Histopathologic grading is of prognostic significance in primary angiosarcoma of breast: Proposal of a simplified 2-tier grading system Journal Article
| Authors: | Kuba, M. G.; Dermawan, J. K.; Xu, B.; Singer, S.; Plitas, G.; Tap, W. D.; D'Angelo, S. P.; Rosenbaum, E.; Brogi, E.; Antonescu, C. R. |
| Article Title: | Histopathologic grading is of prognostic significance in primary angiosarcoma of breast: Proposal of a simplified 2-tier grading system |
| Abstract: | Despite a wide spectrum of clinical presentations, including primary or secondary, most angiosarcomas are considered high grade. One exception is primary breast angiosarcoma, where historically, histologic grading has shown to predict outcome using the Rosen 3-tier system. However, more recent studies have challenged this concept suggesting that even in this specific clinical context angiosarcomas should be considered high grade. This study aimed to critically reevaluate the impact of histologic grade in a clinically uniform cohort managed at a single institution using a newly proposed grading system. Our study included 49 primary breast angiosarcomas diagnosed during 1994 to 2022 (median follow-up: 33 mo), classified as low grade (29%), intermediate grade (20%), and high grade (51%), based on mitotic count, extent of solid components, and necrosis. At last follow-up, 22% patients developed locoregional recurrences, 63% distant metastases, and 47% patients died of disease. As patients with low and intermediate-grade angiosarcomas had relatively similar outcomes, our cohort was further analyzed using a 2-tier system (low grade and high grade). Targeted-DNA next-generation sequencing (505 cancer gene panel) performed in 11 cases found KDR mutations in 78% and PIK3CA mutations in 44% of high-grade lesions. Histologic grade, by either 3-tier or 2-tier grading systems, had a strong impact on survival, with the 2-tier system being an independent predictor of disease-specific survival and overall survival. Based on 2-tier system, the 5-year overall survival was 38% for high-grade angiosarcoma and 74% for low-grade angiosarcoma. PIK3CA mutations alone or concurrent with KDR alterations were identified in angiosarcomas with worse prognosis. © 2023 Lippincott Williams and Wilkins. All rights reserved. |
| Keywords: | adult; cancer chemotherapy; cancer survival; controlled study; human tissue; aged; primary tumor; gene mutation; major clinical study; overall survival; histopathology; cancer recurrence; gemcitabine; nuclear magnetic resonance imaging; follow up; antineoplastic agent; cancer grading; mitosis; gene; platelet derived growth factor alpha receptor; progression free survival; neoplasm recurrence, local; breast; mastectomy; tumor volume; cohort analysis; pathology; vasculotropin receptor 2; angiosarcoma; hemangiosarcoma; distant metastasis; docetaxel; oncogene; tumor suppressor gene; mammography; tumor recurrence; recurrent disease; mitosis rate; dna sequence; neoadjuvant chemotherapy; codon; point mutation; disease specific survival; pik3ca gene; histologic grade; preoperative radiotherapy; shoulder pain; local recurrence free survival; cancer prognosis; high throughput sequencing; neoplasm grading; distant metastasis free survival; breast angiosarcoma; phosphatidylinositol 4,5 bisphosphate 3 kinase; dna sequencing; humans; prognosis; human; male; female; article; class i phosphatidylinositol 3-kinases |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 47 |
| Issue: | 3 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2023-03-01 |
| Start Page: | 307 |
| End Page: | 317 |
| Language: | English |
| DOI: | 10.1097/pas.0000000000001998 |
| PUBMED: | 36376999 |
| PROVIDER: | scopus |
| PMCID: | PMC9974594 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF --Corresponding author is MSK author: Cristina R. Antonescu -- Source: Scopus |
