Respiratory tumors Notes

NOTES NOTES RESPIRATORY TUMORS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Uncontrolled division of epithelial cells lining respiratory tract → formation of solid tumor ▪ Mutated cells become cancerous ▫ Resist inhibitory signals, evade immune surveillance ▪ Malignant tumors invade basement membrane ▫ Carcinoma in situ ▪ Metastasis ▫ Malignant tumors establish secondary tumors at distant site; lung cancer metastasizes quickly ▫ Common sites: mediastinum, hilar lymph nodes, lung pleura, breasts, liver, adrenal glands, brain, bones TYPES Small-cell ▪ Small, immature, neuroendocrine cells; divide rapidly, spread quickly Non-small-cell (most common) ▪ Large cells; divide, spread slowly ▫ Adenocarcinoma (goblet cells) ▫ Squamous cell carcinoma (squamous cells) ▫ Large cell carcinoma ▫ Carcinoid tumors (mature neuroendocrine cells) Nonspecific classification ▪ Small-cell carcinoma with poorer prognosis RISK FACTORS ▪ Age ▫ Malignancy more common in older individuals ▪ Smoking ▫ Direct, linear positive correlation between pack years, risk of lung cancer ▪ Asbestos exposure, radon exposure, ionizing radiation exposure ▪ Chronic obstructive pulmonary disease (COPD) ▪ Tuberculosis MNEMONIC: ABCDE Presentation of lung cancers Bronchial Airway disruption → pneumonia Blood: hemoptysis Cough Distribution: mestastasis whEEzing SIGNS & SYMPTOMS ▪ Asymptomatic in early disease ▪ Nonspecific, wide overlap with other noncancerous lung conditions ▪ Constitutional symptoms: loss of appetite, weight loss, weakness ▪ If located in certain areas (e.g. upper lobe of lung) → compressive symptoms ▫ Nerve compression: hoarseness (recurrent laryngeal nerve), Horner’s syndrome (sympathetic chain), diaphragmatic paralysis (phrenic nerve) ▪ Paraneoplastic syndromes ▫ Digital clubbing, muscle weakness, syndrome of inappropriate antidiuretic OSMOSIS.ORG 923

hormone secretion (SIADH), ectopic adrenocorticotropic hormone (ACTH) secretion, ectopic parathyroid hormone (PTH)-like secretion, hypertrophic pulmonary osteoarthropathy, Eaton– Lambert syndrome ▫ Mostly small cell carcinoma (neuroendocrine cells secrete hormones with systemic effects) LAB RESULTS ▪ Sputum sample ▫ Diagnosis of central (near to main bronchus) tumors, not peripheral tumors ▪ Fine needle aspiration ▫ Histopathologic diagnosis using cytology ▪ Endoscopic biopsy TREATMENT DIAGNOSIS MEDICATIONS DIAGNOSTIC IMAGING ▪ Simple analgesics, opioids (if severe) ▫ Pain management Chest X-ray ▪ Coin lesion CT scan ▪ Asymmetrical, expanding nodule; used for staging; can demonstrate extent of metastasis (e.g. hilar lymph node involvement) PET ▪ Areas of higher glucose turnover ▪ Bronchoscope ▪ Diagnosis of central (near to main bronchus) tumors, not peripheral tumors SURGERY ▪ Intraoperative frozen section if diagnosis of malignancy uncertain ▪ If malignancy confirmed, wedge resection performed for small tumors ▪ Lobectomy performed for larger tumors/ after wedge resection if margins positive OTHER INTERVENTIONS ▪ Chemotherapy, immunotherapy, radiation therapy MESOTHELIOMA osms.it/mesothelioma PATHOLOGY & CAUSES ▪ Cancer of mesothelium; most commonly lungs, chest wall pleural lining (composed of mesothelial cells); sometimes pericardium ▪ Commonly associated with asbestos exposure ▪ Asbestos fibers ▫ Mineral used as construction, insulation material ▫ Jagged in shape, very fine ▫ Increases risk of lung cancer, malignant mesothelioma 924 OSMOSIS.ORG ▪ Asbestos fibers inhaled → phagocytic cells attempt to phagocytose fibers → unable to destroy fibers → apoptosis of phagocytic cells → release of tumor promoting factors → mesothelial cells of pleura inflamed → DNA damage → mesothelial cells divide uncontrollably → tumor formation ▪ Mesothelial plaques cover visceral, parietal pleura; extend around chest cavity ▪ Asbestos fibers can be found in stomach (via swallowing of saliva/mucus containing asbestos) ▪ Mesothelioma can theoretically affect any organ with mesothelial cells, most commonly found in thoracic cavity

