الرحيم الرحمن الله بسم

MEDIASTINAL SYNDROMEDr Tai Al Akawy

Pediatrician and neonatologistAlexandria University Children’s Hospital

• Compression of mediastinal structures by any mass gives rise to a group of symptoms known as mediastinal syndrome

• Mediastinal masses affect patients at any age and can be asymptomatic

• 33% of all masses present in patients less than 15 years old

• If small, usually asymptomatic and found incidentally

• If large, usually present with respiratory distress

IntroductionIntroduction

The The mediastinummediastinum is is the region in the chest the region in the chest between the pleural cavities that contain the between the pleural cavities that contain the heart heart and other thoracic viscera except the lungsand other thoracic viscera except the lungs

Boundaries Boundaries AnteriorAnterior - sternum- sternumPosterior Posterior - vertebral column and paravertebral - vertebral column and paravertebral

fasciafasciaSuperiorSuperior -thoracic inlet -thoracic inletInferiorInferior - diaphragm- diaphragmLateral Lateral - parietal pleura- parietal pleura

Sternal Angle

Thoracic inlet

Thoracic oulet

Boundaries of mediastinum

sternum

Thoracic vertebra

TS: Mediastinum

8

CS: MediastinumCS: Mediastinum

ANATOMY OF MEDIASTINUM

• It is the anatomic space that lies in the midthorax

• It is limited by the diaphragm below and the suprasternal thoracic inlet above.

• It contains several vital structures in a small space,

• Abnormalities can produce important symptoms.

Contents of the mediastinumThe Anterior compartment contains

• The Thymus• Substernal extensions of the thyroid • Parathyroid glands • blood vessels• Pericardium• Lymph nodes

Contents of the mediastinum

The middle compartment contains the • Heart,• Great vessels,• Trachea, • Main bronchi,• Lymph nodes, • Phrenic and • Vagus nerves.

Contents of the mediastinum The posterior compartment

• The vertebrae • Descending aorta• Oesophagus• Thoracic duct• Azygous and Hemizygous veins • Lower portion of the vagus• Sympathetic chains, and• Posterior mediastinal nodes.

Mediastinal masses

Anterior Mediastinal Masses: (4 T's) (30% of mediastinal masses)

• Thymoma • Teratoma • Thyroid (Ectopic) • (Terrible) Lymphoma

Thymoma

• lobulated mass in the anterior mediastinum

thymoma

Thymoma

▪ Located in superior and / or anterior mediastinum. ▪ Can occur in all age groups but mostly seen in in adults▪ 80 % have symptoms of myasthenia gravis Differential diagnosis : ▪ Reactive lymphoid hyperplasia ▪ Cytological distinction between thymus and thymoma

is difficult. ▪ Follicular lymphoma ▪ Precursor T lymphoblastic lymphoma

Hilum can be seen through

mass

this must be an anterior mediastinal mass because it overlaps rather than “pushes out” the main pulmonary arteries

This particular example is a thymoma

The CT-images shows a large soft tissue mass in the anterior mediastinum, which arises in the thymus. There is associated paratracheal adenopathy (arrow).

(a) PA chest radiograph demonstrates a goiter (arrow) extending into the middle mediastinum, causing deviation of the trachea to the left (black

arrowhead) .

Right-sided retrosternal goiter

(b) CT scan shows the mass (arrow) between the trachea and right lung

Lymphoma

Lymphoma is the most common cause of an anterior mediastinal mass in children and the second most common cause of an anterior mediastinal mass in adults.

Lymphomas

–Primary mediastinal large B cell lymphoma–Precursor T lymphoblastic lymphoma/leukemia–Anaplastic large T cell lymphoma , mature T cell lymphoma. –Hodgkin’s lymphoma.

