Definition/General
Introduction:
Small cell lung carcinoma (SCLC) in sputum cytology represents aggressive neuroendocrine malignancy
It comprises 15-20% of all lung cancers
Strongly associated with tobacco smoking (>95% cases)
Rapid growth and early metastases characterize this tumor.
Origin:
Originates from neuroendocrine cells in bronchial epithelium
Derived from Kulchitsky cells (APUD cells)
Central location predominant
Rapid proliferation with high mitotic rate
Early lymphatic and hematogenous spread.
Classification:
WHO classification recognizes small cell carcinoma as distinct entity
Previously divided into oat cell, intermediate cell, and combined types
Current classification: Small cell carcinoma
Combined small cell carcinoma (with non-small cell components).
Epidemiology:
Strong male predominance (3:1 ratio)
Peak incidence 60-70 years
>95% associated with smoking
Rapid doubling time (30-50 days)
Early metastases (80% at presentation)
Poor prognosis (5-year survival <10%).
Clinical Features
Presentation:
Rapid onset of symptoms
Cough with increasing sputum production
Hemoptysis
Dyspnea and chest pain
Superior vena cava syndrome
Paraneoplastic syndromes common
Weight loss and fatigue.
Symptoms:
Cough (70-90% of patients)
Dyspnea (60-70%)
Chest pain (40-50%)
Hemoptysis (25-30%)
Hoarseness (recurrent laryngeal nerve)
Bone pain (metastases)
Neurological symptoms.
Screening:
Low-dose CT screening (high-risk smokers)
Sputum cytology (higher sensitivity than NSCLC)
Chest X-ray (often shows central mass)
Rapid progression requires urgent workup
Staging studies essential.
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Gross Description
Appearance:
Abundant purulent sputum
Blood-streaked or frankly bloody
Thick, viscous consistency
Yellow-green or rust-colored
Necrotic debris common
Foul odor may be present.
Characteristics:
High cellularity specimens
Inflammatory background
Necrotic material abundant
Bacterial contamination common
Mucoid consistency
Good cellular yield typically.
Microscopic Description
Immunohistochemistry
Positive Markers:
Chromogranin A (70-80% positive)
Synaptophysin (90-95% positive)
CD56/NCAM (90-95% positive)
TTF-1 (90% positive)
Neuron-specific enolase (NSE)
INSM1 (95% positive)
CK AE1/AE3 (paranuclear dot pattern).
Negative Markers:
p63 (negative)
CK5/6 (negative)
CK7 (negative or weak)
CK20 (negative)
Napsin A (negative)
Desmoglein-3 (negative)
Calretinin (negative).
Diagnostic Utility:
Synaptophysin most sensitive neuroendocrine marker
Chromogranin A more specific but less sensitive
INSM1 highly sensitive and specific
TTF-1 positivity confirms pulmonary origin
CD56 sensitive but less specific
Combination panel recommended.
Molecular/Genetic
Differential Diagnosis
Similar Entities:
Large cell neuroendocrine carcinoma
Carcinoid tumors
Metastatic small cell carcinoma
Lymphoma
Merkel cell carcinoma
Poorly differentiated adenocarcinoma.
Distinguishing Features:
SCLC: Small cells, nuclear molding, TTF-1+, high mitotic rate
LCNEC: Larger cells, prominent nucleoli
Carcinoid: Larger cells, low mitotic rate
Lymphoma: CD45+, lacks epithelial markers
Merkel cell: CK20+, TTF-1-
Adenocarcinoma: Glandular features, Napsin A+.
Diagnostic Challenges:
Crush artifact obscures morphology
Distinguish from lymphoma
Combined SCLC with NSCLC components
Poorly differentiated non-small cell carcinoma
Metastatic SCLC from other sites
Large cell neuroendocrine carcinoma.
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 with high cellularity
Cellular Findings
Small malignant cells with [specific morphological features]
Nuclear Features
Nuclear molding, hyperchromasia, fine chromatin, inconspicuous nucleoli
Neuroendocrine Features
[present/suggested by morphology]
Background
Necrotic background with inflammatory debris
Diagnosis
Malignant cells consistent with small cell carcinoma
Urgent Recommendations
Immediate tissue confirmation. Neuroendocrine markers. Staging studies. Oncology referral.
Clinical Note
Small cell carcinoma requires urgent staging and treatment planning