title: Squamous cell carcinoma variants of the upper aerodigestive tract: a comprehensive review with a focus on genetic alterations.
abstract: BACKGROUND
  Squamous cell carcinoma of the upper aerodigestive tract is a heterogenous entity. Although conventional squamous cell carcinomas are easily recognized, the morphologic variants of squamous cell carcinoma can present a diagnostic challenge. Familiarity with these variants is necessary because many are associated with unique risk factors and are characterized by specific molecular alterations (eg, nuclear protein in testis midline carcinomas). Perhaps the most important distinction is in identifying viral-related from nonviral-related carcinomas. The accurate diagnosis of these variants is necessary for prognostic and therapeutic reasons.
  
  
  OBJECTIVE
  To provide a clinicopathologic overview and summary of the molecular alterations of the common squamous cell carcinoma variants, including verrucous, spindle cell, acantholytic, adenosquamous, basaloid, and papillary squamous cell carcinoma, as well as nuclear protein in testis midline carcinoma, and to discuss the distinguishing features of human papillomavirus- and Epstein-Barr virus-related squamous cell carcinomas.
  
  
  METHODS
  Published peer-reviewed literature.
  
  
  CONCLUSIONS
  Familiarity with squamous cell carcinoma variants is essential for proper diagnosis and to guide appropriate clinical management. Further insight into the molecular alterations underlying those variants may lead to alterations in existing treatment approaches and to evolution of novel treatment modalities.
authors.affiliation: From the Department of Pathology, University of Virginia Health System, Charlottesville.
authors.forename: Akeesha A
authors.initials: AA
authors.lastname: Shah
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Jeffus
authors.forename: Edward B
authors.initials: EB
authors.lastname: Stelow
mesh_terms: D018196:Carcinoma, Adenosquamous / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D018289:Carcinoma, Verrucous / Q000235:genetics / Q000473:pathology; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000235:genetics; D050596:Oncogene Fusion; D015513:Oncogene Proteins / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology
chemical_list: C000630260:NUTM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins