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CARCINOMA POLMONARE - Coggle Diagram
CARCINOMA POLMONARE
Diagnostic Approach
Radiography: Detects infiltrating lesions, nodules, atelectasis, pleural effusions, pneumonia
CT Scan with Contrast: Essential for identifying tumor vascularization (‘enhancement’), tumor size, and involvement of adjacent structures
PET-CT Scan:
Uses 18-FDG to detect high metabolic activity, aiding diagnosis and staging
SUV index >2-2.5 suggests malignancy
Limitations include false positives (inflammatory diseases), false negatives (neuroendocrine tumors), poor resolution for lesions <5mm, and limited sensitivity in brain lesions
Diabetic or hyperglycemic patients require glycemic control before examination
Cytology:
Sputum cytology useful for endobronchial tumors
Bronchoscopy and EBUS-TBNA:
Inspection and biopsy of central lesions; sampling of lymph nodes (station 7) under ultrasound guidance
Limitations in peripheral tumors due to scope reach
Fine Needle Aspiration Biopsy (FNAB):
CT-guided percutaneous biopsy for peripheral lesions or inaccessible lymph nodes
Risks include pneumothorax, hemoptysis, rare pulmonary embolism
Mediastinoscopy:
For biopsy of mediastinal lymph nodes >1 cm on CT
Access to tracheal, tracheobronchial, azygos, and subcarinal nodes
Inaccessible nodes include anterior mediastinal, para-aortic, aorticopulmonary, and posterior subcarinal nodes
Other techniques: Thoracentesis cytology, Video-Assisted Thoracoscopic Surgery (VATS), thoracotomy as last resort
Treatment
Depends on histology and stage
Operability: Stages I and II operable; IIIA borderline operable; IIIB and IV inoperable
Surgery:
Mortality has decreased historically from ~50% pre-WWII to 2-2.5% currently due to improved surgical and anesthetic techniques
Complication risk depends on patient age, clinical status, cardio-respiratory function, comorbidities, nutritional status, smoking status, neoadjuvant therapy, surgical extent and duration, transfusion needs
Early stages (I-II): Lobectomy with systematic or lobe-specific lymphadenectomy is the standard
Types of surgery include lobectomy, bilobectomy (right lung only), pneumonectomy, sleeve lobectomy (bronchial resection with anastomosis), segmentectomy, wedge resection
Sleeve lobectomy preferred over pneumonectomy when feasible, especially on the right lung due to functional importance
Limited resections reduce functional loss but have higher local recurrence risk
Locally Advanced Disease (Stage III):
Includes T3 parietal (Pancoast and non-Pancoast), T3 central, T4 tumors with mediastinal involvement
Surgery possible with neoadjuvant chemo-radiotherapy in selected cases
N2 lymph node involvement subdivided into symptomatic (inoperable), surgical discovery (better prognosis), and clinical detection (neoadjuvant therapy followed by surgery if restaging negative)
T4 tumors occasionally operable with complex resection and specialist collaboration
Stage IV (Metastatic):
Generally inoperable, but selected cases with single metastasis (brain, muscle) may undergo surgery
Surgical priority often given to brain metastases before lung tumor resection
Multiple pulmonary nodules may represent synchronous primaries rather than metastases, influencing prognosis positively
Palliative Care:
Bronchoscopic debulking and stenting to relieve airway obstruction, improve respiratory function, and support chemo-radiotherapy
Targeted Therapy:
EGFR mutations (exons 19 and 21) treated with tyrosine kinase inhibitors (Gefitinib, Erlotinib, Afatinib) primarily in advanced NSCLC adenocarcinoma
ALK rearrangements (4-5% NSCLC), often in young non-smokers with adenocarcinoma, treated with ALK inhibitors (Crizotinib, Alectinib, Ceritinib)
Immunotherapy targeting immune checkpoints CTLA-4, PD-1, PD-L1 (Ipilimumab, Tremelimumab, Nivolumab, Pembrolizumab) shows survival benefits especially in squamous NSCLC
Small Cell Lung Cancer (Microcytoma):
