Other carcinomas

Large cell

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Last staff update: 20 January 2023

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PubMed Search: Large cell undifferentiated carcinoma of the lung

Emily O. Symes, M.D.
Aliya N. Husain, M.D.
Page views in 2023: 12,384
Page views in 2024 to date: 5,228
Cite this page: Symes EO, Husain AN. Large cell. website. Accessed May 19th, 2024.
Definition / general
  • Resected tumors that lack morphologic or immunohistochemical differentiation toward small cell carcinoma, adenocarcinoma or squamous cell carcinoma (J Thorac Oncol 2015;10:1240)
  • Null or unclear immunophenotype based on IHC analysis with TTF1, p40 and neuroendocrine markers (J Thorac Oncol 2019;14:1213)
Essential features
  • Malignant, poorly differentiated epithelial neoplasm of lung composed of large, atypical cells
  • No morphologic or immunohistochemical evidence of glandular, squamous or neuroendocrine differentiation
  • Diagnosis of exclusion; diagnosis can only be made on resected tumors
  • Synonymous with large cell undifferentiated carcinoma and large cell anaplastic carcinoma
  • Previously, large cell carcinoma included variants such as basaloid carcinoma, large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma, clear cell carcinoma and large cell carcinoma with rhabdoid phenotype
  • As of the 2015 WHO classification, large cell carcinoma is a diagnosis of exclusion, with reclassification of the former large cell carcinoma subtypes into different categories (J Thorac Oncol 2015;10:1243)
ICD coding
  • ICD-O: 8012/3 - large cell carcinoma, NOS
  • ICD-10: C34.90 - malignant neoplasm of unspecified part of unspecified bronchus or lung
  • M > F
  • Average age of 65 years
  • Associated with cigarette smoking
  • Becoming increasingly rare due to immunohistochemical and molecular studies that support the reclassification of entities formerly diagnosed as large cell carcinoma (Sci Transl Med 2013;5:209ra153)
  • Peripheral lung
  • 50% with connection to large airways
Clinical features
  • Cough, chest pain, shortness of breath
  • Typically larger than 5 cm
  • Diagnosis of exclusion
  • Small biopsy specimens and cytology specimens should not be used for diagnosis
    • According to the 2021 WHO, only resection specimens with exclusion of a differentiated component, via thorough sampling, can be classified as large cell carcinoma (J Thorac Oncol 2022;17:362)
  • NSCC, NOS (nonsmall cell carcinoma, not otherwise specified) should be used in small biopsies or cytology specimens
Radiology description
  • Usually large, lobulated or well marginated, peripheral, heterogeneously enhancing mass, often containing central necrosis (Ghosh: Handbook of Imaging in Pulmonary Disease, 1st Edition, 2021)
  • Rapid growth is common with metastasis (chest wall, thoracic lymph nodes, distant) at presentation
  • PET CT preferred over CT for identification of full extent of disease and metastases
Prognostic factors
Case reports
  • Dependent on stage
  • Surgical excision, chemotherapy or radiation therapy
Gross description
Gross images

Contributed by Debra L. Zynger, M.D.
Right lung mass

Right lung mass

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Emily O. Symes, M.D.

Sheets of tumor cells

Necrosis and lymphovascular invasion

Extensive necrosis

Lymphovascular invasion

Spread through air spaces (STAS)

High power tumor cells




Napsin A


Mucin stain

Virtual slides

Images hosted on other servers:
Various images Various images

Undifferentiated large cell carcinoma

Various images Various images

Undifferentiated large cell carcinoma

Cytology description
  • Large pleomorphic cells with a moderate to abundant amount of cytoplasm, vesicular nuclei, prominent nucleoli
Positive stains
Molecular / cytogenetics description
  • Molecular studies show that some null phenotype large cell carcinomas contain mutations seen in conventional adenocarcinoma (e.g., KRAS, NRAS, MET, STK11) and squamous cell carcinoma (e.g., PIK3CA amplification and mutation); this indicates that tumors classified as large cell carcinomas could represent poorly / undifferentiated nonsmall cell lung cancer (NSCLC) (J Thorac Oncol 2019;14:1213, Sci Transl Med 2013;5:209ra153)
Sample pathology report
  • Lung, left, resection:
    • Large cell carcinoma (1.1 cm) (see comment)
    • Comment: Immunohistochemical studies are performed with appropriate controls. The tumor is negative for TTF1, Napsin A, CK5/6 and p40. There is no morphologic evidence of differentiation to adenocarcinoma or squamous cell carcinoma. The histologic features are not those of neuroendocrine carcinoma. Given these findings, the tumor is best classified as large cell carcinoma. PDL1 immunostain shows weak expression in 20% of tumor cells.
Differential diagnosis
Board review style question #1
Large cell carcinoma of the lung will generally stain for which of the following immunohistochemical markers?

  1. CAM5.2
  2. Chromogranin
  3. p40
  4. SOX10
  5. TTF1
Board review style answer #1
A. CAM5.2

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Reference: Large cell carcinoma
Board review style question #2

Which one of the following special stains is shown in the image above?

  1. CK5/6
  2. Chromogranin
  3. TTF1
  4. Mucin
  5. p40
Board review style answer #2
D. Mucin. Tumor cells are negative for mucin immunostaining but show degenerative vacuoles, which can mimic mucin on H&E.

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Reference: Large cell carcinoma
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