title: Lung Adenocarcinoma with Anaplastic Lymphoma Kinase (ALK) Rearrangement Presenting as Carcinoma of Unknown Primary Site: Recognition and Treatment Implications.
abstract: BACKGROUND
  Molecular cancer classifier assays are being used with increasing frequency to predict tissue of origin and direct site-specific therapy for patients with carcinoma of unknown primary site (CUP).
  
  
  OBJECTIVE
  We postulated some CUP patients predicted to have non-small-cell lung cancer (NSCLC) by molecular cancer classifier assay may have anaplastic lymphoma kinase (ALK) rearranged tumors, and benefit from treatment with ALK inhibitors.
  
  
  METHODS
  We retrospectively reviewed CUP patients who had the 92-gene molecular cancer classifier assay (CancerTYPE ID; bioTheranostics, Inc.) performed on tumor biopsies to identify patients predicted to have NSCLC. Beginning in 2011, we have tested these patients for ALK rearrangements and epidermal growth factor receptor (EGFR) activating mutations, based on the proven therapeutic value of these targets in NSCLC. We identified CUP patients with predicted NSCLC who were subsequently found to have ALK rearrangements.
  
  
  RESULTS
  NSCLC was predicted by the molecular cancer classifier assay in 37 of 310 CUP patients. Twenty-one of these patients were tested for ALK rearrangements, and four had an EML4-ALK fusion gene detected. The diagnosis of lung cancer was strongly suggested in only one patient prior to molecular testing. One patient received ALK inhibitor treatment and has had prolonged benefit.
  
  
  CONCLUSIONS
  We report on patients with lung adenocarcinoma and ALK rearrangements originally diagnosed as CUP who were identified using a molecular cancer classifier assay. Although ALK inhibitors treatment experience is limited, this newly identifiable group of lung cancer patients should be considered for therapy according to guidelines for stage IV ALK-positive NSCLC.
authors.affiliation: Sarah Cannon Research Institute and Tennessee Oncology, PLLC, 3322 West End Avenue, Suite 900, Nashville, TN, 37203, USA. John.Hainsworth@scresearch.net.
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.affiliation: Sarah Cannon Research Institute and Tennessee Oncology, PLLC, 3322 West End Avenue, Suite 900, Nashville, TN, 37203, USA.
authors.forename: F
authors.initials: F
authors.lastname: Anthony Greco