TUMORS OF LUNG AND PLEURA TUMORS OF THE
- Slides: 93
TUMORS OF LUNG AND PLEURA
TUMORS OF THE LUNG TYPES : • Carcinomas – 90 -95 % • Carcinoids – 5% • Mesenchymal tumour – 2 -5 %
HISTOLOGIC CLASSIFICATION OF MALIGNANT EPITHELIAL LUNG TUMORS • Squamous Cell Carcinoma • Small Cell Carcinoma • Adenocarcinoma Acinar, papillary, bronchiolo-alveolar, solid, mixed • Large Cell Carcinoma • Large Cell Neuroendocrine Carcinoma
• Adenosquamous Carcinoma • Carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements • Carcinoid tumor – Typical – Atypical. Carcinoma of salivary gland type . Unclassified Carcinoma
Etiology and pathogenesis • Several environmental factors are known to cause genetic damage that transform benign bronchial epithelium to neoplastic tissue
1 -Tobacco Smoking • Overwhelming evidence • 87% lung carcinoma occurs in smokers • 10 fold greater risk – Average smoker • 60 fold greater risk – Heavy smokers • Passive smoking – 3000 deaths per year
Histologic sequence of events: • Normal epithelium • Squamous Metaplasia • Squamous Dysplasia • Carcinoma in situ • Invasive Carcinoma
Cytogenetics : • Mutations in p 53 gene ( G: C > T: A) • • • Carcinogens in cigarette smoke: Polycyclic aromatic hydrocarbons – Benzopyrine Phenol derivatives Radioactive elements – – – Polonium – 210 Carbon – 14 Potassium - 40
Other Contaminants : • Arsenic • Nickel • Molds • Additives
2 -Industrial Hazards • High dose Ionizing Radiation; High incidence in Hiroshima / Nagasaki atomic bomb survivors • Uranium – 4 times increased risk in • nonsmoker uranium miners Asbestos – 5 times increased risk in nonsmokers, 50 -90 times in smokers • Latent period – 10 -30 years
3 -Air Pollution • Indoor air pollution – Radon • Increased incidence in miners.
Molecular Genetics • • -For all practical purposes, lung cancer is divided into two clinical subgroups : a - Small Cell Carcinoma b - Nonsmall Cell Carcinoma -Supported by some specific molecular lesions in each subgroup.
Oncogenes : • C-Myc • Kras • EGFR • c-MET • c-KIT
Tumor Suppression Genes : • p 53 • RB 1 • p 16 ( INK 4 a) • Genes on chromosome 3 p (FHIT, RASSF 1 A )
Small Cell Carcinoma Genes : • C-KIT • MYC N • MYC L • p 53 • 3 p ( Early genetic change ) • RB • BCL 2
Non Small Cell Carcinoma Genes : • EGFR • KRAS ( Late genetic change) • p 53 • p 16 INK 4 a
MORPHOLOGY • Origin : – ¾ in the hilus – Bronchi – ¼ in the periphery – Alveolar septal cells, terminal bronchioles
PRECURSOR LESION PHASE • ( Squamous metaplasia , Dysplasia, Carcinoma in situ ) – Preceed invasive carcinoma – May last for many years – Asymptomatic – No X-Ray changes; Small lesion – Positive diagnostic test ; Cytology ( Sputum, Bronchial lavage fluid/ brushings )
• PRECURSOR LESION
POST INVASION PHASE • Larger tumour mass • Symptomatic, obstruct major bronchus – Infection ( Pneumonia ) – Atelectasis. Grow inside the bronchus; fungating mass. Penetrate the wall of the bronchus into the peribronchial tissue
POST INVASION PHASE INVASIVE LESION
• Cauliflower like intraparenchymal mass • Grey white, firm to hard • Yellowish white mottling and softening • Extension to pleural surface and cavity • Involve pericardium • Regional lymph node involvement (Tracheal, Bronchial, Mediastinal )
Metastasis • Via both lymphatics and hematogenous spread • May be the first manifestation • Any organ; most commonly – Adrenals ( 60 %) – Liver ( 30 -50%) – Brain ( 20% ) – Bone ( 20% )
ADENOCARCINOMA • Malignant epithelial tumour with glandular differentiation or mucin production • Patterns of growth : – Acinar – Papillary – Bronchioloalveolar – Solid with mucin formation
ADENOCARCINOMA; CHARACTERISTICS • • Most common type in : Woman Non-smokers ( 75% v/s > 98% ) Lesion more peripherally located Smaller size Slow growth Early and widespread mets Cytogenetics ; - K RAS ( Specific for adenocarcinoma ) - p 53 , RB 1, p 16 - EGFR ( mutation, amplification ) - C-MET
