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Trisomy 8 as the sole cytogenetic abnormality in a case of extraskeletal mesenchymal chondrosarcoma
Cancer Genetics and Cytogenetics 159 (2005) 151–154
Short communication
Trisomy 8 as the sole cytogenetic abnormality in a case of extraskeletal mesenchymal chondrosarcoma Ken M. Gatter*, Susan Olson, Helen Lawce, Anne E. Rader Department of Pathology and Cytogenetics, Oregon Health and Sciences University, 3181 S.W. Sam Jackson Park, Dillehunt Hall, L471, Portland, Oregon 97201-3098 Received 8 March 2004; received in revised form 12 October 2004; accepted 15 October 2004
Abstract
Mesenchymal chondrosarcoma is a rare malignant tumor that comprises about 3–10% of all sarcomas. Reports of cytogenetic studies of mesenchymal chondrosarcoma are limited and no consistent cytogenetic abnormality has surfaced. Some mesenchymal chondrosarcomas have a t(11;22) translocation suggesting a relationship with the PNET/Ewing tumor family. We report what to our knowledge is the first case of trisomy 8 as the sole cytogenetic abnormality in a mesenchymal chondrosarcoma. 쑖 2005 Elsevier Inc. All rights reserved.
1. Introduction Mesenchymal chondrosarcoma is a rare malignant tumor that comprises about 1–3% of chondrosarcomas. The peak incidence is in the second and third decades, affecting males and females equally. It is more common in the bone than in soft tissues, with between one third to one half arising outside of bone [1]. Extraskeletal mesenchymal chondrosarcomas most commonly involve the head and neck, the dura, the meninges and the lower extremities [2]. whereas skeletal mesenchymal chondrosarcomas typically arise in the jawbone and ribs [3]. Under the microscope a mesenchymal chondrosarcoma is biphasic. There is a portion composed of small, undifferentiated round or slightly spindled cells and a second pattern composed of islands of well-differentiated hyaline cartilage. These two patterns may be distinct or blend gradually together. Reports of cytogenetic studies of mesenchymal chondrosarcoma are relatively limited. We identified only 7 cases with reported cytogenetic abnormalities and all were complex karyotype. No consistent cytogenetic abnormality has surfaced. One interesting report is of a mesenchymal chondrosarcomas with a t(11;22)(q24lq12), a translocation identical to the peripheral primitive neuroendocrine tumor (PNET)/Ewing sarcoma. Although no studies have yet con-
* Corresponding author. Tel.: 503-494-3562; fax: 503-494-8148. E-mail address: [email protected] (K.M. Gatter). 0165-4608/05/$ – see front matter 쑖 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.cancergencyto.2004.10.007
firmed the presence of the EWS/FLI-1 fusion transcript, the report has prompted some commentators to ask whether mesenchymal chondrosarcomas might be within the PNET/ Ewing spectrum [4,5]. The case reported herein is unique because cytogenetic analysis showed trisomy 8 in 15 of 20 metaphase cells and this was the only cytogenetic abnormality. Previous reports include one case of partial deletion of chromosome 8 and one included pentasomy 8 with t(11;22)(q24;q12), [5] but the literature search did not uncover any reports involving trisomy 8 as the sole cytogenetic abnormality.
2. Materials and Methods 2.1. Case history A 10-year-old normal appearing girl presented with a small painless lump in her right lower thigh. The patient and her parents commented that the lesion had enlarged over the last several weeks. A biopsy was performed. Histologically, the tumor demonstrated two distinct patterns of growth. One pattern consisted of discreet lobules and islands of well-differentiated cartilage and the other pattern consisted of diffuse sheets of small round cells with scant cytoplasm, significant cytologic atypia and increased mitotic activity. In the majority of the tumor these two patterns were separated by dense fibrous bands, however, in some areas the two patterns blended at the periphery (Fig. 1). There was no hemangiopericytoma like vascular pattern [6].
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3. Results Fifteen of twenty metaphase cells had an extra chromosome 8 as the only abnormality and five appeared normal female. The karyotype was designated according to the ISCN 1995 [7], as follows: 47,XX,⫹8[15]/46,XX[5] (Fig. 2). FISH confirmed the presence of trisomy 8 in both the low grade cartilaginous portions (block A) and the small round blue cell areas (block B). Of 300 interphase cells scored on one section of block A: 31 showed 1 signal; 208 showed 2 signals; 1 showed 3 signals (20% of cells with trisomy 8). Of 200 interphase cells scored from a section from block B: 41 showed 3 signals (20.5% with trisomy 8).
