Thymic carcinoma is a rare, highly malignant solid tumor originating in the thymic epithelium with malignant cytological characteristics and a high potential for invasion and metastasis. Thymus carcinoma still ranks among the top 10 thoracic neoplasms in terms of mortality. Thymic squamous cell carcinoma (TSCC) is the predominant pathological category of thymic carcinoma, representing an estimated 80% of all thymic carcinomas [2, 8]. Compared to other thymic carcinomas, TSCC exhibited less aggressive behavior with a 5% reduction in OS rates at 5 years (59.5%) and 8 years (54.5%) [9]. CD5 and CD117 are generally used as diagnostic markers for TSCC; however, lung squamous cell carcinoma (LSCC) occasionally expresses CD5 (0–15%) or CD117 (6.2–20%) [10, 11]. In contrast, one case of CD70-positive and CD5/ CD117-negative was observed by Jumpei Kashima et al. These results suggest that each marker cannot completely distinguish TSCC from LSCC independently [12]. Meanwhile, Yohei Taniguchi et al. showed that preferentially expressed antigens in melanoma (PRAME) may be a new TSCC-specific diagnostic marker. This study showed that of the 17 cases of TSCC and 116 thymomas in which PRAME expression was detected by immunohistochemistry, all 17 cases (100%) of TSCC showed diffuse strong expression of PRAME. In comparison, eight cases (6.8%) of the 116 thymomas showed weak focal expression. Seventeen cases (100%) and 16 cases (94.1%) of TSCC were CD117 and CD5 positive, and 1 (0.9%) case of B3 thymoma was double positive for CD5 and CD117. CD5/CD117 positive B3 thymoma was PRAME negative [13]. Consequently, the evaluation of CD70 in combination with CD5 and CD117 or PRAME in combination with CD5 and CD117 may help to diagnose TSCC more accurately. Notably, the independent prognostic factors associated with overall survival were age at diagnosis and SEER stage [14].
However, due to the rarity of thymic carcinoma, a standard postoperative adjuvant protocol remains to be established. One study confirmed that postoperative radiotherapy reduces recurrence of thymic malignancies [15]. In the latest version of the National Comprehensive Cancer Network guidelines, the paclitaxel + carboplatin regimen is recommended as the first-line chemotherapy regimen for TC. This recommendation is based on a phase II study that reported an ORR of 21.7% and a median PFS of 5.0 months with paclitaxel combined with platinum in patients with advanced TC [16]. A subgroup analysis of a phase III study in patients with NSCLC showed a significantly better response to platinum in combination with nab-PAC in squamous cell carcinoma [17]. In this case, adjuvant radiotherapy and chemotherapy were given to the patient, but more clinical trials are needed to verify the effectiveness and safety of this modality.
Based on various genetic and histological data, Chun Jin et al. found that multiple thymic tumors may come from the same tumor clone, suggesting that some thymic tumors in multiple TSCC may be the metastases of the primary tumor. These findings contribute to our understanding of thymic epithelial neoplasms. Therefore, the potential association between primary tumor and metastasis reminds us that there may be communication channels in the thymus lobules that promote tumor recurrence and metastasis. This communication channel may exist in TSCC and thymoma. The findings suggest that, whether thymic carcinoma or thymoma, thymectomy is necessary to reduce the possibility of tumor recurrence and improve survival [18]. In addition, expanded thymectomy can be the most acceptable and effective treatment for thymic carcinoma [19].
Some studies have suggested that histological classification, complete resection, large vessel invasion, or adjuvant therapy impacted the prognosis of thymic cancer. However, few reports have been used for subtype analysis because of the low incidence rate. Patients receiving treatment should achieve local and complete control of tumors and maintain physiological function and quality of life. The treatment model, including surgery, has a considerable impact on the survival of patients. In many studies, total resection is recommended without complex diffusion and metastasis at diagnosis, which is considered a prognostic factor in patients with thymic cancer [20]. In this operation, the preoperative and intraoperative judgment was thymoma, so routine lymph node evaluation was not performed for the time being. Meanwhile, lymph node metastasis is an important factor affecting the prognosis of thymic malignancies. Although lymph node dissection does not improve the long-term prognosis of thymic malignancies, lymph node dissection plays a role in accurate staging and improved prognostic prediction [21]. Therefore, it is necessary to perform expanded thymectomy and lymph node dissection during surgery.
Although thymic carcinoma is considered a highly aggressive tumor, surgical treatment combined with chemotherapy and radiation provides good long-term results for thymus cancer [4]. Therefore, the primary treatment of choice for thymic carcinoma is complete excision. Thymic carcinoma has a postoperative 5-year survival rate of 58–80%, and postoperative complications and mortality are rarely reported [8, 9, 22, 23].
