respiratory9-10

The Respiratory Systemlect-9&10

Cancers of the Respiratory Tract


Carcinoma of the Larynx It is of squamous cell carcinoma. < 2% of all cancers Smoking Chronic alcohol intake, HPV and asbestos inhalation. Ulceration of mucosa Hoarseness, loss of voice Good prognosis 5-year survival rate 75%

Tumors of the lung

90-95% are bronchogenic carcinoma. 5% Carcinoid. 2-5% mesenchymal and other miscellaneous neoplasms.

Lung Cancer-Bronchogenic carcinoma

1/3 of all cancers in US. 1/3 of all cancer deaths in males. Over 7% of all deaths in both sexes. 90% of sufferers are smokers. free radicals, other carcinogens in smoke 5-year survival rate 10-15%.

Aetiology and pathogenesis

Role of tobacco smoke: Strong relationship between the smoking and BC:

1- statistical evidence:

Average smokers have ten fold increase risk of cancer than non smoker. Heavy smoker have 20 fold increase risk of cancer (40 cig./d. fro several years). It depends on amount of daily smoking, tendency to inhale and duration of smoking habit. Cessation of smoking for 10 years reduces risk. Causes cancer of lip, tongue, floor of mouth, pharynx, larynx, esophagus, urinary bladder and pancreas.

2- Clinical evidence:

By observation of histologic changes in the lining epithelium of the respiratory tract in smokers which causes a lot of atypical cells.

3- Experimental work:

There is more than 1200 known materials in smoke, some are initiators (as polycyclic aromatic hydrocarbons, including benzopyrene) and promoters as phenol derivatives, & radioactive elements as polonium 210, carbon-14, potassium40. Also there is contaminants as nickel, arsenic, molds and additives. Protracted exposure to these additives to mice causes skin cancer.

Role of industrial hazards:

Radiation (atomic bombs survivors in H & N show high incidence of bronchogenic carcinoma). Also the Uranium miners have a 4 fold increased risk and about 10 times increased risk if smoker.Asbestos workers also have a 5 fold increased risk and if smokers 90 fold increased risk with a latent period may reach to 10—30 years. It also causes pleural and peritoneal mesotheliomas, with gastrointestinal carcinoma.Nickel, Chromate, Arsenic, Beryllium, Iron, newspaper workers, gold miners and halo-ether workers.

Role of air pollution

Inhalation and bronchial deposition of radioactive decay products that become attached to environmental aerosols.

ROLE OF GENETIC FACTORS:

Some genetic predisposition. Genetic variation of inducible enzyme activating some carcinogens in cigarette smoke. Some familial clustering. Dominant oncogene c-myc in small cell carcinoma. K- ras in adenocarcinoma. Deleted recessive gene P53 and Retinoblastoma gene. ROLE OF SCARRING: Near scars, adenocarcinoma. Scar occur as a result of old infarct, metallic foreign bodies, wounds & granulomatous infections.



Classification


Several microscopic classifications, most widely used (kreyberg): 1- Squamous cell carcinoma: a- well differentiated, b- moderately, c- poorly. 2- Adenocarcinoma: a- Not otherwise specified (NOS). b- Bronchioalveolar. 3- Adenosquamous carcinoma. 4- Small cell carcinoma: a- Classic. b-Mixed small cell/large cell. c-combined 5- Undifferentiated large cell carcinoma. 6- Giant cell carcinoma.

Morphology:

Cavitary scc

Solid peripheral ca.

Microscopy


SQUAMOUS CELL CARCINOMA: Most in men, smoking related, large tumors, central, spread locally and late metastasis. It has high rate of growth, and nearby squamous metaplasia and dysplasia is seen. ADENOCARCINOMA: NOS is bronchial derived, most common type in women, in nonsmokers, peripherally located, small, solid, slowly growing, with little mucin. Bronchioalveolar type arise from terminal bronchioles, which form either single or multiple nodules produces pneumonia like consolidations, with tall columnar cells line the alveolar septa in numerous papillary formations and better prognosis.

Nearby abnormal mucosa

Tad pole cell in sputum

Epithelial pearl of concentric cells

adenocarcinoma

Adenocarcinoma-in p.l.

