Residency · Residency · Respirology

Mediastinal Masses and Lymphadenopathy

Mediastinal Anatomy and Compartments

ITMIG Classification (2014 Revised)

The International Thymic Malignancy Interest Group (ITMIG) 2014 revised classification replaced the traditional anterior, middle, and posterior compartment system with a more anatomically precise framework. The prevascular (anterior) compartment is bounded anteriorly by the sternum and posteriorly by the pericardium and brachiocephalic vessels, and contains the thymus, fat, and lymph nodes. The visceral (middle) compartment contains the heart, pericardium, thoracic aorta, trachea, esophagus, thoracic duct, and lymph nodes. The paravertebral (posterior) compartment encompasses the paravertebral regions bilaterally and contains the sympathetic chain, intercostal vessels, and thoracic spine.

Differential Diagnosis by Compartment

The "4 T's" of Anterior Mediastinal Masses

The classic mnemonic for anterior mediastinal masses encompasses thymoma and thymic neoplasms, terrible lymphoma, teratoma and germ cell tumors, and thyroid (retrosternal goiter). Additional anterior mediastinal entities include thymic cysts and thymolipoma.

Anterior Mediastinal Masses

Thymoma

Thymoma is the most common primary anterior mediastinal neoplasm in adults, accounting for 30-40% of anterior mediastinal masses, with peak incidence between ages 40-60 and no sex predilection. The WHO histologic classification categorizes thymomas as Type A, AB, B1, B2, B3, and thymic carcinoma (Type C). The Masaoka-Koga staging system ranges from Stage I (encapsulated) through Stage IIA (microscopic capsular invasion), IIB (macroscopic capsular invasion), III (invasion into adjacent organs), IVA (pleural or pericardial dissemination), to IVB (distant metastases). Thymoma carries important paraneoplastic associations: myasthenia gravis occurs in 30-50% of thymoma patients with anti-acetylcholine receptor antibodies, and thymectomy may improve MG symptoms. Pure red cell aplasia affects 5-10%, and hypogammaglobulinemia (Good syndrome) occurs in 5-10%, presenting as immunodeficiency with thymoma. Other autoimmune conditions including SLE, polymyositis, and thyroiditis may also be associated. Treatment centers on surgical resection with complete R0 resection being critical for outcomes, adjuvant radiation therapy for Stage II-III disease, and cisplatin-based chemotherapy for advanced or unresectable cases. Thymic carcinoma (Type C) is more aggressive and requires multimodal therapy with a worse prognosis.

Lymphoma

Hodgkin lymphoma, particularly the nodular sclerosing subtype, is the most common lymphoma with anterior mediastinal involvement, typically affecting young adults. Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive subtype predominantly affecting young women, presenting as a bulky anterior mediastinal mass, and treated with R-CHOP or DA-EPOCH-R. An anterior mediastinal mass with superior vena cava syndrome in a young patient should be considered lymphoma until proven otherwise. Tissue biopsy is preferred over empiric treatment, and core needle biopsy is often sufficient for lymphoma subtyping, though fine needle aspiration alone should be avoided as architectural assessment is required for accurate diagnosis.

Germ Cell Tumors

Mediastinal germ cell tumors account for 2-5% of mediastinal tumors, arise in the anterior mediastinum, and predominantly affect young males. Mature teratoma is the most common type and may contain teeth, hair, and fat visible on CT; it is benign but may rupture. Seminoma is radiosensitive and chemosensitive with a good prognosis. Non-seminomatous tumors, including embryonal carcinoma, yolk sac tumor, and choriocarcinoma, require measurement of AFP and beta-hCG and are treated with cisplatin-based chemotherapy. Klinefelter syndrome confers an increased risk of mediastinal germ cell tumors.

Retrosternal Goiter

Retrosternal goiter represents extension of the thyroid gland into the anterior mediastinum, usually in the setting of multinodular goiter. It may cause tracheal compression or deviation, and fine needle aspiration should be performed if suspicious features are present. Thyroidectomy is indicated for symptomatic or suspicious cases.

