Topic: Mediastinum, Solitary Pulmonary Nodule, Lung CA Lecturer: Dr.

Gervasio The Mediastinum - Anatomic space that lies between two pleural cavities and extends from the diaphragm to the thoracic inlet.

Subdivisions of the Mediastinum as seen in cross section anterior mediastinum (1) middle mediastinum (2) posterior mediastinum (3)

A lot of lymph nodes can be found in the mediastinal compartments = a common neoplasm: LYMPHOMA because of lymphatic spread. I. Anatomy a. Borders Thoracic Inlet Superior Diaphragm Inferiorly Sternum Anteriorly Vertebral Column Posteriorly 3 Compartments and Contents: Compartment Contents Anterosuperior Thymus gland, lymph nodes, fat, aortic arch, superior vena cava, parathyroid gland, ectopic thyroid tissue Middle Pericardium, heart, great vessels, trachea, and tracheal bifurcation, main bronchi, phrenic nerves, hilar lymph node Posterior Esophagus, vagus nerves, sympathetic chain, thoracic duct, descending thoracic aorta, azygous vein, hemiazygous vein, paravertebral lymph node

b.

sometimes the thyroid grows too big due to anomalies, so big that it goes into the neck or into the mediastinum.

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Diagnostic a. Chest X-rays mediastinal masses commonly found incidentally b. CT Scan second most common modality used, next to x-ray c. Magnetic Resonance Imaging useful for better visualization of certain vascular structures d. CT Guided Needle Biopsy (FNAB vs Core) e. Mediastinoscopy with biopsy cytopathologists needed to read FNAB better Mediastinoscopy is a surgical procedure to examine the inside of the upper chest between and in front of the lungs (mediastinum). f. VATS (Video-Assisted Thorascopic Surgery) is a minimally invasive surgical technique used to diagnose and treat problems in the chest. During this surgery, one or more small incisions are made in the chest. A tiny fiber-optic camera (called a thorascope) is inserted through one incision, and surgical instruments are inserted through this or other small incisions. The thoracoscope transmits images inside the chest on a video monitor, guiding the surgeon in maneuvering instruments to complete the procedure (sounds a lot like laparascopic surgery right?) g. Radionuclide Scanning a way of imaging bones, organs and other parts of the body by using a small dose of a radioactive chemical. h. Angiography i. Immunologic Staining this is done since it may be difficult to distinguish one mediastinal tumor from the other It is important to know the normal first, before you can understand the abnormal. Below is a normal CXR shown with labels.

absent clavicle on the left side

note gas bubble of left side; dextrocardia

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Mediastinal Tumors and Cysts In Adults o 25-35% malignant; o Neurogenic tumors most common @ 20% o Thymomas (most common anterior mediastinal tumor in adults), congenital cysts, lymphomas (most common in both adults and children but more common in children? Which one is it doc? =/ ) o Usually asymptomatic In Children o 25-45% malignant o Lymphomas (most common), neurogenic tumor

Symptomatology: 1/3 to half of the cases are asymptomatic Non-specifc symptoms include chest pain, cough, dyspnea (Compression Syndrome) Endocrine Symptoms: o Hypertension Pheochromocytoma o Hypercalcemia Parathyroid tumor o Thyrotoxicosis Intrathoracic goiter o Gynecomastia Choriocarcinoma I. Thymoma Most common anterior mediastinal mass in adult Rare in children 1/3 are asymptomatic at diagnosis Symptoms include: mass effects (compression symptoms) and systemic effects due to paraneoplastic syndromes (Myasthenia gravis) Myasthenia gravis is seen in 10-50% of patients with thymomas Thymomas is seen in only 8-15% of patients with Myasthenia gravis Histopathology: proportion of lymphocytes to epithelial cells Malignancy = Invasiveness (capsular or vascular) Treatment: Surgery + radio and chemotherapy Germ Cell Tumor Primary extra-gonadal germ cell tumors are RARE! Only 1% of all mediastinal tumors. Most common in the anterior mediastinum M>F predilection (4:1) Commonly affects young adults Types: Seminoma Embryonal cell carcinoma Choriocarcinoma Malignant Teratoma Endodermal yolk sac tumor Diagnosis: CT Scan and Tumor Markers (B-HCG, A-fetoprotein, Carcinoembryonic antigen or CEA) Treatment: Complete Resection and Adjuvant Therapy Seminomas radiosensitive = better prognosis Other tumors chemotherapy Lymphomas Mediastinal involvement seen in 50% of both Hodgkins and non-Hodgkins lymphoma Most common mediastinal malignancy Most commonly seen in the anterior mediastinum Symptoms include: cough, chest pain, fever and weight loss Diagnosis: Chest X-ray and CT Scan Mediastinotomy/mediastinoscopy with biopsy

II.

