title: Pulmonary squamous cell carcinoma following head and neck squamous cell carcinoma: metastasis or second primary?
abstract: OBJECTIVE
  To distinguish a metastasis from a second primary tumor in patients with a history of head and neck squamous cell carcinoma and subsequent pulmonary squamous cell carcinoma.
  
  
  METHODS
  For 44 patients with a primary squamous cell carcinoma of the head and neck followed by a squamous cell carcinoma of the lung, clinical data, histology, and analysis of loss of heterozygosity (LOH) were used to differentiate metastases from second primary tumors.
  
  
  RESULTS
  Clinical evaluation suggested 38 patients with metastases and 6 with second primaries. We developed a novel interpretation strategy based on biological insight and on our observation that multiple LOH on different chromosome arms are not independent. LOH analysis indicated metastatic disease in 19 cases and second primary squamous cell carcinoma in 24 cases. In one case, LOH analysis was inconclusive. For 25 patients, LOH supported the clinical scoring, and in 18 cases, it did not. These 18 discordant cases were all considered to be second primary tumors by LOH analysis.
  
  
  CONCLUSIONS
  A considerable number of squamous cell lung lesions (50% in this study), clinically interpreted as metastases, are suggested to be second primaries by LOH analysis. For these patients, a surgical approach with curative intent may be justified.
authors.affiliation: Department of ORL, Academic Medical Center, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
authors.forename: Tom W
authors.initials: TW
authors.lastname: Geurts
authors.forename: Petra M
authors.initials: PM
authors.lastname: Nederlof
authors.forename: Michiel W M
authors.initials: MW
authors.lastname: van den Brekel
authors.forename: Laura J
authors.initials: LJ
authors.lastname: van't Veer
authors.forename: Daphne
authors.initials: D
authors.lastname: de Jong
authors.forename: August A M
authors.initials: AA
authors.lastname: Hart
authors.forename: Nico
authors.initials: N
authors.lastname: van Zandwijk
authors.forename: Houke
authors.initials: H
authors.lastname: Klomp
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: Balm
authors.forename: Marie-Louise F
authors.initials: ML
authors.lastname: van Velthuysen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology*; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis* / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000175:diagnosis* / Q000235:genetics