title: Human papillomavirus-associated adenocarcinoma of the base of tongue: potentially actionable genetic changes.
abstract: While human papillomavirus (HPV)-positive squamous and adenosquamous carcinomas of the oropharynx have been well characterized, HPV-associated pure adenocarcinomas are exceptionally rare. Herein we report the clinicopathologic features of one such HPV-associated adenocarcinoma of the base of tongue (BOT). A 70 year-old male presented with a 2.8 cm base of tongue mass and lymphadenopathy. Immunohistochemically, the adenocarcinoma was p63 negative and p16 positive. HPV positivity was shown by in situ hybridization. Features of salivary type tumor or metastasis from a distant primary were absent. IonTorrent™ semiconductor sequencing analysis for 739 cancer-associated mutations in 46 actionable cancer genes was performed and PIK3CA exon 9 (p.E545K) and MET exon 2 (p.E168D) mutations were identified. No PIK3CA or MET amplification was identified by fluorescence in situ hybridization. A re-review of archival HPV-positive oropharyngeal squamous cell carcinomas (n = 89, 1983-2013) showed no additional cases of adenocarcinoma. The clinical follow-up for the three previously reported cases of HPV-associated adenocarcinoma of the BOT was updated. All previously reported cases were tested and were negative for PIK3CA exon 9 and 20 and MET exon 2 mutations. These findings offer a molecular basis for potential therapeutic use of PIK3CA inhibitors in a subset of patients with HPV-associated adenocarcinoma of BOT.
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, 200 Lothrop St, Pittsburgh, PA, 15213, USA.
authors.forename: Ann Margaret V
authors.initials: AM
authors.lastname: Chang
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova
authors.forename: Jonas T
authors.initials: JT
authors.lastname: Johnson
authors.forename: Julie E
authors.initials: JE
authors.lastname: Bauman
authors.forename: Bayardo
authors.initials: B
authors.lastname: Perez-Ordonez
authors.forename: Raja R
authors.initials: RR
authors.lastname: Seethala
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Krane
authors.forename: Simion I
authors.initials: SI
authors.lastname: Chiosea
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000821:virology; D000368:Aged; D058534:Class I Phosphatidylinositol 3-Kinases; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D014062:Tongue Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met