Clear Cell Sarcoma

Fetal fibroblasts myometrium vascular smooth muscle fetal myocardium vascular endothelial cells selected reticulum cells of lymphatic organs some CD30+ lymphoid cells (rarely) selected leiomyosarcomas, epithelioid hemangioendotheliomas, epithelioid angiosarcomas, primitive neuroectodermal tumors and Ewing s sarcomas, malignant peripheral nerve sheath tumors, and clear cell sarcomas... 

KER, keratin, as detected by a mixture of CAM5.2, MAK-6, and AEl /AE3 EMA, epithelial membrane antigen VIM, vimentin DES, desmin MSA, muscle-specific actin SMA, smooth muscle (alpha isoform) actin CALD, h-caldesmon S-IOOP, S-100 protein TY, tyrosinase Ml, MART-1 (melan-A) OGN, osteocalcin EPS, epithelioid sarcoma EPSS, epithelioid synovial sarcoma EAS, epithelioid angiosarcoma EMPNST, epithelioid malignant peripheral nerve sheath tumor CCS, clear cell sarcoma SEFS, sclerosing epithelioid fibrosarcoma ... 

The Wilms tumor-1 (WTl) gene is located on the short arm of chromosome 11 (llpl3). It encodes a protein that is a critical determinant of urogenital development and is expressed in >80% of nephroblastomas. With regard to osseous and soft tissue tumors, WTl protein is not a specific marker and is potentially present in angiosarcoma, malignant peripheral nerve sheath tumor, synovial sarcoma, osteosarcoma, myxoid liposarcoma, and clear-cell sarcoma.Nevertheless, it is most often utilized (in a structured panel with other immunodeter-minants) as an adjunctive indicator of endothelial differentiation in diagnostic practice. ... 

The potential presence of CD34 in diverse polygonal-cell soft tissue tumors, including epithelioid LMS, epithelioid MPNST, clear cell sarcoma, and epithelioid sarcoma, has diminished its potential utility as an indicator of endothelial differentiation." " We also have observed that epithelioid angiosarcomas may be reactive... 

FIGURE 4.24 Clear cell sarcoma labels for S-100 protein in accord with the contention that it is a malignant melanoma of soft tissues. 

Clear cell sarcoma (CCS) was formerly thought to represent a primary soft tissue counterpart of cutaneous malignant melanoma. Nonetheless, it is now known that CCS exhibits a consistent and characteristic t(12 22) chromosomal translocation that is not shared by mela-nocytic lesions of the skin. This neoplasm is typified by an epithelioid and/or spindle cell constituency, with a delicate fibrovascular stroma and clear or lightly eosinophilic cytoplasm. Melanin pigmentation may or may not be observed. 

Cangul IT, van Garderen E, Van der Poel HJ, et al. Tyrosinase gene expression in clear cell sarcoma indicates a melanocytic origin Insight from the first reported canine case. APMIS. 1999 107 982-988. 

Papas-Corden P, Zarbo RJ, Gown AM, et al. Immunohisto-chemical characterization of synovial, epithelioid, and clear cell sarcomas. Surg Pathol. 1989 2 43-58. 

Mooi WJ, Deenik W, Peterse JL, et al. Keratin immunoreactivity in melanoma of soft parts (clear cell sarcoma). Histopathology. 1995 27 61-65. 

Hisaoka M, Ishida T, Kuo TT, et al. Clear cell sarcoma of soft tissue A clinicopathologic, immunohistochemical, and molecular analysis of 33 cases. Am J Surg Pathol. 2008 32 452-460. 

Hiraga H, Nojima T, Abe S, et al. Establishment of a new continuous clear cell sarcoma cell line Morphological and cytogenetic characterization and detection of chimaeric EWS/ATF-1 transcripts. Virchows Arch. 1997 431 45-51. 

Stenman G, Kindblom LG, Angervall L. Reciprocal translocation t(12 22)(ql3]3) in clear-cell sarcoma of tendons and aponeuroses. Genes Chromosomes Cancer. 1992 4 122-127. 

