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PATHOLOGY OF LUNG CANCER
•Walid AL-SALEH MD, D.E.S, Ph.D, MIAC, FIAPth
•AL-BAIROUNI UNIVERSITY HOSPITAL
•May 2010
‘Biopsy’ techniques in lung cancer
diagnosis
•Sputum cytology
•Bronchial brushings and washings
•Fluids
•FNA cytology – primary or mets
•Transbronchial biopsy
•Bronchial biopsy
•Core biopsy – primary or mets
•Liver biopsy
•Mediastinoscopy
•Lymph node excision
•VATS biopsy / resection
•Thoracotomy tumour excision
Increase in
Cell number
and
Tissue architecture
AAH LNMBAC
AdCISInvasive
adenocarcinoma
Large cell
Undifferentiated
&
Sarcomatoid
carcinomas
Bronchial
Squamous
Dysplasia
Squamous
CIS
Invasive
Squamous Cell
carcinoma
De novo development from
unknown precursor ?
?
?
Adenocarcinoma, gross
appearance
Bronchioloalveolar ca, subtypes
Squamous cell carcinoma,
gross appearance
Large cell carcinomaAn undifferentiated malignant epithelial tumour that lacks the
cytologic features of small cell, squamous or adenocarcinoma.
The cells typically have large nuclei, prominent nucleoli and a
moderate amount of cytoplasm
•VariantsLarge cell Neuroendocrine carcinoma (LCNEC)
Basaloid carcinoma
Lymphoepithelioma-like carcinoma
Clear cell carcinoma
Large cell carcinoma with rhabdoid phenotype
•This diagnosis CANNOT be made on small biopsy samples or cytology
•It is only a diagnosis for surgically resected tumours
or (perhaps) large tumour samples
Undifferentiated large cell ca
Adenosquamous
carcinoma(x20)
Bronchial
Squamous
Dysplasia
Squamous
CIS
Invasive
Squamous Cell
carcinoma
Molecular progression of disease in bronchial squamous carcinogenesis
8p21-23 LOH
3p14.2 (FHIT) inactivation *
3p12 (DUTT1) LOH
17p13 (P53) LOH
P53 mutation *5q (APC-MCC)
loss
* Smoking-related
EGFR, HER2/neu,
p53, MCM2,
Bcl2, VEGF all increased
Fhit, p16, RAR-beta
all decreased
Bcl2:bax ratio >1
P63 overexpressed
K-RAS mutations ?
Altered MMP expression
Insulin Growth Factor pathways
p16 INK4A-Cyclin D1-CDK4-RB pathway
Disruption by
P16 loss and
Cyclin D1 increase
13q14 (RB) loss or Rb inactivation less common
The evolving role of
histology and molecular biology
in non-small cell lung cancer
Non-small cell carcinoma is NOT one diseaseDiverse histological types
Multiple tissue origins; myriad molecular characteristics
Prognostic factors poorly understood
Selective therapies being developed
Predictive factors emerging, including histological type
Diagnostic challenges posed
The right drug for the right patient at the right time
Prognostic factors in NSCLC:Likely natural history of tumour
in the absence of clinical intervention
•Stage
•Influence of histology?
•Individual molecular markers
•Gene expression
….amongst many others!
Adenocarcinoma
Squamous cell ca
Large cell carcinoma
Kerr et al, JTO 2007; 2:s4,801-802
n = 202
P<0.05
J Clin Pathol 2006; 59,790-800
Poor prognosis?
HER2 VEGF
CCNE MMP2
Ki67 MMP9
P53 CD44v6
Good Prognosis?
P27 Ecadherin
P16 β-catenin
bcl2
☻
☻☻
☻ ☻
Over-expression results in……
Meta analysis
None convincing
Histology and prognosis:
Squamous carcinomas
•Not all cases behave in the same way
•Better prognosis
–Well differentiated
–Papillary endobronchial
–‘Creeping’ squamous carcinoma (Nakamoto et al,
1993)
•Worse prognosis
–Poorly differentiated
–Basaloid variants
Adenocarcinomas
•Pure BAC – 100% 5YS
•% pattern combinations in mixed adenocarcinoma
–High ‘BAC’ is good
–High Solid is bad
–Papillary ??
•Multifocal disease is biologically different
Large cell carcinomas
• Generally more aggressive
• Basaloid variant is bad
• LCNEC is bad
Sarcomatoid carcinomas
• Highly invasive
• Rapidly growing
• Poor prognosis
Relatively fewlarge studiescontrolled for stage with good pathologicalclassification
Conclusion
•The role of the pathologist is to help the oncologist in providing the right drug for the right patient at the right time!!