Lung Cancer (Respiratory Pathology 1) Flashcards
RFx for lung cancer?
- Smoking: amont, type, duration
- Occupational hazards: asbestos, silica, radon, heavy metals etc.
- Scarring: chronic scarring conditions of the lung
- Molecular genetics: genetic predisposition
What are the clinical features of centrally located lung cancers?
Cough, dyspnoa, wheezing, haemoptysis.
What are the clinical features of peripherally located lung cancers?
- Pleuritic chest pain
- Effusion
What are the 3 major secretions of tumours causing paraneoplastic syndrome?
- ACTH
- ADH
- PTH
What are the biopsy methods of centrally located tumours?
- Sputum
- Bronchial washings/brushings
- EBUS-TBNA (endobronchial ultrasound guided biopsy)
- Bronchial biopsy
What are the biopsy methods of peripherally located tumours?
- FNA (CT-guided, ENB)
- Pleural biopsy
What is the broad classification of lung cancer?
Most impt step: decide whether NSCC or SCC -> initial management v. different.
- Small cell lung carcinoma
- Non-small lung carcinoma
What are the types of non-small cell carcinoma?
- Squamous cell carcinoma
- Adenocarcinoma
- Adenosquamous carcinoma
- Large cell carcinoma
- Sarcomatoid carcinoma
How should positive lung cancer biopsy be further investigated?
- CT Chest - location, size, lymph nodes
- CT Abdo - lung often spreads to adrenals
- FBE: symptomatic investigation (e.g. haeoptysis)
- UEC: baseline renal function
- LFTs: liver mets, ALP evidence of bony mets
- General surgical work up
What are the features of squamous cell carcinoma? (location, appearance, extent etc)
- Generally central
- Frequently involves large airways
- Cavitation seen in 33% cases
- Grey-white > yellow. Often with a dry, flaky appearance that reflects keratinisation.
- Necrosis and haemorrhage common
What are the histological features of squamous cell tumours?
-Intercellular bridges
-Keratinisation
(poorly differentiated tumour may mean features are not obvious; need immunohistochemcial stains)
What are the characteristics of adenocarcinoma? (features, location, extent etc)
- Most common non-small cell
- Less correlation with smoking
- Generally peripheral –> rapidly reach pleura causing effusions.
- Grey-white with necrosis and haemorrhage
How can adenocarcinoma be differentiated as primary or metatastatic?
- Immunohistochemistry -TTF1 (positive in lung alveolar stroma).
- Diagnosis can be made on cytology but cancer line requires staining.
What is small cell carcinoma?
- Tumour showing neuroendocrine differentiation.
- Rapidly growing mass often with local obstruction, regional lymph node or distant metastases.
- Associated with smoking
What are the histological features of small cell carcinoma?
- Neuroendocrine type architecture: nests, trabeculae, ribbons.
- Tumour cells have high N:C ration with enlarged ovoid nuclei, granular nuclear chromatin, inconspicuous nucleoli, nuclear holding and scanty cytoplasm.
- Many mitoses seen + apoptotic bodies + necrosis.
What is large cell carcinoma?
- Poorly differentiated - neither squamous nor adeno.
- Undifferentiated non-small cell carcinoma that lacks cytological features of small cell, adeno or squamous carcinoma.
- Only Dx when entire tumour examined by histology
What are the complications of lung cancer?
- Lipoid pneumonia (due to distal obstructing tumour)
- Atelectasis
- bronchitis, bronchiectasis
- cavitation and abscess formation
- fistula formation
- pleuritis/pleural effusion
- vascular thrombosis
Why should small cell carcinomas be confirmed with immunohistochemistry?
Can mimic other types e.g. lymphoid, basal
How is lung cancer staged?
TNM
- Tumour size
- Number and location of LN mets
- Metastases (distant)
Where does lung cancer metastasise?
- adrenals - >50%
- Liver - 30 - 50% cases
- brain - 20% cases
- bone - 20% cases
What are the two most important specific mutations in non-small cell adenocarcinomas?
EGFR and ALK
Treatment available to target specific mutations; treatment of using these inhibitors leads to superior response rate, prolong progression-free survival and improved QoL.
Who is most affected by EGFR mutations?
Young non- or light-smoking female Asians with low stage disease.
