Differential Diagnosis of Mediastinal Masses
Compartment-Based Approach
The differential diagnosis of a mediastinal mass is best organized by anatomic compartment using the International Thymic Malignancy Interest Group (ITMIG) classification: prevascular (anterior), visceral (middle), and paravertebral (posterior). 1
Prevascular (Anterior) Compartment
Most Common Entities by Frequency
Thymomas (28%) are the most common prevascular mediastinal lesion, particularly in adults over 40 years, and are strongly associated with myasthenia gravis (15-50% depending on histologic subtype). 1, 2
Benign cysts (20%) including thymic cysts, pericardial cysts, and bronchogenic cysts are the second most common. 1, 2
Lymphomas (16%) including both Hodgkin's (particularly nodular sclerosing type) and non-Hodgkin's lymphoma, often presenting with rapid onset of B-symptoms, elevated LDH, and coexistent lymphadenopathy. 1, 2
Germ cell tumors (20% of anterior masses) including teratomas (showing heterogeneous morphology with fat and cystic components on CT), seminomas, and non-seminomatous tumors (the latter two presenting with elevated serum β-hCG or alpha-fetoprotein and often fulminant onset). 1, 2
Key Clinical Discriminators
Myasthenia gravis symptoms (ptosis, diplopia, dysphagia, weakness) strongly suggest thymoma and warrant systematic immunological workup including anti-acetylcholine receptor antibodies. 1, 2
Rapid onset with B-symptoms (fever, night sweats, weight loss), elevated LDH, and multiple lymph node stations favor lymphoma over thymoma. 1, 2
Young male patients with large, rapidly growing masses and elevated tumor markers (β-hCG, AFP) suggest germ cell tumors. 1, 3
Thymic carcinomas present with local symptoms (chest pain, cough, dyspnea) rather than paraneoplastic syndromes and show aggressive features including local invasion, lymphadenopathy, and pleural effusion on imaging. 1, 2
Important Pitfall: Thymic Hyperplasia
Thymic hyperplasia can mimic malignancy but maintains a bi-pyramidal shape with low attenuation and symmetric fatty pattern on CT. 1
Consider rebound hyperplasia after chemotherapy, radiation, corticosteroids, stress, burns, or in patients with myasthenia gravis, hyperthyroidism, or connective tissue disease. 1
Chemical-shift MRI showing homogeneous signal decrease on opposed-phase images (due to microscopic fat) distinguishes hyperplasia from thymoma, which does not suppress. 1
Lesions <30 mm have low risk of malignancy and typically require no intervention. 1
Visceral (Middle) Compartment
Most Common Entities
Benign cysts are most common in the visceral compartment, including bronchogenic cysts, pericardial cysts, and esophageal duplication cysts. 1
Lymphadenopathy from lymphoma, metastatic disease, sarcoidosis, or infectious causes (histoplasmosis, tuberculosis in endemic areas). 1, 4
Vascular lesions including aortic aneurysms and vascular malformations. 1
Infectious Considerations
Histoplasmosis presents as mediastinal lymphadenitis, particularly in endemic areas (Ohio and Mississippi River valleys), and more commonly affects children. 4
Tuberculosis should be considered in high-risk populations (immigrants from endemic areas, prisoners, nursing home residents) with chronic cough (≥2-3 weeks), requiring sputum AFB smears/cultures and chest radiograph. 4
Tissue diagnosis via EBUS-guided TBNA, CT-guided biopsy, or surgical sampling is often necessary as CT cannot reliably differentiate infectious from neoplastic etiologies. 4
Paravertebral (Posterior) Compartment
Most Common Entities
Neurogenic tumors are most common in the paravertebral compartment, including schwannomas, neurofibromas, ganglioneuromas, and neuroblastomas (the latter in children). 1
MRI is superior to CT for evaluating neurogenic tumors due to better depiction of neural and spinal involvement. 1
Age-Specific Considerations
Pediatric Population
Lymphoma (particularly T-lymphoblastic leukemia/lymphoma) is the most common mediastinal mass in children and young adults. 3, 5
Neurogenic tumors are more common in the posterior mediastinum in children. 1
Germ cell tumors should be considered in young males with anterior mediastinal masses. 3
Adults Over 40 Years
- Thymoma is the most likely diagnosis for a homogeneous or slightly heterogeneous prevascular soft tissue mass, especially with myasthenia gravis. 1, 2
Critical Imaging and Diagnostic Approach
Initial Evaluation
CT chest with contrast is the primary imaging modality for definitive compartment localization and tissue characterization (demonstrating calcium, fat, fluid attenuation, and enhancement patterns). 1
Chest radiography can provide initial compartment localization but has limited tissue characterization capability. 1
Advanced Imaging
MRI is superior to CT for tissue characterization, distinguishing thymic hyperplasia from malignancy (chemical-shift imaging), evaluating neurogenic tumors, differentiating low-risk from high-risk thymomas, and assessing invasion across tissue planes. 1
PET-CT is generally not recommended for routine thymic mass evaluation as both benign and malignant lesions can show hypermetabolism, but may be useful for aggressive histologies, advanced staging, or evaluating suspected recurrence. 1
Laboratory Evaluation
Serum tumor markers: β-hCG and alpha-fetoprotein for germ cell tumors. 1, 3
Immunological workup for suspected thymoma: complete blood count with reticulocytes, serum protein electrophoresis, anti-acetylcholine receptor antibodies, and anti-nuclear antibodies. 1
Biopsy Indications
Pretreatment biopsy is NOT required if thymoma is highly probable and upfront surgical resection is achievable. 1
Biopsy is required when diagnosis is uncertain, the mass is unresectable, or when differentiating lymphoma from other entities (as this fundamentally changes management from surgery to chemotherapy). 1
Core-needle biopsy or surgical biopsy (mediastinotomy/mini-thoracotomy) with deep, multiple samples is preferred over fine-needle aspiration, with 91.7% adequacy and 100% diagnostic accuracy when adequate tissue is obtained. 1, 6