain should raise the suspicion of malignancy.

Radiographic Imaging

Enchondroma produces a localized, radiolucent defect with punctate or less frequently linear calcifications (see Figs. 6-2 to 6-5 ). Whether the lesion is sharply defined or has indefinite outlines within bone depends on the skeletal site. The degree of the radiographic calcification can vary considerably. Occasionally, there may not be a sufficient amount of mineralization to be detected on plain radiographs, and the lesion can be purely lytic in appearance (see Figs. 6-6 and 6-7 ). In some radiolucent lesions, computed tomographic (CT) imaging may reveal the presence of calcifications. On magnetic resonance imaging (MRI), calcifications appear as small signal voids. MRI is better suited to demonstrate the noncalcified chondroid lesions within the marrow cavity as a low-signal–intensive area on T1-weighted images and a high-signal–intensive area on T2-weighted images (see Figs. 6-2 to 6-5 ). In the major long bones, the cortex and bone contour are usually not altered, and there is no periosteal new bone formation (see Figs. 6-2 to 6-6 ). Enchondromas that fill the medullary cavity of short tubular bones may show some cortical thinning (see Figs. 6-6 and 6-7 ). The contour of the small bones is typically expanded along with cortical thinning. Radiographic evidence of true extension into soft tissue with a completely disrupted cortex, as well as the presence of reactive periosteal new bone formation, should be regarded as indicators of malignancy. In rare cases, eccentric expansion of one cortex can produce the picture of enchondroma protuberans ( Fig. 6-8 ). In the small tubular bones, the lesion is usually diaphyseal, but epiphyseal extension is also frequently present. In the long tubular bones, enchondromas are most frequently located in the metaphysis. A midshaft or epiphyseal localization is extremely uncommon (see Figs. 6-6 and 6-7 ). In the long bones, enchondromas typically do not show distinct outlines on plain radiographs as they tend to do in short tubular bones. On the other hand, MRIs demonstrate their sharply defined, often lobulated borders (see Figs. 6-2 to 6-5 ).

Gross Findings

Although curettage specimen material is the rule, in the occasionally received intact resection specimen the cartilaginous nature of the lesion is easy to recognize on gross examination ( Figs. 6-9 and 6-10 ). Enchondroma is composed of confluent lobules of cartilage. The lobules vary in size from less than 1 mm through several millimeters to more than 1 cm. The periphery of the lesion is often somewhat irregular because the individual lobules can bulge into the adjacent marrow spaces or separate satellite foci can be present. Occasionally enchondroma can grow in the form of sparsely separated small cartilage nodules. Calcifications, ossifications, or both are responsible for foci of ivory-white, and they may accentuate the overall lobular architecture of the lesion when they are concentrated on the periphery of cartilage islands.

Microscopic Findings

Enchondromas are composed of mature cartilage that has lobular architecture ( Figs. 6-11 and 6-12 ). The individual lobules can be separated by normal bone marrow spaces with hematopoietic elements ( Fig. 6-12 ). More frequently, the individual lobules are incompletely separated by thin fibrovascular septa. Individual lobules of cartilage are often partially encased by mature lamellar bone. This feature is well preserved in incidentally resected enchondromas (see Figs. 6-11 and 6-12 ), but can also be observed in curettage specimens ( Fig. 6-13 ). Lobules of cartilage, especially at the periphery of the lesion, can be sparsely separated and may appear as satellite nodules. In rare instances, lobules of cartilage can grow around the lamellar medullary bone ( Fig. 6-12 ). Such a growth pattern should not be confused with the aggressive infiltration of the medullary cavity frequently seen in chondrosarcoma. The overall cellularity is very low, and in general, enchondromas appear very bland and have relatively few chondrocytes more or less evenly distributed within the hyaline cartilage matrix (see Figs. 6-14 and 6-15 ). More frequently, the cells form loosely arranged clusters, at least focally ( Fig. 6-16 ). The individual chondrocytes are small, lie in lacunar spaces, and have small, dark nuclei (see Figs. 6-14 and 6-16 ). In general, the chondrocytes of enchondromas are similar to those seen in normal hyaline cartilage. Occasional binucleated cells and cells with so-called open nuclear chromatin can be present. The presence of more than one chondrocyte in a lacuna should not be considered an ominous finding and is not equated with binucleation or multinucleation of cartilage cells. The chondroid matrix is typically of hyaline type. Foci of fine or coarse calcifications and even of enchondral ossification can be present. Prominent myxoid change should not be present in enchondroma. If present, even when the cellularity is low, it usually suggests malignancy. One exception to this is in the small bones of the hands and feet, which may show prominent foci of myxoid change. In addition, enchondromas of the acral skeleton may show focal areas of hypercellularity with open chromatin architecture ( Fig. 6-17 ). Such features would be considered a sign of malignancy in cartilage lesions of the major tubular bones but are within the spectrum of changes observed in enchondromas of the acral skeleton when combined with nonaggressive radiographic features. However, even at these skeletal sites, the change should be focal and the overall matrix should be hyaline. The lesion is usually clearly demarcated from the surrounding bone, and the periphery of cartilage lobules often shows encasement by a rim of lamellar bone ( Fig. 6-13 ). In addition, especially in the short tubular bones, mild focal scalloping of the inner cortical surface can be present.

