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Epithelioid mesenchymal neoplasm with FUS::CREM gene fusion in the tongue: Report of a rare and challenging diagnosis

  • Author Footnotes
    1 Yanan Sun and Deyu Liu contributed equally.
    Yanan Sun
    Footnotes
    1 Yanan Sun and Deyu Liu contributed equally.
    Affiliations
    The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China

    Department of Pathology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
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  • Author Footnotes
    1 Yanan Sun and Deyu Liu contributed equally.
    Deyu Liu
    Footnotes
    1 Yanan Sun and Deyu Liu contributed equally.
    Affiliations
    Department of Oral and Maxillofacial Surgery, Affiliated Haikou Hospital, Central South University, Haikou, Hainan, China
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  • Xinming Chen
    Affiliations
    Department of Pathology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
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  • Jiali Zhang
    Affiliations
    Department of Pathology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
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  • Shaodong Yang
    Correspondence
    Corresponding author: Shaodong Yang.
    Affiliations
    The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China

    Department of Pathology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China
    Search for articles by this author
  • Author Footnotes
    1 Yanan Sun and Deyu Liu contributed equally.
Published:December 18, 2022DOI:https://doi.org/10.1016/j.oooo.2022.12.003
      FET (encompassing both EWSR1 and FUS) fusions with genes from the CREB family (CREB1, ATF1, and CREM) are involved in a variety of neoplasms. Recently, FET::CREB fusions were recognized in a group of malignant epithelioid neoplasm with a striking predilection to mesothelial-lined cavities and frequent cytokeratin immunoexpression. Herein, we report a rare mesenchymal neoplasm with epithelioid morphology and nonspecific immunoprofile harboring a FUS::CREM fusion arising in the oral tongue of a 53-year-old man. Histology showed a well-circumscribed tumor composed of epithelioid cells with eosinopohilic or clear cytoplasm with sparse stroma, accompanied by peripheral lymphoplasmacytic infiltrates. Immunohistochemically, an extensive panel revealed only patchy expression of synaptophysin and weak-to-moderate nuclear expression of TFE3, and negativity for other markers including cytokeratins, epithelial membrane antigen, p63/p40, vimentin, S100, smooth muscle actin, CD34, desmin, SOX10, glial fibrillary acidic protein, melan-A, HMB45, and CD68. A FUS::CREM gene fusion was detected by next generation sequencing at an outside institution, and subsequent fluorescence in situ hybridization analysis confirmed the presence of FUS gene rearrangement. The identification and analysis of additional cases should help to clarify the nosologic status and the biologic potential of this tumor.
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      REFERENCES

