Lung Tumours

Haemoptysis

Cough up blood

Name 5 Differential Diagnoses that can have haemoptysis

1. Lung cancer

2. Infection with virulent organism e.g. TB

3. Abscess

4. Bronchiectasis

5. Fungal infection

6 Differential Diagnoses for for non-resolving consolidation on CXR

1. Non-compliance with medication

2. Pneumonia d/t drug-resistant organisms

3. Pneumonia d/t unusual organisms e.g. TB, fungal

4. Atypical or viral pneumonia

5. Abscess

6. Underlying tumour

5 Differential Diagnosis for a peripherally located mass on CXR

1. Benign tumour (neoplasm) e.g. hamartoma

2. Carcinoid tumour

3. Primary lung cancer

4. Metastatic cancer

5. Abscess/organizing inflammation

What is required to make a Primary Lung Carcinoma diagnosis

CXR

CT (inc. PET CT)

Tissue required - biopsy

How is a lung biopsy obtained

Bronchoscopy/EBUS (Bx/aspirate)

CT guided biopsy

Smokers have a ___ fold increase in mortality by 70 yrs

20-fold ↑

Risk of lung cancer goes back to baseline how long after quitting smoking

10 yrs

What % of smokers develop lung cancer

11%

What gases are in tobacco smoke & which of them are carcinogens

CO, Nitrogen dioxide, Hydrogen cyanide, Formaldehyde

Formaldehyde is a carcinogen

Where are most of the carcinogens in tobacco smoke

Particles: 3,000 chemicals (43 known carcinogens)

Name 8 Smoking-related cancers

• Mouth

• Larynx

• Pharynx

• Lung

• Oesophagus

• Pancreas

• Bladder

• Kidney

Smoking is associated with the development of what kind of carcinoma (what cell type)

Squamous Cell Carcinoma (SCC)

What are the cell changes that happen to lead to carcinoma due to smoking

Exposure to what 3 types of radiation are risk factors for lung cancer

Radon (synergistic with smoking; 25 fold inc. risk)

Uranium

Ionizing radiation (Hiroshima and Nagasaki)

Asbestos exposure leads to a what fold increased risk of lung cancer in:

• Non smokers

• Smokers

Non-smokers: 5-fold ↑ risk

Smokers: 50-90 fold ↑ risk

What is the general time between exposure to asbestos and the development of cancer (ie latent period)

10-30 years

Tumours arising centrally will present with what 3 main symptoms, why?

haemoptysis; cough; wheeze - due to bronchial obstruction

What fraction of tumours arising centrally involve 1st, 2nd, 3rd order bronchi

2/3rd

Tumours arising centrally are generally what cell type cancers (2)

SCC (Squamous Cell Carcinoma) or SCUC (Small Cell Undifferentiated Carcinoma)

In what layer of the lung do tumours arising centrally in lung cancer usually grow

Grow along the airway beneath the mucosa (submucosally)

Tumours arising centrally can be complicated by what 4 conditions

pneumonia, abscess, atelectasis, bronchiectasis

Symptoms of someone presenting with tumours Arising Peripherally, & why

Present late (less bronchial obstruction)

Present with cough, pleural irritation (from pleural extension), effusion

Where do Peripheral Tumours arise

1/3 arise in alveoli or terminal bronchioles

What cancer type is associated with Peripheral Tumours

adenocarcinomas

Name 5 types of non-small cell lung cancer

Small Cell Undifferentiated Carcinoma (SCUC) is aka what

Oat cell carcinoma

is Non-small cell carcinoma / Small Cell Undifferentiated Carcinoma (SCUC) more common

Non-small cell

Options for treatment for Non-small cell carcinoma

Surgery & RT & chemotherapy

Options for treatment for SCUC

Chemotherapy & RT

Match to Squamous Cell Carcinoma / Adenocarcinoma

• More common in females ♀

• More common in males ♂

• More common in smokers

• More common in non smokers

• Peripherally located (mostly)

• Usually express lung-specific marker (TTF1+)

• Express cytokeratins & transcription factors specific for the histological type, but not specific for lung origin

Squamous Cell Carcinoma:

• More common in males ♂

• More common in smokers

• Express cytokeratins & transcription factors specific for the histological type, but not specific for lung origin

Adenocarcinoma (AC)

• More common in females ♀

• More common in non smokers

• Often peripherally located

• Usually express lung-specific marker (TTF1+)

What do you see in Squamous Cell Carcinoma histology

Keratin/Intercellular Bridges

What 5 mutations are associated with SCC

Loss and deletions on ch 3, 9; 17

p53 mutations

Loss of Rb

FGFR1 amplification (increased growth)

EGFRvIII mutation

How are driver mutations found

Genomic testing:

