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Giant Solitary Synovial Chondromatosis Mimicking Chondrosarcoma: Report of a Rare Histologic Presentation and Literature Review
Synovial chondromatosis (SCM) is a relatively rare benign lesion of the synovium.1 Its pathogenesis has been thought to be a chondral metaplasia of the subintimal layer of the intra- or extra-articular synovium.2 However, evidence supporting a neoplastic cause of the disease is emerging.3 When intra-articular, any joint can be affected, though large joints are more prone to the disease; the knee, hip, and elbow are the most common locations.4 The synovial layer of tendons or bursae can be the origin of extra-articular SCM.5
Synovial chondrosarcoma (SCS), an even rarer pathology, can be caused by malignant transformation of SCM or can appear de novo on a synovial background.6 Histologic differentiation from SCM might be difficult because of the high incidence of hypercellularity, cellular atypia, and binucleated cells.6 Some features, such as presence of a very large mass or erosion of the surrounding bones, have been indicated as possible signs of malignancy.3 An unusual presentation of SCM, giant solitary synovial chondromatosis (GSSCM), can be hard to distinguish from SCS because of the large volume and possible aggressive radiologic findings.7 Some histologic features, such as presence of necrosis and mitotic cells, have been suggested as distinctive criteria for malignancy.8
In this article, we present a case of benign GSSCM with a histologic feature that has not been considered typical for benign SCM. The patient provided written informed consent for print and electronic publication of this case report.
Case Report
An 18-year-old woman presented with a large mass over the right hip. The mass had been growing slowly for 2 years. One year before presentation, a radiograph showed a large hip mass with fluffy calcification (Figure 1), and magnetic resonance imaging (MRI) showed a large nonhomogeneous mass anterior to the hip capsule and extending into the hip joint back to the posterior part of the joint (Figures 2A, 2B). Open incisional biopsy was performed in a local hospital at the time, and the histologic analysis revealed presence of atypical binucleated cells and pleomorphism, in addition to some mitotic activity (0 to 1 per high-power field) (Figure 3). These findings suggested malignancy. The patient declined surgery up until the time she presented to our hospital, 1 year later.
Clinical examination findings on admission to our hospital were striking. The patient had a large mass in the groin region. It was fairly tender and firm to palpation, immobile, and close to the skin. Hip motion was mildly painful but obviously restricted.
The mass was restaged. New radiographs and MRI did not show any significant changes since the previous year, computed tomography (CT) did not show any bone erosion (Figure 4), and chest radiograph, CT, and whole-body bone scan did not demonstrate any signs of metastasis.
Given the clinical presentation and previous histopathologic findings, a diagnosis of GSSCM with possible malignant transformation was made. The patient was scheduled for surgery. During surgery, the tumor was exposed through the Smith-Petersen approach. The mass was extruding under the fascia between the femoral neurovascular bundle medially and iliopsoas muscle laterally. There was no adhesion of the surrounding structures, including the femoral neurovascular bundle, to the mass. The muscle was sitting on the anterolateral surface of the mass, which was considered located in the iliopsoas bursa but extending to the joint. In the vertical plane, the mass extended down to the subtrochanteric area. The entire solid extra-articular mass was excised en bloc, and hip capsulotomy was performed inferior to the area of emergence of the mass. The joint was occupied by a single solid cartilaginous mass molding around the femoral neck, filling the piriformis fossa and propagating to the posterior joint space. Obtaining enough exposure to the back of the joint required surgical hip dislocation. The visualized acetabular fossa revealed chondral fragments, which were excised. Bone erosion or significant osteoarthritis was not detected in any part of the joint. A nearly total synovectomy was performed, leaving the ascending retinacular vessels intact. Meticulous technique was used to avoid contaminating the extra-articular tissues. The wound was closed in the routine way after hip relocation.
The 16×9.5×9-cm mass (Figure 5A) had a conglomerated internal structure (Figure 5B). Multiple specimens from the intra- and extra-articular portions of the mass were sent for histopathologic analysis, which revealed clusters of mature chondrocytes arranged in a lobular pattern and separated by thin fibrous bands. Areas of calcification and ossification were appreciated as well (Figures 6A-6C). No necrosis, mitosis, or bone permeation was detected. These findings were compatible with typical SCM. Given these pathologic findings and the lack of clinical deterioration over the previous year, a diagnosis of GSSCM with extension along the iliopsoas and obturator externus bursae was made. The already-performed marginal excision was deemed sufficient treatment. At most recent follow-up, 38 months after surgery, the patient was pain-free and had good hip range of motion and no indication of recurrence.
Discussion
SCM is a benign disorder emerging from the synovium as a result of proliferative changes in the synovial membrane of the joints, tendon sheaths, or bursae, leading to the formation of numerous cartilaginous nodules, usually a few millimeters in diameter.8 In a rare presentation of the disease, the nodules may coalesce to form a large mass, or a single cartilaginous nodule may enlarge to form a mass. Edeiken and colleagues7 named this previously unrecognized SCM feature as GSSCM when there was a major single mass larger than 1 cm in diameter. There have been other SCM cases with multiple giant masses.9,10 In the English-language literature, we found 15 GSSCM cases, which include the first reported, by Edeiken and colleagues7 (Table). However, earlier SCM cases would be reclassified GSSCM according to their definition.11
The present case brings the total to 16. Nine of the 16 patients were male. Mean age at presentation was 41 years (range, 10-80 years). The knee was the most common GSSCM site (6 cases), followed by the temporomandibular and hip joints (3 each). Regarding gross pathology, 10 lesions were solid, and 6 (including the present one) were formed by conglomeration of the chondromatosis nodules. Lesions varied in size (16-200 mm), and 2 were primarily extra-articular (foot). One common issue with most of the cases was the initial diagnosis of chondrosarcoma. The exact surgical technique used was described for 6 cases (cases 11-16); the technique was marginal excision. In no case was recurrence 14 to 60 months after surgery reported.
This chondroproliferative process is potentially a diagnostic challenge, as distinguishing it from a chondrosarcoma, a more common lesion, could be difficult based on clinical and imaging findings, and, as is true for other chondral lesions, even histologic differentiation of the conditions might not be conclusive.12,13 Confusion in diagnosis was almost universal in this series of patients.
One important differentiating feature of benign and malignant skeletal lesions is the time course of the disease. Malignant tumors are expected to demonstrate rapid enlargement and local or systemic spread. Unfortunately, often SCS cannot be distinguished by this characteristic, as grade I or II chondrosarcoma is usually a slow-growing tumor and does not metastasize early.14 Although lack of recurrence is assuring, recurrence is not necessarily a sign of malignancy, as a considerable percentage of benign chondromatosis lesions recur.8
Radiologic differentiation between SCM and SCS is another challenge. Although bone erosion caused by a lesion not originating from bone is usually considered a sign of malignancy, GSSCM was reported as causing bone erosion in 5 of the 16 cases in our literature review.7,15 Our patient did not experience any bone erosion. However, lack of bone erosion is not a reliable criterion for excluding SCS, and bone erosion was noted in only 3 of the 9 SCS cases in the series reported by Bertoni and colleagues.6 Moreover, tumor size and propagation of tumor to surrounding tissue could be surprising in GSSCM. Large size (up to 20 cm) and extra-articular spread of a lesion originating in a joint are common findings.6,16 Our case was an obvious extension of a hip GSSCM to the iliopsoas and obturator externus bursa, which is the most common pattern of extracapsular spread of hip SCM.17 An interesting feature of the present case, however, was the relatively superficial location of the mass immediately under the fascia.
Calcified matrix is key in diagnosing a chondral lesion on imaging studies, but, in some cases, SCM does not demonstrate any radiographically detectable calcification at time of diagnosis.18 However, all the GSSCM cases reported to date had obvious calcified matrix.
The hypercellularity, cellular atypia, binucleated cells, and pleomorphism in the histologic examination of the present case are not features of malignancy in SCM.8 On the contrary, several other characteristics, including qualitative differences in the arrangement of chondrocytes (sheets rather than clusters), myxoid matrix, hypercellularity with crowding and spindling of the nuclei at the periphery, necrosis, and, most important, permeation of the trabecular bone with the filling up of marrow spaces, have been assumed to be indicative of malignancy.8 Furthermore, Davis and colleagues8 found no mitotic activity in the histopathologic investigation of 53 SCM cases. Even in 3 cases that developed malignant transformation to SCS, mitosis was not found in the initial biopsy specimens before transformation. This was compatible with the common opinion that SCM is not a neoplastic, but a metaplastic, process. Histopathologic data were available for only 8 of the previous 15 GSSCM cases. There were no reports of mitosis, and necrosis was found in only 1 case.16 In our patient’s case, however, the first biopsy did show remarkable mitotic activity. This was not the case for the second biopsy, when mature chondrocytes associated with marked calcification and ossification were prominent features (Figures 6A, 6B). We presume that, within a limited period during earlier stages of tissue maturation in SCM, mitotic activity might be a possible finding. Of note, none of the other aforementioned histologic criteria for malignancy was seen in the first or second biopsy in the present case (Figures 3, 6C).
The original idea that SCM originates from a metaplasia in the subintimal layer of the synovium, where the synovium is in direct contact with the articular cartilage, has been challenged. The high incidence of hypercellularity, binucleated cells, and cellular atypia was always an argument against a metaplastic origin for the disease. Evidence of clonal chromosomal changes, like translocation of chromosome 1218 and chromosome 5 and 6 abnormalities,19,20 in addition to other alterations,19,21 provide some evidence supporting a neoplastic rather than a metaplastic origin for SCM. Given the presence of mitosis in the present case, the lack of mitotic activity in SCM, as stated by other authors,22 is not a universal feature and cannot be used as an argument against a neoplastic origin for SCM.
