Lung Cancer Flashcards

Lecture notes

1
Q

Describe structure/airflow of the lungs

A
  • Inhaled air (21% O2) passes down the trachea (windpipe) which branches into two bronchi.
  • Each bronchus divides into narrower and narrower branches called bronchi oles
  • Bronchioles terminate in alveoli (small cavity air sacs)
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2
Q

Lung tissue H&E shows

A
  • alveoli and alveolar walls: site of O2 and CO2 exchange
  • cilliated respiratory epithleium
  • bronchiole
  • alveoli separated by an interstitium that contains capillaries involved in gas exchange, connective tissue and a variety of cells involved in alveolar shape and defence.
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3
Q

Alveolar lung tissue H&E components and function
twomain stains used for alveolar histology

A
  • Interstitium lined by 2 morphologicallt distinct types of alveolar cells (type 1 and type 2 pneumocytes
    type 1: squamous alveolar cells involved in gas exchange
    type 2: cubodial alveolar cells involved in modifying surface tension and nehancing macrophage function
    Macrophages: defence from foreign substances in the air
    Erythrocytes (RBCs)
    Reticiulin and H&E stains in alveolus histology
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4
Q

Cell Types in the bronchi and bronchioles

A

bronchi and bronchioles: ciliated cubodial epithelium and a thin layer of smooth muscle. cells produce mucus trapping particles, cilia moved trapped cells along
main cell types: basal cells, neuroendocrine cells, ciliated cells, serous cells, Clara cells and goblet (mucin producing) cells.
In terminal bronchioles: less globlet and ciliated cells, more Clara cells

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5
Q

Cell types in alveoli

A

Predominantly squamous alveolar cells (type 1 pneuomocytes) involved in gas exchange

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6
Q

Testing for lung cancer

A
  • Initial testing: via spirometry, blood tests, chest x-rays, CT scans
  • Bronchoscopy/biopsy: cells/tissues taken and sent to cellular pathology lab for confirmation of diagnosis and TNM staging
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7
Q

Cell path lab diagnosis

A
  • Samples may be cytological (cells) or histological (tissues) - received by the lab are preserved to maintain morphology
  • Processed in the lab to provide a thin layer/section on a glass slide
    Viewed under the microscope by a Consultant Respiratory Pathologist
  • Extra stains/tests requested if necessary to confirm precise type of tumour
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8
Q

Types of lung cancer

A

Small cell lung cancer (SCLC) & Non-small cell (NSCLC)

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9
Q

Reporting standards

A

Royal College of Pathologists
Standards and datasets for reporting cancers
Dataset for histopathological reporting of lung cancer
September 2018

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10
Q

Morphological description of small cell carcinoma (SCLC) for typing

A
  • a malignant epithelial tumour derived from neuroendocrine cells of the bronchial epithelium
  • cells are round, oval or spindle-shaped with scant cytoplasm and ‘nuclear moulding’, and often show fragmentation and a ‘crush artefact’ in small biopsies
  • Immunohistochemistry is positive for neuroendocrine markers
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11
Q

Morphological description of non- small cell carcinomas (NSCLC) for typing

A
  • Adenocarcinoma (NSCLC):
    varies with glandular differentiation or mucin production by tumour cells
    patterns are acinar, papillary, bronchio-alveolar and solid with mucin formation”.
  • Squamous cell carcinoma (NSCLC):
    range from well-differentiated squamous cell neoplasm with keratin formation and intercellular bridges, to poorly differentiated with only minimal residual squamous cell features.
  • Large cell carcinoma (NSCLC):
    poorly differentiated malignant epithelial tumour consisting of sheets or nests of large polygonal or giant multinuclear cells.
    large cell neuroendocrine carcinoma, and confirmation of neuroendocrine differentiation is required using immunohistochemical markers
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12
Q

What is grading? Example of grading levels?

A

GRADE describes the variation of tumour cell morphology from normal cells
Low grade – slow growing , look similar to normal cells (well-differentiated). Unlikely to spread.
Moderate Grade – look more abnormal (moderate differentiation)
High Grade – faster growing , look very abnormal (poorly differentiated). Likely to spread.

