Lecture – Lung Cancer – Flashcards

4th most commonly dx cancer in M + F 80% > 60 Deaths decreased men 32%, increased F 72% so M + F death. 1/6 Australian's smoke 1-3 million death year/worldwide. More than any other cancer 5 year survival = 14% 87% LC caused by smoking RF's = radon, air pollution, asbestos, cigarettes, A1At,

Stroke IHD Asthma Chronic bronchitis Emphysema Resp. bronciologitis Cancer - throat, bladder, trachea, oesophgaus, pancrea, liver, kidney, CRC, cervical, stomach Athero CVD Smokless tobacco = oeophagus, mouth, throat, pancreas Second hand smoking = SIDS, ear infection, cold, pneumonia, bronchiolitis, more severe asthma

Premature birth LBW Stillbirt Abruption Ectopic PROM IUGR - the ONLY RF is Smoking!!!! - small baby and placenta as not enough blood to placenta! Placenta praevia Infertility Worse reduction to IVF

1. AMount of daily smoke 2. Tendency to inhale 3. Duration of smoking 4. Age of smoking initiation 1 pack per day = 22x risk of dying from lung cancer 2 ppd = 45x Passive smoking = 1.25x risk

15 years. But may also never be the same

Tobacco --> ROS --> inactivates anti-proteases --> increased neutrophils --> increased neutrophil elastase (may have genetic predisposition to decreased inactivaiton of anti-proteases by A1AT deficiency) --> tissue damage is end result Inflammation around bronchi and bronchioles Damage causes enlarged air spaces next to normal appearing lung Bullae formation - air spaces greater than 1cm o Bullae can rupture and cause pleuritis and pain o Can undergo inflammation and turn into an abscess Carbon pigment in lung Fibrosis and scarring Usually more severe in the upper lobes (apical segments) Lung carcinoma

Smoking A1At Other = IVDU, HIV, Ct sz (Marfan's etc), Salla dz

Occult malignancy. Such as AC of the lung

1. Dx incidentally 2. Sympatomtic 2. Screening - USA and Europe

Asymp - 15% New/change cough - 45-80% Haemoptysis (ddx infxn, bronchiectasis), - 30-70% Weight loss - 46-68% Chest pain - 27-49% (pleural/rib invasion) SOB - endobronchial obstruction/effusion - 37-60% Bone pain - 20% Hoarseness - 8-18% Failure of chest infection to resolve Loss of energy/lethargy Cachexia Clubbing Anaemia or polycythaemia (SCLC) Hypertrophic pulmonary osteoathropathy (wrist pain) - NSCLC Raised LN's Trosseau's syndrome (AC) SIADH, ectopic ACTH, Eaton-Lambert, Cushing's, renin + EPO production(SCLC) PTH (SCC) Regional spread - SVC syndrome - SVC obstruction - Hoarseness - Recurrent laryngeal nn palsy - Raised hemidiagphragm + worsening SOB = Phrenic nerve palsy - Horner's = Brachial nerve root compress - Pancoast/s superior sulcus tumour - Dysphagia = oesophagus compression - SOB = airway compression - Wheeze = bronchogenic obstruction - Pleural effusion - Pleuritis Extrapulmonary invasion - Bone - hypercalcaemia, anaemia, bone pain, SC compression - Liver - hepatomegaly, LFT changes - Brain - focal neuro signs, cerebellar syndrome, proximal myopathy, peripheral neuropathy, confusion, fit - Adrenals - Addison's disease

Cough Haemoptysis (more blood vessels) SOB Wheeze Postobstructive pneumonia Chest pain

Pain SOB Pleural effusions Cough Wt loss --> often silent

Local invasion Mets Endocrine - SIADH, Cushing's, PTH Non-met neuro symptoms

SMOKING - 90%!! Asbestos, radon, halogens, arsenic, nickel, chromium Ionising radiation RT Air pollution Genetic (young, asian, F, non smoker = AC - good pronosis) ?HIV

- 10-25% of lung cancers. Mostly AC - F ;;;;;;; M (hormones???) - Passive smoking, workplace carcinogens, genetic factors, other? - Increase: ECGF mutations + EML4-ALK fusions (young Asian non-smokers - AC) - Decrease: p53 muts, KRAS muts

MAIN: - Flexible bronchoscopy with biopsy x 4 +/- bronchial brushing cytology (endobronchial lesions) - CT guided FNA/core biopsy (peripheral lesions). (NB: can cause pneumothorax, increased risk if emphysema) - EBUS/Mediastinoscopy for biopsy of nodal disease - Sputum sample if central - Pleural fluid if peripheral Other: - CXR/CT thorax and upper abdomen - old films are critical - Blood tests - PET scan, CT guided by symptoms, full body bone scan - Assess pulmonary reserve spiratory/lung volume/transfer factors - Comorbidities considerations!