Incidence 30 -50% in this population; 10-20% in Western population.
Epidemiology of lung cancer?
- 18% cancer deaths (common)
- 2.7M:1F
- Age avg = 60
Histology of adenocarcinoma?
- Well to moderately differentitated tumour
- Glandular and/or papillary structures
- Produce mucin by showing cytoplasmic mutinous vacuoles or mucin extending into the stroma
What is adenocarcinoma in situ?
Previously BAC (bronchiole-alveolar carcinoma in situ). -adenocarcinoma showing growth of neoplastic cells along pre-existing alveolar structures (lepidic growth) w/o evidence of stromal, vascular or pleural invasion.
How may adenocarcinoma in situ present?
-Well demarcated single
or
-multiple nodules
-pneumonic pattern (with involvement of entire lobe)
What should be suspected if there is non-resolving consolidation / pneumonia?
Adenocarcinoma in situ
What are the histological subtypes of adenocarcinoma in situ?
- Non-mucinous (commonest)
- Mucinous (~25%)
- Mixed (very rare)
Immunohistochemistry squamous cell carcinoma markers?
- CK5/6
- p63
Immunohistochemistry adenocarcinoma?
- CK7
- TTF1
Immunohistochemistry Small cell carcinoma?
- synpatophysin
- chromogranin
- CD56
Tumour morphology suggestive of EGFR mutation?
Well differentiated tumours with predominant lepidic growth; no necrosis.
Are all EGFR mutations treatment sensitive?
No- different EGFR mutations occur. Some are resistant to treatment with inhibitors.
Epidemiology ALK mutation?
- Usually younger men; 40-60y.
- Light or non-smoking history.
ALK tumour morphology?
- Solid pattern
- Signet ring cells
- Prominent host inflammatory response
What is ALK inhibitor therapy?
Crizotinib
Epidemiology carcinoid tumours?
- Mean age 55y
- Up to 50% incidental radiological finding
Common symptoms carcinoid tumours?
Cough and haemoptysis. Relate to bronchial obstruction.
Are carcinoid tumours benign?
No. All have metastatic potential and should not be considered benign.
Macroscopic appearance carcinoid tumours?
- Mostly ass/w large bronchus (peripheral lesions uncommonly seen)
- Well demarcated
- Soft tan colour
- May have areas of congestion and haemorrhage
Histology of carcinoid tumours?
- Neuroendocrine architecture: nests, trabeculae, ribbons, rosettes.
- Tumour cells: round to ovoid nuclei, granular chromatin, small nucleoli, moderate amts granular cytoplasm
Histology of atypical carcinoid?
See more mitoses +/- necrosis
How is carcinoid tumour diagnosis confirmed?
Diagnosis confirmed by immunostaining:
- synaptophysin
- chromogranin
- CD56
Prognosis carcinoid tumour?
- Better cf small cell carcinoma
- up to 20% typical carcinoids have regional LN involvement; up to 70% in atypical carcinoids
Prognosis large cell neuroendocrine carcinoma?
Poor. Similar to that of small cell carcinoma.
Which sites commonly metastasise to lung?
- Breast
- Lower GIT
- Melanoma
- Renal cell carcinoma
What are the patterns of lung mets?
- Multiple nodules
- Solitary met
- Lymphangitis mets
- Endobronchial mets
- Pleural mets
- Interstitial spread
How is metastatic disease confirmed?
- Clinical and radiological correlation
- Histology with morphological assessment
- Immunohistochemical staining
What is superior vena cava syndrome?
Obstruction of SVC causing neck and facial swelling + dyspnoea + cough
(Other Sx: hoarseness, swollen tongue, epistaxis, haemoptysis)
Signs of superior vena cava syndrome?
- Dilated neck veins
- Increased number of collateral veins covering anterior chest wall
- Cyanosis
- Oedema of face, arms, chest
- Pemberton’s sign
What is Pemberton’s sign?
Facial flushing, cyanosis and distension of neck veins on raising both arms above the head.
Common sites of lung primary v met?
- 2/3 primary in upper lung
- 2/3 of mets in lower lung
CIx for surgical management lung Ca?
- Spread to contralateral LN or distant sites
- poor pulmonary status
- SCLS (generally)
