Novel NCOA2/3‐rearranged low‐grade fibroblastic spindle cell tumors: A report of five cases

Abstract

Spindle cell mesenchymal neoplasms are a diverse and often challenging diagnostic group. While morphological impression is sufficient for some diagnoses, increasingly immunohistochemical and even molecular data is required to render an accurate diagnosis, which can lead to the characterization of new entities. We describe five cases of novel mesenchymal neoplasms with rearrangements in the NCOA2 and NCOA3 genes partnered with either CTCF or CRTC1. Three tumors occurred in the head and neck (palate, auditory canal), while the other two were in visceral organs (lung, urinary bladder). All cases occurred in adults (range 33–86) with a median age of 42 and fairly even sex distribution = (male‐to‐female = 3:2). Morphologically, they had similar features consisting of monotonous, bland spindle to ovoid cells with fascicular and reticular arrangements in a myxohyaline to collagenous stroma. However, immunophenotypically they had essentially a null phenotype, with only two tumors staining partially for CD34 and smooth muscle actin. Targeted RNA sequencing detected in‐frame CTCF::NCOA2 (one case), CRTC1::NCOA2 (two cases), and CTCF::NCOA3 (two cases) fusions. Treatment was surgical resection in all cases. Local recurrence and/or distant metastases were not observed in any case (median follow‐up, 7.5 months; range, 2–19 months). Given their morphologic, immunohistochemical, and molecular similarities, we believe that these cases may represent an emerging family of low‐grade NCOA2/3‐rearranged fibroblastic spindle cell neoplasms.

Aggressive prostate myxoid mesenchymal neoplasm with novel CRTC1::NCOA2 fusion

“…Our neoplasm shares the same newly discovered novel fusion including similar breakpoints with two other tumours from the palate and bladder, 1 which were just reported 1 month prior to our submission in a very small series of five cases collectively categorized as NCOA2/3-rearranged fibroblastic tumours with lowgrade features. 1 These two tumours and ours demonstrate lobular growth, reticular arrangement of spindle cells positive for SMA and CD34, and myxohyaline stroma.…”

“…NCOA2 is a transcriptional coactivator for nuclear hormone receptors involved in spindle cell rhabdomyosarcoma (PAX3::NCOA2) and mesenchymal chondrosarcoma (HEY1::NCOA2). 1 Primary prostatic mesenchymal tumours are exceedingly rare. The most important differential diagnoses include extraskeletal myxoid chondrosarcoma (EMC), gastrointestinal stromal tumour (GIST), soft-tissue myoepithelioma, and prostatic stromal sarcoma (PSS).…”

Pediatric NCOA3‐rearranged low‐grade fibroblastic tumor with nuclear beta‐catenin immunoreactivity

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To the EditorWe read with great interest the recent article by Bakhshwin et al, which described five adult patients with low-grade spindle cell fibroblastic neoplasms with recurrent rearrangements of NCOA2 or NCOA3 (nuclear factor co-receptor) genes. 1 We share our recent experience of a low-grade fibroblastic tumor with CTCF:: NCOA3 fusion presenting in a pediatric patient, with a previously undescribed finding of beta-catenin immunohistochemical expression.A 7-year-old previously healthy female presented with a left lat-

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