title: Secondary biopsy of non-oncogenic-driven lung cancer may reveal a clinically sensible histologic change. A brief report of two paradigmatic cases.
abstract: After an initial benefit, non-small-cell lung cancer (NSCLC) patients receiving therapy with tyrosine kinase inhibitors develop drug resistance through a variety of mechanisms. Among these, tumor histology changes are a mechanism of acquired resistance in epidermal growth factor receptor-mutated and anaplastic lymphoma kinase-rearranged NSCLC cases. The current availability of therapeutic approaches to overcome tyrosine kinase inhibitor resistance in oncogenic-driven lung cancers justifies secondary tumor biopsy in these patients. On the other hand, little is known about the mechanism of disease progression in non-oncogenic driven NSCLC. Nevertheless, NSCLC lacking "druggable" genetic alterations are not considered for secondary biopsy, as it is commonly believed that these tumors cannot develop histologic or molecular changes. Herein, we report two paradigmatic cases of wild-type NSCLC showing histologic "change" on secondary biopsy, allowing for a successful switch in therapeutic strategy.
authors.affiliation: Department of Pathology, Pathology Unit, University Hospital Policlinico of Modena, Modena, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mengoli
authors.affiliation: Department of Oncology, University Hospital Policlinico of Modena, Modena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Orsi
authors.affiliation: Unit of Thoracic Surgery, Arcispedale Santa Maria Nuova-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Lococo
authors.affiliation: Department of Oncology, University Hospital Policlinico of Modena, Modena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Grizzi
authors.affiliation: Department of Oncology, University Hospital Policlinico of Modena, Modena, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Barbieri
authors.affiliation: Department of Oncology, University Hospital Policlinico of Modena, Modena, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Bertolini
authors.affiliation: Department of Pathology, Pathology Unit, Azienda USL Valle d'Aosta, Hospital "Parini", Aosta, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Department of Oncology, S. Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
mesh_terms: D001706:Biopsy; D016190:Carboplatin / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D055752:Small Cell Lung Carcinoma / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D000068437:Pemetrexed; D005047:Etoposide; D016190:Carboplatin
keywords: 
  CEA
  ; 
  NSE
  ; histological change; lung cancer; wild-type