Lung Cancer Flashcards
What does TTF1 stain for?
Lung cancer / thryoid malignancies
What does P63 stain?
Squamous differentiation
What does ALKD5F3 stain?
Specific genetic rearrangement
If test positive for ALKDF3 what you do?
FISH
What is ALK-rearranged lung adenocarcinoma
Stage 4 disease
What do you treat ALK rearranged lung adenocarcinoma with?
Crizotinib
Initial dramatic response
How is lung cancer diagnosed?
Sputum sample
Bronchial washings and brushings
Bronchoalevolar lavage
Transbronchial FNA (EBUS)
Percutaneous transthoracic FNA
What is the sputum technique?
Early sample
Pick and smear - fixation 95% alc
Whati s bronchial washing?
1st to 3rd bronchial lesions
During bronchoscopy
Wash saline over bronci
Reaspirate
Taken back to lab
Prepared by cytocentrifuge or liquid based method
What is bronchial brushing?
Direct sample of mucosal
Brush scraped over lesion
Get cells out of brush
What is bronchoalveolar lavage?
Goes deeper
5th - 6th bronchi
Distal lung irrigated with 20- 50ml aliquots of saline
re-aspiration
What is transbronchial DNA (EBUSCOPE)
Standard practice
Ultrasound guided
Fiberoptic
Direct visualisation
Sample nodes or disease just outside airways
What is FNA?
Fine needle aspiration
Whati s percutaneous transthoracic FNA CT guided?
Peripheral lung lesion
Go from outside body
Higher risk
How does FNA squash smear prep work?
Take that piece of tissue
Squish between two slides
WTF
What is cell block preparation?
Material washed in saline Centrifuged Plasma added Thrombin added Fish out clot Fixed in formalin
What are reporting categories for cytology?
Benign/neg Atypical Suspicious malig Malig Non-diagnostic/unsatisfactory
What are the major categories of lung cancers?
Adenocarcinoma (38%)
Squamous cell carcinoma (20%)
Small cell carcinoma (14%)
Large cell carcinoma
Adenosquamous carcinoma
Sarcomatoid carcinoma
What is adenocarcinoma?
Invasive malignant epithelial tumour with glandular differentiation or mucin production
M=F
Most smokers
Increasing incidence compared to SqCCa
more peripheral than central
Extrathoracic metastases
-adrenal, bone, brain
Cohesive group of malignant cells
What is adenocarcinoma in situ?
Neoplastic glandular proliferation 3cm or less that has a pure lepidic growth along alveolar walls
Precurser lesion, metastatic potential
If resected, curable
No stromal, vascular or pleuran invasion
Rarely mucinous
What does lepidic mean?
Implies cells are resting on top of aleolar walls, but not invading tissue
What doe adenocarcinoma in situ look like?
Glass nodule/opacity
What is squamous cell carcinoma?
Malignant epithelial tumour showing keratinisation and / or intercellular bridges
Smoking pattern
More M > F
Central > peripheral
Precurser lesion of squamous dysplasia / carcinoma in-situ
Prone to necrosis and cavitation
Locally aggressive. less frequent metastasis
What is small cell carcinoma?
Highly aggressive malignant epithelial tumour, v. strongly associated with smoking
Central»_space;»> peripheral
Extopic hormone production common
- cushing etc
Highly aggressive, widespread metastases and virtually always fatal
Treated with chemoradiation
What does SCC look like in histology?
Scant cytoplasm Finely granular chromatin Absent/inconspicuous nucleoli Nuclear molding, necrosis Mitoses++ Immunohistochemistry: - CD5/6 - Synaptophysin - Chromogranin - TTF1
Electron microscopy:
- Neuroendocrine granules in 2/3
What ancillary studies are available on neoplastic cytology specimens?
Cytochemical stains Immunocytochemical stains Flow cytometry Electron microscopy PCR based techniques FISH
Why do you subtype NSCLC?
Non small cell lung cancer means adeno or squamous
Approx 70% of patients have unresectable disease
Cytology sample is all you get
Want to define adeno or squamous now though
How do you subtype NSCLC?
Morphology and Immunohistochemistry
PAD+d (mucin)
TTF1 - confirm lung + adeno
p63 - squamous
CK5/6 - squamous
New markers Napsin A
P40
What is mucin?
Protein commonly upregulated in adenocarcinomas
Why subtype?
Clinicians and drugs/treatments
Give appropriate treatment
Dont give bevacizumab to squamous :/
What are the two main mutations and treatments in adenocarcinoma?
EGFR mutation - treated with –EGFR inhibitors
ALK-rearranged adenocarcinoma
-Crizotinib
Pemetrexed
Where are the mutations in EGFR-mutated lung adenocarcinoma?
exon 19 and 21
What race is most likely to exhibit EGFR mutations?
east asian 30-50%
Non smokers
Lepidic growth
PCR-based detection
Predicts response to EGFR TKIs
Erlotinib gefitinib
Eventual resistance
Where do you find ALK-rearranged lung adenocarcinomas?
First described in 2007
Uncommon ~4% of NSCLC
Younger people
Adenocarcinoma with solid signet ring or mucinous cribiform pattern
Detection via IHC, FISH and RT-PCR
- Fish = gold standard
Vysis ALK fish break apart fish probe
What drug do you use to treat ALK lung cancer?
Crizotinib
