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Grade 1 Chondrosarcoma of Bone: a Diagnostic and Treatment Dilemma

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Grade 1 Chondrosarcoma of Bone: a Diagnostic and Treatment Dilemma 149 Original Article Grade 1 Chondrosarcoma of Bone: A Diagnostic and Treatment Dilemma R. Lor Randall, MD, and William Gowski, MD, Salt Lake City, Utah Key Words Enchondromas, by definition, are benign in- Chondrosarcoma, low grade, diagnosis, dilemma, enchondroma, tramedullary cartilage tumors that do not metastasize. treatment They are typically found incidentally. Most commonly, they are found in the metacarpals and their adjacent pha- Abstract langes, but they may occur in the long bones also. Cartilaginous lesions of bone are relatively common and cover a Radiographically, they appear as small cartilage nests (usu- large spectrum from latent enchondroma to aggressive dediffer- ally less than 5 cm in diameter) with multiple intrale- entiated chondrosarcoma. Differentiating among these lesions, par- ticularly benign enchondroma and low-grade chondrosarcoma, can sional calcifications. Occasionally, very mild endosteal be challenging. Differentiating involves assimilation and interpre- scalloping will occur; however, true cortical invasion and tation of clinical, radiographic, and histologic criteria. Molecular the involvement of adjacent soft tissues are rare.1 His- techniques to assist in distinguishing among the various subtypes are tologically, islands of normal hyaline cartilage (Figure 1) being developed, but these techniques have not yielded any clini- are found surrounded by lamellar bone. On rare occa- cally significant contribution. As a result of an imperfect diagnostic schema, a consensus on treatment algorithms has been elusive. This sions, enchondromas will become symptomatic or lead review highlights the specific clinical, radiographic, and histologic to pathologic fracture and will require surgical treatment. criteria currently used clinically to differentiate between benign en- More concerning are the malignant cartilaginous le- chondroma and low-grade chondrosarcoma. We discuss the prom- sions, or chondrosarcomas, the lower grade variants of ise of emerging molecular technologies. Finally, we provide a review which can often be quite difficult to differentiate from be- of the available literature on treatment outcomes, along with a dis- cussion of our own particular preferences. (JNCCN 2005;3:149–156) nign lesions. These are classified in several ways, includ- ing histologic grade (I–III plus dedifferentiated); location within the bone and body (peripheral vs. central, axial Cartilaginous tumors can be found in any bone in the hu- skeleton vs. appendicular skeleton); whether the lesion man body and cover a spectrum of lesions that range from is primary or secondary (arising de novo vs. secondary to 1 completely benign to dangerously aggressive. Although the a premalignant lesion such as an osteochondroma); or radiographic characteristics that are typical of cartilaginous whether it fits into a specific histologic subtype (clear bone lesions can be consistent, specialists are often chal- cell, mesenchymal, base of skull, soft parts). lenged when differentiating among the different varieties. To date, the single most important factor in evaluat- Though difficult, making these distinctions is crucial in ing the malignant potential of a chondrosarcoma is its determining appropriate treatment. histologic grade.2–5 These tumors are divided into three his- tologic grades based on microscopic appearance. Grade I (“low-grade”) tumors most resemble normal hyaline car- From the Department of Orthopedics, Huntsman Cancer Institute & Primary Children’s Medical Center, University of Utah, Salt Lake City, tilage, but may surround areas of lamellar bone (a feature Utah. not seen in benign lesions) or show mild cellular atypia Submitted November 25, 2004; accepted for publication January 4, 2005. including binucleate forms. Grade III (“high-grade”) tu- The authors have no financial interest, arrangement, or affiliation with the manufacturers of any products discussed in the article or their com- mors have significant areas of marked pleomorphism, petitors. Correspondence: R. Lor Randall, MD, FACS, Sarcoma Services, Huntsman large cells with hyperchromatic nuclei, occasional giant Cancer Institute, 2000 Circle of Hope, Suite 4260, Salt Lake City, UT cells, and abundant necrosis. Grade II (“intermediate- 84112-5550. E-mail: [email protected] grade”) tumors lie somewhere in the middle and may have © Journal of the National Comprehensive Cancer Network | Volume 3 Number 2 | March 2005 150 Original Article Randall and Gowski agement options and the salient points of the deci- sion tree will be presented. History and Physical Most patients with a chondrosarcoma will have pain.10–13 Marco et al.13 reported on 58 cases