Myoepithelial and oral intracranial myxoid mesenchymal tumor-like neoplasms as diagnostic considerations of the ever-expanding extracranial myxocollagenous tumors harboring FET-CREB fusions

• Published in: Pathology, research and practice research and practice, 2022-01, Vol.229, p.153700-153700, Article 153700
• Main Authors: Lee, Pei-Hang, Kao, Yu-Chien, Hsieh, Tsung-Han, Liao, Jia-Bin, Li, Chien-Feng, Lee, Jen-Chieh, Chang, Yi-Ming, Chang, Ching-Di, Huang, Shih-Chiang, Chen, Tzu-Ju, Liu, Ting-Ting, Yu, Shih-Chen, Huang, Hsuan-Ying
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiomatoid fibrous histiocytoma; Brain Neoplasms - diagnosis; Brain Neoplasms - etiology; Brain Neoplasms - pathology; CREB; CREB-Binding Protein - physiology; Extracranial; Female; FET; Humans; Male; Middle Aged; Myoepithelial; Myxocollagenous; Neoplasm Invasiveness; Neoplasms, Connective and Soft Tissue - diagnosis; Neoplasms, Connective and Soft Tissue - etiology; Neoplasms, Connective and Soft Tissue - pathology; Young Adult
• ISSN: 0344-0338; 1618-0631
• DOI: 10.1016/j.prp.2021.153700

Intracranial myxoid mesenchymal tumors (IMMTs) with fusions between EWSR1/FUS and CREB transcription factors have morphologic overlap with myxoid angiomatoid fibrous histiocytoma (mAFH) and myoepithelial tumor/carcinoma (MET/MEC). We aimed to study the clinicopathologic and genetic spectrum of extracranial IMMT-like tumors and their relationships with mAFH and MET/MEC. Twelve extracranial tumors harboring EWSR1/FUS-CREB fusions across different histologic groups were characterized using RNA sequencing, FISH and/or RT-PCR. There were 4 IMMT-like neoplasms, 3 MET/MECs, and 5 mAFHs from the tibia (n=1), oral cavity (n=2), and soft tissues (n=9; 5 in the extremities), harboring EWSR1-ATF1 in 4 cases, FUS-CREM and EWSR1-CREM in 3 each, and EWSR1-CREB1 in 2. Multinodular growth, reticular/cording/trabecular arrangements, myxocollagenous matrix, and lymphocytic infiltrates variably prevailed among the 3 groups. mAFHs were characterized by cells with syncytial cytoplasm. IMMT-like neoplasms and MET/MECs shared cells with distinct boundaries, but only MET/MECs expressed GFAP and/or S100. MUC4 and ALK were expressed in some IMMT-like neoplasms (2/4; 2/4) and mAFH (2/5; 1/5). Pan-TRK reactivity was observed in two IMMT-like neoplasms with upregulated NTRK3 mRNA and one MEC. Local recurrences, typically ≥ 12 months postoperatively, developed in 2/3 IMMT-like neoplasms, 1/2 MET/MECs, and 0/4 mAFHs with follow-up. No definite associations were found between fusion types and histology, immunoprofile or outcome. We demonstrated the similarities and differences among 3 extracranial myxocollagenous tumor groups sharing EWSR1/FUS-CREB fusions. Oral IMMT-like neoplasms harboring FUS-CREM or EWSR1-ATF1 and FUS-CREM-positive. ●Molecular testing enables identification of rare extracranial FET-CREB-positive myxocollagenous tumors, including morphologically overlapped myxoid angiomatoid fibrous histiocytoma, myoepithelial neoplasm, and those resembling so-called intracranial myxoid mesenchymal tumor (IMMT).●Oral IMMT-like neoplasms harboring FUS-CREM or EWSR1-ATF1 and FUS-CREM-positive myoepithelial neoplasm should join as new members of this ever-expanding family with clinicopathologic heterogeneity.●These tumor types often but variably express MUC4, ALK, and pan-TRK with NTRK3 mRNA upregulation.