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See Soon's notes

  • Smoking --> squamous cell and small cell lung cancer
  • Types of pulmonary neoplasm
    • Benign (rare adenoma and pleural lesions)
    • Malignant
      • Primary
        • NSCLC: squamous cell [25-40%], adenocarcinoma [25-40%], large cell carcinoma
        • SCLC [20-25%]
    • Highly malignant, different staging system
    • More likely to metastasise, 70% at presentation
      • Secondary
        • Common: breast,
  • Treatment options
    • Surgery
      • High mortality
      • Need to assess co-morbidities
  • Small cell lung cancer has a poor prognosis: at presentation, 70% have systemic spread, 90% have it through the mediastinum
    • Don't stage with TNM because very advanced at presentation normally
    • Neuroendocrine differentiation (neurosecretory granules and S100 antigen positive)
  • 90% lung cancers caused by smoking
  • Cough caused by (DDx) inflammation, constriction, compression of airway.
    • DDx: pneumonia, chronic bronchitis, bronchiectasis, TB
  • Breathlessness: MI (hypoxaemia, hypercapnia), cardiac failure/pulmonary oedema
  • 65 yo male presents to local doctor
    • Worsening dyspnoea, cough, haemoptysis for 6 weeks
    • Smoked pack of cigarettes/day for 40 years
  • Haemoptysis ddx:
    • Pulmonary neoplasm (or any tumour)
    • Pulmonary embolus
      • If pulmonary infarction, especially people with pre-existing lung disease, not sufficient collaterals
    • PulmonaryTB
    • Bronchiectasis
      • Permanent, irreversible dilation of bronchi
        • Fill with mucus + recurrent infections
      • Vs asthma: reversible dilation
    • Pulmonary abscess
    • Severe LV failure with MS, raised pulmonary arterial pressure
    • Bleeding diathesis (drugs e.g. warfarin, heparin)
    • Foreign bodies, AV malformations
  • Physical examination:
    • Cachexia
      • catabolic state due to cytokine release by protein [paraneoplastic]
    • Smoker
      • tar stains, bulging pocket, dry skin etc.
    • Pale
      • anaemia
    • Vitals:
      • Increased respiratory rate
      • Paraneoplastic effect may cause hypertension (effects of tumour but not directly; e.g. cachexia)
    • COPD, IHD
  • Most lesions themselves cannot be detected, detect complications instead
    • Tumour in bronchus and obstruction:
      • Atelectasis of distal part
      • Consodliation, pneumonia
    • Tumour in lymphatics
      • Pleural effusion
        • stony dullness on examination
    • Anatomical
      • Phrenic nerve palsy
      • SVC obstruction – Pemberton’s sign (facial flushing, distended neck and head superficial veins,

inspiratory stridor (recurrent laryngeal nerve palsy - http://emedicine.medscape.com/article/1923100-overview), elevated JVP when raise arms)

    • Pancoast tumour and Horner’s syndrome (NB: brachial plexus involvement) - ptosis, miosis, anhidrosis, enopthalmus
    • LNs pread:
      • Pulmonary
      • Mediastinal
      • inoperable
    • Haematogenous sites:

***Brain, bone, liver, adrenal gland [peculiar to lung]

    • Paraneoplastic
      • Cachexia, anaemia
      • Neurological changes
      • Clubbing, HPO: hypertrophic pulmonary osteoarthropathy
  • Investigations:
    • CXR
      • Loss of airspace in L lung, full of fluid
    • Unilateral pleural effusion (DDx: malignancy, CHF, infection)
      • Tracheal deviation (massive effusion
      • Mediastinal shift
    • Causes of unilateral pleuraleffusion
      • Cancer
      • Pneumonia, pulmonary abscess +/- empyema
    • Pulmonary TB
      • Mesothelioma
      • Benign asbestos effusion
      • CT disorders
    • CT: staging, lymphadenopathy
    • Drain fluid to relieve breathlessness
      • Send for MCS
  • Arterial and venous bloods:
  • FBCs, LFTs, Ca, Mg, EUC
    • Hypercalcaemia
      • PTH-related peptide, prostaglandin, IL-1, TNF
      • Osteolytic bony metastasis
      • Coincidental hyperparathyroidism (primary: adenoma of PT, or hypercellular PT; secondary: renal failure).
      • NB corrected calcium for albumin changes
    • Hypophosphataemia
      • Renal excretion increases with PTH, thus lower in blood
    • Vs osteolytic hypercalcaemia: phosphate high
      • Thus, abnormalities due to paraneoplastic effect of PTH-related peptide [SCC]
    • Other investigations:
      • CT scan
      • Sputum cytology, microbiology
      • Pleural tap: cytology, pathology, microbiology

*Bronchoscopy and biopsy (can do percutaneously under radiological guidance if close to surface), bronchoalveolar lavage

  • Spirometry
  • Sputum cytology
    • Adequate sample
      • Neutrophils – normal
      • Ciliated Pseudostratified columnar cells from bronchus
      • Squamous epithelium from mouth
    • Normal squamous epithelium from mouth
      • Slough
    • Abnormal malignant cells
      • Cytological features of malignancy
        • High N:C ratio
        • Hyperchromasia
        • Notched nucleus: nuclear irregularity
    • PAP stain
        • Keratin inside cells stains orange


