title: Alveolar rhabdomyosarcoma of the head and neck region in older adults: genetic characterization and a review of the literature.
abstract: Alveolar rhabdomyosarcoma is remarkably rare in adults older than 45 years. Initial immunoprofiling of a small cell neoplasm of the head and neck region in an older adult may not include myogenic markers. A valuable diagnostic aid and important prognostic parameter in alveolar rhabdomyosarcoma is the identification of PAX3-FOXO1 [t(2;13)(q35;q14)] or PAX7-FOXO1 [t(1;13)(p36;q14)] rearrangements. The purpose of this study was to document the clinicopathologic, immunophenotypic, and genetic features of head/neck alveolar rhabdomyosarcoma in older adults. Prior isolated descriptions of 3 patients were included. Five patients were female and 2 male (median age, 61 years). Each neoplasm was composed of undifferentiated, small round cells in a predominantly solid pattern. Initially, ordered immunostains corresponded with early diagnostic impressions of a hematologic malignancy or neuroendocrine carcinoma. CD56 was positive in 5 of 5 tumors and synaptophysin in 1 of 6. Given the virtual absence of other lymphoid or epithelial markers, muscle immunostains were performed and these were positive. Definitive alveolar rhabdomyosarcoma diagnoses were confirmed genetically. This study illustrates the diagnosis of head/neck alveolar rhabdomyosarcoma in older adults is complicated by its rarity, lack of an alveolar pattern, and a potentially misleading immunoprofile (CD56 and synaptophysin immunoreactivity) if myogenic markers are not used. Both PAX3- and PAX7-FOXO1 alveolar rhabdomyosarcomas were identified in these patients. In children, PAX7-FOXO1 alveolar rhabdomyosarcoma is associated with a significantly longer event-free survival. In contrast, adult alveolar rhabdomyosarcoma behaves more aggressively with a worse overall survival than pediatric alveolar rhabdomyosarcoma. Further follow-up and additional cases are required to assess the prognostic relevance of these fusion transcripts in the context of advanced age.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA.
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Yasuda
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Perry
authors.forename: Marilu
authors.initials: M
authors.lastname: Nelson
authors.forename: Marilyn M
authors.initials: MM
authors.lastname: Bui
authors.forename: Aejaz
authors.initials: A
authors.lastname: Nasir
authors.forename: Robert
authors.initials: R
authors.lastname: Goldschmidt
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Gnepp
authors.forename: Julia A
authors.initials: JA
authors.lastname: Bridge
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002869:Chromosome Aberrations; D002882:Chromosomes, Human, Pair 13; D002889:Chromosomes, Human, Pair 2; D020732:Cytogenetic Analysis; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor / Q000235:genetics*; D051761:Paired Box Transcription Factors / Q000235:genetics*; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014178:Translocation, Genetic
chemical_list: D014408:Biomarkers, Tumor; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D015514:Oncogene Proteins, Fusion; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; D051761:Paired Box Transcription Factors