Definition/General
Introduction:
Large cell lung carcinoma (LCLC) in sputum cytology represents undifferentiated non-small cell lung cancer
It comprises 10-15% of all lung cancers
Diagnosis of exclusion lacking squamous or glandular differentiation
Aggressive behavior with poor prognosis.
Origin:
Originates from bronchial epithelium without clear differentiation
Undifferentiated malignant epithelial cells
May represent dedifferentiated adenocarcinoma or squamous carcinoma
Peripheral or central location possible
High-grade malignancy.
Classification:
WHO classification includes several variants
Large cell carcinoma, NOS
Large cell neuroendocrine carcinoma (LCNEC)
Basaloid carcinoma
Lymphoepithelioma-like carcinoma
Clear cell carcinoma
Large cell carcinoma with rhabdoid phenotype.
Epidemiology:
Male predominance (2:1 ratio)
Peak incidence 60-70 years
Strong smoking association (>90% cases)
Decreasing incidence with improved classification
Poor prognosis similar to squamous carcinoma
Rapid growth and early metastases.
Clinical Features
Presentation:
Cough with increasing sputum production
Hemoptysis
Dyspnea and chest pain
Weight loss and anorexia
Central or peripheral mass
Rapid progression
Early metastases common.
Symptoms:
Persistent cough (60-80% of patients)
Hemoptysis (30-50%)
Chest pain (40-60%)
Dyspnea (50-70%)
Weight loss (40-60%)
Fatigue and weakness
Fever (post-obstructive pneumonia).
Risk Factors:
Tobacco smoking (most important - >90% cases)
Heavy smoking history
Occupational exposures (asbestos, radon)
Air pollution
Chronic lung disease
Family history of lung cancer
Previous malignancy.
Screening:
Low-dose CT screening (high-risk patients)
Sputum cytology (variable sensitivity)
Chest X-ray (often shows mass)
Bronchoscopy with biopsy
Molecular testing increasingly important
Smoking cessation counseling.
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Gross Description
Appearance:
Purulent sputum with thick consistency
Blood-streaked or frankly bloody
Yellow-green discoloration
Mucoid to mucopurulent
Necrotic debris may be present
Foul odor possible.
Characteristics:
Variable cellularity
Inflammatory background
Necrotic material
Bacterial contamination frequent
Thick, viscous consistency
Adequate specimens for diagnosis.
Microscopic Description
Immunohistochemistry
Positive Markers:
Cytokeratin AE1/AE3 (confirms epithelial origin)
CK7 (variable positivity)
p53 (frequently overexpressed)
Ki-67 (high proliferation index >50%)
TTF-1 (variable - 20-30%)
Vimentin (co-expression possible).
Negative Markers:
p63 (negative - excludes squamous)
CK5/6 (negative)
Napsin A (negative)
Chromogranin and synaptophysin (negative unless LCNEC)
CD56 (negative unless neuroendocrine)
Thyroglobulin (negative).
Diagnostic Utility:
Diagnosis of exclusion
CK positivity confirms carcinoma
p63 negativity excludes squamous differentiation
Napsin A negativity excludes adenocarcinoma
Neuroendocrine markers exclude LCNEC
Molecular testing increasingly important.
Molecular/Genetic
Differential Diagnosis
Similar Entities:
Poorly differentiated adenocarcinoma
Poorly differentiated squamous carcinoma
Large cell neuroendocrine carcinoma
Pleomorphic carcinoma
Metastatic carcinoma
Sarcomatoid carcinoma.
Distinguishing Features:
Large cell carcinoma: Lacks differentiation markers
Adenocarcinoma: Napsin A+, TTF-1+, mucin+
Squamous carcinoma: p63+, CK5/6+, keratinization
LCNEC: Neuroendocrine markers+
Metastatic: Site-specific markers, clinical correlation
Sarcomatoid: Spindle cells, vimentin+.
Diagnostic Challenges:
Diagnosis of exclusion requires extensive workup
Overlapping morphology with other NSCLC
Limited tissue for complete characterization
Molecular classification evolving
Heterogeneous group of tumors.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Sputum specimen, [collection method], [volume] ml
Specimen Adequacy
Adequate for cytological evaluation
Cellular Findings
Large malignant cells with [specific morphological features]
Differentiation Features
Lacks squamous or glandular differentiation
Nuclear Features
Large vesicular nuclei with prominent nucleoli and pleomorphism
Cytoplasmic Features
Abundant eosinophilic cytoplasm without specific features
Diagnosis
Malignant cells consistent with large cell carcinoma/undifferentiated NSCLC
Limitations
Definitive subtyping requires tissue confirmation with IHC
Recommendations
Tissue biopsy for definitive diagnosis. IHC panel. Molecular testing for targeted therapy.