<image>A three-panel anatomical diagram of the mediastinal compartments based on the ITMIG classification. Panel 1: axial CT-level illustration showing prevascular, visceral, and paravertebral compartments with labeled boundaries and contained structures. Panel 2: a table listing the most common masses in each compartment with approximate frequency: Prevascular (thymoma, lymphoma, germ cell tumor, thyroid), Visceral (lymphadenopathy, foregut cysts, tracheal tumors, esophageal tumors), Paravertebral (neurogenic tumors, meningocele, vertebral lesions). Panel 3: representative CT images or illustrations of one classic mass from each compartment with characteristic imaging features labeled.</image>

Middle Mediastinal Masses

Mediastinal Lymphadenopathy

Mediastinal lymphadenopathy is the most common cause of a middle mediastinal mass. Etiologies span malignant causes (lymphoma, metastatic carcinoma from lung, breast, gastrointestinal, melanoma, or renal primary sites, and leukemia), granulomatous diseases (sarcoidosis with bilateral hilar and mediastinal involvement, tuberculosis, and fungal infections including histoplasmosis and coccidioidomycosis), and reactive conditions (viral and bacterial infections, Castleman disease, IgG4-related disease, and amyloidosis). Bilateral symmetrical hilar lymphadenopathy is most commonly caused by sarcoidosis, followed distantly by lymphoma and infection. Unilateral hilar lymphadenopathy should be considered lung cancer until proven otherwise, though lymphoma and infection remain in the differential.

Foregut Cysts

Bronchogenic cysts are the most common mediastinal cysts, located in a paratracheal or subcarinal position, appearing smooth, homogeneous, and well-defined on CT, though they may appear solid if the protein content is high. They are usually asymptomatic and managed with surgical resection if symptomatic or diagnostically uncertain. Esophageal duplication cysts are posterior to the esophagus and managed similarly. Pericardial cysts most commonly occur at the right cardiophrenic angle, are benign, and may be observed if asymptomatic.

Vascular Lesions

Aortic aneurysms may present as mediastinal masses and are diagnosed definitively by CT angiography. Aberrant subclavian artery (arteria lusoria) may cause dysphagia lusoria through esophageal compression.

Posterior Mediastinal Masses

Neurogenic Tumors

Neurogenic tumors are the most common posterior mediastinal masses, accounting for 75% of lesions in this compartment. Nerve sheath tumors include schwannoma, the most common in adults, which is encapsulated and benign, and neurofibroma, which is associated with neurofibromatosis type 1 and carries a risk of malignant transformation. Sympathetic ganglia tumors include ganglioneuroma (benign, occurring in adults), ganglioneuroblastoma, and neuroblastoma (predominantly in children). Paraganglioma is rare and may be functional (catecholamine-secreting) or non-functional.

Other Posterior Masses

Additional posterior mediastinal entities include lateral thoracic meningocele associated with neurofibromatosis type 1, extramedullary hematopoiesis occurring in the setting of thalassemia or myelofibrosis, and vertebral body lesions from metastases, infection (Pott disease), or multiple myeloma.

Diagnostic Approach

Imaging

CT chest with contrast is the first-line imaging modality, characterizing location, density (cystic versus solid), enhancement pattern, calcification, and fat content. MRI is superior for evaluating neurogenic tumors, vascular assessment, and distinguishing cystic from solid lesions, and is also useful for characterizing thymic pathology. PET-CT is employed for staging known or suspected malignancy, with active lymphoma, thymic carcinoma, and metastatic disease being FDG-avid, while thymoma shows variable uptake and mature teratoma is typically non-avid.

Tissue Diagnosis

EBUS-TBNA is the first-line approach for mediastinal lymphadenopathy and paratracheal or subcarinal masses, with a yield exceeding 85%. EUS-B-FNA (endoscopic ultrasound performed via the bronchoscope) provides access to subcarinal, para-aortic, and inferior pulmonary ligament nodes. CT-guided biopsy is used for accessible masses not amenable to endoscopic approaches. Mediastinoscopy or anterior mediastinotomy (Chamberlain procedure) is reserved for situations where minimally invasive techniques are insufficient. Core biopsy is preferred over FNA for suspected lymphoma, as architectural assessment is critical for accurate subtyping.