Fig. 1. Mesenchymal chondrosarcoma with a focus of undifferentiated small round tumor cells adjacent to an island of well-differentiated cartilage (hematoxylin-eosin stain ×200).
Immunohistochemical analysis included negative stains for CD45, desmin, actin, CD30, HMB-45 and CD99. The biopsy was interpreted as a high-grade mesenchymal chondrosarcoma. The patient received two courses of chemotherapy. She then underwent definitive resection of the right thigh mass, with a wide excision margin. The histology of the resection specimen confirmed that the margins of excision did not involve the sarcoma, but also showed that the chemotherapy had little visible killing effect on the tumor, since there were no areas of necrosis on the paraffin sections of the tumor. Histologic sections also confirmed the lack of any visible boney involvement. A pre-operative PET scan showed reduced tumor activity but a pre-operative MRI did not show any significant reduction in tumor size. The patient has no clinical evidence of local recurrence or metastatic disease ten months after diagnosis. 2.2. Cytogenetic analysis A representative sample of the soft tissue tumor was submitted for cytogenetic analysis. Cells were cultured for six days in closed flasks containing either RPMI or Chang medium. Harvesting and preparation of slides were performed according to standard laboratory protocol. Twenty GTW-banded (G-banding by trypsin/Wright stain) metaphases at approximately the 400 band level were analyzed; three of these were karyotyped. Fluorescent in situ hybridization (FISH) was performed on tumor tissue in paraffin using Vysis CEP 8 probes to verify the presence of trisomy 8 in the low-grade cartilaginous areas (block A) and in the areas of small round blue cells (block B). Additional FISH was performed on paraffin embedded tumor tissue from blocks A and B using the following probe for N-MYC: Vysis LSI N-MYC/CEP 2 probe.
4. Discussion To our knowledge, this is the first published case of isolated trisomy 8 in a mesenchymal chondrosarcoma. Prior publications of cytogenetic abnormalities in mesenchymal chondrosarcomas all reported complex abnormalities [7]. Unlike extraskeletal myxoid chondrosarcomas, which have a characteristic translocation resulting in a fusion gene involving the CHN (TEC) gene at 9q22, cytogenetic studies of mesenchymal chondrosarcomas have shown a lack of any characteristic abnormality [8]. Despite the significant cytogenetic heterogeneity in chondrosarcomas, commentators generally agree that the karyotypic abnormalities in chondromatous tumors are not random [9]. Naumann, et al., recently reported two cases of extraskeletal mesenchymal chondrosarcoma and suggest that the small number of reported cytogenetic findings of mesenchymal chondrosarcoma may contain some shared chromosomal abnormalities [10]. Both of the cases reported by Naumann, et al., had a Robertsonian translocation, der(13;21)(q10;q10), loss of chromosome 8 and 20 material, and gain of chromosome 12. The authors noted that disruption of the 20q13 breakpoint and extra copies of all or part of chromosome 12 were previously described in mesenchymal chondrosarcomas and may represent a relatively consistent finding. Interestingly, disruption of the 20q13 breakpoint, easily observed in the first case reported by Naumann, et al. [10], was only clearly evident in the second case with the aid of spectral karyotypic analysis (SKY) and fluorescence in situ hybridization (FISH) studies. The authors speculate that the addition of molecular cytogenetic techniques like SKY and FISH might uncover additional shared chromosomal abnormalities, especially when the tumor contains marker chromosomes (chromosomes for which the origin cannot be identified by banding techniques). Several authors have noted the importance of finding t(11;22)(q24;q12) in mesenchymal chondrosarcoma, because the translocation is characteristic of PNET/Ewing sarcoma and its presence suggests a relationship with neuroectodermal tumors [10]. However, the mesenchymal chondrosarcoma containing t(11;22)(q24;q12) contained
K.M. Gatter et al. / Cancer Genetics and Cytogenetics 159 (2005) 151–154
153
Fig. 2. Representative G-banded karyotype showing 47,XX,⫹8[15]/46,XX[5].
