TUMORS OF LUNG AND PLEURA TUMORS OF THE

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TUMORS OF LUNG AND PLEURA

TUMORS OF LUNG AND PLEURA

TUMORS OF THE LUNG TYPES : • Carcinomas – 90 -95 % • Carcinoids

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

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

• 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

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 •

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 •

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)

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

Other Contaminants : • Arsenic • Nickel • Molds • Additives

2 -Industrial Hazards • High dose Ionizing Radiation; High incidence in Hiroshima / Nagasaki

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.

3 -Air Pollution • Indoor air pollution – Radon • Increased incidence in miners.

Molecular Genetics • • -For all practical purposes, lung cancer is divided into two

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

Oncogenes : • C-Myc • Kras • EGFR • c-MET • c-KIT

Tumor Suppression Genes : • p 53 • RB 1 • p 16 (

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 •

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)

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

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 ) –

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

• PRECURSOR LESION

POST INVASION PHASE • Larger tumour mass • Symptomatic, obstruct major bronchus – Infection

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

POST INVASION PHASE INVASIVE LESION

 • Cauliflower like intraparenchymal mass • Grey white, firm to hard • Yellowish

• 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

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

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

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

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

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

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

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

• • • 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

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 • Cytogenetics : - p 53 mutation - RB 1 mutation

Small Cell Carcinoma • • Histology : Clusters of relatively small round/oval/spindle shaped neoplastic

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

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

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

Combined Carcinoma • Histology similar to two or more of usual lung carcinomas

Complications of CA Lung • Emphysema • Atelectasis • Severe suppurative /ulcerative bronchitis •

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

CLINICAL PRESENTATION • Cough • Weight loss • Chest pain • Dyspnoea

INVESTIGATIONS • Chest X-Ray • Sputum for Cytology • Bronchial washings / brushings for

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

TREATMENT Early stage disease ( 15% ) – Lobectomy – Pneumonectomy Last stage Disease – Chemotherapy – Radiotherapy – EGFR inhibitors

SURVIVAL RATE • Early stage : 48% • Last stage : 10 -15 %

SURVIVAL RATE • Early stage : 48% • Last stage : 10 -15 %

NEUROENDOCRINE NEOPLASMS 1. Benign tumorlet : Small nests of hyperplastic neuroendocrine cells adjacent to

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

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

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

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 •

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

MISCLENOUS TUMOURS • • • Inflammatory Myofibroblastic Tumor Fibroma Fibrosarcoma Lymphangioleiomyomatosis Leiomyoma Haemangiopericytoma Chordoma Langerhan Cell Histiocytosis Hamartoma

Inflammatory Myofibroblastic Tumor

Inflammatory Myofibroblastic Tumor

Langerhan Cell Histiocytosis

Langerhan Cell Histiocytosis

Hamartoma Lung

Hamartoma Lung

Hamartoma Lung

Hamartoma Lung

METASTASIS TO LUNG • More common than any of the other lung malignancy •

METASTASIS TO LUNG • More common than any of the other lung malignancy • From any carcinoma/sarcoma

 • TUMORS OF PLEURA

• TUMORS OF PLEURA

PLEURAL TUMORS Solitary Fibrous Tumor • Size – Variable; small 1 -2 cm to

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

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

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

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

Malignant Mesothelioma Treatment : • Extrapleural pneumonectomy • Chemotherapy • Radiotherapy