title: SMARCB1 (INI-1)-deficient Sinonasal Carcinoma: A Series of 39 Cases Expanding the Morphologic and Clinicopathologic Spectrum of a Recently Described Entity.
abstract: To more fully characterize the clinical and pathologic spectrum of a recently described tumor entity of the sinonasal tract characterized by loss of nuclear expression of SMARCB1 (INI1), we analyzed 39 SMARCB1-deficient sinonasal carcinomas collected from multiple medical centers. The tumors affected 23 males and 16 females with an age range of 19 to 89 years (median, 52). All patients presented with locally advanced disease (T3, n=5; T4, n=27) involving the sinuses (mainly ethmoid) with variable involvement of the nasal cavity. Thirty patients received surgery and/or radiochemotherapy with curative intent. At last follow-up, 56% of patients died of disease 0 to 102 months after diagnosis (median, 15), 2 were alive with disease, and 1 died of an unrelated cause. Only 9 patients (30%) were alive without disease at last follow-up (range, 11 to 115 mo; median, 26). The original diagnosis of retrospectively identified cases was most often sinonasal undifferentiated carcinoma (n=14) and nonkeratinizing/basaloid squamous cell carcinoma (n=5). Histologically, most tumors displayed either a predominantly basaloid (61%) or plasmacytoid/rhabdoid morphology (36%). The plasmacytoid/rhabdoid form consisted of sheets of tumor cells with abundant, eccentrically placed eosinophilic cytoplasm, whereas similar cells were typically rare and singly distributed in the basaloid variant. Glandular differentiation was seen in a few tumors. None of the cases showed squamous differentiation or surface dysplasia. By immunohistochemistry, the tumors were positive for pancytokeratin (97%), CK5 (64%), p63 (55%), and CK7 (48%); and they were negative for NUT (0%). Epstein-Barr virus and high-risk human papillomavirus was not detected by in situ hybridization. Immunohistochemical loss of SMARCB1 (INI1) expression was confirmed for all 39 tumors. Investigation of other proteins in the SWI/SNF complex revealed co-loss of SMARCA2 in 4 cases, but none were SMARCA4 deficient or ARID1A deficient. Of 27 tumors with SMARCB1 fluorescence in situ hybridization analysis, 14 showed homozygous (biallelic) deletions and 7 showed heterozygous (monoallelic) deletions. SMARCB1-deficient sinonasal carcinoma represents an emerging poorly differentiated/undifferentiated sinonasal carcinoma that (1) cannot be better classified as another specific tumor type, (2) has consistent histopathologic findings (albeit with some variability) with varying proportions of plasmacytoid/rhabdoid cells, and (3) demonstrates an aggressive clinical course. This entity should be considered in any difficult-to-classify sinonasal carcinoma, as correct diagnosis will be mandatory for optimizing therapy and for further delineation of this likely underdiagnosed disease.
authors.affiliation: *Institute of Pathology Departments of ¶Otorhinolaryngology Head and Neck Surgery ¶¶Radiation Therapy, University Hospital of Erlangen, Erlangen ∥Institute of Pathology, St Vincent's Hospital, Karlsruhe **Institute of Pathology, Klinikum Augsburg, Augsburg ‡‡Pathology Laboratory, Frankfurt am Main, Germany †Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY ‡Department of Pathology, University of Pittsburgh Medical Center, Presbyterian Hospital, Pittsburgh, PA §Division of Anatomic and Molecular Pathology, Washington University School of Medicine, St Louis, MO #Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN ††Department of Pathology, University of Virginia, Charlottesville, VA §§Department of Neuropathology, Pathology Queensland, Royal Brisbane Hospitals Campus, Herston, Qld, Australia ∥∥Department of Histopathology, Charing Cross Hospital & Imperial College Healthcare NHS Trust, London, UK ##Department of Anatomical Pathology, University of Calgary, Calgary, AB, Canada ***Departments of Pathology, Otolaryngology-Head and Neck Surgery, and Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Abbas
authors.initials: A
authors.lastname: Agaimy
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
authors.forename: Simion I
authors.initials: SI
authors.lastname: Chiosea
authors.forename: Samir K
authors.initials: SK
authors.lastname: El-Mofty
authors.forename: Helene
authors.initials: H
authors.lastname: Geddert
authors.forename: Heinrich
authors.initials: H
authors.lastname: Iro
authors.forename: James S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Bruno
authors.initials: B
authors.lastname: Märkl
authors.forename: Stacey E
authors.initials: SE
authors.lastname: Mills
authors.forename: Marc-Oliver
authors.initials: MO
authors.lastname: Riener
authors.forename: Thomas
authors.initials: T
authors.lastname: Robertson
authors.forename: Ann
authors.initials: A
authors.lastname: Sandison
authors.forename: Sabine
authors.initials: S
authors.lastname: Semrau
authors.forename: Roderick H W
authors.initials: RH
authors.lastname: Simpson
authors.forename: Edward
authors.initials: E
authors.lastname: Stelow
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.forename: Justin A
authors.initials: JA
authors.lastname: Bishop
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000172:deficiency* / Q000235:genetics; D001706:Biopsy; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D005858:Germany; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008279:Magnetic Resonance Imaging; D008297:Male; D008444:Maxillary Sinus Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D059747:Nasal Surgical Procedures; D009367:Neoplasm Staging; D009669:Nose Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D010256:Paranasal Sinuses / Q000737:chemistry* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D000071796:SMARCB1 Protein / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human