CYP1A1 immunohistochemistry is highly specific for angiofibroma of soft tissue among morphological mimics

Aims Angiofibroma of soft tissue (AFST) is a benign, morphologically distinctive tumour type that harbours recurrent AHRR :: NCOA2 fusions in 60–70% of cases and shows a non‐specific immunophenotype, expressing EMA in roughly half of cases. The AHRR :: NCOA2 fusion results in increased expression of cytochrome P450 1A1 (CYP1A1); a recent study demonstrated CYP1A1 immunohistochemistry (IHC) to be moderately sensitive and highly specific for AFST. Methods and results In this study, we sought to validate these findings in a larger independent cohort of 30 AFST, as well as 215 morphological mimics, including 30 solitary fibrous tumours, 29 myxoid liposarcomas, 28 low‐to‐intermediate grade myxofibrosarcomas (MFS), 20 atypical spindle cell lipomatous tumours (ASCLT), 20 cellular angiofibromas, 10 cases each of spindle cell lipoma, neurofibroma, malignant peripheral nerve sheath tumour, superficial angiomyxoma, cellular myxoma, soft tissue perineurioma and deep fibrous histiocytoma, and nine cases each of low‐grade fibromyxoid sarcoma and mammary‐type myofibroblastoma. We found CYP1A1 IHC to be 70% sensitive for AFST, with granular cytoplasmic staining in 21 of 30 tumours, and 98% specific, with staining in only five morphological mimics: two deep fibrous histiocytomas, one MFS, one cellular angiofibroma and one ASCLT. Conclusions These findings confirm that CYP1A1 is 70% sensitive, consistent with the prevalence of AHRR :: NCOA2 fusions that up‐regulate this protein, and that it is highly specific among morphological mimics.