Neoplasms of Lung and Pleura

William K. Funkhouser, M.D. Ph.D.– x 3-1069 – Bill_Funkhouser@med.unc.edu

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 PulmonaryNodule

BivalvedHamartoma

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, CO2, 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. 109 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

Bronchiolo-alveolar carcinoma

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

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

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

VisibleC-PAngle

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

Metastaticrenal cell carcinoma

MetastaticENT carcinoma

Metastatic sarcomas

• Osteosarcomas

• Soft tissue sarcomas

Metastaticosteosarcoma

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

Thanks for your time.

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