In this case, enlarged lymph nodes are seen in the right paratracheal , hilar and subcarinal areas without thymus

involvement

Anterior mediastinal teratoma - A large heterogenous left anterior mediastinal mass containing soft tissue , fatty and calcific components. Germ Cell Tumour

Germ cell tumors

▪ Seminoma ▪ Embryonal carcinoma ▪ Yolk sac tumors ▪ Choriocarcinoma ▪ Teratoma ; mature ▪ Teratoma; immature

Teratoma

▪ Most common mediastinal germ cell tumor ( 50-70 % )– Mature teratoma : adult type tissue – Immature teratoma: immature embryonal type of tissue;

▪ Mostly benign; ▪ Mixture of somatic tissue of 3 germ layers ; ectoderm,

endoderm, mesoderm. ▪ Immature teratoma : biphasic cell pattern ; loose aggregates

of small round cells in fibrillary matrix represents neuronal component.

▪ Malignant transformation can occur : MC is SCC or adenocarcinoma.

Embryonal carcinoma

▪ Rare type of non seminomatous germ cell tumor in young males.

▪ Often associated with teratoma ( teratocarcinoma ), Choriocarcinoma, or seminoma.

▪ Cytologically embryonal carcinoma is indistinguishable from poorly differentiated carcinoma of non germ cell origin.

▪ Mitotically active tumor with malignant cells arranged in poorly cohesive 3 D clusters , with syncitial growth pattern.

▪ Occur either as mixed or pure form. AFP levels are elevated in all cases.

Yolk sac tumor / endodermal sinus tumor

▪ Rare mediastinal tumor can occur both in paediatric ( female predilection ) as well as in adults ( male predilection ).

▪ Commonly associated with elevated AFP levels. ▪ Coagulative tumor necrosis is abundant ▪ Schiller- Duval bodies/ Glomeruloid bodies – diagnostic are

seldom seen. ▪ Identification of eosinophilic “ basal –lamina like “ substances

and intra-cytoplasmic hyaline globules ( PAS + & diastase resistant), give clue to diagnosis.

Choriocarcinoma

▪ Pure medastinal choriocarcinoma is extremely rare – virtualy non existent in children.

▪ Highly aggresive tumor. ▪ Elevated S.β HCG level. ▪ Mixture of syncytiotrophoblasts and cystotrophoblasts

against haemorrhagic background. ▪ Syncytiotrophoblastic giant cells with eosinophilic

cytoplasm , pleomorphic nuclei, prominent nucleoli,▪ Cytotrophoblasts are medium sized cells with

vaculated basophilic cytoplasm.

.

Middle Mediastinal masses

Middle Mediastinal Masses (30% of mediastinal masses)

• Adenopathy : infection [bacterial, granulomatous] neoplasm [leukemia / lymphoma, metastases]• Bronchopulmonary or foregut malformations:

Esophageal duplication cyst, Bronchogenic cyst, Sequestration

MEDIASTINAL LYMPHADENOPATHY

• Middle mediastinum is the commonest site of intrathoracic lymphadenopathy.

• Gross lymphadenopathy is a feature of 1)Tuberculosis 2)Histoplasmosis 3) Metastatic malignancy 4) Lymphomas 5)Sarcoidosis

Foregut cysts in the middle mediastinum are classified as bronchogenic or enteric. Bronchogenic cysts are lined by respiratory epithelium and most are located in the subcarinal or right paratracheal area

Enteric cysts are lined by gastrointestinal mucosa and are located in the middle or posterior mediastinum near the esophagus

(Right) AP radiograph shows large, smooth, homogeneous, left retrocardiac parenchymal mass (arrows).(Left) Axial T2 MRI shows homogeneous, well circumscribed ovoid mass (arrow) with signal greater than CSF (curved arrow).

BRONCHOGENIC CYST

Enteric foregut cyst

The images show a well defined lesion in the lower mediastinum in close proximity to the esophagus, which is typical for an enteric foregut cyst.

Posterior Mediastinal masses

NEUROGENIC TUMOURS There are 4 histological types.1.NEURILEMMOMA Benign and is classically a dumbbell-shaped mass.

compress the spinal cord and produce pressure symptoms.

2.GANGLIONEUROMABenign, elongated and large. Usually occurs in children but may be found at any age.

Causes flushing,hypertension,headache,sweating,diarrhoea.3.NEUROFIBROMA

Associated with generalized neurofibromatosis (von Recklinghausen's disease).