Although mitotic activity is uncommon in SCM, the present case illustrates the possible presence of mitotic activity in GSSCM. The simple presence of mitotic activity, a common finding in some other chondral tumors,23,24 does not preclude the diagnosis of benign SCM, as suggested before,8 and correlation of the clinical and radiologic manifestations with histopathologic findings is crucial for a correct diagnosis.
1. Milgram JW. Synovial osteochondromatosis: a histopathological study of thirty cases. J Bone Joint Surg Am. 1977;59(6):792-801.
2. Trias A, Quintana O. Synovial chondrometaplasia: review of world literature and a study of 18 Canadian cases. Can J Surg. 1976;19(2):151-158.
3. Murphey MD, Vidal JA, Fanburg-Smith JC, Gajewski DA. Imaging of synovial chondromatosis with radiologic-pathologic correlation. Radiographics. 2007;27(5):1465-1488.
4. Milgram JW. Synovial osteochondromatosis in association with Legg-Calve-Perthes disease. Clin Orthop Relat Res. 1979;(145):179-182.
5. Sim FH, Dahlin DC, Ivins JC. Extra-articular synovial chondromatosis. J Bone Joint Surg Am. 1977;59(4):492-495.
6. Bertoni F, Unni KK, Beabout JW, Sim FH. Chondrosarcomas of the synovium. Cancer. 1991;67(1):155-162.
7. Edeiken J, Edeiken BS, Ayala AG, Raymond AK, Murray JA, Guo SQ. Giant solitary synovial chondromatosis. Skeletal Radiol. 1994;23(1):23-29.
8. Davis RI, Hamilton A, Biggart JD. Primary synovial chondromatosis: a clinicopathologic review and assessment of malignant potential. Hum Pathol. 1998;29(7):683-688.
9. Goel A, Cullen C, Paul AS, Freemont AJ. Multiple giant synovial chondromatosis of the knee. Knee. 2001;8(3):243-245.
10. Dogan A, Harman M, Uslu M, Bayram I, Akpinar F. Rocky form giant synovial chondromatosis: a case report. Knee Surg Sports Traumatol Arthrosc. 2006;14(5):465-468.
11. Eisenberg KS, Johnston JO. Synovial chondromatosis of the hip joint presenting as an intrapelvic mass: a case report. J Bone Joint Surg Am. 1972;54(1):176-178.
12. Lohmann CH, Köster G, Klinger HM, Kunze E. Giant synovial osteochondromatosis of the acromio-clavicular joint in a child. A case report and review of the literature. J Pediatr Orthop B. 2005;14(2):126-128.
13. Cai XY, Yang C, Chen MJ, Jiang B, Wang BL. Arthroscopically guided removal of large solitary synovial chondromatosis from the temporomandibular joint. Int J Oral Maxillofac Surg. 2010;39(12):1236-1239.
14. Gil-Salu JL, Lazaro R, Aldasoro J, Gonzalez-Darder JM. Giant solitary synovial chondromatosis of the temporomandibular joint with intracranial extension. Skull Base Surg. 1998;8(2):99-104.
15. Kang CH, Park JH, Lee DH, Kim CH, Park JM, Lee WS. Giant synovial chondromatosis of the knee mimicking a parosteal osteosarcoma: a case report. J Korean Bone Joint Tumor Soc. 2010;16(2):95-98.
16. Nihal A, Read CJ, Henderson DC, Malcolm AJ. Extra-articular giant solitary synovial chondromatosis of the foot: a case report and literature review. Foot Ankle Surg. 1999;5(1):29-32.
17. Robinson P, White LM, Kandel R, Bell RS, Wunder JS. Primary synovial osteochondromatosis of the hip: extracapsular patterns of spread. Skeletal Radiol. 2004;33(4):210-215.
18. Tallini G, Dorfman H, Brys P, et al. Correlation between clinicopathological features and karyotype in 100 cartilaginous and chordoid tumours. A report from the Chromosomes and Morphology (CHAMP) Collaborative Study Group. J Pathol. 2002;196(2):194-203.
19. Sah AP, Geller DS, Mankin HJ, et al. Malignant transformation of synovial chondromatosis of the shoulder to chondrosarcoma. A case report. J Bone Joint Surg Am. 2007;89(6):1321-1328.
20. Buddingh EP, Krallman P, Neff JR, Nelson M, Liu J, Bridge JA. Chromosome 6 abnormalities are recurrent in synovial chondromatosis. Cancer Genet Cytogenet. 2003;140(1):18-22.
21. Rizzo M, Ghert MA, Harrelson JM, Scully SP. Chondrosarcoma of bone: analysis of 108 cases and evaluation for predictors of outcome. Clin Orthop Relat Res. 2001;(391):224-233.
22. Davis RI, Foster H, Arthur K, Trewin S, Hamilton PW, Biggart DJ. Cell proliferation studies in primary synovial chondromatosis. J Pathol. 1998;184(1):18-23.
23. Ishikawa E, Tsuboi K, Onizawa K, et al. Chondroblastoma of the temporal base with high mitotic activity. Neurol Med Chir (Tokyo). 2002;42(11):516-520.
24. Kirin I, Jurisic D, Mokrovic H, Stanec Z, Stalekar H. Chondromyxoid fibroma of the second metacarpal bone—a case report. Coll Antropol. 2011;35(3):929-931.
Synovial chondromatosis (SCM) is a relatively rare benign lesion of the synovium.1 Its pathogenesis has been thought to be a chondral metaplasia of the subintimal layer of the intra- or extra-articular synovium.2 However, evidence supporting a neoplastic cause of the disease is emerging.3 When intra-articular, any joint can be affected, though large joints are more prone to the disease; the knee, hip, and elbow are the most common locations.4 The synovial layer of tendons or bursae can be the origin of extra-articular SCM.5
Synovial chondrosarcoma (SCS), an even rarer pathology, can be caused by malignant transformation of SCM or can appear de novo on a synovial background.6 Histologic differentiation from SCM might be difficult because of the high incidence of hypercellularity, cellular atypia, and binucleated cells.6 Some features, such as presence of a very large mass or erosion of the surrounding bones, have been indicated as possible signs of malignancy.3 An unusual presentation of SCM, giant solitary synovial chondromatosis (GSSCM), can be hard to distinguish from SCS because of the large volume and possible aggressive radiologic findings.7 Some histologic features, such as presence of necrosis and mitotic cells, have been suggested as distinctive criteria for malignancy.8
In this article, we present a case of benign GSSCM with a histologic feature that has not been considered typical for benign SCM. The patient provided written informed consent for print and electronic publication of this case report.
Case Report
An 18-year-old woman presented with a large mass over the right hip. The mass had been growing slowly for 2 years. One year before presentation, a radiograph showed a large hip mass with fluffy calcification (Figure 1), and magnetic resonance imaging (MRI) showed a large nonhomogeneous mass anterior to the hip capsule and extending into the hip joint back to the posterior part of the joint (Figures 2A, 2B). Open incisional biopsy was performed in a local hospital at the time, and the histologic analysis revealed presence of atypical binucleated cells and pleomorphism, in addition to some mitotic activity (0 to 1 per high-power field) (Figure 3). These findings suggested malignancy. The patient declined surgery up until the time she presented to our hospital, 1 year later.
Clinical examination findings on admission to our hospital were striking. The patient had a large mass in the groin region. It was fairly tender and firm to palpation, immobile, and close to the skin. Hip motion was mildly painful but obviously restricted.
The mass was restaged. New radiographs and MRI did not show any significant changes since the previous year, computed tomography (CT) did not show any bone erosion (Figure 4), and chest radiograph, CT, and whole-body bone scan did not demonstrate any signs of metastasis.
Given the clinical presentation and previous histopathologic findings, a diagnosis of GSSCM with possible malignant transformation was made. The patient was scheduled for surgery. During surgery, the tumor was exposed through the Smith-Petersen approach. The mass was extruding under the fascia between the femoral neurovascular bundle medially and iliopsoas muscle laterally. There was no adhesion of the surrounding structures, including the femoral neurovascular bundle, to the mass. The muscle was sitting on the anterolateral surface of the mass, which was considered located in the iliopsoas bursa but extending to the joint. In the vertical plane, the mass extended down to the subtrochanteric area. The entire solid extra-articular mass was excised en bloc, and hip capsulotomy was performed inferior to the area of emergence of the mass. The joint was occupied by a single solid cartilaginous mass molding around the femoral neck, filling the piriformis fossa and propagating to the posterior joint space. Obtaining enough exposure to the back of the joint required surgical hip dislocation. The visualized acetabular fossa revealed chondral fragments, which were excised. Bone erosion or significant osteoarthritis was not detected in any part of the joint. A nearly total synovectomy was performed, leaving the ascending retinacular vessels intact. Meticulous technique was used to avoid contaminating the extra-articular tissues. The wound was closed in the routine way after hip relocation.
The 16×9.5×9-cm mass (Figure 5A) had a conglomerated internal structure (Figure 5B). Multiple specimens from the intra- and extra-articular portions of the mass were sent for histopathologic analysis, which revealed clusters of mature chondrocytes arranged in a lobular pattern and separated by thin fibrous bands. Areas of calcification and ossification were appreciated as well (Figures 6A-6C). No necrosis, mitosis, or bone permeation was detected. These findings were compatible with typical SCM. Given these pathologic findings and the lack of clinical deterioration over the previous year, a diagnosis of GSSCM with extension along the iliopsoas and obturator externus bursae was made. The already-performed marginal excision was deemed sufficient treatment. At most recent follow-up, 38 months after surgery, the patient was pain-free and had good hip range of motion and no indication of recurrence.