Various approaches for thoracoscopic resection of thymic tumors have been developed, including median sternotomy, unilateral, bilateral, subxiphoid single-port, and triple-incision approaches [6, 24,25,26,27,28].
Whether it is thymoma or thymic carcinoma, median sternotomy is the preferred surgical method, but it has disadvantages such as large postoperative trauma, heavy postoperative pain, and an unaesthetic scar [29]. Therefore, minimally invasive surgical techniques for thymus gland disease treatment are very important. Right thoracoscopic thymectomy with less invasive approach is now being accepted by more and more thoracic surgeons [30, 31], but the left side of the thymus cannot be completely removed. Thus, to date, there is no consensus on the standard thoracoscopic approach for thoracoscopic thymectomy, especially for enlarged thymectomy. Surgeons usually choose a thoracoscopic approach based on their training experience and preferences. Marcin Zieliński et al. [32, 33] used double raising of the sternum in thoracoscopic thymectomy, which required the combination of transcervical and subxiphoid incisions. Learning was complicated, requiring too much time and too many incisions.
Marcin Zieliński et al. [25] used a sternal-assisted retractor with incisions above the sternal notch and below the xiphoid process to better expose the anterior mediastinum. Still, its disadvantages were that there were too many incisions, a large trauma surface, and poor postoperative appearance. Ren Xiang Jia et al. [34] created a 3-mm port at the level of the right third intercostal paraspinal line to elevate the sternum based on thoracoscopic thymectomy of the right thorax, and the fatty tissue of the upper pole of the thymus and the left costal diaphragm could be seen, but it is difficult to completely expose the contralateral side and remove all mediastinal adipose tissues. Francesco Caronia et al. [35, 36] studied bilateral thoracoscopic thymectomy. Although bilateral thymus tissues and fat pads can be more effectively removed compared with the above-mentioned procedure, more incisions are required, which may increase surgical trauma and postoperative pain. Qiang Lu et al. [6] investigated the treatment of myasthenia gravis with a “three-port” thoracoscopic expanded thymectomy under the costal arch under the xiphoid process, in which carbon dioxide was injected into the thoracic cavity to elevate the sternum and expose the anterior mediastinal space. Its advantages lie in the excellent visualization of the entire anterior mediastinum, facilitating removal of fatty tissues and minimizing the chance of accidental surgical injuries, such as accidental blood vessel tear or bilateral diaphragmatic nerve injury. Furthermore, single-lumen double-lung ventilation can be applied to patients who cannot tolerate single-lung ventilation and have a poor cardiopulmonary function, increasing the chances of surgery for more patients. However, its disadvantage lies in the relatively close location of the three incisions under the costal arch under the xiphoid process, which greatly affects the coordination of surgical instruments and the thoracic lens.
Therefore, based on the premise of the three-incision surgery, we proposed a new, improved thoracoscopic extended thymectomy under the xiphoid subcostal arch, which removed the 3-cm incision under the xiphoid process, retained the 1-cm incision of the bilateral costal arch, and added a 5-mm incision at the right 6th intercostal junction with the axillary front. Compared to the ideas proposed by previous investigators, the new approach ensures an adequate exposure of the anterior mediastinum, bilateral phrenic nerves, left innominate vein, right internal mammary vein, and bilateral pericardial fat pads, allows more patients who are unable to tolerate single-lung ventilation to have access to the procedure, and facilitates the operator's manipulation without interfering with the assistant's instruments as much as possible. By changing the thoracoscopic entrance to the bilateral costal arches and retraction, the supra-diaphragmatic adipose tissue and thymic tissue around the main-pulmonary artery window can be better exposed for the purpose of enlarged thymectomy. In addition, a chest drain is placed diagonally upwards through the 6th intercostal space to allow for better drainage of gas and fluid, reducing the length of stay and improving patient satisfaction. Therefore, the modified subxiphoid subcostal arch thoracoscopic enlarged thymectomy is not only suitable for TSCC but also for thymic cysts, thymomas, locally invasive thymomas, and thymic carcinomas, thus providing new options to surgeons. However, large-scale randomized and controlled clinical trials are necessary to demonstrate the procedure's safety and efficacy, and this surgical method still has some shortcomings. First, the diameter of the thymic tumor is too large to be removed from the minimally invasive incision. Second, subxiphoid surgery is not suitable for patients with large hearts who do not fully expose the anterior mediastinum. Third, midline sternotomy is still recommended for severe intraoperative thymic carcinoma involving the heart and large vessels.