4.NEUROBLASTOMA Malignant and found frequently in children.

Neuroblastoma

The CT-images show a calcified mass in the posterior mediastinum extending over several vertebrae, which grows into the vertebral canal.

Neuroblastoma

See sharp margin

above clavicle

Mass is in posterior mediastinum, because it remains sharply outlined in apex of thorax, indicating that it is surrounded by lung.This particular example is a ganglioneuroma

An approach to mediastinal syndrome and masses

• Epithelial tumors – Thymoma– Thymic carcinoma

• Germ cell tumors – Pure GCT’s : GCT’s with only one histological type– Mixed GCT : GCT with more than one histological type – GCT’s with somatic type malignancy – GCT’s with associated malignancy

WHO Classification of thymic tumors and mediastinal tumors

• Mediastinal lymphomas and haematopoietic neoplasms: – B-cell lymphoma– T-cell lymphoma – Hodgkin’s lymphoma – Histiocytic and dendritic cell tumors – Myeloid sarcoma and extra-medullary acute myeloid leukaemia

• Mesenchymal tumors of mediastinum: – Thymolipoma – Lipoma of mediastinum – Liposarcoma of mediastimum – Solitary fibrous tumors – Synovial sarcomas

– Vascular neoplasms – Rhabdomyosrcoma – Leiomyomatous tumors

• Peripheral nerve sheeth tumors • Ectopic tumors of mediastinum

– Ectopic tumors of thymus – Ectopic tumors of thyroid – Ectopic tumors of parathyroid

• Metastasis to thymus and to anterior mediastinum

To simplify

Benign Maliganat

Thymoma Benign teratoma Neurilemmnoma Neurofibroma Paraganglioma

Thymic carcinoamaLymphoma Seminoma Embryona carcinoma Yolk sac tumorChoriocarcinoma Immature teratoma Neuroblastoma Metastatic tumors

Clinical Presentation

▪ Mediastinal lesions are symptomatic in 50%-75% of patients

▪ Symptoms can be caused by local mass effects, systemic effects of the tumor, or infection

▪ Local effects are dependent on the size and location of the lesion and result from compression of adjacent structures

▪ Symptoms are also more common with malignant tumors because they invade adjacent structures.

Organ involved Symptoms and signs

1. Trachea, main bronchi :Stridor, dyspnoea, cough, features of lung collapse 2. Esophagus : Dysphagia (extrinsic compression on barium swallow) 3. Superior vena cava : Engorged non-pulsatile neck veins, oedema and cyanosis of face, neck and arms 4. Left recurrent laryngeal nerve: Hoarseness of voice, bovine cough 5. Phrenic nerve: Hemi-diaphragm paralysis 6. Sympathetic trunk: Horner’s syndrome

Specific symptoms and signs

Superior vena cava syndrome

Clinical manifestation resulting from partial or complete obstruction of

the superior vena cava

Clinical PresentationClinical Presentation

Superior vena cavaSuperior vena cavaVulnerable to extrinsic compression and Vulnerable to extrinsic compression and obstruction because it is thin walled and obstruction because it is thin walled and its intravascular pressure is lowits intravascular pressure is low

Bronchogenic carcinoma and lymphoma Bronchogenic carcinoma and lymphoma are the most common etiologiesare the most common etiologies

Superior vena cava syndromeSuperior vena cava syndrome

Results from Results from the increase venous pressure the increase venous pressure in the upper thorax , head and neck in the upper thorax , head and neck

Characterized by dilation of the collateral Characterized by dilation of the collateral veins in the upper portion of the bodyveins in the upper portion of the body

Edema and plethora of the face, neck and Edema and plethora of the face, neck and upper chest, edema of the conjunctiva upper chest, edema of the conjunctiva

Cerebral symptoms such as headache, Cerebral symptoms such as headache, disturbance of consciousness and visual disturbance of consciousness and visual distortiondistortion

Diagnostic Evaluation

• RADIOLOGY– Plain chest x-ray taken in two planes,

posteroanterior and left lateral basic information about the location of the mass within the mediastinum

– Diaphragm fluoroscopy to evaluate paradoxical motion of the diaphragm on rapid inspiration indicative of phrenic nerve paralysis

• USG : – via percutaneous route ; it provides both

spatial orientation as well as real time monitoring with out exposure to radiation

– Via bronchoscopy / endoscopy via oesophagus.