Discussion
SCM is a benign disorder emerging from the synovium as a result of proliferative changes in the synovial membrane of the joints, tendon sheaths, or bursae, leading to the formation of numerous cartilaginous nodules, usually a few millimeters in diameter.8 In a rare presentation of the disease, the nodules may coalesce to form a large mass, or a single cartilaginous nodule may enlarge to form a mass. Edeiken and colleagues7 named this previously unrecognized SCM feature as GSSCM when there was a major single mass larger than 1 cm in diameter. There have been other SCM cases with multiple giant masses.9,10 In the English-language literature, we found 15 GSSCM cases, which include the first reported, by Edeiken and colleagues7 (Table). However, earlier SCM cases would be reclassified GSSCM according to their definition.11
The present case brings the total to 16. Nine of the 16 patients were male. Mean age at presentation was 41 years (range, 10-80 years). The knee was the most common GSSCM site (6 cases), followed by the temporomandibular and hip joints (3 each). Regarding gross pathology, 10 lesions were solid, and 6 (including the present one) were formed by conglomeration of the chondromatosis nodules. Lesions varied in size (16-200 mm), and 2 were primarily extra-articular (foot). One common issue with most of the cases was the initial diagnosis of chondrosarcoma. The exact surgical technique used was described for 6 cases (cases 11-16); the technique was marginal excision. In no case was recurrence 14 to 60 months after surgery reported.
This chondroproliferative process is potentially a diagnostic challenge, as distinguishing it from a chondrosarcoma, a more common lesion, could be difficult based on clinical and imaging findings, and, as is true for other chondral lesions, even histologic differentiation of the conditions might not be conclusive.12,13 Confusion in diagnosis was almost universal in this series of patients.
One important differentiating feature of benign and malignant skeletal lesions is the time course of the disease. Malignant tumors are expected to demonstrate rapid enlargement and local or systemic spread. Unfortunately, often SCS cannot be distinguished by this characteristic, as grade I or II chondrosarcoma is usually a slow-growing tumor and does not metastasize early.14 Although lack of recurrence is assuring, recurrence is not necessarily a sign of malignancy, as a considerable percentage of benign chondromatosis lesions recur.8
Radiologic differentiation between SCM and SCS is another challenge. Although bone erosion caused by a lesion not originating from bone is usually considered a sign of malignancy, GSSCM was reported as causing bone erosion in 5 of the 16 cases in our literature review.7,15 Our patient did not experience any bone erosion. However, lack of bone erosion is not a reliable criterion for excluding SCS, and bone erosion was noted in only 3 of the 9 SCS cases in the series reported by Bertoni and colleagues.6 Moreover, tumor size and propagation of tumor to surrounding tissue could be surprising in GSSCM. Large size (up to 20 cm) and extra-articular spread of a lesion originating in a joint are common findings.6,16 Our case was an obvious extension of a hip GSSCM to the iliopsoas and obturator externus bursa, which is the most common pattern of extracapsular spread of hip SCM.17 An interesting feature of the present case, however, was the relatively superficial location of the mass immediately under the fascia.
Calcified matrix is key in diagnosing a chondral lesion on imaging studies, but, in some cases, SCM does not demonstrate any radiographically detectable calcification at time of diagnosis.18 However, all the GSSCM cases reported to date had obvious calcified matrix.
The hypercellularity, cellular atypia, binucleated cells, and pleomorphism in the histologic examination of the present case are not features of malignancy in SCM.8 On the contrary, several other characteristics, including qualitative differences in the arrangement of chondrocytes (sheets rather than clusters), myxoid matrix, hypercellularity with crowding and spindling of the nuclei at the periphery, necrosis, and, most important, permeation of the trabecular bone with the filling up of marrow spaces, have been assumed to be indicative of malignancy.8 Furthermore, Davis and colleagues8 found no mitotic activity in the histopathologic investigation of 53 SCM cases. Even in 3 cases that developed malignant transformation to SCS, mitosis was not found in the initial biopsy specimens before transformation. This was compatible with the common opinion that SCM is not a neoplastic, but a metaplastic, process. Histopathologic data were available for only 8 of the previous 15 GSSCM cases. There were no reports of mitosis, and necrosis was found in only 1 case.16 In our patient’s case, however, the first biopsy did show remarkable mitotic activity. This was not the case for the second biopsy, when mature chondrocytes associated with marked calcification and ossification were prominent features (Figures 6A, 6B). We presume that, within a limited period during earlier stages of tissue maturation in SCM, mitotic activity might be a possible finding. Of note, none of the other aforementioned histologic criteria for malignancy was seen in the first or second biopsy in the present case (Figures 3, 6C).
The original idea that SCM originates from a metaplasia in the subintimal layer of the synovium, where the synovium is in direct contact with the articular cartilage, has been challenged. The high incidence of hypercellularity, binucleated cells, and cellular atypia was always an argument against a metaplastic origin for the disease. Evidence of clonal chromosomal changes, like translocation of chromosome 1218 and chromosome 5 and 6 abnormalities,19,20 in addition to other alterations,19,21 provide some evidence supporting a neoplastic rather than a metaplastic origin for SCM. Given the presence of mitosis in the present case, the lack of mitotic activity in SCM, as stated by other authors,22 is not a universal feature and cannot be used as an argument against a neoplastic origin for SCM.
Although mitotic activity is uncommon in SCM, the present case illustrates the possible presence of mitotic activity in GSSCM. The simple presence of mitotic activity, a common finding in some other chondral tumors,23,24 does not preclude the diagnosis of benign SCM, as suggested before,8 and correlation of the clinical and radiologic manifestations with histopathologic findings is crucial for a correct diagnosis.
Synovial chondromatosis (SCM) is a relatively rare benign lesion of the synovium.1 Its pathogenesis has been thought to be a chondral metaplasia of the subintimal layer of the intra- or extra-articular synovium.2 However, evidence supporting a neoplastic cause of the disease is emerging.3 When intra-articular, any joint can be affected, though large joints are more prone to the disease; the knee, hip, and elbow are the most common locations.4 The synovial layer of tendons or bursae can be the origin of extra-articular SCM.5
Synovial chondrosarcoma (SCS), an even rarer pathology, can be caused by malignant transformation of SCM or can appear de novo on a synovial background.6 Histologic differentiation from SCM might be difficult because of the high incidence of hypercellularity, cellular atypia, and binucleated cells.6 Some features, such as presence of a very large mass or erosion of the surrounding bones, have been indicated as possible signs of malignancy.3 An unusual presentation of SCM, giant solitary synovial chondromatosis (GSSCM), can be hard to distinguish from SCS because of the large volume and possible aggressive radiologic findings.7 Some histologic features, such as presence of necrosis and mitotic cells, have been suggested as distinctive criteria for malignancy.8
In this article, we present a case of benign GSSCM with a histologic feature that has not been considered typical for benign SCM. The patient provided written informed consent for print and electronic publication of this case report.
Case Report
An 18-year-old woman presented with a large mass over the right hip. The mass had been growing slowly for 2 years. One year before presentation, a radiograph showed a large hip mass with fluffy calcification (Figure 1), and magnetic resonance imaging (MRI) showed a large nonhomogeneous mass anterior to the hip capsule and extending into the hip joint back to the posterior part of the joint (Figures 2A, 2B). Open incisional biopsy was performed in a local hospital at the time, and the histologic analysis revealed presence of atypical binucleated cells and pleomorphism, in addition to some mitotic activity (0 to 1 per high-power field) (Figure 3). These findings suggested malignancy. The patient declined surgery up until the time she presented to our hospital, 1 year later.
Clinical examination findings on admission to our hospital were striking. The patient had a large mass in the groin region. It was fairly tender and firm to palpation, immobile, and close to the skin. Hip motion was mildly painful but obviously restricted.
The mass was restaged. New radiographs and MRI did not show any significant changes since the previous year, computed tomography (CT) did not show any bone erosion (Figure 4), and chest radiograph, CT, and whole-body bone scan did not demonstrate any signs of metastasis.
Given the clinical presentation and previous histopathologic findings, a diagnosis of GSSCM with possible malignant transformation was made. The patient was scheduled for surgery. During surgery, the tumor was exposed through the Smith-Petersen approach. The mass was extruding under the fascia between the femoral neurovascular bundle medially and iliopsoas muscle laterally. There was no adhesion of the surrounding structures, including the femoral neurovascular bundle, to the mass. The muscle was sitting on the anterolateral surface of the mass, which was considered located in the iliopsoas bursa but extending to the joint. In the vertical plane, the mass extended down to the subtrochanteric area. The entire solid extra-articular mass was excised en bloc, and hip capsulotomy was performed inferior to the area of emergence of the mass. The joint was occupied by a single solid cartilaginous mass molding around the femoral neck, filling the piriformis fossa and propagating to the posterior joint space. Obtaining enough exposure to the back of the joint required surgical hip dislocation. The visualized acetabular fossa revealed chondral fragments, which were excised. Bone erosion or significant osteoarthritis was not detected in any part of the joint. A nearly total synovectomy was performed, leaving the ascending retinacular vessels intact. Meticulous technique was used to avoid contaminating the extra-articular tissues. The wound was closed in the routine way after hip relocation.
