Case Presentations 1

Case Presentations

Gamal Rabie Agmy ,MD ,FCCP

Professor of Chest Diseases, Assiut University

Case No. 1

• A 77-year-old man comes to the ED complaining of the acute onset of dyspnea and presyncope that occurred 2 hours ago while retrieving his luggage after a 6-h plane flight.

• He didn’t notice any chest pain or hemoptysis.

• His medical history is remarkable for long-standing, poorly controlled hypertension; diastolic heart failure; and an ischemic stroke 6 weeks ago with a residual mild right-sided hemiparesis.

• His medications include:

Aspirin, 325 mg daily;

Lisinopril, 40 mg daily; and

Verapamil, 360 mg daily.

• On physical examination, he appears anxious. He has a BP of 122/83 mm Hg, heart rate of 113/min, temperature of 36.6C, respiratory rate of 26/min, and oxygen saturation of 86% on room air.

• Laboratory studies reveal the following:

D-dimer level of 9.57 g/mL (52.40 nmol/L), Brain natriuretic peptide level of 968.2 pg/mL (968.2 ng/L), and

Cardiac troponin T level of 0.06 ng/mL (0.06 g/L).

• CT pulmonary angiogram are shown:

• An echocardiogram is performed, which reveals left ventricular hypertrophy with normal systolic function. The right ventricle is moderately enlarged, and there is severe basal RV systolic dysfunction. Paradoxical septal motion and a D-shaped intraventricular septum are noted in both systole and diastole. The inferior vena cava expiratory diameter is dilated. Moderate tricuspid regurgitation is noted with an estimated right ventricle systolic pressure of 65 mm Hg. There are no other valvular abnormalities. At the main pulmonary artery bifurcation, there is an area of increased echogenicity protruding into both main pulmonary arteries that could represent a clot.

• The patient receives supplemental oxygen and IV unfractionated heparin (UFH), and is admitted for close monitoring.

• Two hours after admission, his BP drops to 86/52 mm Hg.

• He is given fluid without any response and vasopressor support is initiated. In addition to continuing the fluids and vasopressors,

• Your next best step is to:

A. Switch to a low-molecular-weight heparin (LMWH).

B. Insert an inferior vena cava filter.

C. Perform catheter embolectomy.

D. Administer systemic thrombolytic therapy.

large bilateral central clot on CT angiography

According to ACCP antithrombotic guidelines published (2008)

• Recommend thrombolytic therapy for all patients with hemodynamic compromise unless there are major contraindications owing to bleeding risk (Grade 1B).

Major contraindications include

• A history of intracranial hemorrhage

• Known intracranial aneurysm or arteriovenous malformation

• Significant head trauma

• Active internal bleeding

• Known bleeding diathesis

• Intracranial or intraspinal surgery within 3 months

• A cerebrovascular accident within 2 months.

Relative contraindications include:

• Recent internal bleeding

• Recent surgery or organ biopsy

• Uncontrolled hypertension

• Pregnancy

• Age 75 years.

• This patient has a major and several relative contraindications, so systemic thrombolysis would not be the best option (choice D is incorrect).

• The ACCP guidelines also recommend that, in patients with massive PE who cannot receive thrombolysis because of contraindications or time, interventional catheterization techniques are used if appropriate expertise is available (Grade 2B). Catheter-directed therapy provides a less extreme advanced treatment option than surgical embolectomy.

• Many experts agree that patients that meet the following criteria should be considered for catheter embolectomy:

(1) acute PE with hemodynamic instability;

(2) subtotal or total filling defect in the left and/or right main pulmonary artery; and

(3) the presence of a major contraindication to systemic thrombolysis, including ischemic stroke. and thus is an ideal candidate (choice C is correct).

Summary

• This patient has massive pulmonary embolism (PE) (confirmed acute PE with shock and obvious right ventricular dysfunction) in the setting of several contraindications to systemic thrombolysis

So the next best step is to:

A. Switch to a low-molecular-weight heparin (LMWH).

B. Insert an inferior vena cava filter.

C. Perform catheter embolectomy.

D. Administer systemic thrombolytic therapy.

Thrombolytics in Acute Pumonary Embolism



1 = “recommendation” 2 = “suggestion” A = based on strong evidence from randomized trials B = moderate evidence that may include randomized trials or observational studies C = weak evidence, mostly consensus opinion

The ACCP’s recommendation classification system:

Which patients with acute pulmonary embolism should I treat with systemic thrombolytics?

The ACCP suggests using systemic thrombolytics to treat patients with acute PE who are hypotensive (they propose a cutoff of systolic blood pressure less than 90 mm Hg). (Grade 2C).


ACCP recommends against treating most patients with acute PE without hypotension with systemic thrombolytics (Grade 1C).


*However, patients deemed to be at high risk for becoming hypotensive according to clinical course are suggested to receive systemic thrombolytics, if they have a low bleeding risk (Grade 2C). *“Looking sick,” dyspneic and hypoxic, right ventricular dysfunction on echocardiogram, elevated troponins, elevated neck veins, severe tachycardia have all been proposed as risk factors.

How should I treat acute pulmonary embolism with systemic thrombolytics?

*A short infusion time of 2 hours for systemic thrombolytics is suggested, rather than a longer infusion (Grade 2C). Tissue plasminogen activator (tPA) has a short infusion time and has been recommended as the best agent for this reason. *Infuse systemic thrombolytics through a peripheral vein, rather than a pulmonary artery catheter (Grade 2C).


