What is the diagnosis and treatment for a patient with suspected thymic hyperplasia, possibly associated with myasthenia gravis?

Thymic Hyperplasia: Diagnosis and Management

Diagnostic Approach

For suspected thymic hyperplasia, particularly when associated with myasthenia gravis, contrast-enhanced chest CT is the initial imaging modality of choice, followed by chemical-shift MRI in equivocal cases to differentiate hyperplasia from thymoma. 1

Initial Imaging Strategy

• CT scan is the primary imaging modality and should assess for low-attenuation, symmetric, fatty pattern maintaining the bi-pyramidal shape of the thymus 1
• Chemical-shift MRI should be performed when CT findings are inconclusive, as thymic hyperplasia demonstrates homogeneous signal decrease on opposed-phase images (due to microscopic fat interspersion), which is not observed in thymoma 1
• PET scan is not recommended for routine assessment, as thymic hyperplasia can show hypermetabolism similar to thymomas, making it unreliable for differentiation 1

Mandatory Laboratory Assessment

All patients with suspected thymic hyperplasia require systematic immunological workup 1:

• Complete blood count with reticulocytes 1
• Serum protein electrophoresis 1
• Anti-acetylcholine receptor antibodies (essential for myasthenia gravis screening) 1
• Anti-nuclear antibodies 1
• Serum β-hCG and alpha-fetoprotein to exclude germ cell tumors 1

Clinical Context Recognition

Thymic lymphoid hyperplasia is most commonly observed in myasthenia gravis but also occurs with hyperthyroidism, connective tissue disease, or vascular disease 1. Rebound hyperplasia should be considered after chemotherapy, radiation therapy, corticosteroids, stress, burns, or injuries 1.

Size-Based Management Algorithm

Lesions <30mm

Therapeutic intervention is usually not required for lesions <30mm, given the low risk of progression or thymic malignancy 1. Observation with follow-up imaging is appropriate 1.

Lesions ≥30mm

Complete surgical resection via median sternotomy with total thymectomy is indicated for lesions ≥30mm due to increased malignancy risk and the inability to reliably exclude thymoma radiologically 2, 3, 4, 5.

Surgical Management

When Surgery is Indicated

• Preoperative biopsy is not required if upfront surgical resection is achievable and thymic pathology is highly suspected 1
• If biopsy is necessary, fine-needle aspiration is not recommended; core-needle biopsy or surgical biopsy via mediastinotomy is preferred 1
• Avoid transpleural approach during biopsy to prevent tumor cell seeding 1

Surgical Technique

• Median sternotomy provides optimal exposure and is the standard approach 1, 2, 3
• Complete thymectomy (removal of entire thymus gland and perithymic fat) is preferred over partial resection 1, 2, 3
• Surgical clips should be placed to mark areas of concern if complete resection is challenging 2

Critical Preoperative Consideration

All patients must have serum anti-acetylcholine receptor antibody levels measured before surgery, even if asymptomatic, to avoid respiratory failure during the procedure 1. Patients with confirmed myasthenia gravis require preoperative treatment by an experienced neurologist 1.

Differential Diagnosis Pitfalls

The distinction between thymic hyperplasia and thymoma is challenging radiologically 1, 3, 6:

• Thymoma typically presents as a homogeneous or slightly heterogeneous prevascular soft tissue mass in patients >40 years, especially with myasthenia gravis symptoms 1
• Thymic hyperplasia maintains bi-pyramidal shape with fatty infiltration on chemical-shift MRI 1
• Thymic epithelial tumors account for 35% of anterior mediastinal masses, with lymphomas (25%) and germ cell tumors (20%) as key differentials 1

Special Considerations for Myasthenia Gravis

• Approximately 30-50% of patients with thymomas have myasthenia gravis 1
• Thymic lymphoid hyperplasia is found in up to 65% of MG patients at onset, while thymoma occurs in 15% 6
• Immunosuppressive therapy with methylprednisolone is highly effective in MG patients with thymic hyperplasia, potentially obviating the need for surgery in some cases 7
• However, thymectomy remains the preferred treatment for MG patients with thymomas 7

Post-Resection Follow-Up

• Follow-up imaging should confirm resolution of any mass effect or cardiac displacement 2
• Histopathological examination will definitively distinguish true thymic parenchymal hyperplasia (no lymphoid follicles, preserved corticomedullary architecture) from lymphoid follicular hyperplasia or thymoma 5, 8
• Long-term prognosis for true thymic hyperplasia after complete resection is excellent, with all patients alive and well at 5-15 years follow-up 5