Malignant melanoma is genetically distinct from clear cell sarcoma of tendons and aponeurosis (malignant melanoma of soft parts)

Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
British Journal of Cancer (Impact Factor: 4.82). 03/2001; 84(4):535-8. DOI: 10.1054/bjoc.2000.1628
Source: PubMed

ABSTRACT 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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    ABSTRACT: Although the presence of the t(12;22)(q13;q12) translocation (the defining molecular feature of malignant melanoma of soft parts/clear cell sarcoma) in cutaneous melanoma has been investigated, no large-scale studies have been performed among mucosal melanoma (MucM). In this study we assessed the prevalence of the EWSR1 rearrangement in primary MucM, and analyzed gross and microscopic features with their potential impact on diagnosis and prognosis. Overall, 132 specimens from 84 patients were included. A total of 55 cases had an intramucosal component. Survival of MucMs of the head and neck was associated with two independent factors: size and histology. Tumors more than 3 cm in greatest dimension had an average survival of 12.75 months; those 3 cm or less had an average survival of 38.3 months (P=0.035). Purely epithelioid tumors had an average worse survival of 16.8 months (P=0.028). A cut-off value of 1 mm for Breslow depth provided a statistically significant difference in survival at both 3 and 5 years (P=-0.02) by multivariate analysis in the gynecologic tract. At the molecular level three cases had a EWSR1 rearrangement by fluorescent in-situ hybridization, but only one with an intramucosal component. None of the 58 cases tested by PCR showed the presence of the EWSR1 rearrangement. With the exception of vulvar melanomas, the prognosis of mucosal-associated melanomas was poor and there was a suggestion that spindle morphology may be more favorable. Our study also showed that the EWSR1 rearrangement was very uncommon among MucM. Though 'clear cell sarcoma' is embedded in the sarcoma literature, the synonym 'melanoma of soft parts' has considerable justification in light of our evolving understanding of the molecular genetics in the family of malignant melanomas.
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    ABSTRACT: Background: Clear cell sarcoma of tendons and aponeuroses is a rare, high grade malignant soft tissue tumor resembling melanoma and soft tissue sarcomas. Clinical and Imaging Presentation: The median age at presentation is 27 years and the most common location are the foot and the ankle. MR imaging typically shows a benign looking, well defined, homogenous mass; on T1-weighted MR images, it is usually homogeneous and isointense or slight hyperintense to muscle, whereas on T2-weighted MR images, it is usually more heterogeneous with variable signal intensity. Pathology: Microscopically, the clear cell appearance is due to the accumulation of glycogen. The cells show no or minimal pleomorphism, and paucity of mitotic figures that is in concordance with the slow-growing behavior of the tumor. Scattered multinucleated giant cells are commonly present; areas of necrosis and melanin pigment may be identified. The reciprocal translocation t(12;22)(q13;q12) is observed in more than 90% of clear cell sarcoma cases. In addition, polysomy of chromosome 8 has been observed as a secondary abnormality in many cases of clear cell sarcoma. The differential diagnosis of clear cell sarcoma should include melanoma, epithelioid malignant peripheral nerve sheath tumor, melanotic schwannoma, paraganglioma-like dermal melanocytic tumor, perivascular epithelioid cell neoplasms (PEComas), cellular blue naevus, synovial sarcoma (monophasic type), alveolar soft part sarcoma, paraganglioma, epithelioid sarcoma and carcinomas. Treatment and Prognosis: The treatment of choice for clear cell sarcoma is wide surgical resection. If complete excision is achieved, adjuvant treatments are not unnecessary. Chemotherapy is predominantly employed in patients with metastatic disease. The 5 to 20 year survival of the patients with clear cell sarcoma range from 67% to 10%. The rates of local recurrence ranges up to 84%, late metastases up to 63%, and metastases at presentation up to 30%.
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