Immunohistochemical and FISH Analysis of Angiosarcoma Arising in Organ Allograft Recipients and in a Patient with Long-Standing Orthopedic Metal Implant.
Bibianna M Purgina, Michael A Nalesnik, Kathleen Cieply, Mark A Goodman, Richard L McGough, Uma NM Rao. UPMC, Pittsburgh, PA
Background: Angiosarcoma (AS) comprises less than 1% of sarcomas and is considered high-grade. We examined a selected series of AS occurring in patients with prior organ transplants and one that occurred at the site of metal orthopedic implant and compared them with paired samples of primary and recurrent conventional AS.
Design: Paraffin blocks from 15 patients with AS were retrieved from archived files at our institution. 10 had recurrent AS, 4 had metastases. Follow-up clinical data was available for 10 patients including two AS in organ transplant recipients (one also had NF1), and AS of the proximal tibia containing an orthopedic metal implant for more than 25 years. The rest of AS were primary in subcutaneous soft tissue. We categorized AS histologically as low grade and epithelioid. Immunohistochemistry included antibodies for at least 3 vascular markers, cytokeratins, ckit, Ki67, and in older and/or immunocompromised patients, HHV8 and EBV. Paired samples of primary and metastatic AS in 4 patients, including a transplant patient were selected for FISH analysis for EGFR using LSI EGFR/CEP7 dual-color probe (7p12).
Results: All cases demonstrated positivity with one or more vascular markers. The 4 cases of metastatic AS demonstrated epithelioid features. Low-grade AS without epithelioid features were positive for more than two vascular markers, and all were negative for cytokeratins. Epithelioid AS were focally positive for CD31, variable for the other vascular markers and focally positive with cytokeratins. Ki67 positivity ranged from 5% in low-grade AS to over 90% in epithelioid AS. HHV8, EBV and ckit were negative. None of the 4 cases demonstrated EGFR amplification but 4 of the 6 samples demonstrated hyperploidy in the range of 13-36%. Epithelioid AS had much more aggressive course with multiple recurrences, metastatic disease and proved fatal in three patients including the patient with metal-associated AS.
Conclusions: AS with epithelioid features had fewer positive vascular markers, possibly reflecting a lack of differentiation. There were no differences in pattern of immunoreactivity with post transplant and conventional AS. Primary bones AS associated with metal orthopedic implants are exceedingly rare. EGFR hyperploidy was likely related to copy number gains of chromosome 7. Even though AS is a rare tumor, the aggressive and rapidly lethal course warrants continued investigation in order to identify new therapeutic targets.
Category: Bone & Soft Tissue
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 12, Monday Morning