Definition/General
Introduction:
Small cell lung carcinoma is a highly aggressive neuroendocrine carcinoma
Represents 15% of all lung cancers
Shows rapid growth and early metastases
Smoking-related malignancy.
Origin:
Arises from neuroendocrine cells (Kulchitsky cells) in bronchial epithelium
Shows neuroendocrine differentiation
Central location typical
Tobacco-induced malignancy.
Classification:
WHO 2021: Small cell carcinoma
Combined SCLC: SCLC with NSCLC component
High-grade neuroendocrine carcinoma
Two-stage system: Limited vs Extensive disease.
Epidemiology:
Peak incidence 6th-7th decades
Male predominance
Strong smoking association (>95%)
Central location
Rapid doubling time.
Clinical Features
Presentation:
Rapid onset of symptoms
Cough and dyspnea
Chest pain
Superior vena cava syndrome
Paraneoplastic syndromes (30%)
Metastases at presentation (70%).
Symptoms:
Persistent cough
Hemoptysis
Shortness of breath
Facial swelling (SVC syndrome)
Neurological symptoms (brain metastases)
Bone pain (bone metastases).
Risk Factors:
Tobacco smoking (strongest association)
Environmental tobacco smoke
Occupational exposures
Radon exposure
Family history
Prior chest radiation.
Screening:
Low-dose CT screening (high-risk)
Chest imaging
Staging workup essential
Brain MRI
Bone scan/PET-CT
Paraneoplastic workup.
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Gross Description
Appearance:
Large, bulky mass
Gray-white, soft
Central/hilar location
Extensive necrosis
Hemorrhage common
Mediastinal invasion.
Characteristics:
Soft, friable consistency
Tan-gray color
Extensive necrosis
Ill-defined margins
Endobronchial growth
Bulky lymphadenopathy.
Size Location:
Central location (80%)
Hilar/perihilar mass
Large at presentation (>3 cm)
Mediastinal extension
Endobronchial component
Compression of structures.
Multifocality:
Usually single mass
Extensive mediastinal involvement
Early metastases
Brain metastases (60-70%)
Liver and bone involvement
Pleural/pericardial spread.
Microscopic Description
Histological Features:
Small cells with scant cytoplasm
High nuclear-cytoplasmic ratio
Fine chromatin
Inconspicuous nucleoli
Fragile cells (crush artifact)
High mitotic rate (>10/10 HPF).
Cellular Characteristics:
Small lymphocyte-sized cells
Hyperchromatic nuclei
Finely granular chromatin
Absent/small nucleoli
Scant cytoplasm
Fragile cell membranes.
Architectural Patterns:
Sheets and nests
Streaming pattern
Rosette formation (rare)
Extensive necrosis
Crush artifact common
Vascular invasion.
Grading Criteria:
High-grade by definition
Mitotic rate >10/10 HPF
Extensive necrosis
Ki-67 >50%
No formal grading system.
Immunohistochemistry
Positive Markers:
TTF1 - positive (85%)
Synaptophysin - positive
Chromogranin A - positive (variable)
CD56 - positive
Neural cell adhesion molecule - positive
Insulinoma-associated protein 1 - positive.
Negative Markers:
CK7 - variable
CK20 - negative
p63 - negative
p40 - negative
CDX2 - negative
PSA - negative.
Diagnostic Utility:
Neuroendocrine markers essential
TTF1 positivity supports pulmonary origin
Synaptophysin most reliable
CD56 sensitive but not specific
Ki-67 very high (>50%).
Molecular Subtypes:
Classic SCLC: TTF1+, neuroendocrine markers+
Combined SCLC: Additional NSCLC markers
SCLC-A: ASCL1+
SCLC-N: NEUROD1+
SCLC-P: POU2F3+.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (>90%)
RB1 mutations (>90%)
CREBBP mutations
EP300 mutations
NOTCH family mutations
MYC family amplifications.
Molecular Markers:
p53/RB pathways inactivated
MYC amplification
BCL2 overexpression
High mutational burden
DNA repair defects
Chromosomal instability.
Prognostic Significance:
Stage (limited vs extensive)
Performance status
LDH levels
Brain metastases
Paraneoplastic syndromes
Response to initial therapy
Very poor prognosis overall.
Therapeutic Targets:
Platinum-etoposide chemotherapy
Concurrent radiation (limited disease)
Prophylactic cranial irradiation
Immunotherapy (atezolizumab)
Topoisomerase I inhibitors
PARP inhibitors.
Differential Diagnosis
Similar Entities:
Large cell neuroendocrine carcinoma
Carcinoid tumor
Lymphoma
Metastatic small cell carcinoma
Poorly differentiated adenocarcinoma
Ewing sarcoma.
Distinguishing Features:
SCLC: TTF1+, high Ki-67, neuroendocrine markers+
LCNEC: Larger cells, nucleoli
Carcinoid: Low Ki-67, organoid pattern
Lymphoma: CD45+, B/T markers
Adenocarcinoma: Napsin A+, mucin
Ewing: CD99+, younger age.
Diagnostic Challenges:
Crush artifact
Limited biopsy material
LCNEC vs SCLC
Combined SCLC
Metastatic vs primary
Transformation from adenocarcinoma.
Rare Variants:
Combined SCLC (with NSCLC)
SCLC with large cell component
SCLC with rhabdoid features.
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
[Biopsy/cytology] specimen from [location]
Tumor Description
Small cell carcinoma with [location] and [size if known]
Microscopic Features
Small cells with high N:C ratio, fine chromatin, inconspicuous nucleoli, and high mitotic activity. [Crush artifact present/minimal]
Neuroendocrine Differentiation
Neuroendocrine differentiation confirmed by positive [markers]
Immunohistochemistry
TTF1: [result], Synaptophysin: Positive, Chromogranin A: [result], CD56: Positive, Ki-67: >50%
Stage Assessment
[Limited disease/Extensive disease] based on [staging findings]
Final Diagnosis
Small cell lung carcinoma (SCLC), [limited/extensive] disease
Prognostic Factors
High-grade neuroendocrine carcinoma with [stage], performance status important for treatment planning