Bronchioloalveolar Carcinoma • Arises in terminal bronchioloalveolar region • 1 -9 % • Gross : – Single / multiple nodules in lung periphery – Solid, grey white areas like pneumonia
Bronchioloalveolar Carcinoma Histology : • Growth along the preexisting structures • Preservation of alveolar architecture • No stromal, vascular or pleural invasion Sub types : - Mucinous: Tall columnar cells with cytoplasmic / intraalveolar mucin - Non-mucinous: Columnar or cuboidal cells
SEQUENCE OF EVENTS -Atypical adenomatous hyperplasia (Well demarcated focus of cuboidal to low columnar epithelium) | -Bronchioloalveolar Carcinoma | -Invasive Adenocarcinoma (Poorly demarcated invasive lesion/tumor)
SQUAMOUS CELL CARCINOMA • Most common lung cancer in Males • Strong correlation with smoking • Arise from segmental bronchi HISTOLOGY : – Sheets / clusters of atypical squamous cells – Keratinization / squamous pearls varies with grade of tumour – Intercellular bridges
• • • Histologic Grades : Well differentiated Moderately differentiated Poorly differentiated Cytogenetics : - p 53 mutation; Most common - RB 1, p 16 ( INK 4 a), EGFR - Alleles at 3 p, 9 p, 17 p - EGFR overexpression
SMALL CELL CARCINOMA • Highly malignant tumour • Strong correlation to cigarette smoking (Only 1% in non-smokers) • May arise centrally or peripherally • No percursor / preinvasive lesion • Widely metastatic • Surgically incurable • Ectopic hormone production
Small Cell Carcinoma • Cytogenetics : - p 53 mutation - RB 1 mutation
Small Cell Carcinoma • • Histology : Clusters of relatively small round/oval/spindle shaped neoplastic epithelial cells with scant cytoplasm, illdefined cell borders Salt and pepper chromatin Absent /inconspicuous nucleoli Prominent nuclear molding High mitotic count Azzopardi effect Necrosis
Small Cell Carcinoma • • Immunohistochemistry : Synaptophysin Chromogranin CD 57 Parathyroid hormone- like product Electron Microscopy : Dense core neurosecretory granules
LARGE CELL CARCINOMA • Large neoplastic cells • Increased N/C ratio • Prominent Nucleoli • Represent poorly differentiated Squamous Cell • Carcinoma and Adenocarcinoma Histologic variants : – Large cell neuroendocrine carcinoma; organoid nests, trabeculae, rosette-like and pallisading patterns – Neuroendocrine features both on Immunohistochemistry and Electron Microscopy
Combined Carcinoma • Histology similar to two or more of usual lung carcinomas
Complications of CA Lung • Emphysema • Atelectasis • Severe suppurative /ulcerative bronchitis • Bronchiectasis • Lung Abscess • Superior vena cava syndrome • Pericarditis • Pleuritis
CLINICAL PRESENTATION • Cough • Weight loss • Chest pain • Dyspnoea
INVESTIGATIONS • Chest X-Ray • Sputum for Cytology • Bronchial washings / brushings for Cytology • CT guided lung biopsy • CT Scan / MRI
TREATMENT Early stage disease ( 15% ) – Lobectomy – Pneumonectomy Last stage Disease – Chemotherapy – Radiotherapy – EGFR inhibitors
SURVIVAL RATE • Early stage : 48% • Last stage : 10 -15 %
NEUROENDOCRINE NEOPLASMS 1. Benign tumorlet : Small nests of hyperplastic neuroendocrine cells adjacent to scarring / chronic inflammation 2. Carcinoids - Typical - Atypical 3. Small Cell Carcinoma 4. Large Cell Neuroendocrine Carcinoma
Carcinoid tumour • 1 -5 % • < 40 years of age • 20 -40 % nonsmokers • Behavior; low grade malignant epithelial neoplasm • Subclassified into : • • Typical Atypical • Central / peripheral origin
Carcinoid Tumor Morphology : • Gross : – Finger- like or spherical polypoidal masses – Project into the lumen of mainstem bronchi – Covered by intact mucosa – Size ; usually < 3 -4 cm
Carcinoid Tumor Histology : • Patterns – Organoid, trabecular, pallisading, • • • ribbon or rosette-like Delicate fibrovascular stroma Regular, uniform, round cells with moderate cytoplasm Mitosis; < 2 /10 x HPF – Typical Carcinoid. 2 -10 /10 x HPF – Atypical Carcinoid.
