Tumors of lung and pleura

Dr Vijay Shankar S

TUMORS OF LUNG AND PLEURA

• Most common cause of cancer mortality worldwide

Sir Richard Doll1912 –2005

 British physiologist & epidemiologist

Austin Bradford Hill1897 –1991

 English epidemiologist and statistician

Ernst Ludwig Wynder1922-1999

 American epidemiology and public

health researcher

Evarts Ambrose Graham

1883–1957

professor, a physician, and

a surgeon.

• Sir Richard Doll's 1950 paper

demonstrating the association between smoking and lung cancer has become a public health classic.

 Indian-born (1970 ) American

 physician, scientist A hematologist and oncolog

ist

• On average, smokers increase their risk of lung cancer between 5 and 10-fold and in developed countries,

• smoking is responsible for upwards of 80% of all lung cancers.

• in a report from India, roughly two-thirds of all patients with lung cancer were smokers, using either cigarettes and/or bidis, hand-rolled tobacco.

TUMORS OF THE LUNG

TYPES :• Carcinomas – 90-95 %• Carcinoids – 5%• Mesenchymal tumour – 2-5 %

HISTOLOGIC CLASSIFICATION OF MALIGNANT EPITHELIAL LUNG TUMORS

• Squamous Cell Carcinoma • Adenocarcinoma• Adenosquamous Carcinoma• Large Cell Carcinoma • Small cell 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 p53 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 .

Small Cell Carcinoma Genes :

• C-KIT• MYC N• MYC L• p53• 3p ( Early genetic change )• RB• BCL 2

Non Small Cell Carcinoma Genes :

• EGFR• KRAS ( Late genetic change)• p53• p16 INK4a

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 )

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% )

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 :- p53 mutation; Most common- RB1, p16 ( INK4a), EGFR- Alleles at 3p, 9p, 17p - EGFR overexpression

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 )- p53 , RB1, p16

- EGFR ( mutation, amplification ) - C-MET

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 : - p53 mutation - RB1 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• Necrosis

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

Small Cell Carcinoma

Immunohistochemistry :• Synaptophysin• Chromogranin• CD 57• Parathyroid hormone- like product

Electron Microscopy :Dense core neurosecretory granules

Combined Carcinoma

• Histology similar to two or more of usual lung carcinomas

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

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

“Na Nose”

TREATMENT

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

SURVIVAL RATE

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

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.

Carcinoid tumor of the lung. A central carcinoid tumor (arrow) is circumscribed and protrudes into the lumen of the main bronchus. The compression of the bronchus by the tumor caused the postobstructive pneumonia seen in the distal lung parenchyma (right).

A microscopic view shows ribbons of tumor cells embedded in a vascular stroma.

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

METASTASIS TO LUNG

• More common than any of the other lung malignancy

• From any carcinoma/sarcoma

• TUMORS OF PLEURA

PLEURAL TUMORS

Pleural Tumors Malignant Mesothelioma :• Asbestos exposure ; 7-10 %• Latent period ; 25-45 years -Histology :• Asbestos bodies in the lung• Asbestos plaque -Cytogenetics :

Del 1p, 3pCq ,9p or 22qp16 mutation p53 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