Sandbox:Trusha

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] Associate Editor(s)-in-Chief: Trusha Tank, M.D.[3]

Differential diagnosis of mediastinal mass

Wide variety of medical conditions can present as a mediastinal mass on radiological imaging.

• Mediastinal mass may cause obstruction, entrapment or infiltration of other mediastinal organs such as: Trachea, bronchi, esophagus, aorta, superior vena cava (SVC) or heart.
• Disorder caused by any kind of mediastinal mass is collectively known as: Mediastinal syndromes
• Mediastinal syndrome includes:
  • Compression of the trachea: Dyspnea and respiratory insufficiency.
  • Compression of the esophagus: Dysphagia.
  • Compression of SVC causes superior vena cava syndrome: Vein distention, edema of the face or upper extremities and a positive Pemberton's sign.
    • Pemberton's sign: Development of suffusion, plethora, or duskiness upon elevation of the arms above the head in patient
    • Superior vena cava syndrome is the most severe complication of mediastinal syndrome and a medical emergency.

ABBREVIATIONS: N/A: Not available, SOB: Shortness of breath, M/C: Most common, RI: Respiratory insufficiency, NM: Neuromuscular system, SVCS: Superior vena cava syndrome, SLE: Systemic lupus erythematosus disease, T3: Triiodothyronine, T4: Thyroxine, TSH: Thyroid stimulating hormone, TFT: Thyroid function test
Disease	Causes/risk factors	Clinical presentation				Paraclinical findings
		General symptoms	Mediastinal syndrome
			Dyspnea/ RI	Dysphagia	SVCS	Gold standard	Image	Additional findings
Anterior mediastinal mass
Tumors
Thymoma	Human foamy virus Epstein-Barr virus Human T-cell lymphotropic virus MEN 1 syndrome	Cough wheezing Chest pain Muscle weakness (MG) Anemia	+	+	+	Biopsy: Epithelial cells Immature lymphocytes Immature T cells		Associated condition NM Myasthenia gravis Neuromyotonia Rippling muscle disease Polymyositis/dermatomyositis Encephalitis (limbic, cortical and brain stem) Intestinal pseudoobstruction Hematological Anemia: pure red cell aplasia, pernicious anemia, hemolytic anemia, aplastic anemia Other isolated cytopenias: eosinophils, basophils neutrophils Immunodeficiencies: hypogammaglobulinemia/- T-cell deficiencies (Good syndrome) Dermatological Pemphigus (foliaceus or paraneoplastic) Lichen planus Alopecia areata Endocrine Addison disease Grave's disease Cushing's disease Hepato-renal Glomerulonephritis Autoimmune hepatitis Systemic Autoimmune Diseases SLE Sjögren's syndrome Systemic sclerosis Graft-versus-host disease
Disease	Etiology	Symptoms	Dyspnea/ RI	Dysphagia	SVCS	Gold standard	Image	Additional findings
Fatty mass	Steroid use Cushing's syndrome Obeses	Mostly asymptomatic	-	-	-	MRI: Well-defined encapsulated mas Extensive fat content Small amounts of solid areas Fibrous septa		Fatty mass can be: Lipoma Liposarcoma Thymolipoma
Non-Hodgkin lymphoma	Age (above 60 years) Caucasians > African and Asian Americans Positive family history of first degree relative B-cell activating autoimmune disorders Radiation exposure Infections (HIV, Hep C, HTLV-1, EBV, HHV-8, H. pylori, psittacosis, Campylobacter jejuni) Previous cancer treatment Exposure to chemicals and drugs (pesticides, methotrexate, TNF inhibitors, trichloroethylene) Cigarette smoking for ≥ 40 years BMI ≥30 kg/m2 Diet Hair dyes Breast implants	Painless lymphadenopathy Fever Weight loss and anorexia Night sweats Constant fatigue Itchy skin Cough Shortness of breath Abdominal pain or swelling Constipation Nausea Vomiting Headache Personality changes Seizures	+/-	+/-	+/-	Excisional lymph node biopsy with immunohistochemical study CD 20+ cells		Anemia: Involvement of bone marrow Autoimmune hemolysis and bleeding Thrombocytopenia, leukopenia, or pancytopenia Lymphocytosis with malignant cell Thrombocytosis
Disease	Etiology	Symptoms	Dyspnea/ RI	Dysphagia	SVCS	Gold standard	Image	Additional findings