other cytogenetic abnormalities and did not include verification of the EWS/FLI-1 fusion transcript. Interestingly, additional chromosomal abnormalities involving the characteristic PNET/Ewing’s sarcoma translocation included pentasomy 8 and trisomy 21. To further confound matters, others have reported trisomy 8 in Ewing’s sarcoma and have suggested that trisomy 8 may indicate tumor progression [11]. Our case differs from previous reports of cytogenetic findings in mesenchymal chondrosarcoma. It contains none of the chromosomal abnormalities reported by Naumann, et al. [10]. Neither does our case have a marker chromosome that might benefit from SKY or FISH to uncover perhaps a portion of a chromosome previously reported. Moreover, the 400 band level resolution was sufficient to rule out t(11;22) and any other major rearrangement. Our results, showing trisomy 8 as the sole karyotypic abnormality in 15 of 20 metaphases, suggest that trisomy 8 is the predominant abnormality in this case. Moreover, FISH results confirmed trisomy 8 in both the low grade cartilaginous areas and the small round blue cell mesenchymal areas. This finding suggests that the cytogenetic properties of the well-differentiated cartilage islands are similar, perhaps identical to the undifferentiated portions, since trisomy 8 was the only karyotype.
Trisomy 8 is not a specific for a particular tumor. It is associated with many hematologic malignancies and some epithelial neoplasms, like breast cancer and ovarian teratomas. Sarcomas also frequently involve trisomy 8, but as a secondary change. For example, Maurici, et al. [12], looked at 52 Ewing sarcomas and found trisomy 8 in 24 (46%) of the examined cases. Trisomy 8 is consistently present in infantile fibrosarcoma [13], in about 20% of myxoid liposarcomas, and in about 50% of embryonal rhabdomyosarcomas. Trisomy 8 is also a consistent finding in some non-neoplastic fibrosing conditions like Dupuytren’s contracture and desmoids [14]. Investigators do not know how trisomy 8 contributes to tumorigenesis. A recent article reported a microarray comparison of acute myeloid leukemia (AML) with trisomy 8 as the sole cytogenetic abnormality and AML showing normal cytogenetics [15]. The cohort with the trisomy 8 showed a strong association with overexpression of genes on chromosome 8, thereby suggesting a possible role for gene dosage. Another group of investigators examined ten chondrosarcomas and showed overexpression of C-MYC in two of ten chondrosarcomas. The role of C-MYC in tumorigenesis was not clear because the two chondrosarcomas were diploid and aneuploid [16]. Our case may similarly involve amplification
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K.M. Gatter et al. / Cancer Genetics and Cytogenetics 159 (2005) 151–154
of the C-MYC proto-oncogene on chromosome 8, but whether or to what extent this may contribute to malignant evolution requires additional investigation.
Acknowledgment Thanks to Susan Oliver for administrative assistance.
References [1] Huvos AG, Rosen G, Dabska M, Marcove RC. Mesenchymal chondrosarcoma: a clinicopathologic analysis of 35 patients with emphasis on treatment. Cancer 1983;51:1230–7. [2] Gussion JG, Font RL, Enzinger FM, et al. Extraskeletal mesenchymal chondrosarcoma. Arch Pathol 1973;95:336. [3] Nakashima Y, Unni KK, Shives TC, Swee RG, Dahlin DC. Mesenchymal chondrosarcoma of bone and soft tissue: A review of 111 cases. Cancer 1986;57:2444–53. [4] Sainati L, Scapinello A, Montaldi S, Bolcato S, Ninfo V, Carli M, Basso G. A mesenchymal chondrosarcoma of a child with the reciprocal translocation (11;22)(q24;q12). Cancer Genet Cytogenet 1993;71: 144–7. [5] Dobin SM, Donner LR, Speights VO. Mesenchymal chondrosarcoma: A cytogenetic, immunohistochemical and ultrastructural study. Cancer Genet Cytogenet 1995;83:56–60. [6] Kempson RL, Fletcher CDM, Evans HL, et al. Tumors of the soft tissues: Cartilaginous and osseous tumors. Atlas of Tumor Pathology 1998;30:407.