Randomized trials show that thrombolytics improve pulmonary artery pressures, oxygenation, and cardiac performance on echocardiography within 24 hours in people with acute pulmomary embolism. However, this comes at a significantly higher risk of bleeding compared to other therapies.


ACCP’s recommendations to provide thrombolytics to people with massive PE (with hypotension) or who are high risk for soon becoming that way. In large part, this is based on the observed mortality seen in series of patients with acute pulmonary embolism: ~5% of people with pulmonary embolus who receive treatment die (from that or another PE) within 7 days. ~2% mortality in patients without hypotension; ~30% mortality when there is shock necessitating inotropes; ~70% mortality if cardiopulmonary arrest occurs.

Catheter-Based Thrombus Removal for the Initial Treatment of

Patients With PE

In patients with acute PE associated with hypotension and who have (i) contraindications to thrombolysis, (ii) failed thrombolysis, or (iii) shock that is likely to cause death before systemic thrombolysis can take effect (eg, within hours), if appropriate expertise and resources are available, we suggest catheter-assisted thrombus removal over no such intervention (Grade 2C).

What shall I do with the heparin infusion during administration of thrombolytic therapy for acute PE?

*There is no ACCP recommendation for this question, stating it is “acceptable … to continue or suspend the unfractionated heparin infusion during administration of thrombolytics.” *In the U.S., regulatory bodies advise stopping unfractionated heparin during t-PA infusion and restarting it when aPTT is <= 80 sec after t-PA is complete. *In many other countries, heparin infusion is continued during t-PA.

Recommendations

Contraindications

Saddle PE :that lodges at the bifurcation of the

main pulmonary artery

Multidetector-CT

Findings

• Partial or complete filling defects in lumen of pulmonary arteries – Most reliable sign is filling defect forming acute

angle with vessel wall with defect outlined by contrast material

– “Tram-track sign” • Parallel lines of contrast surrounding thrombus in vessel

that travels in transverse plane

– “Rim sign” • Contrast surrounding thrombus in vessel that travels

orthogonal to transverse plane

• RV strain indicated by straightening or leftward bowing of interventricular septum

Macdonald S; Mayo J. Semin. Ultrasound CT. 2003;24(4):271-231.

Large saddle thrombus with extensive clot burden. Arrows

demonstrating tram-track sign (A), rim sign (B), complete

filling defect (C), and a fully non-contrasted vessel (D)

Embolic burden scoring system. Schematic of the pulmonary

arterial tree with scores for nonocclusive emboli according to

vessel. Emboli in a segmental pulmonary artery are given a score of

1. Emboli in more proximal pulmonary arteries are given a score

based on the total number of segmental pulmonary arteries

supplied.

http://radiology.rsna.org/content/242/3/889/F4.expansion.html

Thrombotic and Nonthrombotic

Pulmonary Arterial Embolism

By

Gamal Rabie Agmy , MD , FCCP Professor of Chest Diseases ,Assiut University

Acute Pulmonary Embolism Saddle PE :that lodges at the bifurcation of the main

pulmonary artery

Multidetector-CT

Findings

• Partial or complete filling defects in lumen of pulmonary arteries – Most reliable sign is filling defect forming acute

angle with vessel wall with defect outlined by contrast material

– “Tram-track sign” • Parallel lines of contrast surrounding thrombus in vessel

that travels in transverse plane

– “Rim sign” • Contrast surrounding thrombus in vessel that travels

orthogonal to transverse plane

• RV strain indicated by straightening or leftward bowing of interventricular septum

Macdonald S; Mayo J. Semin. Ultrasound CT. 2003;24(4):271-231.

Large saddle thrombus with extensive clot burden. Arrows

demonstrating tram-track sign (A), rim sign (B), complete

filling defect (C), and a fully non-contrasted vessel (D)

Acute pulmonary embolism and deep venous thrombosis (DVT) in a 48-year-old woman. (a) Contrast material–enhanced pulmonary CT arteriogram (1.25-mm collimation) obtained at the level of the basal subsegmental pulmonary artery shows multifocal low-attenuation emboli (arrows) in segmental and subsegmental arteries in the right lower lobe. (b) Contrast-enhanced indirect CT venogram (5-mm collimation) obtained at the level of the pelvic inlet 3 minutes after injection shows large low-attenuation thrombi filling the left common iliac vein (arrow).

Acute pulmonary embolism in a 41-yearoldwoman. Coronal gadolinium-enhanced three-dimensional pulmonary MR angiogram shows a large embolus (arrows) in the proximal

right interlobar artery.