Chapter 130 Respiratory Tumors TYPES Malignant ▪ Prognosis is poor, unless caught early; extremely resistant to treatment; spread to multiple organs Benign ▪ Prognosis is excellent; surgery for isolated lesions usually curative SIGNS & SYMPTOMS TREATMENT MEDICATIONS ▪ Chemotherapy SURGERY ▪ Excision OTHER INTERVENTIONS ▪ Radiation ▪ Angina, dyspnea, recurrent pleural effusions, weight loss, cough ▪ If tumor invades blood vessel ▫ Blood-tinged sputum DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray, CT scan ▪ Visualize mesothelioma lesions LAB RESULTS Biopsy ▪ Video assisted thoracoscopic surgery (VATS) ▪ Tissue sample immunostained with antibody that reacts to calretinin ▫ Calretinin: calcium-binding protein that regulates calcium levels inside cells ▫ Distinguishes mesotheliomas from other tumors ▪ Cancerous cells have “fried egg” appearance Figure 130.1 A CT scan of the chest in the coronal plane demonstrating a mesothelioma occupying the lower thoracic cavity. Figure 130.2 Immunohistochemical staining with calretinin reveals the architecture of this pleural mesothelioma. OSMOSIS.ORG 925

Figure 130.3 The histological appearance of epithelioid mesothelioma. The malignant cells are cuboidal, have moderate amounts of cytoplasm and display conspicuous nucleoli. Figure 130.4 The gross pathology of a large mesothelioma of the thoracic cavity. The tumor completely encases the normal lung tissue (outlined). NASOPHARYNGEAL CARCINOMA osms.it/nasopharyngeal-carcinoma PATHOLOGY & CAUSES ▪ Cancer of nasopharynx (upper throat, behind nose) ▪ Most common malignant tumor of nasopharynx ▪ Can be clinically silent for long periods, difficult to detect early ▪ Often metastasizes to cervical lymph nodes ▪ Associated with Epstein–Barr virus (EBV) ▪ Prognosis ▫ Five year survival rate, 60% (all types) TYPES Keratinized squamous cell carcinoma ▪ Worst prognosis, least radiosensitive Nonkeratinized squamous cell carcinoma ▪ Best prognosis 926 OSMOSIS.ORG MNEMONIC: NASOPharyngeal Types of Nasopharyngeal malignant cancers Nasopharyngeal Adenocarcinoma Squamous cell carcinoma Olfactory neuroblastoma Plasmacytoma Undifferentiated/basaloid carcinoma (lymphoepithelioma) ▪ Most radiosensitive RISK FACTORS ▪ More common in individuals who are biologically male, < 55 years ▪ Family history ▪ Common in Asia, Africa (esp. children); in southern China, common in adults, rare in children

Chapter 130 Respiratory Tumors ▪ Diets high in nitrosamines (fermented foods), alcohol ▪ Smoking, certain chemical fumes, formaldehyde COMPLICATIONS ▪ Radiation ▫ Death of healthy tissue, brain stem injury, blindness, xerostomia SIGNS & SYMPTOMS ▪ Altered vision, recurrent ear infections, headache, tinnitus, nosebleeds, sore throat, facial paresthesia ▪ Lump in neck, epistaxis, nasal obstruction DIAGNOSIS DIAGNOSTIC IMAGING TREATMENT MEDICATIONS ▪ Monoclonal antibodies ▫ Synthetic antibodies, target epidermal growth factor receptors (EGFRs); adverse effects (Type III hypersensitivity infusion reaction, rash, fatigue, headache, fever, diarrhea) SURGERY ▪ Surgical resection OTHER INTERVENTIONS ▪ Intensity-modulated radiation therapy (standard) ▫ High-precision radiation, minimizes damage to surrounding tissues; better outcome, less adverse effects than conventional radiation therapy CT scan, MRI, PET, X-ray, nasopharyngoscopy/nasal endoscopy ▪ Visualize carcinoma LAB RESULTS Biopsy ▪ Squamous cell carcinoma/undifferentiated OTHER DIAGNOSTICS ▪ Physical exam ▫ Neck swelling Figure 130.5 An MRI scan of the head in the sagittal plane demonstrating a large nasopharyngeal carcinoma blocking the choanae and invading the skull base. OSMOSIS.ORG 927