Hodgkin's lymphoma	Epstein-Barr virus A history of infection with the Epstein-Barr virus (EBV) Family history First-degree relatives Siblings of the same sex HIV infection HIV infection increases risk Autoimmune diseases Rheumatoid arthritis Systemic lupus erythematosus Ulcerative colitis Immune thrombocytopenic purpura Sarcoidosis Immunodeficiency Severe combined immunodeficiency (SCID) Hypogammaglobulinemia Hyperimmunoglobulin M syndrome Congenital immunodeficiency Organ transplant or allogeneic bone marrow transplant Tobacco smoking	Painless lymphadenopathy with a rubbery consistency Systemic B symptoms: Fever (Pel-Ebstein fever): persistent temperature >38°C (>100.4°F) Drenching night sweats Unexplained weight loss >10% of total body weight within the past 6 months Other Pruritus Fatigue Mass effect Chest pain Cough Pain or feeling of fullness below the ribs due to swollen spleen or liver Pain in lymph nodes after drinking alcohol Skin blushing or flushing Bone pain	+			Lymph node biopsy with immunohistochemistry Reed-Sternberg cells CD15 and CD30 +		Positron emission tomography (PET) Detect small deposits Monitor the response to treatment Detect recurrences Quantitate the size of lymph nodes with precision Assess for bone marrow involvement
Mediastinal germ cell tumor (Non-teratomatous)	Exclusively in males 20s - 40s age	Chest pain Cough Wheezing Stridor Weight loss Fever Night sweats	+	-	-	Biopsy: Yolk sac tumor Endodermal sinus tumor Embryonal carcinoma Choriocarcinoma Mixed germ cell tumor		CT scan: Homogenous appearance Hemorrhage and coagulation necrosis Metastasis to lymph nodes and bone Non-seminomatous germ cell tumors present as large masses with marked heterogeneous attenuation Invasion of adjacent structures and distant metastasis Pleural and pericardial effusion Laboratory finding: AFP and ß-hCG levels
Teratoma	Benign equal in men and women Malignant more common in men Pediatric population higher risk	Benign Asymptomatic Malignant Cough Chest pain Trichoptysis	+/-	+/-	+/-	Chest CT scan: Location Metastasis Intrinsic structure Soft tissue Fat Calcification		N/A
Thyroid gland disease
Thyroid cancer	Hx of goiter Family Hx of thyroid disease Female gender Asian race Radiation exposure MEN syndrome	Lump in the neck Dysphonia Lymphadenopathy Cough Sore throat Neck pain	+	+	-	US guided biopsy: Papillary thyroid cancer Follicular thyroid cancer Medullary thyroid cancer Anaplastic thyroid cancer Lymphoma		TFT Elevated T3 Elevated T4 Low TSH
Mediastinal goiter	Iodine deficiency Female gender Age over 50 years Personal or family history Certain medications Immunosuppressants Antiretrovirals Amiodarone Lithium Radiation	A visible swelling at the base of your neck Tight feeling in throat Cough Hoarseness Fatigue	+	+	-	Radioactive iodine scan: Nodules Size Function of the gland: ↑ or ↓		Hyperavtive gland (hyperthyroid): Grave's disease Hypoactive gland (hypothyroid): Hashimoto thyroiditis Normal functioning gland (euthyroid): Benign thyroid enlargement (non toxic multinodular goiter)
Disease	Etiology	Symptoms	Dyspnea/ RI	Dysphagia	SVCS	Gold standard	Image	Additional findings
Middle mediastinal mass
Cardiovascular Disease
Pericardial effusion	Acute myocardial infarction Aortic dissection Aortic rupture Myocardial rupture Rupture of ventricular aneurysm Uremic pericarditis Rheumatic pericarditis Tuberculous pericarditis Uremic pericarditis Viral pericarditis Dressler's syndrome Cardiac catheterization Cardiomyopathy Chemotherapy Chest trauma Collagen vascular disease Congestive heart failure Neoplasm Postpericardiotomy syndrome Postirradiation	Chest pain The positional change affecting the chest pain Orthopnea Fever symptoms of infection, injury or systemic disease causing the effusion	+	+/-	-	Echocardiography guided pericardiocentesis: Therapeutic Diagnostic pericardial disease Hemodynamic parameters Volume Effusion content (blood/exudate/transudate) Microbial culture		Physical findings: Pulsus paradoxus Hypotension in cardiac tamponade Jugular venous distension with a prominent Y descent Kussmaul's sign EKG: Electrical alternans Echo: Presence of effusion Reversal of RA and RV diastolic trans-mural pressures Cardiac chamber indentation or collapse Respiratory variation of atrioventricular valves increased.
