Malignant melanoma is genetically distinct from clear cell sarcoma of tendons and aponeurosis

Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
British Journal of Cancer (Impact Factor: 4.84). 03/2001; 84(4):535-8. DOI: 10.1054/bjoc.2000.1628
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Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts) and conventional malignant melanoma may demonstrate significant morphologic overlap at the light microscopic and ultrastructural level. Consequently, the clinically relevant distinction between primary clear cell sarcoma and metastatic melanoma in the absence of a known primary cutaneous, mucosal or ocular tumour may occasionally cause diagnostic problems. A balanced translocation, t(12;22)(q13;q13), which can be detected, amongst others, using the reverse transcriptase polymerase chain reaction (RT-PCR) or fluorescent in situ hybridization (FISH), has been identified in a high percentage (50-75%) of clear cell sarcomas and is presumed to be tumour specific. Whether this chromosomal rearrangement is present in malignant melanoma has, to date, not as yet been studied by molecular genetic or molecular cytogenetic techniques. Using RT-PCR and FISH, a series of metastases from 25 known cutaneous melanomas and 8 melanoma cell lines (5 uveal and 3 cutaneous) were screened for the t(12;22)(q13;q13) translocation. Primers for RT-PCR were chosen based upon published breakpoint sequences. The Cosmids G9 and CCS2.2, corresponding to the 5' region of EWS and 3' region of ATF-1 respectively, were used as probes. The translocation was not identified in any of the melanomas or melanoma cell lines analysed in this study; in contrast this translocation was identified in 3 out of 5 clear cell sarcomas using these techniques. This allows distinction between translocation positive cases of clear cell sarcoma and malignant melanoma at a molecular genetic level. Consequently, in diagnostically challenging cases, this represents a valuable tool for the clinicopathologic differentiation between these two entities, with an important impact on patient management and prognosis.

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    • "Absence of the detectable EWS/AFT1 rearrangement may occasionally lead to erroneous exclusion of a translocation-negative CCS. Therefore, histological assessment is essential for the correct diagnosis of CCS [6]. In addition, CCS accounts for <1% of soft tissue sarcomas, and this tumor is so rare that there are no standard regimens. "
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    ABSTRACT: Background Clear cell sarcoma (CCS) and malignant melanoma share overlapping immunohistochemistry with regard to the melanocytic markers HMB45, S100, and Melan-A. However, the translocation t(12; 22)(q13; q12) is specific to CCS. Therefore, although these neoplasms are closely related, they are now considered to be distinct entities. However, the translocation is apparently detectable only in 50%–70% of CCS cases. Therefore, the absence of a detectable EWS/AFT1 rearrangement may occasionally lead to erroneous exclusion of a translocation-negative CCS. Therefore, histological assessment is essential for the correct diagnosis of CCS. Primary CCS of the bone is exceedingly rare. Only a few cases of primary CCS arising in the ulna, metatarsals, ribs, radius, sacrum, and humerus have been reported, and primary CCS arising in the pubic bone has not been reported till date. Case presentation We present the case of an 81-year-old man with primary CCS of the pubic bone. Histological examination of the pubic bone revealed monomorphic small-sized cells arranged predominantly as a diffuse sheet with round, hyperchromatic nuclei and inconspicuous nucleoli. The cells had scant cytoplasm, and the biopsy findings indicated small round cell tumor (SRCT). Immunohistochemical staining revealed the tumor cells to be positive for HMB45, S100, and Melan-A but negative for cytokeratin (AE1/AE3) and epithelial membrane antigen. To the best of our knowledge, this is the first case report of primary CCS of the pubic bone resembling SRCT. This ambiguous appearance underscores the difficulties encountered during the histological diagnosis of this rare variant of CCS. Conclusion Awareness of primary CCS of the bone is clinically important for accurate diagnosis and management when the tumor is located in unusual locations such as the pubic bone and when the translocation t(12; 22)(q13; q12) is absent.
    BMC Cancer 11/2012; 12(1):538. DOI:10.1186/1471-2407-12-538 · 3.36 Impact Factor
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    • "Recent cytogenetic studies have shown that clear cell sarcoma has a t(12;22) (q13;q12) translocation, a feature not encountered in malignant melanoma [8,9]. This chromosomal translocation of clear cell sarcoma has been detected in 50-75% of patients [10]. Cytogenetic analysis was performed in only one of the six previously presented cases of primary clear cell sarcoma of bone and no chromosomal abnormality was detected in that case [11]. "
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    ABSTRACT: We report a case of primary clear cell sarcoma occurring in the humerus. A 20 year old girl was referred to our hospital two years ago with painless swelling of the soft tissue surrounding the proximal right humerus. The conventional radiographic image showed an ill-defined, aggressive, osteolytic lesion associated with a partial cortical defect of the proximal right humerus. Magnetic resonance imaging found an irregularly shaped extraosseous mass extending from the proximal shaft of the right humerus, penetrating through the destroyed bone and invading the biceps brachii. After preoperative chemotherapy, a total tumor resection, internal fixation and bone cement implantation were performed. Histological studies of the resected tumor found that fibrous septa divided into well-defined nests and polygonal and fusiform cells with clear cytoplasm. Immunohistochemical studies demonstrated strong positive cytoplasmic staining with S-100 and scattered positivity with HMB-45. These findings led to a final, definitive diagnosis of clear cell sarcoma of the humerus. After routine postoperative chemotherapy, a 2-year follow-up showed no metastasis. Our findings in this report point out that primary clear cell sarcoma can originate from within the humerus and that limb salvage surgery can obtain a good result.
    World Journal of Surgical Oncology 12/2011; 9(1):163. DOI:10.1186/1477-7819-9-163 · 1.41 Impact Factor
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    • "Int J Gynecol Cancer 1995;/ 5:/ 396Á9. [8] Hetzel DJ, Stanhope CR, O'Neill BP, Lennon VA. Gynecologic cancer in patients with subacute cerebellar degeneration predicted by anti-Purkinje cell antibodies and limited in metastatic volume. "

    Acta oncologica (Stockholm, Sweden) 02/2008; 47(8):1593-5. DOI:10.1080/02841860701843068 · 3.00 Impact Factor
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