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

Agaimy A, Molligan J, Alruwaii FI, Antonescu CR, Demicco EG, Dickson BC, Gross J, Michal M, Perry K, Tögel L, Stöhr R, Din NU, Folpe AL (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Virchows Archiv Springer Verlag (Germany)

DOI: 10.1007/s00428-025-04199-y

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.

Authors with CRIS profile

Abbas Agaimy Medizinische Fakultät Lars Tögel Institute of Pathology Robert Stöhr Medizinische Fakultät

Involved external institutions

Mayo Clinic US United States (USA) (US) Henry Ford Health System (HFHS) US United States (USA) (US) Memorial Sloan Kettering Cancer Center US United States (USA) (US) Johns Hopkins University (JHU) US United States (USA) (US) Univerzita Karlova v Praze / Charles University in Prague CZ Czech Republic (CZ) University of Michigan US United States (USA) (US) University of Miami US United States (USA) (US)

How to cite

APA:

Agaimy, A., Molligan, J., Alruwaii, F.I., Antonescu, C.R., Demicco, E.G., Dickson, B.C.,... Folpe, A.L. (2025). 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. Virchows Archiv. https://doi.org/10.1007/s00428-025-04199-y

MLA:

Agaimy, Abbas, et al. "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." Virchows Archiv (2025).

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