        • Thway K
        • Fisher C.
        Angiomatoid fibrous histiocytoma: the current status of pathology and genetics.
        Arch Pathol Lab Med. 2015; 139: 674-682
        • Yoshida A
        • Wakai S
        • Ryo E
        • et al.
        Expanding the phenotypic spectrum of mesenchymal tumors harboring the EWSR1-CREM fusion.
        Am J Surg Pathol. 2019; 43: 1622-1630
        • Lee PH
        • Kao YC
        • Hsieh TH
        • et al.
        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; 229153700
        • Chapman E
        • Skalova A
        • Ptakova N
        • et al.
        Molecular profiling of hyalinizing clear cell carcinomas revealed a subset of tumors harboring a novel EWSR1-CREM fusion: report of 3 cases.
        Am J Surg Pathol. 2018; 42: 1182-1189
        • Rivera CM
        • Faquin WC
        • Thierauf J
        • et al.
        Detection of EWSR1 fusions in CCOC by targeted RNA-seq.
        Oral Surg Oral Med Oral Pathol Oral Radiol. 2022; 134: 240-244
        • Kao YC
        • Sung YS
        • Zhang L
        • et al.
        EWSR1 fusions with CREB family transcription factors define a novel myxoid mesenchymal tumor with predilection for intracranial location.
        Am J Surg Pathol. 2017; 41: 482-490
        • Sloan EA
        • Chiang J
        • Villanueva-Meyer JE
        • et al.
        Intracranial mesenchymal tumor with FET-CREB fusion-A unifying diagnosis for the spectrum of intracranial myxoid mesenchymal tumors and angiomatoid fibrous histiocytoma-like neoplasms.
        Brain Pathol. 2021; 31: e12918
        • Dermawan JK
        • Vanoli F
        • Herviou L
        • et al.
        Comprehensive genomic profiling of EWSR1/FUS::CREB translocation-associated tumors uncovers prognostically significant recurrent genetic alterations and methylation-transcriptional correlates.
        Mod Pathol. 2022; 35: 1055-1065
        • Argani P
        • Harvey I
        • Nielsen GP
        • et al.
        EWSR1/FUS-CREB fusions define a distinctive malignant epithelioid neoplasm with predilection for mesothelial-lined cavities.
        Mod Pathol. 2020; 33: 2233-2243
        • Shibayama T
        • Shimoi T
        • Mori T
        • et al.
        Cytokeratin-positive malignant tumor in the abdomen with EWSR1/FUS-CREB fusion: a clinicopathologic study of 8 cases.
        Am J Surg Pathol. 2022; 46: 134-146
        • Agaimy A
        • Stoehr R
        • Otto M
        • et al.
        Intra-abdominal EWSR1/FUS-CREM-rearranged malignant epithelioid neoplasms: two cases of an emerging aggressive entity with emphasis on misleading immunophenotype.
        Virchows Arch. 2022; 480: 481-486
        • Dickson BC
        • Antonescu CR
        • Argyris PP
        • et al.
        Ectomesenchymal chondromyxoid tumor: a neoplasm characterized by recurrent RREB1-MKL2 fusions.
        Am J Surg Pathol. 2018; 42: 1297-1305
        • Agaimy A.
        What is new in epithelioid soft tissue tumors?.
        Virchows Arch. 2020; 476: 81-96
        • Antonescu CR
        • Rosenberg AE
        • Xie Z
        • Zhang L
        • Perell KA
        • Loya AC.
        Sarcomas with sclerotic epithelioid phenotype harboring novel EWSR1-SSX1 fusions.
        Genes Chromosomes Cancer. 2021; 60: 616-622
        • Nakamura H
        • Kukita Y
        • Takenaka S
        • Yagi T.
        Malignant epithelioid soft-tissue tumour with the NRID1-MAML1 fusion.
        Histopathology. 2021; 79: 1112-1114
        • Underwood CIM
        • Cardona DM
        • Bentley RC
        • et al.
        Epithelioid hyalinizing sarcoma with MGA-NUTM1 fusion.
        Am J Clin Pathol. 2020; 154: 859-866
        • Zhong H
        • Xu C
        • Chen X
        • Guo X
        • Yang S.
        GLI1-altered epithelioid soft tissue tumor: a newly described entity with a predilection for the tongue.
        Oral Surg Oral Med Oral Pathol Oral Radiol. 2022; 134: e14-e22
        • Suurmeijer AJH
        • Dickson BC
        • Swanson D
        • et al.
        A morphologic and molecular reappraisal of myoepithelial tumors of soft tissue, bone, and viscera with EWSR1 and FUS gene rearrangements.
        Genes Chromosomes Cancer. 2020; 59: 348-356
        • Yang S
        • Li L
        • Zeng M
        • Zhu X
        • Zhang J
        • Chen X.
        Myoepithelial carcinoma of intraoral minor salivary glands: a clinicopathological study of 7 cases and review of the literature.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 110: 85-93
        • Yang S
        • Zhang J
        • Chen X
        • Wang L
        • Xie F.
        Clear cell carcinoma, not otherwise specified, of salivary glands: a clinicopathologic study of 4 cases and review of the literature.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008; 106: 712-720
        • Sbaraglia M
        • Zanatta L
        • Toffolatti L
        • et al.
        Clear cell sarcoma-like/malignant gastrointestinal neuroectodermal tumor of the tongue: a clinicopathologic and molecular case report.
        Virchows Arch. 2021; 478: 1203-1207
        • Feasel PC
        • Cheah AL
        • Fritchie K
        • Winn B
        • Piliang M
        • Billings SD.
        Primary clear cell sarcoma of the head and neck: a case series with review of the literature.
        J Cutan Pathol. 2016; 43: 838-846
        • Flucke U
        • Mentzel T
        • Verdijk MA
        • et al.
        EWSR1-ATF1 chimeric transcript in a myoepithelial tumor of soft tissue: a case report.
        Hum Pathol. 2012; 43: 764-768
        • Leckey Jr, BD
        • John I
        • Reyes-Múgica M
        • Naous R
        EWSR1-ATF1 fusion in a myoepithelial carcinoma of soft tissue with small round cell morphology: a potential diagnostic pitfall.
        Pediatr Dev Pathol. 2021; 24: 258-263