lung+tumourssh25.pdf

Lung Tumours: BCR Lecture 57 DT Mc Manus [email protected] he/him Internal Medicine Examines Neck Veins Lung Tumours LEARNING OBJECTIVES: To use the specific example of lung tumours to illustrate the general properties of benign and malignant tumours includin...

Lung Tumours: BCR Lecture 57 DT Mc Manus [email protected] he/him Internal Medicine Examines Neck Veins Lung Tumours LEARNING OBJECTIVES: To use the specific example of lung tumours to illustrate the general properties of benign and malignant tumours including invasion and metastasis Classify lung tumours as benign/malignant; primary/secondary and list common tumours that can metastasise to the lungs Explain how primary lung carcinomas are classified and outline their histogenesis List complications of lung tumours resulting from invasion of local structures, integrating with current anatomy teaching List common anatomical sites that lung cancers metastasise to and outline the TNM staging system Explain what is meant by paraneoplastic syndrome. Give examples of paraneoplastic syndromes specific to lung cancer Define malignant mesothelioma and recognise the significance of its association with asbestos exposure Explain why a molecular pathology classification of lung cancer may yet replace existing histopathological classification systems  MLA....and progress testing Presentations Conditions mla-content-map-_pdf-85707770.pdf (gmc-uk.org) Clinical Research and Scholarship: Pathology of Diabetes and Endocrine Pathology: Year 2 lecture Lung Tumours LEARNING OBJECTIVES: Classify lung tumours as benign/malignant; primary/secondary and list common tumours that can metastasise to the lungs Explain how primary lung carcinomas are classified and outline their histogenesis List complications of lung tumours resulting from invasion of local structures, integrating with current anatomy teaching List common anatomical sites that lung cancers metastasise to and outline the TNM staging system Explain what is meant by paraneoplastic syndrome. Give examples of paraneoplastic syndromes specific to lung cancer Define malignant mesothelioma and recognise the significance of its association with asbestos exposure Explain why a molecular pathology classification of lung cancer may yet replace existing histopathological classification systems Classification of lung tumours Primary (benign) lung tumours: Metastases to lungs pulmonary hamartoma/chondroma As common or indeed more common than primary malignant lung tumours Primary ( malignant ) lung tumours: Multiple bilateral tumours (pulmonary carcinoid) ( indolent Haematogenous spread can give large impressive low grade malignant) cannonball tumours from sarcomas, melanomas, Bronchogenic carcinoma malignant testicular germ cell tumours and carcinomas like renal cell carcinoma Malignant mesothelioma Lymphatic spread can result in a more diffuse pattern Malignant Lymphoma of involvement: Lymphangitis carcinomatosa eg Certain types of soft tissue spread from breast carcinoma (mesenchymal) sarcoma Malignant pleural effusions  Case courtesy of Jeremy Jones Pulmonary metastases | Radiology Reference Article | Multiple variably-sized tan rounded masses are Radiopaedia.org seen in all lung fields. These are characteristic for This chest radiograph demonstrates a nodular metastatic carcinoma. pattern resulting from multiple small metastases to the lung from a breast adenocarcinoma Metastases to Lungs Commonest malignancies to Primaries that most frequently present with pulmonary metastasise to lungs: metastases: Choriocarcinoma Lung Cancer Ewings sarcoma Colorectal cancer Malignant melanoma Renal cell carcinoma Osteogenic sarcoma Pancreatic carcinoma Testicular germ cell tumours Breast Carcinoma Thyroid carcinoma Pancreatic carcinoma Pulmonary Chondroma/Hamartoma https://webpath.med.utah.edu/LUNGHTML/LUNG077. html Hamartoma Disordered proliferation of mature cartilage, fat, smooth muscle with entrapped respiratory epithelial lined clefts Males > Females Central>peripheral Solitary Example of hamartoma Lung Tumours LEARNING OBJECTIVES: Classify lung tumours as benign/malignant; primary/secondary and list common tumours that can metastasise to the lungs Explain how primary lung carcinomas are classified and outline their histogenesis List complications of lung tumours resulting from invasion of local structures, integrating with current anatomy teaching List common anatomical sites that lung cancers