Angiomatoid Fibrous Histiocytoma: The Current Status of Pathology and Genetics

Abstract

Context.-Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of intermediate biologic potential and uncertain differentiation, most often arising in the superficial extremities of children and young adults. While it has characteristic histologic features of nodular distributions of ovoid and spindle cells with blood-filled cystic cavities and a surrounding dense lymphoplasmacytic infiltrate, there is a significant morphologic spectrum, which coupled with its rarity and lack of specific immunoprofile can make diagnosis challenging. Angiomatoid fibrous histiocytoma is associated with 3 characteristic gene fusions, EWSR1-CREB1 and EWSR1-ATF1, which are also described in other neoplasms, and rarely FUS-ATF1. Angiomatoid fibrous histiocytoma is now recognized at an increasing number of sites and is known to display a variety of unusual histologic features.Objective.-To review the current status of AFH, discussing putative etiology, histopathology with variant morphology and differential diagnosis, and current genetics, including overlap with other tumors harboring EWSR1-CREB1 and EWSR1-ATF1 fusions.Data Sources.-Review of published literature, including case series, case reports, and review articles, in online medical databases.Conclusions.-The occurrence of AFH at several unusual anatomic sites and its spectrum of morphologic patterns can result in significant diagnostic difficulty, and correct diagnosis is particularly important because of its small risk of metastasis and death. This highlights the importance of diagnostic recognition, ancillary molecular genetic confirmation, and close clinical follow-up of patients with AFH. Further insight into the genetic and epigenetic changes arising secondary to the characteristic gene fusions of AFH will be integral to understanding its tumorigenic mechanisms.

EWSR1 Fusions With CREB Family Transcription Factors Define a Novel Myxoid Mesenchymal Tumor With Predilection for Intracranial Location

“…Although CREB1 and ATF1 are interchangeable gene partners, there is a striking propensity for EWSR1-CREB1 to occur in AFH and GICCS, and for EWSR1-ATF1 in CCS. 2–6 To date, only EWSR1-ATF1 fusion has been detected in hyalinizing clear cell carcinoma, 7 while only EWSR1-CREB1 was reported in PPMS. Apart from the gene fusion overlap, these tumors show different clinical presentations, morphologic features, immunoprofiles and patient outcomes.…”

Pathologically Benign Lymph Nodes Can Mimic Malignancy on Imaging in Patients With Angiomatoid Fibrous Histiocytoma

“…Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of unclear origin [14]. It is most commonly found superficially in the extremities of patients younger than 30 years [3,5], although it has been found in other sites including the soft tissues of the neck and trunk, brain, lungs, peritoneum, retroperitoneum, gynecologic tract, and bone, and at ages ranging from infancy to the elderly [2,14]. AFH was first reported as a subtype of malignant fibrous histiocytoma [4], but has since been reclassified as a distinct pathologic process [3].…”

The spectrum of EWSR1-rearranged neoplasms at a tertiary sarcoma centre; assessing 772 tumour specimens and the value of current ancillary molecular diagnostic modalities

“…Its role in cancer cell progression is still unclear, although it may play a critical role in DNA damage response and cell division (Li et al , 2007; Paronetto, 2013). While initially thought specific for Ewing sarcoma (formerly the Ewing sarcoma/primitive peripheral neuroectodermal tumour (PNET) family of tumours) (Dockhorn Dworniczak et al , 1994), characteristic rearrangements between EWSR1 and partner genes have been documented in both tumours of mesenchymal and non-mesenchymal lineage, including desmoplastic small round cell tumour (DSRCT; Ladanyi and Gerald, 1994; Antonescu et al , 1998), myxoid liposarcoma (MLPS; Panagopoulos et al , 1996; Dal Cin et al , 1997; Hosaka et al , 2002), extraskeletal myxoid chondrosarcoma (EMC; Sciot et al , 1995; Clark et al , 1996), angiomatoid fibrous histiocytoma (AFH; Hallor et al , 2005; Rossi et al , 2007; Thway and Fisher, 2015; Thway et al , 2015b), clear cell sarcoma of soft tissue (CCS; Hisaoka et al , 2008; Wang et al , 2009) and clear cell sarcoma-like tumours of the gastrointestinal tract (CCSLGT; Thway and Fisher, 2012; Wang and Thway, 2015), primary pulmonary myxoid sarcoma (PPMS; Thway et al , 2011), myoepithelial tumours of skin, soft tissue and bone (Antonescu et al , 2010a; Antonescu et al , 2010b; Thway and Fisher, 2014; Thway et al , 2015a), and more rarely in low-grade fibromyxoid sarcoma (LGFMS; Lau et al , 2013) and sclerosing epithelioid fibrosarcoma (SEF; Doyle et al , 2012; Arbajian et al , 2014). EWSR1 rearrangements can be easily detected in the routine setting by fluorescence in situ hybridisation (FISH) with break-apart probes, and corresponding fusion transcripts by reverse transcription–PCR (RT–PCR) studies, usually using commercial probes and primers respectively.…”