title: Adamantinoma-like Ewing family tumors of the head and neck: a pitfall in the differential diagnosis of basaloid and myoepithelial carcinomas.
abstract: Ewing sarcoma family tumors (EFTs) of the head and neck are rare and may be difficult to diagnose, as they display significant histologic overlap with other more common undifferentiated small blue round cell malignancies. Occasionally, EFTs may exhibit overt epithelial differentiation in the form of diffuse cytokeratin immunoexpression or squamous pearls, resembling the so-called adamantinoma-like EFTs and being challenging to distinguish from bona fide carcinomas. Furthermore, the presence of EWSR1 gene rearrangement correlated with strong keratin expression may suggest a myoepithelial carcinoma. Herein, we analyze a series of 7 adamantinoma-like EFTs of the head and neck, most of them being initially misdiagnosed as carcinomas because of their anatomic location and strong cytokeratin immunoexpression, and subsequently reclassified as EFT by molecular techniques. The tumors arose in the sinonasal tract (n=2), parotid gland (n=2), thyroid gland (n=2), and orbit (n=1), in patients ranging in age from 7 to 56 years (mean, 31 y). Microscopically, they departed from the typical EFT morphology by growing as nests with peripheral nuclear palisading and prominent interlobular fibrosis, imparting a distinctly basaloid appearance. Moreover, 2 cases exhibited overt keratinization in the form of squamous pearls, and 1 sinonasal tumor demonstrated areas of intraepithelial growth. All cases were positive for CD99, pancytokeratin, and p40. A subset of cases showed synaptophysin, S100 protein, and/or p16 reactivity, further confounding the diagnosis. Fluorescence in situ hybridization assays showed EWSR1 and FLI1 rearrangements in all cases. Our results reinforce that a subset of head and neck EFTs may show strong cytokeratin expression or focal keratinization, and are therefore histologically indistinguishable from more common true epithelial neoplasms. Thus, CD99 should be included in the immunopanel of a round cell malignancy regardless of strong cytokeratin expression or anatomic location, and a strong and diffuse CD99 positivity should prompt molecular testing for the presence of EWSR1 gene rearrangements.
authors.affiliation: *Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD §Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA ‡Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY †Department of Pathology, Padova University Hospital, Padova, Italy.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Bishop
authors.forename: Rita
authors.initials: R
authors.lastname: Alaggio
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Raja R
authors.initials: RR
authors.lastname: Seethala
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
mesh_terms: D000071443:12E7 Antigen; D050398:Adamantinoma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D001859:Bone Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000032:analysis; D002454:Cell Differentiation; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D015321:Gene Rearrangement; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007633:Keratins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009208:Myoepithelioma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics; D012512:Sarcoma, Ewing / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C061828:CD99 protein, human; D002148:Calmodulin-Binding Proteins; D015815:Cell Adhesion Molecules; C500986:EWSR1 protein, human; C078433:FLI1 protein, human; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; D007633:Keratins