title: Large cell carcinoma of the lung: a tumor in search of an author. A clinically oriented critical reappraisal.
abstract: Large cell carcinoma (LCC) is a merely descriptive term indicating a subtype of lung cancer with no specific features of small-cell lung cancer (SCLC), adenocarcinoma (ADC) or squamous cell carcinoma (SQC). This diagnosis is allowed on surgical specimens only, whereas its counterpart in biopsy/cytology samples is non-small-cell lung carcinoma (NSCLC), not otherwise specified (NOS). Although these two terms do not fulfill the same concept, they can be interchangeable synonyms at the clinical level, reflecting, in different ways, the inability to define a specific subtype. Immunohistochemistry (IHC), next generation sequencing (NGS) analysis and, historically, electron microscopy have been unveiling diverse cell differentiation lineages in LCC, resulting in LCC-favor ADC, LCC-favor SQC and LCC-favor large-cell neuroendocrine carcinoma (LCNEC), the latter hopefully to be included into the neuroendocrine tumor (NET) group in the future. Paradoxically, however, the interpretation issues of LCC/NSCLC-NOS are not diminishing, but even increasing albeight an accurate diagnosis is oncologically required and crucial. Also, rare LCC/NSCLC-NOS cases exhibiting null/unclear phenotype, are difficult to classify, and this terminology could be maintained for the sake of classification (basically these tumors are serendipitous ADC, as also confirmed by the lack of p40). In this review article, seven relevant issues to LCC have been addressed by using a question-answer methodology, with final key points discussing major interpretation issues. In conclusion, most LCC/NSCLC-NOS may be eventually re-classified and addressed by exploiting IHC and/or molecular testing to satisfy the criteria of precision medicine (the right drug, to the right patient, at the right time).
authors.affiliation: Department of Pathology and Laboratory Medicine, Istituto Nazionale Tumori, Milan, Italy; Department of Biomedical and Clinical Sciences "Luigi Sacco", Università degli Studi di Milano, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pelosi
authors.affiliation: Operative Unit of Pathology, Hospital S. Chiara, Trento, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Barbareschi
authors.affiliation: Division of Pathology, Arcispedale S. Maria Nuova I.R.C.C.S., Reggio Emilia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cavazza
authors.affiliation: Division of Pathology, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Foggia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Graziano
authors.affiliation: Section of Pathologic Anatomy, Azienda Ospedaliero-Universitaria Policlinico of Modena, Modena, Italy. Electronic address: giurossi68@gmail.com1.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor; D018287:Carcinoma, Large Cell / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor
keywords: Classification; Diagnosis; Genetic profile; Immunohistochemistry; Large cell carcinoma; Lung; Pathology