The 16×9.5×9-cm mass (Figure 5A) had a conglomerated internal structure (Figure 5B). Multiple specimens from the intra- and extra-articular portions of the mass were sent for histopathologic analysis, which revealed clusters of mature chondrocytes arranged in a lobular pattern and separated by thin fibrous bands. Areas of calcification and ossification were appreciated as well (Figures 6A-6C). No necrosis, mitosis, or bone permeation was detected. These findings were compatible with typical SCM. Given these pathologic findings and the lack of clinical deterioration over the previous year, a diagnosis of GSSCM with extension along the iliopsoas and obturator externus bursae was made. The already-performed marginal excision was deemed sufficient treatment. At most recent follow-up, 38 months after surgery, the patient was pain-free and had good hip range of motion and no indication of recurrence.
Discussion
SCM is a benign disorder emerging from the synovium as a result of proliferative changes in the synovial membrane of the joints, tendon sheaths, or bursae, leading to the formation of numerous cartilaginous nodules, usually a few millimeters in diameter.8 In a rare presentation of the disease, the nodules may coalesce to form a large mass, or a single cartilaginous nodule may enlarge to form a mass. Edeiken and colleagues7 named this previously unrecognized SCM feature as GSSCM when there was a major single mass larger than 1 cm in diameter. There have been other SCM cases with multiple giant masses.9,10 In the English-language literature, we found 15 GSSCM cases, which include the first reported, by Edeiken and colleagues7 (Table). However, earlier SCM cases would be reclassified GSSCM according to their definition.11
The present case brings the total to 16. Nine of the 16 patients were male. Mean age at presentation was 41 years (range, 10-80 years). The knee was the most common GSSCM site (6 cases), followed by the temporomandibular and hip joints (3 each). Regarding gross pathology, 10 lesions were solid, and 6 (including the present one) were formed by conglomeration of the chondromatosis nodules. Lesions varied in size (16-200 mm), and 2 were primarily extra-articular (foot). One common issue with most of the cases was the initial diagnosis of chondrosarcoma. The exact surgical technique used was described for 6 cases (cases 11-16); the technique was marginal excision. In no case was recurrence 14 to 60 months after surgery reported.
This chondroproliferative process is potentially a diagnostic challenge, as distinguishing it from a chondrosarcoma, a more common lesion, could be difficult based on clinical and imaging findings, and, as is true for other chondral lesions, even histologic differentiation of the conditions might not be conclusive.12,13 Confusion in diagnosis was almost universal in this series of patients.
One important differentiating feature of benign and malignant skeletal lesions is the time course of the disease. Malignant tumors are expected to demonstrate rapid enlargement and local or systemic spread. Unfortunately, often SCS cannot be distinguished by this characteristic, as grade I or II chondrosarcoma is usually a slow-growing tumor and does not metastasize early.14 Although lack of recurrence is assuring, recurrence is not necessarily a sign of malignancy, as a considerable percentage of benign chondromatosis lesions recur.8
Radiologic differentiation between SCM and SCS is another challenge. Although bone erosion caused by a lesion not originating from bone is usually considered a sign of malignancy, GSSCM was reported as causing bone erosion in 5 of the 16 cases in our literature review.7,15 Our patient did not experience any bone erosion. However, lack of bone erosion is not a reliable criterion for excluding SCS, and bone erosion was noted in only 3 of the 9 SCS cases in the series reported by Bertoni and colleagues.6 Moreover, tumor size and propagation of tumor to surrounding tissue could be surprising in GSSCM. Large size (up to 20 cm) and extra-articular spread of a lesion originating in a joint are common findings.6,16 Our case was an obvious extension of a hip GSSCM to the iliopsoas and obturator externus bursa, which is the most common pattern of extracapsular spread of hip SCM.17 An interesting feature of the present case, however, was the relatively superficial location of the mass immediately under the fascia.
Calcified matrix is key in diagnosing a chondral lesion on imaging studies, but, in some cases, SCM does not demonstrate any radiographically detectable calcification at time of diagnosis.18 However, all the GSSCM cases reported to date had obvious calcified matrix.
The hypercellularity, cellular atypia, binucleated cells, and pleomorphism in the histologic examination of the present case are not features of malignancy in SCM.8 On the contrary, several other characteristics, including qualitative differences in the arrangement of chondrocytes (sheets rather than clusters), myxoid matrix, hypercellularity with crowding and spindling of the nuclei at the periphery, necrosis, and, most important, permeation of the trabecular bone with the filling up of marrow spaces, have been assumed to be indicative of malignancy.8 Furthermore, Davis and colleagues8 found no mitotic activity in the histopathologic investigation of 53 SCM cases. Even in 3 cases that developed malignant transformation to SCS, mitosis was not found in the initial biopsy specimens before transformation. This was compatible with the common opinion that SCM is not a neoplastic, but a metaplastic, process. Histopathologic data were available for only 8 of the previous 15 GSSCM cases. There were no reports of mitosis, and necrosis was found in only 1 case.16 In our patient’s case, however, the first biopsy did show remarkable mitotic activity. This was not the case for the second biopsy, when mature chondrocytes associated with marked calcification and ossification were prominent features (Figures 6A, 6B). We presume that, within a limited period during earlier stages of tissue maturation in SCM, mitotic activity might be a possible finding. Of note, none of the other aforementioned histologic criteria for malignancy was seen in the first or second biopsy in the present case (Figures 3, 6C).
The original idea that SCM originates from a metaplasia in the subintimal layer of the synovium, where the synovium is in direct contact with the articular cartilage, has been challenged. The high incidence of hypercellularity, binucleated cells, and cellular atypia was always an argument against a metaplastic origin for the disease. Evidence of clonal chromosomal changes, like translocation of chromosome 1218 and chromosome 5 and 6 abnormalities,19,20 in addition to other alterations,19,21 provide some evidence supporting a neoplastic rather than a metaplastic origin for SCM. Given the presence of mitosis in the present case, the lack of mitotic activity in SCM, as stated by other authors,22 is not a universal feature and cannot be used as an argument against a neoplastic origin for SCM.
Although mitotic activity is uncommon in SCM, the present case illustrates the possible presence of mitotic activity in GSSCM. The simple presence of mitotic activity, a common finding in some other chondral tumors,23,24 does not preclude the diagnosis of benign SCM, as suggested before,8 and correlation of the clinical and radiologic manifestations with histopathologic findings is crucial for a correct diagnosis.
1. Milgram JW. Synovial osteochondromatosis: a histopathological study of thirty cases. J Bone Joint Surg Am. 1977;59(6):792-801.
2. Trias A, Quintana O. Synovial chondrometaplasia: review of world literature and a study of 18 Canadian cases. Can J Surg. 1976;19(2):151-158.
3. Murphey MD, Vidal JA, Fanburg-Smith JC, Gajewski DA. Imaging of synovial chondromatosis with radiologic-pathologic correlation. Radiographics. 2007;27(5):1465-1488.
4. Milgram JW. Synovial osteochondromatosis in association with Legg-Calve-Perthes disease. Clin Orthop Relat Res. 1979;(145):179-182.
5. Sim FH, Dahlin DC, Ivins JC. Extra-articular synovial chondromatosis. J Bone Joint Surg Am. 1977;59(4):492-495.
6. Bertoni F, Unni KK, Beabout JW, Sim FH. Chondrosarcomas of the synovium. Cancer. 1991;67(1):155-162.
7. Edeiken J, Edeiken BS, Ayala AG, Raymond AK, Murray JA, Guo SQ. Giant solitary synovial chondromatosis. Skeletal Radiol. 1994;23(1):23-29.
8. Davis RI, Hamilton A, Biggart JD. Primary synovial chondromatosis: a clinicopathologic review and assessment of malignant potential. Hum Pathol. 1998;29(7):683-688.
9. Goel A, Cullen C, Paul AS, Freemont AJ. Multiple giant synovial chondromatosis of the knee. Knee. 2001;8(3):243-245.
10. Dogan A, Harman M, Uslu M, Bayram I, Akpinar F. Rocky form giant synovial chondromatosis: a case report. Knee Surg Sports Traumatol Arthrosc. 2006;14(5):465-468.
11. Eisenberg KS, Johnston JO. Synovial chondromatosis of the hip joint presenting as an intrapelvic mass: a case report. J Bone Joint Surg Am. 1972;54(1):176-178.
12. Lohmann CH, Köster G, Klinger HM, Kunze E. Giant synovial osteochondromatosis of the acromio-clavicular joint in a child. A case report and review of the literature. J Pediatr Orthop B. 2005;14(2):126-128.
13. Cai XY, Yang C, Chen MJ, Jiang B, Wang BL. Arthroscopically guided removal of large solitary synovial chondromatosis from the temporomandibular joint. Int J Oral Maxillofac Surg. 2010;39(12):1236-1239.
14. Gil-Salu JL, Lazaro R, Aldasoro J, Gonzalez-Darder JM. Giant solitary synovial chondromatosis of the temporomandibular joint with intracranial extension. Skull Base Surg. 1998;8(2):99-104.
15. Kang CH, Park JH, Lee DH, Kim CH, Park JM, Lee WS. Giant synovial chondromatosis of the knee mimicking a parosteal osteosarcoma: a case report. J Korean Bone Joint Tumor Soc. 2010;16(2):95-98.
16. Nihal A, Read CJ, Henderson DC, Malcolm AJ. Extra-articular giant solitary synovial chondromatosis of the foot: a case report and literature review. Foot Ankle Surg. 1999;5(1):29-32.
