Respiratory System Pathology - Lung Tumors

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95% of primary lung tumors are:

Primary Lung cancers

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Statistics for Lung carcinoma:

Most important cause of cancer-related deaths in industrialized countries One third of cancer deaths in men Leading cause of cancer deaths in women

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The peak incidence of lung cancer is in patients how old?

50s-60s

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What is the prognosis for lung cancer?

1) The 5- year survival rate for all stages of lung cancer combined is about 16%, 2) Disease localized to the lung, the 5-year survival rate is 45%

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The four major histologic types of carcinomas of the lung are:

1) Adenocarcinoma 2) Squamous cell carcinoma 3) Small cell carcinoma, 4) Large cell carcinoma

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Carcinomas of the lung were classified into two groups:

1) Small cell lung cancer (SCLC) 2) Non-small cell lung cancer (NSCLC); adenocarcinomas and squamous cell carcinomas

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Difference between SCLC and NSCLC:

1) SCLCs have metastasized by the time of diagnosis Are not curable by surgery Treated by chemotherapy, with or without radiation therapy 2) NSCLCs were more likely to be resectable Usually responded poorly to chemotherapy

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Now therapies are available that target specific mutated gene products present in

NSCLC Especially adenocarcinomas

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Etiology of lung cancers:

1) Cigarette smoking/environment changes 2) 90% of lung cancers occur in active smokers 3) Procarcinogens activated via P- 450 monooxygenase enzyme system for conversion into carcinogens 4) Polymorphisms involving P-450 genes 5) Women more likely

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Relationship between smoking and lung cancer:

1) Cessation smoking decreases risk over time 2) Passive smoking increases risk 2x that of nonsmokers 3) Smoking of pipes and cigars also increases the risk- modestly 4) Increased incidence in workers exposed arsenic, chromium, uranium asbestos

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Relationship between asbestos exposure and lung cancer:

Exposure to asbestos increases the risk of lung cancer fivefold in nonsmokers Heavy smokers exposed to asbestos have 55x greater risk for development of lung cancer than that for nonsmokers not exposed to asbestos

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Pathogenesis of lung cancers:

Stepwise accumulation of a multitude of genetic abnormalities that result in transformation of benign progenitor cells in the lung into neoplastic cells

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Gene mutations in lung cancer:

1) Inactivation of tumor suppressor genes located on 3p 2) TP53 mutations or activation of the KRAS 3) In Adenocarcinomas a) Activating mutations of EGFR b) MET tyrosine kinase gene c) EML4-ALK tyrosine kinase fusion genes

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Characteristics of ALK tyrosine kinase fusion genes

These abnormalities, while rare, are important because of their therapeutic implications, as they can be targeted with tyrosine kinase inhibitors

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Morphology of Squamous cell carcinoma:

Arise centrally in major bronchi and spread to local hilar nodes Disseminate outside the thorax Large lesions undergo central necrosis- cavitation Squamous metaplasia or dysplasia in bronchial epithelium Mass obstructs the lumen of a major bronchus

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Morphology of adenocarcinomas:

May occur as central lesions but usually are more peripherally located, many with a central scar Grow slowly and form smaller masses thanother subtypes Metastasize widely

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What is the most common type of lung cancer in women and nonsmokers?

Adenocarcinomas

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On histologic examination, adenocarcinomas may assume a variety of forms, including:

1) Acinar(gland-forming) 2) Papillary 3) Mucinous which often is multifocal and may manifest as pneumonia 4) Solid types:Requires demonstration of intracellular mucin production by special stains

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The precursor of peripheral adenocarcinomas is atypical adenomatous hyperplasia which progresses to

1) Adenocarcinoma in situ 2) Minimally invasive adenocarcinoma (tumor less than 3 cm and invasive component measuring 5 mm or less) 3) Invasive adenocarcinoma (tumor of any size that has invaded to depths greater than 5 mm)

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Adenocarcinomain situ (AIS) AKA

bronchioloalveolarcarcinoma

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Adenocarcinomain situ (AIS) appears as

a single nodule

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The key features of AIS are:

a. Diameter of 3 cm or less b. Growth along preexisting structures c. Preservation of alveolar architecture d. Does not demonstrate destruction of alveolar architecture or stromal invasion with desmoplasia

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Morphology of SCLCs

a. Centrally located with extension into the lung parenchyma b. Early involvement of the hilar and mediastinal nodes c. Are composed of tumor cells with a round shape, scant cytoplasm, and finely granular chromatin with many mitotic figures

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Additional notes about SCLC morphology:

Necrosis is invariably present and may be extensive Fragile cells that show fragmentation and "crush artifact". Nuclear molding resulting from close apposition of tumor cells that have scant cytoplasm

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For all of these neoplasms, it is possible to trace involvement of

successive chains of nodes in carina, in the mediastinum, and in the neck (scalene nodes) and clavicular regions and then distant metastases

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What involvement is characteristic of primary tumors?

Involvement of the left supraclavicular node (Virchow node)

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If the tumor infiltrates the superior vena cava, it can cause:

Venous congestion Vena caval syndrome

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Pancoast syndrome is caused by:

Apical neoplasms

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What are the characteristics of pancoast syndrome?

Invasion of the brachial or cervical sympathetic plexus to cause severe pain in the distribution of the ulnar nerve to produce Horner syndrome Destruction of the first and second ribs and sometimes thoracic vertebrae

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What are the clinical symptoms of Horner syndrome?

ipsilateral enophthalmos- posterior displacement of the eye Ptosis- eye drooping Miosis- eye contraction Anhidrosis- inability to sweat normally

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Clinical course of lung tumors:

1) Silent, spread significantly before symptoms produced 2) Chronic cough 3) Hoarseness, chest pain, superior vena cava syndrome, pleural effusion appear -prognosis is bad 4) Symptoms resulting from metastatic spread to the brain ,liver, or bones

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About 3% to 10% of all patients with lung cancer develop

clinically overt paraneoplastic syndromes

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Secretion of a parathyroid hormone-related peptide by squamous cell carcinoma causes

Hypercalcemia

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Small cell carcinoma, via production of the Adrenocorticotropic hormone, can cause

Cushings syndrome

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Small cell carcinoma can also cause a syndrome called:

Syndrome of inappropriate secretion of antidiuretic hormone

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Patients with lung cancer can develop neuromuscular syndromes like;

Myasthenic syndrome Peripheral neuropathy Polymyositis

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Any type of carcinoma can cause which bone abnormalities:

Clubbing of the fingers Hypertrophic pulmonary osteoarthropathy

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Created by: Ulaisl

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