NON-SMALL-CELL LUNG CARCINOMA osms.it/nsclc PATHOLOGY & CAUSES ▪ Lung cancers not of small-cell type ▪ Grow, spread more slowly TYPES Squamous-cell carcinoma ▪ Centrally located, strongly associated with smoking Adenocarcinoma ▪ Develops peripherally in bronchiole/alveolar sac, no link to smoking Large-cell carcinomas ▪ Found throughout lungs; centrally, peripherally ▪ Diagnosis of exclusion; if criteria for adenocarcinoma/squamous-cell carcinoma not met Bronchial carcinoid tumor ▪ Low-grade malignancy of neuroendocrine cells ▪ Same cell of origin as small-cell carcinoma; malignant potential low DIAGNOSIS LAB RESULTS Fine needle aspiration (lung) ▪ Cells demonstrate cardinal features of malignancy ▫ Variation in nuclear size, shape; irregularly distributed nuclear chromatin; large prominent nucleoli TREATMENT SURGERY ▪ Contraindicated in cases of metastasis outside of chest ▪ Recurrence likely even after complete resection OTHER INTERVENTIONS ▪ Radiation, chemotherapy SIGNS & SYMPTOMS ▪ ▪ ▪ ▪ ▪ ▪ 928 OSMOSIS.ORG Cough Hemoptysis Hoarseness Chest pain Weight loss Neurologic symptoms (brain metastasis is common) Figure 130.6 A cytological preparation of a bronchial washing containing malignant squamous cells.

Chapter 130 Respiratory Tumors Figure 130.8 The histological appearance of squamous cell carcinoma of the lung. The tumor cells have large amounts of eosinophilic cytoplasm, have irregular nuclear forms and are forming islets. The surrounding lung demonstrates a chronic inflammatory cell reaction. Figure 130.7 The gross pathological appearance of squamous cell carcinoma of the lung. There is a large primary tumor in the upper lobe with intrapulmonary metastases in the lower lobe. Figure 130.9 The histological appearance of adenocarcinoma of the lung. The tumor is forming slit like spaces called acini, which are lined by malignant cells. OSMOSIS.ORG 929

PANCOAST TUMOR osms.it/pancoast-tumor PATHOLOGY & CAUSES ▪ Pulmonary neoplasm located in lung apices ▪ Location enables them to impinge nerves, vessels ▪ Majority ▫ Non-small-cell lung tumors (adenocarcinoma/squamous cell carcinoma) ▪ Structures most vulnerable to compression/ invasion ▫ Cervical sympathetic nerves, brachial plexus, laryngeal nerves, superior vena cava (SVC) MNEMONIC: Horner has a MAP of the Coast PanCoast → Horner’s syndrome, including: Miosis Anhidrosis Ptosis SIGNS & SYMPTOMS ▪ Cough, angina, dyspnea, hemoptysis, wheezing ▪ Recurrent pneumonia ▪ Constitutional symptoms ▫ Loss of appetite, weight loss, weakness Local inflammation and compression ▪ Tumor causes local inflammation, invasion of nearby nerves/vessels, direct compression ▪ Pain, upper extremity weakness due to brachial plexus impingement ▪ Compression ▫ Cervical sympathetic nerves: Ipsilateral Horner syndrome (ptosis, miosis, anhidrosis) 930 OSMOSIS.ORG ▫ Brachial plexus: ipsilateral paresthesia ▫ Laryngeal nerves: voice hoarseness ▫ SVC: SVC syndrome (facial flushing, edema, dyspnea) DIAGNOSIS DIAGNOSTIC IMAGING CT scan/chest X-ray ▪ Tumor in lung apex LAB RESULTS Biopsy ▪ Confirm tumor type OTHER DIAGNOSTICS ▪ Physical examination TREATMENT ▪ Impingement of important nerve /vessel; shrink tumor before resection MEDICATIONS ▪ Chemotherapy ▫ Late stages: chemotherapy alone; prophylactic radiation to decrease chance of brain metastases SURGERY ▪ Surgical resection OTHER INTERVENTIONS ▪ Radiation ▫ Early stages: used with chemotherapy