17. Robinson P, White LM, Kandel R, Bell RS, Wunder JS. Primary synovial osteochondromatosis of the hip: extracapsular patterns of spread. Skeletal Radiol. 2004;33(4):210-215.
18. Tallini G, Dorfman H, Brys P, et al. Correlation between clinicopathological features and karyotype in 100 cartilaginous and chordoid tumours. A report from the Chromosomes and Morphology (CHAMP) Collaborative Study Group. J Pathol. 2002;196(2):194-203.
19. Sah AP, Geller DS, Mankin HJ, et al. Malignant transformation of synovial chondromatosis of the shoulder to chondrosarcoma. A case report. J Bone Joint Surg Am. 2007;89(6):1321-1328.
20. Buddingh EP, Krallman P, Neff JR, Nelson M, Liu J, Bridge JA. Chromosome 6 abnormalities are recurrent in synovial chondromatosis. Cancer Genet Cytogenet. 2003;140(1):18-22.
21. Rizzo M, Ghert MA, Harrelson JM, Scully SP. Chondrosarcoma of bone: analysis of 108 cases and evaluation for predictors of outcome. Clin Orthop Relat Res. 2001;(391):224-233.
22. Davis RI, Foster H, Arthur K, Trewin S, Hamilton PW, Biggart DJ. Cell proliferation studies in primary synovial chondromatosis. J Pathol. 1998;184(1):18-23.
23. Ishikawa E, Tsuboi K, Onizawa K, et al. Chondroblastoma of the temporal base with high mitotic activity. Neurol Med Chir (Tokyo). 2002;42(11):516-520.
24. Kirin I, Jurisic D, Mokrovic H, Stanec Z, Stalekar H. Chondromyxoid fibroma of the second metacarpal bone—a case report. Coll Antropol. 2011;35(3):929-931.
1. Milgram JW. Synovial osteochondromatosis: a histopathological study of thirty cases. J Bone Joint Surg Am. 1977;59(6):792-801.
2. Trias A, Quintana O. Synovial chondrometaplasia: review of world literature and a study of 18 Canadian cases. Can J Surg. 1976;19(2):151-158.
3. Murphey MD, Vidal JA, Fanburg-Smith JC, Gajewski DA. Imaging of synovial chondromatosis with radiologic-pathologic correlation. Radiographics. 2007;27(5):1465-1488.
4. Milgram JW. Synovial osteochondromatosis in association with Legg-Calve-Perthes disease. Clin Orthop Relat Res. 1979;(145):179-182.
5. Sim FH, Dahlin DC, Ivins JC. Extra-articular synovial chondromatosis. J Bone Joint Surg Am. 1977;59(4):492-495.
6. Bertoni F, Unni KK, Beabout JW, Sim FH. Chondrosarcomas of the synovium. Cancer. 1991;67(1):155-162.
7. Edeiken J, Edeiken BS, Ayala AG, Raymond AK, Murray JA, Guo SQ. Giant solitary synovial chondromatosis. Skeletal Radiol. 1994;23(1):23-29.
8. Davis RI, Hamilton A, Biggart JD. Primary synovial chondromatosis: a clinicopathologic review and assessment of malignant potential. Hum Pathol. 1998;29(7):683-688.
9. Goel A, Cullen C, Paul AS, Freemont AJ. Multiple giant synovial chondromatosis of the knee. Knee. 2001;8(3):243-245.
10. Dogan A, Harman M, Uslu M, Bayram I, Akpinar F. Rocky form giant synovial chondromatosis: a case report. Knee Surg Sports Traumatol Arthrosc. 2006;14(5):465-468.
11. Eisenberg KS, Johnston JO. Synovial chondromatosis of the hip joint presenting as an intrapelvic mass: a case report. J Bone Joint Surg Am. 1972;54(1):176-178.
12. Lohmann CH, Köster G, Klinger HM, Kunze E. Giant synovial osteochondromatosis of the acromio-clavicular joint in a child. A case report and review of the literature. J Pediatr Orthop B. 2005;14(2):126-128.
13. Cai XY, Yang C, Chen MJ, Jiang B, Wang BL. Arthroscopically guided removal of large solitary synovial chondromatosis from the temporomandibular joint. Int J Oral Maxillofac Surg. 2010;39(12):1236-1239.
14. Gil-Salu JL, Lazaro R, Aldasoro J, Gonzalez-Darder JM. Giant solitary synovial chondromatosis of the temporomandibular joint with intracranial extension. Skull Base Surg. 1998;8(2):99-104.
15. Kang CH, Park JH, Lee DH, Kim CH, Park JM, Lee WS. Giant synovial chondromatosis of the knee mimicking a parosteal osteosarcoma: a case report. J Korean Bone Joint Tumor Soc. 2010;16(2):95-98.
16. Nihal A, Read CJ, Henderson DC, Malcolm AJ. Extra-articular giant solitary synovial chondromatosis of the foot: a case report and literature review. Foot Ankle Surg. 1999;5(1):29-32.
17. Robinson P, White LM, Kandel R, Bell RS, Wunder JS. Primary synovial osteochondromatosis of the hip: extracapsular patterns of spread. Skeletal Radiol. 2004;33(4):210-215.
18. Tallini G, Dorfman H, Brys P, et al. Correlation between clinicopathological features and karyotype in 100 cartilaginous and chordoid tumours. A report from the Chromosomes and Morphology (CHAMP) Collaborative Study Group. J Pathol. 2002;196(2):194-203.
19. Sah AP, Geller DS, Mankin HJ, et al. Malignant transformation of synovial chondromatosis of the shoulder to chondrosarcoma. A case report. J Bone Joint Surg Am. 2007;89(6):1321-1328.
20. Buddingh EP, Krallman P, Neff JR, Nelson M, Liu J, Bridge JA. Chromosome 6 abnormalities are recurrent in synovial chondromatosis. Cancer Genet Cytogenet. 2003;140(1):18-22.
21. Rizzo M, Ghert MA, Harrelson JM, Scully SP. Chondrosarcoma of bone: analysis of 108 cases and evaluation for predictors of outcome. Clin Orthop Relat Res. 2001;(391):224-233.
22. Davis RI, Foster H, Arthur K, Trewin S, Hamilton PW, Biggart DJ. Cell proliferation studies in primary synovial chondromatosis. J Pathol. 1998;184(1):18-23.
23. Ishikawa E, Tsuboi K, Onizawa K, et al. Chondroblastoma of the temporal base with high mitotic activity. Neurol Med Chir (Tokyo). 2002;42(11):516-520.
24. Kirin I, Jurisic D, Mokrovic H, Stanec Z, Stalekar H. Chondromyxoid fibroma of the second metacarpal bone—a case report. Coll Antropol. 2011;35(3):929-931.
Unusual Form and Location of a Tumor: Multiosseous Ewing Sarcoma in the Foot
Ewing sarcomas are characterized as primitive malignant round cell tumors.1 These tumors are diagnosed by neuroectodermal differentiation and by their common histologic and immunohistochemical properties.2 Ewing sarcoma is the second most common malignant bone tumor in adolescents and young adults. It is the fourth most common primary malignant tumor, accounting for about 9% of all malignant tumors of bone. The most common primary bone tumors are multiple myeloma, osteosarcoma, and chondrosarcoma.3
The diaphyses of long bones (eg, femur, tibia, humerus) and flat bones (eg, pelvis, scapula) are the most commonly involved sites. Involvement of bones in the hands and feet is uncommon (3%-5% of reported cases).4 The foot bones most commonly involved include the calcaneus and the metatarsals, in the series by Casadei and colleagues.5
About 90% of Ewing sarcoma cases present before age 20 years (mean age, 13 years).6 Typical presentation is that of localized pain at the involved site. Some patients have systemic symptoms, such as fever, malaise, weight loss, leukocytosis, and increased erythrocyte sedimentation rate (ESR) mimicking infection. Radiographically, Ewing sarcoma appears as a permeative destructive bone lesion with a moth-eaten appearance (almost 76% of cases).7 This is usually associated with lamellated periosteal new bone formation or an “onion skin” appearance. Less commonly, a sunburst configuration with an associated soft-tissue mass can be seen. Computed tomography (CT) and magnetic resonance imaging (MRI) show the osseous extent of the tumor and the presence or absence of the soft-tissue component of the tumor. Radionuclide bone scans show increased technetium-99m methylene diphosphonate accumulation and are typically hot.6
Histopathologically, the tumor is composed of small, uniformly sized cells characterized by an almost clear eosinophilic cytoplasm and very little intercellular matrix. There are lobules and strands divided by prominent septa. Macroscopically, appearance can range from a soft, fleshy solid mass to an almost liquid form, as the lesion does not produce any matrix. At time of surgery, the tumor may have a liquefied component and the appearance of pus.6 Prognostic factors are tumor site in foot and treatment according to the series by Casadei and colleagues.5 Patients with large central tumors, especially in the pelvis, have worse outcomes than patients with distal tumors.8
In this article, we report a case of multifocal Ewing sarcoma involving multiple bones in the foot. Given the multifocal nature of the disease confined to the foot, the initial impression was that of osteomyelitis. We describe the histologic, radiologic, and diagnostic features of the tumor and outline treatment and prognosis. To our knowledge, this is the first report of multifocal Ewing sarcoma involving multiple bones in the foot. The patient provided written informed consent for print and electronic publication of this case report.