metastasise to and outline the TNM staging system Explain what is meant by paraneoplastic syndrome. Give examples of paraneoplastic syndromes specific to lung cancer Define malignant mesothelioma and recognise the significance of its association with asbestos exposure Explain why a molecular pathology classification of lung cancer may yet replace existing histopathological classification systems Classification of primary lung carcinoma Classified on the basis of histology ( currently!) Squamous Carcinoma ( 20-30 %) Adenocarcinoma ( 30-40 %) Large cell ( undifferentiated carcinoma) (10-15%) Sometimes the above 3 are classified together as “Non-small cell carcinoma” Small cell carcinoma ( 15-20%) Histological classification of primary lung carcinoma Squamous Adenocarcinoma: Carcinoma: keratin gland forming: pearls and Moderate intercellular differentiation. bridges Small cell carcinoma: very malignant tumour Large cell characterised by (undifferentiated) high proliferation Carcinoma: fraction and anaplastic/poorly increased apoptosis differentiated; and neuroendocrine high grade diferentiation. Underwood’s Pathology: a clinical approach Fig 14.28 Pathogenesis Cigarette smoking and other causes of repeated injury to bronchial epithelium ( eg bronchiectasis) are associated with metaplasia: a permanent change from a respiratory ciliated bronchial epithelial lining to an abnormal squamous epithelium Dysplastic change may supervene with progression to carcinoma in situ and eventually invasive squamous carcinoma, often centrally situated, close to hilum of the lung Adenocarcinomas often develop more peripherally, associated with areas of fibrous scarring and the precursor lesion is thought to be atypical adenomatous hyperplasia  Classification of primary lung carcinoma Central (Hilar) tumour: most often Peripheral tumour: most often squamous cell carcinoma adenocarcinoma Tissue Diagnosis: Bronchoscopy with Tissue Diagnosis: cytology and CT guided core bronchial biopsy biopsy Underwood’s Pathology: a clinical approach Fig 14.26 & 14.27 rg.346140178 (rsna.org) Small Cell Carcinoma Lung Tumours LEARNING OBJECTIVES: Classify lung tumours as benign/malignant; primary/secondary Explain how primary lung carcinomas are classified and outline their histogenesis List complications of lung tumours resulting from invasion of local structures, integrating with current anatomy teaching List common anatomical sites that lung cancers metastasise to and outline the TNM staging system Explain what is meant by paraneoplastic syndrome. Give examples of paraneoplastic syndromes specific to lung cancer Define malignant mesothelioma and recognise the significance of its association with asbestos exposure Explain why a molecular pathology classification of lung cancer may yet replace existing histopathological classification systems Hilar Surfaces /Anatomical relations Paquette CM. Published Online: May 05, 2012 https://doi.org/10.1148/rg.323115129  Mass Effect Collapse of Lung distal to tumour: Local Effects: atelectasis, infection Ulceration of pulmonary artery or Ulceration veins/branches: haemoptysis Superior vena cava: fixed elevated JVP Recurrent laryngeal nerve: hoarseness Invasion of local Phrenic nerve: elevation of anatomical structures hemidiaphragm Pericardium: malignant pericardial effusion; atrial fibrillation and other arrythmias Pleura: Malignant pleural effusion Invasion of carina, oesophagus and vertebra Pancoast Tumour The growing tumour can cause compression of the superior vena cava resulting in a fixed raised jugular venous pressure Compression/infiltration of the sympathetic /stellate ganglion can result in Horner’s syndrome: miosis, ptosis and anhidrosis www.radiopedia.org Lung Tumours LEARNING OBJECTIVES: Classify lung tumours as benign/malignant; primary/secondary Explain how primary lung carcinomas are classified and outline their histogenesis List complications of lung tumours resulting from invasion of local structures, integrating with current anatomy teaching List common anatomical sites that lung cancers metastasise to and outline the TNM staging system Explain what is meant by paraneoplastic syndrome. Give examples of paraneoplastic syndromes specific to lung cancer Define malignant mesothelioma and recognise the significance of its association with asbestos exposure Explain why a molecular pathology classification of lung cancer may yet replace existing histopathological classification systems  TNM System adopted for most malignant tumours Staging is informed by clinical examination and radiological investigations: clinical Stage Lung Staging is also informed by pathological examination of specimens: p prefix used Cancer Staging Adapted from: https://www.scientificanimations.com Underwood’s Pathology: a clinical approach Fig 10.34 TNM 8: Lung Cancer Dataset: Royal College of Pathologists Metastatic Lung Carcinoma: Sometimes described as Stage IV disease Not curable by conventional treatments Lung cancer can spread to other lung, pleural cavity, liver, bones , brain……. And the adrenal glands?!  