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PathY5 > Respiratory Histopathology (Cancer) > Flashcards

Respiratory Histopathology (Cancer) Flashcards

1
Q

What are the characteristics of benign lung tumours?

A

Do not metastasise

Can cause local complications
Airway obstruction

E.g. chondroma

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2
Q

What are the characteristics of malignant lung tumours?

A

Potential to metastasise, but variable clinical behaviour from indolent to aggressive

Commonest are epithelial tumours, and of these main types (90-95%)

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3
Q

What are the non small cell carcinomas and how much of total lung cancer burden do each of these make up?

A

Squamous cell carcinoma (30%)
Adenocarcinoma (30%)
Large cell carcinoma (20%)

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4
Q

What % of the lung cancer burden does small cell lung cancer make up?

A

20%

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5
Q

What are the common sites of lung cancer?

A

Left main bronchus
Bronchioles
Lung base
Pleura

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6
Q

What is the epidemiology of lung cancer?

A

1 in 7 new cancer cases
Almost 40,000 cases lung cancer in 2007
Men:women 4:3, but increasing numbers of women (1960’s ratio 6:1)
Men – second commonest to prostate cancer
Women – third commonest after breast and bowel cancer
Global cancer

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7
Q

What causes lung cancer?

A

Smoking - small cell and squamous cell

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8
Q

What does smoke contain?

A

Tumour initiators: Polycyclic aromatic hydrocarbons
Tumour promotors: N Nitrosamines, Nicotine, Phenols
Complete carcinogens: Nickel, Arsenic

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9
Q

25% of lung ca in non-smokers attributed to passive smoking

A

25% of lung ca in non-smokers attributed to passive smoking

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10
Q

Does stopping cigarette smoking decrease you risk of lung cancer?

A

Yes

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11
Q

What are non smoking risk factors of lung cancer?

A

Environment:

  1. Asbestos exposure (Asbestos + smoking = 50 fold increase risk)
  2. Radiation (Radon exposure, theraputic radiation, uranium miners)
  3. Air pollution
  4. Other: Heavy metals (Chromates, arsenic, nickel)

Genetics: Familial lung cancers rare, 1st degree relative (young age, non-smoking cases), Susceptibility genes

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12
Q

Which susceptibility genes exist for lung cancer?

A

Chemical modification of carcinogens
Polymorphisms in genes for cytochrome p450 (CYP1A1) and glutathione S transferases which play a role in eliminating carcinogens
Susceptibility to chromosome breaks and DNA damage
Nicotine addiction

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13
Q

How does lung cancer develop?

A

Multistep pathways:
metaplasia, dysplasia, carcinoma-in-situ to invasive carcinoma.

Associated with accumulation of gene mutations leading to disordered unregulated growth, tissue invasion, angiogenesis

Pathways different for different tumour types

For some lung tumours a precursor lesion is not identifiable e.g. small cell carcinoma

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14
Q

Which Mutation confers the most risk of SCC?

A

Gene methylation (p16ink4)

3pLOH, microsatellite alterations (50-80% of SCC)

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15
Q

Summarise Invasive Squamous Cell Carcinoma

A

Frequency
35% pulmonary carcinoma

Risk factor
Closely associated with smoking

Site
Traditionally centrally located arising from bronchial epithelium, however increasing number of peripheral squamous cell carcinomas

Behaviour
Local spread, metastasise late.

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16
Q

What is the precursor lesion to Adenocarcinoma (AC)

A

Precursor lesion: Atypical adenomatous hyperplasia
Proliferation of atypical cells lining the alveolar walls.
Increases in size and eventually can become invasive.

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17
Q

How does AAH progress to AC?

A

AAH
Non mucinous BAC
Mixed pattern adrenocarcinoma

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18
Q

What are the molecular pathways to adenocarcinoma?

A

Stem cells identified in TRU mice
in mice with kras mutation - serial changes from aah to bac to adenocarcinoma

Other pathways TRU - non ras non EGFR (motoi 0/7 egfr, 2/7 ras)
Other pathways - mucinous BAC from bronchial mucus cells, CCAM
BCD?

19
Q

How frequent is an invasive adenocarcinoma?