[7] Szymanska J, Tarkkanen M, Wiklund T, Virolainen M, Blomqvist C, Asko-Seljavaara S, Tukiainen E, Elomaa I, Knuutila S. Cytogenetic study of extraskeletal mesenchymal chondrosarcoma. A case report. Cancer Genet Cytogenet 1996;86:170–3. [8] Sjogren H, Meis-Kindblom J, Kindblom LG, Aman P, Stenman G. Fusion of the EWS-related gene TAF2N to TEC in extraskeletal myxoid chondrosarcoma. Cancer Res 1999;59:5064–7. [9] Mandahl N, Sverre H, Arheden K, Rydholm A, Willen H, Mitelman F. Chromosomal rearrangements in chondromatous tumors. Cancer 1990;65:242–8. [10] Naumann S, Krallman PA, Unni KK, Fidler ME, Neff JR, Bridge JA. Translocation der(13;21)(q10;q10) in skeletal and extraskeletal mesenchymal chondrosarcoma. Mod Pathol 2002;15:572–6. [11] Mugneret F, Lizard S, Aurias A, Turc-Carel C. Chromosomes in Ewing’s sarcoma. II. Nonrandom additional changes, trisomy 8 and der(16)t(1;16). Cancer Genet Cytogenet 1988;32:239–45. [12] Maurici D, Perez-Ataydec A, Grier H, Baldini N, Serra M, Fletcher J. Frequency and implications of chromosome 8 and 12 gains in Ewing sarcoma. Cancer Genet Cytogenet 1998;100:106–10. [13] Schofield DE, Fletcher JA, Grier HE, Yunis EJ. Fibrosarcoma in infants and children: application of new techniques. Am J Surg Pathol 1994;18:24. [14] Dal Cin P, Sciot R, Aly MS, Delabie J, Stas M, De Wever I, Van Damme den Berghe H. Some desmoid tumors are characterized by trisomy 8. Genes Chromosomes Cancer 1994;10:131–5. [15] Virtaneva K, Wright F, Tanner S, Yuan B, Lemon W, Caligiuri M, Bloomfield C, Chapele A, Krahe R. Expression profiling reveals fundamental biologic differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics. Proc Nat’l Acad Sci USA 2001; 98:1124–9. [16] Castresana JS, Barrios C, Gomez L, Kreicbergs A. Amplification of the c-myc proto-oncogene in human chondrosarcoma. Diag Mol Pathol 1992;1:235–8.
Short communication
Trisomy 8 as the sole cytogenetic abnormality in a case of extraskeletal mesenchymal chondrosarcoma Ken M. Gatter*, Susan Olson, Helen Lawce, Anne E. Rader Department of Pathology and Cytogenetics, Oregon Health and Sciences University, 3181 S.W. Sam Jackson Park, Dillehunt Hall, L471, Portland, Oregon 97201-3098 Received 8 March 2004; received in revised form 12 October 2004; accepted 15 October 2004
Abstract
Mesenchymal chondrosarcoma is a rare malignant tumor that comprises about 3–10% of all sarcomas. Reports of cytogenetic studies of mesenchymal chondrosarcoma are limited and no consistent cytogenetic abnormality has surfaced. Some mesenchymal chondrosarcomas have a t(11;22) translocation suggesting a relationship with the PNET/Ewing tumor family. We report what to our knowledge is the first case of trisomy 8 as the sole cytogenetic abnormality in a mesenchymal chondrosarcoma. 쑖 2005 Elsevier Inc. All rights reserved.
1. Introduction Mesenchymal chondrosarcoma is a rare malignant tumor that comprises about 1–3% of chondrosarcomas. The peak incidence is in the second and third decades, affecting males and females equally. It is more common in the bone than in soft tissues, with between one third to one half arising outside of bone [1]. Extraskeletal mesenchymal chondrosarcomas most commonly involve the head and neck, the dura, the meninges and the lower extremities [2]. whereas skeletal mesenchymal chondrosarcomas typically arise in the jawbone and ribs [3]. Under the microscope a mesenchymal chondrosarcoma is biphasic. There is a portion composed of small, undifferentiated round or slightly spindled cells and a second pattern composed of islands of well-differentiated hyaline cartilage. These two patterns may be distinct or blend gradually together. Reports of cytogenetic studies of mesenchymal chondrosarcoma are relatively limited. We identified only 7 cases with reported cytogenetic abnormalities and all were complex karyotype. No consistent cytogenetic abnormality has surfaced. One interesting report is of a mesenchymal chondrosarcomas with a t(11;22)(q24lq12), a translocation identical to the peripheral primitive neuroendocrine tumor (PNET)/Ewing sarcoma. Although no studies have yet con-
* Corresponding author. Tel.: 503-494-3562; fax: 503-494-8148. E-mail address: [email protected] (K.M. Gatter). 0165-4608/05/$ – see front matter 쑖 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.cancergencyto.2004.10.007
firmed the presence of the EWS/FLI-1 fusion transcript, the report has prompted some commentators to ask whether mesenchymal chondrosarcomas might be within the PNET/ Ewing spectrum [4,5]. The case reported herein is unique because cytogenetic analysis showed trisomy 8 in 15 of 20 metaphase cells and this was the only cytogenetic abnormality. Previous reports include one case of partial deletion of chromosome 8 and one included pentasomy 8 with t(11;22)(q24;q12), [5] but the literature search did not uncover any reports involving trisomy 8 as the sole cytogenetic abnormality.
