Clear cell sarcomas are aggressive, rare soft tissue tumors and their classification among melanoma or sarcoma is still undetermined due to their clinical, pathologic, and molecular properties found in both types of tumors. This is a retrospective study of 52 patients with CCS seen between April 1979 and April 2005 in two institutions. The EWS-ATF-1 fusion transcript was studied in 31 patients and an activating mutation of the BRAF or NRAS gene was researched in 22 patients. 30 men and 22 women, with a mean age of 33 were studied. Forty-three tumors (82.69%) were located in the extremities, specially the foot (19 tumors). Median initial tumor size was 4.8？cm (1 to 15？cm). Necrosis involving more than 50% of the tumor cells was found in 14 cases (26.92%). High mitotic rate (>10) was found in 25 cases (48.07%). The EWS/ATF-1 translocation was found in 28 (53.84%) of 31 patients studied, and mutation of BRAF or NRAS was found in only 2 of 22 patients analyzed cases (3.84%). Among the tumor-associated parameters, only tumor size (>4？cm) emerged as a significant prognostic factor. Forty-nine patients had a localized disease at diagnosis (94.23%) and underwent surgical resection immediately (90%) or after neoadjuvant chemotherapy (CT) (10%). Various CT regimens were used in 37 patients (71.15%) with no significant efficacy. The 5- and 10-year OS rates were 59% and 41%, respectively. Tumor size was the only emerging prognosis factor in our series. Complete surgical resection remains the optimal treatment for this aggressive chemoresistant tumor. 1. Introduction Clear cell sarcoma (CCS) is a rare malignant tumor that was described first by Enzinger in 1965 [1]. CCS shows a predilection for the deep soft tissues of the lower extremities close to the tendon, fascia, or aponeuroses [2]. It occurs preferentially in adolescents and young adults and is associated with a high propensity of local recurrence, regional lymph node metastases, and distant metastases [1, 2]. Because of its close clinic and histologic kinship with malignant melanoma (high frequency of lymph node metastases, presence of melanin, ultrastructural evidence of melanosomes, and immunohistochemical staining for S-100 protein and melanoma-associated antigen HMB-45), Chung and Enzinger proposed the name malignant melanoma of soft parts [2]. However, despite these similarities, CCS and melanoma should be considered 2 distinct entities. Unlike melanomas, most CCS tumors are characterized by a recurrent chromosomal translocation, t(12; 22), resulting in fusion of the EWS gene on 22q12 with the ATF1 gene
References
[1]
F. M. Enzinger, “Clear-cell sarcoma of tendons and aponeuroses: an analysis of 21 cases,” Cancer, vol. 18, pp. 1163–1174, 1965.
[2]
E. B. Chung and F. M. Enzinger, “Malignant melanoma of soft parts. A reassessment of clear cell sarcoma,” American Journal of Surgical Pathology, vol. 7, no. 5, pp. 405–413, 1983.
[3]
J. Zucman, O. Delattre, C. Desmaze et al., “EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts,” Nature Genetics, vol. 4, no. 4, pp. 341–345, 1993.
[4]
I. Panagopoulos, F. Mertens, M. Debiec-Rychter et al., “Molecular genetic characterization of the EWS/ATF1 fusion gene in clear cell sarcoma of tendons and aponeuroses,” International Journal of Cancer, vol. 99, no. 4, pp. 560–567, 2002.
[5]
R. M. Patel, E. Downs-Kelly, S. W. Weiss et al., “Dual-color, break-apart fluorescence in situ hybridization for EWS gene rearrangement distinguishes clear cell sarcoma of soft tissue from malignant melanoma,” Modern Pathology, vol. 18, no. 12, pp. 1585–1590, 2005.
[6]
N. H. Segal, P. Pavlidis, W. S. Noble et al., “Classification of clear-cell sarcoma as a subtype of melanoma by genomic profiling,” Journal of Clinical Oncology, vol. 21, no. 9, pp. 1775–1781, 2003.
[7]
E. Kaplan and P. Meier, “Nonparametric estimation from incomplete observations,” American Statistical Association, vol. 53, pp. 457–481, 1958.
[8]
D. Cox, “Regression models and life-tables,” Journal of the Royal Statistical Society: Series B, vol. 34, pp. 187–220, 1972.
[9]
A. S. Sara, H. L. Evans, and R. S. Benjamin, “Malignant melanoma of soft parts (clear cell sarcoma): a study of 17 cases, with emphasis on prognostic factors,” Cancer, vol. 65, pp. 367–374, 1990.
[10]
A. K. El-Naggar, N. G. Ordó？ez, A. Sara, D. McLemore, and J. G. Batsakis, “Clear cell sarcomas and metastatic soft tissue melanomas: a flow cytometric comparison and prognostic implications,” Cancer, vol. 67, no. 8, pp. 2173–2179, 1991.
[11]
D. R. Lucas, A. G. Nascimento, and F. H. Sim, “Clear cell sarcoma of soft tissues: Mayo Clinic experience with 35 cases,” American Journal of Surgical Pathology, vol. 16, no. 12, pp. 1197–1204, 1992.
[12]
E. A. Montgomery, J. M. Meis, A. G. Ramos, D. M. Frisman, and K. L. Martz, “Clear cell sarcoma of tendons and aponeuroses: a clinicopathologic study of 58 cases with analysis of prognostic factors,” International Journal of Surgical Pathology, vol. 1, pp. 89–100, 1993.
[13]
W. Deenik, W. J. Mooi, E. J. Rutgers, et al., “Clear cell sarcoma (malignant melanoma) of soft parts: a clinicopathologic study of 30 cases,” Cancer, vol. 86, pp. 969–975, 1999.
[14]
J. William Finley, B. Hanypsiak, B. Mcgrath, W. Kraybill, and J. F. Gibbs, “Clear cell sarcoma: the Roswell Park experience,” Journal of Surgical Oncology, vol. 77, no. 1, pp. 16–20, 2001.
[15]
A. Ferrari, M. Casanova, G. Bisogno et al., “Clear cell sarcoma of tendons and aponeuroses in pediatric patients: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group,” Cancer, vol. 94, no. 12, pp. 3269–3276, 2002.
[16]
T. Takahira, Y. Oda, S. Tamiya et al., “Alterations of the p16INK4a/p14ARF pathway in clear cell sarcoma,” Cancer Science, vol. 95, no. 8, pp. 651–655, 2004.
[17]
A. Kawai, A. Hosono, R. Nakayama et al., “Clear cell sarcoma of tendons and aponeuroses: a study of 75 patients,” Cancer, vol. 109, no. 1, pp. 109–116, 2007.
[18]
J. J. Eckardt, D. J. Pritchard, and E. H. Soule, “Clear cell sarcoma. A clinicopathologic study of 27 cases,” Cancer, vol. 52, no. 8, pp. 1482–1488, 1983.
[19]
W. B. Al-Refaie, M. W. Ali, D. Z. Chu, I. B. Paz, and S. L. Blair, “Clear cell sarcoma in the era of sentinel lymph node mapping,” Journal of Surgical Oncology, vol. 87, no. 3, pp. 126–129, 2004.
[20]
F. Picciotto, A. Zaccagna, G. Derosa et al., “Clear cell sarcoma (malignant melanoma of soft parts) and sentinel lymph node biopsy,” European Journal of Dermatology, vol. 15, no. 1, pp. 46–48, 2005.
