Lung Tumours 2023 Year 1 PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Lung Tumours Class Course Lecturer Date Year 1 Lung tumours Pathology Prof Paul Murray Learning Outcomes • Classify lung tumours – Benign, malignant • Discuss the aetiology of malignant lung neoplasms • Explain the dia...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Lung Tumours Class Course Lecturer Date Year 1 Lung tumours Pathology Prof Paul Murray Learning Outcomes • Classify lung tumours – Benign, malignant • Discuss the aetiology of malignant lung neoplasms • Explain the diagnostic approach to lung neoplasms • Describe the clinical, microscopic features of lung neoplasms • Explain the staging of primary lung carcinoma • Discuss the management of Lung neoplasms, including targeted therapies Classification of Lung Tumours - malignant Primary • Epithelial (>95%) • Non-epithelial Metastatic (common) • Colon • Breast • Renal cell carcinoma • Prostate • Melanoma Classification of Lung Tumours Hamartoma (commonest) Hamartoma Hamartoma Benign • Papilloma • Adenoma • Chondroma • Haemangioma Hamartoma- mixture of cartilage, fat, blood vessels, fibrous tissue and epithelium, usually incidental finding on CXR as ‘coin’ lesion • Management: Biopsy: benign, PET scan: ‘cold’ on PET Malignant Lung Tumours Primary epithelial malignancies • Non small cell carcinoma § Adenocarcinoma § Squamous cell carcinoma § Large cell carcinoma § NSCLC, NOS • Neuroendocrine carcinoma § Small cell carcinoma § Large cell neuroendocrine carcinoma § Carcinoid tumour (typical and atypical) Incidence (Ireland) • Approximately 2750 cases/year • M>F; although rising incidence in females • Lung carcinoma causes more deaths per year than any other invasive carcinoma Aetiology • Cigarette Smoking § § § 85% of lung carcinoma occurs in smokers Cigarette smoke contains 18 hydrocarbons; act as a chemical carcinogen Approx. 1 in 9 smokers will develop lung carcinoma • City Living • Other types of smoking § Tobacco use (cigar and pipe smoking), weaker risk • Industrial Exposure § § Asbestos Haematite • Radon • Other lung disease e.g. COPD, fibrotic lung disease • Genetic factors Bronchogenic carcinoma Bronchogenic carcinoma is any type or subtype of lung cancer. The term was once used to describe only certain lung cancers that began in the bronchi and bronchioles, the passageways to the lungs. However, today it refers to any type. Presentation of lung carcinoma • Depends on Site and Stage • Local • Intrathoracic • Distant metastases • Non-metastatic manifestations • Asymptomatic - chest X-ray Local effects • Mass surrounding main bronchus • Mucosa ulcerated, roughened or nodular • Cough • Haemoptysis • Pleural/mediastinal involvement § § Pneumothorax Pleural effusion • Recurrent pneumonia distal to obstructing tumour § § § § Carcinoma narrows lumen of bronchus -> obstruction -> retention of secretions -> infection -> pneumonia -> abscess formation Spread • Intrathoracic spread to hilar and mediastinal lymph nodes • Superior mediastinal obstruction Superior mediastinal obstruction, can occur in patients with lung cancer, caused by compression or invasion of the superior vena cava (SVC) with obstruction of trachea. PANCOAST Tumour - apical lung tumours • HORNER SYNDROME- due to invasion of sympathetic chain and the stellate ganglion • Miosis • Ptosis • Anhidrosis • Shoulder and arm pain and weakness and atrophy of hand muscles Horner syndrome is a relatively rare disorder characterised by a constricted pupil (miosis), drooping of the upper eyelid (ptosis), absence of sweating of the face (anhidrosis), and sinking of the eyeball into the bony cavity that protects the eye (enophthalmos). DISTANT METASTASES • Lymph nodes § Axilla, cervical, other • Bone § Pathological fracture, pain • Liver • Brain § Seizures, stroke, headache Brain metastases NON-METASTATIC SYSTEMIC MANIFESTATIONS • Cachexia - late symptom § Weight loss, anorexia • Clubbing of fingers Mechanism of clubbing in lung cancer not fully understood, but believed to be related to the release of various inflammatory mediators and growth factors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and transforming growth factor-beta (TGF-β) which increase blood flow to the fingertips You do not need this for the exam but remember Cachexia is driven by metabolic changes induced by the tumour A further non-metastatic effect is paraneoplastic syndromes • Paraneoplastic syndromes are a consequence of carcinoma, but not due to cancer mass • can be mediated through: § § § § Cross reacting antibodies Production of physiologically active factors Interference with normal metabolic pathways Idiopathic • Mostly seen in small cell lung carcinoma • Can also be seen in squamous cell carcinoma and adenocarcinoma Paraneoplastic Syndromes • Neuropathy, myopathy • Cushing Syndrome – ACTH or ACTH-like substance production (small cell carcinoma) • Hypercalcaemia – PTHRP, TGF-alpha, IL-1 (squamous cell carcinoma) • Hyponatraemia – SIADH (small cell carcinoma) • Encephalopathies • Hypertrophic osteoarthropathy (HPOA) (adenocarcinoma) • Gynaecomastia • Lambert-Eaton myasthenic syndrome - muscle weakness proximal arms and legs, difficulty climbing stairs and rising from a sitting position Lung cancer- investigations • Radiology § § § CXR CT thorax PET scan • Bloods § FBC, Calcium, LFT, U&E • Bronchoscopy § Washings/lavage/biopsy • Tissue sampling CT guided biopsy Endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA) § CT guided biopsy of a metastasis § § Adenocarcinoma • Gland forming tumour • Often peripheral lesions • Can arise as ‘scar’ carcinoma AIS • Relatively slow growing: § Atypical adenomatous hyperplasia (AAH)->adenocarcinoma in situ (AIS) -> invasive adenocarcinoma • CT correlate of AIS is ground glass opacity • IHC positive for TTF-1, napsin A Scar carcinomas are more commonly seen in individuals who have a history of pulmonary tuberculosis, but they can also be seen in those who have had prior lung surgery or radiation therapy. Squamous cell carcinoma • More common centrally (major bronchi) • Stepwise progression: Squamous metaplasia-> dysplasia -> carcinoma in situ -> invasive squamous cell carcinoma • Well/moderately/poorly differentiatedkeratin production, intercellular bridges • Necrosis and cavitation common • IHC: CK5/6 and p63 positive Squamous metaplasia is a pre-neoplastic change of the bronchial epithelium observed in the lungs in response to toxic injury induced by cigarette smoke- pseudostratified epithelium becomes squamous in phenotype Molecular targeting in lung carcinoma • Some lung carcinomas harbour mutations in oncogenes or tumour suppressor genes • Identification of specific molecular alterations and driver mutations in lung carcinomas have resulted in development of targeted therapies • They include: § EGFR § ALK § ROS-1 § RET § B-RAF Management-non-small cell carcinoma TNM staging - Tumour size, nodal involvement, distant metastases, see https://www.pathologyoutlines.com/topic/lungtumorstaging.html § Surgery § § Chemotherapy § Radiotherapy § Molecular targeted therapies § Immune checkpoint inhibitors Immunotherapy: immune checkpoint inhibitors e.g. PD-1/PD-L1 ECOG Status • Patient with lung carcinoma often have numerous comorbidities § frequently heavy smokers with severe COPD and heart disease • In addition to tumour stage, the ECOG status (ECOG 0-4) is evaluated • Pulmonary function tests are also essential prior to surgery or radiotherapy to assess lung function Eastern Cooperative Oncology Group Small cell carcinoma A. Giemsa Stain C. CD56 B. TTF1 • Small to medium sized cells • Scant cytoplasm • Necrosis and prominent mitoses • May get combined tumours: small cell carcinoma with squamous cell carcinoma or adenocarcinoma D. Chromogranin Management- Small cell carcinoma Limited vs extensive stage § Chemotherapy - Extremely chemo-sensitive; platinum and etoposide § Radiotherapy § Poor survival § § Why do you think survival is poor? Staging of non small cell carcinoma Limited stage, the cancer has only reached one area, for instance, it may be found in one lung or cells may have spread to lymph nodes in the same area of the chest In these cases, radiation is typically needed in only one area of the body. Extensive stage means the cancer has spread all over the lung and may have metastasized: •To the other lung •To lymph nodes in the opposite area of the chest •To pleural cavity or other locations e.g bones Carcinoid tumours • Neuroendocrine neoplasm • Mean age of presentation is 40 years • 2-5% of pulmonary neoplasms • Usually arise in the central, large bronchi, showing intraluminal growth • Presentation: haemoptysis (very vascular tumours), cough, recurrent pneumonia (due to proximal obstruction), asymptomatic (incidental finding on CXR) Chromogranin Positive for CD56, synaptophysin and chromogranin Carcinoid tumours • Grade depends on number of mitoses, percentage of cells in cell cycle (Ki67 immunostain) • Prognosis is excellent in typical carcinoid. Atypical carcinoid tumours have a higher mitotic rate and can be associated with lymph node metastases, but generally also have a very good prognosis • Treatment is by surgical excision • Only rarely induce carcinoid syndrome Immunohistochemistry-summary • Immunohistochemistry stains in carcinomas, squamous cell carcinoma, adenocarcinomas, positive for AE1-3, cytokeratin 7 • Squamous cell carcinoma cytokeratin 5/6 • Adenocarcinoma TTF1, Napsin A • Neuroendocrine tumours, small cell carcinoma, carcinoid chromogranin, synaptophysin, CD56 (small cell carcinoma TTF1) • Metastatic tumours – melanoma S100, Melan-A, hmb45, SOX-10 • Metastatic colorectal tumour – cytokeratin 20, CdX2 • Metastatic breast – GATA-3 oestrogen receptor • Head and neck squamous cell carcinomas, cervix squamous cell carcinomas may be P16 positive (HPV related)