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13
Q

Staging of lung cancer - RCPath TNM - Primary Tumour (T)

A

TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
Tis Carcinoma in situ
T1 Tumour ≤30 mm
T2 Tumour >30 mm but not >50mm
T3 >50 mm but not >70mm
T4 >70mm

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14
Q

Staging of lung cancer - RCPath TNM - Regional Lymph Nodes (N)

A

NX Regional lymph nodes cannot be assessed
N0 No regional node involvement
N1 Metastasis in ipsilateral peribronchial and/or ipsilateral hilar nodes and/or intrapulmonary nodes (node stations 10–14)
N2 Metastasis in ipsilateral mediastinal and/or subcarinal node(s) (node stations 1–9)
N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular nodes

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15
Q

Staging of lung cancer - RCPath TNM - Distant Metastasis (M)

A

M1 Distant metastasis
M1a Separate tumour nodule(s) in a contralateral lobe; tumour with pleural nodules or malignant pleural or pericardial effusion
M1b Single extra-thoracic metastasis in a single organ and involvement of a single distant (non-regional) lymph node
M1c Multiple extra-thoracic metastases in one of several organs

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16
Q

IHC in a normal lung

A

normal lung shows expression of TFF1 (thyroid transcription factor) positive cells.
Postiive staining seen in bronchial epithelial and pneumocytes

17
Q

IHC- lung adenocarcinoma

A

Lung cancer (poorly differentiated adenocarcinoma) with expression of TTF1 in tumour cells.

18
Q

Squamous cell or adenocarcinoma? Using IHC markers..

A

TTF1 and P63 differentiate between adenocarcinoma (TFF1+) and sqaumous cell carcinoma (p63+)
- Adenocarcinoma: TTF1+, P63-ve
- Squamous cell carcinoma: TTF1-ve, P63+ve

19
Q

Accurate diagnosis of tumour pathology

A

main areas of interest at present.
- Development of more targeted therapies/drugs -> pressure for Histopathologists to provide more detailed information with regards to -tumour sub-classification, and predicted response to the various therapies available.
- increasing need to investigate down to the molecular/genetic level.
- Type, grade, stage of tumour PLUS cause (genetic) /therapeutic targets / prediction of (non)-response to drugs available
- A close link between histopathology & molecular pathology laboratories is therefore essential.

20
Q

Role of molecular pathology in lung cancer

A
  • Enables research into properties of tumour cells including genetic alterations
  • can be used to supplement histopathological diagnosis by sub-classifying tumours & predicting response to particular therapies.
  • improves patient outcome : more specific diagnoses and effective treatment options
21
Q

Molecular biology techniques for pathology investigation

A
  • DNA/RNA sequencing (blotting, PCR, NGS)
    PCR (Polymerase Chain Reaction) – copy/amplify DNA sequences/genes
    NGS (Next Generation Sequencing) – rapid, high throughput, millions of DNA samples, gene profiling
  • FISH (Fluorescence In Situ Hybridisation)
  • Gene micro array assays
22
Q

Genetic alterations

A

More research = More therapuetic targets = more testing requirements for tumors at a molecular level to indicate which genes are affected in which tumor type and how they are altered.
- Drugs being developed to target altered genes- new drugs for NSCLC patients mean specific subtyping of lung cancer is required

23
Q

Lab identification of genetic mutations

A

IHC and/or molecular methods
Commonly being used in combination: IHC as a pre-screening tool to highlight samples requiring additional molecular testing.
example genes: ALK1, PD-L1, ROS1, EGFR

24
Q

ALK1 gene mutation

A
  • EML4-ALK fusion gene responsible for 3-5% NSCLCs
  • ALK D5F3 IHC now the gold standard
  • Positive cases sent for FISH to confirm the gene re-arrangement)
25
Q

PD-L1 Gene Mutation

A

-Transmembrane protein
- Expression on NSCLC cells confers a poor prognosis
- Strong expressors more likely to respond to Pembrolizumab
- Detected by IHC

26
Q

New genes of interest

A

-New gene of interest in lung cancers
- Several ROS1 gene re-arrangements
- Only 2% of lung cancer patients are ROS1 +ve; usually ALK1 –ve
- IHC pre-screen -> FISH to confirm ROS1 gene re-arrangement

27
Q

Epidermal Growth Factor Receptor - EGFR Gene mutation

A

Transmembrane receptor
When stimulated by EGF, cell proliferates
Some forms of NSCLC (adenoca) have EGFR mutation – receptor is always on; predict response to tyrosine kinase inhibitors
Treatments act by blocking the tyrosine kinase part of the receptor
Monoclonal antibody treatments against Epidermal Growth Factor Receptor
Can be detected by IHC (FISH currently the gold standard)