Routine bloods cytology CXR FNA or biopsy CT chest - upper abdo for staging and guiding bronchoscopy 18F-deoxyglucose PET/PET scan - useful to prove a doubtful lesion Radionucleide bone scan if suspected mets Lung function testing for suitability for lobectomy

If Low risk of malignancy --> consider CXR or nothing If high risk malignancy --> CXR --> multidectector CT --> - Normal - consider bronchoscopy - Central neoplasm - bronchoscopy + biopsy - Peripheral neoplasm - Percutaneous FNAC - Vascular abnormality - Angiography

- CT scan of chest and upper abdomen (include liver and adrenal glands) - PET/CT - Bone scan - MRI scan - FBC + diferential - Serum chemistry studies, including creatinine, electrolytes and Ca - Alkaline phosphate - Aspartate aminotransferase - Pulmonary function testing (if surgical resection considered) - Mediastinosocpy

Local = 49% Regional = 16% Distant stage = 2%

NSCLC stage at presentation, performance score, weight loss SCLC stage at presentation, performance score, weight loss, elevated lactate dehydrogenase level, Male, hyponatremia, elevated ALK phos level

Stage 1 = 50% 5 years Stage 2 = 30% Stage 3a = 15% Stage 3b = 5% Stage 4 = 2%

Surgical resection

Surgery +/- RT

Surgery +/- CTX Incidental finding on histology = +/- adjuvant therapy During surgery = radical resection + adjuvant Prior to surgery = pre-op chemo + radical resection Bulky nodes = chemo + radiation +/- surgery (only if significant response to chemo)

Surgery +/- CTX Resection not generally recommended Combined chemo + radiation preferred treatment

CTX Radiation and pleurodesis for symptoms control Stenting of airways and endobronchial resections

Micromets at diagnosis means that it will eventually relapse. Relapses are almost invariably incurable. The ANITA, JBR and LACE studies show that adjuvant CTX increase median survival and disease free survival

T1a = 2-3cm T1b = 3-/= 2cm distal to carina OR invades main bronchus ;/= 2cm distal to the carina, atelectasis/obstructive pneumonia extending to hilum but not entire lung T3 = ;7cm OR invading chest wall/diaphragm/phrenic nerve/mediastinal pleura/parietal pericardium OR in main bronchus ;2cm distal to the carina OR separate tumour nodules in the same lobe T4 = any size with invasion to heart, gret vessels, trachea, recurrent laryngeal nerve, oesophagus, vertebral body or carina OR separate tumour nodule-s in I/L different lobe N1 = I/L peribronchial/perihilar/intrapulmonary nodes N2 = I/L mediastinal and/or subcranial nodes N3 = C/L mediastinal, C/L hilar, I/L or C/L scalene/supraclavicular M1a = local intrathoracic spread M1b = disseminated/extra-thoracic disease

Stage Ia = T1, N0, M0 Stage Ib = T2, N0, M0 Stage IIa = T1, N1, M0 Stage IIb = T2, N1, M0 OR T3, N0, M0 Stage IIIa = T3, N1, M0 OR T1-3, N2, M0 Stage IIIb = any T4, and N any M Stage 4 = Any T, any N, M1

Liver, bone, brain, adrenal gland, others

- Age 35, non-smoking, carcinoma probability = 1% - Age 35, smoker, carcinoma probability = 5% - Age 70, non-smoking, carcinoma probability = 7% - Age 7-, smoker carcinoma probability = 50%

- Size/growth rate o General rule, if ; 3cm = malignant o Need to be ;9mm before reliably detect on CXR - Density o Best found on CT - 10-20x more sensitive o Calcification Thin layer Ca = granuloma. Central calficiation = granuloma (or lung cancer that has engulfed a granuloma). Popcorn calficiation = hamartomas Can be seen in primary and mets to lungs - Shape/margin o Smooth peripheral margin = likely benign. o Linear strands (spiculation) extending from nodule margin = 90% of primary carcinomas o Pleural tag = linear area of high attenutation surrounded by aertated lung, originating from the edge of the mass and extending peripherally to contact the pleural surface. - Cavitation - Contrast enhancement

Bronchoalverolar subtype of AC

Extends through visceral and parietal pleural layers May mimic bronchoalverolar Peripheral locations, central aras of latency (pseudocavitation), irregular masses forming star-like patterns, pleural tags, heterogenous attenuation Expansile pulmonary consolidation without air bronchograms, lobar atelectasis or single/multiple cavitary lesions

Neoplasm - primary or secondary Pulmonary Haematoma Bullet FB Harmatoma (charply marginated lesion w small focal areas of calcification and fat) AVM Haemorrhagic cyst Abscesses Granuloma Carcinoid tumour Encysted effusion - fluid, blood, pus Skin tumor

Sputum Cytology - Simple and cheap - Sputum is collected by forceful coughing into a container - When properly done, good for cancer typing, especially central hilar located - Up to 85% sensitive w 3 good samples Tissue Diagnosis: - Endobronchial biopsy - central lesion, as far as 6th order distal cartilaginous bronchi. Sample mucosa, musculature, cartilage - Transbronchial - central, sample lung parenchyma distal to cartilaginous bronchi - Bronchi brushings, washings, bronchioalverolar lavage - mucosa and lung parenchyma - CT guided DNA - peripheral lung lesions

