Definition/General
Introduction:
Adenocarcinoma in sputum cytology represents malignant glandular tumors of the lung
It is the most common lung cancer type (40-50%)
Peripheral location makes sputum detection challenging
Associated with EGFR mutations and targeted therapies.
Origin:
Originates from peripheral alveolar epithelium
Arises from type II pneumocytes or Clara cells
Peripheral lung location predominant
Adenocarcinoma in situ (formerly BAC) precursor
EGFR pathway alterations common.
Classification:
Classified by histological patterns
Acinar (gland-forming)
Papillary (papillae with fibrovascular cores)
Micropapillary (detached papillae)
Solid (with mucin production)
Lepidic (spreading along alveoli)
Invasive mucinous adenocarcinoma.
Epidemiology:
Most common lung cancer (40-50%)
Equal gender distribution
Less smoking association than squamous cell
Common in non-smokers (especially women)
Younger age at presentation
Asian populations higher incidence
EGFR mutations more common in Asians.
Clinical Features
Presentation:
Peripheral lung nodule (often incidental)
Cough (usually non-productive)
Dyspnea on exertion
Chest pain (pleuritic)
Weight loss and fatigue
Pleural effusion possible
Metastases at presentation (40%).
Symptoms:
Cough (40-75% of patients)
Dyspnea (40-60%)
Chest pain (25-40%)
Weight loss (30-50%)
Fatigue and weakness
Hemoptysis (less common than squamous)
Bone pain (metastases).
Risk Factors:
Tobacco smoking (weaker association than squamous)
Radon exposure
Asbestos exposure
Air pollution
Cooking oil vapors
Family history
Prior lung disease
Hormonal factors (women).
Screening:
Low-dose CT screening (high-risk patients)
Sputum cytology (limited sensitivity for peripheral tumors)
Chest X-ray (often shows nodule)
Bronchoscopy (peripheral lesions difficult)
CT-guided biopsy
Molecular testing essential.
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Gross Description
Appearance:
Scant sputum production typically
Clear to white mucoid sputum
Minimal hemoptysis
Low cellularity specimens common
Mucus-rich background
Clean background compared to squamous carcinoma.
Characteristics:
Low yield in sputum cytology
Mucoid consistency
Absence of purulence
Minimal inflammatory debris
Clear to slightly opaque
Good preservation when cells present.
Microscopic Description
Immunohistochemistry
Positive Markers:
TTF-1 (nuclear, 70-80% positive)
Napsin A (cytoplasmic, 80-90% positive)
CK7 (cytoplasmic)
Surfactant protein (SP-A, SP-B)
CEA (cytoplasmic)
Mucin markers (MUC1, MUC4)
Villin (enteric-type).
Negative Markers:
p63 (negative - distinguishes from squamous)
CK5/6 (negative)
p40 (negative)
CK14 (negative)
Desmoglein-3 (negative)
Chromogranin and synaptophysin (negative unless NE differentiation).
Diagnostic Utility:
TTF-1 and Napsin A combination highly specific
TTF-1 positivity excludes squamous carcinoma
Napsin A more specific than TTF-1
CK7 positive in most cases
p63 negativity excludes squamous
Molecular subtyping essential.
Molecular/Genetic
Differential Diagnosis
Similar Entities:
Squamous cell carcinoma with adenoid features
Large cell carcinoma
Adenosquamous carcinoma
Metastatic adenocarcinoma
Reactive pneumocytes
Mesothelioma (pleural fluid).
Distinguishing Features:
Adenocarcinoma: TTF-1+, Napsin A+, p63-
Squamous carcinoma: p63+, TTF-1-, keratinization
Large cell: Lacks differentiation markers
Metastatic: Site-specific markers, clinical correlation
Reactive: Benign nuclear features, inflammation
Mesothelioma: Calretinin+, WT-1+.
Diagnostic Challenges:
Poorly differentiated adenocarcinoma difficult
Solid pattern without glands
Adenosquamous carcinoma components
Metastatic adenocarcinoma distinction
Small cell carcinoma with glandular features
Reactive pneumocytes in inflammation.
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/inadequate] - [criteria and limitations noted]
Cellular Findings
Malignant cells with [specific morphological features]
Glandular Features
[gland formation/mucin production/architectural patterns]
Nuclear Features
[nuclear characteristics and chromatin pattern]
Background
[clean/mucoid/inflammatory] background with [components]
Diagnosis
Malignant cells consistent with adenocarcinoma
Limitations
Limited sensitivity for peripheral adenocarcinoma in sputum
Recommendations
Tissue confirmation. Molecular testing for EGFR, ALK, ROS1. PD-L1 testing.