Morphological variants of Lung Cancer - Squamous cell carcinoma - Adenocarcinoma - Small Lung Cell Carcinoma (SLCC) - Carcinoid airway

y cancer Stats Leading cause of death Men > women Trend is increasing in women now Peak incidence in 50s and 60s

Systemic: (paraneo symptoms) - Cachexia - Paraneoplastic syndrome - Clubbing - Pulm. Osteoarthropathy. - Bone pain - CNS dysfunction

Eitiology - Tobacco smoke mutations - Proportional to duration, amount & quality of smoking & deep inhaling. - 90% are smokers and 10% are non smokers - 20 fold risk if >40cigarettes per day - >100 fold combined with Asbestos, coal, radon, etc. Smoke carcinogens. - Initiators Benzo-pyrenes - Promoters Phenol derivatives - Radioactive substances Polonium, C14, K40 - Overall: damage p53 and KRAS etc. Overall causes: - Smoking* - Occupational exposure: - Asbestosis, Nickel, chromates, mustard gas, arsenic coal-tar distillation. - Fibrosis/scaring - TB, Pneumoconiosis, honeycomb lung Ad.ca. - Radioactive gases - Radon, Atomic bomb survivors. Clinical Features: - Weight loss Cytokines.. IL6, IL8, PIF. - Cough Bronchus, obstruction, necrosis. - Haemoptysis Invasion, less stroma, necrosis. Complications Local: - Obstruction - Effusion - Pneumonia* lipid, other. - Bronchiectasis - Atelectasis lung collapse - Haemoptysis - COPD (risk) Bronchogeni c Ca (95%) Small cell ca. SCC 15-20% (oat cell ca) Non Small cell NSCC 80% Squamous cell carcinoma 20-30% Adeno carcinoma (+Broncho-alveolar) 30-40% Large cell anaplastic carcinoma (rare) Bronchial Carcinoid Tumor (5%) Miscellaneous Tumors Metastatis Tumors of Pleura (angio(sarco)ma, fibro(sarco)ma, etc) (<1%) (more common than primary) Benign Rare Mesothelioma asbestosis * but can be idiopathic Mediastinal Tumours Thymic & other Lymphoma, Teratoma.

Adenoma Hamartoma

Investigations - Imaging X-Ray, US, MRI, CT, PET - Cytology sputum, Bronchial lavage - Bronchoscopy - Biopsy Needle, excision - Tumor markers. - Staging investigations: History, exam & CT scan chest & Pathogenesis abdomen Irritation Carcinogens Initiation Promotion Ca. Complete blood count & differential Serum chemistry Liver, Kidney, Electro. & Ca+ K-Ras Pulm.FT & Mediastinoscopy for C-myc surgery. p53 PET Scan. SCC - early spread - NO surgery - Responds to chemo NSCC - Late spread localized - Staging & Surgery - OK - Does not respond to chemo.

Multiple Mutations..oncogene activation cancer.

Cdewqd

Metaplasia Dysplasia Neoplasia

Cilia Goblet cell Nucleus Loss of Cilia & Columnar cells Cell death. Stratified Squamous Epithelium (metaplasia)

Normal Hyperplasia Metaplasia Dysplasia Mild Severe Dysplasia Malignancy

Adenocarcinoma peripheral (unlike squamous) Squamous Cell Carcinoma (NSCC) - M>W - Highly associated with smoking - Most arise near the hilum, and big bronchi (CENTRAL) LARGE AIRWAYS Micro - Dysplasia and carcinoma in situ - Thickening and irregularity of the bronchial mucosa may be seen with a bronchoscope - Prominent keratin production and intercellular bridges Macro - Often have prominent necrosis and may cavitate - Tend to spread locally and metastasize later than other patterns

Lung cancer AP view

Lung cancer Lateral view CT squamous cell carcinoma (NSCC bronchogenic) central location

Central near hilum + cavitate

u rs l oke Sm
gi Clear Mar n

ng

Origin in main bronchus

Spread

IF PINK SQUAMOUS CELL KERATIN!!!

Note: pink (keratinized) cancer cells (dysplastic)

CYTOLOGY (above) rest = microscopy

Keratin pearls large nests of Keratin

Cavitation in squamous cell carcinoma

Microscopy

Peripheral Adeno

Adenocarcinoma - Less associated with smoking than squamous or small cell carcinomas, but most - 75% patients have a history of smoking - Most common type of lung cancer in women and nonsmokers! Gross - Peripherally located; may be associated with a scar Micro - Gland formation mucus - more well differentiated - Columnar or cuboidal cells with pleomorphic nuclei, often large nucleoli - 80% contain mucin (MUCUS) Cytology - Round/ oval/cuboidal cells - Blue! - Prominent nuclei Examin with needle biopsy as in periphery of lung! SMALL AIRWAYS

Peripheral adeno a non-smoker woman!