Staging dichotomized into limited disease (confined to one hemithorax with ipsilateral lymph nodes) and extensive disease (distant metastases)
Surgery rarely used due to early metastasis
Chemotherapy and radiotherapy are mainstays of treatment
Prophylactic cranial irradiation often applied due to high risk of brain metastases
Risk Factors
Cigarette Smoking:
Accounts for 85-90% of lung cancers, acting as both a risk factor and primary cause
Contains over 40,000 chemicals with more than 55 carcinogens (e.g., polycyclic hydrocarbons, N-nitrosamines)
Strongly linked especially to squamous cell carcinoma and small cell carcinoma
Risk increases proportionally with daily cigarette consumption, duration of smoking, and tar content
Risk decreases after smoking cessation but never returns to baseline non-smoker levels even after 16 years
Passive smoking contributes to about 20% of lung cancers in non-smokers
Occupational Carcinogens:
Asbestos (8-fold increased risk when combined with smoking), chromium, arsenic, vinyl chloride, radon, polycyclic hydrocarbons
Environmental Pollution: Both indoor and outdoor air pollution increase risk
Genetic Factors: Polymorphisms in CYP1A1 and GSTM1 genes increase susceptibility to carcinogens
Pre-existing Lung Diseases: Idiopathic pulmonary fibrosis, silicosis, tuberculosis, COPD increase cancer risk
Immunosuppression: Congenital or acquired immunodeficiency predisposes to tumor progression
Histological Types and Features
Macroscopic Presentation:
Infiltrating lesions originating from bronchial walls causing endobronchial obstruction leading to atelectasis or obstructive pneumonia
Peripheral pulmonary nodules often associated with pleural infiltration and effusion
Malignant Epithelial Tumors:
Non-Small Cell Lung Cancer (NSCLC, 80%): Squamous cell carcinoma, adenocarcinoma, large cell carcinoma
Small Cell Lung Cancer (SCLC, 20%): Also called microcytoma, highly malignant neuroendocrine tumor
Squamous Cell Carcinoma:
Originates from bronchial epithelial cells; p63 positive
Central location (hilar or perihilar), 30% of lung carcinomas
Strongly linked to smoking
Endobronchial exophytic growth causing obstruction, atelectasis, pneumonia
Histologically graded as well, moderately, or poorly differentiated based on keratinization and cellular structure
Adenocarcinoma:
Represents 35-50% of lung carcinomas
Usually peripheral; more common in women and non-smokers
Markers include CK7, TTF-1; frequently harbors mutations in ALK, KRAS, ROS1, EGFR
Tends to infiltrate pleura causing effusions and early distant metastases
Derived from type II pneumocytes and Clara cells
Includes bronchioloalveolar carcinoma (BAC) subtype which maintains alveolar structure and presents variably (multicentric, solitary nodule, or localized consolidation)
Large Cell Carcinoma:
Comprises 20% of lung carcinomas
Highly undifferentiated, peripheral location, high metastatic potential
Similar biology and therapy response to adenocarcinoma
Small Cell Lung Cancer (Microcytoma):
20% of lung cancers, neuroendocrine origin from Kulchitsky cells
Aggressive, often diagnosed at advanced metastatic stage
Early mediastinal lymph node metastasis and brain metastases common
Surgery rarely indicated due to advanced stage at diagnosis
Clinical Presentation
Asymptomatic in early stages due to absence of pain fibers in visceral pleura
General Symptoms: Fatigue, low-grade fever (neoplastic or abscess-related), weight loss, anorexia
Local Symptoms:
Cough (new onset or character change) indicating bronchial obstruction
Chest pain (late symptom) due to pleural infiltration
Dyspnea from underlying lung disease, atelectasis, or pleural effusion
Hemoptysis due to tumor capillary rupture
Pleural effusion and hydro-pneumothorax in advanced cases
Extrapulmonary Syndromes:
Pancoast Syndrome: Tumor in upper lobe affecting brachial plexus and sympathetic chain causing shoulder/arm pain, muscle atrophy, Horner’s syndrome (ptosis, miosis, anhidrosis)
