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what is a pulmonary hamartoma?
- developmental disorder of CELL GROWTH.
- excessive growth of cells and tissues normally present at that site
- rare
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what is the most common fatal malignancy?
bronchial carcinoma
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what are the risk factors for bronchial carcinoma?
- tobacco smoking
- industrial: uranium mining, asbestos, arsenic, nickel
- radiation
- air pollution: car exhausts, radon gas
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what is the stepwise pathogenesis of bronchial carcinoma?
- normal epithelium
- hyperplasia
- squamous metaplasia
- dysplasia
- carcinoma in situ
- invasive carcinoma
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what are the symptoms of bronchial carcinoma? and cause of them
- cough - mucosal irritation
- chest pain - invasion of chest wall
- dyspnoea - atelectasis, obstruction
- weight loss - cancer cachexia
- present late so high mortality
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what are the clinical complications of bronchial carcinoma?
- hoarseness of voice: left laryngeal nerve palsy
- haemoptyis: vascular invasion
- pneumonia, bronchiectasis, abscess: obstruction
- dysphagia: oesophageal invasion
- SVC syndrome: SVC obstruction
- pleural effusion: pleural invasion
- pericarditis: pericardial invasion
- diaphragm paralysis: phrenic nerve invasion
- horner's syndrome: sympathetic ganglia invasion
- pancoast's humour: apical tumour causing hornets, shoulder, arm pain from brachial plexus involvement, hoarseness from laryngeal nerve palsy
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what causes the paraneoplastic syndromes of bronchial carcinoma?
- often ectopic hormone production
- NOT due to local or met spread
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name some endocrine paraneoplastic syndromes
- hyperCa: PTH or PTHrP or PGE secertion esp scc
- Cushing's syndrome: ACTH secreting tumour esp scc
- SIADH: esp. in small cell carcinoma, get hyponatraemia leading to cerebral confusion and oedema
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what are the non-endocrine paraneoplastic syndromes?
- Eaton-Lambert syndrome: autoAb against pre-synaptic VGCC on NMJ leading to muscle weakness
- Hypertrophic pulmonary osteoarthropathy (HPOA): wrist and ankle pain due to periosteal new bone formation in small long bones also causing arthritis of adjacent joints; clubbing
- Acanthosis nigricans: due to secretion of epidermal growth factor
- Dermatomyositis: autoAb production
- Trousseau's syndrome: migratory thrombophelbitis due to mucins that activate clotting
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what are the 3 types of non small cell lung cancer?
- squamous cell carcinoma
- adenocarcinoma
- large cell carcinoma
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which type of bronchial carcinoma has the strongest association with smoking?
- small cell carcinoma (99% are smokers)
- squamous cell carcinoma (98% are smokers)
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what is the most common paraneoplastic syndrome in squamous cell carcinoma and where in the lung are they located?
- hypercalcaemia
- central location
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what are the histological signs of squamous cell carcinoma?
- keratin production
- intercellular bridges
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which bronchial carcinoma is least assoc. with smoking?
adenocarcinoma
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what is the gender difference between squamous and adenocarcinoma of lung?
- squamous cell: m>f
- adenocarcinoma: f>m, but increase is in males
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what is the location of adenocarcinomas in lung? and which are associated with scarring?
- peripheral as well as central
- peripheral cancers associated with scarring
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what is the difference in pathogenesis of squamous cell and adenocarcinoma of lung?
- squamous: metaplasia then dysplasia
- adeno: dysplasia without metaplasia
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what is the histological feature of poorly differentiated adenocarcinoma of lung?
- cells are vacuolated
- cells produce lots of mucin WITHIN the individual cell, not as a gland
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what is bronchioalveolar carcinoma? where is it located? what does it arise from and where does it extend to?
- rare subtype of adenocarcinoma
- usually peripheral
- arises from distal bronchi/bronchioles
- extends to alveolar spaces
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what is the other name for large cell carcinoma? and why?
- anaplastic carcinoma
- lack of differentiation: no keratin/mucin/glands seen
- when you cannot recognise if it is squamous or adeno
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what is the prognosis of large cell carcinoma compared to other NSCLC?
- poorly differentiated so worse prognosis than squamous and adeno
- paraneoplastic phenomena are rare
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where are large cell carcinomas located?
centrally, with cavitation due to necrosis
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what do cells of large cell carcinoma look like?
- large
- nuclear pleomorphism
- high mitotic activity
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which type of cells due squamous and adeno carcinoma arise from?
stem cell population
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which type of cells do small cell carcinomas arise from?
neuroendocrine cells
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which gender does small cell carcinoma affect more?
male
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what are the paraneoplastic syndromes of small cell carcinoma?
- Cushing's: ectopic ACTH
- SIADH: hyponatraemia
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where are small cell carcinomas located?
central
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what grade are small cell carcinomas? what is their stage at presentation?
- high grade
- already metastasised early even when the primary is small
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what are the cytological features of small cell carcinoma
- small cells
- little cytoplasm
- speckled chromatin (salt and pepper)
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what is identifiable on electron microscopy and immunohistochemistry?
- EM: neurosecretory granules
- immunohistochemistry: secretory SUBSTANCES
- confirm neuroendocrine tumour
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what are the 2 treatment options for small cell cancer?
- chemotherapy: as already disseminated, cant resect
- radiotherapy: is SVC obstruction
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what is the treatment of NSCLC?
- 25% are resectable
- if not: radiotherapy
- if mets: chemotherapy, but poor response
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what is the difference between staging small cell and NSCLC?
- NSCLC: TNM staging
- small cell: not TNM as most already mets, so use limited v extensive
- limited: disease confined to ipsilateral thorax, including supraclavicular fossa and pleural effusion. survival 1-2yrs
- extensive: all other pts. survical 6-12months
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what age group do neuroendocrine tumours affect and are they more B or M?
- young, under 40
- 90% benign
- no known relationship with smoking
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what is carcinoid syndrome due to?
5HT production and enters SYSTEMIC circulation
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what are the symptoms of carcinoid syndrome?
- skin: flushing
- GI: abdo pain, N&V
- lungs: bronchospasm: cough and wheeze
- carcinoid heart disease: endocardial scarring affecting tricuspid and pulmonary valves - 5HT has damaging effects on right heart. rare on left as 5HT is broken down by MAO as it passes through the pulmonary system
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how are neuroendocrine tumours identified?
immunohistochemistry: stains for 5HT
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where are the 3 most common lung mets originally from? and what histological type?
- breast
- GI
- kidney
- adenocarcinoma
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what are the 2 main ways of spread to lung and what do the mets look like?
- haematogenous spread: discrete nodule
- lymphatic spread: diffuse dissemination, aka lymphangitis carcinomatosa
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what is the differential for lymphangitis carcinomatosa on CXR?
miliary TB
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what are the 2 main types of pleural tumours?
- primary: malignant mesothelioma
- secondary: i.e. metastatic (more common)
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what is a complication of pleural tumours?
- pleural effusion
- fibrous adhesions from pleural mets
- what are the most common primary sites of pleural mets? and what histological type?
- lung
- breast
- GI
- ovary
- adenocarcinoma
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what is the way of spread to pleural mets?
lymphatics
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which cells does malignant mesothelioma arise from? and what do these look like in malignancy?
- mesothelioma cells
- atypical, multinucleate, pleomorphic
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what is the spread of mesothelioma like?
- DIRECT invasion is aggressive: into lung and mediastinum
- metastatic spread is less common
- hilar nodes and liver are most common sites
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what is mesothelioma linked to?
- asbestos exposure: mining, fabrication, insulation, electricians
- latency period up to 40 years
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what is the presentation of mesothelioma?
- cough
- dyspnoea
- pleural effusion
- weight loss
- chest pain
- clubbing
- fine end inspiratory crackles
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what is the main differential of mesothelioma? and why? how is it distinguished?
- metastatic adenocarcinoma
- as the histology is variable
- can be spindle cell sarcoma like areas
- or acinar adenocarcinoma like areas
- distinguished: immunohistochemistry
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what is the macroscopic picture of mesotheioma?
pleural thickening and extension into lung
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what is the treatment and prognosis of mesothelioma?
- treatment: cant resect, chemo and radio give poor response
- prognosis poor: 50% dead in a year
- occupational exposure then unnatural cause of death so compensation
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at the death of a pt with mesothelioma, who must it be refered to?
if diagnosis not confirmed in life then refer to Coroner at post portem. if diagnosed, it needs a Coroners inquest
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what different investigations are done in lung cancer diagnosis?
- history: cough, haemoptysis, wt loss, cheeps pain, dyspnoea..paraneo
- examination: consolidation (dull to percussion, reduced chest expansion), pleural effusion (stony dull, reduced air entry, reduced chest expansion), collapse (reduced expansion, dull percusion, reduced breath sounds)
- CXR: but some not visible, need lateral view too. mimics consolidation
- CT: high specificity
- location: all central, adeno (inc bronchioalveolar) can be peripheral too
- pathological diagnosis:
- sputum cytology:gd if +ve as wont need invasive invest
- pleural fluid
- bronchoscopic specimens: bronchial washings, brushings, transbronchial FNA, (trans)bronchial biopsy. these are all best for central lesions
- transthoracic FNA/biopsy (CT guided): best for peripheral lesions
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how are central lesions pathologically diagnosed?
bronchoscopic sampling: washings, brushings, transbronch FNA or biopsy, bronch biopsy
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how are peripheral lesions pathologically diagnosed?
CT guided transthoracic FNA or biopsy
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how are pleural lesions pathologically diagnosed?
- pleural fluid cytology
- CT guided transthoracic FNA or biopsy
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what is bronchoalveolar lavage used for?
- samples the alveolar space
- so good for pneumocystis (PCP), aspergillus, inflam lung disease
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What is the management of mesothelioma?
- 1. breaking bad news, as poor prognosis
- 2. radiotherapy to the drain site.. to prevent seeding to the skin
- 3. refer to an oncologist to be put into a chemotherapy trial
- 4. refer to palliative care for symptom control and for support for the patient and their family
- 5. if asbestos exposure and mesothelioma – coroner’s inquest for compensation for the family
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Histology: for malignant mesothelioma, what 2 types of cells does it resemble?
- 1. splindle cells – sarcoma
- 2. acinar – adenocarcinoma
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if the atypical cells infiltrate the fat, what does this indicate?
It is a MALIGNANT process, not just reactive mesothelial cells
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what are the different asbestos associated diseases?
- 1.malignant mesothelioma
- 2.asbestosis – interstitial fibrosis
- 3.pleural plaques
- 4.bronchial carcinoma
- 5.extra pulmonary malignancy eg mesothelioma of peritoneal cavity or paratesticular
- 6.Pleural effusion alone
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