Aortic dissection	Atherosclerosis Chest trauma Chronic hypertension Complication of cardiac procedures Connective tissue disorders Vasculitis Advanced age Smoking Dyslipidaemia Cocaine Connective tissue disorders	Severe acute chest pain Back pain Pain radiating to neck, throat, jaw, and/or unilateral face Abdominal pain Claudication Hemoptysis Horner syndrome Oliguria/ Anuria Paraplegia, paralysis Hoarseness	+	+/-	+	MRI: Location of the intimal tear Involvement of branches of aorta Other vascular pathology		TEE: Identify true and false lumens Intimal flap Thrombosis in the false lumen Pericardial effusion Aortic regurgitation Proximal coronaries CTA: Beak sign: An acute angle between the dissection flap and the arterial wall Aortic cobwebs: Fibroelastic bands Size: False lumen larger than the true lumen Displaced intimal calcification: True lumen
Disease	Etiology	Symptoms	Dyspnea/ RI	Dysphagia	SVCS	Gold standard	Image	Additional findings
Superior vena cava obstruction	Compression of SVC from: Aortic aneurysm Bronchogenic carcinoma Breast cancer Cystic hygroma Goiter Histoplasmosis Indwelling catheter Lung cancer Lymphoma Non Hodgkin's lymphoma Small cell lung cancer Thymoma Tuberculosis	Cough Hoarseness Chest pain Problems swallowing and/or talking Hemoptysis Headache Dizziness Decreased alertness Dizziness Fainting Sensation of head or ear "fullness" Vision changes	+	+	++	Contrast-enhanced CT scan: Location and severity of the obstruction Superimposed thrombosis Mediastinal mass or lymphadenopathy Collateral vessels and associated lung masses		Invasive contrast venography: Etiology of obstruction Exact location of the obstruction
Partial anomalous pulmonary venous connection	Uncommon congenital abnormality Associated with an ASD Turner's syndrome (monosomy X) The scimitar syndrome	Asymptomatic Episodic exertional dizziness Neck pain Diaphoresis	+	-	-	MRI with contrast: Provide better anatomic definition Associated defects Condition of heart chambers		Associated with Adult onset pulmonary arterial hypertension (PAH) Right ventricular volume overload (RV failure) Cardiac catheter: Pressure and O2 Sat in heart chambers PFT: Normal despite of severe SOB
Gastrointestinal tract disease
Esophageal achalasia	Idiopathic Chagas disease Gastric carcinoma Herpes zoster HSV-1 Measles virus Paraneoplastic syndrome Sarcoidosis	Dysphagia for solids and liquids of patients respectively Regurgitation of undigested food Cough Aspiration Weight loss Chest pain, radiate to the back, jaw, neck, and arms Heartburn Hiccup Difficulty belching	+	+	-	High resolution manometry (HRM): Residual pressure of LES > 10 mmHg Incomplete relaxation of the LES. Increased resting tone of LES Aperistalsis High intra-esophageal pressure (due to stasis of food)		X ray: "Bird's beak image" or "rat tail" appearance Dilated esophageal body Air fluid level due to absent peristalsis Absence of gastric air bubble In advanced achalasia - sigmoid appearance CT scan: Dilatation of the esophagus Air fluid levels Exclude pseudoachalasia Echalasia symptoms resulting from esophageal cancer
Disease	Etiology	Symptoms	Dyspnea/ RI	Dysphagia	SVCS	Gold standard	Image	Additional findings
Esophageal cancer	Age over 60 Male gender Smoking Alcohol consumption Obesity Lye Ingestion Nitrosamine in food Plummer-Vinson syndrome Tylosis or Howel-Evans syndrome Radiation therapy GERD Barrett's esophagus Achalasia	Dysphagia to solid food Heartburn Weight loss Changes in diet Anorexia Regurgitation of food or saliva Hoarseness or loss of voice Intractable cough Blood in stools Frequent pneumonia	-	+	-	Endoscopy with biopsy: Friable lesion Superficial plaques Superfcial nodules Superficial ulcerations Strictures Ulcerated mass Circumferential masses		Barium swallow: Tapering stricture known as a "rat's tail" Irregular stricture Pre-stricture dilatation Shouldering CT scan: Eccentric or circumferential wall thickening >5 mm Peri-esophageal soft tissue and fat stranding Dilated fluid and debris filling the esophageal lumen Tracheobronchial invasion Aortic invasion
Esophageal rupture	Seizures Severe straining Vomiting Childbirth Prolonged coughing or laughing	Mackler's triad: Chest pain Vomiting Subcutaneous emphysema Other: Odynophagia Fever Tachypnea Tachycardia Cyanosis, and hypotension Pleural effusion Patients with cervical perforations can present with Neck pain Dysphonia	+	+	-	Esophagogram: The location Extent of perforation		CT scan: Esophageal wall edema and thickening Peri-esophageal fluid Mediastinal widening Air and fluid in the pleural spaces, retroperitoneum, or lesser sac
Hiatus hernia	50 or older age Obesity Female > Male Trauma: when undergoing surgery Frequent coughing Straining with constipation Heavy lifting Congenital Smoking Stress	Nausea Vomiting Regurgitation Heart burn Regurgitation Dysphagia	-	+	-	High resolution manometry with esophageal pressure topography (EPT): Evidence of separation of the crural diaphragm from the lower esophageal sphincter(LES) Real-time localization of the gastroesophageal junction Identification of intermittent herniation		Ultrasound: Location of gastroesophageal junction Bowel diameter measured at the diaphragmatic hiatus Ultrasound in pediatric population: Measurement of intra-abdominal esophagus which is less than 2 cm in diameter Sign of a beak at the gastroesophageal junction CT scan: Retrocardiac air-fluid level Organs within the hernia sac Focal fat collection in the middle of the mediastinum Visualise contents, length, orientation of herniated stomach inside the lower thorax Herniated contents lie adjoining to the esophagus Widening of esophageal hiatus Dehiscence of diaphragmatic crura (>15 mm)
Disease	Etiology	Symptoms	Dyspnea/ RI	Dysphagia	SVCS	Gold standard	Image	Additional findings
Pulmonary disease
Hilar lymphadenopathy	Lymphadenopathy: Tuberculosis Tubercular hilar lymphadenopathy in adult particularly in immunocompromised (HIV infection) Bronchogenic carcinoma Lymphoma Sarcoidosis Infection (fungal, atypical mycobacteria, viral, tularemia, and anthrax) Exposure to silica and certain drugs	Constituitional symptoms like: Fatigue Fever Malaise Flu- like illness Nausea and vomiting Night sweats Weight loss and Cachexia	+	-	-	Lymph node biopsy and histopathology		CT scan 10 mm in short-axis Loss of fatty hilum Focal necrosis Cystic necrotic nodes Long-to-short axis ratio (>2cm - usually benign)
Pneumomediastinum	Endoscopic procedures Intubation/extubation Central vascular access procedure Pleural cavity instrumentation Chest or abdominal surgery Direct chest wall trauma Tracheostomy Pulmonary barotrauma (scuba diver, free diver, airplane passenger)	Severe, acute pain in the chest (pain may radiate to the shoulders or back) Shortness of breath Fever Cervical pain (Subcutaneous emphysema) Jaw pain (Subcutaneous emphysema) Swelling of neck, face, chest, abdomen, shoulder (subcutaneous emphysema) Dysphonia Dysphagia Emesis	+	-	-	CT scan: Subcutaneous emphysema Naclerio V sign: Pneumomediastinum secondary to an esophageal rupture Pneumopericardium: Gas anterior to pericardium Ring around artery sign: Gas around pulmonary artery and main branches Tubular artery sign: Gas outlining major aortic branches Double bronchial wall sign: Gas outlining bronchial wall Continuous diaphragm sign: Gas trapped posterior to pericardium Extrapleural sign: Gas between parietal pleura and diaphragm Gas in pulmonary ligament Pediatric pneumomediastinum: Thymic wing sign: Elevated thymus Haystack sign (the heart appears like a haystack in a Monet painting)		Physical exam: Mediastinal crunch or click on auscultation over the cardiac apex and the left sternal border synchronous with the heart sound (Hamman's sign) Subcutaneous crepitation
Sarcoidosis	African american race People of Scandinavian descent Exposure to dusty/moldy environments People between 25 and 40 years Genetic factors The first-degree relatives have 55 fold increased the risk HLA-DRB1*1101 is associated with cardiac sarcoidosis and hypercalcemia Lofgren's syndrome, HLA-DRB1*03 is 4 times higher BTNL-2 (butyrophilin-like 2) gene Immune System Higher expression of serum amyloid A Immune system exhaustion and failure of effective antigen clearence Drug side effect Adalimumab Etanercept Ipilimumab Infliximab	cough chest pain fatigue malaise fever weight loss. Cutaneous sarcoidosis Papular, nodular, plaque-like, lupus pernio, erythema nodosum, subcutaneous sarcoidosis Ocular sarcoidosis dry eye, blurred vision, photophobia, red eye, pain Intraocular sarcoidosis Anterior, intermediate, and posterior uveitis Extraocular orbital sarcoidosis Involvement of lacrimal glands, conjunctiva, extraocular muscles, optic nerve, and a mass Upper respiratory tract Cough Nasal congestion Nasal crusting anosmia epistaxis Nasal polyposis Cardiac sarcoidosis Palpitations syncope lightheadedness chest pain sudden cardiac death (SCD) Neurosarcoidosis Peripheral facial nerve palsy Polyuria - polydipsia Disturbance in body temperature and libido due to hypothalamic inflammation Seizures Impairment in sleep Reticuloendothelial system Neck or axillary mass Lymphadenopathy Hepatosplenomegaly Musculocutaneous Acute sarcoid arthritis or acute polyarthritis Chronic arthritis Myopathy(diffuse granulomatous myositis) Lofgren syndrome erythema nodosum hilar lymphadenopathy Migratory polyarthralgia fever Exocrine glands Painless swelling of salivary glands and parotid gland Sicca syndrome and xerostomia Renal & electrolyte Renal colic caused by nephrolithiasis Uremia due to interstitial nephritis	+	-	-	Endoscopy with biopsy and histopathology Granulomas can be detected in any organ		Laboratory findings: Serum ACE levels greater than two times the upper limit of normal CT scan: Honeycombing parenchymal nodules and opacities along bronchovascular bundles as well as in subpleural locations
Infectious disease
Mediastinitis	Infection: Group A beta-hemolytic streptococci Streptococcus milleri Mycobacterium tuberculosis Histoplasma capsulatum Bacillus anthracis Candida albicans Risk factors: Recent chest surgery Endoscopy Obesity Smoking Immunodeficiency Intensive care unit stay > 2 days COPD Drug users Diabetes Kidney failure Peripheral vascular disease	Chest pain Cough Chills Fever Malaise Abdominal pain Hemoptysis Tachycardia	+	-	-	Culture and sensitivity of mediastinal tissue collected by biopsy/aspiration		Physical exam Chest wall tenderness Wound drainage Unstable chest wall CBC Leukocytosis CT scan Mediastinal or hilar mass Infiltrative region of soft-tissue attenuation which obliterates normal mediastinal fat planes and encases or invades adjacent structures Calcifications of the central mass or associated lymph nodes (especially if there has been preceding histoplasmosis) Tracheobronchial narrowing Pulmonary infiltrates