A notable exception to that statement is represented by clear cell sarcoma of soft tissue ( melanoma of soft parts ), which clearly does exhibit true melanocytic dif-ferentiation.2° 2° Because the immunohistologic profiles of that tumor and MM are superimposable, other specialized studies are usually necessary to separate them in cases where clinical findings make the diagnosis uncertain. In particular, clear cell sarcoma regularly shows the presence of a t(12 22) chromosomal translocation, apposing the EWS and ATFl genes, which is not present in melanomas. 

Langezaal SM, Gtaadt van Ro en JF, et al. Malignant melanoma is genetically distinct from clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts). Br J Cancer. 2001 84 535-538. 

Curry CV, Dishop MK, Hicks MJ, et al. Clear cell sarcoma of soft tissue diagnostic utility of fluorescence in-sim hybridization and reverse transcriptase polymerase chain reaction. J Cutan Pathol. 2008 35 411-417. 

Clear cell sarcoma (melanoma of soft parts) Young adults. Deep soft tissue with nodal and lung metastases. Mixed epithelioid and spindle cells in nested growth pattern S100+, HMB45+, melanA+ RT-PCR for EWS-ATF1 (not seen in cutaneous melanoma)... 

Clear cell sarcoma, adenoid cystic carcinoma, small cell lung carcinoma, Ewing sarcoma, synovial sarcoma, osteosarcoma, angiosarcoma, AML,... 

Clear cell sarcoma, angiosarcoma, adrenal oncocytoma, Kaposi s sarcoma, rhabdomyosarcoma... 

SlOO Melanomas, schwannoma, neuroendocrine tumors Malignant peripheral nerve sheath tumors, chondrosarcoma and chondroblastoma clear cell sarcomas, myoepithelial tumors, granulosa cell tumor Neural crest cells (glial cells, Schwann cells, melanocytes and nevus cells), chondrocytes, adipocytes, myoepithelial cells, macrophages, adrenal medulla and paraganglia, Langerhans cells, dendritic cells... 

TLEl protein Synovial sarcoma Hemangiopericytoma, schwannoma, solitary fibrous tumor, fibroxanthoma, clear cell sarcoma, carcinosarcoma, chondrosarcoma ... 

Myxoid liposarcoma Myxoid liposarcoma Acute myeloid leukemia Acute myeloid leukemia Ewing s sarcoma Ewing s sarcoma Ewing s sarcoma Clear cell sarcoma... 

Molecular Detection of Clear Cell Sarcoma (Malignant Melanoma of Soft Tissue)... 

In addition to this translocation, additional genetic abnormalities are also described in association with clear cell sarcoma such as the trisomy of the 2, 7, 8 and 22 chromosomes but they are not specific for this tumor. Furthermore, the transloca-... 

As the t(12 22)(ql3 ql2) translocation has not been reported in association of malignant melanoma or any other type of malignancies, it is suitable to be used as a specific molecular marker for the diagnosis and monitoring of clear cell sarcoma. 

Malignant melanoma is associated with a broad spectrum of cytogenetic abnormalities, which frequently involve chromosomes 1, 5 and 6. The t(12 22) translocation is not a feature for malignant melanoma but is a characteristic genetic abnormality for clear cell sarcoma described in a prior section. 

Pellin, A., Moteagudo, C. et al. (1998) New type of chimeric fusion product between the EWS and ATFl genes in clear cell sarcoma (malignant melanoma of soft parts). Genes Chromosomes Cancer, 23, 358—360. 

Sonobe, H., Takeuchi, T., Taguchi, T. et al. (1999) Further characterization of the human clear cell sarcoma cell line HS-MM demonstrating a specific t(12 22)(ql3 ql2) translocation and hybrid EWS/ATF-1 transcript. J Pathol, 187, 594-597. 

Antonescu, C.R., Tschernyavsky, S.J., Wodruff J.M. et al. (2002) Molecular diagnosis of clear cell sarcoma. Detection of EWS-ATEl and MITE-M transcripts and histopathological and ultrastructural analysis of 12 cases. J Mol Diag, 4, 44—52. 

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