Neoplastic Conditions

Question 1

What is a neoplasia?

Answer 1

• Mass of tissue with purposeless growth
• Not confined to normal growth constraints
• Benign or malignant
• Primary or metastatic
• Commonest primary neoplasm is carcinoma

Question 2

What is the aetiology of lung cancer?

Answer 2

• Cigarette smoking
• Atmospheric pollution
• Ionising radiation
• Asbestos (promoting role)
• Interstitial lung disease

Question 3

What is the effect of smoking on respiratory epithelium?

Answer 3

• Bronchial squamous metaplasia

- Mutations (due to carcinogens found in smoke)

Question 4

What is squamous metaplasia?

Answer 4

• Not neoplastic

- Adaptive response to chronic irritation

Question 5

Describe the pathogenesis of lung cancer

Answer 5

• Etiologically most likely caused my cigarette smoke
• Small cell carcinoma/ Non small cell
  Non small cell:
• Adenocarcinoma and squamous cell carcinoma

Squamous metaplasia-> Dysplasia -> In situ carcinoma -> Invasive carcinoma -> Stepwise accumulation of mutations

Question 6

How can cytology be used to diagnose lung cancer?

Answer 6

• Sputum (not most ideal)
• Bronchial brushing (BBS)
• Bronchiole-alveolar lavage (BAL)
• Endoscopic bronchial ultrasound fine needle aspiration/ biopsy (EBUS-FNA)

Question 7

How can radiology be used to diagnose lung cancer?

Answer 7

• Radiogically-guided percutaneous biopsy

- Through the skin

Question 8

How can histology be used to diagnose lung cancer?

Answer 8

• Biopsy- bronchoscopy
• Thorascopy
• Wedge biopsy
• Removal of lobe/entire lung (pneumonectomy)
• -> +/- chest wall / lymph nodes
• Intra-operative frozen section
• -> benign/malignant
• -> primary/metastasis
• Biopsy of metastasis

Question 9

What is a cytology cell block?

Answer 9

• Suspension of cells

- Epithelial cells may form glands

Question 10

What are some diagnostic tools that can be used for lung cancer?

Answer 10

• Frozen section
• Formalin-fixed paraffin-embedded tissue
• Molecular tests

Question 11

How does formalin-fixed paraffin-embedded tissue work?

Answer 11

• H&E staining
• Histochemical stains (DPAS)
• Immunohistochemistry- cell/tissue origin
• Predictive markers- ALK, PD-11

Question 12

What are the molecular tests that can be used to diagnose lung cancer?

Answer 12

• ALK, ROS rearrangements

- Extracted DNA: EGFR mutation analysis

Question 13

What are the histological subtypes of lung cancer?

Answer 13

• Squamous cell carcinoma- 20%
• -> keratinisation or intercellular bridges
• Adenocarcinoma (38%)
• -> glandular differentiation, cytoplasmic mucin vacuoles
• Small cell carcinoma (14%)
• Large cell carcinoma (3%)
• Others (25%)

Question 14

Compare non-small cell and small cell carcinomas

Answer 14

• Major differences in clinical presentation, pattern of spread and response to therapy
• Non-small cell can be treated with a lobectomy
• Small cell cannot, most likely chemotherapy

Question 15

Describe squamous cell carcinoma

Answer 15

• Central aspect of lung

- Keratin and intracellular bridges

Question 16

What is adenocarcinoma?

Answer 16

• Formation of malignant flans

- Atypical architecture

Question 17

Describe lung tumours with neuroendocrine differentiation

Answer 17

• Carcinoid (typical or atypical)
• Large cell neuroendocrine carcinoma
• Small cell carcinoma
• Low grade (Carcinoid) to high grade (small cell carcinoma)

Question 18

Describe atypical carcinoma

Answer 18

• Hyperchromatic

- More white spaces

Question 19

Describe small cell carcinoma

Answer 19

• Solid nests of tumour cells

- Nuclear moulding

Question 20

What are the local clinical effects of lung cancer?

Answer 20

• Cough
• Breathlessness
• Haemoptysis
• Pain
• Pleural effusion

Question 21

What are the systemic effects of lung cancer?

Answer 21

• Ectopic hormone production (e.g. ADH)
• Finger clubbing
• Myopathies
• Neuropathies
• Cachexia (weight loss)
• Metastases (locoregional and distant)

Question 22

Give two examples of mesenchymal tumours

Answer 22

• Chondroid hamartoma

- Synovial sarcoma

Question 23

What is a chondroid hamartoma?

Answer 23

• Not a neoplasm
• Benign mesenchymal tumous
• Variable proportions of cartilage, storm, adipose
• ‘shell-out’ of tissue in macroscopic appearance

Question 24

What is a synovial sarcoma?

Answer 24

• Monophasic, biphasic or poorly differentiated
• Molecular diagnostic marker
• t (X;18) on reverse transcriptase-PCR or FISH (fluorescent in situ hybridisation)
• High grade

Question 25

What is lymphoproliferative disease?

Answer 25

• Marginal zona lymphoma

- Low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT)

Question 26

What are other tests that can be done to inform management to patients?

Answer 26

• EGFR (epidermal growth factor receptor)
• ALK (anaplastic lymphoma kinase)
• PD-L1 expression

Question 27

What is EGFR?

Answer 27

• Mutation analysis

- Tyrosine kinase inhibitors, e.g. geftinib and erlotinib

Question 28

What is ALK?

Answer 28

• ROS1 gene rearrangements

- ALK/MET inhibitors, e.g. nivolumab and pembrolizumab

Question 29

What is the most common site of metastatic neoplasms?

Answer 29

Lung

Question 30

What is a malignant mesothelioma?

Answer 30

• Malignant tumour of pleura

- High grade aggressive malignancy

Question 31

What is the main aetiological factor for malignant mesothelioma?

Answer 31

• Asbestos
• Potential for compensation if occupational exposure
• 20-40 year lag exposure to clinical disease onset

Question 32

What are the two different types of asbestos fibre?

Answer 32

• White asbestos- chrysotile, serpentine fibres (90% asbestos, less/non-carcinogenic)
• Blue asbestos: crocidolite, straight fibres (main mesothelioma carcinogen in UK)\

Question 33

What is the pattern of disease?

Answer 33

• Calcified pleural plaques mark of exposrue
• Relates to expsorue
• Brief heavy exposure- mesothelioma
• Sustained heavy exposure- asbestosis (diffuse pulmonary fibrosis)

Question 34

What are the different types of growth pattern for malignant mesothelioma?

Answer 34

• Epithelioid
• Sarcomatoid
• Biphasic