Special Techniques

Special techniques are of little or no help in the diagnosis of enchondroma. Ultrastructurally, the cartilage cells have irregular cell surfaces and centrally located nuclei with condensed chromatin and a convoluted nuclear envelope ( Fig. 6-18 ).

Similar to other cartilage lesions, in enchondroma, a thickening of the inner nuclear membrane is present. Immunohistochemically, the cells of enchondroma are positive for S-100 protein and vimentin. Enchondromas express cartilage lineage differentiation markers and invariably show nuclear positivity for SOX9 protein. SOX9 protein is also positive on all other tumors, benign or malignant, that express cartilage lineage differentiation. The cartilaginous nature of enchondroma is clearly evident on conventional hematoxylin-eosin sections, and special techniques are practically never required to support the diagnosis. Special techniques are also of no help in differentiating an enchondroma from a low-grade chondrosarcoma.

Image analysis and DNA flow cytometry show a diploid DNA histogram pattern with low proliferation rate. Cytogenetic studies detect diploid or near-diploid chromosomal complement with structural aberrations and translocations most often involving chromosomes 6, 12, and 24. Occasionally enchondromas may exhibit complex translocations involving several chromosomes such as 12, 15, and 21. Interestingly, chromosomal aberrations involving 6q13-21 have been associated with locally aggressive behavior of several benign cartilage lesions, including enchondroma. Recent identification of isocitrate dehydrogenases 1 and 2 ( IDH1 and IDH2 ) gene mutations mapping to the long arms of chromosomes 2 and 15, respectively, in solitary enchondromas, chondrosarcomas, and multiple enchondromas of Ollier's disease and Maffucci's syndrome provide interesting clues concerning the biology of cartilage neoplasia. Approximately 40% of solitary enchondromas show mutations of IDH1 or IDH2 , whereas nearly 80% of multiple enchondromas and hemangiomas associated with Ollier's disease and Maffucci's syndrome show mutations of those genes, suggesting an important and possible driver role of these mutations in the development of cartilage neoplasia. Surprisingly, the same genes are frequently mutated in gliomas of the central nervous system and acute myeloid leukemia and less frequently in some other solid tumors. More detailed descriptions of the role of the IDH1 and IDH2 genes in the biology of cartilage neoplasia is provided in the section on enchondromatosis below.

Differential Diagnosis

Enchondromas must be distinguished from low-grade chondrosarcomas , particularly when they involve the metaphyses of long bones in middle-aged to elderly patients. The distinction can usually be made on the basis of absence of pain, no disturbance of the architecture of the surrounding cancellous bone or adjacent cortex, and a lack of cytologic atypia. The nuclei of cartilage cells in an enchondroma are small and uniform, and a homogeneous chromatin pattern is present. Multinucleated chondrocytes are infrequent, and the chondroid matrix is well formed, without prominent myxoid features.

Chondroid differentiation in fibrous dysplasia can be distinguished from large solitary enchondromas on radiographs by the more diaphyseal localization and ground-glass appearance of the fibroosseous areas. The presence of fibroosseous elements in the sections adjacent to cartilaginous nodules is diagnostic for fibrocartilaginous dysplasia.

Enchondroma in Different Anatomic Sites

Enchondromas have a very characteristic anatomic distribution that differs significantly from that of chondrosarcoma. For that reason, the specific anatomic location of the lesion and its radiographic features are important and often decisive elements of the differential diagnosis. Therefore we provide separate descriptions of enchondroma with some principles of differential diagnosis in various anatomic sites.