Nasal cavity --> paranasal sinuses --> nasopharynx --> trachea --> bronchi --> main --> lobar/secondary --> segmental/tertiary (Have cartilage rings, seromucinous submucosal glands, SM) --> bronchioles --> terminal bronchiole --> respiratory bronchiole (bronchiole has no cartilage or SM glands, SM only) --> alveoli ducts --> alveolar sacs

1. Pseudostratified columnar ciliated with goblet cells in the trachea (also has submucosal seromucinous glands) to bronchioles 2. Ciliated columnar with increase n.o Clara cells (club cells) instead of goblet cells in the terminal and respiratory bronchioles 3. Simple squamous (type 1 pneumocytes = 40%), rounded type 2 pneumocytes (60%) and Clara cells (club cells) a. Type 1 pneumocyte flat for gas exchange. They look like there are more of them rather than 40% but they are just bigger. Very flat. b. Type 2 pneumocyte rounded for surfactant secretion. Much more cuboidal c. Clara cells non-ciliated, exocrine granultes (surfactant component + detox enzymes), stem cells

- Scattered throughout - Secrete peptide hormones such as serotonin/5HT for regulation of mm tone - Clusters = neuroepithelial bodies

Normal bronchial mucosa --> bronchial mucosa w squamous metaplasia --> dysplasia --> CIS Squamous metaplasia = because tougher from the assault. This is reversible! Dysplasia = no breach in BM

SCLC = 15% NSCLC = 85% - AC = 35-40% - SCC = 25-30% - LCC = 10-15%

CENTRAL +/- hilar nodes spread Extrathoracic dissemination later than other types M ; F Macro = pale, cream colour w central necrosis (see necrosis = SCC until proven otherwise) Micro: 1. Intracellular bridges 2. Keratinisation, keratin pearls, single cells

PERIPHERAL Slower growing, but disseminate widely and early in disease progression Most common primary tumour in F, non-smoker, pt ; 45 Macro = puckers in the pleura Micro = 1. Glands surrounded by desmoplastic strome 2. Mucin 3. Acinar, papillary and solid types on histology

CENTRAL Rapid growth, early dissemination, hilar/mediastinal LN's Presentation is usually disseminated malignancy The primary may be impossible to find. Paraneoplastic syndrome (ACTH, EPO, renin) w/out primary or primary presenting later. Derived from NE cells of the lung Macro = solid looking Micro = 1. Cells - minimal cytoplasm 2. Molding - barely any cytoplasm touching each other 3. Hyperchromatic cells 4. Salt and peper chromatin (pebbled, granular), no prominent nuclei

NSCLC = surgery (I/II), curative RT if resp reserve is poor, CTX +RT in advanced SCLC = chemo, invariably relapse

Peripheral or central Lack cytological differentiation, large cells w large nuclei. Essentially, we know it's a carcinoma, but can't tell if it's AC or SCC as too poorly differentiated to tell! Spread distal sites, early in the course = Poor prognosis Micro = 1. Undifferentied/anaplastic 2. Spindle or giant cell variants 3. Intermediate filaments

SCC - CK5/6, p53, p40 SCLC = Synaptophysin + Chromogranin AC = CK7, CK20, TTF-1, Napsin A Use additional stains to exclude AC from other sites e.g. CD20/Villin for bowel cancer

Tumor at apex involving brachial plexus. Often involves vertebra and ribs posteriorly. Often have Horner's syndrome due to involvement of stellate ganglion. Tx = pre-operative chemo/RT and enbloc resection of tumour and chest wall

- Mets - Withstanding surgery --> Advanced stage, comorbidities, patient fitness - Patients who do not have longer than 1-2 years life expectancy due to other disease - C/L LN involvement - Extensive involvement of mediastinum

1. Lobectomy - e.g. tumour in RUL 2. Pneumonectomy - e.g. central tumour, would take out whole lung 3. Segmentectomy - e.g. smaller and localised tumour 4. Sleeve resection - attempts to preserve lung. E.g. tumour in RUL but more central, rather than take out whole lobe, take out some of the bronchus and lung and then stitch end of bronchus back up 5. Wedge resection - generally not recommended as local recurrence high, just a part of the lung. Unless in really bad shape

Symptom based treatment involves: - Palliative care - Narcotics - Steroids/NSAIDS - Specific complications e.g. hypercalcaemia - Laxatives - Counselling - Advanced life directives

- RT = bronchial obstruction, SVC obstruction, haemoptysis, bone pain, cerebral mets - SVC stent + RT = SVC obstruction - Endobronchial therapy, tracheal stenting, cytotherapy, laser, brachytherapy - Pleural drainage/pleurodesis = symptomatic pleural effusions - Drugs = analgesia, steroids, antiemetics, cough linctus, bronchodilators, anti-depressants

Triage Pass onto oncologist, surgeon, radiation oncologist

- ; 40 - Never smoked - Lesion ; 2cm - Round and regular margin - Calcification - Doubling time 500 days - Cavitation - benign has thin and regular walls, malignant have thick and irregular walls