title: High-grade neuroendocrine carcinoma.
abstract: OBJECTIVE
  This review presents an update on classification, diagnosis and potentially 'drugable' molecular alterations of small cell carcinoma (SCC) and large cell neuroendocrine carcinoma (LCNEC) of the lung.
  
  
  RESULTS
  The main controversies in the classification of lung neuroendocrine tumors are: whether SCC and LCNEC should remain separated or should be unified into a high-grade category; and what the role is of Ki67 as an adjunct to the classical parameters (mitotic rate and necrosis). Regarding the diagnosis of SCC and LCNEC, in difficult cases it requires the combined evaluation of clinical-radiological data, histological and cytological material and selected immunostains. The prognosis of both tumors remains very poor. Despite the promising identification of potential molecular targets on preclinical studies, including antiangiogenetic drugs and tricyclic antidepressants, at the moment no specific molecular-driven therapy is available.
  
  
  CONCLUSIONS
  The field of high-grade neuroendocrine carcinomas remains complex in several respects, and studies on molecular targets are urgently needed.
authors.affiliation: aUnit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena bDepartment of Oncology and Advanced Technologies, Unit of Pathology, Azienda Arcispedale S. Maria Nuova/I.R.C.C.S., Reggio Emilia, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bisagni
authors.forename: Alberto
authors.initials: A
authors.lastname: Cavazza
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000473:pathology*; D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000473:pathology*; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000235:genetics*; D008175:Lung Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D058990:Molecular Targeted Therapy; D060787:Neoplasm Grading; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen