Thymic Carcinoma

Thymic carcinoma is a rare epithelial malignancy of the thymus with overtly malignant cytology and a worse outlook than thymoma. It makes up about 10 to 15% of thymic epithelial tumors, usually in patients aged 50 to 60 years, with a slight male predominance. It is rarely associated with myasthenia gravis (under 5%).

Subtypes: squamous cell (the most common), lymphoepithelioma-like (possibly Epstein-Barr virus associated), basaloid, mucoepidermoid, clear cell, sarcomatoid, undifferentiated and adenocarcinoma. Tumor cells are positive for CD5, CD117 and p63, and KIT mutations occur in a minority. Staging follows the thymoma invasion stages.

Behavior is invasive. Most patients present with stage III or IV disease, with spread to the pleura, lung, lymph nodes (about 30 to 40%), liver, bone and brain. Five-year survival is 30 to 50% overall, 70% for resected stage I and II, and under 20% for stage IVB. Complications: superior vena cava syndrome, pericardial and pleural effusion, tumor compression of the airway and metastatic disease.

• Chest pain, cough, dyspnea, weight loss and fatigue
• Superior vena cava syndrome (facial swelling, venous distension)
• Pleural or pericardial effusion
• Often incidental on chest imaging
• Red flags: dyspnea with effusion, tamponade physiology, rapid enlargement and bone pain

1. CT chest and upper abdomen with contrast: an irregular, infiltrating anterior mediastinal mass with necrosis, vessel and pericardial invasion, lymphadenopathy and pleural nodules.
2. Fluorodeoxyglucose PET-CT: high uptake, and staging of distant disease.
3. Core needle biopsy (image-guided or through anterior mediastinotomy). Immunohistochemistry: CD5, CD117, p63 and GLUT1 positive, TTF-1 and napsin A negative, with terminal deoxynucleotidyl transferase absent. These separate thymic carcinoma from lung squamous carcinoma and B3 thymoma.
4. Brain MRI and bone imaging when clinically indicated, and AFP and beta-hCG to exclude germ cell tumor.
5. Next-generation sequencing (KIT, TP53, CDKN2A) and PD-L1 testing.

Differentials: thymoma (B3), lung squamous carcinoma with mediastinal extension, germ cell tumor, lymphoma, metastasis, neuroendocrine carcinoma of the thymus.

1. Resectable disease (stage I to III): complete resection with the thymus, surrounding fat, involved pericardium or pleura and nodes. Cefazolin 2 g IV before incision (3 g if over 120 kg), enoxaparin 40 mg SC daily until mobile. Add adjuvant radiotherapy 50 to 60 Gy in 25 to 30 fractions.
2. Locally advanced unresectable disease: induction chemotherapy with carboplatin AUC 6 IV day 1 and paclitaxel 200 mg/m2 IV day 1 every 3 weeks for 3 to 4 cycles, followed by surgery if resectable, or definitive chemoradiotherapy 60 to 66 Gy in 30 to 33 fractions with concurrent weekly carboplatin AUC 2 and paclitaxel 45 to 50 mg/m2.
3. Metastatic disease, first line: carboplatin AUC 5 to 6 with paclitaxel 175 to 200 mg/m2 every 3 weeks for 4 to 6 cycles. Alternatives are cisplatin 50 mg/m2, doxorubicin 40 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks, or carboplatin with etoposide.
4. Later lines:
   • Lenvatinib 24 mg orally once daily (monitor blood pressure, proteinuria, wound healing and risk of hemorrhage).
   • Pembrolizumab 200 mg IV every 3 weeks (the autoimmune risk is lower than in thymoma but still significant, so check thyroid function, liver tests, glucose and cortisol every 4 to 6 weeks).
   • Sunitinib 50 mg orally once daily for 4 weeks followed by 2 weeks off.
   • Imatinib 400 mg orally once daily for KIT-mutant tumors.
5. Supportive care:
   • Pleural effusion: drainage with an indwelling catheter or talc pleurodesis (4 to 5 g).
   • Pericardial effusion: drainage and window.
   • Superior vena cava syndrome: stenting, radiotherapy and dexamethasone 8 mg IV or orally twice daily.
   • Palliative radiotherapy 20 Gy in 5 fractions to symptomatic sites.
6. Oligometastatic disease: resection or stereotactic radiotherapy of selected metastases.

Follow-up: CT chest every 3 to 4 months for 2 years, then every 6 months. Counsel on prognosis and offer early palliative care.