ALK-rearranged mesenchymal neoplasms: a clinicopathological and molecular study of eight additional cases of an emerging group of tyrosine kinase fusion mesenchymal tumours

Abstract

AimsMesenchymal neoplasms characterised byALKfusions mainly include inflammatory myofibroblastic tumour (IMT) and epithelioid fibrous histiocytoma (EFH). Most recently,ALK-rearranged mesenchymal tumours that are not IMT or EFH have been reported. Our aim is to further characterise eight such neoplasms, with a detailed clinicopathological, immunohistochemical and molecular analysis.MethodsClinicopathological features were assessed and partner agnostic targeted RNA-sequencing on clinically validated platforms was performed.ResultsThe patients consisted of seven males and one female with a median age of 47 years (28 –59 years). The tumours ranged in size from 2.0 to 10.0 cm (mean=3.0 cm) and involved superficial and deep soft tissue (n=6) and visceral locations (n=2). Of the seven patients with follow-up (9–130 months), two developed distant metastases and five had no disease recurrence or metastasis. The tumours demonstrated diverse architectures and variable cellularity and cellular morphologies. The main constitutive cells appeared in elongated spindled in three, primitive to ovoid in two and round to epithelioid in three cases. We expanded the histopathological spectrum to include mildly to moderately cellular spindled to stellate cells in a multinodular growth in a prominent myxoid and vascularised stroma (n=2). All tumours expressed ALK(D5F3); seven were positive for S100 protein and six were positive for CD34. By fluorescence in situ hybridisation,ALKrearrangement was identified in all eight tumours.ALKfusion partners were identified by RNA-sequencing in all cases, including previously reported:EML4(n=3), DCTN(n=1), CLIP1(n=1) andPLEKHH2(n=1), and also two novel fusion partners:TKT(n=1) andMMP2(n=1).ConclusionsOur study expands the clinicopathological and molecular spectrum ofALK-rearranged mesenchymal neoplasms.