Cutaneous intravascular epithelioid hemangioma. A clinicopathological and molecular study of 21 cases

Luzar, Boštjan; Ieremia, Eleni; Antonescu, Cristina R.; Zhang, Lei; Calonje, Eduardo

doi:10.1038/s41379-020-0505-4

Cited by 12 publications

(15 citation statements)

References 38 publications

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“…The morphologic spectrum of EH exhibits a wide range of appearances, including cellular/solid proliferation, atypical cytomorphology, prominent inflammatory infiltrate, and intravascular growth[ 19 ]. Due to this diverse histomorphologies the diagnosis of EH remains challenging, being confused at one end of the spectrum with inflammatory conditions (e.g.…”

Section: Discussionmentioning

confidence: 99%

Novel GATA6-FOXO1 fusions in a subset of epithelioid hemangioma

et al. 2021

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The genetic hallmark of epithelioid hemangioma (EH) is the presence of recurrent gene fusions involving FOS and FOSB transcription factors, which occur in one third of the cases. Certain clinical, pathologic and genotypic correlations have been described, with FOS -related fusions being more often detected in skeletal and cellular variants of EH, while FOSB gene rearrangements are more commonly associated with atypical histologic features and penile location. These fusions are infrequently detected in the cutaneous or head and neck EH. Overall, two-thirds of EH lack these canonical fusions and remain difficult to classify, especially when associated with atypical features and/or clinical presentations. Triggered by an index case of an intravascular soft tissue EH with a novel GATA6-FOXO1 gene fusion by targeted RNA sequencing (Archer® FusionPlex® Sarcoma Panel), we have investigated 27 additional EH cases negative for FOS and FOSB gene rearrangements for this novel abnormality to determine its recurrent potential and its association with clinical and pathologic features. Four additional EH cases were found to display GATA6-FOXO1 fusions (18 %). There were 3 females and 2 males, with a mean age of 32 years old. Three lesions occurred in the head and neck (dura, nasopharyngeal, cheek), one in the back and one in the leg. Two of these lesions were cutaneous and one was intravascular in the subcutis of the leg. Microscopically, the tumors showed a variegated morphology, with alternating vasoformative and solid components, extravasated red blood cells and mild to moderate cytologic atypia. None showed brisk mitotic activity or necrosis. Tumors were negative for FOS and FOSB by immunohistochemistry. In conclusion, we report a new GATA6-FOXO1 fusion in a subset of EH, with a predilection for skin and head and neck location. The relationship of this novel molecular subset with the more common FOS/FOSB -fusion positive EH remains to be determined.

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Section: Discussionmentioning

confidence: 99%

Novel GATA6-FOXO1 fusions in a subset of epithelioid hemangioma

et al. 2021

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“…However, only one‐third of EHs overall harbour FOS / FOSB gene fusions, 30,37 although the incidence varies significantly with anatomical location, with osseous EH showing the highest proportion of fusions (>70%) 33 . Interestingly, FOS and FOSB rearrangements are exceedingly rare in cutaneous intravascular EH, with only one case of 21 harbouring a FOS rearrangement 38 . FOS ‐rearranged tumours have a predilection for bone and are more commonly classified as cellular EH 33,37 .…”

Section: Haemangiomasmentioning

confidence: 99%

“…33 Interestingly, FOS and FOSB rearrangements are exceedingly rare in cutaneous intravascular EH, with only one case of 21 harbouring a FOS rearrangement. 38 FOS-rearranged tumours have a predilection for bone and are more commonly classified as cellular EH. 33,37 In a large series of 58 EH cases, 29% of cases harboured FOS rearrangements.…”

Section: E P I T H E L I O I D H a E M A N G I O M A S ( E H S ) Hmentioning

confidence: 99%

The genetics of vascular tumours: an update

Torrence

Antonescu

2021

Histopathology

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Recent molecular advances have shed significant light on the classification of vascular tumours. Except for haemangiomas, vascular lesions remain difficult to diagnose, owing to their rarity and overlapping clinical, radiographic and histological features across malignancies. In particular, challenges still remain in the differential diagnosis of epithelioid vascular tumours, including epithelioid haemangioma and epithelioid haemangioendothelioma at the benign/low‐grade end of the spectrum, and epithelioid angiosarcoma at the high‐grade end. Historically, the classification of vascular tumours has been heavily dependent on the clinical setting and histological features, as traditional immunohistochemical markers across the group have often been non‐discriminatory. The increased application of next‐generation sequencing in clinical practice, in particular targeted RNA sequencing (such as Archer, Illumina), has led to numerous novel discoveries, mainly recurrent gene fusions (e.g. those involving FOS, FOSB, YAP1, and WWTR1), which have resulted in refined tumour classification and improved diagnostic reproducibility for vascular tumours. However, other molecular alterations besides fusions have been discovered in vascular tumours, including somatic mutations (e.g. involving GNA family and IDH genes) in a variety of haemangiomas, as well as copy number alterations in high‐grade angiosarcomas (e.g. MYC amplifications). Moreover, the translation of these novel molecular abnormalities into diagnostic ancillary markers, either fluorescence in‐situ hybridisation probes or surrogate immunohistochemical markers (FOSB, CAMTA1, YAP1, and MYC), has been remarkable. This review will focus on the latest molecular discoveries covering both benign and malignant vascular tumours, and will provide practical diagnostic algorithms, highlighting frequently encountered pitfalls and challenges in the diagnosis of vascular lesions.

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“…2 In addition to the lack of overt vasoformation, the locoregionally confined intravascular growth pattern is also uncommonly described, particularly in non-cutaneous EH. 3 An eosinophilic stromal infiltrate is a classic feature of EH, as reflected in the original description of this entity, angiolymphoid hyperplasia with eosinphilia (ALHE). However, it has since been recognised that the eosinophilic stromal infiltrate is only occasionally seen in deep seated soft tissue or bone EH, 4 as illustrated in this case.…”

mentioning

confidence: 99%

“…Of note, FOSB gene rearrangements were not detected in a recent case series of cutaneous intravascular EH, suggesting different genetic underpinnings of cutaneous versus non-cutaneous intravascular EHs. 3 The FOS gene family consists of four members: FOS (chromosome 14q24.3), FOSB (chromosome 19q13.32), FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerise with proteins of the JUN family, constituting the major components of the transcription factor complex AP-1 (Activating Protein-1).…”

mentioning

confidence: 99%