Tumors of the lung Carcinoma 90-95% Carcinoid 5 % Mesenchymal and others 2-5 %

Tumors of the lung

Carcinoma 90-95%

Carcinoid 5 %

Mesenchymal and others 2-5 %

Tumors of the lung

Etiology directly related to cigarette smoking

- Statistical evidence for positive relationship between tobacco

smoking and lung carcinoma.

- 87% lung cancers occur in active smokers

- Risk = Average smokers (x10), heavy smokers (>40/day) (x60)

- Passive smokers also have higher risk

Tumors of the lung

Etiology directly related to cigarette smoking

- Clinical evidence.

- Changes in bronchial epithelium in habitual smokers (metaplasia,

dysplasia, carcinoma in situ, squamous carcinoma)

Tumors of the lung

Etiology directly related to cigarette smoking

- Experimental evidence.

Lung carcinoma

- Other Environmental factors:

Radiation, air pollution (radon), asbestos

Lung carcinoma

Series of genetic abnormalities occurring in a step-wise manner,

triggered by a combination of genetic and environmental factors

Oncogenes associated with lung cancer

- cMYC, K-RAS, EGFR, HER-2/Neu

- p53, RB, p16

Initiators:polycyclic aromatic hydrocarbons

Promotors:phenol derivatives

WHO classification (epithelial tumors)

- Squamous

- Small cell

- Adeno (with variants)

- Large cell

- Adeno-squamous

- Ca with pleomorphic sarcomatous elements

- Carcinoid

- Salivary gland type

- Unclassified

IncidenceSquamous 25-40%

Adeno 25-40%**

Small cell 20-25%

Large cell 10-15%

Practical aspect:

- Small cell Ca: metastasize, show high initial chemoresponsiveness

- Non-small cell ca: less metastases, less chemoresponsiveness

Cancers (except adeno) are centrally located

Increasing incidence of adenoca- Women smokers- Type of cigarettes

Increasing incidence of adenoca- Women smokers- Type of cigarettes

Lung Carcinoma - Morphology (squamous)

- Most are centrally located (except adenocarcinomas), from first to third

order bronchi

Squamous cell carcinoma:

- Close correlation with smoking history

- Begins as dysplasia - carcinoma in situ -

irregular warty growth with elevation and erosion

of bronchial mucosa

- fungates into the lumen

- penetrate bronchus and infiltrate along wall

- cauliflower like intraparenchymal mass

- extension to pleura

- spread to lymphnodes (>50% cases)

- distant spread

Squamous cell carcinoma:

- Histology:

- Malignant squamous cells with

keratinization and intercellular bridges

- Varying degrees of differentiation

- Genetic alterations

- highest frequency of p53 mutations

- this increases with increasing grade

- high expression of EGFR

Adenocarcinoma- Most common cancer in women and nonsmokers

- More peripherally located and smaller in size

- Often show mixed pattern (acinar, papillary, bronchiolo-alveolar, solid with mucin

- Grow more slowly when compared to squamous, but metastasize widely

Bronchioloalveolar carcinoma

- Almost always peripheral

- Usually appears as multiple nodules

with pneumonia like consolidation

- Nodules have mucoid feel

- Microscopic growth pattern is

characteristic and resembles butterflies

on a fence

- Mucinous and non mucinous subtypes

- Nonmucinous tumors are surgically

resectable

Bronchioloalveolar carcinoma

Small cell carcinoma

Central location

Whitish appearance

Small cells

Granular chromatin

High mitotic activity

Nuclear moulding

Dense core neuro-

secretory granules

Aggressive tumors, strong relationship to smoking

Staging of lung cancer:

TNM staging is used for staging cancer based on anatomic extent of tumor (T),

lymph node metastases (N), and distant hematogenous metastases (M).

Useful for comparing treatment results from different centers

Adenocarcinoma and squamous cell carcinoma tend to be localized for longer

periods.

Small cell carcinoma is particularly responsive to radiation and chemotherapy

Clinical Course

- Most insidious and aggressive neoplasm

- Cough, weight loss, hemoptysis, chest pain, dyspnoea

- Paraneoplastic syndromes due to hormone like substances

Small cell carcinoma - ADH, ACTH,

Squamous cell carcinoma - PTH,

Carcinoid tumors - Serotonin, Bradykinin

Others - Calcitonin, Gonadotropins,

Eaton-Lambert syndrome (Ca channel antibodies)

Peripheral neuropathies, clubbing

Clinical Course

Local tumor effects:

Pneumonia, abscess, collapse Airway obstruction

Lipid pneumonia Secondary to obstruction

Pleural effusion Tumor spread

Hoarseness RLN invasion

Dysphagia Esophageal invasion

Diaphragm paralysis Phrenic nerve invasion

Rib destruction Chest wall invasion

SVC syndrome SVC compression

Horner syndrome Symp ganglia invasion

Pericarditis / tamponade Pericardial invasion

Metastatic tumors

Usually multiple “cannon-ball” lesions more in the periphery

Variety of other patterns may also be seen

Malignant mesothelioma:

- From parietal / visceral pleura

- Related to asbestos exposure

- Diffuse involvement of pleural space with

effusion and invasion of thoracic structures

- Microscopically, epithelioid and sarcomatoid

subtypes