Laboratory Investigations

AFP and beta-hCG must be measured in all anterior mediastinal masses in young males to evaluate for germ cell tumors. LDH may be elevated in lymphoma and germ cell tumors. Anti-acetylcholine receptor antibodies should be checked to evaluate for myasthenia gravis in the setting of anterior mediastinal masses. Thyroid function tests assess for retrosternal goiter. ACE and calcium screening evaluates for sarcoidosis. Flow cytometry on aspirated material facilitates lymphoma subtyping.

<image>A clinical decision algorithm for evaluating a mediastinal mass. Start with detection on CXR or CT. First branch: identify compartment (prevascular, visceral, paravertebral) using ITMIG criteria. For each compartment, show the differential diagnosis ranked by probability. For prevascular: check age/sex -> young male: AFP/beta-hCG (germ cell tumor), young female: PMBCL; older adult: thymoma; thyroid studies. For visceral: lymphadenopathy workup (EBUS-TBNA), cystic lesion (bronchogenic/esophageal cyst - MRI to confirm), vascular (CTA). For paravertebral: MRI for neurogenic tumor characterization. Show biopsy decision tree: EBUS-TBNA (mediastinal nodes), CT-guided biopsy (solid accessible mass), surgical biopsy (if minimally invasive approach insufficient or lymphoma requires architectural assessment). Include red flags for urgent evaluation: SVC syndrome, tracheal compression, rapid growth.</image>

SVC Syndrome

Etiology

Superior vena cava syndrome has a malignant etiology in 60-85% of cases, including lung cancer (especially SCLC and NSCLC), lymphoma, mediastinal germ cell tumors, and metastatic disease. Non-malignant causes, which are increasing in frequency, include thrombosis related to central venous catheters and devices, fibrosing mediastinitis, granulomatous disease, and aortic aneurysm.

Clinical Features

The clinical presentation includes facial and upper extremity edema, plethora, dilated collateral veins on the chest wall, and Pemberton sign (facial congestion and arm cyanosis with arms raised above the head). Severity ranges from mild edema to the rare true emergency of cerebral edema and upper airway compromise.

Management

Tissue diagnosis should be obtained before treatment whenever possible, as treatment varies dramatically by etiology. Endovascular stenting provides rapid symptom relief and is particularly useful in malignant SVC syndrome. Specific treatment depends on the underlying cause: chemotherapy and radiation therapy for SCLC and lymphoma (which often respond rapidly), and anticoagulation for thrombosis. Glucocorticoids may be effective for lymphoma-associated SVC syndrome but should be avoided before biopsy when possible, as steroids can obscure the lymphoma diagnosis.

Key Clinical Pearls

• An anterior mediastinal mass in a young male should prompt immediate AFP and beta-hCG testing to rule out germ cell tumor before any other workup
• Bilateral symmetrical hilar lymphadenopathy in a young patient is sarcoidosis until proven otherwise; however, always consider lymphoma and obtain tissue if clinical picture is atypical
• Core biopsy (not FNA alone) is essential for suspected lymphoma; architectural assessment is required for accurate subtyping and treatment planning
• Thymoma is associated with myasthenia gravis (30-50%), but MG can also occur without thymoma; anti-AChR antibodies should be checked in all anterior mediastinal masses
• SVC syndrome is rarely a true emergency requiring empiric treatment; tissue diagnosis should be obtained before treatment whenever feasible, as management differs dramatically between SCLC, lymphoma, and germ cell tumor

References

1. Carter BW, Benveniste MF, Madan R, et al. ITMIG Classification of Mediastinal Compartments and Multidisciplinary Approach to Mediastinal Masses. Radiographics. 2017;37(2):413-436.
2. Detterbeck FC, Nicholson AG, Kondo K, et al. The Masaoka-Koga Stage Classification for Thymic Malignancies: Clarification and Definition of Terms. J Thorac Oncol. 2011;6(7 Suppl 3):S1710-S1716.
3. Tomiyama N, Honda O, Tsubamoto M, et al. Anterior Mediastinal Tumors: Diagnostic Accuracy of CT and MRI. Eur J Radiol. 2009;69(2):280-288.
4. Amin MB, Edge SB, Greene FL, et al. AJCC Cancer Staging Manual. 8th ed. Springer; 2017. (Thymic tumors chapter)
5. Yu L, Jian L, Li Z, et al. Mediastinal Lymphadenopathy: Diagnostic Approach with Endobronchial Ultrasound. Respiration. 2021;100(5):429-437.

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