Genetics of a combined lung small cell carcinoma and large cell neuroendocrine carcinoma with adenocarcinoma

Giovanni Fellegara, Tiziana D'Adda, Francesco P. Pilato, Elisabetta Froio, Luca Ampollini, Michele Rusca, Guido Rindi

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Combined nonneuroendocrine-neuroendocrine lung tumors are relatively infrequent and little is known as for their genetic basis. Here, we report the case of a 69-year-old male with a solitary neoplasm in the upper lobe of the right lung. At histological examination, the tumor showed two components. The main part was an adenocarcinoma of the acinar type. The second part showed morphological and immunohistochemical phenotype of a neuroendocrine carcinoma composed of a small cell lung carcinoma and a large cell neuroendocrine carcinoma. The aim of our study was to investigate the genetic relationship between neuroendocrine and nonneuroendocrine tumor components. To this purpose, we performed a loss of heterozygosity (LOH) analysis with 40 chromosomal microsatellite markers. Microallelotyping revealed a common genetic profile in the different tumor areas. In 9 of 30 informative regions analyzed, LOH involved the same allele in all components, regardless of their histological type and grade. These findings support the true combined nature of this exocrine-neuroendocrine carcinoma of the lung and suggest a common monoclonal origin from a pluripotent epithelial (alveolar or bronchial) precursor cell for the two different tumor components.

Original languageEnglish
Pages (from-to)107-115
Number of pages9
JournalVirchows Archiv
Issue number1
Publication statusPublished - Jul 2008


  • Adenocarcinoma
  • Combined lung cancer
  • Large cell neuroendocrine carcinoma
  • Pluripotent epithelial precursor
  • Small cell lung carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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