Case Report
A 19-year-old man visited our clinic with the chief complaints of left foot pain and swelling. The pain started 10 months earlier and was followed by swelling. Complaints started after a minor local trauma. The man sought outside medical attention 8 months after pain onset. At his first visit at another institution, an initial radiograph was reported as normal, and all laboratory measures, including complete blood cell count (CBC) differential, ESR, and C-reactive protein (CRP) level, were within normal limits. Under the erroneous diagnosis of infection, the patient was treated with cloxacillin 500 mg 4 times a day for 4 weeks.
The patient’s pain had started 10 months before presentation (2 months after antibiotic therapy was initiated) (Figure 1). Physical examination at our institution revealed a palpable mass on the dorsum of the left foot. Anteroposterior and lateral plain radiographs showed a permeative lytic lesion with cortical destruction in the left calcaneus, navicular, cuboid, and cuneiform bones and in all metatarsal bones except the first (Figure 2). A soft-tissue mass around the involved bones was noted as well. The talus was not involved (Figure 3).
CT showed permeative destruction of left foot bones, including the calcaneus, navicular, cuboid, and cuneiform bones and all metatarsal bones except the first. Invasion through the overlying cortex of the involved bones indicated aggressive biological activity of the tumor (Figure 4). MRI showed a destructive bony lesion of the mentioned bones associated with the soft-tissue mass (Figure 3).
Bone scan showed increased uptake in the involved areas (Figure 5). Chest plain radiographs and CT showed no distant metastasis. An incisional biopsy was performed, and histopathology showed a malignant small round cell tumor, identified as Ewing sarcoma (Figure 6). An immunohistochemistry study demonstrated positive CD99 and negative cytokeratin, leukocyte common antigen, desmin, and synaptophysin.
The patient was started on 4 cycles of adjuvant chemotherapy. Cycles 1 and 3 involved cyclophosphamide 2 g, vincristine 2 g, and doxorubicin 50 mg; cycles 2 and 4 involved ifosfamide 3.5 g and etoposide 200 mg. Tumor shrinkage occurred after chemotherapy. Clinical response to preoperative chemotherapy was documented by a decrease in tumor size at follow-ups. The patient underwent below-knee amputation.
Postoperative histopathology confirmed the diagnosis of Ewing sarcoma of the calcaneus, navicular, cuboid, and cuneiform bones and all metatarsal bones except the first (Figure 7). At 2-year follow-up, the patient had no evidence of local recurrence or distant metastasis based on chest CT and clinical examination of the affected site.
Discussion
Ewing sarcoma is the prototype of round small cell malignancies that arise from the long bones and the flat bones. It seldom involves the hands or feet. To our knowledge, this is the first report of Ewing sarcoma of the foot with multiple-bone involvement. Our literature review found a case of Ewing sarcoma of the first phalanx of the third toe, the second metatarsal bone, the cuneiform, the cuboid, and the talus, with lesser soft-tissue extension compared with our patient’s case.9
As this foot tumor is rare, there are few reports on its clinical aspects, appropriate treatment, and long-term outcome. For treatment of nonmetastatic Ewing sarcoma, limb-salvage surgery is advised if response has been good and there is a reasonable expectation of negative margins and good functional results.
Radiation and surgery may be part of the overall treatment plan. Radiation without surgery has a unique role in pelvic Ewing sarcoma, in contrast to extremity Ewing sarcoma. In our opinion, margins and histologic necrosis in the resection specimen are examined after surgery, and, if the margins are widely negative and histologic response is good, no further local control is advised. If the margin is positive, postoperative radiation therapy is recommended.1 Amputation has gradually become a (rare) choice in the treatment of extremity sarcomas.9 In our patient’s case, surgery was preferred over radiation therapy after chemotherapy because of the low risk of local side effects and the expected high efficacy. In addition, radiation at such high doses for Ewing sarcoma in the foot causes functional impairment. Because of the multiple-bone involvement, a salvage procedure was not possible for our patient. Given the calcaneal involvement, however, below-knee amputation was considered safer than ankle disarticulation.
Multiple-bone involvement occurs in the advanced stage of Ewing sarcoma, usually after visceral and pulmonary metastases are detected.9 The case reported by Rammal and colleagues9 had both multiple-bone involvement in the foot and pulmonary metastasis. The authors indicated that hematogenous spread of the tumor was discerned because the lesions were noncontiguous.9 Our patient had no distant metastases. We think his tumor originated in a tarsal or midtarsal bone and extended to adjacent bones. Therefore, it probably spread through its capsular and ligamentous attachment among tarsal and midtarsal bones, as the involvement was contiguous rather than distinct.
Average delay from symptom onset to diagnosis was reported to be 34 weeks.3 Average physician delay from initial visit to correct diagnosis was reported to be 19 weeks.3 Patients may have erythema, fever, and swelling, suggestive of osteomyelitis.3 Laboratory results may show increased white blood cell count and elevated ESR and CRP level.3 In addition, needle biopsy of the tumor may reveal an appearance grossly similar to that of pus.3 Therefore, physicians may send all the tissue out for microbiological analysis (according to the erroneous diagnosis of infection) and none out for pathologic analysis. The situation can be further complicated when Ewing sarcoma occurs in the foot, an uncommon site. In this special case, multiple-bone involvement can present a misleading clinical picture of infection.10 In other words, infection is one of the best choices in the differential diagnosis.7 Also to be considered are multicentric giant cell tumor, fibrosarcoma,11 and osteosarcoma.12
1. Herring JA. Malignant tumors of bone. In: Herring JA, ed. Tachdjian’s Pediatric Orthopaedics. Philadelphia, PA: Saunders Elsevier; 2008:2324-2327.
2. Cavazzana AO, Miser JS, Jefferson J, Triche TJ. Experimental evidence for a neural origin of Ewing’s sarcoma of bone. Am J Pathol. 1987;127(3):507-518.
3. Canale ST, Beaty JH. Malignant tumors of bone. In: Canale ST, ed. Campbell’s Operative Orthopaedics. Philadelphia, PA: Mosby Elsevier; 2008:910-913.
4. Unni KK. Ewing sarcoma. In: Unni KK, ed. Dahlin’s Bone Tumor: General Aspects and Data on 11087 Cases. Philadelphia, PA: Lippincott-Raven; 1996:121-142.
5. Casadei R, Magnani M, Biagini R, Mercuri M. Prognostic factors in Ewing’s sarcoma of the foot. Clin Orthop. 2004;(420):230-238.
6. Greenspan A, Jundt G, Remagen W. Bone-forming (osteogenic) lesions. In: Greenspan A, Jundt G, Remagen W, eds. Differential Diagnosis in Orthopaedic Oncology. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007:114.
7. Metcalfe JE, Grimer RJ. Ewing’s sarcoma of the foot masquerading as osteomyelitis. Foot Ankle Surg. 2004;10(1):29-33.
8. Hoffmann C, Ahrens S, Dunst J, et al. Pelvis Ewing sarcoma: a retrospective analysis of 241 cases. Cancer. 1999;85(4):869-877.
9. Rammal H, Ghanem I, Torbey PH, Dagher F, Kharrat K. Multifocal Ewing sarcoma of the foot. J Pediatr Hematol Oncol. 2008;30(4):298-300.
10. Ledermann HP, Morrison WB, Schweitzer ME. MR image analysis of pedal osteomyelitis: distribution, patterns of spread, and frequency of associated ulceration and septic arthritis. Radiology. 2002;223(3):747-755.
11. Dhillon MS, Prabhudev Prasad AP, Virk MS, Aggarwal S. Multicentric giant cell tumor involving the same foot: a case report and review of literature. Indian J Orthop. 2007;41(2):154-157.
12. Baraga JJ, Amarami KK, Swee RG, Wold L, Unni KK. Radiographic features of Ewing’s sarcoma of the bones of the hand and feet. Skeletal Radiol. 2001;30(3):121-126.
Ewing sarcomas are characterized as primitive malignant round cell tumors.1 These tumors are diagnosed by neuroectodermal differentiation and by their common histologic and immunohistochemical properties.2 Ewing sarcoma is the second most common malignant bone tumor in adolescents and young adults. It is the fourth most common primary malignant tumor, accounting for about 9% of all malignant tumors of bone. The most common primary bone tumors are multiple myeloma, osteosarcoma, and chondrosarcoma.3
The diaphyses of long bones (eg, femur, tibia, humerus) and flat bones (eg, pelvis, scapula) are the most commonly involved sites. Involvement of bones in the hands and feet is uncommon (3%-5% of reported cases).4 The foot bones most commonly involved include the calcaneus and the metatarsals, in the series by Casadei and colleagues.5
About 90% of Ewing sarcoma cases present before age 20 years (mean age, 13 years).6 Typical presentation is that of localized pain at the involved site. Some patients have systemic symptoms, such as fever, malaise, weight loss, leukocytosis, and increased erythrocyte sedimentation rate (ESR) mimicking infection. Radiographically, Ewing sarcoma appears as a permeative destructive bone lesion with a moth-eaten appearance (almost 76% of cases).7 This is usually associated with lamellated periosteal new bone formation or an “onion skin” appearance. Less commonly, a sunburst configuration with an associated soft-tissue mass can be seen. Computed tomography (CT) and magnetic resonance imaging (MRI) show the osseous extent of the tumor and the presence or absence of the soft-tissue component of the tumor. Radionuclide bone scans show increased technetium-99m methylene diphosphonate accumulation and are typically hot.6
Histopathologically, the tumor is composed of small, uniformly sized cells characterized by an almost clear eosinophilic cytoplasm and very little intercellular matrix. There are lobules and strands divided by prominent septa. Macroscopically, appearance can range from a soft, fleshy solid mass to an almost liquid form, as the lesion does not produce any matrix. At time of surgery, the tumor may have a liquefied component and the appearance of pus.6 Prognostic factors are tumor site in foot and treatment according to the series by Casadei and colleagues.5 Patients with large central tumors, especially in the pelvis, have worse outcomes than patients with distal tumors.8
In this article, we report a case of multifocal Ewing sarcoma involving multiple bones in the foot. Given the multifocal nature of the disease confined to the foot, the initial impression was that of osteomyelitis. We describe the histologic, radiologic, and diagnostic features of the tumor and outline treatment and prognosis. To our knowledge, this is the first report of multifocal Ewing sarcoma involving multiple bones in the foot. The patient provided written informed consent for print and electronic publication of this case report.
