title: Keratin-positive Ewing's sarcoma: an ultrastructural study of 12 cases.
abstract: Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET) is an aggressive neoplasm of bone and soft tissue. Histologically, it is characterized by the presence of small round blue cells, which usually express MIC-2 and FLI-1 immunohistochemically. The most specific feature for diagnosis, however, is cytogenetic or molecular evidence of a consistent abnormality, the t(11;22)(q24;q12), or variants thereof. The immunohistochemical expression of keratins in a significant proportion of these cases has been highlighted in several recent studies. The ultrastructural features of these keratin-positive tumors have not, however, been characterized in detail. In this study we analyzed the ultrastructural features of 12 well-documented EWS/PNETs that stained strongly for pankeratin by immunohistochemistry. Ultrastructurally, the tumor cells contained a few organelles, which included a small number of mitochondria, poorly developed Golgi complexes, free ribosomes, and inconspicuous rough-endoplasmic reticulum. Rudimentary cell junctions were seen in 2 tumors while prominent junctions were observed in the remaining 10. Five tumors contained intracytoplasmic filaments, and definite tonofibrils were identified in 2. Well-developed basal lamina around tumor cells were also demonstrated in 2 tumors. Follow-up information was available for all cases. Seven patients died of disease, 2 are alive with disease, and 3 have no current evidence of disease. The cohort includes 5 patients with a type-1 translocation, which has been associated with a better prognosis in some studies; 4 of these patients have died of their disease, and 1 is alive with recurrent disease. This study shows that keratin-positive EWS/PNETs have evidence of epithelial differentiation ultrastructurally, and may possibly represent a more aggressive subset of the EWS/PNET group of tumors.
authors.affiliation: Department of Pathology, Tufts-New England Medical Center, Boston, MA 02114, USA.
authors.forename: Amitabh
authors.initials: A
authors.lastname: Srivastava
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Rosenberg
authors.forename: Martin
authors.initials: M
authors.lastname: Selig
authors.forename: Brian P
authors.initials: BP
authors.lastname: Rubin
authors.forename: G Petur
authors.initials: GP
authors.lastname: Nielsen
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D001859:Bone Neoplasms / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure*; D002648:Child; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008297:Male; D046529:Microscopy, Electron, Transmission; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051789:Proto-Oncogene Protein c-fli-1; D012334:RNA, Neoplasm / Q000032:analysis; D034802:RNA-Binding Protein EWS; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012512:Sarcoma, Ewing / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure*; D012983:Soft Tissue Neoplasms / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D012334:RNA, Neoplasm; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors; D007633:Keratins