Embolic burden scoring system. Schematic of the pulmonary

arterial tree with scores for nonocclusive emboli according to

vessel. Emboli in a segmental pulmonary artery are given a score

of 1. Emboli in more proximal pulmonary arteries are given a

score based on the total number of segmental pulmonary arteries

supplied.

http://radiology.rsna.org/content/242/3/889/F4.expansion.html

Helical CT Findings in Chronic PTE

Cardiac abnormalities Right ventricular enlargement Right atrial enlargement Thrombi in the right atrium or ventricle*

Vascular abnormalities Eccentric, flattened defect at an obtuse angle with the vessel wall* Irregular or nodular arterial wall Abrupt narrowing of the vessel diameter Abrupt cutoff of distal lobar or segmental artery Recanalization of thrombosed vessel Webs or bands (less frequent)

Parenchymal abnormalities Bronchial artery dilatation Bronchiectasis Areas of decreased attenuation in the lung (mosaic perfusion pattern)

Septic Pulmonary Embolism Septic pulmonary embolism in a 28-year-old intravenous drug abuser with human immunodeficiency viral infection. Repeated blood cultures disclosed a positive culture for Nocardia. (a) Radiograph shows multiple cavitary nodules throughout both lungs. (b) CT scan (10-mm collimation) obtained at the level of the azygos arch demonstrates the feeding vessel sign (vessel leading directly to the nodule) in several nodules

Hydatid Embolism

Fat Embolism

Amniotic Fluid Embolism

Tumor Embolism

Air Embolism

Talc Embolism

Cement (Polymethylmethacrylate) Embolism

Iodinated oil embolism

Miscellaneous Foreign Body Embolism

Case No. 2

• History of exposure to asbestos more than 45 years ago.

• He had long-standing bilateral pleural plaques, upper lobe nodules, and interstitial disease in a UIP pattern, the latter two of which are attributable to the RA

• The patient began to notice streaky hemoptysis mixed with yellowish sputum about 5 months ago, but it cleared spontaneously after a few weeks, only to recur 3 weeks ago.

• A 72-year-old man is seen for evaluation of hemoptysis.

• He had a 14-year history of rheumatoid arthritis (RA) previously treated with hydroxychloroquine, methotrexate, gold, penicillamine, and etanercept.

• Currently, he is taking adalimumab and an NSAID.

• He had a 40 pack-year smoking history but quit 10 years ago and

• He denied any fever, sweats, chills, or weight loss and stated that his chronic respiratory symptoms were stable.

• His only complaint was severe neck pain attributable to severe, unstable cervical spine disease with planned fusion surgery.

• Physical examination revealed bibasilar late inspiratory crackles halfway up both lung fields.

• There was nothing to suggest pulmonary hypertension.

• His spirometry revealed an FEV1 of 2.49 L (78% of predicted) and an FVC of 2.98 L (71% predicted), with an FEV1/FVC of 0.84.

• A representative image from his CT scan is shown in Figure

• Bronchoscopy revealed some old blood in the left upper lobe but no active bleeding or endobronchial lesions were seen.

• Results of cytologic studies and initial smears for infectious organisms were negative.

Which is the best-recommended therapy at the present time?

A. Bronchial artery embolization.

B. Itraconazole.

C. Surgical resection.

D. Oral corticosteroids

• The CT scan reveals a left upper lobe cavity with a mass inside, highly suggestive of a fungus ball.

• Preferred therapy in a patient with reasonably preserved lung function, as in this patient, is surgical resection (choice C is correct).

• For patients who are considered poor operative candidates, a number of alternative, to surgery exist.

• These include bronchial artery embolization if an area of active bleeding can be found in a patient with massive hemoptysis. This is really a temporizing measure because bleeding tends to recur due to the development of massive collaterals (choice A is incorrect).

• Inhaled, intracavitary, and endobronchial instillations of antifungal agents have been tried in small numbers of patients without consistent success.

• The most promising results have been with the use of oral itraconazole, perhaps related to its high tissue penetration.

• However, it works slowly and would not be recommended in patients with significant hemoptysis who were otherwise good surgical candidates (choice C is incorrect).

• There are some older reports on the use of radiation therapy or corticosteroids to control hemoptysis, but neither affects long-term outcomes, and steroids carry the risk of dissemination or fungus ball enlargement (choice D incorrect)

• A fungus ball, or mycetoma, is the saprophytic colonization of a preexisting parenchymal cavity. This cavity may be due to previous infection (eg, TB), bronchiectasis, bullous emphysema, sarcoidosis, and rheumatoid arthritis, among others.

• The fungus ball is made up of fungal hyphae matted together with mucus, fibrin, and tissue debris that together cause local inflammation. The fungus ball may move around within the cavity, making diagnosis easier, but rarely invades the surrounding parenchyma of the lung.

• The most common fungus causing a mycetoma is Aspergillus, hence, the use of the term aspergilloma, but other fungal species, including Zygomycetes and Fusarium, have also been reported as a cause.

• The majority of patients with a mycetoma are asymptomatic, but somewhere between 50% and 74% of affected individuals will develop hemoptysis that can be life threatening.

• Cough, fever, weight loss, and dyspnea have all been reported, but many of these may be related to the underlying pulmonary condition.

• The majority of patients will have sputum or bronchoalveolar lavage fluid cultures that are positive for Aspergillus species, most commonly A niger.

• CT scanning usually shows an intracavitary mass, as in this patient, often with an air crescent sign.

• Treatment of choice, as discussed previously, is surgical resection once hemoptysis starts but before it becomes too severe.

• Surgical mortality ranges from 7% to 23% and is usually attributable to the underlying condition and poor pulmonary function.

• Poor prognostic factors includes:

1. The severity of the underlying lung disease.

2. Increasing size or number of lesions seen on chest radiographs.

3. Immunosuppression(including corticosteroids)

4. Recurrent large volume hemoptysis

5. Underlying HIV infection.

Surgical resection revealed

classic fungus ball (fig-1)

containing numerous fungal organisms on staining (Fig 2), some of which were invading the surrounding lung tissue, somewhat suggestive of necrotizing aspergillosis

• An aortic erosion from the Aspergillus cavity was also found and repaired.

So........

The best-recommended therapy at the present time?

A. Bronchial artery embolization.

B. Itraconazole.

C. Surgical resection.

D. Oral corticosteroids

Spectrum of Pulmonary Aspergillosis



Pulmonary Aspergillosis

Pulmonary aspergillosis can be subdivided into five categories: (a) saprophytic aspergillosis (aspergilloma), (b) hypersensitivity reaction (allergic bronchopulmonary aspergillosis), (c) semi-invasive (chronic necrotizing) aspergillosis, (d) airway-invasive aspergillosis (acute tracheobronchitis, bronchiolitis, bronchopneumonia, obstructing bronchopulmonary aspergillosis), and (e) Angioinvasive aspergillosis.

Saprophytic Aspergillosis (Aspergilloma)

*Saprophytic aspergillosis (aspergilloma) is characterized by Aspergillus infection without tissue invasion.It typically leads to conglomeration of intertwined fungal hyphae admixed with mucus and cellular debris within a preexistent pulmonary cavity or ectatic bronchus. * The most common underlying causes are tuberculosis and sarcoidosis. Other conditions that occasionally may be associated with aspergilloma include bronchogenic cyst, pulmonary sequestration,and pneumatoceles secondary to Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome (AIDS) (3–5). Although aspergillomas are usually single, they may also be present bilaterally.


*Although patients may remain asymptomatic, the most common clinical manifestation of saprophytic aspergillosis is hemoptysis. Surgical resection is indicated for patients with severe lifethreatening hemoptysis, and selective bronchial artery embolization can be performed in those with poor lung function.



Hypersensitivity Reaction (Allergic Bronchopulmonary Aspergillosis)

*Allergic bronchopulmonary aspergillosis is seen most commonly in patients with long-standing bronchial asthma. *Acute clinical symptoms include recurrent wheezing, malaise ith low-grade fever, cough, sputum production, and chest pain. Patients with chronic allergic bronchopulmonary aspergillosis may also have a history of recurrent pneumonia.

Allergic Bronchopulmonary Aspergillosis

Semi-invasive (Chronic Necrotizing) Aspergillosis

*Factors associated with the development of this form of aspergillosis include chronic debilitating illness, diabetes mellitus, malnutrition, alcoholism, advanced age, prolonged corticosteroid therapy, and chronic obstructive pulmonary disease. * Clinical symptoms are often insidious and include chronic cough, sputum production, fever, and constitutional symptoms. In patients with chronic obstructive pulmonary disease, semiinvasive aspergillosis may manifest with a variety of nonspecific clinical symptoms such as cough, sputum production, and fever lasting more than 6 months. Hemoptysis has been reported in 15% of affected patients

Semi-invasive (Chronic Necrotizing) Aspergillosis

Airway-invasive Aspergillosis

*It occurs most commonly in immunocompromised neutropenic patients and in patients with AIDS * Clinical manifestations include acute tracheobronchitis, bronchiolitis, and bronchopneumonia.



Obstructing bronchopulmonary aspergillosis is a noninvasive form of aspergillosis characterized by the massive intraluminal overgrowth of Aspergillus species, usually A fumigatus, in patients with AIDS .Affected patients exhibit cough,fever, and new onset of asthma. Patients may cough up fungal casts of the bronchi and present with severe hypoxemia.

Angio-invasive Aspergillosis

*Angioinvasive aspergillosis occurs almost exclusively in immunocompromised patients with severe neutropenia.

*Increase risk of invasive asprigellosis is due to the development of new intensive chemotherapy regimens for

solid tumors, difficult-to-treat lymphoma, myeloma,and resistant leukemia as well as an increase in the number of solid organ transplantations and increased use of

immunosuppressive regimens for other autoimmune diseases. Despite having a normal neutrophil count, affected patients have functional neutropenia because the

function of the neutrophils is inhibited by the use of high-dose steroids.

Angio-invasive Aspergillosis

Case No. 3

• A 38-year-old man has new-onset pressure in the right side of his neck with accompanying dyspnea on exertion.

Chest radiographs

CT scan

• The most likely etiology of the lesion is:

A. Thymoma.

B. Bronchogenic cyst.

C. Schwannoma.

D. Lymphoma.

• The very large mass is identified to be in the posterior mediastinum.

• The posterior mediastinum is bounded anteriorly by the pericardium, posteriorly by the vertebral bodies, and laterally by the mediastinal pleura.

• Contained with this compartment is the thoracic descending aorta, the greater and lesser azygos veins, splanchnic nerves, the esophagus, thoracic duct, and lymphatic tissue.

• Schwannomas, neurofibromas, and malignant tumors of the nerve sheath originate from the peripheral nerves while ganglioneuromas, ganglioneuro-blastomas, and neuroblastomas develop in the sympathetic ganglia. Together, they account for 30% to 50% of posterior mediastinal masses (choice C is correct).

• Schwannomas and neurofibromas affect men and women equally, appearing in the third to fourth decades of life. These tumors are spherical and sharply demarcated.

• Surgical resection is the treatment of choice in patients who are symptomatic.

• Neurogenic tumors are the most common cause of posterior mediastinal masses. They account for 20% of all adult mediastinal masses and 35% of pediatric mediastinal masses.