Clinical Effects of Malignant Lung Tumours Underwood’s Pathology: a clinical approach Fig 14.25 Persistent cough Weight loss /cachexia Haemoptysis Fatigue Dyspnoea Finger clubbing Pleuritic Chest pain Clinical Indications of locally irresectable/incurable lung cancer Clinical Finding Pathological Implications LOCAL OPERABILITY Horner’s syndrome Involvement of upper sympathetic chain Hoarseness Involvement of left recurrent laryngeal nerve Upper body venous congestion/fixed Involvement of superior vena cava elevated JVP DISSEMINATED/METASTATIC DISEASE Scalene lymph node enlargement Nodal spread outside operative field Hepatomegaly Hepatic metastases Focal bone pain Bone metastases Skin deposits Cutaneous metastases Headache/behavioural/balance Cerebral/cerebellar metastases disturbance Adapted from Table 22.3 Cardiothoracic Surgery Principles and Practice of Surgery 6th ED Lung Tumours LEARNING OBJECTIVES: Classify lung tumours as benign/malignant; primary/secondary Explain how primary lung carcinomas are classified and outline their histogenesis List complications of lung tumours resulting from invasion of local structures, integrating with current anatomy teaching List common anatomical sites that lung cancers metastasise to and outline the TNM staging system Explain what is meant by paraneoplastic syndrome. Give examples of paraneoplastic syndromes specific to lung cancer Define malignant mesothelioma and recognise the significance of its association with asbestos exposure Explain why a molecular pathology classification of lung cancer may yet replace existing histopathological classification systems  Paraneoplastic Syndromes Syndromes not explained by local effect or metastases or by production of hormones indigenous to the tissue from which the tumour arose. Occur in about 10% of patients with malignancy.  Paraneoplastic Syndromes Arise from tumour secretion of hormones, peptides, or cytokines or from immune cross-reactivity between malignant and normal tissues. Most commonly associated malignancies include Small cell lung cancer Breast cancer Gynaecological tumours Haematological malignancies Recognition of these syndromes may permit diagnosis of cancer in patients with confusing mixture of symptoms and signs  Examples of Paraneoplastic Syndromes Neurologic Paraneoplastic syndromes Eaton-Lambert syndrome: immune mediated myasthenia-like syndrome Endocrine Paraneoplastic syndromes Cushing's syndrome Musculoskeletal Hypertrophic osteoarthropathy Other Paraneoplastic Syndrome Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH),  Cushing Syndrome Approximately 5% - 10% of cases of Cushing syndrome are paraneoplastic. Approximately 50% - 60% of these paraneoplastic cases are lung tumours (Small cell lung cancer and bronchial carcinoids). Patients often present with symptoms of paraneoplastic Cushing syndrome before a cancer diagnosis is made. More information on this in Year 2: Pathology of Diabetes and Endocrine System  Hypertrophic Osteoarthropathy Prominent with certain lung cancers Manifests as 1. painful swelling of the joints (knees, ankles, wrists, elbows, metacarpophalangeal joints) 2. Finger-clubbing. SIADH The Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH), Hypo-osmotic, euvolemic hyponatremia (Decreased sodium levels ), Affects 1%-2% of all patients with cancer. Small cell lung cancer -approximately 10% to 45% of all patients with small cell lung cancer develop SIADH. Arises from tumour cell production of antidiuretic hormone (ADH) and atrial natriuretic peptide. Hypercalcaemia Occurs in up to 30% of patients Humoral hypercalcaemia: with malignancy PTHrP mediated hypercalcaemia: approx In severe cases associated with 80% severe neurocognitive Commonly associated with squamous cell dysfunction, volume depletion carcinoma of the head and neck, and renal insufficiency/failure oesophagus or