Superior Vena Cava Syndrome: Venous congestion causing facial/neck edema, venous distension, cyanosis, neurological symptoms, often linked to brain metastases
Mediastinal Spread: Hoarseness (laryngeal nerve), dysphagia (esophageal compression), hiccups or diaphragmatic paralysis (phrenic nerve), bradycardia and cough (vagus nerve)
Metastatic Symptoms: Neurological, hepatic, bone pain, lymphadenopathy
Paraneoplastic Syndromes:
Hematologic: Thrombocytopenia, leukocytosis
Endocrine: Cushing’s syndrome (ectopic ACTH, mainly SCLC), SIADH (hyponatremia), hypercalcemia (PTHrP), hyperthyroidism, hypocalcemia, hyperglycemia
Osteoarticular: Digital clubbing, Pierre-Marie hypertrophic osteoarthropathy, migratory arthralgias
Neuromuscular: Limbic encephalitis, cerebellar degeneration, optic neuropathy, Lambert-Eaton syndrome (autoimmune calcium channelopathy causing limb weakness)
Cardiovascular: Migratory thrombophlebitis, nonbacterial thrombotic endocarditis, disseminated intravascular coagulation
Cutaneous: Acanthosis nigricans, dermatomyositis
Epidemiology
Lung cancer is the most frequently diagnosed carcinoma globally and the leading cause of cancer mortality worldwide
High incidence in adults aged 55-75, median age around 65
Second most frequent cancer in men, third in women (after breast cancer in women and prostate cancer in men)
Diagnosis often delayed, resulting in poor prognosis with approximately 15% five-year survival rate
Etiopathogenesis
Lung cancer develops over years through progression of bronchial epithelial changes: hyperplasia → metaplasia (squamous metaplasia) → dysplasia → carcinoma in situ → invasive carcinoma
Genetic alterations involve oncogenes (K-RAS, c-myc, Cyclin D, C-erb2) and tumor suppressor genes (FHIT, pRb, p53, p21, p27, p16) mostly in non-small cell lung cancer (NSCLC)
Targetable mutations include EGFR, ALK, ROS1, RET fusions
Deregulation of BARD1 gene, a tumor suppressor related to BRCA1, plays a role in early carcinogenesis and may serve as diagnostic marker
Staging
Comprehensive staging involves total body CT (brain, chest, abdomen), abdominal ultrasound, brain MRI, bone scintigraphy, PET-CT, mediastinoscopy
Functional evaluation for operability includes spirometry, blood gases, lung perfusion scan, DLCO, ECG, echocardiogram, 6-minute walk test, carotid Doppler, 24h ECG, myocardial scintigraphy, stress test, cardiac catheterization, coronary angiography
TNM Classification (8th edition, 2017):
T (Tumor size and invasion): Ranges from TX (unknown) to T4 (tumor >7 cm or invading adjacent structures)
N (Lymph nodes): NX (not assessed), N0 (none), N1 (bronchopulmonary/hilar), N2 (ipsilateral mediastinal/subcarinal), N3 (contralateral mediastinal, hilar, scalene, supraclavicular)
M (Metastasis): M0 (none), M1a-c (intrathoracic nodules, pleural/pericardial effusion, single or multiple extrathoracic metastases)
Stage Grouping from I to IVB based on T, N, M combinations
Metastatic Pathways
Lymphatic: Early hilar lymph node metastasis in squamous cell carcinoma; peripheral adenocarcinoma may metastasize to supraclavicular nodes
Hematogenous: Via bronchial or pulmonary veins to contralateral or ipsilateral lung, adrenal glands, brain, liver, bones, and pericardium in advanced stages
Pleural metastases occur by direct invasion
Types of Lung Tumors
Benign Tumors:
Epithelial: Papilloma, Adenoma
Connective: Fibroma, Chondroma, Neurinoma, Hamartoma (most frequent)
Bronchial Adenoma: Located bronchially or peribronchially; can cause obstructive bronchial diseases leading to atelectasis
Malignant Tumors:
Epithelial, Connective, and Lymphoproliferative origins
Predominantly bronchial epithelial in origin
Prognostic Factors
Adverse prognosis associated with:
Presence of pulmonary symptoms
Tumor size >3 cm
Non-squamous histology
Multiple lymph node station metastases
Vascular invasion and increased tumor-infiltrating veins
Additional factors: Age, sex, performance status, comorbidities, access to therapies