A

Increasing incidence: 27% pulmonary carcinomas

20
Q

What are the risk factors for an invasive adenocarcinoma?

A

Smoking + other

Commoner in far east, females and non-smokers

21
Q

What is the site and behaviour of an invasive adenocarcinoma?

A

Site
Peripheral and more often multicentric

Behaviour
Extrathoracic metastases common and early (80% present with mets)

22
Q

What is the histology of an invasive adenocarcinoma?

A

Histology shows evidence of glandular differentiation

23
Q

What is a large cell carcinoma?

A

Peripheral or central 10% of tumours

Poorly differentiated tumours composed of large cells

No histological evidence of glandular or squamous differentiation

Poorer prognosis

24
Q

What does electron microscopy of a large cell carcinoma show?

A

BUT on electron microscopy many show some evidence of glandular, squamous or neuroendocrine differentiation
i.e are probably very poorly differentiated adeno/squamous cell carcinomas

25
Q

When and where are small cell carcinomas?

A

When: 20% of tumours, smokers
Where: Near bronchi (central)

26
Q

How do small cell carcinomas act?

A

80% present with advanced disease
Although very chemosensitive, have an abysmal prognosis
Paraneoplastic syndromes

Small poorly differentiated cells
p53 and RB1 mutations common

27
Q

Which non small cell lung cancer currently has the highest incidence?

A

Adenocarcinoma

28
Q

How is survival different between small cell and non small cell lung cancers?

A

SC: Survival 2-4 months untreated, 10-20 months with current therapy

NSC: Early Stage 1: 60% 5 yr survival
Late Stage 4: 5% 5 yr survival

29
Q

Which type of lung cancer is more chemosensitive?

A

Small cell lung cancer

30
Q

Which NSCLC are important to differentiate for treatment?

A

Particularly : Adenocarcinoma vs squamous cell carcinoma
Some adenocarcinomas show a variety molecular changes which can be targeted by specific therapies.
EFGR mutation
ALK translocation
Ros1 translocation
In contrast some patients with squamous cell carcinoma develop fatal haemorrhage with some new chemotherapeutic drugs (Bevacizumab)

31
Q

What can you look at in cytology?

A 
Cytology - looking at cells
Sputum
Bronchial washings and brushings
Pleural fluid
Endoscopic fine needle aspiration of tumour/enlarged lymph nodes
32
Q

What can you look at in histology?

A

Histology - looking at tissue
Biopsy at bronchoscopy - central tumours
Percutaneous CT guided biopsy - peripheral tumours
Mediastinoscopy and lymph node biopsy - for staging
Open biopsy at time of surgery if lesion not accessible otherwise - frozen section
Resection specimen - confirm excision and staging

33
Q

What treatment pathway aims to be curative?

A

Curative: Surgery +/- radical chemoradiotherapy +/- immunemodulatory therapy

34
Q

Which treatment pathway aims to be palliative?

A

Palliative: Chemoradiotherapy, immunemodulatory, targeted therapy

35
Q

What do you look for in molecular testing?

A

EGFR mutation
Responder mutation
Resistance mutation

Alk translocation

Ros1 translocation

36
Q

What are the types of molecular testing?

A

ALK, immunohistochemistry and FISH

37
Q

What is a mesothelioma?

A

Malignant tumour of pleura (lining of the lung and chest wall)

38
Q

Summarise a malignant mesothelioma

A

Frequency
<1% of cancer deaths, but increasing incidence
? Peak in incidence in about 2010.

Aetiology
asbestos exposure

Behaviour
Essentially a fatal disease

Medicolegal implications of diagnosis
compensation

39
Q

Who gets mesothelioma?

A

Most patients have history of asbestos exposure
Long lag time: Tumour develops decades after exposure
males>females, approx 3:1
50-70 years of age

Present with shortness of breath, chest pain

Dismal prognosis

40
Q

What can help in ALK translocation in cancers?

A

Crizotinib

41
Q

What can be used to treat lung cancer?

A

mAbs

Immunotherapy

42
Q

What % of lung cancers in the UK develop in non smokers?

A

10-20%

43
Q

Stopping at any point reduces risk of lung cancer

A

Stopping at any point reduces risk of lung cancer

PathY5 (98 decks)

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