III.

Sometimes immunohistopathology is done if pathologists cant figure it out! Treatment: Radiotherapy and Chemotherapy Surgery done mainly for diagnosis Resection is NOT done for lymphomas

IV.

Teratomas Mostly in adolescents 80-85% of cases are benign Contains all 3 germ layers: endoderm, mesoderm, and ectoderm Many are asymptomatic; others have symptoms related to compression (cough, pleuritic chest pains, dyspnea) Diagnosis: X-ray and CT Scan (smooth walled cystic or solid lesions) Treatment: Total Surgical Excision

Middle Mediastinal Lesions o usually cystic o 2 most common lesions: Pericardial Cyst Usually asymptomatic Found on chest x-ray at cardiophrenic angle Surgery is both diagnostic and therapeutic Bronchogenic Cyst Arise posterior to the carina May be asymptomatic or may cause compression symptoms Treated by excision Patients often complain of compression symptoms (+) lining of the cyst on CXR differentiates it from pneumothorax Posterior Mediastinal Lesions o mostly neurogenic lesions along the paravertebral gutter o 25% are malignant o 75% of cases occur in children (<4 years old) Higher probability of malignancy Surgery may not be an option in most malignant cases Dumbbell tumors tumors that grow inside the spinal canal with another extension outside; surgically a cause for concern; may cause rapid bleeding death More diagnostic tools are implicated to study the spinal canal o
Neurilemomas from Schwann cells; slow growing; well circumscribed and have a defined capsule

Common histologic types:

Neurofibromas has malignant potential; poorly encapsulated and consists of randomly arranged spindle-shaped cells Neurosarcomas originate by malignant degeneration of either neurilemomas or neurofibromas, in addition to developing de novo; usually occurs in adults Ganglioneuromas from sympathetic ganglia; well encapsulated Neuroblastomas also from sympathetic chain; highly invasive (have already metastasize before diagnosis) Pheochromocytoma Rarely occurs; behave similarly to adrenal lesions

Symptoms: Chest pain Spinal cord compression Endocrine symptoms Fever, vomiting, diarrhea and cough in Neuroblastoma o Treatment: Surgery and Radiotherapy (for malignant lesions) In the recording doc said chemo and radiotherapy?? o Superior Vena Cava Syndrome o 85% of cases are due to Bronchogenic CA (most commonly small cell type 40%) o Causes: Mediastinal tumors Fibrosing mediastinitis Thoracic aortic aneurysm SVC thrombosis due to catherization/instrumentation o Presents as venous distention, facial edema, plethora, headache, and respiratory symptoms o Diagnosis: CT Scan o Treatment: Radiation and Chemotherapy (palliative) Steroids and Diuretics still questionable Bypass or Vein Reconstruction (for benign lesions) Stenting: Endovascular Procedure IV. Mediastinal Infections Acute Mediastinitis fulminant infection with high morbidity and mortality Rapid spread through areolar planes, within 24 hours, to involve neck and lungs Both gram (+) and (-) bacteria Symptoms: chest pain, dysphagia, respiratory distress, subcutaneous crepitation Diagnosis: Chest X-ray, Water soluble contrast study Treatment: hydration, drainage, control of primary problem (must be early and aggressive) **antibiotics are also given Etiology: Esophageal or tracheal perforations Open heart surgery more indolent course; usually due to Staphylococcus (MRSA)
Esophageal perforation a very real complication; rare in trauma; more commonly injured in endoscopic procedures or intentional intake of corrosive substances (acid ingestion is common in the phils)

Chronic Mediastinitis Chronic fibrosis and inflammation Usually due to granulomatous infections (TB, Histoplasmosis)

SOLITARY PULMONARY NODULE SPN: 3 cm or less in diameter About 40% malignant Lung mass: greater than 3 cm Vast majority are malignant size = risk of it being malignant it is important to rule out malignancy! Differential Diagnosis of SPN Neoplasm Infection (commonly TB) Inflammation Vascular Trauma Congenital Rheumatoid nodule Lymph node Sarcoidosis by examining the CXR, one can have an idea if it is malignant or being consider px risk factors, medical Hx Factors Influencing Probability of Malignancy Size Growth rate
25% in diameter = doubling of the volume more malignant = shorter doubling time dont rely on just one radiologic examination, usually a series of radiographs must be reviewed to compare the size of the tumor seen in older films

Number Density Circumstances of CT Patient age Gender Smoking history Spirometry Occupational history Endemic granulomatous disease Size of SPN Most SPN are less than 2 cm in diameter Malignant nodules 40% less than 2 cm 15% less than 1 cm 1% less than 7 mm 0% less than 5 mm Growth Rate: Doubling Time 3 Volume = 4/3 r 25% increase in diameter results in doubling of volume Non-malignant disease: less than 20 days or greater than 400 days Malignant lesions: 30 to 180 days note: germ cell tumors, melanomas, sarcoma can grow in 2 weeks classically; thyroid can take months Radiographic Characteristics Malignant disease Spiculated (primary) 90% malignant Round, smooth, and peripheral (metastatic) 20% malignant Thick walled cavity Eccentric calcification

Benign disease Characteristic calcifications Smaller than 5 mm Non-solid lesion 5-9 mm Thin walled cavity Satellite nodules **no growth in the last 2 yrs? Probably benign

Note: Eccentric calcifications can occur in malignancies, especially at scar sites, so called scar carcinomas

SPN: RUL

SPN: RUL: Spiculated lesion

Malignancy, Right upper lobe, posterior segment TB almost never affects anterior segment

SPN: Lesion behind rib

One of the reasons they do the Apico-lordotic view

SPN: Posterior lesion

Primary lung cancer, RUL, posterior segment

Central calcification Popcorn calcification

WORK-UP OF SPN Multidisciplinary Approach PCP Radiology Pulmonary Thoracic surgery Oncology Review prior films! Others: Advanced directives Stratification of care Information regarding possible outcomes Pt advocate and shepard Imaging and Procedures CXR CT Scan CT Scan with contrast to evaluate mediastinum Serial scans at 3, 6, 12, and 24 months Can consider trial of antibiotics prior to repeat scan in 6 weeks Newer CT techniques Volumetric analysis Multi-slice scanner PET ScanPositron Emission Tomography 18-FDG (fluorodeoxyglucose) increased uptake by metabolically active cells (like tumor cells, but not exclusivelyso correlate clinically) does not enter glycolysis Allows more accurate identification of tumors, lymph nodes, and metastatic disease Benign disease Malignant disease 96% sensitivity 96% sensitivity 88% specificity 77% specificity Note: Can more clearly determine if a lesion is malignant; Can detect LN mets and unsuspected metastatic disease Limitations of PET Scans Spatial resolution 7-8 mm thus unreliable for lesions less than 1 cm False positives in infection or inflammation False negatives in tumors with low uptake such as bronchoalveolar cell carcinoma High post test likelihood of malignancy (14%) in high risk patients with negative PET Utilization of PET Scans Negative PET in high risk patients still need tissue diagnosisso why get it? PET not usually indicated unless it will change management PET not indicated if surgery is planned PET not indicated with known malignancy Bronchoscopy Limited role Transbronchial needle aspiration of mediastinal lymph node Useful for large central lesions and endobronchial lesions Can detect infection No use in peripheral nodules BiopsyCT guided Transthoracic needle aspiration (TTNA) Increasing utilization of TTNA Not indicated for patients committed to surgery Accuracy for detecting malignancy 64-100% Yield increased when cytopathologist present Three results: Malignant Specific benign, e.g. TB Non-specific benign, e.g. bronchoalveolar hyperplasia Complications: Pneumothorax 25%, chest tube <5%, Hemoptysis <10% Relative contraindications: Pulmonary HTN, severe COPD, AVMs, coagulopathy Absolute contraindication: One lung or bilateral lung transplant No change in two years - no further Fine needle aspiration (FNA)
evaluation Characteristic calcifications of benign Surgical disease Video Assisted Thoracic Surgery (VATS) Lateral films for hidden lesions peripheral nodules within 2 cm of pleura Initial CXR then serial CT Scans for solid lesions; superficial lesions (lung surface) for lesions not diagnosed by other means Open Thoracotomycommitment to resection with curative intent; if lesion is not located superficially