Anthrax	People at higher risk Veterinarians Laboratory professionals dealing the bacteria Health care workers Livestock producers People who handle animal products Mail handlers, military personnel, and response workers, in case of bioterrorism People who make or play animal hide drums Travelers, particularly to the follow areas: Central and South America Sub-Saharan Africa Central and southwestern Asia Southern and eastern Europe The Caribbean	Inhalation or Pulmonary Anthrax Fatigue Body pain Fever and chills Sweating Headache Confusion or dizziness Sore throat Cough Chest discomfort Shortness of breath Nausea Vomiting Stomach pains	+	-	-	Culture and sensitivity: Serum Plasma Blood Pleural fluid CSF Biopsy specimen		CT scan Mediastinal widening Hyperdense lymph nodes in the mediastinum Lymph node hemorrhage and necrosis following spore germination and vegetative growth with exotoxin elaboration Edema of mediastinal fat PCR Confirms virulence of organism by virulence factor genes Primers to the toxin gene Primer for the enzyme of capsule formation gene
Tularemia	F. tularensis Arthropod bites Tick bites Contact with infected mammals (particularly rabbits) Muskrat handling Deer-fly bites Lawn mowing or cutting brush Drinking water Laboratory exposures Pneumonic tularemia (bioterrorism)	Sudden fever Chills Headaches Diarrhea Muscle aches Joint pain cough Progressive weakness Ulcers on the skin or mouth Swollen and painful lymph glands Swollen and painful eyes Sore throat. Clinical syndromes: Ulceroglandular glandular oropharyngeal pneumonic oculoglandular typhoidal Lymphadenopathy may mimick bubonic plague Lymph node involvement is accompanied by a high fever Death may result	-	-	-	Culture and sensitivity		Laboratory Findings: Staining of F. tularensis reveals tiny, 0.2-0.5-μm X 0.7-1.0 μm, pleomorphic, poorly staining, gram-negative coccobacilli seen mostly as single cells Microscopic demonstration of F. tularensis using fluorescent-labeled antibodies is a rapid diagnostic procedure
Cystic mass
Bronchogenic cyst	Abnormal ventral budding or branching of the tracheobronchial tree during embryologic development	Pleuritic chest pain Cough Hemoptysis Fever Pneumonia secondary to airway obstruction	+	-	-			CT scan: Spherical or oval mass Smooth outline Unilocular Noncalcified Demonstrating the size and shape of the cyst Determining its position in relation to other structures Bronchogenic cysts can mimic hydatid cysts Pneumonitis, pneumothorax, or empyema may present
Duplication cysts			+	-	-
Thymic cyst
Mediastinal neuroenteric cysts
Lymphangioma
Pancreatic pseudocyst
Chronic inflammatory disease
Churg-Strauss syndrome
Disease	Etiology	Symptoms	Dyspnea/ RI	Dysphagia	SVCS	Gold standard	Image	Additional findings
Posterior mediastinal mass
Central nervous system disease
Meningocele
Neurilemmoma
ABBREVIATIONS: N/A: Not available, SOB: Shortness of breath, M/C: Most common, RI: Respiratory insufficiency, NM: Neuromuscular system, SVCS: Superior vena cava syndrome, SLE: Systemic lupus erythematosus disease, T3: Triiodothyronine, T4: Thyroxine, TSH: Thyroid stimulating hormone, TFT: Thyroid function test

1. Superior vena cava obstruction
2. Partial anomalous pulmonary venous connection
3. Esophageal achalasia
4. Esophageal cancer
5. Esophageal rupture
6. Hiatus hernia
7. Hilar lymphadenopathy
8. Pneumomediastinum
9. Sarcoidosis
10. Lymphoma
11. Neurilemmoma
12. Non-Hodgkin lymphoma
13. Teratoma
14. Thymoma

1. Thyroid cancer
2. Goitre
3. Mediastinal germ cell tumor,
4. Mediastinal tumor,
5. Mediastinitis

1. Churg-Strauss syndrome
2. Bronchogenic cyst,
3. Dermoid cyst
4. Anthrax:
5. Tularemia

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CT scan showing a smooth anterior mediastinal mass, with a mixed internal density of containing both enhancing soft tissue and cystic areas. The outline of the mass is relatively well defined. No lymphadenopathy, pleural effusion or infiltration. Case courtesy of Dr. Abdallah Al Khateeb (Picture courtesy: Radiopedia)

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CT scan showing excessive fatty tissue deposition within the posterior mediastinum with anterior displacement of the esophagus. Case courtesy of Dr. Ahmed Abdrabou (Picture courtesy: [1])