• 90% of all neurogenic tumors occur in the posterior mediastinum. The vast majority of neurogenic tumors, 70% to 80%, are benign and slow growing.

• Nearly one-half of all tumors are asymptomatic and found incidentally.

• In those that are symptomatic, regional compressive symptoms or neurologic impairment occurs.

• The tumors arise from the peripheral nerves, sympathetic ganglia, and on rare occasions, the parasympathetic ganglia

• Thymomas are the most common tumors of the anterior mediastinum, comprising 20% of anterior mediastinal neoplasms in adults (choice A is incorrect).

• Bronchogenic cysts are congenital abnormalities that develop as the result of anomalous budding of the laryngotracheal groove. Bronchogenic cysts are well defi ned, round masses often arising adjacent to the carina within the middle mediastinum (choice B is incorrect).

• Mediastinal lymphoma is typically an extension of widespread regional or systemic disease.

• Primary mediastinal lymphoma, accounting for 10% mediastinal lymphomas, may occur in any of the three compartments but typically arises in the anterior mediastinum (choice D is incorrect)

Mediastinal Mass



Symptoms associated with mediastinal masses

No symptoms (discovery by chance)

Paraneoplastic

Local

retrosternal pain

cough

dyspnea (compression, phrenic palsy)

signs of malignancy

SVC- Syndrome

Claude Bernard Horner

Pericardial / pleural effusion

Phrenic / recurrent palsy

Mediastinal masses

Local symptoms

SVC- syndrome

Mediastinal tumors

Localisation within mediastinal compartments

anterior

middle

posterior

Lymphoma

Thymoma

Teratoma

Goiter

Cysts

Lymph nodes

Neurogenic

tumors

Mediastinal masses within mediastinal compartments

Lung nodule Mediastinal lesion

Lateral chest RX

Distinction between parenchymal and mediastinal lesion

Lymphoma

Thymoma

Teratoma

Goiter

Anterior mediastinal compartment

60% of mediastinal masses

60% malign

23% of tumors in anterior mediastinum in adults

Young adults

Policyclic nodular aspect

Non-surgical treatment (chemotherapy /chemo-radiation)

Lymphoma

CT-guided biopsy (true-cut) usually sufficient

Lymphoma

Biopsy by anterior parasternal mediastinotomy (Chamberlain)

Lymphoma

Residual mediastinal Hodkin’s disease after radiochemotherapy:

Establishing proof of recurrence may require excisional biopsy

Lymphoma

Isolated mediastinal lymphoma

Surgical resection after

chemotherapy

30d-mortality Survival Ricci (n= 14) 0 Free of disease (1-14 y)

Bacha (n=16) 6% 5y- survival 85%

Thymic tumors

47 % of tumors in anterior mediastinum in adults

Age 50-70 years

Slowly growing tumors

Thymic tumors

CT: unique mass in the anterior

mediastinum

Thymic hyperplasia

Children and young adults

after infections, antibiotherapy, chemotherapy, irradiation

Thymic tumors

Paraneoplastic syndroms

Neuromuscular (myasthenia gravis, Eaton-Lambert)

Hematological (red cell hyperplasia, pancytopenia)

Dermatological (pemphigus, candidosis)

Endocrine (hyperparathyroidism, Addison, Hashimoto)

Renal (nephrotic syndrome)

Skeletal (hypertrophic osteo-arthropathy)

Immunodeficiency

Collagenosis (lupus, polyarthritis, Sjögren)

Myasthenia gravis

Weakness of striated muscles

Predominance ocular (ptosis, diplopia)

bulbar (dysarthria, broncho-aspiration)

Auto-immune disease (antibodies against acetylcholine receptors)

Diagnosis / treatment acetylcholinesterase-inhibitor (prostigmine)

Acetylcholin-Receptor

ACH

Nerve

Striated muscle

Acetylcholinesterase

Degradation

ACH Receptor

ACH


Degradation

ACH

Myasthenia gravis

Antibody

ACH Receptor


Degradation

ACH

Diagnosis / treatment myasthenia gravis

Antibody

ACHE inhibitor

ACH Receptor

40% of patients with thymoma have myasthenia gravis

20% of patients with myasthenia gravis have thymoma

Thymic tumors and myasthenia gravis

No difference in MG remission after thymectomy (+ thymoma)

No influence on survival after thymectomy for thymoma (+ MG)

Wright CD, Thorac Cardiovasc Surg 2005

Thymic tumors

Classification according Masaoka

I Encapsulated without infiltration (macroscopic / microscopic)

II Microscopic invasion

Capsule (A)

Mediastinal fat (B)

Stage I /II

III Infiltration of neighbouring structures

(Pericardium, lung, phrenic nerve, SVC)

Thymic tumors


Infiltration of SVC

IVA Pleural /pericardial dissemination

IVB Lymph node metastases / distant metastases

Thymic tumors


Pleural deposits

Thymic tumors

Histological WHO (Müller-Hermelink)

classification

A (medullary) AB (mixed)

A: « atrophic », the thymic cells of adult life

B: « bioactive » biologically active organ of the fetus / infant

C: « carcinoma »

B1 (organoid) B2 (cortical) B3 (WDTC)



C: « carcinoma »

Thymic tumors


classification

C (thymic carcinoma)



C: « carcinoma »

Thymic tumors


classification

Thymic carcinoma associated with

MEN I (multiple endocrine neoplasia)