Approach to mediastinum

RADIOLOGY

– CT of the chest has replaced plain chest radiography as the diagnostic procedure of choice for mediastinal masses

– CT : locating small lesion in thoracic inlet, hilum and middle mediastinum , via supraclavicular, suprasternal and parasternal approach. But continues real time monitoring is not possible without radiation exposure.

– MRI may enhance the diagnostic abilities of chest CT

– Echocardiography and positron emission tomography(PET) have been used invasive thymomas and lymphoma

CXR

Lymphoma is the most common cause of an anterior mediastinal mass in children

Histologic

– FNA or needle biopsy with CT guidance of a mediastinal mass may provide sufficient tissue for diagnosis of thymic carcinoma or other defined neoplasms

– Mediastinoscopy, or intrathoracic biopsy may be considered for lymphomas in particular, and thymomas and neural tumors

The biopsy can be obtained through • Traditional bronchoscopy or • Echo-guided endoscopy, • Superficial node biopsy, • Mediastinoscopy, • Mediastinotomy, • Transthoracic needle biopsy, • Thoracoscopy, • Cervical or supraclavicular biopsies; • Thoracotomy and sternotomy are rarely indicated

Diagnosis requires combination of clinical, radiological, biochemical, and cytomorphological information.

• Age : In children : commonest thymic tumor is NHL. Thymoma is extremely

rare in childhood. Adults : mets and benign mediastinal cyst of celomic origin or GI origin. In adults : thymoma represents commonest primary thymic tumor,

followed by mediastinal lymphoma.

Approach to mediadiastinal tumors

Step 1 : clinical history

• located in which part of mediastinum

– Extremely useful in diagnosis of tumors – Depending on predominant cell morphology

diagnosis can be approached.

Step 2 : radiological localisation

Step 3 : cytomorphology

History and relevant information for diagnosis

Treatment

Therapy should be causative

Mediastinal syndrome management priority is depending on the

1. Severity of symptoms2. Etiology 3. Prognosis

Supportive Care

Elevate the patient’s head to decrease the hydrostatic pressure and thereby the congesion

Oxygen Glucocorticoid therapy (dexamethasone, every 6

hours) Glucocorticoids reduce the tumor burden in

lymphoma and thymoma and are therefore more likely to reduce the obstruction

Loop diuretics are also commonly used

Chemotherapy is used in lymphomas, small-cell lung cancer and germ cell tumors.

Besides chemotherapy, Radiotherapy is used to shrink the tumor

mass

Some cases must be approached as an emergency

Acute lifethreatening presentation is the only situation in which radiotherapy before histological diagnosis can be considered.

However, this approach should be avoided, whenever possible.

RT prior to biopsy may obscure the histologic diagnosis.

Current guidelines stress the importance of accurate histologic diagnosis prior to starting therapy,

and the use of endovascular stents in severely symptomatic patients to provide more rapid relief than can be achieved using RT.

Kvale PA, Selecky PA, Prakash UB, American College of Chest Physicians. Palliative care in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007; 132:368S.

Important exceptions to this general approach are pts who present with stridor due to central airway obstruction or severe laryngeal edema, and those with coma from cerebral edema.

These situations represent a true medical emergency, and these patients require immediate treatment (stent placement and radiotherapy) to decrease the risk of sudden respiratory failure and death.

Radiation therapy

RT provides considerable relief by reducing tumor burden

Symptomatic improvement is usually apparent within 72 hours.

Eight year old male with a heart murmur

PA and lateral chest films show a large anterior mediastinal mass causing narrowing and rightward deviation of the trachea.

CT exam show a low density mass in the anterior mediastinum with irregular walls with calcium in it.

