title: Morphologic Accuracy in Differentiating Primary Lung Adenocarcinoma From Squamous Cell Carcinoma in Cytology Specimens.
abstract: BACKGROUND
  -The National Cancer Care Network and the combined College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology guidelines indicate that all lung adenocarcinomas (ADCs) should be tested for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. As the majority of patients present at a later stage, the subclassification and molecular analysis must be done on cytologic material.
  
  
  OBJECTIVE
  -To evaluate the accuracy and interobserver variability among cytopathologists in subtyping non-small cell lung carcinoma using cytologic preparations.
  
  
  METHODS
  -Nine cytopathologists from different institutions submitted cases of non-small cell lung carcinoma with surgical follow-up. Cases were independently, blindly reviewed by each cytopathologist. A diagnosis of ADC or squamous cell carcinoma was rendered based on the Diff-Quik, Papanicolaou, and hematoxylin-eosin stains. The specimen types included fine-needle aspiration from lung, lymph node, and bone; touch preparations from lung core biopsies; bronchial washings; and bronchial brushes. A major disagreement was defined as a case being misclassified 3 or more times.
  
  
  RESULTS
  -Ninety-three cases (69 ADC, 24 squamous cell carcinoma) were examined. Of 818 chances (93 cases × 9 cytopathologists) to correctly identify all the cases, 753 correct diagnoses were made (92% overall accuracy). Twenty-five of 69 cases of ADC (36%) and 7 of 24 cases of squamous cell carcinoma (29%) had disagreement (P = .16). Touch preparations were more frequently misdiagnosed compared with other specimens. Diagnostic accuracy of each cytopathologist varied from 78.4% to 98.7% (mean, 91.7%).
  
  
  CONCLUSIONS
  -Lung ADC can accurately be distinguished from squamous cell carcinoma by morphology in cytologic specimens with excellent interobserver concordance across multiple institutions and levels of cytology experience.
authors.affiliation: From the Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (Drs Zakowski and Rekhtman); the Department of Pathology, Royal Victoria Hospital, Montreal, Quebec, Canada (Dr Auger); the Department of Pathology, Cleveland Clinic Main Campus, Cleveland, Ohio (Dr Booth); the Department of Pathology, Walter Reed Army Medical Center, Washington, DC (Dr Crothers); the Department of Pathology, Peacehealth Laboratory, Vancouver, Washington (Dr Ghofrani); the Department of Pathology, University of Pittsburgh Medical Center Shadyside, Pittsburgh, Pennsylvania (Dr Khalbuss); the Department of Pathology, Baylor College of Medicine, Houston, Texas (Dr Laucirica); the Department of Pathology, AmeriPath, Indianapolis, Indiana (Dr Moriarty); the Department of Pathology, University of California, San Francisco (Dr Tabatabai); and the Department of Pathology, Loyola University Medical Center, Maywood, Illinois (Dr Barkan). Dr Zakowski is no longer affiliated with Memorial Sloan Kettering Cancer Center. Dr Khalbuss is now with GE Clarient Diagnostic Services, Riyadh, Saudi Arabia. Dr Moriarty is no longer affiliated with AmeriPath.
authors.forename: Maureen F
authors.initials: MF
authors.lastname: Zakowski
authors.forename: Natasha
authors.initials: N
authors.lastname: Rekhtman
authors.forename: Manon
authors.initials: M
authors.lastname: Auger
authors.forename: Christine N
authors.initials: CN
authors.lastname: Booth
authors.forename: Barbara
authors.initials: B
authors.lastname: Crothers
authors.forename: Mohiddean
authors.initials: M
authors.lastname: Ghofrani
authors.forename: Walid
authors.initials: W
authors.lastname: Khalbuss
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Laucirica
authors.forename: Ann T
authors.initials: AT
authors.lastname: Moriarty
authors.forename: Z Laura
authors.initials: ZL
authors.lastname: Tabatabai
authors.forename: Güliz A
authors.initials: GA
authors.lastname: Barkan
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics; D003581:Cytodiagnosis / Q000379:methods* / Q000706:statistics & numerical data; D003937:Diagnosis, Differential; D066246:ErbB Receptors / Q000235:genetics; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics; D009154:Mutation; D015588:Observer Variation; D000072142:Pathologists / Q000706:statistics & numerical data; D010338:Pathology, Clinical / Q000379:methods / Q000706:statistics & numerical data; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases