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Carcinoma of the Lungs Dr.CSBR.Prasad, M.D.

Carcinoma - Lung

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Page 1: Carcinoma - Lung

Carcinoma of the Lungs

Dr.CSBR.Prasad, M.D.

Page 2: Carcinoma - Lung

CLASSIFICATION

I. Non small cell lung Ca (70 - 75 %)

II. Small cell lung carcinoma (20 – 25%)

III. Combined patterns (5 - 10 %)

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CLASSIFICATION

I. Non small cell lung Ca (70 - 75 %)

a. Squamous cell carcinoma (3 to 50%)

b. Adenocarcinoma (30-35 %)

c. Large cell carcinoma (10 -15 %)

II. Small cell lung carcinoma (20 – 25%)

III. Combined patterns (5 - 10 %)

a. Mixed SCC & Adeno Ca

b. Mixed SCC & SCLC

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EPIDEMIOLOGY

• Cigarette smoking

• Asbestos

• Industrial chemicals

• PETROCHEMICAL

• METAL REFINING

• ARSENIC

• Diet - Deficiency of

• Vit-E

• ß-Carotene

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5 main histologic types of lung cancer

1. Squamous cell ca (3 to 50%)

2. Small cell ca (20 to 25 %)

3. Adenocarcinoma (15 to 35 %)

4. Large cell ca (10 to 15 %)

5. Adenosquamous ca (1 to 3 %)

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Ca lung – 3 therapeutic groups.

1. Small cell carcinoma (20 to 25 %)

2. Non – small cell ca (70 to 75 %)

(squamous, adeno ca, large cell ca)

3. Combined / Mixed patterns (5 to 10 %)

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Etiology of Bronchogenic carcinoma

• 40 - 70 yrs [peak 50 - 60 yrs]

• Tobacco smoking

• Industrial hazards

• Air pollution

• Dietary factors

• Genetic factors

• Scarring of lung tissue

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Tobacco smoking

1. Statistical evidence

2. Clinical evidence

3. Experimental evidence

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Tobacco smoking - Statistical evidence

• Amount of daily smoking

• Tendency to inhale

• Duration of smoking habit

average smoker – 10x risk

40 cigarettes/day/yrs – 20x risk

8% lung cancer in smokers, Lip, tongue, floor of

mouth, pharynx, larynx, esophagus, urinary

bladder, pancreas, kidney

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Tobacco smoking – clinical evidence

• Histologic evidence –

Atypical hyperplastic changes

10 % smokers

1 to 2 % of filter tipped cigarettes

96 % who died of ca lung

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Tobacco smoking - Experimental evidence

• 1200 substances, initiators / promoters

• Initiators:

• Polycyclic hydrocarbons

• Benzo(a)pyrene

• Promoters - Phenol derivatives

• Radioactive elemets - Polonium 210

Carbon 14

Potassium 40

• Contaminants - Arsenic, Nickle, Moulds

• Bronchioalveolar carcinoma NOT strongly associated with smoking

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Sir Richard Doll, the scientist who first confirmed

the link between smoking and lung cance

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Air pollution

• Indoor air pollution - Radon

• Ubiquitous radioactive gas

• Inhalation - bronchial deposition of

radioactive decay products and attachment

to environment aerosols

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Molecular studies

• 10 to 20 genetic mutations

• Dominant oncogenes (activated)

c-myc in small cell carcinoma

k-ras in adenocarcinoma

• Deleted recessive genes (inactive)

p53, RB-gene

Unknown gene in short arm of chromosome #5

• Role of polymorphisms in cytochrome P 450 gene CYPIA 1

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Industrial hazards

• All radiations are carcinogenic

• Hiroshima, Nagasaki uranium is weakly

radioactive

• Smoking in miners - 10x higher incidence

• Asbestos latent period 10 to 30 yrs

• Nickel, chromates, coal, mustard gas, arsenic,

beryllium, iron, news papers workers, African

gold miners, halothane workers

Page 16: Carcinoma - Lung

Scarring

• Scar cancer – Adenocarcinoma

• Old infarct, metallic foreign body, wounds,

granulomatous infections ex - TB

Name the other scar cancers?

Marjolin’s ulcer – SCC arising in an old skin scar

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Precursor lesions

1. Squamous dysplasia and Ca in situ

2. Atypical adenomatous hyperplasia

3. Diffuse idiopathic pulmonary

neuroendocrine cell hyperplasia

Sq cell ca: Smoking > Sq Metaplasia

> Dysplasia > Ca in situ

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Precursor lesions of squamous cell carcinomas

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Feature Small cell Ca Non small cell Ca

Immunophenotyping Mutation p53 / RB

gene

Inactivation of p16

/ CDK / N2A gene

Response to Rx Chemotherapy

Surgery

Main differences between Small Cell &

Non-small cell carcinomas

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Morphology - General Considerations:

• Except Adeno ca, lung cancers arise centrally

Right lung > Left lung

Upper lobes > Lower lobes

• Ulceration Hemoptysis

• Airway obstruction

a ) Absorption collapse

b ) Impaired drainage

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Morphology - Bronchogenic carcinoma

• ¾ ths – I, II, III order bronchi

• Periphery - terminal bronchiole / alveolar septa

• Area of atypia, 1cm, Irrregular warty excrescence

• Intramural growth - parenchymatous growth

• Cavity, spread to pleura

• Distant - adrenals, liver, brain, bone

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Morphology cont.….

• Adenocarcinoma – bronchial derived

bronchioalveolar derived

Mucin producing, slow growth

• Small cell ca – 2x times size of small Lymphocyte

E/M- dense core granules

• Large cell Ca: intracellular mucin, giant cell, spindle

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Morphology - Squamous cell carcinoma

• More in men than women

• Arise centrally local hilar LN

• Disseminate later than other histologic types

• Histologically : WD to PD carcinomas

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Centrally

located gray

white tumor

with cavitation

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Morphology - Adenocarcinoma

• Patients < 40, women, non smokers

• More peripherally located

• Related to lung scars

• Form smaller masses but metastasizes early

• DD from metastatic Adeno Ca is difficult

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Peripherally

located gray

white tumor -

typical of

adenocarcinoma

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Morphology –

Bronchioloalveolar carcinoma

• Not related to: Gender, occupation, social

class, cigarette smoking

• Highly diff Ca, grows upon the walls of pre-

existing alveoli – lepidic spread

• Histologically cells have peg like luminal

aspects with no stromal reaction

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Radiologically they mimic Pneumonia

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Morphology - Small cell carcinoma

• Early dissemination

• Associated with paraneoplastic syndrome

• Varieties - a) Oat cell Ca

b) Polygonal SCLC

c) Spindle cell SCLC

• EM - dense core cytoplasmic granules

• IHC - NSE

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Gray white

tumor

spreading

along the

bronchial tree

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Morphology - LARGE CELL CARCINOMA

• Def: Non small cell carcinoma in which

there is neither SQUAMOUS nor

ADENOCARCINOMA differentiation

• Cells – large, polygonal, vesicular nuclei

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Local effects of lung tumor spread

Pneumonia, abscess,

collapse

Tumor obstruction

Lipid pneumonia Foamy macrophage with

cellular lipid

Hoarseness Recurrent laryngeal nerve

invasion

Dysphagia Esophageal invasion

Diaphragm paralysis Phrenic nerve invasion

Page 50: Carcinoma - Lung

Local effects of lung tumor spread cont….

Rib destruction Chest wall invasion

SVC syndrome SVC compression by tumor

Horner syndrome

Sympathetic ganglia

invasion

Pericarditis, tamponade Pericardial involvement

Page 51: Carcinoma - Lung

Paraneoplastic syndromes

Hormone Clinical manifestation

ADH Hyponatremia

ACTH Cushing’s syndrome

PTH, PRP, PG Hypercalcemia

Calcitonin Hypocalcemia

Gonadotropins Gynecomastia

Serotonin , Bradykinin Carcinoid syndrome

Page 52: Carcinoma - Lung

Paraneoplastic syndrome

• Lambert-Eaton syndrome

• Peripheral neuropathy

• Acanthosis nigricans

• Leukemoid reaction

• Hypertrophic pulmonary osteoarthropathy

• Horner syndrome

• Pancoast tumor

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Horner’s syndrome

• Enophthalmos

• Ptosis

• Miosis

• Anhidrosis

on the same side of the lesion

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Horner’s syndrome

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Pancoast tumor

• Apical lung cancers in superior pulmonary

sulcus

• Invasion of neural structures around

trachea + cervical sympathetic plexus

• Severe pain along distribution of ulnar

nerve

• Horner’s syndrome

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Staging of LUNG CANCER

• T1 - Tumor < 3 cm without pleural / main stem bronchus involvement

• T2 - Tumor 3 cm / involvement of main stem bronchus 2

cm from carina, visceral, pleural, lobar atelectasis

• T3 - Tumor with involvement of chest wall, diaphragm,

mediastinum pleura, pericardium, main stem bronchus 2 cm

from carina, entire lung atelectasis

• T4 - Tumor with invasion of mediastinum, heart, great

vessels, trachea, oesophagus, vertebral body, carina, pleural

effusion

Page 61: Carcinoma - Lung

• N0 - No demonstrable metastasis to regional LNs

• N1 - Ipsilateral hilar / peribronchial LNs

• N2 - Ipsilateal mediastinal / subcarinal LNs

• N3 - Contralateral mediastinal / hilar, ipsilateral /

contralateral scalene or supraclavicular LN

• M0 - No distant metastasis

• M1 - Distant metastasis present

Page 62: Carcinoma - Lung

STAGE GROUPING

• Stage Ia T1 N0 M0

• Stage Ib T2 N0 M0

• Stage IIa T1 N1 M0

• Stage IIb T2 N1 M0

• Stage IIIa T1-3 N2 M0

T3 N1 M0

• Stage IIIB AnyT N3 M0

T3 N3 M0

T4 Any N M0

• Stage IV Any T Any N M1

Page 63: Carcinoma - Lung

Clinical Features

• Cough, weight loss, chest pain, dyspnoea

• Increased sputum

• Tumor cells in sputum on cytology

• FNAC / BAL

Page 64: Carcinoma - Lung

Figure 15-43 Cytologic diagnosis of lung cancer is often possible.

A, A sputum specimen shows an orange-staining, keratinized

squamous carcinoma cell with a prominent hyperchromatic nucleus

(arrow). B, A fine-needle aspirate of an enlarged lymph node shows

clusters of tumor cells from a small cell carcinoma, with molding

and nuclear atypia characteristic of this tumor. [Note the size of the

tumor cells compared with normal polymorphonuclear leukocytes in

the left lower corner].

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Prognosis

• Outlook POOR in most patients

• 5 year survival -- 9%

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CARCINOID TUMOR

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CARCINOID TUMOR

• Low grade malignant epithelial neoplasm

• Show neuroendocrine differentiation

• 1- 5 % of primary lung tumors

• M = F

• Neither smoking nor environmental pollution is a

risk factor

• Peak incidence at a younger age < 40yrs

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Gross:

• Finger like / polypoid masses

projecting into lumen of bronchus

• Collar button lesion

• Covered by intact epithelium

• Rarely exceed 3 - 4 cms

• Site: Main stem bronchus

Page 69: Carcinoma - Lung

Microscopy

• Nests / cords / masses separated by delicate

fibrovascular stroma

• Individual cells - uniform round nuclei

• Salt & Pepper chromatin

• Infrequent mitosis

• Cytoplasm is moderately eosinophilic

• EM - Dense core granules

• IHC – Chromogranin, Synaptophysin

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Active peptides

• Serotonin

• NSE

• Bombesin

• Calcitonin

• Other peptides ex: VIP

Page 73: Carcinoma - Lung

Clinical features:

• Intraluminal growth can cause obstructive

symptoms: Collapse, Chronic Pneumonia

• Carcinoid syndrome

Intermitant attacks of

- Flushing

- Cyanosis

- Anxiety

- Diarrhea

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Prognosis:

• GOOD

• Amenable to surgery

Histological type 5yr survival 10yr survival

Typical carcinoid 87% 87%

Atypical carcinoid 56% 35%

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E N D goto Pleura

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