Dx Teratoma, Anterior Mediastinal

Three year old male with an incidentally noted chest

mass

single slice from an enhanced chest CT exam shows the mass to be non-enhancing, posterior to the right bronchi, and next to the esophagus. Dx: Esophageal Duplication

Eleven year old male with upper respiratory

symptoms and wheezing

Slice from an enhanced chest CT exam shows a multi-loculated non enhancing mass in the anterior mediastinum Dx-Thymic Cyst

Twelve year old female with a chest symptoms and some

neck swellings

Fever ,night sweating ,loss of weight

PA chest films show a large, lobulated anterior mediastinal mass displacing the trachea to the right.

A chest CT exam shows the mass to extend from the neck to the diaphragm, compressing the tracheal and left mainstem bronchus leading to left lower lobe atelectasis. The chest wall mass is partially eroding the sternum.Dx: Lymphoma, Hodgkin, Anterior Mediastinal, Sternal Involvement

Fourteen year old male presented with chest pain,

cough, dyspnea, hoarseness, and superior

vena caval syndrome

Two contiguous slices from an enhanced chest CT show a homogenous, solid, anterior mediastinal mass and a large right pleural effusion

Dx-LymphomaNon-Hodgkin, Anterior Mediastinal

Ancillary techniques for mediastinal tumors

Conclusion

There are multiple causes of mediastinal masses, but the differential diagnosis can be

narrowed based upon the compartment involved ,the

clinical presentation , appearance of the mass on CT

scan and tissue diagnosis

REFERENCES

• 1. Wright CD, Mathisen DJ. Mediastinal tumors: diagnosis and treatment. World J Surg 2001;25:204–9.

• 2.Wychulis AR, Payne WS, Clagett OT, Woolner LB. Surgical treatment of mediastinal tumors: a 40 year experience.J Thorac Cardiovasc Surg 1971;62:379–92.

• 3. Fraser RS, Pare JA, Fraser RG, et al. The normal chest. In:Fraser RS, Pare JA, Fraser RG, et al, editors. Synopsis of diseases of the chest. 2nd ed. Philadelphia: W.B. Saunders;1994:1-116.

• 4. Fraser RS, Muller NL, Colman N, et al. The mediastinum.In: Fraser RS, Muller NL, Colman N, et al, editors. Fraser and Pare’s diagnosis of diseases of the chest. 4th ed. Philadelphia:W.B. Saunders; 1999:196–234.

• 5. Park DR, Pierson DJ. Tumors and cysts of the mediastinum.In: Murray JF, Nadel JA, editors. Textbook of respiratory medicine. 3rd ed. Philadelphia: W.B. Saunders;2000:2123-37.

• 6. Armstrong P. Mediastinal and hilar disorders. In: Armstrong P, Wilson AG, Dee P, Hansell DM, editors. Imaging of diseases of the chest. 3rd ed. London: Mosby; 2000:789-892.

• 7. Wychulis AR, Payne WS, Clagett OT, Woolner LB. Surgical treatment of mediastinal tumors: a 40 year experience.J Thorac Cardiovasc Surg 1971;62:379–92.

• 8. Davis RD Jr, Oldham HN Jr, Sabiston DC Jr. Primary cysts and neoplasms of the mediastinum: recent changes in clinical presentation, methods of diagnosis, management,

and results. Ann Thorac Surg 1997;44:229–37.

• 9. Strickler JG, Kurtin PJ. Mediastinal lymphoma. Semin Diagn Pathol 1991;8:2–13.• 10. Keller AR, Castleman B. Hodgkin’s disease of the thymus gland. Cancer 1974;33:1615–23.• 11. Costello P, Jochelson M. Lymphoma of the mediastinum and lung. In: Taveras JM, Ferrucci

JT, editors. Radiology:diagnosis, imaging, intervention. Philadelphia: J.B. Lippincott Co.; 1986:1–13.

• 12. Dandapat MC, Mishra BM, Dash SP, Kar PK. Peripheral lymph node tuberculosis: a review of 80 cases. Br J Surg 1999;911:77-2

• 13. Rosado-de-Christenson ML, Galobardes J, Moran CA. Thymoma:radiologic-pathologic correlation. Radiographics 1992;151:12-68.