Cutaneous clear cell sarcoma: a clinicopathologic, immunohistochemical, and molecular analysis of 12 cases emphasizing its distinction from dermal melanoma

Abstract

Clear cell sarcoma (CCS) of tendons and aponeuroses/malignant melanoma (MM) of soft parts is a rare tumor and in the majority of cases presents a characteristic reciprocal translocation t(12;22)(q13;q12) that results in fusion of the EWS and ATF1 genes. Although the melanocytic differentiation of CCS is indisputable, its precise lineage remains unclear. Typically, the slowly growing tumor affects the extremities of adolescents or young adults, especially around the ankle and foot. CCS is classically regarded as a deep soft tissue tumor associated with tendons or aponeuroses. This traditional view is put into perspective by the description of primary CCS of the gastrointestinal tract that may have a variant fusion gene EWSR1-CREB1. We describe 12 cases of cutaneous CCS and discuss the differential diagnoses. These 12 cases share an identical immunohistochemical profile with MM and thus can easily be confused with a dermal variant of spindle cell MM or metastasis of MM. The patients' ages ranged from 6 to 74 years (median: 25 y), and there was a female predominance (10 females, 2 males). Most tumors (n = 9) were located on the extremities, 2 tumors arose on the back, and 1 on the abdomen. The mean tumor size was 0.97 cm (range, 0.4 to 1.7 cm). Six cases showed invasion of the subcutis, the other 6 cases were entirely dermal. Tumor necrosis was evident in 2 cases, melanin pigment in 2 cases, and ulceration in 1 tumor. All cases showed uniform nests and fascicles of pale spindled or slightly epitheloid cells with finely granular eosinophilic or clear cytoplasm. There was fair pleomorphism with plump spindled nuclei and significantly prominent nucleoli. Multinucleated wreath-like tumor giant cells were observed in two-thirds of cases, but were usually present only focally. The dense cellular aggregates were encased by delicate fibrous septa. The stroma showed a sclerotic reticulated pattern. Partly, the nests of spindle cells bordered the epidermis, prima vista mimicking junctional nests of melanocytes. The specific translocation pattern was confirmed in all cases by fluorescence in situ hybridization. Local recurrences and metastases developed in 2 and 3 patients, respectively, and 1 patient died of the disease.

Figure 1

(A-D) A primary dermal CCS (Case 1) with fascicles of spindle cells bordering the epidermis. The spindle cells show pale eosinophilic or clear cytoplasm and elongated moderately pleomorphic oval nuclei with prominent nucleoli. In transversely cut fascicles and cells nuclei appear round. The cells show a homogenous expression of S100.

Figure 1

(A-D) A primary dermal CCS (Case 1) with fascicles of spindle cells bordering the epidermis. The spindle cells show pale eosinophilic or clear cytoplasm and elongated moderately pleomorphic oval nuclei with prominent nucleoli. In transversely cut fascicles and cells nuclei appear round. The cells show a homogenous expression of S100.

Figure 1

(A-D) A primary dermal CCS (Case 1) with fascicles of spindle cells bordering the epidermis. The spindle cells show pale eosinophilic or clear cytoplasm and elongated moderately pleomorphic oval nuclei with prominent nucleoli. In transversely cut fascicles and cells nuclei appear round. The cells show a homogenous expression of S100.

Figure 1

(A-D) A primary dermal CCS (Case 1) with fascicles of spindle cells bordering the epidermis. The spindle cells show pale eosinophilic or clear cytoplasm and elongated moderately pleomorphic oval nuclei with prominent nucleoli. In transversely cut fascicles and cells nuclei appear round. The cells show a homogenous expression of S100.

Figure 2

(A, B) A primary dermal CCS (Case 12). Fascicles of S100-positive spindle cells border closely the epidermis mimicking prima vista junctional nests. Melanocytes are neither increased nor scattered in the epidermis.

Figure 2

(A, B) A primary dermal CCS (Case 12). Fascicles of S100-positive spindle cells border closely the epidermis mimicking prima vista junctional nests. Melanocytes are neither increased nor scattered in the epidermis.

Figure 3

(A, B) The smallest primary dermal CCS in our series (Case 6) presents few multinucleated giant cells among the fascicles of spindle cells.

Figure 3

(A, B) The smallest primary dermal CCS in our series (Case 6) presents few multinucleated giant cells among the fascicles of spindle cells.

Figure 4

A characteristic feature of cutaneous CCS is fascicles of spindle cells encased by a reticulated pronounced hyalinized and sclerotic stroma (Case 4, overview and detail).

Figure 4

A characteristic feature of cutaneous CCS is fascicles of spindle cells encased by a reticulated pronounced hyalinized and sclerotic stroma (Case 4, overview and detail).

Figure 5

FISH analysis for the detection of EWSR1 translocation by EWSR1-break apart probe. Left half of the picture shows a positive result in Case 1 where signals are in different areas of the nucleus. In the right half (negative control) signals are very close together.