Men <40 years

Thymic tumors

I II III IV

A (medullary) 5 0 2 0

AB (mixed) 13 4 1 0

B1 (organoid) 9 4 1 0

B2 (cortical) 4 4 3 0

B3 (WDTC) 1 3 7 3

C (carcinoma) 0 0 4 1

Thymic tumors

Correlation histology and Masaoka classification (n=71)

Lardinois D, Ann Thorac Surg 2000

(p < 0.001)

Small (< 5 cm) encapsulated

lesion

Thymic tumors

Management

Thymectomy

Port J, Chest Surg Clin N Am 2001

1. Thymic gland (mediastinal pleura and fatty tissue)

2. Infiltrated neighbouring structures (lung, phrenic nerve,

pericardium, innominate vein)

Thymic tumors

Management


Complete en bloc resection

Thymic tumors

Management

Resection of pericardium






Thymic tumors

Management

Resection of VCS






Thymic tumors

Management

Resection by minimally invasive approach (VATS)

Risk of incomplete resection / pleural dissemination

Thymic tumors

Management

40y old female: VATS resection of thymoma



Thymic tumors

Management

7 years later recurrence (thymic carcinoma)



Thymic tumors

Management

Pleural dissemination 2 years later

Minimally invasive resection B2 thymoma



Small (< 5 cm) encapsulated

lesion

Thymic tumors

Management

Thymectomy

Stage p I no RT

Stage p II, III RT


Resection of thymic tumors

Results (n=71)1

Mortality during follow up 27%

Tumor-related mortality 14%

Recurrence local 14%

local and distant 4%

Lardinois D, Ann Thorac Surg 2000

1Mean follow up 8.3 years; complete follow up 97%

Age ns

Gender ns

Myasthenia gravis ns

Masaoka classification p < 0.05

Histology p < 0.05

Results after resection of thymic tumors

Predictors for survival

Age ns

Gender ns

Myasthenia gravis ns

Masaoka classification p < 0.0001

Histology p < 0.004

Results after resection of thymic tumors

Predictors for disease-free survival

1. Biopsy (true-cut)

2. Induction chemotherapy

3. Resection

Thymic tumors

Management

Tumors > 5 cm

Tumors with invasive pattern


Stage III thymic tumors

Partial response after chemotherapy

Before CHT After CHT


Clamshell incision Replacement of

VCS

4y follow up

Resection after induction chemotherapy


Induction therapy

Cisplatin-based combination CHT

Response rates 79 - 100%

Resectability rates 36 - 69%

Machiarini P, Cancer 1991

Rea F, J Thorac Cardiovasc Surg 1993

Loehrer PJ, J Clin Oncol 1997

Shin DM, Ann Intern 1998

Berutti A, Br J Cancer 1999

Kim ES, Proc Am Soc Clinic Oncol 2001


Induction therapy1 resection CHT/RT

Venuta F, Ann Thorac Surg 2003

Mortality 10y-survival R0 resection Recurrence

Venuta (n=15) 0 90% 87% 27%

1response rate 13% complete

53% partial

Stage IVA B3 thymic tumors (WDTC)

Induction therapy pleuropneumonectomy CHT/RT

Wright CD, Ann Thorac Surg 2006

Mortality Survival Recurrence

5y 10y

Wright (n=5) 0 75% 50% peritoneal (3)

Masaoka

I

II

III

IV

resection

resection RT

Histology

A AB B1/2 B3 / C

CHT resection + CHT/RT

Mediastinal germ cell tumors (MGCT)

15% of tumors in anterior mediasinum in adults

Average age 30 years (1-73)

Teratoma men = women

Malignant MGCT men 95%


Teratoma (66%) asymptomatic

Seminoma local symptoms (cough, dyspnea, pain)

Non-seminoma tumors local symptoms (VCS syndrome)

sick patients (fever, pleural effusion)


Teratoma

2 germinal layers

HCG / a FP negative

Complete resection without adjuvant therapy

CT: fat / cartilage, delimitated


Seminoma

Large, infiltrating tumors

High or low levels of HCG /FP

Radiosensitive /chemosensitive tumors


Non-seminoma tumors

Large, infiltrating tumors

Mediastinal shift, pleural effusion

Commonly associated with metastases

high level HCG / FP

Chemotherapy

Resection of residual masses

(growing teratoma syndrome) Cave Bleomycin!


Chemotherapy

Resection

Normal markers

Biopsy: Seminoma

Small

RT

Elevated markers

Large / mets

CHT

FNA: Non-seminoma tumor

CT: residual resectable lesions

Symptoms?

Diagnosis?

Goiter

Compression of airways (intra / extrathoracic)

Resection through cervicotomy

Residual tracheal deformation: video-assisted tracheopexy

Diagnosis?

Subclavian artery aneurysm

Cysts

20% of mediastinal masses

benign

Middle mediastinal compartment

Neurogenic tumors

Posterior mediastinal compartment

20% of mediastinal tumors in adults

> 90% benign (adults)

Intraspinal extension in 10% (MRI!)

Neurogenic tumors

Benign Malignant

Nerve sheath Schwannoma Neurofibrosarcoma

Neurofibroma

Granular cell tumor

Ganglion cell Ganglioneuroma Ganglioneuroblastoma

Paraganglionic Chemodectoma

Pheochromocytoma

Neurogenic tumors

Most common neurogenic mediastinal tumors

Asymptomatic, slow growing

Complete resection recommended (VATS)

Neurogenic tumors

Nerve sheath tumors

Cave localisation thoracic inlet

supraclavicular plexus dissection by experienced plexux

surgeon!

Neurogenic tumors

Nerve sheath tumors

Von Recklinghausen‘s neurofibromatosis

Multiple neuorfibromas

Risk of malingant degenereration (neurofibrosarcoma)

Neurogenic tumors

Nerve sheath tumors

Young adults

Sympathetic chain

Asymptomatic

Intraspinal extension (MRI): simultaneous combined resection

Complete resection (thoracotomy): local resurrence uncommon

Neurogenic tumors

Ganglioneuroma

Mediastinal Lymphadenopathy



Lymph

nodes Anatomic Considerations

Retrosternal Prevascular Retrocaval

Aortic window Carinal

Subcarinal Hilar

Z-esophageal Circm-cardiac

3 3

Lymph




Subcarinal Hilar


6 5

Lymph




Subcarinal Hilar


7

7

8

9

Lymph

nodes

X-Rays

Enlarged hilar shadow with lobulated outlines

Normal

Lymph

nodes

CT MRI

Multiple masses at the anatomic locations of lymph nodes

http://radiographics.rsnajnls.org/cgi/content/full/20/2/449/F4

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Regional lymph node classification for lung cancer staging adapted from the American Thoracic Society mapping scheme

Supraclavicular nodes 1. Low cervical, supraclavicular and sternal notch nodes From the lower margin of the cricoid to the clavicles and the upper border of the manubrium. The midline of the trachea serves as border between 1R and 1L.

Superior Mediastinal Nodes 2-4

2R.Upper Paratracheal

2R nodes extend to the left lateral border of the trachea. From upper border of manubrium to the intersection of caudal margin of innominate (left brachiocephalic) vein with the trachea.

2L.Upper Paratracheal

From the upper border of manubrium to the superior border of aortic arch. 2L nodes are located to the left of the left lateral border of the trachea.

http://www.radiologyassistant.nl/data/bin/a5097977aaaadb_mediast-3-met-vcs.jpg


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3A. Pre-vascular These nodes are not adjacent to the trachea like the nodes in station 2, but they are anterior to the vessels.

3P.Pre-vertebral Nodes not adjacent to the trachea like the nodes in station 2, but behind the esophagus, which is prevertebral.

4R. Lower Paratracheal From the intersection of the caudal margin of innominate (left brachiocephalic) vein with the trachea to the lower border of the azygos vein. 4R nodes extend from the right to the left lateral border of the trachea.

4L. Lower Paratracheal From the upper margin of the aortic arch to the upper rim of the left main pulmonary artery.



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Aortic Nodes 5-6 5. Subaortic These nodes are located in the AP window lateral to the ligamentum arteriosum. These nodes are not located between the aorta and the pulmonary trunk but lateral to these vessels.

6. Para-aortic These are ascending aorta or phrenic nodes lying anterior and lateral to the ascending aorta and the aortic arch.

Inferior Mediastinal Nodes 7-9 7.Subcarinal Nodes below carina. 8. Paraesophageal 9. Pulmonary Ligament Nodes lying within the pulmonary ligaments.




Hilar, Lobar and (sub)segmental Nodes 10-14 These are all N1-nodes. 10. Hilar nodes These include nodes adjacent to the main stem bronchus and hilar vessels. On the right they extend from the lower rim of the azygos vein to the interlobar region. On the left from the upper rim of the pulmonary artery to the interlobar region.


1. Supraclavicular zone nodes

1. Supraclavicular zone nodes These include low cervical, supraclavicular and sternal notch nodes.

Upper border: lower margin of

cricoid. Lower border: clavicles and upper border of manubrium.

The midline of the trachea serves as border between 1R and 1L.

http://www.radiologyassistant.nl/data/bin/a5097977aab320_station-1B.jpg

2R. Right Upper Paratracheal 2R nodes extend to the left lateral border of the trachea. Upper border: upper border of

manubrium. Lower border: intersection of caudal margin of innominate (left brachiocephalic) vein with the trachea. 2L. Left Upper Paratracheal Upper border: upper border of

manubrium. Lower border: superior border of aortic arch. On the left a station 2 node in front of the trachea, i.e. a 2R-node. There is also a small prevascular node, i.e. a station 3A node

3. Prevascular and Prevertabral nodes Station 3 nodes are not adjacent to the trachea like station 2 nodes. They are either:

3A anterior to the vessels or 3B behind the esophagus, which lies prevertebrally. Station 3 nodes are not accessible with mediastinoscopy.

3P nodes can be accessible with endoscopic ultrasound (EUS).

3A and 3P nodes

On the left a 3A node in the prevascular space.

Notice also lower paratracheal nodes on the right, i.e. 4R nodes.

4R. Right Lower Paratracheal Upper border: intersection of caudal margin of innominate (left brachiocephalic) vein with the

trachea. Lower border:lower border of azygos

vein. 4R nodes extend to the left lateral border of the trachea.

http://www.radiologyassistant.nl/data/bin/a5097977aacdb4_4R.jpg

On the left we see 4R paratracheal nodes.

In addition there is an aortic node lateral to the aortic arch, i.e. station 6 node.

