Angiomatoid fibrous histiocytoma occurring at distal/acral extremity sites: clinicopathological and molecular study of 26 cases highlighting frequent myxoid histology and site-dependent genotypic variation Journal Article
| Authors: | Agaimy, A.; Molligan, J.; Alruwaii, F. I.; Antonescu, C. R.; Demicco, E. G.; Dickson, B. C.; Gross, J.; Michal, M.; Perry, K.; Tögel, L.; Stoehr, R.; Din, N. U.; Folpe, A. L. |
| Article Title: | Angiomatoid fibrous histiocytoma occurring at distal/acral extremity sites: clinicopathological and molecular study of 26 cases highlighting frequent myxoid histology and site-dependent genotypic variation |
| Abstract: | Angiomatoid fibrous histiocytoma (AFH) is a rare mesenchymal neoplasm of borderline malignancy (locally recurring, rarely metastasizing), most often involving the limbs, trunk, and head/neck. Rarely, AFH may involve unusual locations. Herein, we characterize the clinicopathologic features of 26 AFH of the distal extremities, including acral sites. The tumors occurred in 19 females and 7 males ranging in age from 12 to 76 years (median, 23 years). Tumors involved the upper (n = 19) and lower (n = 6) distal extremity; one affected an unspecified digital site. Twenty-two cases occurred in acral locations (hands and feet). Subsets of cases showed the following morphologic features: multinodular architecture (26/26), lymphoid cuffs (23/26), prominent stromal myxoid change (11/25), angiomatoid features (9/26), and cytologic pleomorphism (8/26). The average mitotic count was 1/10 HPF; 3 cases showed brisk mitotic activity (> 10 mitoses/10 HPF). Immunohistochemistry revealed variable expression of desmin (16/25), EMA (14/21) and ALK (5/8). Molecular testing revealed EWSR1 rearrangements in 17/18 cases (94%). Among 12 tumors with known fusion partners, the fusions partner was CREB1 in 6 cases (50%), CREM in 4 tumors (33%), ATF1 in one tumor (8%) and PBX3 (8%) in another tumor. Prominent myxoid features were noted in 75% CREM versus 33% of CREB1 versus 0% of ATF1-fused tumors. AFH occurring in distal extremity/acral locations have a predilection for females, upper extremity locations, frequent unusual (solid, non-angiomatoid and myxoid) morphology and higher frequency of CREM over ATF1 fusions. Awareness of the morphologic spectrum of these rare neoplasms is essential for correct classification. |
| Keywords: | genes; sarcoma; tumor; clear cell sarcoma; variant; profiling; precision medicine; genetic landscape; mimics; ewsr1-creb1 fusion; targeted next generation sequencing |
| Journal Title: | Virchows Archiv |
| ISSN: | 0945-6317 |
| Publisher: | Springer |
| Publication status: | Online ahead of print |
| Date Published: | 2025-01-01 |
| Online Publication Date: | 2025-01-01 |
| Language: | English |
| ACCESSION: | WOS:001542556100001 |
| DOI: | 10.1007/s00428-025-04199-y |
| PROVIDER: | wos |
| Notes: | Article; Early Access -- Source: Wos |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work