Ewing's sarcoma/
primitive neuroectodermal tumor (ES/
PNET) is an extraordinarily rare primary
tumor in the kidney and can be mistaken for a variety of other round cell
tumors, including blastema-predominant
Wilms' tumor (WT). Approximately 90% of ES/
PNET have a specific t(11;22), which results in a chimeric
EWS-FLI-1 protein. Immunohistochemistry for the carboxy-terminus of FLI-1 is sensitive and highly specific for the diagnosis of ES/
PNET. WT-1, the WT-associated tumor suppressor gene, is overexpressed in WT but not in ES/
PNET. No study has examined FLI-1 or WT-1 expression in renal ES/
PNET. The clinicopathologic features of 11 renal ES/
PNET were studied along with immunohistochemistry for
cytokeratin,
desmin, CD99, FLI-1, and WT-1. WT were also immunostained for CD99 (5 cases), FLI-1 (10 cases), and WT-1 (9 cases). The patients (6 men, 5 women) ranged from 18 to 49 years of age (mean, 34 yr). The mean
tumor size was 11.8 +/- 3.8 cm (mean +/- standard deviation). Presenting symptoms included abdominal/
flank pain and/or
hematuria. Grossly, all
tumors showed
necrosis and
hemorrhage, and 4 had cystic change. Microscopically, all
tumors showed vaguely lobular growth, primitive round cells, and variable rosette formation. Epithelial, myogenous, or cartilaginous differentiation was not seen. Immunohistochemical results on the renal ES/
PNET were
cytokeratin (2/8 focal),
desmin (0/9), CD99 (8/8), FLI-1 (5/8), and WT-1 (0/8). In comparison, the WT only rarely expressed CD99 (1/5) and did not express FLI-1 (0/10), but were usually WT-1-positive (7/9). Follow-up on 8 cases (mean, 28 mo; range, 6-64 mo) showed 4 lung and pleural
metastases, 1 bone
metastasis, liver
metastasis, 2 local recurrences, and 5 deaths from disease (median time to death, 16.8 mo). No case had distant metastatic disease at presentation. Adjuvant
therapy included
chemotherapy (8 cases), radiation (3 cases), and
bone marrow transplantation (1 case). Our study affirms a unique proclivity of renal ES/
PNET for young adults and that it is a highly aggressive
neoplasm, with rapid death in many cases, usually after the development of treatment-resistant lung
metastases. These
tumors must be distinguished from blastema-predominant WT and other primitive renal
tumors that require different
therapy. FLI-1 and WT-1 immunohistochemistry may be valuable in this differential diagnosis, given the known immunophenotypic overlap between ES/
PNET and blastema-predominant WT with regard to CD99,
cytokeratin, and
desmin. The accurate distinction between these two entities has clear prognostic and therapeutic implications.