Neoplasms of Lung and Pleura William K. Funkhouser, M.D. Ph.D. –x

Neoplasms of Lung and Pleura Primary Neoplasms of Lung Primary Neoplasms of Pleura Metastatic Neoplasms to Lung and/or Pleura

Neoplasms of Lung and Pleura: Classification by Lineage Epithelial – most common Melanocytic Stromal Mesothelial

Benign Lung Neoplasms Hamartoma Squamous papillomatosis Pleomorphic adenoma (ENT)

Hamartoma Clin: Adolescence  adulthood None in newborns - not congenital Rad: Solitary nodule +/- popcorn calcification Peripheral > central Path: Gross: solitary, lobulated, cartilagenous Micro: normal tissues in excess/disarray

Hamartoma Solitary Pulmonary Nodule

Bivalved Hamartoma

Cartilage in excess and disarray

Malignant epithelial neoplasms (Carcinomas) Squamous cell carcinoma Adenocarcinoma Large cell undifferentiated carcinoma Small cell undifferentiated carcinoma

Lung Carcinomas: Epidemiology Estimated Incidence (2003): 172,000 (US) Estimated Mortality (2003): 157,000 (US) >85% of lung carcinoma deaths (and 30% of all cancer deaths) occur in cigarette smokers Risk = f(# cigarettes smoked), 15-30X in heavy smokers, 50-60X in asbestos workers who smoke Risk decreases with cessation of cigarette smoking: baseline after 15 years

USA Tobacco Use 25% of US adults smoke cigarettes M=F US adults consume 2,400 cigs/person/year 36% of US high school students smoke est. 1.8 million new smokers/year (65% < 18 yo)

Tobacco: Morbidity and Mortality Premature ASVD: major risk factor Emphysema: Linear with exposure: 7%/10 years Chronic bronchitis Carcinomas of pharynx, larynx, lung, esophagus, bladder, kidney Fetal tobacco syndrome

Tobacco: Chemistry 80% air, 20% gases and particulates Gases: CO, CO 2, formaldehyde, acrolein, methanol, phenol, anthracenes, pyrenes Nicotine: 1% of smoke 85% absorbed in lung equivalent to 1 mg IV

Tobacco: Chemistry Particulates: –resin cores in 0.5  M diameter water droplets –est particles/ml –50% deposited in and cleared by cilia – remainder: phagocytosis, lymphatic transport Overall: 4,000 chemical compounds, of which 43 are considered carcinogenic

Squamous cell carcinoma Clin: Smokers (98%) 20-30% of common carcinomas May secrete PTH-like compound Rad: central > > peripheral Path: Bronchi > Larynx > Trachea +/- Desmosomes (intercellular bridges) +/- Keratin production, e.g. keratin pearls

Normal

Squamous cell carcinoma

Squamous cell carcinoma in situRespiratory mucosa

Invasive Squamous Carcinoma Keratin Desmosomes

Metastatic squamous cell carcinoma to lymph node Normal lymph node lymphocytes Mets in subcapsular sinuses

Adenocarcinoma Clin: 30-40% of common carcinomas Most common carcinoma in non-smokers, but 80% of adenoCAs occur in smokers Rad: peripheral > central Path: +/- glands +/- mucin Bronchiolo-alveolar carcinoma subset

Adenocarcinoma Primary Pleural effusion

Adenocarcinoma Gland formation

Adenocarcinoma Mucin production (red on PASd stain)

Bronchioloalveolar carcinoma (BAC) Clin: Rising incidence (presently 20-25%) Not associated with cigarette smoking Rad: Peripheral, can be multifocal and bilateral Path: Lepidic (butterfly-like) growth pattern Mucinous or non-mucinous Unifocal or multifocal Distinction of multifocal primary from mets

Bronchiolo-alveolar carcinoma

Large cell undifferentiated carcinoma Clin: 10% of common carcinomas Rad: non-specific Path: H&E: Undifferentiated EM: ? adenocarcinomas cDNA microarrays: distinct disease

Large cell undifferentiated carcinoma

Non-Small Cell Lung Carcinomas: Prognostic variables Definitely: Stage, performance status, weight loss Possibly gender, ploidy, k-ras mutation, p53 protein accumulation Not age, histology

Small cell carcinoma Clin: Smokers 20 % of common carcinomas Ectopic ACTH, ADH, Eaton-Lambert, carcinoid s. Commonly high stage at presentation Responsive to chemo/RT, but low 5 yr survival Rad: Central in >90% Frequent metastases to LNs and distant sites Path: Malignant cytology No nucleoli High mitotic activity and necrosis

Small cell undifferentiated carcinoma At diagnosis Response to therapy

Small cell undifferentiated carcinoma Viable carcinoma Necrotic carcinoma

Small cell undifferentiated carcinoma

Metastatic small cell carcinomaNormal lymphocytes

Small Cell Lung Carcinoma: Prognostic variables Definitely: Stage, performance status Probably: Gender, age, # of metastatic sites

Neoplasms of Lung & Pleura: Classification by Lineage Epithelial Melanocytic Stromal Mesothelial Metastases

Mesothelioma Clin: Associated with asbestos exposure Rad: Diffuse pleural involvement May have associated effusion Path: Malignant Deeply invasive growth pattern Epithelial, spindle cell, or biphasic Immuno: Keratin (+) EM: long microvilli

Mesothelioma: PA Chest Visible C-P Angle Loss of C-P Angle = Pleural effusion or mass

Mesothelioma: CT Thickened pleura Normal thickness pleura

Normal thin pleura

Deeply invasive mesothelioma (cytokeratin immunostain)

Epithelioid cytology of this mesothelioma mimics adenocarcinoma

Adenocarcinoma Mesothelioma N. Weidner

Asbestos body (Ferruginous body)

Neoplasms of Lung & Pleura: Metastases Most common malignant neoplasms involving the lung Multiple nodules favor metastases over primary neoplasms (except BAC) Carcinomas Sarcomas Melanoma

Metastatic carcinomas Breast adenoCA GI adenoCA Renal adenoCA Head/neck squamous cell CA

Metastatic Breast CA Pleural Thickening due to Metastases +/- Pleural Effusion

Metastatic breast carcinoma

Metastatic colon carcinoma

Metastatic renal cell carcinoma

Metastatic ENT carcinoma

Metastatic sarcomas Osteosarcomas Soft tissue sarcomas

Metastatic osteosarcoma

Metastatic melanoma Clin: Extrapulmonary 1  melanoma much more common than pulmonary 1  No known 1  in 5-10% of cases Path: Variable architecture & cytology May be pigmented Use immunohistochemistry to confirm

Metastatic melanoma

Neoplasms of Lung and Pleura 1  Lung Neoplasms - Most are carcinomas 1  Pleural Neoplasms - Mesotheliomas Mets to Lung and/or pleura – All lineages possible

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