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There is still a role for cytology in the ‘liquid biopsy’ era. A lesson from a TKI-treated patient showing adenocarcinoma to squamous cell carcinoma transition during disease progression
  1. Eduardo Clery1,
  2. Pasquale Pisapia1,
  3. Salvatore Feliciano2,
  4. Elena Vigliar1,
  5. Antonio Marano1,
  6. Caterina De Luca1,
  7. Umberto Malapelle1,
  8. Giancarlo Troncone1,
  9. Claudio Bellevicine1
  1. 1 Department of Public Health, University of Naples Federico II, Naples, Italy
  2. 2 Department of Oncology, A.O.R.N. A. Cardarelli, Naples, Italy
  1. Correspondence to Professor Giancarlo Troncone, Department of Public Health, University of Naples Federico II, via Sergio Pansini 5, Naples I-80131, Italy; giancarlo.troncone{at}


Non-small cell lung carcinoma harbouring epidermal growth factor receptor (EGFR) mutation, usually progress after an initial response to tyrosine-kinase inhibitors (TKI). Liquid biopsy enables with a simple blood draw the accurate detection of EGFR p.T790M mutation, the most common resistance mechanism, avoiding the more invasive tissue re-biopsy. However, in a subset of cases, resistance mechanisms are more complex featuring both genetic and morphological changes. Here we report the case of a 67 years-old woman, affected by an EGFR mutated lung adenocarcinoma and treated by TKI. At disease progression, the patient developed a morphological transition to squamous cell carcinoma in association to the arising of a PIK3CA p.E542K mutant subclone. This case illustrates that, even in the “liquid biopsy” era, cytology can have still a role by providing an overall assessment of both morphology and genetic TKI resistance mechanisms.

  • EGFR

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  • *EC and PP contributed equally.

  • Handling editor Runjan Chetty

  • Contributors CB and GT conceived the study, wrote the original manuscript draft and contributed as pathologists. EC, PP and EV contributed as a pathologist and wrote the original manuscript draft. SF contributed as oncologist. CDL contributed as biotechnologist and performed the molecular tests. UM set up, validated and developed the molecular assay.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.