of grade I chondrosarcoma and found that 60% had night pain or rest pain, 21% had vague regional pain, and only 19% had lesions that were encountered inci- dentally in the absence of pain. This is in contrast to individuals with benign cartilaginous lesions (who rarely have pain that can be attributed to the le- sion14) and patients with grade II or III chondrosar- Figure 1 Low power photomicrograph of an enchondroma demon- coma (who will have pain in up to 80% of cases15). strating extensive extracellular chondroid matrix with sparse benign chondrocytes. Patients will present with pathologic fracture in a relatively small number of cases (3%–8%) of low- some aspects of each of those.6 The fourth histologic grade chondrosarcoma.10,13,15 subtype, known as dedifferentiated, is less common. It Subtle clinical findings to be cognizant of include is typically thought of as arising from one of the other antalgic gait, decreased range of motion at adjacent three histologic subtypes or from a benign precursor. joints, and mild atrophy of the affected extremity. Dedifferentiated chondrosarcomas have malignant Rarely, a mild increase in the Westergren erythrocyte spindle cells (with no identifiable cartilage origin) ad- sedimentation rate will be seen, but the remainder of jacent to areas of neoplastic chondrocytes. laboratory findings will be normal. Chondrosarcomas are then staged using either the When the lesion arises in the proximal humeral method of Enneking et al.1,7 or the AJCC method.8,9 metaphysis, a very common site, the clinician must The majority of chondrosarcomas are low-grade le- very carefully differentiate between signs and symp- sions. They are typically seen in adults between the toms arising from the lesion and those arising from third and sixth decades of life and are more common rotator cuff arthropathy. Both can potentially cause in men than in women. The most common locations pain at night. The patient’s presenting interview and are (in order of decreasing frequency) the pelvis, femur, examination must be meticulously documented, be- ribs, humerus, scapula, and tibia. Chondrosarcomas cause symptoms may change with invasive procedures are found most commonly in the metaphysis, but such as biopsy and may obscure both the patient and diaphyseal tumors can occur as well. In general, the physician’s understanding of the disease. prognosis for low-grade lesions is very good, with a very low rate of local recurrence and pulmonary metastasis if adequate resection is performed. Radiologic Findings Metastases as late as 9.8 years, although rare, have Differentiating between the radiographic findings of been reported.2 benign cartilaginous lesions and grade I chondrosar- Distinguishing between low-grade chondrosar- coma can be challenging. Both can show the classic coma and benign enchondroma is perhaps one of the stippled calcified appearance of cartilaginous bony most challenging endeavors in the field of muscu- lesions (Figure 2). Endosteal scalloping can be a hint loskeletal oncology. Even with diligent clinical prac- toward the increasing likelihood that the lesion has tice and advanced radiographic and histologic malignant potential, but it is not necessarily confir- technologies, the diagnosis may still prove elusive. It matory. Murphey et al. published on 95 cases of chon- is the purpose of this review is to highlight some of the drosarcoma, in which 75% had endosteal scalloping difficulties in making this distinction, with a particu- of more than two thirds of cortical thickness versus lar focus on the significant clinical, radiographic, and 92 cases of enchondroma in which 9% had similar histologic features that can assist. A review of man- findings.11 © Journal of the National Comprehensive Cancer Network | Volume 3 Number 2 | March 2005 Original Article 151 Grade 1 Chondrosarcoma of Bone ing polyostotic disease. Using the method of Murphey et al.,11 lesions seen on bone scan can be compared with internal controls. Those lesions showing a higher degree of uptake are more likely to be of higher his- tologic grade. However, most enchondromas exhibit some amount of uptake, and some will uptake sufficient label to erroneously appear as malignancy. Great cau- tion therefore should be used in drawing conclusions from bone scan results, but these results can add to the overall clinical picture and better inform the de- cision making process. Axial computed tomography (CT) can assist in de- termining the extent of bony destruction and in bet- ter delineating bony architecture. CT will also help in better understanding intralesional calcifications. As with plain radiographs, disappearance or change in the nature of calcifications with repeat scanning can suggest malignancy. Magnetic resonance imaging (MRI) can be help- ful in differentiating between benign and malignant lesions in several ways.
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