Case Report
A 19-year-old man visited our clinic with the chief complaints of left foot pain and swelling. The pain started 10 months earlier and was followed by swelling. Complaints started after a minor local trauma. The man sought outside medical attention 8 months after pain onset. At his first visit at another institution, an initial radiograph was reported as normal, and all laboratory measures, including complete blood cell count (CBC) differential, ESR, and C-reactive protein (CRP) level, were within normal limits. Under the erroneous diagnosis of infection, the patient was treated with cloxacillin 500 mg 4 times a day for 4 weeks.
The patient’s pain had started 10 months before presentation (2 months after antibiotic therapy was initiated) (Figure 1). Physical examination at our institution revealed a palpable mass on the dorsum of the left foot. Anteroposterior and lateral plain radiographs showed a permeative lytic lesion with cortical destruction in the left calcaneus, navicular, cuboid, and cuneiform bones and in all metatarsal bones except the first (Figure 2). A soft-tissue mass around the involved bones was noted as well. The talus was not involved (Figure 3).
CT showed permeative destruction of left foot bones, including the calcaneus, navicular, cuboid, and cuneiform bones and all metatarsal bones except the first. Invasion through the overlying cortex of the involved bones indicated aggressive biological activity of the tumor (Figure 4). MRI showed a destructive bony lesion of the mentioned bones associated with the soft-tissue mass (Figure 3).
Bone scan showed increased uptake in the involved areas (Figure 5). Chest plain radiographs and CT showed no distant metastasis. An incisional biopsy was performed, and histopathology showed a malignant small round cell tumor, identified as Ewing sarcoma (Figure 6). An immunohistochemistry study demonstrated positive CD99 and negative cytokeratin, leukocyte common antigen, desmin, and synaptophysin.
The patient was started on 4 cycles of adjuvant chemotherapy. Cycles 1 and 3 involved cyclophosphamide 2 g, vincristine 2 g, and doxorubicin 50 mg; cycles 2 and 4 involved ifosfamide 3.5 g and etoposide 200 mg. Tumor shrinkage occurred after chemotherapy. Clinical response to preoperative chemotherapy was documented by a decrease in tumor size at follow-ups. The patient underwent below-knee amputation.
Postoperative histopathology confirmed the diagnosis of Ewing sarcoma of the calcaneus, navicular, cuboid, and cuneiform bones and all metatarsal bones except the first (Figure 7). At 2-year follow-up, the patient had no evidence of local recurrence or distant metastasis based on chest CT and clinical examination of the affected site.
Discussion
Ewing sarcoma is the prototype of round small cell malignancies that arise from the long bones and the flat bones. It seldom involves the hands or feet. To our knowledge, this is the first report of Ewing sarcoma of the foot with multiple-bone involvement. Our literature review found a case of Ewing sarcoma of the first phalanx of the third toe, the second metatarsal bone, the cuneiform, the cuboid, and the talus, with lesser soft-tissue extension compared with our patient’s case.9
As this foot tumor is rare, there are few reports on its clinical aspects, appropriate treatment, and long-term outcome. For treatment of nonmetastatic Ewing sarcoma, limb-salvage surgery is advised if response has been good and there is a reasonable expectation of negative margins and good functional results.
Radiation and surgery may be part of the overall treatment plan. Radiation without surgery has a unique role in pelvic Ewing sarcoma, in contrast to extremity Ewing sarcoma. In our opinion, margins and histologic necrosis in the resection specimen are examined after surgery, and, if the margins are widely negative and histologic response is good, no further local control is advised. If the margin is positive, postoperative radiation therapy is recommended.1 Amputation has gradually become a (rare) choice in the treatment of extremity sarcomas.9 In our patient’s case, surgery was preferred over radiation therapy after chemotherapy because of the low risk of local side effects and the expected high efficacy. In addition, radiation at such high doses for Ewing sarcoma in the foot causes functional impairment. Because of the multiple-bone involvement, a salvage procedure was not possible for our patient. Given the calcaneal involvement, however, below-knee amputation was considered safer than ankle disarticulation.
Multiple-bone involvement occurs in the advanced stage of Ewing sarcoma, usually after visceral and pulmonary metastases are detected.9 The case reported by Rammal and colleagues9 had both multiple-bone involvement in the foot and pulmonary metastasis. The authors indicated that hematogenous spread of the tumor was discerned because the lesions were noncontiguous.9 Our patient had no distant metastases. We think his tumor originated in a tarsal or midtarsal bone and extended to adjacent bones. Therefore, it probably spread through its capsular and ligamentous attachment among tarsal and midtarsal bones, as the involvement was contiguous rather than distinct.
Average delay from symptom onset to diagnosis was reported to be 34 weeks.3 Average physician delay from initial visit to correct diagnosis was reported to be 19 weeks.3 Patients may have erythema, fever, and swelling, suggestive of osteomyelitis.3 Laboratory results may show increased white blood cell count and elevated ESR and CRP level.3 In addition, needle biopsy of the tumor may reveal an appearance grossly similar to that of pus.3 Therefore, physicians may send all the tissue out for microbiological analysis (according to the erroneous diagnosis of infection) and none out for pathologic analysis. The situation can be further complicated when Ewing sarcoma occurs in the foot, an uncommon site. In this special case, multiple-bone involvement can present a misleading clinical picture of infection.10 In other words, infection is one of the best choices in the differential diagnosis.7 Also to be considered are multicentric giant cell tumor, fibrosarcoma,11 and osteosarcoma.12
Ewing sarcomas are characterized as primitive malignant round cell tumors.1 These tumors are diagnosed by neuroectodermal differentiation and by their common histologic and immunohistochemical properties.2 Ewing sarcoma is the second most common malignant bone tumor in adolescents and young adults. It is the fourth most common primary malignant tumor, accounting for about 9% of all malignant tumors of bone. The most common primary bone tumors are multiple myeloma, osteosarcoma, and chondrosarcoma.3
The diaphyses of long bones (eg, femur, tibia, humerus) and flat bones (eg, pelvis, scapula) are the most commonly involved sites. Involvement of bones in the hands and feet is uncommon (3%-5% of reported cases).4 The foot bones most commonly involved include the calcaneus and the metatarsals, in the series by Casadei and colleagues.5
About 90% of Ewing sarcoma cases present before age 20 years (mean age, 13 years).6 Typical presentation is that of localized pain at the involved site. Some patients have systemic symptoms, such as fever, malaise, weight loss, leukocytosis, and increased erythrocyte sedimentation rate (ESR) mimicking infection. Radiographically, Ewing sarcoma appears as a permeative destructive bone lesion with a moth-eaten appearance (almost 76% of cases).7 This is usually associated with lamellated periosteal new bone formation or an “onion skin” appearance. Less commonly, a sunburst configuration with an associated soft-tissue mass can be seen. Computed tomography (CT) and magnetic resonance imaging (MRI) show the osseous extent of the tumor and the presence or absence of the soft-tissue component of the tumor. Radionuclide bone scans show increased technetium-99m methylene diphosphonate accumulation and are typically hot.6
Histopathologically, the tumor is composed of small, uniformly sized cells characterized by an almost clear eosinophilic cytoplasm and very little intercellular matrix. There are lobules and strands divided by prominent septa. Macroscopically, appearance can range from a soft, fleshy solid mass to an almost liquid form, as the lesion does not produce any matrix. At time of surgery, the tumor may have a liquefied component and the appearance of pus.6 Prognostic factors are tumor site in foot and treatment according to the series by Casadei and colleagues.5 Patients with large central tumors, especially in the pelvis, have worse outcomes than patients with distal tumors.8
In this article, we report a case of multifocal Ewing sarcoma involving multiple bones in the foot. Given the multifocal nature of the disease confined to the foot, the initial impression was that of osteomyelitis. We describe the histologic, radiologic, and diagnostic features of the tumor and outline treatment and prognosis. To our knowledge, this is the first report of multifocal Ewing sarcoma involving multiple bones in the foot. The patient provided written informed consent for print and electronic publication of this case report.
Case Report
A 19-year-old man visited our clinic with the chief complaints of left foot pain and swelling. The pain started 10 months earlier and was followed by swelling. Complaints started after a minor local trauma. The man sought outside medical attention 8 months after pain onset. At his first visit at another institution, an initial radiograph was reported as normal, and all laboratory measures, including complete blood cell count (CBC) differential, ESR, and C-reactive protein (CRP) level, were within normal limits. Under the erroneous diagnosis of infection, the patient was treated with cloxacillin 500 mg 4 times a day for 4 weeks.
The patient’s pain had started 10 months before presentation (2 months after antibiotic therapy was initiated) (Figure 1). Physical examination at our institution revealed a palpable mass on the dorsum of the left foot. Anteroposterior and lateral plain radiographs showed a permeative lytic lesion with cortical destruction in the left calcaneus, navicular, cuboid, and cuneiform bones and in all metatarsal bones except the first (Figure 2). A soft-tissue mass around the involved bones was noted as well. The talus was not involved (Figure 3).
