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Large Cell Neuroendocrine Carcinoma


Epidemiology

  • Incidence: 2-3.5% in resected lung specimens; probably higher in inoperable patients due to its aggressive nature
  • Etiology: Smoking probably causative; 85-95% of patients have history of heavy tobacco use
  • Median age at diagnosis: 66 years
  • Present predominately in lung periphery (cough, hemoptysis, or post-obstructive PNA are not common presenting symptoms)


Histology

  • Historically grouped under neuroendocrine tumors of the lung (small cell, atypical carcinoid (LCNEC), typical carcinoid)
  • In 1999 reassigned by WHO to Large Cell Carcinoma group, which includes several other unrelated but large cell histologies
  • Cell size is typically 3X larger than for small cell CA
  • Mitotic index is high, approaching that of small cell CA
  • Cells contain neurosecretory granules, and typically stain positive for either neural cell adhesion molecule, chromogranin A, or synaptophysin
  • Molecular markers suggest similarity of LCNEC and SCC, and difference from other large cell histologies (Ki-67+, p53+, Rb-)


Survival

  • 5-year OS of resected patients: ~30-40%
  • Stage-adjusted survival is significantly worse than NSCLC


Treatment Overview

  • Most series reported are surgical
  • Currently no definitive survival advantage for adjuvant chemotherapy
  • Octreotide may have activity, and appears to control metastatic disease


  • Washington University, 2005 (1988-2002) PMID 15999058 -- "Large cell neuroendocrine carcinoma: an aggressive form of non-small cell lung cancer." (Battafarano RJ, J Thorac Cardiovasc Surg. 2005 Jul;130(1):166-72.)
    • Retrospective. 2099 resected patients in database, 82 (4%) had large cell histology. LCNEC 45 patients, 50% Stage IA
    • 5-year OS: overall 47%; LCNEC 30%, mixed neuroendocrine 30%, large cell carcinoma 71% (SS). Stage I LCNEC 5-year OS 32%
    • Conclusion: LCNEC significantly worse survival after resection, even in Stage I disease

Review

  • 2006 PMID 17075564 -- "Large-cell neuroendocrine carcinoma of the lung." (Fernandez FG, Cancer Control. 2006 Oct;13(4):270-5.)
    • Recommend classifying separately from NSCLC as Grade III neuroendocrine carcinoma, large-cell type
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