Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Clinical features | Diagnosis | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Cytology description | Positive stains | Negative stains | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Wu R. Large cell. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungtumorlargecell.html. Accessed January 24th, 2021.
Definition / general
- Restrict diagnosis of large cell carcinoma to resected tumors that lack any clear morphologic or immunohistochemical differentiation (J Thorac Oncol 2015;10:1243)
- Immunohistochemical markers can reclassify many cases of large cell carcinoma as neuroendocrine, glandular or squamous carcinoma (Virchows Arch 2014;464:61, Am J Clin Pathol 2011;136:773)
Essential features
- Malignant, poorly differentiated epithelial neoplasm of lung composed of large atypical cells
- Tumors lack morphologic and immunohistochemical evidence of glandular, squamous or neuroendocrine differentiation
- Diagnosis of exclusion, which may overlap or be synonymous with pleomorphic carcinoma
Terminology
- Large cell undifferentiated carcinoma and large cell carcinoma are synonymous
- Previously, large cell carcinoma included variants such as basaloid carcinoma, large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma, clear cell carcinoma, large cell carcinoma with rhabdoid phenotype
- As of 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)
- May overlap or be synonymous with pleomorphic carcinoma; diagnostic terminology still evolving
ICD coding
- Use code specific for location of tumor
- C34.90 Malignant neoplasm of unspecified part of unspecified bronchus or lung
Epidemiology
- 80% men, adults aged 50 - 70
- Associated with smoking
Sites
- 50% with connection to large airway
- Periphery of lungs
Pathophysiology
- Behavior similar to other poorly differentiated lung carcinoma
Clinical features
- Similar to other poorly differentiated non small cell carcinoma, i.e. cough, chest pain, shortness of breath
- Typically larger than 5 cm
Diagnosis
- Diagnosis of exclusion, therefore cannot definitively diagnose on small biopsies or in lymph node metastases
- NSCC NOS (non small cell carcinoma, not otherwise specified) can be used on small biopsy / cytology specimens
- Diagnosis of entity began to decline when TTF1 immunohistochemical staining was introduced
Prognostic factors
- Generally poor prognosis
Case reports
- 58 year old man presenting with paroxysmal abdominal pain (World J Surg Oncol 2012;10:26)
Treatment
- Dependent on stage: surgical excision, chemotherapy / radiation
Gross description
- Usually peripheral lung and unifocal; spherical tumor with well defined borders and bulging, lobulated, homogeneous gray white "fish flesh" cut surface
- Internal necrosis and hemorrhage common
- No anthracosis
- Frequently involves thoracic wall
Microscopic (histologic) description
- Large, polygonal and anaplastic cells growing in sheets or solid nests
- No clear adenocarcinoma, squamous or neuroendocrine morphology
- Moderately abundant cytoplasm, well defined cell borders, vesicular nuclei, prominent nucleoli
- Foci of central necrosis and hemorrhage may be present
Microscopic (histologic) images
Cytology description
- Large pleomorphic cells with a moderate to abundant amount of cytoplasm, vesicular nuclei, prominent nucleoli
Positive stains
- Broad spectrum and low molecular weight cytokeratins, such as CAM5.2
Negative stains
- TTF1, Napsin, p40, p63, synaptophysin, chromogranin, CD56
Differential diagnosis
- Basaloid carcinoma: expresses squamous markers, i.e. p40
- Large cell neuroendocrine carcinoma: expresses neuroendocrine markers, i.e. chromogranin, synaptophysin, CD56
- Metastatic carcinoma
- Solid adenocarcinoma: expresses pneumocyte markers, i.e. TTF1 or Napsin A
Additional references
Board review style question #1
Large cell carcinoma of lung will generally stain for which of the following immunohistochemical markers?
- CAM5.2
- Chromogranin
- p40
- SOX10
- TTF1
Board review style answer #1
A. CAM5.2