CT showed permeative destruction of left foot bones, including the calcaneus, navicular, cuboid, and cuneiform bones and all metatarsal bones except the first. Invasion through the overlying cortex of the involved bones indicated aggressive biological activity of the tumor (Figure 4). MRI showed a destructive bony lesion of the mentioned bones associated with the soft-tissue mass (Figure 3).
Bone scan showed increased uptake in the involved areas (Figure 5). Chest plain radiographs and CT showed no distant metastasis. An incisional biopsy was performed, and histopathology showed a malignant small round cell tumor, identified as Ewing sarcoma (Figure 6). An immunohistochemistry study demonstrated positive CD99 and negative cytokeratin, leukocyte common antigen, desmin, and synaptophysin.
The patient was started on 4 cycles of adjuvant chemotherapy. Cycles 1 and 3 involved cyclophosphamide 2 g, vincristine 2 g, and doxorubicin 50 mg; cycles 2 and 4 involved ifosfamide 3.5 g and etoposide 200 mg. Tumor shrinkage occurred after chemotherapy. Clinical response to preoperative chemotherapy was documented by a decrease in tumor size at follow-ups. The patient underwent below-knee amputation.
Postoperative histopathology confirmed the diagnosis of Ewing sarcoma of the calcaneus, navicular, cuboid, and cuneiform bones and all metatarsal bones except the first (Figure 7). At 2-year follow-up, the patient had no evidence of local recurrence or distant metastasis based on chest CT and clinical examination of the affected site.
Discussion
Ewing sarcoma is the prototype of round small cell malignancies that arise from the long bones and the flat bones. It seldom involves the hands or feet. To our knowledge, this is the first report of Ewing sarcoma of the foot with multiple-bone involvement. Our literature review found a case of Ewing sarcoma of the first phalanx of the third toe, the second metatarsal bone, the cuneiform, the cuboid, and the talus, with lesser soft-tissue extension compared with our patient’s case.9
As this foot tumor is rare, there are few reports on its clinical aspects, appropriate treatment, and long-term outcome. For treatment of nonmetastatic Ewing sarcoma, limb-salvage surgery is advised if response has been good and there is a reasonable expectation of negative margins and good functional results.
Radiation and surgery may be part of the overall treatment plan. Radiation without surgery has a unique role in pelvic Ewing sarcoma, in contrast to extremity Ewing sarcoma. In our opinion, margins and histologic necrosis in the resection specimen are examined after surgery, and, if the margins are widely negative and histologic response is good, no further local control is advised. If the margin is positive, postoperative radiation therapy is recommended.1 Amputation has gradually become a (rare) choice in the treatment of extremity sarcomas.9 In our patient’s case, surgery was preferred over radiation therapy after chemotherapy because of the low risk of local side effects and the expected high efficacy. In addition, radiation at such high doses for Ewing sarcoma in the foot causes functional impairment. Because of the multiple-bone involvement, a salvage procedure was not possible for our patient. Given the calcaneal involvement, however, below-knee amputation was considered safer than ankle disarticulation.
Multiple-bone involvement occurs in the advanced stage of Ewing sarcoma, usually after visceral and pulmonary metastases are detected.9 The case reported by Rammal and colleagues9 had both multiple-bone involvement in the foot and pulmonary metastasis. The authors indicated that hematogenous spread of the tumor was discerned because the lesions were noncontiguous.9 Our patient had no distant metastases. We think his tumor originated in a tarsal or midtarsal bone and extended to adjacent bones. Therefore, it probably spread through its capsular and ligamentous attachment among tarsal and midtarsal bones, as the involvement was contiguous rather than distinct.
Average delay from symptom onset to diagnosis was reported to be 34 weeks.3 Average physician delay from initial visit to correct diagnosis was reported to be 19 weeks.3 Patients may have erythema, fever, and swelling, suggestive of osteomyelitis.3 Laboratory results may show increased white blood cell count and elevated ESR and CRP level.3 In addition, needle biopsy of the tumor may reveal an appearance grossly similar to that of pus.3 Therefore, physicians may send all the tissue out for microbiological analysis (according to the erroneous diagnosis of infection) and none out for pathologic analysis. The situation can be further complicated when Ewing sarcoma occurs in the foot, an uncommon site. In this special case, multiple-bone involvement can present a misleading clinical picture of infection.10 In other words, infection is one of the best choices in the differential diagnosis.7 Also to be considered are multicentric giant cell tumor, fibrosarcoma,11 and osteosarcoma.12
1. Herring JA. Malignant tumors of bone. In: Herring JA, ed. Tachdjian’s Pediatric Orthopaedics. Philadelphia, PA: Saunders Elsevier; 2008:2324-2327.
2. Cavazzana AO, Miser JS, Jefferson J, Triche TJ. Experimental evidence for a neural origin of Ewing’s sarcoma of bone. Am J Pathol. 1987;127(3):507-518.
3. Canale ST, Beaty JH. Malignant tumors of bone. In: Canale ST, ed. Campbell’s Operative Orthopaedics. Philadelphia, PA: Mosby Elsevier; 2008:910-913.
4. Unni KK. Ewing sarcoma. In: Unni KK, ed. Dahlin’s Bone Tumor: General Aspects and Data on 11087 Cases. Philadelphia, PA: Lippincott-Raven; 1996:121-142.
5. Casadei R, Magnani M, Biagini R, Mercuri M. Prognostic factors in Ewing’s sarcoma of the foot. Clin Orthop. 2004;(420):230-238.
6. Greenspan A, Jundt G, Remagen W. Bone-forming (osteogenic) lesions. In: Greenspan A, Jundt G, Remagen W, eds. Differential Diagnosis in Orthopaedic Oncology. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007:114.
7. Metcalfe JE, Grimer RJ. Ewing’s sarcoma of the foot masquerading as osteomyelitis. Foot Ankle Surg. 2004;10(1):29-33.
8. Hoffmann C, Ahrens S, Dunst J, et al. Pelvis Ewing sarcoma: a retrospective analysis of 241 cases. Cancer. 1999;85(4):869-877.
9. Rammal H, Ghanem I, Torbey PH, Dagher F, Kharrat K. Multifocal Ewing sarcoma of the foot. J Pediatr Hematol Oncol. 2008;30(4):298-300.
10. Ledermann HP, Morrison WB, Schweitzer ME. MR image analysis of pedal osteomyelitis: distribution, patterns of spread, and frequency of associated ulceration and septic arthritis. Radiology. 2002;223(3):747-755.
11. Dhillon MS, Prabhudev Prasad AP, Virk MS, Aggarwal S. Multicentric giant cell tumor involving the same foot: a case report and review of literature. Indian J Orthop. 2007;41(2):154-157.
12. Baraga JJ, Amarami KK, Swee RG, Wold L, Unni KK. Radiographic features of Ewing’s sarcoma of the bones of the hand and feet. Skeletal Radiol. 2001;30(3):121-126.
1. Herring JA. Malignant tumors of bone. In: Herring JA, ed. Tachdjian’s Pediatric Orthopaedics. Philadelphia, PA: Saunders Elsevier; 2008:2324-2327.
2. Cavazzana AO, Miser JS, Jefferson J, Triche TJ. Experimental evidence for a neural origin of Ewing’s sarcoma of bone. Am J Pathol. 1987;127(3):507-518.
3. Canale ST, Beaty JH. Malignant tumors of bone. In: Canale ST, ed. Campbell’s Operative Orthopaedics. Philadelphia, PA: Mosby Elsevier; 2008:910-913.
4. Unni KK. Ewing sarcoma. In: Unni KK, ed. Dahlin’s Bone Tumor: General Aspects and Data on 11087 Cases. Philadelphia, PA: Lippincott-Raven; 1996:121-142.
5. Casadei R, Magnani M, Biagini R, Mercuri M. Prognostic factors in Ewing’s sarcoma of the foot. Clin Orthop. 2004;(420):230-238.
6. Greenspan A, Jundt G, Remagen W. Bone-forming (osteogenic) lesions. In: Greenspan A, Jundt G, Remagen W, eds. Differential Diagnosis in Orthopaedic Oncology. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007:114.
7. Metcalfe JE, Grimer RJ. Ewing’s sarcoma of the foot masquerading as osteomyelitis. Foot Ankle Surg. 2004;10(1):29-33.
8. Hoffmann C, Ahrens S, Dunst J, et al. Pelvis Ewing sarcoma: a retrospective analysis of 241 cases. Cancer. 1999;85(4):869-877.
9. Rammal H, Ghanem I, Torbey PH, Dagher F, Kharrat K. Multifocal Ewing sarcoma of the foot. J Pediatr Hematol Oncol. 2008;30(4):298-300.
10. Ledermann HP, Morrison WB, Schweitzer ME. MR image analysis of pedal osteomyelitis: distribution, patterns of spread, and frequency of associated ulceration and septic arthritis. Radiology. 2002;223(3):747-755.
11. Dhillon MS, Prabhudev Prasad AP, Virk MS, Aggarwal S. Multicentric giant cell tumor involving the same foot: a case report and review of literature. Indian J Orthop. 2007;41(2):154-157.
12. Baraga JJ, Amarami KK, Swee RG, Wold L, Unni KK. Radiographic features of Ewing’s sarcoma of the bones of the hand and feet. Skeletal Radiol. 2001;30(3):121-126.
