A bimodal approach to thymic carcinoma with pericardial sac invasion

Abstract

Thymic carcinoma is a rare tumour of the thymus, representing less than 1% of thymic malignancies. ¹ It has an annual incidence of 0.15–0.32 per 1 00 000 person-years. ² It is found incidentally in 30% of the patients as an opacity on chest X-ray or with non-specific complaints of persistent cough, chest pain, fatigue, shortness of breath, arm and facial swelling, and upper airway congestion related to tumour extension. We present the case of a 59-year-old man with a history of Graves’ disease status post radiation treatment presenting with cough and left lingual opacity on chest X-ray, confirmed to be thymic carcinoma with pericardial invasion and lymph node metastasis. We aim to discuss the presentation, treatment modalities and outcome associated with this rare tumour.

Background

Thymic carcinomas are most commonly located in the anterosuperior mediastinum and are often confused with thymomas. They have a high predilection for frequent metastases to regional lymph nodes (LNs), bone, liver and lung on initial presentation. Staging remains prognostic, with early-stage patients exhibiting a remarkably better survival. Due to paucity of cases, treatment protocols have not been vetted by randomised controlled trials (RCTs), and a multimodal approach involving surgery, radiation and chemotherapy is often used in the treatment of this malignancy.

Case presentation

A 59-year-old man with a medical history of Graves’ disease status post radio-iodine treatment, hypertension, hyperlipidaemia and 15-pack-year smoking history initially presented to his primary care physician’s (PCP) office with complaints of productive cough associated with shortness of breath for 7 days. His chest X-ray (CXR) showed left lingual opacity, and he was treated with a 7-day course of levofloxacin for presumed community-acquired pneumonia (figure 1). Subsequently, the patient was lost to follow up for 3 months; he visited his PCP’s office for non-resolving symptoms and worsening shortness of breath. His vitals were blood pressure 130/90 mm Hg, heart rate 64 beats/min, temperature 98.4°F and respiratory rate 16 breaths/min. The rest of the physical examination was unremarkable.

Figure 1.

CXR AP view showing left lingual lobe opacity. AP, anteroposterior; CXR, chest X -ray.

Investigations

Routine complete blood count and basic metabolic panel were normal. A repeat CXR showed persistent left lingual lobe opacity and was followed up with a CT scan of the chest, which showed a 7x8 cm large anterior mediastinal mass with diffuse peripheral interstitial thickening associated with a small left subpleural nodule and interlobar LN (figure 2). Cardiothoracic surgery was consulted, and the patient underwent mediastinotomy with biopsy of the mass showing malignancy concerning possible thymic carcinoma.

Figure 2.

CT chest axial view showing a 7x8 cm large anterior mediastinal mass.

After discussions with the multidisciplinary tumour board, positron emission tomography (PET)–CT was recommended, which showed a diffusely metabolically active superior mediastinal mass of 12x6 cm with no metabolically active lesions in the lungs or LNs (figure 3). Brain MRI was unremarkable for any evidence of metastasis.

Figure 3.

PET–CT showing a diffusely metabolically active superior mediastinal mass of 12x6 cm with standardized uptake value  (SUV_max) 8.6. PET, positron emission tomography.

Differential diagnosis

• Thymic tumours.

• Lymphoma.

• Germ cell tumour.

• Intrathoracic goitre.

Treatment

The patient underwent median sternotomy with mediastinal mass resection and anterior pericardial sac and mediastinal aortopulmonary window LN resection. Final biopsy was positive for high-grade thymic carcinoma invading the adherent pericardium with one of six LNs positive for metastasis (figures 4 and 5). On immunohistochemical staining, malignant cells were positive for CD5, BCL2, CD117 and p63 markers. The patient was stage IVa according to the American Joint Committee on Cancer and subsequently underwent 6 weeks of adjuvant radiation therapy.

Figure 4.

H&E (200×) staining showing high-grade thymic carcinoma.

Figure 5.

H&E (400×) staining of LN positive for metastatic thymic carcinoma. LN, lymph node.

Outcome and follow-up

Follow-up PET scan after 1 year of treatment was negative for uptake in the tumour bed or locoregional LN or structures (figure 6). The patient has been in remission for 2 years. Ongoing annual imaging studies would be performed over the next 5 years for our patient.

Figure 6.

Repeat PET–CT at 1-year follow-up negative for uptake after postoperative radiotherapy. PET, positron emission tomography.

Discussion

Anterior mediastinum is defined as the space between the posterior surface of the sternum and the anterior aspect of great vessels and the pericardium. Anterior mediastinal masses are commonly recognised as incidental findings on routine chest imaging being performed for other purposes. It is also the most common location for mediastinal masses. Generally, four common masses associated with this space are thymic masses, thyroid  masses, germ cell tumours and lymphoma, with thymic masses being most commonly seen in adults.

Thymic carcinoma arises as a result of disorganised cellular growth from the thymic epithelium and is often confused with thymoma on initial presentation. Cough, chest pain, nerve palsy and superior vena cava syndrome are common presenting complaints, some of which were also seen in our patient.^{3 4}

Commonly masses presenting in the anterosuperior mediastinum as incidental finding on chest radiographic examination. Approximately 40% of the encountered individuals would have lymphadenopathy present on the initial encounter as it was seen with our patient.⁵ Hephzibah et al and Sung et al reported regarding the importance of PET–CT in the evaluation of thymic tumours for initial workup, treatment response, prognosis and aid in distinguishing thymoma from thymic carcinoma.^{6 7}

Due to rarity of thymic carcinomas, most of the data regarding treatment are obtained from non-randomised studies and have been extrapolated from the treatment of thymoma, their relatively benign counterpart. Thymomas and thymic carcinomas were first clearly classified as different entities by the 2004 WHO criteria; since then, ongoing research has shown differences in terms of biomarker and clinical outcomes. Our patient was treated in accordance to National Comprehensive Cancer Network (NCCN) guidelines. A complete resection was attempted, and our patient had tumour-free margins with removal of the associated structures like the anterior pericardium. A bimodal approach involving postoperative radiotherapy (PORT) was used in our patient based on advanced stage, high-grade cellular atypia and invasion of the anterior pericardium. Although the role of PORT in reducing mortality has not been defined, there is convincing evidence that it is associated with reducing local recurrence.^8–11 Okuma et al reported in their pooled analysis of more than 15 studies that cisplatin-based chemotherapy might hold superiority in the treatment of advanced thymic carcinoma; however, they re-emphasised that the role of chemotherapy in treatment has not been well studied.¹²

In conclusion, thymic carcinoma has 5-year survival rates between 30% and 50%, with significant difference between early and late stages at the time of presentation. Although the advancement in imaging techniques has aided in the diagnosis of this rare cancer, the treatment protocol remains speculative at its best. Large prospective RCTs are required to learn more about the management of thymic carcinoma.

Learning points.

• High index of suspicion is warranted and follow-up imaging for non-resolving chest X-ray opacities may be the only initial clue to diagnosis.

• Positron emission tomography–CT is an emerging diagnostic tool in the evaluation of thymic masses for initial workup, treatment response, prognosis and aid in distinguishing thymoma from thymic carcinoma.

• Postoperative radiotherapy has been shown to decrease the rates of local recurrence in patients with advanced thymic carcinoma on presentation.