Slide

Pneumonectomy, virtual slide: SCC lung

    • Normal ciliated pseudostratified columnar epithelium
    • Squamous metaplasia with cytological atypia (dysplasia)
    • Squamous: keratin prodution (keratin whirls), cell bridges
      • Carcinoma in situ
    • Invasion
      • Invasion through muscle layer
      • Desmoplasia, inflammation
      • Invasion past cartilage plate, but not yet through bronchus wall
    • Report:
      • Section at hilum of lung:
        • Hilar fat, lymph nodule (lower left)
        • Normal lung parenchyma (upper right)
        • Bronchus
      • Invasive SCC arising in bronchus (cells arranged into tongues/sheets; cytological features of malignancy: prominent nucleoli, high N:C ratio, abundant eosinophilic cytoplasm, mitotic figures, etc)
        • On a background of squamous dysplasia, metaplasia and carcinoma in situ
        • Goes into lung parenchyma
        • Invade past cartilage plate, but not yet through bronchus wall
      • Grade – moderately differentiated
      • No evidence of lymphatic or vascular invasion in this slide
  • Extracellular keratin whirls/pearls
  • SCC tends to arise from bronchi, adenocarcinoma tends to be more peripheral
  • SCCs tend to become necrotic in the middle

Case 2

  • 59yo female
    • Unproductive cough and chest pain
    • Bronchoscopy, biopsy showed small cell carcinoma of bronchus
    • Treatment with chemotherapy (operation not appropriate)
      • Likely to have metastasised (poor prognosis: metastasises quickly and widely; liver, back to lung), operation not appropriate, SCLC normally responds well to chemo
  • Clinical chemistry
    • High bilirubin, high ALP, high GGT, high AST, ALT
      • Suggestive of liver metastasis with obstruction
      • Albumin ok – liver not failing
    • Upper range of normal sodium, hypokalaemia, high bicarbonate (it's metabolic alkalosis), high glucose
      • High levels of cortisol
        • Mineralocorticoid effect (high levels of cortisol can have mineralocorticoid effects), glucocorticoid effect (mobilise your glucose stores)
        • Normally there is an enzyme (11 beta dehydroxysteroid dehydrogenase) that converts cortisol to cortisone (inactivating it). If you have lots of cortisol, it overwhelms the enzyme --> cortisol
        • Not cushingoid because they die due to hypokalemic alkalosis first.
          • Hypertension, oedema, hypokalemia
    • Kidney: ion exchange causing high bicarbonate and low K+
    • All cells: increased release of glucose from stores
      • hyperglycaemia
  • Hypokalaemic, metabolic alkalosis, hyperglycaemia
    • Paraneoplastic syndrome: inappropriate (ectopic) ACTH production
      • Others: inapprorpriate ADH release, serotonin, neuromuscular: lambert-eaton myasthenic syndrome, hypercoagulative state, fever, weight loss
    • NB: H+-K+ pump means that high H+ in blood will cause K+
  • Abnormalities at autopsy
    • Cachexic
    • Tar-staining
    • Pleural effusion + primary lesion
    • Liver metastasis
    • Adrenal mets, brain mets
    • Jaundiced
    • Big liver, ascites
  • Macroscopic features: 507.8
    • Pot shows R lung + section of liver
    • Small lesion is in a central location of lung
      • Local metastasis to pleural surface
      • Multiple cream well circumscribed nodules in liver
      • metastasis
    • Diagnosis:
      • Small cell lung cancer with multiple mets to pleural surface and liver
  • Virtual slide: subpleural metastatic small cell lung cancer (got their via small vessels on pleural surface)
    • Invasive tissue into subpleural parenchyma
    • Cytological atypia
      • Poorly differentiated
      • High N:C ratio, hyperchromasia
      • Not much cytoplasm; small cells
      • No nucleolus
    • Angiogenesis
    • Haematogenous spread
    • Other features of small cell lung cancer:
      • Salt-and pepper chromatin
      • Moulding cytology (cells snuggle each other)
  • Virtual slide liver mets
    • Sinusoidal invasion
    • Normal hepaticcords
    • Partially-autolysed cells
  • SCLC: commonly has a small central primary in lung, with peripheral subpleural metastases and nodular mets in liver
  • Singular coin lesion (favours secondary) on x-ray in periphery, virtual slide: adenocarcinoma (adenocarcinomas typically arise peripherally). >1 lesion peripherally: metastatic lesion
    • Appearance of a stellate primary lesion - favours primary
    • Cytological features of malignancy
      • Large nuceolus, high N:C ratio, pleomorphism, mitoses
    • Glandular differentiation with mucin
    • Desmoplasia secondary to carcinoma ("scar cancer of the lung")
    • Diagnosis:adenocarcinoma
      • Primary (rather than secondary)
        • Scar tissue- slow growing
        • Stellate appearance
        • Singular
      • Secondary
        • Where is the metastasis?
        • another in the lung?
  • Immunoperoxidase stains helpful in determining primary vs secondary
  • Lymphocytes also present in the tumour
  • Macroscopic 1017.8
    • Pot of the lung
    • Abnormality: carcinoma starting on the pleural surface and invading inwards to the hilum
      • Anthracosis
    • Diagnosis: likely to be an adenocarcinoma of lung

Task 8

  • 56 yo woamn died from dissemianted malignancy with unknown primary tumour
  • Virtual slide tumour emboli
    • BVs and lymphatics filled with metastatic tissue
    • Favour carcinoma
  • Tumour embolus
    • Lots of big blood vessels, dilated due to cells blocking the vessel (cells with cytological feature of malignancy)
      • Can stain for different molecular weight keratin to decide whether this is epithelial
    • Finding primary
      • Stain for hormones
        • Breast ER PR, thyroid TG, prostate PSA, melanoma markers, adenocarcinomas etc, lymphoid markers
      • Use clinical history
  • Melanoma melanin, lymphoma CD20, adenocarcinoma mucin
  • Can have an unknown primary