Histology Atypical Carcinoid : • Increased pleomorphism • Necrosis • Disorganised growth pattern • Lymphatic invasion • Mitoses 2 -10 /10 HPF
MISCLENOUS TUMOURS • • • Inflammatory Myofibroblastic Tumor Fibroma Fibrosarcoma Lymphangioleiomyomatosis Leiomyoma Haemangiopericytoma Chordoma Langerhan Cell Histiocytosis Hamartoma
Inflammatory Myofibroblastic Tumor
Langerhan Cell Histiocytosis
Hamartoma Lung
Hamartoma Lung
METASTASIS TO LUNG • More common than any of the other lung malignancy • From any carcinoma/sarcoma
• TUMORS OF PLEURA
PLEURAL TUMORS Solitary Fibrous Tumor • Size – Variable; small 1 -2 cm to very large tumour • Histology : -Whorls of reticulin and collagen fibres with scattered fibroblast- like spindle cells • CD 34 + • Keratin – • D/D : Mesothelioma
Pleural Tumors Malignant Mesothelioma : • Asbestos exposure ; 7 -10 % • Latent period ; 25 -45 years -Histology : • Asbestos bodies in the lung • Asbestos plaque -Cytogenetics : Del 1 p, 3 p. Cq , 9 p or 22 q p 16 mutation
Malignant Mesothelioma Morphology : Gross : • Thick layer of soft, gelatinous greyish pink tumour “ensheathing” the lung Histology : . Epithelioid- 60 %; Cuboidal /Columnar cells, tubules or papillary. Sarcomatoid- 20%; spindle cell growth resembling Fibrosarcoma. Mixed- 20%
Malignant Mesothelioma - Clinical Presentation : • Chest pain • Dyspnoea • Recurrent pleural effusions • Hilar Lymphadenopathy • Distant mets ; liver etc. - Prognosis : 50% die within 12 months
Malignant Mesothelioma Treatment : • Extrapleural pneumonectomy • Chemotherapy • Radiotherapy
- Pleural nerve supply
- Peter hino md
- Benign and malignant tumors
- Teratoma
- Cervical ectropion
- Response evaluation criteria in solid tumors (recist)
- Codman triangle
- Bone tumors
- Spinal cord tumors
- Brain tumors
- Chest wall tumors
- Brain tumors
- Ipmn
- Local invasion
- Classification of tumors
- Odontogenic tumors classification
- Enneking
- Odontogenic tumors
- Ameloblastoma rtg
- Thyroid tumors
- Transudate
- Coxal region
- Nerve fibers
- Purulent diseases of lungs and pleura
- Pleurele
- Costo mediastinal recess
- Lung fissures surface anatomy
- Fibroserous
- Apex of the lungs
- Ligamento interpleural de morosow
- Toro tubario
- Double layered membrane
- Pleura parietal visceral
- Pleuricy
- Medial view of lung
- Emphysemas mellkas
- Surface marking of pleura
- Respiratory mucosa
- Pleura
- Respirazione toracica
- Tractus respiratorius
- Analisis cairan pleura
- Tenziós ptx
- Pleura
- Mellkascsapolás
- Analisis cairan pleura
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