Large cell lung cancer

Last revised by Joshua Yap on 29 May 2023

Large cell lung cancer is one of the histological types of non-small cell carcinomas of the lung diagnosed only on resection, after exclusion of adenocarcinomatous or squamous differentiation. 

It is thought to account for approximately 10% of lung cancers 1.

According to the last international consensus, the diagnosis of large cell carcinoma should not be achieved based on small biopsy or cytology samples and is, therefore, restricted to resection specimens where the tumor is completely sampled to exclude a differentiated component 4.

Patients present with dyspnea, chronic cough, and hemoptysis.

Microscopically, large cell carcinoma is characterized by large nuclei/nucleoli with a moderate amount of cytoplasm, hence the name. This undifferentiated tumor lacks distinctive features of small cell carcinoma, glandular, or squamous differentiation.

On immunophenotyping, characteristic features include 2:

  • loss of staining with CK5/6

  • CK14 positive in most squamous cell carcinoma (SCC)

  • lack of MOC 31 positive in most adenocarcinomas

  • positive immunoreactivity to EGFR, PDGFR-alpha and c-kit

The subtype large cell neuroendocrine carcinoma is now grouped under the pulmonary neuroendocrine tumors since the last WHO review in 2015 5

Large cell lung cancer is typically seen as a large peripheral mass of solid attenuation and irregular margin. Focal necrosis can be present. Other characteristics include rapid growth and early metastasis. 

The histologic subtype of large cell neuroendocrine tumor has a more aggressive pattern and is associated with a poorer prognosis.

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Cases and figures

  • Case 1: apical location invading the chest wall
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