Respiratory System II the Next Generation Bronchogenic carcinoma



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Respiratory System II

The Next Generation


Bronchogenic carcinoma:
Most common malignant disease of men

Etiologic factors include cigarette smoking, industrial pollutants, etc

Cigarette smoking is a major etiologic factor

Asbestos workers often at risk for mesothelioma- discussed later

Scar cancers are lung cancers which arise within the vincinity of scars, usually adenocarcinoma


DISEASE

MORPH/PATH

S?S

CLINICAL

Primary lung tumor, benign

Hamartoma

Pulmonary hamartoma, benign and uncommon. Consists of islands of cartilage, smooth muscle cells, adipose tissue and clefts lined by epithelium. Rarely greater than 3 to 4 cm. 50% of all benign pulm neoplasms. Avg age 45, central site in origin.

Coin lesion on CXR

Coughing hemoptysis

Lobar collapse


Surgical excision?

Squamous cell carcinoma

Most commonly found in men and associated with cigarette smoking. Begins as in situ cytologic atypia and progresses into small area of mucosal thickening. Grows into elevated, irregular mass. Narrow or obliterate bronchial lumen. Necrosis and hemorrhage common. Close to hilum, not towards peripherly. Much more malignant.

Lesions in hilum.

Coughing, hemoptysis



Usually arise from major bronchus, may start from metaplasia.

May infiltrate into mediastinum



Adenocarcinoma
(Bronchogenic)


Cancer secondary to scarring. May be well differentiated with glandular elements or poorly differentiated. Mucin production s often present. Site is quite different, towards periphery. Not frequently associated with smoking. Most common in females and non smokers.

Coughing

Hemoptysis


Pleural effusion

Blood in pleural effusion.
Typical glandular appearance

Small Cell carcinoma
(Bronchogenic)


Highly malignant and aggressive. Mostly seen in males and strong association with cigarette smoking. Tumor consists of sheets of clusters of small compact round or oval cells with dense hypochromatic nucleus. Most malignant. Some contain neurosecrectory ranules. ++ early metastasis. Hilar tumor as well. Classic cell is the OAT cell. See 16-41-C, in Robbins.
Electron microscopic studies show dense-core neurosecretory granules in some of these tumor cells. Granules are similar to those found in Kulchitsky (APUD) cells present along bronchial epithelium.

-MOSTLY HILAR OR CENTRAL


-MOST AGGRESSIVE
-WIDE METASTASIS
-MOST COMMON PATTERN ASSOCIATED WITH ECTOPIC HORMONE PRODUCTION

Coughing

Hemoptysis

Paraneoplastic syndromes


LN involvement in carina

Small oval cells with dense nucleus

Ectopic hormone production, paraneoplastic syndromes common
APUD cells common in lung: amine producing. Implicated in paraneoplasms.
Less than 1 yr life expectancy post diagnosis and usually not surgical


Bronchogenic carcinoma, overview

From Robbins: public enemy number one. Bronchogenic refers to origin of tumors in the bronchial and sometimes bronchiolar epithelium. Most common visceral malignancy in men. Related to tobacco smoking. Several subtypes include:
Squamous cell caricinoma- 25-40%
Adenocarcinoma- 25-40%
Small cell carcinoma- 20-25%
Large cell carcinoma- 10-15%

These tumors are most often found in the hilus of the lung. Three fourths of these tumors take origin in the first, second, or third order bronchi. Small number arise in the periphery. Usually begins as an area of atypia that, over an unknown interval, results in thickening/piling up of mucosa. Outlook for pts with these tumors is often poor despite advances in detection, chemo, and radiotherapy.


