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 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 .
Oncogenes :
• C-Myc
• Kras
• EGFR
• c-MET
• c-KIT
Tumor Suppression Genes :
• p53
• RB1
• p16 ( INK 4a)
• Genes on chromosome 3p (FHIT, RASSF
1A )
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 )
•
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 )
- p53 , RB1, p16
- 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 :
- p53 mutation; Most common
- RB1, p16 ( INK4a), EGFR
- Alleles at 3p, 9p, 17p
- 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 :
- 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
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
Haemangioma
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 1p, 3pCq ,9p or 22q
p16 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