Pulmonary Large Cell Neuroendocrine Carcinoma

Pathol Oncol Res. 2022 Oct 11:28:1610730. doi: 10.3389/pore.2022.1610730. eCollection 2022.


Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of malignant pulmonary tumor. The incidence rate of LCNEC was reported to be 0.3%-3% in lung cancers. Although LCNEC is classified as non-small cell lung cancer (NSCLC), it is more aggressive and malignant than other NSCLC, and its biological behavior is similar to that of small cell lung cancer (SCLC). Most of the LCNEC patients are elderly smoking male and the clinical manifestations are not specific. The imaging manifestations of the tumors are often located in the periphery and the upper lobes, and the enlargement of mediastinal or hilar lymph nodes is common. The diagnosis is mainly based on pathology by the histological features and immunohistochemistry (IHC). Specific neuroendocrine markers such as chromogranin A (CgA), synaptophysin (Syn) and CD56 are usually diffusely positive in LCNEC, and found that insulinoma-associated protein (INSM1) and high rate of Ki-67 are helpful for diagnosis. More differential diagnoses also increase the difficulty of correctly diagnosing LCNEC. The rise of LCNEC molecular typing in recent years may be helpful for diagnosis and subsequent treatment. This review focuses on the epidemiological features, imaging studies, pathology, diagnosis, treatment, and prognosis of LCNEC.

Keywords: LCNEC; diagnosis; imaging examination; pathologic features; prognosis; treatment.

Publication types

  • Review

MeSH terms

  • Aged
  • Biomarkers, Tumor
  • Carcinoma, Large Cell* / epidemiology
  • Carcinoma, Large Cell* / pathology
  • Carcinoma, Neuroendocrine* / diagnosis
  • Carcinoma, Neuroendocrine* / pathology
  • Carcinoma, Non-Small-Cell Lung*
  • Humans
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / epidemiology
  • Lung Neoplasms* / metabolism
  • Male
  • Repressor Proteins
  • Small Cell Lung Carcinoma*


  • Biomarkers, Tumor
  • INSM1 protein, human
  • Repressor Proteins