NB: Partial obstruction may cause marked focal emphysema. Impaired airway drainage is a common cause for sevrre suppurative or ulcerative bronchitis or bronchiectasis. Pulmonary abscesses sometimes call attention to silent carcinoma. Secondary pathology includes:
Pericarditis
Pleural involvement
Superior vena caval syndrome

Large Cell Carcinoma
(Bronchogenic)


Pleomorphic or anaplastic types of sqamous/adenocarcinomas? Poorly differentiated. Again towards hilum, may be elsewhere if started from adenocacinoma. Some exhibit large polygonal cells and vesicular nuclei. Represent squamous/adenocarcinomas that are so poorly differentiated as to be unrecognizable. Some contain intracellular mucin.

Bronchioalveolar carcinoma
(Bronchogenic)


Uncommon form of adenocarcinoma found in periphery. Arise in terminal BRONCHIOALVEOLAR region. Males and females equally affected. Not associated with cigarette smoking. Late metastasis. Tumor comprised of tall, columnar mucus producing cells lining terminal air spaces. Can spread from alveolus to alveolus during respiration. That’s one important point that you need to make a note. Metastasis is late compared to other types, this cancer is less malignant. Prognosis much better

Carcinoid tumor, bronchial gland neoplasm
(Neuroendocrine)


Quite important- you need to make a note. In connection with carcinoid syndrome. Bronchial carcinoid tumor to differentiate from other tumors. Low malignancy. Locally invasive, developed from neuroendocrine cells of bronchial mucosa. Neuroendocrine cells are counterpoints of argentaffin of Kulchitsky cells of GIT. Cells belong to DNS/APUD system. Neurosecretory granules contain serotonin, calcitonin, etc. Though mitoses are rare, all bronchial carcinoid tumors are malignant. Age of onset usually less than 40. Usually involve large bronci and less than 4 cm in diameter. Not associated with cigarette smoking. Serotonin is the most common chemical produced by this tumor.

APUD: Amine producing uptake/decarboxylation system



Iceberg Tumor”: only tip of tumor seen via bronchoscopy.
-YOUNG AGE
-NEUROLOGICAL SEQUELAE, NOT ASSOCIATED WITH SMOKING

Cough

Hemoptysis

Secondary infection.

DDX via bronchoscopy or FNA/C

Empyema

Bronchiectasis



Impaired drainage
S/S similar


Prognosis much better, different than small cell carcinoma.

Approx 40% metastasize to regional lymph nodes, 5-10% to liver. Rarely produce Carcinoid syndrome:


Diarrhea

Wheezing

Flushing

Cyanosis

Look for metabolites of serotonin in urine.



Adenoid cystic carcinoma, bronchial gland neoplasm

Little detail, non common. Similar to salivary tumors. Glands become distended and cystic.

Mucoepidermoid carcinoma

Little detail, not common

Pleural tumors


Primary: Benign mesothelioma, malignant mesothelioma

Secondary: serosanguinous. Always think of CA if blood is in pleura.


Most pleural tumors are from the lung. Tumors can arise from hilum or periphery (as in adenocarcinoma) and can infiltrate pleura.
Advanced mammary carcinomas frequently penetrate the thoracic wall and involve parietal pleura. Malignancy from ANY organ can involve the pleural space. Be suspicious if pleural effusion is serous or sero-sanguinous

SOME CAUSES OF PLEURAL EFFUSION:

-Increased hydrostatic pressure, as in CHF states

-Increased vascular permeability, as in pneumonia

-Decreased oncotic pressure, as in nephritic syndrome

-Increased negative intrapleural pressure, as in atelectasis

-Decreased lymphatic drainage



BENIGN MESOTHELIOMA: Similar to a fibroma, not common. Usually not large. Often attached to pleural via a pedicle. Consist of dense fibrous tissue with occasional cysts filled with viscid fluid. Tumors show whorls of reticulin and collagen fibers. Tumor cells are keratin negative (as apposed to MM histologic pattern. No relationship to asbestos exposure.

