Clinicopathological and genetic heterogeneity of the head and neck solitary fibrous tumours: A comparative histological, immunohistochemical and molecular study of 36 cases

Aims: Solitary fibrous tumour (SFT) harbours recurrent inv12(q13q13)-derived NAB2-STAT6 fusions, resulting in STAT6 nuclear expression. SFTs affecting the head and neck are rare, for which we reported their clinicopathological, immunohistochemical, and genetic features. Methods and results: With 19 cases assessable for NAB2-STAT6 fusions, 36 head and neck SFTs (18 males; 18 females) diagnosed between 13 and 79 years (median, 47 years) of age were analysed for clinicopathological features and STAT6 immunoexpression. These SFTs, ranging from 5 to 80 mm (median, 25 mm), affected the oral cavity/pharynx (12), orbit (11), sinonasal structures (seven), and somatic soft tissues or skull (six). Histologically, 20 SFTs were conventional, six were giant-cell angiofibroma-like, one was fat-forming, four were cellular/atypical, and five were malignant (two developing metastases). STAT6 distinctively decorated the tumoral nuclei in 35 (97.2%) SFTs, but not in 29 site-relevant histological mimics categorized into 12 entities. Sixteen (84.2%) SFTs showed NAB2-STAT6 fusions with highly heterogeneous exon compositions, including NAB2ex6-STAT6ex17 in four cases, NAB2ex4-STAT6ex2 in three cases, NAB2ex2-STAT6ex2, NAB2ex4-STAT6ex4, NAB2ex6-STAT6ex16 and NAB2ex6-STAT6ex18 in two cases each, and NAB2ex3-STAT6ex19 in one case. Conclusions: Nuclear STAT6 immunoexpression is sensitive and specific for distinguishing SFT from mimics. However, considerable heterogeneity exists in the head and neck SFTs regarding the locations, histological patterns, and NAB2-STAT6 fusion variants.