Case 4 -

Cutaneous Clear Cell Sarcoma Thomas Mentzel Friedrichshafen, Germany

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Case History: A 19-year-old female patient developed a dermal neoplasm on the right lateral foot. After diagnosis a wide reexcision with tumour free margins was performed, and the patient received postoperative radiotherapy (60 Gy). Two months later a solitary inguinal lymph metastasis was excised; eight other lymph nodes were tumour free. The patient received intraoperatively (10 Gy) and postoperatively (45 Gy) additional radiotherapy. There is no sign of recurrence at 13 months. Histologically, an ill-defined dermal neoplasm with infiltration of superficial subcutaneous tissue is seen. The neoplasm is composed of atypical, plump spindled and round tumour cells containing enlarged nuclei and an ill-defined pale eosinophilic or clear cytoplasm. Scattered multinucleated giant cells are present. Tumour cells are arranged in short bundles and confluent nests, and Ki-67 stainings show an increased proliferative acitivity. Immunohistochemical stainings revealed a homogeneous expression of melanocytic markers by neoplastic cells (S-100 protein, Melan-A, HMB-45, MiTF1), whereas epithelial and muscle markers were all negative. In addition EWS-translocation has been detected by FISH-analysis. Case 4 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 4 - Figure 1 Low-power view shows an ill-defined, cellular dermal neoplasm with infiltration of superficial parts of the subcutis. Case 4 - Figure 2 Plump spindled tumour cells are arranged in confluent nests and bundles. Tumour cells contain a pale eosinophilic or clear cytoplasm and enlarged nuclei. Case 4 - Figure 3 Scattered multinucleated giant cells (wreath-like giant cells) are present. Case 4 - Figure 4 Spindled and round tumour cell nuclei are enlarged. Note scattered mitotic figures (arrow). Case 4 - Figure 5 Hyalinisation of the tumour stroma. Case 4 - Figure 6 Immunohistochemically, tumour cells cells stain homogeneously positive for S-100 protein. Case 4 - Figure 7 The majority of neoplastic cells stains positively for HMB-45. Case 4 - Figure 8 Nuclear expression of MiTF1 is seen. Case 4 - Figure 9 Ki-67 antibodies reveal an increased proliferative activity of atypical tumour cells. Case 4 - Figure 10 Lymph node metastasis. Most of the lymphatic tissue is replaced by confluent nests and bundles composed of atypical fusiform tumour cells. Case 4 - Figure 11 Tumour cells stain positively for Melan-A. Differential Diagnosis: The differential diagnosis includes a number of benign and malignant melanocytic and mesenchymal neplasms: Malignant melanoma rare in this age group usually evidence of an intraepithelial component usually no multinucleated (wreath-like) giant cells no EWS-translocation Cellular blue naevus characteristic architecture (the tumour often bulges into the subcutis) biphasic growth of fascicles of hyperpigmented dendritic spindled cells and nests of epithelioid and plump spindled cells with a rather pale cytoplasm no EWS-translocation Cutaneous PEComa lace-like vascular pattern predominantly perivascular arrangement of tumour cells S-100 protein usually negative no EWS-translocation Cellular dermatofibroma storiform/fascicular growth pattern plump spindled/histiocytoid tumour cells no expression of melanocytic markers Cellular neurothekeoma S-100 protein negative often focal expression of ASMA Diagnosis: Cutaneous Clear Cell Sarcoma Bullet Points sarcomas of all lines of differentiation may occur also in superficial location, however, there are considerable differences in regard to the incidence and clinical behaviour the diagnosis of rare sarcomas in an unusual clinical setting may require additional diagnostic techniques cytogenetic and molecular analysis is often necessary in establishing the diagnosis of rare sarcomas in distinction from other neoplasms References: Antonescu CR, Tschernyavsky SJ, Woodruff JM et al. Molecular diagnosis of clear cell sarcoma: detection of EWS-ATF1 and MITF-M transcripts and histopathological and ultrastructural analysis of 12 cases. J Mol Diagn 2002; 4: 44-52 Antonescu CR, Nafa K, Segal NH et al. EWS-CREB1: a recurrent variant fusion in clear cell sarcoma associated with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res 2006; 15: 5356-5362 Clark MA, Johnson MB, Thway K et al. Clear cell sarcoma (melanoma of soft parts): The Royal Marsden Hospital experience. Eur J Surg Oncol 2007; 23: Coindre JM, Hostein I, Terrier P et al. Diagnosis of clear cell sarcoma by real-time reverse transcriptase-polymerase chain reaction analysis of paraffin embedded tissues: clinicopathologic and molecular analysis of 44 patients from the French sarcoma group. Cancer 2006; 107: 1055-1064 Dim DC, Cooley LD, Miranda RN. Clear cell sarcoma of tendons and aponeuroses: a review. Arch Pathol Lab Med 2007; 131: 152-156 Garcia JJ, Kramer MJ, O`Donnell RJ et al. Mismatch repair expression and microsatellite instability: a comparison of clear cell sarcoma of soft parts and metastatic melanoma. Mod Pathol 2006; 19: 950-857 Kawai A, Hosono A, Nakayama R et al. Clear cell sarcoma of tendons and aponeuroses: a study of 75 patients. Cancer 2007; 109: 109-116 Langezaal SM, Graadt van Roggen JF, Cleton-Jansen AM et al. Malignant melanoma is genetically distinct from clear cell sarcoma of tendons and aponeurosis (malignant melanoma of soft parts). Br J Cancer 2001; 84: 535-538 Mrozek K, Karakousis CP, Perez-Mesa C et al. Translocation t(12;22)(q13;q12.2-12.3) in a clear cell sarcoma of tendons and aponeuroses. Genes Chromosomes Cancer 1993; 6: 249-252 Patel RM, Downs-Kelly E, Weiss SW et al. Dual-color, break-apart fluorescence in situ hybridization for EWS gene rearrangement distinguishes clear cell sarcoma of soft tissue from malignant melanoma. Mod Pathol 2005; 18: 1585-1590 Schaefer KL, Brachwitz K, Wai-DH et al. Expression profiling of t(12;22) positive clear cell sarcoma of soft tissue cell lines reveals characteristic upregulation of potential new marker genes including ERBB3. Cancer Res 2004; 15: 3395-3405 Segal NH, Pavlidis P, Noble WE et al. Classification of clear-cell sarcoma as a subtype of melanoma by genomic profiling. J Clin Oncol 2003; 21: 1775-1781