Definition/General
Introduction:
Lung adenocarcinoma is the most common histologic type of lung cancer, representing 40% of all lung cancers and 50% of non-small cell lung cancers
It shows glandular differentiation and mucin production.
Origin:
Arises from peripheral lung parenchyma, often from terminal bronchioles and alveolar epithelium
May develop through adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) precursors.
Classification:
WHO Classification includes lepidic, acinar, papillary, micropapillary, and solid predominant patterns
Special variants include invasive mucinous adenocarcinoma and colloid adenocarcinoma.
Epidemiology:
Most common lung cancer in women and non-smokers
Peak incidence 60-70 years
Rising incidence worldwide
Strong association with specific genetic alterations.
Clinical Features
Presentation:
Often asymptomatic until advanced
Peripheral nodule on imaging
Cough, dyspnea, chest pain
Hemoptysis less common than squamous cell carcinoma
Constitutional symptoms in advanced disease.
Symptoms:
Persistent cough (75%)
Dyspnea (50%)
Chest pain (40%)
Weight loss (35%)
Fatigue
Hemoptysis (25%)
Recurrent pneumonia.
Risk Factors:
Cigarette smoking (85% of cases)
Secondhand smoke exposure
Radon exposure
Occupational carcinogens (asbestos, chromium)
Air pollution
Family history.
Screening:
Low-dose CT screening for high-risk individuals
Molecular testing mandatory for treatment planning
PD-L1 expression testing
Staging by CT/PET scans.
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Gross Description
Appearance:
Gray-white mass with irregular margins
Often peripheral location
Cut surface may show central scarring
Necrosis and hemorrhage in larger tumors.
Characteristics:
Size varies from small nodules (<1 cm) to large masses (>10 cm)
Firm consistency
May show anthracotic pigmentation
Pleural involvement common.
Size Location:
Peripheral location in 75% of cases
Upper lobes more common
May involve pleura
Multifocal disease possible (especially lepidic pattern).
Multifocality:
Multifocal adenocarcinoma possible
May represent separate primaries vs intrapulmonary metastases
Lepidic pattern may be multifocal.
Microscopic Description
Histological Features:
Glandular architecture with mucin production
Five growth patterns: lepidic, acinar, papillary, micropapillary, solid
Nuclear pleomorphism and mitotic activity variable.
Cellular Characteristics:
Cuboidal to columnar cells
Vesicular nuclei with prominent nucleoli
Eosinophilic to clear cytoplasm
Mucin vacuoles
Signet-ring cells possible.
Architectural Patterns:
Acinar (most common): Well-formed glands
Papillary: Fibrovascular cores
Lepidic: Growth along alveolar walls
Micropapillary: Small papillary tufts
Solid: >75% solid growth.
Grading Criteria:
Grade based on predominant pattern: Low-grade (lepidic, acinar, papillary)
High-grade (micropapillary, solid)
Nuclear features also considered.
Immunohistochemistry
Positive Markers:
TTF-1 positive (85%)
Napsin A positive (85%)
CK7 positive (90%)
Surfactant protein positive
CEA positive
MOC-31 positive.
Negative Markers:
CK5/6 negative
p63 negative
CK20 negative (usually)
Chromogranin negative
Synaptophysin negative
WT1 negative.
Diagnostic Utility:
TTF-1+/Napsin A+ profile highly specific for lung primary
CK7+/CK20- pattern supports lung origin
Helps distinguish from squamous cell carcinoma and metastases.
Molecular Subtypes:
EGFR-mutated (15% Caucasians, 50% Asians)
ALK-rearranged (5%)
ROS1-rearranged (1-2%)
KRAS-mutated (25-30%)
PD-L1 high (>50% in 25%).
Molecular/Genetic
Genetic Mutations:
KRAS mutations (25-30%)
EGFR mutations (10-15% overall, higher in Asians/non-smokers)
TP53 mutations (50%)
STK11/LKB1 mutations (15%)
PIK3CA mutations (5%).
Molecular Markers:
ALK rearrangements (5%)
ROS1 rearrangements (1-2%)
RET rearrangements (1-2%)
MET amplification/mutations
BRAF mutations (2-3%).
Prognostic Significance:
EGFR mutations better prognosis with targeted therapy
ALK rearrangements good prognosis with targeted therapy
KRAS G12C mutations now targetable.
Therapeutic Targets:
EGFR inhibitors (erlotinib, gefitinib, osimertinib)
ALK inhibitors (crizotinib, alectinib)
KRAS G12C inhibitors (sotorasib)
Immune checkpoint inhibitors.
Differential Diagnosis
Similar Entities:
Metastatic adenocarcinoma
Mesothelioma
Squamous cell carcinoma with glandular features
Large cell carcinoma
Atypical adenomatous hyperplasia.
Distinguishing Features:
Primary lung: TTF-1+, Napsin A+
Metastatic breast: ER+, GATA3+
Metastatic GI: CDX2+, CK20+
Mesothelioma: Calretinin+, WT1+.
Diagnostic Challenges:
Distinction from metastatic adenocarcinoma
Recognition of lepidic pattern
Differentiating from large cell carcinoma
Poorly differentiated cases.
Rare Variants:
Invasive mucinous adenocarcinoma (former mucinous BAC)
Colloid adenocarcinoma
Fetal adenocarcinoma
Enteric adenocarcinoma
Minimally invasive adenocarcinoma.
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
Lung resection specimen, [lobe], measuring [size] cm
Tumor Size
Tumor measures [X] x [Y] x [Z] cm
Histologic Type
Adenocarcinoma, [conventional/variant] type
Predominant Pattern
[Lepidic/Acinar/Papillary/Micropapillary/Solid] predominant ([X]%)
Histologic Grade
[Low/Intermediate/High] grade
Extent of Invasion
Tumor invades [lung parenchyma/pleura/chest wall/other] (pT[X])
Lymph Nodes
[X] of [Y] lymph nodes involved (pN[X])
Margins
Surgical margins: [negative/positive], closest margin [distance] cm
Lymphovascular Invasion
Lymphovascular invasion: [Present/Absent]
Pleural Invasion
Pleural invasion: [Absent/Visceral pleura/Parietal pleura]
Immunohistochemistry
TTF-1: [positive/negative], Napsin A: [positive/negative]
Molecular Testing
EGFR: [mutation status], ALK: [rearrangement status], PD-L1: [expression level]%
TNM Staging
pT[X]N[X]M[X], Stage [I/II/III/IV]
Final Diagnosis
Final diagnosis: Lung adenocarcinoma, [predominant pattern], [grade], pT[X]N[X]M[X], Stage [X]