Treatment and Behavior

Enchondromas of long bones that are small and asymptomatic require no treatment. The patient is advised to report the onset of symptoms, particularly any pain in the affected area, and is followed by serial radiographs and clinical evaluation. Lesions that are borderline in size, symptomatic, or predominantly lytic or that appear otherwise suspicious in nature should be curetted and evaluated under the microscope. It is important to evaluate the entire lesion. Limited sampling may not reveal the focal features indicative of malignancy. Enchondromas of the small tubular bones are frequently treated with curettage and bone grafting, especially if they expand the bone contour or disturb the function of the affected site in any way. The approach to biopsy of suspected cartilaginous lesions of the trunk bones should take into account the fact that most of them are clinically aggressive. In fact, lesions that involve the ribs, sternum, scapula, or pelvis are best treated by wide local excision on the basis of clinical and radiographic evidence and should be subjected to careful pathologic evaluation. This reduces the likelihood of local tissue contamination and thereby decreases the risk of local recurrence if the lesion proves to be low-grade chondrosarcoma. Enchondromas typically heal with consolidation after curettage and bone grafting. Recurrence of enchondroma suggests malignancy, especially in lesions that affect the long bones. Nevertheless, an incompletely curetted enchondroma, especially in the short tubular bones, can occasionally recur and can be successfully treated by a second curettage. Rare and somewhat questionable examples of enchondroma progressing to a chondrosarcoma have been described.

Personal Comments

In the assessment of cartilaginous lesions of bone in general and of enchondromas in particular, it is essential that an orderly and stepwise procedure be followed. The age of the patient and the anatomic site of the lesion should first be considered in addition to the presence or absence of clinical symptoms. The presence of pain is extremely important and may be the only indicator of malignancy. Other causes of pain should be ruled out before factoring this finding into the equation. Pathologic fractures in short tubular bones containing enchondromas are very common and do not suggest unusual aggressiveness.

Next, radiographs should be examined to determine the precise anatomic site, the size of the lesion, the presence of matrix calcification, the character of the lesion's borders, the presence or absence of endosteal scalloping or thickening of the adjacent cortex, the involvement of any associated periosteal bone, and possible extension of the tumor to the surrounding soft tissue. Evidence of multiple lesions or characteristic features of a cartilage dysplasia, such as Ollier's disease, should be sought. Only after these factors have been considered should the histologic features be studied and a diagnostic conclusion reached in the context of all available clinical and radiographic data. Omission of any of these steps or taking “shortcuts” to the diagnosis of a cartilage tumor is fraught with danger. Serious errors have been made in overdiagnosis of incidentally discovered enchondromas, as well as underestimation of medullary cartilage tumors, which, in retrospect, showed indisputable radiologic features of aggressiveness.

Central cartilage tumors of acral parts of the skeleton are almost invariably benign but may become malignant if they are part of the picture of dyschondroplasia (Ollier's disease). Central cartilage tumors of the ribs, sternum, and pelvis are unlikely to be benign, particularly if they exceed 4 cm in size.

Definition

Periosteal chondroma is a benign cartilage neoplasm that develops on the surface of bone under the periosteum. It is also referred to as juxtacortical chondroma.

Incidence and Location

Periosteal chondromas are rare lesions and account for less than 1% of all chondromas. The majority of cases are diagnosed during the second and third decades of life. The limited experience with these lesions indicates that male patients are probably more frequently affected than are female patients. Periosteal chondromas typically affect the long tubular bones of the extremities. The proximal humerus is the single most frequently affected site; nearly 50% of cases are diagnosed at this site. The acral skeleton with the involvement of the short tubular bones of the hands is the second most frequently affected site. Rare examples of periosteal chondroma have been described in the spine, clavicle, ribs, and toes. The peak age incidence and most commonly affected skeletal sites are shown in Figure 6-19 .

Clinical Symptoms

This surface lesion most often presents as a palpable mass. Because periosteal chondromas are frequently found near tendon insertion sites and disturb their function, pain and local discomfort on activity can be initial symptoms. Periosteal chondromas are sometimes discovered incidentally on radiographs.

