Clear cell sarcomas (CCS) of soft tissue are malignant mesenchymal tumors with melanocytic differentiation and an extraordinary nested growth pattern. They are classified as soft tissue tumors of uncertain differentiation.
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Terminology
The term ‘malignant melanoma of soft parts’ has been discouraged 1.
Epidemiology
Clear cell sarcoma is a rare tumor accounting for <1% of all soft tissue neoplasms. It is mostly found in the younger adult population in the third and fourth decade with women slightly more frequently affected than men 1-3.
Diagnosis
Soft tissue clear cell sarcomas are diagnosed based on histology and immunohistochemistry 1.
Diagnostic criteria
Diagnostic criteria according to the WHO classification of soft tissue and bone tumors (5th edition) 1:
fascicular or nest-like architecture
plump to epithelioid spindle cells with prominent nucleoli and pale eosinophilic cytoplasm
wreath-like multinucleated giant cells
positive immunoreactivity for melanocytic markers such as S100, SOX10, melan A and HMB45
EWSR1-ATF1 fusions in a high number of cases
Clinical presentation
The typical clinical presentation is a palpable mass of variable duration, often months or years. Tenderness or pain is a feature described in about a third to half of the cases 1,4.
Pathology
Clear cell sarcomas show melanocytic differentiation and a distinctive fascicular growth pattern 1. The clear cell appearance is because of a pale eosinophilic cytoplasm due to glycogen accumulation 2,3.
Etiology
The etiology of clear cell sarcomas is unknown 1.
Location
Clear cell sarcomas are most often found in deep-seated regions of the extremities and have been associated with tendons and aponeuroses such as the ankle and foot, which are the most common sites. Less common and rare locations include head and neck, trunk and visceral regions as well as from skin and oral mucosa 1-4.
Macroscopic appearance
The macroscopic appearance of clear cell sarcomas usually shows a circumscribed mass with a lobulated form and a tannish-grey to white color with a coarse texture. Some of the clear cell sarcomas might display cystic changes necrosis or melanin pigmentation 1,2.
Microscopic appearance
Microscopically clear cell sarcomas display the following histological features 1-3:
fascicular or nest-like architecture
epithelioid to plump spindled cells embedded by fibrous septa
pale eosinophilic cytoplasm and vesicular nuclei
wreath-like multinucleated giant cells
minimal pleomorphism
low mitotic count
Immunophenotype
Immunohistochemistry stains usually express melanocytic markers as S100, SOX10, melan A and HMB45 1-3.
Genetics
Clear cell sarcomas of soft tissue are associated with EWSR1-ATF1 gene fusions in 70-90% 1-3 and EWSR1-CREB1 fusions in a subset of tumors 1,2.
Radiographic features
Clear cell sarcomas have been characterized as well-defined homogeneous lesions with a benign-looking appearance 2.
MRI
MRI is considered the most suitable modality to identify the tumor and its relations to the adjacent structures, even if a definitive diagnosis cannot be made and differentiation from other malignant tumors is difficult 3. On MRI, clear cell sarcomas have been described as homogeneous, lobulated well-circumscribed lesions 2-4. Bone destruction is seen in a minority of cases 4.
Signal characteristics
T1: homogeneous iso to hyperintense compared to muscle
T2: heterogeneous with variable signal intensity and hypointense foci
STIR/PDFS: hyperintense
T1C+ (Gd): variable inhomogeneous and heterogeneous enhancement
Radiology report
The radiological report should include a description of the following:
form, location and size
tumor margins and transition zone
relations to the muscular fascia
relation to adjacent neurovascular structures
relations to bones
Treatment and prognosis
Clear cell sarcomas are aggressive tumors and treatment usually includes wide surgical excision with an acceptable amount of tumor-free surrounding tissue. Local recurrence is seen in up to 40% metastasis to lung or lymph nodes occurs in 30-50% of patients. Radiation therapy can be done to improve local tumor control in case of close resection margins. Chemotherapy is mostly administered in metastatic disease. Overall survival rates have been reported to be in the range of about 60%, 35% and 10% for 5, 10 and 20 years respectively. Tumor size >5 cm, tumor necrosis as well as nodal involvement, are considered unfavorable prognostic factors 1-3.
History and etymology
The “clear cell sarcoma of tendons and aponeuroses” was first described by the Austrian-American pathologist Franz Michael Enzinger in 1965 2-5.
Differential diagnosis
Tumors or conditions which can mimic the presentation and/or appearance of clear cell sarcomas of soft tissue include 2,3: