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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
what is the most common fatal malignancy?
what are the risk factors for bronchial carcinoma?
- tobacco smoking
- industrial: uranium mining, asbestos, arsenic, nickel
- air pollution: car exhausts, radon gas
what is the stepwise pathogenesis of bronchial carcinoma?
- normal epithelium
- squamous metaplasia
- carcinoma in situ
- invasive carcinoma
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
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
what causes the paraneoplastic syndromes of bronchial carcinoma?
- often ectopic hormone production
- NOT due to local or met spread
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
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
what are the 3 types of non small cell lung cancer?
- squamous cell carcinoma
- large cell carcinoma
which type of bronchial carcinoma has the strongest association with smoking?
- small cell carcinoma (99% are smokers)
- squamous cell carcinoma (98% are smokers)
what is the most common paraneoplastic syndrome in squamous cell carcinoma and where in the lung are they located?
- central location
what are the histological signs of squamous cell carcinoma?
- keratin production
- intercellular bridges
which bronchial carcinoma is least assoc. with smoking?
what is the gender difference between squamous and adenocarcinoma of lung?
- squamous cell: m>f
- adenocarcinoma: f>m, but increase is in males
what is the location of adenocarcinomas in lung? and which are associated with scarring?
- peripheral as well as central
- peripheral cancers associated with scarring
what is the difference in pathogenesis of squamous cell and adenocarcinoma of lung?
- squamous: metaplasia then dysplasia
- adeno: dysplasia without metaplasia
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
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
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
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
where are large cell carcinomas located?
centrally, with cavitation due to necrosis
what do cells of large cell carcinoma look like?
- nuclear pleomorphism
- high mitotic activity
which type of cells due squamous and adeno carcinoma arise from?
stem cell population
which type of cells do small cell carcinomas arise from?
which gender does small cell carcinoma affect more?
what are the paraneoplastic syndromes of small cell carcinoma?
- Cushing's: ectopic ACTH
- SIADH: hyponatraemia
where are small cell carcinomas located?
what grade are small cell carcinomas? what is their stage at presentation?
- high grade
- already metastasised early even when the primary is small
what are the cytological features of small cell carcinoma
- small cells
- little cytoplasm
- speckled chromatin (salt and pepper)
what is identifiable on electron microscopy and immunohistochemistry?
- EM: neurosecretory granules
- immunohistochemistry: secretory SUBSTANCES
- confirm neuroendocrine tumour
what are the 2 treatment options for small cell cancer?
- chemotherapy: as already disseminated, cant resect
- radiotherapy: is SVC obstruction
what is the treatment of NSCLC?
- 25% are resectable
- if not: radiotherapy
- if mets: chemotherapy, but poor response
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
what age group do neuroendocrine tumours affect and are they more B or M?
- young, under 40
- 90% benign
- no known relationship with smoking
what is carcinoid syndrome due to?
5HT production and enters SYSTEMIC circulation
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
how are neuroendocrine tumours identified?
immunohistochemistry: stains for 5HT
where are the 3 most common lung mets originally from? and what histological type?
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
what is the differential for lymphangitis carcinomatosa on CXR?
what are the 2 main types of pleural tumours?
- primary: malignant mesothelioma
- secondary: i.e. metastatic (more common)
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?
what is the way of spread to pleural mets?
which cells does malignant mesothelioma arise from? and what do these look like in malignancy?
- mesothelioma cells
- atypical, multinucleate, pleomorphic
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
what is mesothelioma linked to?
- asbestos exposure: mining, fabrication, insulation, electricians
- latency period up to 40 years
what is the presentation of mesothelioma?
- pleural effusion
- weight loss
- chest pain
- fine end inspiratory crackles
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
what is the macroscopic picture of mesotheioma?
pleural thickening and extension into lung
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
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
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
how are central lesions pathologically diagnosed?
bronchoscopic sampling: washings, brushings, transbronch FNA or biopsy, bronch biopsy
how are peripheral lesions pathologically diagnosed?
CT guided transthoracic FNA or biopsy
how are pleural lesions pathologically diagnosed?
- pleural fluid cytology
- CT guided transthoracic FNA or biopsy
what is bronchoalveolar lavage used for?
- samples the alveolar space
- so good for pneumocystis (PCP), aspergillus, inflam lung disease
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
Histology: for malignant mesothelioma, what 2 types of cells does it resemble?
- 1. splindle cells – sarcoma
- 2. acinar – adenocarcinoma
if the atypical cells infiltrate the fat, what does this indicate?
It is a MALIGNANT process, not just reactive mesothelial cells
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