title: MYC immunohistochemistry in angiosarcoma and atypical vascular lesions: practical considerations based on a single institutional experience.
abstract: Angiosarcoma (AS) is an uncommon vascular malignancy with an aggressive clinical course. Radiation-associated angiosarcoma (RAAS) and Stewart-Treves syndrome are associated with MYC gene amplification and protein overexpression, while other radiation-associated vascular lesions including atypical vascular lesions (AVL) are not associated with MYC overexpression. In contrast, de novo AS represent a group of molecularly heterogeneous tumours, for which MYC expression has not been extensively examined. In this study, MYC immunohistochemistry (IHC) was performed on representative whole tissue sections of a large retrospective cohort of de novo AS, RAAS, Stewart-Treves syndrome, and AVL and evaluated using a semi-quantitative scoring method. MYC is strongly expressed in the majority of RAAS and Stewart-Treves syndrome. De novo AS demonstrate variable MYC expression, with high-grade tumours showing significantly higher MYC expression than low-grade tumours. In contrast, MYC expression in AVL is predominantly negative but may occasionally show focal staining. These results indicate that unequivocal strong MYC IHC staining supports the diagnosis of RAAS. In rare cases of RAAS without strong MYC expression, however, particularly relatively low-grade tumours for which the differential diagnosis includes AVL, the distinction between these lesions should be made on morphological grounds using previously established criteria (i.e., significant atypia, deep invasion, infiltrative growth, etc.). Increased MYC expression in high-grade de novo AS suggests that MYC overexpression may play a role in the pathogenesis of these tumours, and MYC IHC may be a prognostic and/or therapeutic biomarker in a subset of these tumours.
authors: Department of Pathology, University of Michigan Health System, Ann Arbor, MI, United States.
authors: Aaron M
authors: AM
authors: Udager
authors: Department of Pathology, University of Michigan Health System, Ann Arbor, MI, United States.
authors: Martin K
authors: MK
authors: Ishikawa
authors: Department of Pathology, University of Michigan Health System, Ann Arbor, MI, United States.
authors: David R
authors: DR
authors: Lucas
authors: Department of Pathology, University of Michigan Health System, Ann Arbor, MI, United States.
authors: Jonathan B
authors: JB
authors: McHugh
authors: Department of Pathology, University of Michigan Health System, Ann Arbor, MI, United States. Electronic address: rajivpat@med.umich.edu.
authors: Rajiv M
authors: RM
authors: Patel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006394:Hemangiosarcoma / Q000175:diagnosis*; D006801:Humans; D007150:Immunohistochemistry; D008204:Lymphangiosarcoma / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000175:diagnosis*; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000096:biosynthesis*; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc
keywords: AVL; MYC; angiosarcoma; atypical vascular lesion; immunohistochemistry; radiation-associated