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

Pei-Hang Lee; Yu-Chien Kao; Tsung-Han Hsieh; Jia-Bin Liao; Chien-Feng Li; Jen-Chieh Lee; Yi-Ming Chang; Ching-Di Chang; Shih-Chiang Huang; Tzu-Ju Chen; Ting-Ting Liu; Shih-Chen Yu; Hsuan-Ying Huang

doi:10.1016/j.prp.2021.153700

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

Pathol Res Pract. 2022 Jan:229:153700. doi: 10.1016/j.prp.2021.153700. Epub 2021 Nov 24.

Authors

Affiliations

¹ Department of Anatomical Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
² Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
³ Joint Biobank, Office of Human Research, Taipei Medical University, Taipei 110, Taiwan.
⁴ Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
⁵ Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan.
⁶ Department and Graduate Institute of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
⁷ Department of Pathology, Tri-service General Hospital and the Graduate Institute of Medical Sciences, National Defense Medical center, Taipei, Taiwan.
⁸ Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
⁹ Department of Anatomic Pathology, Linkou Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
¹⁰ Department of Clinical Pathology, Chi-Mei Medical Center, Tainan, Taiwan.
¹¹ Department of Anatomical Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Medical Laboratory Science, I-Shou University, Kaohsiung, Taiwan.
¹² Department of Anatomical Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: a120600310@yahoo.com.

PMID: 34929603
DOI: 10.1016/j.prp.2021.153700

Abstract

Aims: 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.

Methods: Twelve extracranial tumors harboring EWSR1/FUS-CREB fusions across different histologic groups were characterized using RNA sequencing, FISH and/or RT-PCR.

Results: 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.

Conclusions: 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.

Keywords: Angiomatoid fibrous histiocytoma; CREB; Extracranial; FET; Myoepithelial; Myxocollagenous.

MeSH terms

Adult
Aged
Brain Neoplasms / diagnosis*
Brain Neoplasms / etiology*
Brain Neoplasms / pathology
CREB-Binding Protein / physiology*
Female
Humans
Male
Middle Aged
Neoplasm Invasiveness
Neoplasms, Connective and Soft Tissue / diagnosis*
Neoplasms, Connective and Soft Tissue / etiology*
Neoplasms, Connective and Soft Tissue / pathology
Young Adult

Substances

CREB-Binding Protein