Bronchioalveolar

Bronchioalveolar

With invasion

Large cell carcinoma

Small cell carcinoma:


Highly malignant, small cells, with little cytoplasm, round or oval nuclei as the shape of lymphocytes (but it is double size) = classic oat cell. Some are spindle shape or polygonal. EM: show dense core neurosecretory granules, so able to secrete polypeptide hormones. Positive immunohistochemical stains are neuron specific enolase, parathormone like products. Strong relationship to smoking. Most often hilar or central and most aggressive type, metastasize widely and incurable by surgical means and associated with ectpoic hormone secretions.

Oat cell carcinoma

Moulding in sputum malignant cells

Oat cell carcinoma

High mitotic rate in oat c.c.

Neurosecretory granules in EM

Bone invasion with moulding

Bone marrow invasion

Brain and meninges invasion

Small cell carcinoma with mixed type

Large cell carcinoma:


Anaplastic type with large cells totally undifferentiated with high cellular atypia. May see giant cells in the same type or separated into single group of giant cell carcinoma. SECONDARY PATHOLOGY: Partial obstruction may cause marked focal emphysema. Total obstruction may lead to atelectasis, impaired drainage causes severe suppuration with ulcerative bronchiectasis, or abscess. Compression or invasion of superior vena cava causes venous congestion, dusky head and arm edema =superior vena cava syndrome. Extension to pericardial or pleura sacs may cause pericarditis or pleuritis with effusions.

Staging of NSCLC

TNM classification Consistent, reproducible description of the extent of disease Identifies groups of patients with similar prognosis and therapies Analysis of outcomes

TMN Classification of Lung Cancer

Tumor (T) TX Occult cancer (cells in sputum/washings but no tumor seen by imaging studies or Bronchoscopy) T1 Tumor < 3 cm surrounded by lung / visceral pleura, not proximal to lobar bronchus T2 Tumor > 3 cm, or involvement of main bronchus 2 cm distal to carina or with pleural invasion, or atelectasis / obstructive pneumonia extending to hilar region T3 Tumor invading chest wall, diaphragm, mediastinal pleura, of parietal pericardium; or tumor within 2 cm of carina; or atelectasis of entire lung T4 Tumor invading mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or carina, or ipsilateral pleural effusion, satellite nodule within same lobe Nodes (N) N0 No regional lymph node metastases N1 Metastases to ipsilateral peribronchial or hilar nodes N2 Metastases to ipsilateral mediastinal or subcarinal nodes N3 Metastases to contralateral mediastinal or hilar or to any scalene or supraaclavicular nodes Distant Metastases (M) M0 No distant metastases M1 Distant metastases

Staging Groups for Lung Cancer

Stage T N M Occult Tx N0 M0 Stage I A T1 N0 M0 Stage IB T2 N0 M0 Stage IIA T1 N1 M0 Stage IIB T2-3 N0-1 M0 Stage IIIA T3 N1 M0 T1-3 N2 M0 Stage IIIB T4 N0-2 M0 T1-4 N3 M0 Stage IV Any T Any N M1

CLINICAL FEATURES - Thoracic Symptoms-most are of local effects

Centrally located lesionsCough, stridor, wheezing, hemoptysis, dyspnea, and chest painSuperior Vena Caval SyndromePeripheral Chest pain, cough, and dyspnea (rib invasion)Large peripheral tumorsMay present as lung abscessesIntrathoracic extensionRecurrent laryngeal nerve - hoarsenessEsophagus – dysphagiaPericarditis, tamponade.

CLINICAL FEATURESThoracic Symptoms-cont.

Pancoast syndrome - Superior sulcus tumor Local extension at apex of lungInvolves 8th cervical / 1st thoracic nerveIpsilateral shoulder / arm painPhrenic nerve invasion: diaphragm paralysis.Horner’s syndromeParavertebral extension and sympathetic nerve involvementEnophthalmos, ptosis, meiosis, and ipsilateral anhidrosis

Para-neoplastic Syndromes

NSCLC Cachexia, PTH/hypercalcemia, hypertrophic pulmonary osteoarthropathy, and neurologic syndromes SCLC Weight loss, anorexia, neuromyopathies ADH, ACTH, Calcitonin, PTH PTH-like peptide: hypercalcemia ACTH excess (Cushing Syndrome) ADH excess (Edema)

Clubbing of fingers

Solitary Pulmonary Nodule
Definition Size (1 - 4 cm) Small, spherical density / surrounded by lung parenchyma Incidence of Malignancy Geographic location 30 - 50%

Solitary Pulmonary Nodule

Etiology Neoplasms Benign Malignant Infectious Granulomas Systemic diseases

Solitary Pulmonary Nodule

Malignant nodule Doubling time - 30 to 400 days Size > 3 cm (>80%) CT enhancement > 20HU Benign nodule Stable > 2 yrs Coin lesion by x ray. Mostly hamartoma. Presence of calcifications

X-ray ca

Initial stages not detectable on chest X-rays

Lung Cancer Chest X-Ray

Diffuse interstitial ca. + R. diap.