Radiographic Imaging

Periosteal chondroma presents as a well-circumscribed surface lesion of bone with punctate calcifications on radiographs (see Figs. 6-20 to 6-22 ). The degree of matrix mineralization can vary from purely lytic to heavily calcified (see Figs. 6-20 to 6-22 ). In a typical case, the cartilaginous nature of juxtacortical chondroma is easy to recognize on plain radiographs. The cortex beneath the lesion is usually eroded, with elevated edges forming a craterlike excavation (see Figs. 6-20 to 6-22 ). The presence of an elevated periosteum overlying the lesion is best documented on MRI (see Figs. 6-20 and 6-22 ). It can sometimes be clearly seen on plain radiographs or CT ( Fig. 6-21 ). The affected area may also show minimal evidence of a zone of subcortical sclerosis beneath the lesion. Although the cortex underlying the lesion is excavated, there is no complete cortical disruption, and the lesion is clearly demarcated from the medullary cavity by a continuous rim of cortical bone (see Figs. 6-20 to 6-22 ). CT or MRI may be needed to evaluate the extent of involvement and the relationship between the lesion and adjacent structures. The elevated periosteum surrounding the lesion is represented on plain radiographs by solid buttresses of mature subperiosteal bone that can sometimes slightly overhang the edges of the central excavation. This appearance is quite characteristic for smaller periosteal chondromas.

Gross Findings

On gross examination, periosteal chondroma is a lobulated cartilaginous mass covered by fibrous tissue that represents an elevated periosteum (see Figs. 6-21 and 6-23 ). Calcifications can often be seen within the lobules. The cortex beneath is eroded and usually smoothly excavated, but sometimes it has a scalloped border. The lesion is clearly separated from the medullary cavity by a rim of sclerotic cortical bone. The size of periosteal chondromas varies from less than 1 cm to 5 cm.

Microscopic Findings

Microscopic features are those typical of a chondroma with a hyaline cartilage matrix (see Figs. 6-22 to 6-24 ). On average, juxtacortical chondromas are more cellular than are enchondromas of long bones and can show mild nuclear atypia or binucleated chondrocytes. Scalloping and erosion of the outer cortex are seen microscopically. A sectioning artifact may give the impression of small satellite cartilaginous foci of cellular cartilage in the sclerotic border (see Figs. 6-25 and 6-26 ). This does not indicate invasiveness. Some periosteal chondromas may bulge for a short distance into the underlying medullary cavity, but there is always a border of intervening lamellar bone.

Special Techniques

Similar to enchondromas, periosteal chondromas expresses a full roster of markers characteristic of cartilage lineage differentiation. In such a sense, these lesions are immunohistochemically indistinguishable from ordinary enchondromas. Like enchondroma, periosteal chondromas harbor mutations of IDH1 and IDH2 genes. Several distinct clonal chromosomal abnormalities have been described in periosteal chondromas; they include rearrangements of 2q37, 4q21-25, 11q13-15, and 12q13.

Differential Diagnosis

Juxtacortical chondrosarcoma can usually be distinguished with ease by the large size of the lesion (>5 cm) and the absence of radiologic evidence of solid periosteal new bone buttressing at the margins. The latter is a characteristic feature of periosteal chondroma. Microscopically, the degree of cellularity, variation in size and shape of nuclei, and frequent multinucleate chondrocytes are the basis for differentiating these two tumors. Juxtacortical chondrosarcomas are also more likely to show irregular invasion of surrounding soft tissue and lack the limiting periosteal shell that is present in periosteal chondromas. Periosteal osteosarcoma, a predominantly cartilaginous form of surface osteosarcoma, can be recognized by the feathery perpendicular calcific striae seen on radiographs. Although Codman's triangles may be seen at the limits of this tumor, periosteal osteosarcoma usually lacks the solid buttresses seen in periosteal chondroma. Periosteal osteosarcoma is diagnosed from the presence of sheets of primitive mesenchymal cells between the cartilage lobules, with tumor osteoid and bone deposition between the cells.

Treatment and Behavior

Because periosteal chondromas may demonstrate radiologic overlap with juxtacortical chondrosarcoma, the preferable mode of treatment is wide local excision that includes the underlying cortex. Earlier reports on frequent local recurrences after curettage of juxtacortical chondroma are controversial because some of these lesions might have been surface chondrosarcomas. In selected skeletal sites such as the ribs and fibula, segmental resection is the preferable mode of treatment. In other sites, en bloc excision is preferred over curettage. The latter may be followed by recurrence and require reoperation. Complete local excision of juxtacortical chondroma is a curative procedure. In some instances periosteal chondroma may cause growth disturbance of the affected bone. In such cases the presence of the lesion is associated with shortening of the bone.