Epithelioid sarcoma: New insights based on an extended immunohistochemical analysis

Archives of Pathology & Laboratory Medicine, Sep 2003 by Laskin, William B, Miettinen, Markku

With the introduction of new and diverse antibodies to the surgical pathology armamentarium, we decided to expand the knowledge base regarding the immunohistochemical profile of ES with the intention of using this information for diagnostic purposes and perhaps to gain a better understanding of the histogenesis of this unique sarcoma.

MATERIALS AND METHODS

Archived examples of epithelioid sarcoma were retrieved from the files of the Soft Tissue Registry of the Armed Forces Institute of Pathology. A total of 95 epithelioid sarcomas were collected and histologically subtyped as classic ES (n = 73), angiomatoid ES (n = 8), large cell/rhabdoid or proximal type ES (n = 7), and fibroma-like ES (n = 7). Histologically defined, tumors subtyped as examples of classic ES (Figure 1, A) consisted of modestly atypical epithelioid and plump spindled cells arranged in vague nodules and bordering central foci of necrosis or myxohyaline change. The cells possessed eosinophilic cytoplasm, well-defined cell borders, and vesicular nuclei with small, conspicuous nucleoli. Cytologically identical cells that proliferated around cystlike spaces containing blood characterized the angiomatoid variant (Figure 1, B). The fibroma-like ES (Figure 1, C) was composed chiefly of mildly atypical spindled cells and a subpopulation of epithelioid tumor cells arranged in whorled and storiform growth patterns. The large cell variant (Figure 1, D) was characterized by a sheetlike or bulky nodular growth pattern of epithelioid cells, including a variable number of "rhabdoid"-appearing tumor cells, with abundant cytoplasm, large vesicular nuclei, and sometimes prominent nucleoli. Nine examples of invasive cutaneous squamous cell carcinoma were retrieved for comparison staining.

Immunohistochemical studies were performed using the avidin-biotin peroxidase complex technique with diaminobenzidine as the chromogen. The primary antibodies, dilutions, and pretreatments are listed in Table 1. Appropriate positive controls were evaluated.

All immunohistochemical results were analyzed and semiquantitatively scored on a scale from 0 to 4 as follows: 0, no detectable immunoreactivity; 1, 10% or less of tumor cells positive; 2, 11% to 25% of tumor cells reactive; 3, 26% to 50% of tumor cells reactive; 4, more than 50% of tumor cells positive.

RESULTS

Clinical

The salient clinical findings for patients with ES in our study are summarized in Table 2. The patients ranged in age from 4 to 65 years with a mean age of 31 years. With the exception of the large cell/rhabdoid variant, the other histologic subtypes of ES showed a significantly higher male predominance. The distal extremities (hands, forearm, feet, or calf) was the most common site of origin of classic ES (58%) and fibroma-like ES (86%), whereas 5 of 8 examples of the angiomatoid variant occurred in inguinal, perineal, or penile soft tissue.

Keratin Subtypes in ES

Immunohistochemical results for ES are summarized in Table 3 and illustrated in Figure 2. K 14 immunoreactivity was observed in 31 of 64 (48%) tumors tested. The frequency of reactivity varied, but in 21 examples of classic ES, 2 cases of angiomatoid ES and 1 case each of the large cell/rhabdoid and fibroma-like variants, 10% or less of cells were positive. Two large cell/rhabdoid variants and 2 classic ESs exhibited K 14 expression in more than 25% of cells (Figure 3, A). K 5/6 expression was identified in 10 of the 33 tumors evaluated. Ten percent or less of tumor cells were positive in 9 cases, including 6 classic examples, 2 fibroma-like ESs, and 1 large cell/rhabdoid variant. One classic ES exhibited reactivity in 11% to 25% of cells (Figure 3, B). Only scattered tumor cells demonstrated reactivity for K 20 (11/71) (Figure 3, C) and K 15 (3/23), including 9 classic ESs, 2 cases each of the angiomatoid and large cell/rhabdoid variant, and 1 example of the fibroma-like ES. No reactivity was demonstrated for K 2 (n = 50), K 5 (n = 26), and K 10 (n = 16).