2. Materials and Methods 2.1. Case history A 10-year-old normal appearing girl presented with a small painless lump in her right lower thigh. The patient and her parents commented that the lesion had enlarged over the last several weeks. A biopsy was performed. Histologically, the tumor demonstrated two distinct patterns of growth. One pattern consisted of discreet lobules and islands of well-differentiated cartilage and the other pattern consisted of diffuse sheets of small round cells with scant cytoplasm, significant cytologic atypia and increased mitotic activity. In the majority of the tumor these two patterns were separated by dense fibrous bands, however, in some areas the two patterns blended at the periphery (Fig. 1). There was no hemangiopericytoma like vascular pattern [6].
152
K.M. Gatter et al. / Cancer Genetics and Cytogenetics 159 (2005) 151–154
3. Results Fifteen of twenty metaphase cells had an extra chromosome 8 as the only abnormality and five appeared normal female. The karyotype was designated according to the ISCN 1995 [7], as follows: 47,XX,⫹8[15]/46,XX[5] (Fig. 2). FISH confirmed the presence of trisomy 8 in both the low grade cartilaginous portions (block A) and the small round blue cell areas (block B). Of 300 interphase cells scored on one section of block A: 31 showed 1 signal; 208 showed 2 signals; 1 showed 3 signals (20% of cells with trisomy 8). Of 200 interphase cells scored from a section from block B: 41 showed 3 signals (20.5% with trisomy 8).
Fig. 1. Mesenchymal chondrosarcoma with a focus of undifferentiated small round tumor cells adjacent to an island of well-differentiated cartilage (hematoxylin-eosin stain ×200).
Immunohistochemical analysis included negative stains for CD45, desmin, actin, CD30, HMB-45 and CD99. The biopsy was interpreted as a high-grade mesenchymal chondrosarcoma. The patient received two courses of chemotherapy. She then underwent definitive resection of the right thigh mass, with a wide excision margin. The histology of the resection specimen confirmed that the margins of excision did not involve the sarcoma, but also showed that the chemotherapy had little visible killing effect on the tumor, since there were no areas of necrosis on the paraffin sections of the tumor. Histologic sections also confirmed the lack of any visible boney involvement. A pre-operative PET scan showed reduced tumor activity but a pre-operative MRI did not show any significant reduction in tumor size. The patient has no clinical evidence of local recurrence or metastatic disease ten months after diagnosis. 2.2. Cytogenetic analysis A representative sample of the soft tissue tumor was submitted for cytogenetic analysis. Cells were cultured for six days in closed flasks containing either RPMI or Chang medium. Harvesting and preparation of slides were performed according to standard laboratory protocol. Twenty GTW-banded (G-banding by trypsin/Wright stain) metaphases at approximately the 400 band level were analyzed; three of these were karyotyped. Fluorescent in situ hybridization (FISH) was performed on tumor tissue in paraffin using Vysis CEP 8 probes to verify the presence of trisomy 8 in the low-grade cartilaginous areas (block A) and in the areas of small round blue cells (block B). Additional FISH was performed on paraffin embedded tumor tissue from blocks A and B using the following probe for N-MYC: Vysis LSI N-MYC/CEP 2 probe.
