title: Primary Ewing's sarcoma/primitive neuroectodermal tumor of the kidney: a clinicopathologic and immunohistochemical analysis of 11 cases.
abstract: 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.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Jimenez
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Folpe
authors.forename: Rosanna L
authors.initials: RL
authors.lastname: Lapham
authors.forename: Jae Y
authors.initials: JY
authors.lastname: Ro
authors.forename: Patricia A
authors.initials: PA
authors.lastname: O'Shea
authors.forename: Sharon W
authors.initials: SW
authors.lastname: Weiss
authors.forename: Mahul B
authors.initials: MB
authors.lastname: Amin
mesh_terms: D000071443:12E7 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000032:analysis; D002648:Child; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000032:analysis; D003893:Desmin / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D007680:Kidney Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018242:Neuroectodermal Tumors, Primitive / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D012512:Sarcoma, Ewing / Q000737:chemistry / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D015534:Trans-Activators / Q000032:analysis; D025721:WT1 Proteins / Q000032:analysis; D009396:Wilms Tumor / Q000737:chemistry / Q000235:genetics / Q000473:pathology
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D003893:Desmin; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D025721:WT1 Proteins; D007633:Keratins