Lung tumors & pleural lesions Ali Al Khader, M.D. Faculty of Medicine Al-Balqa’ Applied University Email: ali.alkhader@bau.edu.jo

A brief introduction 95% of lung tumors are carcinomas Among the remaining 5%, we will discuss: -Hamartoma …the most common benign lung tumor …spherical, “coin lesion” on x-rays …small (1-4cm) …consists mainly of mature cartilage admixed with fat, fibrous tissue, and blood vessels in various proportions -Carcinoid…a semi-benign/semi-malignant tumor…considered as malignant

Carcinomas, overview The most common cause of cancer death in men & women Decreasing among men and increasing among women Peak incidence: 50s & 60s Prognosis is bad in general…even if localized in the lung, the 5-year survival rate is near 45%

Lung cancer, 4 major histologic types Previously: Small cell lung cancer (SCLC) …aggressive, metastasis common since diagnosis with median survival of 1 year …much mitotic and apoptotic activity, necrosis, crushing artifacts and Azzopardi effect …always needs chemotherapy 1- Small cell carcinoma 2- Adenocarcinoma 3- Squamous cell carcinoma 4- Large cell carcinoma …others, some are “mixed” Previously: Non-small cell lung cancer (NSCLC) Note: Small cell carcinoma & carcinoid are both considered “neuroendocrine tumors”

The most common primary lung tumor in USA now is: Adenocarcinoma (replaced squamous cell carcinoma because smoking in comparison to the past) Smoking Small and squamous cell carcinomas have the strongest association with smoking …but smoking is also a risk for adenocarcinoma Adenocarcinomas are the most common primary tumors arising in: -women -never-smokers -individuals younger than 45 years of age 90% of lung cancers occurs in smokers or who stopped recently Women are more susceptibile to carcinogens in tobacco smoke than men Cessation of smoking decreases the risk…but never to baseline Also passive smokers, pipes, and cigars…lesser risk

Molecular pathogenesis of lung cancer Abnormalities in tumor suppressors on the short arm of chromosome 3…an early event TP53 tumor suppressor gene mutations and KRAS oncogene mutations…later Changes accumulate in smokers in a stepwise fashion and in large areas (field effect) forming a fertile soil for cancer to occur A subset of adenocarcinomas (10% in whites & 30% in Asians) harbor EGFR mutations…a receptor tyrosine kinase (oncogene)…targeted therapy KRAS is downstream of EGFR and their mutations are mutually exclusive (do not occur at the same time) Other tyrosine kinases that may be mutated in adenocarcinoma and can respond to their specific targeted therapies: ALK, ROS1, HER2, c-MET …the concept of “personalized lung cancer therapy”: molecular pathogenesis guides the treatment

Important event sequences Atypical adenomatous hyperplasia adenocarcinoma in situ invasive adenocarcinoma …this is proposed for some adenocarcinomas Squamous metaplasia squamous dysplasia squamous cell carcinoma in situ invasive squamous cell carcinoma These precursor lesion may last for many years

Other environmental & occupational risk factors Uranium Asbestos (alone: 5-fold increased risk, with smoking: 55-fold) Chromium Arsenic Nickel Vinyl chloride

Morphology of lung cancer Adenocarcinoma…peripherally more Squamous cell and small cell carcinomas…centrally more (in major bronchi) Adenocarcinoma…may be glandular (acinar), papillary, mucinous or solid Adenocarcinoma in situ…previously called: bronchioalveolar carcinoma …characteristic growth along preexisting alveolar septa, without invasion

TTF-1 (thyroid transcription factor 1)…especially positive in lung Adenocarcinoma and small cell carcinoma Adenocarcinoma in situ Adenocarcinoma…gland-forming

Squamous cell carcinoma, some notes Necrosis with cavitation is more common Metastasis outside thorax is slower than others Earlier precursor events can be detected as abnormal cells in cytopathologic examination of sputum or bronchoalveolar lavage Variable morphology (from well differentiated (much more keratin) to poorly differentiated)

Some clinical presentations Involvement of left supraclavicular lymph node = Virchow node Compression of superior vena cava with venous congestion of the face…Vena caval syndrome Apical tumors if compressing sympathetic plexus…Horner syndrome? …these apical neoplasms are called: Pancoast tumors

Paraneoplastic syndromes of lung cancer In 3-10% of cases Mainly: 1-Hypercalcemia (parathyroid hormone-related peptide)…squamous cell carcinoma 2-Cushing syndrome (ACTH)…small cell carcinoma…also carcinoid 3-SIADH (syndrome of inappropriate ADH secretion)…small cell carcinoma 4-Neuromuscular syndromes…small cell carcinoma 5-Clubbing of fingers and pulmonary osteoarthropathy 6-Coagulation abnormalities (migratory thrombophlebitis, DIC) 7-Carcinoid syndrome…carcinoid tumor…also small cell carcinoma

Carcinoid tumors Mainly intrabronchial growth, well-circumscribed The cells contain neurosecretory granules (features of neuroendocrine tumors) It is better to consider them as: low-grade neuroendocrine carcinomas (malignant) May rarely secrete hormonally active polypeptides…carcinoid syndrome Classified as typical (indolent) and atypical (worse) Resectable and curable Young adults (mean 40 years) Sometimes as part of MEN syndrome 5-15% metastasize to hilar lymph nodes, but distal metastasis is rare

Carcinoid tumors, morphology Typical carcinoid: nests of uniform cells that have regular round nuclei with “salt-and-pepper” chromatin, absent or rare mitoses and little pleomorphism Atypical carcinoid: necrosis and more mitoses

Carcinoid tumors, clinical notes Symptoms related to bronchial location (cough, hemoptysis, obstruction & infection) Peripheral carcinoids are often asymptomatic and discovered incidentally Rarely: carcinoid syndrome (intermittent attacks of diarrhea, flushing and cyanosis) The reported 5- and 10-year survival rates for typical carcinoids are above 85%, while these rates drop to 56% and 35%, respectively, for atypical carcinoids

Metastases to the lung Any pattern of growth …but remember that multiplicity is more with metastatic than primary (not always)

A brief note on malignant mesothelioma of the pleura A rare cancer of mesothelial cells, usually arising in the parietal or visceral pleura; it also occurs much less commonly in the peritoneum and pericardium 80% to 90% of individuals with this cancer have a history of exposure to asbestos (shipyard workers, miners, insulators) The latent period for developing malignant mesothelioma after the initial exposure is long, often 25 to 40 years The combination of cigarette smoking and asbestos exposure greatly increases the risk for developing lung carcinoma, but it does not increase the risk for developing malignant mesothelioma The lifetime risk after exposure does not diminish over time (unlike with smoking, in which the risk decreases after cessation) BAP1 mutations are common (a tumor suppressor gene important for DNA repair)

Pleural effusions Transudates or exudates…transudate = hydrothorax The most common cause of bilateral hydrothorax is: Congestive heart failure An exudate, characterized by protein content greater than 30 g/L and, often, inflammatory cells, suggests pleuritis The four principal causes of pleural exudate formation are: infection (suppurative pleuritis or empyema)-cancer (commonly hemorrhagic)- pulmonary infarction-viral pleuritic …others: connective tissue diseases and uremia

Pneumothorax Simple/spontaneous…without known lung disease…young healthy men Secondary…with known thoracic or lung disorder

Other pleural fluid accumulations

Thank You