Chapter 130 Respiratory Tumors Figure 130.10 The gross pathological appearance of squamous cell carcinoma of the lung. There is a large primary tumor in the upper lobe with intrapulmonary metastases in the lower lobe. Figure 130.11 A CT scan of the chest in the coronal plane demonstrating a pancoast tumor at the apex of the right lung. SMALL-CELL LUNG CANCER osms.it/sclc PATHOLOGY & CAUSES ▪ Uncontrolled proliferation of small, immature, neuroendocrine cells ▪ Strongly associated with smoking ▪ Usually develops centrally in lung, near main bronchus ▪ Grows fastest, rapidly metastasizes to other organs; intrapulmonary metastasis also common ▪ Secretes hormones → paraneoplastic syndromes ▫ Cushing’s syndrome: excretion of cortisol from adrenal glands → elevated blood glucose, high blood pressure ▫ SIADH: release of antidiuretic hormone (ADH) from tumor → water retention → high blood pressure, edema, concentrated urine ▫ Eaton–Lambert myasthenic syndrome (Type II hypersensitivity): small-cell carcinoma stimulates production of autoantibodies → destroy neurons TYPES Limited ▪ Contained within one lung, supraclavicular nodes (no extension to cervical/axillary nodes) ▪ Prognosis ▫ Five year survival, 10% (median survival 15–20 months) Extensive ▪ Spreads beyond one lung, supraclavicular nodes ▪ Prognosis ▫ Five year survival, 1% (median survival 8–13 months) OSMOSIS.ORG 931

SIGNS & SYMPTOMS ▪ ▪ ▪ ▪ Dyspnea Wheezing Cough Hemoptysis DIAGNOSIS LAB RESULTS ▪ Histology ▫ Large cells with limited cytoplasm, nuclear moulding Figure 130.12 The histological appearance of small cell carcinoma. The cells have minimal cytoplasm and moulded nuclei. TREATMENT SURGERY ▪ Usually not curative OTHER INTERVENTIONS ▪ Limited ▫ Combination of chemotherapy, radiation therapy ▪ Extensive ▫ Chemotherapy, prophylactic radiation Figure 130.13 A PET-CT scan in the coronal plane demonstrating high-uptake in the left upper lobe, corresponding with a small cell carcinoma of the lung. The left ventricle also demonstrates high uptake, but this is normal. Figure 130.14 A cytology specimen demonstrating the characteristic features of small cell carcinoma; nuclear moulding, salt and pepper chromatin and minimal cytoplasm. 932 OSMOSIS.ORG

Chapter 130 Respiratory Tumors SUPERIOR VENA CAVA SYNDROME osms.it/svc-syndrome PATHOLOGY & CAUSES SIGNS & SYMPTOMS ▪ Constellation of signs, symptoms when blood flow through SVC obstructed ▪ Obstruction → increase in venous pressure behind obstruction → blood rerouted through collateral vessels → blood drains into inferior vena cava, right atrium → dilation of collateral veins → venous pressure decreases with full dilation of collateral veins ▪ Collateral vessels ▫ Azygos vein, internal mammary vein, lateral thoracic vein, esophageal venous systems ▪ Edema of face, neck; inspiratory stridor; voice changes; flushed appearance (backup of blood, venous stasis); dilated neck, chest veins; dyspnea (blockage of SVC → decreased return of blood to heart → less blood pumped to lungs); hoarseness of voice (compression of laryngeal nerve/ muscles of larynx from excess fluid) CAUSES ▪ Obstruction (external/internal) ▫ Tumor invasion, mass effect (inflammation, swelling) ▫ Lung cancer most common (e.g. Pancoast tumor), tumor of lymph nodes (e.g. lymphomas) ▫ Blood clot (develops in individuals with long-term device; e.g. indwelling central venous catheter) COMPLICATIONS ▪ Edema, dysphagia, cerebral ischemia ▪ Severe cerebral edema → compression of blood vessels in brain → cerebral ischemia DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray/CT scan/venous angiography ▪ Visualize tumors, collateral vessel dilation, obstruction LAB RESULTS Biopsy ▪ Evaluate tumor; determine type, staging TREATMENT MEDICATIONS ▪ Steroids ▫ Reduce swelling around tumor ▪ Anticoagulants ▫ Treat blood clot OTHER INTERVENTIONS ▪ Combination of surgery, chemotherapy, radiation therapy ▪ Keep head above level of heart to help drain fluid from head, neck to heart OSMOSIS.ORG 933

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