4. Discussion To our knowledge, this is the first published case of isolated trisomy 8 in a mesenchymal chondrosarcoma. Prior publications of cytogenetic abnormalities in mesenchymal chondrosarcomas all reported complex abnormalities [7]. Unlike extraskeletal myxoid chondrosarcomas, which have a characteristic translocation resulting in a fusion gene involving the CHN (TEC) gene at 9q22, cytogenetic studies of mesenchymal chondrosarcomas have shown a lack of any characteristic abnormality [8]. Despite the significant cytogenetic heterogeneity in chondrosarcomas, commentators generally agree that the karyotypic abnormalities in chondromatous tumors are not random [9]. Naumann, et al., recently reported two cases of extraskeletal mesenchymal chondrosarcoma and suggest that the small number of reported cytogenetic findings of mesenchymal chondrosarcoma may contain some shared chromosomal abnormalities [10]. Both of the cases reported by Naumann, et al., had a Robertsonian translocation, der(13;21)(q10;q10), loss of chromosome 8 and 20 material, and gain of chromosome 12. The authors noted that disruption of the 20q13 breakpoint and extra copies of all or part of chromosome 12 were previously described in mesenchymal chondrosarcomas and may represent a relatively consistent finding. Interestingly, disruption of the 20q13 breakpoint, easily observed in the first case reported by Naumann, et al. [10], was only clearly evident in the second case with the aid of spectral karyotypic analysis (SKY) and fluorescence in situ hybridization (FISH) studies. The authors speculate that the addition of molecular cytogenetic techniques like SKY and FISH might uncover additional shared chromosomal abnormalities, especially when the tumor contains marker chromosomes (chromosomes for which the origin cannot be identified by banding techniques). Several authors have noted the importance of finding t(11;22)(q24;q12) in mesenchymal chondrosarcoma, because the translocation is characteristic of PNET/Ewing sarcoma and its presence suggests a relationship with neuroectodermal tumors [10]. However, the mesenchymal chondrosarcoma containing t(11;22)(q24;q12) contained
K.M. Gatter et al. / Cancer Genetics and Cytogenetics 159 (2005) 151–154
153
Fig. 2. Representative G-banded karyotype showing 47,XX,⫹8[15]/46,XX[5].
other cytogenetic abnormalities and did not include verification of the EWS/FLI-1 fusion transcript. Interestingly, additional chromosomal abnormalities involving the characteristic PNET/Ewing’s sarcoma translocation included pentasomy 8 and trisomy 21. To further confound matters, others have reported trisomy 8 in Ewing’s sarcoma and have suggested that trisomy 8 may indicate tumor progression [11]. Our case differs from previous reports of cytogenetic findings in mesenchymal chondrosarcoma. It contains none of the chromosomal abnormalities reported by Naumann, et al. [10]. Neither does our case have a marker chromosome that might benefit from SKY or FISH to uncover perhaps a portion of a chromosome previously reported. Moreover, the 400 band level resolution was sufficient to rule out t(11;22) and any other major rearrangement. Our results, showing trisomy 8 as the sole karyotypic abnormality in 15 of 20 metaphases, suggest that trisomy 8 is the predominant abnormality in this case. Moreover, FISH results confirmed trisomy 8 in both the low grade cartilaginous areas and the small round blue cell mesenchymal areas. This finding suggests that the cytogenetic properties of the well-differentiated cartilage islands are similar, perhaps identical to the undifferentiated portions, since trisomy 8 was the only karyotype.
Trisomy 8 is not a specific for a particular tumor. It is associated with many hematologic malignancies and some epithelial neoplasms, like breast cancer and ovarian teratomas. Sarcomas also frequently involve trisomy 8, but as a secondary change. For example, Maurici, et al. [12], looked at 52 Ewing sarcomas and found trisomy 8 in 24 (46%) of the examined cases. Trisomy 8 is consistently present in infantile fibrosarcoma [13], in about 20% of myxoid liposarcomas, and in about 50% of embryonal rhabdomyosarcomas. Trisomy 8 is also a consistent finding in some non-neoplastic fibrosing conditions like Dupuytren’s contracture and desmoids [14]. Investigators do not know how trisomy 8 contributes to tumorigenesis. A recent article reported a microarray comparison of acute myeloid leukemia (AML) with trisomy 8 as the sole cytogenetic abnormality and AML showing normal cytogenetics [15]. The cohort with the trisomy 8 showed a strong association with overexpression of genes on chromosome 8, thereby suggesting a possible role for gene dosage. Another group of investigators examined ten chondrosarcomas and showed overexpression of C-MYC in two of ten chondrosarcomas. The role of C-MYC in tumorigenesis was not clear because the two chondrosarcomas were diploid and aneuploid [16]. Our case may similarly involve amplification
154
K.M. Gatter et al. / Cancer Genetics and Cytogenetics 159 (2005) 151–154
of the C-MYC proto-oncogene on chromosome 8, but whether or to what extent this may contribute to malignant evolution requires additional investigation.