Peripheral adenocarcinoma

Cytology

Cuboidal cells Glandular shapes/ formation BLUE! colour

Glandular, cuboildal, mucus Bronchoalveolar - A subtype of adenocarcinoma - peripherally located - arise in terminal bronchioles or alveoli - Show appearance on CXR like pneumonia extensive invasion of lung - Any age, both sexes equally. Morphology: - Multiple diffuse nodules more like pneumonia - Columnar-to-cuboidal epithelial cells that line up along alveolar septa without destruction. - tall columnar to cuboidal epithelial cells (differentiation along lines of mucinsecreting bronchiolar cells, Clara cells, and/or type II pneumocytes) - Malignant cells grow along septal wall of alveoli without invading them Clinical - Cough, hemoptysis, and pain, but atelectasis and emphysema are infrequent. - Metastases are not widely disseminated and do not occur early;

Glands Lumen filled with mucin Vacuolated

Overall survival rate is approximately 25%.

Note: - Adenocarcinoma can progress to this - Cancer cells IN the alveoli (the cells that line up along alveolar) - Show bronchopneumonia like diffuse consolidation (NOT the tumour but the inflammatory response causes this)

The tumor cells diffusely infiltrate the alveolar spaces mimicking a pneumonic process

Malignant cells grow along alveolar septum without disturbing it

Atypical adenomatous hyperplasia (AAH): o A form of Adenocarcinoma o Cytologic atypia is less marked o Typically <1 cm - Look like bronchoalveolar but smaller (AAH is 5mm)
Large Cell Carcinoma - Poorly differentiated/ undifferentiated squamous cell or Adenocarcinoma - usually central - highly aggressive and destructive lesions with necrosis and hemorrhage - histologically there is gross nuclear pleomorphism with numerous bizarre mitoses. - No squamous or glandular differentiation is seen in light micrsocopy although such evidence is often found ultra-structurally Many differential possible Could be a spreading adenocarcinoma (peripheral) or a squamous cell carcinoma OVERALL: LARGE, AGGRESSIVE, CENTRAL, UNDIFFERNTIATED

Bronchogenic Cancer - Can be Adeno, Squamous, Large cell cancers

Bronchogenic cancer SCC Arising from major bronchus infiltration

Bronchogenic Mesothelioma (pleural)

Small Cell Lung Carcinoma (SCLC) - >95% smokers - centrally located masses near hilum - invade/extension into the lung parenchyma early spread to hilar and medistinal lymph nodes - Aggressive and invasive metastatis widespread Paraneoplastic syndrome - These tumors are derived from neuroendocrine cells of the lung = they express a variety of neuroendocrine markers - SLCC secrete neuroendocrinal paraneoplastic syndromes Macroscopic - LARGE central airways - 70% of cases present as perihilar mass - Extensive lymph node metastases are common - Typically peribronchial; endobronchial lesions are uncommon - neuroendocrine differentiation Microscopic - SMALL cells - Round to fusiform shape (look like lymphocytes) reduced cytoplasm + large relative hyperchromatic neuclei (nuclei>cytoplasm) - Salt/ pepper granulated chromatin - nuclear molding; faint or absent nucleoli; scant cytoplasm - Extensive necrosis Three histologic categories: o Small cell o Mixed small cell/large cell o Combined small cell/adeno- or squamous cell Carcinoma

SCLC affecting the hilar lymph nodes + bronchus

Infiltration pattern around major 1 bronchus - Irregular border - Spread along bronchus lymph nodes

Infiltration pattern around bronchus Note: black spots in lung = smokers lung

SCC some bronchiactiac changes

Oat cells SCC - BAL bronchio-alveolar lavage fluid. - Gets sample of cells with brush during bronchoscopy and stained for visualization - Small Cell Barely any cytoplasm and mostly purple nucleus (cells are bigger than lymphocytes)

Large nuclei

Large nuclei compared to cytoplasm Round small cells Cytology

Looks like inflammatory cells Carcinoid Tumours

Overview

Slow growing, malignant tumour of from cells of the neuroendocrine system. 1% to 5% of all lung tumors Mainly occur in individuals <40 years of age. No relation to smoking

Overall, most bronchial carcinoids dont have secretory activity and dont metastasize to distant sites but follow a relatively benign course for long periods and are therefore amenable to resection.

Morphology - Small (<4cm) in diameter - Grow as finger like or spherical polypoid masses that commonly project into the lumen of the bronchus - Usually covered by an intact mucosa. - Confined to the main stem bronchi. Pathogenesis - Arise from neuroendocrine cells = hormone secretion mainly serotonin = carcinoid syndrome

Diagnosis - Ultrasound examination confirms the presence of liver secondary deposits

Bronchial Carcinoid Tumour:

Clinical Features - The clinical manifestations emanate from their intraluminal growth, their capacity to metastasize and the ability of some of the lesions to elaborate vasoactive amines. - Respiratory signs persistent cough, hemoptysis, impairment of drainage or respiratory passages with secondary infections, bronchiectasis, emphysema, atelactasis. - Carcinoid syndrome although rare, some functioning lesions are capable of producing a range of hormones, including serotonin causing an attack of carcinoid syndrome; characterized by intermittent attacks of diarrhoea, flushing and cyanosis. - Cardiac abnormalities are found in 50% of patients and consist of pulmonary stenosis or tricuspid incompetence. It occurs in 5% of patients with carcinoid tumours and only when there is liver metastases.

Note: Benign gross appearance. Round cell clusters. (Neuroendocrine cells)

and the major metabolite of serotonin, is found in high concentrations in the urine.

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