title: 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.
abstract: 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 ofEGFRp.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 anEGFRmutated 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 aPIK3CAp.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.
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Clery
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pisapia
authors.affiliation: Department of Oncology, A.O.R.N. A. Cardarelli, Naples, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Feliciano
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Vigliar
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Marano
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: De Luca
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Malapelle
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Troncone
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Claudio
authors.identifier: http://orcid.org/0000-0002-7479-6457
authors.initials: C
authors.lastname: Bellevicine
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D058990:Molecular Targeted Therapy; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: CYTOLOGY; EGFR; LUNG CANCER; MOLECULAR PATHOLOGY; MORPHOLOGY