Pulmonary Specific Preoperative Evaluation Prior to Lung Resection PFTs are predictive of post-op complications and mortality DLCO correlates with risk of post-op mortality better than FEV1 PaCO2 > 45 not an independent risk factor Three stages: PFTs Quantitative Lung Scan Exercise Testing Stage I Assessment: PFTs Stage II Assessment: Stage III Assessment: Predictors of Low Quantitative V/Q Scan Exercise Testing Complication Rates No further work-up and no Patients who do not meet Cardio-pulmonary exercise limitations:FEV1 > 2 L and Stage I criteria testing (CPET) DLCO > 60% predicted VO2 > 20 ml/kg/min 133 Ventilation: Xe acceptable risk 99 Pneumonectomy:FEV1 > 2 Perfusion: Tc labeled VO2 < 15 L and DLCO > 60% predicted macroaggregates ml/kg/minincreased risk VO2 > 20 ml/kg/min Lobectomy:FEV1 > 1L and Radioactive uptake correlates correlates with 5 flights DLCO > 50% predicted with lung function Stair Climbing 3 flights: FEV1 > 1.7 L Wedge / Segmentectomy: Post-op FEV1 = (pre-op 5 flights: FEV1 > 2 L FEV1 > 0.6 L and DLCO > 50% FEV1) x (% of radioactive predicted uptake of non-operated lung) Pneumonectomy: ppo FEV1 > 40% of predicted ppo DLCO > 40% of predicted Exceptions to the Rules CHEST 2005; 127:1984-1990

Foundation of Algorithms No change in 24 months on CXR or CT requires no further evaluation Serial CT Scans at 3, 6, 12, and 24 months TTNA for those not committed to surgery Surgical biopsy with curative intent Pre-op evaluation prior to surgery

Sample Pre-biopsy Algorithm CHEST 2004; 125:1522-1529

Sample Post-biopsy Algorithm CHEST 2004; 125:1522-1529

Sample Preoperative Evaluation Algorithm CHEST 2003; 123:2096-2103

Cases Case I: 20 yo female, family history of TB, non-smoker, with calcified 1 cm nodule in posterior segment of RUL also seen in x-ray 6 months ago Work-up: Observation and serial imaging if indicated (because risk for lung CA is ) Case II: 60 yo male history of O2 dependent COPD, remote colon cancer, 40+ pk yr smoker, with 2.5 cm irregular nodule in anterior segment of RUL Work-up: Tissue diagnosisBiopsy with curative intentPreoperative evaluation with PFTs, DLCO, and quantitative lung scan if indicatedTTNA if surgery not an option (because risk of malignancy is ) Summary SPN by definition is 3 cm or less 40% are malignant NSCLC 5-year survival Stage I 60% Stage IV 1% Doubling times of cancer can be 30 days REVIEW PRIOR FILMS!!! No change in 2 yearsno further work-up Serial CT Scans at 3, 6, 12, and 24 months TTNA for those not committed to surgery Surgical biopsy with curative intent Pre-op evaluation prior to surgeryPFTs, Quantitative Lung Scan, CPET LUNG CANCER BRONCHOGENIC CARCINOMA Leading cause of cancer death 40 years old and above (>95%) Etiology: Smoking implicated in 75% or more at least 20 pack-years impact of second-hand smoke Asbestos Petroleum products Radioactive materials (Role of Genetics ) - oncogenes

there is a 20 year lag between smoking & lung CA cessation of smoking = risk of developing lung CA compared to those who continue smoking, however, risk is still compared to never-smokers

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PRIMARY LUNG CANCER: CLASSIFICATION Non-small cell CA Squamous / Epidermoid Adenocarcinoma Scar carcinoma Bronchoalveolar cell CA (variant) Adenosquamous Large cell anaplastic / undifferentiated overall 5 yr survival < 15% 50% mets at diagnosis surgery an option up to 70% 5 yr survival for Stage IA Small cell / oat cell

overall <10% 5 yr survival 70% mets at diagnosis surgery not an option usually more aggressive more proximal near tracheobronchial tree more common associated with smoking

develops more in the periphery incidence number of female cases can also be attributed to previous injury to the lung PTB is a possible risk factor (fibrosis) Metastasis is not uncommon

Undifferentiated CA Tend to rapidly evolve and spread Tx: surgery Can grow anywhere, but usually centrally located

Aggressive type of tumor Very poor prognosis Tx: non-surgical Usually diagnosed late Generally responsive to chemotherapy, but because patients are diagnosed late = advanced disease = poor prognosis

BRONCHOGENIC CA: DIAGNOSIS Chest x-ray - Since the chest is a 3D structure, it is useful to get CXR - Request for upright PA (postero-anterior) view - Also request for the lateral upright CXR - Can detect 1cm nodules Sputum cytology May still be of some use in certain cancers But most useful for infectious diseases Bronchoscopy - helps assess the resectability of the tumor CT + percutaneous needle biopsy = most useful - to obtain cytologic specimens (washing / brushing / biopsy) - to assess bronchial/carinal involvement (assess resectability)

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Percutaneous needle biopsy CT Scan - to assess tumor location, size, extension (useful for staging, but biopsy is still needed to come up with actual Dx of CA - to assess mediastinal lymph node status (problem: inflammatory vs neoplastic) - with biopsy, to get histologic diagnosis Mediastinoscopy / mediastinotomy Thoracotomy - frozen section rapid histopathology - not routinely done CLINICAL MANIFESTATIONS May be asymptomatic; seen only on chest x-ray Often in advanced stages when symptomatic, and on diagnosis Pulmonary symptoms: cough fever dyspnea chest pain sputum production Extrapulmonary symptoms - related to site of metastasis - may be secondary to hormone-like substance produced by the tumor (e.g. Small cell CA Cushings Syndrome)

PANCOAST TUMOR Superior pulmonary sulcus tumor Different from apical lung carcinoma Symptoms may be due to: Brachial plexus involvement Sympathetic ganglia involvement Vertebral body involvement / collapse Horners syndrome ptosis miosis anhydrosis enophthalmos BROCHOGENIC CA: STAGING Based on the TNM Classification T tumor size, location, extent N regional lymph node involvement M distant metastasis Considers Host Performance Status Ho (normal activity) H4 (bedridden) Categories: c - clinical s - surgical p postsurgical / pathologic r retreatment a - autopsy
**paralysis of the hemodiaphragm consider possible involvement of the phrenic nerve **hourseness consider involvement of the laryngeal nerve **each lung lobe has its own arterial supply, drainage, etc each can function independently **lobectomy is usually done (lobectomy) **a px can even tolerate removal of one whole lung (Pneumonectomy)

BRONCHOGENIC CA: TREATMENT - Surgery for early lesions ( up to IIIA ) Lobectomy usually minimum resection Pneumonectomy or variant at times - Radiotherapy - as adjuvant / palliative tx; usually given after surgery of if surgery is not possible - Chemotherapy as neoadjuvant / adjuvant / palliative tx - Immunotherapy still being developed **after surgical resection body compensates lungs tend to hyperinflate **if a whole lung is removed replaced with fluid solidification fibrosis

BRONCHOGENIC CA: CONTRAINDICATIONS TO SURGERY Malignant pleural effusion Recurrent laryngeal nerve involvement (manifests with hoarseness, but also rule out laryngitis before considering matastasis) Distant metastasis Contralateral mediastinal LN involvement Carinal / high paratracheal LN involvement Scalene or supraclavicular LN involvement Tumor invasion of the heart, great vessels, esophagus, trachea, vertebral body Superior vena cava syndrome (secondary to compression by the tumor) Phrenic nerve paralysis Poor pulmonary function (relative contraindication; in line with thissome surgeons would still do a segmentectomy (less than a lobectomy) just to reduce the tumor load in order to improve the pulmonary function)

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**sometimes a tumor might obstruct the airway, usually the primary and secondary bronchi. So if possible, laser ablation is done to re-establish the airway. A stent is sometimes inserted just to open up the airway

PALLIATIVE TREATMENT Surgery USUALLY NOT ADVOCATED Radiotherapy / Chemotherapy Bronchoscopic obliteration of tumor by laser for bronchial obstruction PROGNOSIS Depends on: Cell type and differentiation Stage at the time of diagosis Various host factors NSCLC Survival Rates Stage I Stage II Stage IIIA Stage IIIB Stage IV 60% 23% 11% 5% 1% surgery no surgery

**Distinction between IIIA and IIIB is key due to surgical intervention **Malignant effusion is IIIB, surgery not indicated, therefore tap the effusion

Small Cell Lung Cancer **Surgery rare and limited to very small localized early disease **Brain mets occur in 10% at diagnosis **Paraneoplastic syndromes.SIADH, Eaton Lambert, Limited (30-40%) confined to one hemithorax one RT portal chemo and RT median survival: 18 mo 5 yr survival: < 18% Extensive (60-70%) not limited cannot fit in one RT portal chemo, palliative RT median survival: 7 mo 5 yr survival: < 2%

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METASTATIC LUNG CANCER Fairly common May be the only site of metastasis from a nonpulmonary tumor Spread to lungs is by direct infiltration, lymphatics, blood (more important route) SURGICAL TREATMENT: PRINCIPLES Single or multiple metastatic tumors, even when in both lungs, CAN be removed as part of treatment (usually the sarcomas) as long as you can: - preserve as much normal lung - have adequate margins of resection Exclusion of other metastatic sites is important The primary site must be controlled Other modalities of treatment not effective

END OF TRANSCRIPTION Hi homer leelee baggie rencie markie jemelee =)

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