Hilar tumor + LN

Neuroendocrine tumors-bronchial Carcinoid

1-5 % of all lung tumors. 90% of bronchial adenomas, which is old name that include also in 10% adenoid cystic carcinoma & mucoepidermoid carcinoma. Most are young patients less than 40 years, with no relation to smoking.

Grossly:

Show neurosecretory granules and markers. finger like or polypoid masses that commonly project into the lumen. Size rarely exceeds 3-4 cm. Most confined to main stem bronchus. May penetrate wall and form collar button lesion.

Microscopically:

Nests, cords and masses of cells separated by delicate stroma Regular cells with uniform round nuclei and infrequent mitoses.

Lung Cancer

More lung cancers are result of other tumors metastasizing in the lung via blood, lymph vesselsMetastatic tumors breast cancer, non-Hodgkin’s lymphoma, osteosarcoma, neuroblastoma, Wilms tumor.Almost any cancer can spread to the lungs, and metastases are found in 20 to 40% of patients dying of various cancers. The incidence of metastatic cancer to the lung is 6 out of 100,000 people.

RCC-Hematogenous lung metastasis

Lymphatic lung metastasis-breast

Pleural diseases

Most are secondary. Primary include: 1- Primary intrapleural bacterial infections. 2- Primary neoplasm=mesothelioma. Pleural effusion is most common manifestation of both primary and secondary diseases. Normally 15 ml of serous fluid, clear and acellular. Increased fluid in: 1- Increase hydrostatic pressure as R. sided HF. 2- Increased vascular permeability as pneumonia. 3- Decreased oncotic pressure as nephrotic syndrome. 4- Increased intrapleural negative pressure as atelectasis. 5- Decreased lymphatic drainage as mediastinal carcinomatosis.

Inflammatory pleural effusion

1- Serous, serofibrinous and fibrinous pleuritis, same processes. Common causes: Inflammatory as tuberculosis, pneumonia, lung infarcts, lung abscess and bronchiectasis. Rheumatoid arthritis, SLE, uremia, and other systemic disorders. Radiation. 2- Empyema: purulent pleural exudate. As yellow-green creamy pus composed of masses of neutrophils admixed with other leukocytes. May end by organization with dense fibrous adhesions. 3- True hemorrhagic pleuritis: sanguineous exudate seen in hemorrhagic diatheses, rickettsial diseases, neoplastic involvement.

Non inflammatory pleural effusions

Called as hydrothorax, clear and straw color, unilateral or bilateral according to the cause.Bilateral in HF, RF, Liver cirrhosis.Isolated right sided hydrothorax occurs in Meig’s syndrome (hydrothorax, ascites, ovarian firboma).Local collections seen in adhesions.Hemothorax is escape of blood to pleural cavity, fatal complication of ruptured aortic aneurysm or vascular trauma, form clot without inflammatory response.If nonfatal, organize and form adhesions.Chylothorax: milky fluid usually of lymphatic origin.Occur due to thoracic duct obstruction or trauma.

Pneumothorax

Air or gas in the pleural cavity, spontaneous, traumatic or therapeutic. Caused by emphysema, asthma and tuberculosis. Air resorbed after sealing of opening. Spontaneous is idiopathic and occur in young age. Tension Pneumothorax with flap valve. Air in pleural cavity.

Pleural tumors

Secondary metastatic tumors are more common, and most from lung and breast, and also ovarian carcinoma which tends to cause widespread implants and result in serous or serosanguineous effusions contain malignant cells seen by cytological examination of the fluid. Primary: 1- Pleural firboma (benign mesothelioma): Localized growth that is often attached to pleural surface by a pedicle, small 1-2 cm, with no effusion. Grossly: dense fibrous tissue with cyst. Microscopy: whorls of reticulin and collagen fibers and fibroblasts.

Malignant mesothelioma:

25-45 year exposure to asbestos and has no relation to smoking. Grossly: there is wide spread diffuse lesions with effusion and direct invasion of thoracic structures. Microscopically: Mixture of two types of cells, mesenchymal stromal cells and epithelium like lining cells. (both are malignant).

Pleural mesothelioma

Malignant and benign mesotheliomas