lung Commonest associated Local osteolytic hypercalcaemia: malignancies: lung, multiple extensive boney metastases myeloma and renal carcinoma esp mutiple myeloma , breast cancer; Cancer-Related Hypercalcemia | JCO Oncology Practice (ascopubs.org) release of cytokines from tumours Lung Tumours LEARNING OBJECTIVES: Classify lung tumours as benign/malignant; primary/secondary and list common tumours that can metastasise to the lungs Explain how primary lung carcinomas are classified and outline their histogenesis List complications of lung tumours resulting from invasion of local structures, integrating with current anatomy teaching List common anatomical sites that lung cancers metastasise to and outline the TNM staging system Explain what is meant by paraneoplastic syndrome. Give examples of paraneoplastic syndromes specific to lung cancer Define malignant mesothelioma and recognise the significance of its association with asbestos exposure Explain why a molecular pathology classification of lung cancer may yet replace existing histopathological classification systems  Malignant Mesothelioma Malignant tumour arising from mesothelial lining cells of pleura Strongly associated with exposure to asbestos; may see calcified pleural plaques on Cxr or CT Most commonly shipyard workers, electricians , plumbers Notifiable to coroner: Coroners autopsy required in all cases to confirm cause of death/diagnosis Civil litigation very common Fig 14.30: Underwood’s Pathology: a systemic approach https://webpath.med.utah.edu/LUNGHTML/ LUNG082.html Lung Tumours LEARNING OBJECTIVES: Classify lung tumours as benign/malignant; primary/secondary and list common tumours that can metastasise to the lungs Explain how primary lung carcinomas are classified and outline their histogenesis List complications of lung tumours resulting from invasion of local structures, integrating with current anatomy teaching List common anatomical sites that lung cancers metastasise to and outline the TNM staging system Explain what is meant by paraneoplastic syndrome. Give examples of paraneoplastic syndromes specific to lung cancer Define malignant mesothelioma and recognise the significance of its association with asbestos exposure Explain why a molecular pathology classification of lung cancer may yet replace existing histopathological classification systems  Conventional treatments for cancer and non-small cell lung carcinoma include surgery, radiotherapy and chemotherapy Small cell carcinoma generally not treated by surgery because of high rates of metastasis: classification of non-small cell carcinoma vs small cell carcinoma Prognosis very poor in all lung cancer histological types and patients often poor performance status ( co-morbidity: COPD) may not be suitable candidates for radical surgery or systemic cytotoxic chemotherapies This has driven development and adoption of innovative targeted treatments jptm-2017-04-10f2.gif (608×371) (jpatholtm.org) Lung Tumours LEARNING OBJECTIVES: Classify lung tumours as benign/malignant; primary/secondary and list common tumours that can metastasise to the lungs Explain how primary lung carcinomas are classified and outline their histogenesis List complications of lung tumours resulting from invasion of local structures, integrating with current anatomy teaching List common anatomical sites that lung cancers metastasise to and outline the TNM staging system Explain what is meant by paraneoplastic syndrome. Give examples of paraneoplastic syndromes specific to lung cancer Define malignant mesothelioma and recognise the significance of its association with asbestos exposure Explain why a molecular pathology classification of lung cancer may yet replace existing histopathological classification systems  Anaplastic: poorly differentiated or no discernible differentiation Atelectasis: collapse of part of the lung Cushing's syndrome: Clinical syndrome caused by excess cortisol secondary to excess ACTH production or exogenous steroid treatment or overproduction of cortisol because of adrenal disease ( Cushing's disease) Cachexia: weight loss and muscle wasting secondary to cancer or other serious chronic diseases Dyspnoea: air hunger/shortness of breath Glossary Haemoptysis: blood in sputum Horner's syndrome: ptosis ( drooping of eyelid) miosis ( constricted pupil) anhidrosis ( lack of sweating) due to interruption of sympathetic innervation Hyponatraemia: Low serum sodium Hypercalcaemia: High serum calcium