Acknowledgment Thanks to Susan Oliver for administrative assistance.
References [1] Huvos AG, Rosen G, Dabska M, Marcove RC. Mesenchymal chondrosarcoma: a clinicopathologic analysis of 35 patients with emphasis on treatment. Cancer 1983;51:1230–7. [2] Gussion JG, Font RL, Enzinger FM, et al. Extraskeletal mesenchymal chondrosarcoma. Arch Pathol 1973;95:336. [3] Nakashima Y, Unni KK, Shives TC, Swee RG, Dahlin DC. Mesenchymal chondrosarcoma of bone and soft tissue: A review of 111 cases. Cancer 1986;57:2444–53. [4] Sainati L, Scapinello A, Montaldi S, Bolcato S, Ninfo V, Carli M, Basso G. A mesenchymal chondrosarcoma of a child with the reciprocal translocation (11;22)(q24;q12). Cancer Genet Cytogenet 1993;71: 144–7. [5] Dobin SM, Donner LR, Speights VO. Mesenchymal chondrosarcoma: A cytogenetic, immunohistochemical and ultrastructural study. Cancer Genet Cytogenet 1995;83:56–60. [6] Kempson RL, Fletcher CDM, Evans HL, et al. Tumors of the soft tissues: Cartilaginous and osseous tumors. Atlas of Tumor Pathology 1998;30:407.
[7] Szymanska J, Tarkkanen M, Wiklund T, Virolainen M, Blomqvist C, Asko-Seljavaara S, Tukiainen E, Elomaa I, Knuutila S. Cytogenetic study of extraskeletal mesenchymal chondrosarcoma. A case report. Cancer Genet Cytogenet 1996;86:170–3. [8] Sjogren H, Meis-Kindblom J, Kindblom LG, Aman P, Stenman G. Fusion of the EWS-related gene TAF2N to TEC in extraskeletal myxoid chondrosarcoma. Cancer Res 1999;59:5064–7. [9] Mandahl N, Sverre H, Arheden K, Rydholm A, Willen H, Mitelman F. Chromosomal rearrangements in chondromatous tumors. Cancer 1990;65:242–8. [10] Naumann S, Krallman PA, Unni KK, Fidler ME, Neff JR, Bridge JA. Translocation der(13;21)(q10;q10) in skeletal and extraskeletal mesenchymal chondrosarcoma. Mod Pathol 2002;15:572–6. [11] Mugneret F, Lizard S, Aurias A, Turc-Carel C. Chromosomes in Ewing’s sarcoma. II. Nonrandom additional changes, trisomy 8 and der(16)t(1;16). Cancer Genet Cytogenet 1988;32:239–45. [12] Maurici D, Perez-Ataydec A, Grier H, Baldini N, Serra M, Fletcher J. Frequency and implications of chromosome 8 and 12 gains in Ewing sarcoma. Cancer Genet Cytogenet 1998;100:106–10. [13] Schofield DE, Fletcher JA, Grier HE, Yunis EJ. Fibrosarcoma in infants and children: application of new techniques. Am J Surg Pathol 1994;18:24. [14] Dal Cin P, Sciot R, Aly MS, Delabie J, Stas M, De Wever I, Van Damme den Berghe H. Some desmoid tumors are characterized by trisomy 8. Genes Chromosomes Cancer 1994;10:131–5. [15] Virtaneva K, Wright F, Tanner S, Yuan B, Lemon W, Caligiuri M, Bloomfield C, Chapele A, Krahe R. Expression profiling reveals fundamental biologic differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics. Proc Nat’l Acad Sci USA 2001; 98:1124–9. [16] Castresana JS, Barrios C, Gomez L, Kreicbergs A. Amplification of the c-myc proto-oncogene in human chondrosarcoma. Diag Mol Pathol 1992;1:235–8.