*Department of Pathology and Oncology Johns Hopkins University School of Medicine, Baltimore, MD†Department of Pathology, Children’s Hospital of Philadelphia, Philadelphia§Department of Pathology, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine Pittsburgh PA‡Department of Pathology, Cincinnati Children’s Hospital, Cincinnati, OH∥Department of Pathology, University of Texas Southwestern Medical Center Dallas, TX¶Department of Pathology, Memorial Sloan Kettering Cancer Center New York NY
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To the Editor:Clear cell sarcoma of the kidney (CCSK) comprises ∼3% of pediatric renal neoplasms, but accounts for a disproportionate number of diagnostically problematic cases.1,2 The classic pattern of CCSK features regular branching fibrovascular septa separating cords and trabeculae of neoplastic cells containing nonoverlapping nuclei with fine, evenly dispersed chromatin and inconspicuous cytoplasm. However, CCSK may adopt numerous variant histologic patterns, including epithelioid, spindle cell, myxoid, sclerosing, palisading, and anaplastic. Therefore, CCSK may mimic and be mimicked by every other major pediatric renal neoplasm. Previously, immunohistochemistry (IHC) has had little role in supporting the diagnosis of CCSK, except to exclude various entities in the differential diagnosis. CCSK is uniformly negative for vascular markers (CD34), neural markers (S100 protein), muscle markers (desmin), and epithelial markers (cytokeratins and epithelial membrane antigen). Cyclin D1, TLE1, SATB2, vimentin, Bcl-2, and CD10 are frequently expressed in CCSK, though none of these is highly specific.3–6CCSK has recently been shown to harbor internal tandem duplications in the last exon of the BCOR gene in over 90% of cases,7–9 with a smaller subset harboring YWHAE-NUTM2B/E10 or BCOR-CCNB3 gene fusions.6 All of these genetic abnormalities result in a transcriptional signature characterized by high BCOR mRNA expression.11 Nuclear labeling for BCOR by IHC has been demonstrated to be a highly sensitive marker of CCSK.5 All 8 cases of CCSK previously studied by our group demonstrated strong diffuse strong nuclear labeling for BCOR.5 Wong et al12 found nuclear labeling in 73% (8/11) CCSK: the lower sensitivity in the latter study may relate to the different antibody dilution used as well as differences in the IHC platforms used (which was not specifically stated in the latter study12). Diffuse strong nuclear labeling for BCOR is highly specific for BCOR-related sarcomas of soft tissue, with the 1 exception being synovial sarcomas; ∼50% of synovial sarcomas label for BCOR. The specificity of BCOR IHC in the context of pediatric renal neoplasia has not previously been systematically studied.We therefore evaluated whole tissue sections from 79 neoplasms, including 34 Wilms tumors (including 21 with a stromal component), 17 congenital mesoblastic nephromas (2 classic, 10 cellular, 5 mixed), 9 CCSK, 11 metanephric stromal tumors, 4 rhabdoid tumors of the kidney, 1 renal primitive neuroectodermal tumor, and 3 sclerosing epithelioid fibrosarcomas. We performed IHC for BCOR using clone C-10 (SC-514576; Santa Cruz, Dallas, TX) generated against the N-terminus of BCOR at a dilution of 1:150 as done previously.5 Tumors were evaluated on the basis of intensity of labeling (strong, moderate, weak, or negative) and the percentage of positive neoplastic cells. Only nuclear labeling was counted, and slides were scored using a ×10 eyepiece (×100 total magnification). Neoplasms with no labeling were considered negative. Neoplasms with <10% labeling of any intensity were considered minimally positive, neoplasms with labeling in 10% to 50% of neoplastic cells of any intensity were considered focally positive, while neoplasms with strong labeling in >50% of cells were considered diffusely positive.We found diffuse strong nuclear labeling for BCOR to be both highly sensitive and specific for the diagnosis of CCSK in the setting of pediatric renal neoplasia (Table 1). All 9 CCSK tested in this study (which included none of the 8 cases tested previously and found to be diffusely positive5) demonstrated diffuse, strong nuclear labeling for BCOR, ranging from 80% to 100% of neoplastic cells (Fig. 1).