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SDL 9 Lung Cancer One of the most common cancers affecting humans; most related to tobacco smoking Lung cancer is the leading cause of death due to cancer in both men and women Lung cancer terminology encompasses bronchogenic carcinoma including non-small cell carcinomas and small cell carcinomas Promising new screening methodologies and targeted therapies will likely improve these statistics General signs & Sx: o Hemotptysis o Weight loss o Fatigue o Cough o Hoarseness o Pain Risk factors: o Tobacco smoking o Exposure to radiation (e.g., Radon) o Genetic risks o One does not have to be a tobacco smoker to develop primarylung cancer. o MOST COMMON type of lung cancer is metastatic cancer from other anatomic locations. Carcinogens/toxins in tobacco smoke: acetaldehyde, acrylonitrile, arsenic, benzene, formaldehyde, furan, hydrazine, lead, polonium-210, vinyl chloride, nitromethane, isoprene Radiology in Dx: o Chest x-ray is the starting place o Abnormal areas identified on plan x-ray of chest will likely be followed by compute tomography scanning (CT) which is more helpful in identifying anatomic extent of disease; LN involvement o CT guided needle biopsy of suspicious area helptul in definitive Dx. Other Means of Dx: o Bronchoscopy & biopsy lesion with or near bronchial tree o Bronchial lavage & sputum analysis by cytology Old Means of Dx: o In the past: surgical biopsy with mediastinoscopy for lung cancer staging significant morbidity/mortality o Today, diagnosis may be established in a less invasive way with endobronchial U/S (EBUD) by either a specifically trained pulmonologist Can sample tumor w/in or near bronchial tree LN stations may be sampled to stage the patient Pathologist is on-site at procedure to interpret cytologic preparations to help guide collection of samples and ensure adequate material for molecular pathology Next step after Dx: PET (positron emission tomography) scanning may be performed to help highlight metabolically active tumor metastases Head CT to rule out brain/CNS metastases and initial work-up for staging Pathology Classification: Old classification: non-small cell carcinoma and small cell carcinoma (primary bronchogenic) Today: must discriminate between types of primary lung cancer Primary Tumors: o Small cell carcinoma (neuroendocrine carcinoma) Large cell neuroendocrine carcinoma o Non-small cell carcinoma Adenocarcinoma Squamous cell carcinoma Large cell carcinoma o Other types of lung tumors Carcinoid tumor (well-differentiated neuroendocrine carcinoma) Sarcomas Pleural mesothelioma Incidence in U.S.: o 40% - Adenocarcinoma o 30% - Squamous cell carcinoma o 15% - Large cell carcinoma o 15% - Small cell carcinoma Metastatic Lung tumors o Carcinomas: breast, liver, colon, etc o Malignant melanoma o Sarcoma ADENOCARCINOMA Carcinoma composed of malignant glands; tends to be more peripheral in lung (e.g., subpleural scar carcinoma) Precursor lesion: AAH (atypical adenomatous hyperplasia) Non-invasive types: bronchioloalveolar cell carcinoma (BAC) or adenocarcinoma in-situ Adenocarcinoma A) Atypical adenomatous hyperplasia B) Bronchioalveolar cell carcinoma; adenocarcinoma in-situ Adenocarcinoma progression o Histologically normal → Paraneoplastic → Preinvasive → Invasive → Metastatic (squamous cell carcinoma) EGF-R mutations and Alk gene rearrangement are rarely identified in these tumors Overexpression of the EGF-R as assessed by immunohistochemistry can be used as a therapeutic agent (Adenocarcinoma on bronchial brushing or lavage) Molecular pathology testing - targeted therapy o Pts w/EGF-R (epidermal growth factor receptor) mutations tend to have longer disease free progression and survival than those w/out them o Pts may be eligible for small Tyr kinase inhibitors (e.g., geftinib) which block EGF-R signal transduction o Pts who harbor mutations tend to be never-smokers, women & of Asian decent Alk Gene rearrangement o Pts w/Alk gene rearrangement were documented to have dramatic response to drug Crizotinib o Testing for Alk gene rearrangement is by FISH o Pts w/Alk gene rearrangement tend to be neversmokers LARGE CELL CARCINOMA Poorly differeniated carcinoma composed of malignant tumor cells w/out features of either adenocarcinoma or squamous cell carcinoma (large cell carcinoma) SMALL CELL CARCINOMA Aka small cell (undifferentiated) neuroendocrine carcinomas Tumor tents to be located in central location Precursor lesion thought to be atypical with LN or distant metastases at the time of Dx Unlike non-small cell carcinoma, surgical intervention is typically not a Tx (FISH) SQUAMOUS CELL CARCINOMA Malignant tumor of lug - tends to be in central location Precursor lesions: squamous metaplasia → dysplasia Important to document squamous characteristice because pts w/squamous lung carcinoma are not eligible for Tx w/bevacuzimab (Avastin), an inhibitor of VEGF involved in angiogenesis in tumors (risk of pulmonary hemorrhage) (Small cell carcinoma as it may appear on bronchial brushing or lavage) Pts w/small cell carcinoma typically do not harbor specific therapeutically exploitable genetic abnormalities Pts typically have an initial dramatic response to systemic chemotherapy which often includes platinumcontaining compounds (e.g., cisplatin, oxaliplatin) PLEURAL MESOTHELIOMA Exposure to asbestos (primarily amphibole type asbestos: crocidolite and amosite) Pleural based malignancy Few good Tx and very poor prognosis Encases the lung - metastatic deposits MOST COMMON histology is epitheloid histology (others include sarcomatoid and biphasic types) Big medico-legal issues: careful documentation and establishing the diagnosis beyond any doubt - expert consultation Asbestos bodies Asbestos Mineral & EM Other pulmonary tumors o Carcinoid tumor (well-differentiated neuroendocrine carinoma) o Soft tissue tumors (solitary fibrous tumor, synovial sarcoma, leiomyosarcoma, others) o Pediatric malrignancies (peluropulmonary blastoma) QUIZ QUESTIONS Most common pulmonary tumor? Metastatic tumors What mutation is associated with therapeutic response to Tyr inhibitors such as gefitinib? EGF-R mutations Why is it important to recognize squamous carcinoma features in pts w/lung cancer? Drug BEVACUZIMAB/Avastin is CI for use due to risk of pulmonary hemorrhage