4L. Left Lower Paratracheal 4L nodes are lower paratracheal nodes that are located to the left of the left tracheal border, between a horizontal line drawn tangentially to the upper margin of the aortic arch and a line extending across the left main bronchus at the level of the upper margin of the left upper lobe bronchus. These include paratracheal nodes that are located medially to the ligamentum arteriosum.

Station 5 (AP-window) nodes are located laterally to the ligamentum arteriosum.

http://www.radiologyassistant.nl/data/bin/a5097977aadc6f_4L.jpg

On the left an image just above the level of the pulmonary trunk demonstrating lower paratracheal nodes on the left and on the right. In addition there are also station 3 and 5 nodes

On the left an image at the level of the lower trachea just above the carina.

To the left of the trachea 4L nodes. Notice that these 4L nodes are between the pulmonary trunk and the aorta, but are not located in the AP-window, because they lie medially to the ligamentum arteriosum.

The node lateral to the pulmonary trunk is a station 5 node.

5. Subaortic nodes Subaortic or aorto-pulmonary window nodes are lateral to the ligamentum arteriosum or the aorta or left pulmonary artery and proximal to the first branch of the left pulmonary artery and lie within the mediastinal pleural envelope.

6. Para-aortic nodes Para-aortic (ascending aorta or phrenic) nodes are located anteriorly and laterally to the ascending aorta and the aortic arch from the upper margin to the lower margin of the aortic arch.

7. Subcarinal nodes These nodes are located caudally to the carina of the trachea, but are not associated with the lower lobe bronchi or arteries within the lung. On the right they extend caudally to the lower border of the bronchus intermedius. On the left they extend caudally to the upper border of the lower lobe bronchus. On the left a station 7 subcarinal node to the right of the esophagus.

8 Paraesophageal nodes

These nodes are below the carinal nodes and extend caudally to the diaphragm. On the left an image below the carina. To the right of the esophagus a station 8 node.

On the left a PET image demonstrating FDG uptake in a station 8 node.

On the corresponding CT image the node is not enlarged (blue arrow).

The probability that this is a lymph node metastasis is extremely high since the specificity of PET in unenlarged nodes is higher than in enlarged nodes.

9. Pulmonary ligament nodes

Pulmonary ligament nodes are lying within the pulmonary ligament, including those in the posterior wall and lower part of the inferior pulmonary vein.

The pulmonary ligament is the inferior extension of the mediastinal pleural reflections that surround the hila.

10 Hilar nodes

Hilar nodes are proximal lobar nodes, distal to the mediastinal pleural reflection and nodes adjacent to the intermediate bronchus on the right.

Nodes in station 10 - 14 are all N1-nodes, since they are not located in the mediastinum.

http://www.radiologyassistant.nl/data/bin/a5097977ab6857_10B.jpg

10 Hilar nodes

Hilar nodes are proximal lobar nodes, distal to the mediastinal pleural reflection and nodes adjacent to the intermediate bronchus on the right.

Nodes in station 10 - 14 are all N1-nodes, since they are not located in the mediastinum.

http://www.radiologyassistant.nl/data/bin/a5097977ab6857_10B.jpg

Axial CT of Lymph Nodes Scroll through the images on the left. 1-Sternal notch nodes are just seen at this level and above this level 2-Upper Paratracheal: below clavicles and on the right above the intersection of caudal margin of innominate (left brachiocephalic) vein with the trachea and on the left above the aortic arch. 3-Pre-vascular and Retrotracheal : anterior to the vessels (3A) or prevertebral (3P) 4-Lower Paratracheal : below upper margin of aortic arch down to level of main bronchus 5-Subaortic (A-P window): nodes lateral to ligamentum arteriosum or lateral to aorta or left pulmonary artery 6-Para-aortic: nodes lying anterior and lateral to the ascending aorta and the aortic arch beneath the upper margin of the aortic arch 7-Subcarinal 8-Paraesophageal (below carina) 9-Pulmonary Ligament: nodes lying within the pulmonary ligament. 10--14: nodes are all N1 nodes

Axial CT of Lymph Nodes

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Conventional mediastinoscopy The following nodal stations can be biopsied by cervical mediastinoscopy: the left and right upper paratracheal nodes (station 2L and 2R), left and right lower paratracheal nodes (station 4L and 4R) and the subcarinal nodes (station 7). Station 1 nodes are located above the suprasternal notch and are not routinely accessed by cervical mediastinoscopy.

Axial CT of Lymph Nodes

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Mediastinoscopy and EUS

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http://www.radiologyassistant.nl/data/bin/a5097977abe163_scopy-convent.jpg

http://www.radiologyassistant.nl/data/bin/a5097977abe163_scopy-convent.jpg

Extended mediastinoscopy Left upper lobe tumors may metastasize to the subaortic lymph nodes (station 5) and paraaortic nodes (station 6). These nodes can not be biopsied through routine cervical mediastinoscopy. Extended mediastinoscopy is an alternative for the anterior-second interspace mediastinotomy which is more commonly used for exploration of mediastinal nodal stations. This procedure is far less easy and therefore less routinely performed than conventional mediastinoscopy.

EUS-FNA Endoscopic Ultrasound with Fine Needle Aspiration can be performed of all the mediastinal nodes that that can be assessed from the oesophagus. In addition the left adrenal gland and the left liver lobe can be visualized.EUS particularly provides access to nodes in the lower mediastinum (station 7,8 and 9)

http://www.radiologyassistant.nl/data/bin/a5097977ac058e_EUS.jpg

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