MALIGNANT MESOTHELIOMA (MM): Compared to lung tumors, relatively rare. Once you get it, “it is the end.”Not associated with cigarette smoking but very strongly associated with asbestos. Highly aggressive. Two types: sarcomatoid and epitheliod. Involves pleural thickening. Histologic signs that favor MM include: positive staining for acid mucopolysaccharide, lack of staining for CEA, and other epithelial glycoprotein antigens, markers generally expressed by adenocarcinomas, strong keratin staining, long microvilli and abundant tonofilaments.Cytogenetic abnormalities occur but are not typically diagnostic of MM. Extremely poor prognosis. Pneumonectomy, chemo, and radiation has occasionally improved outcome. Pts generally survive less than two years with MM.


SECONDARY PATHOLOGY of LUNG SYMPTOMS:

Result from obstruction or compression and include emphysema, atelectasis, bronchiectasis, superior vena caval syndrome

Direct spread: to mediastinum, pericardium, esophagus. Apical tumors may involve the cervical sympathetic chain

HORNER’s SYNDROME: enopthalmos, ptosis, miosis, and anhydrosis on same side of lesion. ENOPTHALMOS, so very important, you need to make a note.
Pancoast’s syndrome: Tumors that spread up symp chain and induce Horner’s syndrome. Towards apices of lung. May also infiltrate brachial plexus.
Lymphatic spread: Occurs early with invasion of hilar, tracheobronchial, and other mediastinal LN’s. Tumor may spread to other nodes from there

Blood spread: Occurs early in disease as well. Mets occur to any organ but frequrntly to bone, brain, and adrenals

Peripheral tumor: pleural effusion, blood stained, pneumothorax

Apical tumor: invasion of brachial plexus also may occur.

SVC syndrome: Mass presses on SVC and causes obstruction. Plethoric complexion, JVD, venous congestion of head and neck. May be extremely severe. + vein distention when arm is raised to facilitate drainage.

Clinical Features:


Paraneoplastic syndrome: ACTH, PTH, Calcitonin, Gonadotropins, Serotonins. S/S are not commonly related to cancer in question. Lung is not an endocrine organ, but all sorts of endocine/pathological problems occur. S/S vary according to what type of hormones are secreted. Serotonin is same as 5-HT may give rise to CNS problems, known as carcinoid syndrome. Will be talked about later.
Other systemic implications include myopathy, peripheral neuropathy, hypertrophic pulmonary osteoarthropathy.

Hypertrophic pulmonary osteoarthropathy: Can get this in other lung pathologies, not specific for cancer. Soft tissues involved. Clubbing often seen.

Cushing’s Syndrome: From hyper ACTH secretion

Hypercalcemia: From osteoclast activity. Parathyroid hormone, prostaglandins, and some cytokines are also involved in hypercalcemia.

Hypocalcemia: From excessive calcitonin secretion

Trosseau’s Syndrome: Disseminated blood clots due to metastatic cancer. Hypercoagulable state. Thrombosis in arm, leg, etc.

Neuromuscular complications as well.

Lambert-Eaton syndrome: Musculoskeletal involvement, pt cant get up from chair.

Staging much more important than grading because it integrates clinical picture. TMN system used.

Also recall that the lung is a common site for secondary metastasis of other cancers.
Primary tumors are most of the time a SINGLE mass. Metastatic tumors are usually multiple, may involve bilateral lung parenchya

Refresher of TMN staging system, mets appear at stage IV

-T1: Tumor 3cm without pleural or main stem involvement

-T2: Tumor 3cm or involvement of main stem bronchus 2cm from carina, visceral, pleural, or lobar atelectasis

-T3: Tumor with chest wall involvement, diaphragm, pleura, pericardium, main stem 2cm from carina, or entire lung atelectasis

-T4: Tumor with mediastinal invasion, invasion of heart, great vessels, verterbral body, or malignant pleural effusion.

Stage I

T1-2

No nodes

No mets

Stage II

T1-3 (stage 2b is involves T3 per robbins)

1 node

No mets

Stage III

Any T

N2-3 nodes (nodes elsewhere like axillary, supraclavicular, etc)

No mets

Stage IV

Any T

Any N

Metastasis



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