Expression of Fli-1, a nuclear transcription factor, distinguishes vascular neoplasms from potential mimics.

Fli-1 protein, a member of the ETS family of DNAbinding transcription factors, is involved in cellular proliferation and tumorigenesis. Approximately 90% of Ewing's sarcoma/primitive neuroectodermal tumors (ES/PNET) have a specific translocation, t(11;22)(q24;q12), which results in fusion of EWS to Fli-1, and production of an EWS-Fli-1 fusion protein. We have recently shown that immunohistochemistry for the carboxy terminal of Fli-1 protein is sensitive and highly specific for the diagnosis of ES/PNET. In our earlier study we noted that among normal tissues only endothelial cells and small lymphocytes expressed Fli-1. Fli-1 expression in vascular neoplasms has not been previously studied. Formalin-fixed paraffin-embedded tissue from 54 vascular tumors and 75 nonvascular tumors were immunostained for Fli-1 (1:120, Sc 356, Santa Cruz Biotechnology, Santa Cruz, CA), after steam heat-induced epitope retrieval. Only cases with >10% of cells showing nuclear staining were accepted as positive. Cases without positive internal controls (endothelium and small lymphocytes) were not scored. Positive internal controls were present in 122 of 129 cases (95%). One vascular tumor (Kaposi's sarcoma) and 7 nonvascular tumors (2 epithelioid sarcomas and 5 carcinomas) without internal controls were not scored. Fli-1 was expressed by 50 of 53 vascular tumors scored (94%), including 20 of 22 angiosarcomas, 11 of 12 hemangioendotheliomas, 7 of 7 hemangiomas, and 12 of 12 Kaposi's sarcomas. In contrast, Fli-1 expression was absent in the 68 nonvascular tumors scored (0 of 68), including 16 sarcomas, 7 melanomas, and 45 carcinomas. The results of this study strongly suggest a role for Fli-1 as a novel marker of both benign and malignant vascular tumors. The sensitivity (94%) and specificity (100%) of Fli-1 with regards to the cases evaluated in this study equal or exceed those of the established vascular markers, CD31, CD34, and von Willebrand factor. As the first nuclear, rather than cytoplasmic or membranous marker of endothelium, Fli-1 immunostaining also generally lacks cytoplasmic staining artifacts that are the result of endogenous peroxidases or biotin.

Aortic valve rheumatoid nodules producing clinical aortic regurgitation and a review of the literature.

The majority of cardiac involvement in rheumatoid arthritis (RA) is an incidental finding at postmortem, as less than 3% of patients with RA have clinical cardiac signs or symptoms. Most cardiac involvement in RA involves the pericardium and has been known since Charcot first described an RA patient with pericarditis in 1881. Cardiac involvement takes two different forms: non-specific inflammatory changes and specific granuloma formation. Specific rheumatoid nodules in the heart are an infrequent complication of RA. This is the first case report of a surgically excised heart valve with rheumatoid nodules. A 74-year-old RA patient with a high seropositive rheumatoid factor presented with severe aortic regurgitation and underwent a valve replacement. The native aortic valve showed significant stenosis with multiple, classic rheumatoid nodules.