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Lung tumor

Other carcinoma

Carcinoma-general

Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 12 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
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● 95% of lung tumors are bronchogenic carcinoma
● Others are bronchial carcinoid, mesenchymal, miscellaneous neoplasms
● In US, lung cancer is #1 cause of cancer death in men and women; causes 30% of cancer deaths in men
● 2012: estimated 226,160 new cases in US, 160,000 deaths (National Cancer Institute)
● Incidence in men is 74 per 100,000 vs. 31 per 100,000 for women
● Peaks at ages 50-69 years; 2% occur before age 40 years

Cigarette smoking
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● Causes most cases of lung cancer
● Relative risk of smokers vs. nonsmokers is 10:1, but is 20:1 for >40 cigarettes/day
● Risk strongly related to number of cigarettes smoked, described in pack years (number of packs per day x number of years smoking)
● Cigarette smoking also associated with carcinomas of lip, tongue, pharynx, larynx, esophagus, bladder, pancreas, kidney, floor of mouth
● 10% of smokers have atypia or hyperplasia of bronchial epithelium
● Carcinogens in tobacco smoke are benzo [a] pyrene (an initiator) and phenol derivatives (promoters)
● Usually associated with squamous cell and small cell carcinoma, less likely with adenocarcinoma

Other causes of lung cancer
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● Radiation exposure, uranium (RR with uranium exposure is 4:1 for nonsmokers, 10:1 for smokers vs. general population)
● Asbestos (RR is 5:1 for nonsmokers, 50-90:1 for smokers vs. general population); causes of death for asbestos workers are: 20% lung cancer, 10% mesothelioma, 10% GI carcinomas
● Also exposure to arsenic, beryllium, chromate, coal, gold ore, iron, mustard gas, nickel, radon, vinyl chloride

Symptoms
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● Cough, weight loss, chest pain, shortness of breath, increased sputum production
● Also acanthosis nigricans, hypertrophic pulmonary osteoarthropathy (clubbing), Horner’s syndrome (enophthalmos, ptosis, miosis, anhidrosis) due to apical lung tumors called Pancoast tumors, Lambert-Eaton myasthenic syndrome (muscle weakness due to antibodies to neuronal calcium channel), leukemoid reaction, pain in distribution of ulnar nerve, sensory peripheral neuropathy, superior vena cava syndrome (compression/invasion of SVC causes venous congestion, circulatory compromise, dusky head, arm edema)

Spread and classification
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● Spreads along bronchus distally and proximally, into lung parenchyma to mediastinum or pleura, causing pleural seeding, pleural effusion, involvement of diaphragm and chest wall
● 50% have nodal involvement at resection (usually hilar, mediastinal and supraclavicular)
● Also metastases to adrenals (50%), liver (30%), brain, bone
● Also opposite lung, pericardium, kidneys

Survival (pre-EGFR inhibitors)
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● Overall 5 year survival is 10-15%
● Only 30% have limited disease at diagnosis making resection for cure an option
● For stage I non-small cell carcinoma, 5 year survival is 60%
● Poor prognostic factors: high TNM stage, weight loss >10% of body weight, age < 40 years or women (usually are high stage), small cell or giant cell subtypes, angiolymphatic invasion, pleural effusion, lack of lymphoplasmacytic reaction

Gross description
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● Arise near hilus
● Hemorrhage, necrosis, cavities are common
● 2-5% are multiple
● Peripheral tumors are usually adenocarcinomas

Micro description
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● See also specific subtypes
● Begins with atypia, then warty excrescence, then fungates into lumen, penetrates wall of bronchus growing along broad front to produce a cauliflower like intraparenchymal mass
● 80% have vascular invasion

Virtual slides
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Tumor emboli

Positive stains
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● May be positive for neuroendocrine markers but with no neuroendocrine morphology - recommended to either ignore neuroendocrine stain results or to diagnose as tumor with neuroendocrine features

Negative stains
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● CDX2 (marker of intestinal origin, Am J Surg Pathol 2003;27:141), Hep Par1 (hepatocyte marker, Mod Pathol 2003;16:137)

Molecular description
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● Dominant oncogenes are Kras (see below), c-myc (small cell carcinomas), p53, Rb, 3p suppressor gene
● High Kras mutation rate in Western countries in lung adenocarcinoma / nonsmall cell lung cancer (25%) but less in Asian countries (0% in China, Onkologie 2008;31:174, 5% in Taiwan, Cancer 2008;113;3199, 11% in Japan, Oncol Rep 2007;18:623)
● Kras mutations are associated with mucinous versus nonmucinous adenocarcinoma (J Mol Diagn 2007;9:320)
● In Western patients, similar rate of Kras mutations between never, former and current smokers, although mutations were different (Clin Cancer Res 2008;14:5731)
● Kras mutations are associated with poor prognosis and EGFR tyrosine kinase resistance (Curr Opin Pharmacol 2008;8:413)

Molecular images
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H&E and FISH of Kras mutation

End of Lung tumor > Other carcinoma > Carcinoma-general

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