• Next generation sequencing (NGS)

• RT-PCR

• IHC

• ISH

What do you see in Adenocarcinoma histology

Gland formation seen

Does SCC or AC present with metastases more

Adenocarcinoma (AC)

Where in the lung would you find the Lepidic Subtype of AC

Peripheral location

Grows along pre-existing structures/septae

Lepidic Subtype of AC structure

Single or multiple coalescing nodules

Origin type II pneumocytes, clara or bronchiolar cells

Lepidic Subtype of AC can mimic what other condition radiologically

Mimic pneumonia radiologically

There are Different subtypes of AC. Does mucinous have a good/bad prognosis

Mucinous has excellent outcome

2 main driver mutations associated with lung AC

KRAS

EGFR

True/False In AC, somatic changes are usually mutually exclusive

True - if you have 1 mutation, you won’t have another

How are EGFR mutation ACs treated (agent type & drug name)

EGFR inhibitors - erlotinib

How are EML4‑ALK / ROS1 rearrangement ACs treated (drug name)

Crizotinib

Is Small Cell Undifferentiated Carcinoma associated with smoking

Yes

Where Central/Peripheral is Small Cell Undifferentiated Carcinoma (SCUC)

Central or peripheral

SCUC presents early/late with/without metastases

Presents late with metastases

SCUC presents histologically with what

Large pleomorphic nuclei

Scanty cytoplasm

Crush artefact

Neuroendocrine differentiation of SCUC is done with what stains

H&E and IHC

What info helps us decide on TNM Staging

Imaging CT, XRay, MRI, PET, RI bone scan, US of brain, chest, abdomen and bones

Pathology (if tissue sampled and post surgery)

Lung cancers are most commonly diagnosed at what stage

Stage IV

What % of lung cancer is suitable for surgery

20%

What’s the % 5-year survival if lung cancer is localised

50% 5-year survival if localised

What’s the % 5-year survival overall

18%

Which has a better prognosis: non-Small Cell carcinoma / SCUC

non-Small Cell carcinoma

Average survival of how long for SCUC

2-9 months - most are metastatic at presentation

Which of these spreads (non-localised) 1st:

• Adenocarcinomas

• SCC

• SCUC

SCUC

Lung also has CK20

Problem with imaging of cancer with TTF1 marker cancers

Thyroid appears normal on imaging

(TTF1 → Thyroid cancer)

Lung Cancer can directly spread to where

- Regional nodes

- Pulmonary artery

- Regional organs/structures: e.g. pericardium, mediastinum, superior vena cava , cervical sympathetic ganglia (Horner’s syndrome)

Lung Cancer directly spreading to which regional structure is considered an emergency

Superior vena cava!!

What would be a sign that lung cancer spread to the SVC

Engorgement of the jugular veins

Lung cancer can spread through the blood to where

Adrenal, liver, brain, bone, breast

What is Paraneoplastic syndrome

An effect that is not explained directly by the presence of tumour or by secretion of substances native to the organ from which tumour arose (generally caused by substances the tumour secretes)

Common hormonal association with SCC

PTH (Parathyroid Hormone)

2 Common hormonal associations with SCUC

ADH

ACTH

Paraneoplastic effects of ADH with lung cancer

Hyponatraemia

Paraneoplastic effects of Parathormone with lung cancer

Hypercalcaemia

Paraneoplastic effects of ACTH with lung cancer

Cushing’s syndrome

Paraneoplastic effects of Calcitonin with lung cancer

Hypocalcaemia

Paraneoplastic effects of Gonadotrophins with lung cancer

Gynaecomastia

Paraneoplastic effects of Serotonin with lung cancer

Carcinoid syndrome

6 Common primary tumours that metastasise to the lung

Breast

Renal

Prostate

Oesophagus

Testicular tumours

Sarcomas

Malignant Mesothelioma is common/rare

Rare

Malignant Mesothelioma is cancer where caused by what (2)

Arises from mesothelial cells

Related to Asbestos exposure & smoking

Name a benign tumour

Hamartoma

Hamartoma are found how?

Incidentally - they don’t cause issues so generally found by accident

Hamartoma are generally found more in adults/children

Adults

Hamartoma structure

Mixture of mesenchymal tissue native to lung (smooth muscle, cartilage, fat) with entrapped bronchial glands

Hamartoma is found centrally/peripherally

Usually peripheral

With what form of testing are Hamartomas usually identified

Radiological features usually specific

(If not, biopsy may be necessary)

Name a neuroendocrine lung tumour

Carcinoid lung tumours

In what age group are Neuroendocrine tumour most common

< 40 yrs

Are Lung carcinoid tumours malignant

Has low-grade malignant potential

Possible risk of Lung carcinoid tumour

Carcinoid syndrome (rare)