Surgical treatment of intermediate to high grade thymic neuroendocrine neoplasms: case series of five patients and literature review

Abstract

Background: Thymic neuroendocrine neoplasms (Th-NENs) are extremely rare. Th-NENs are divided into four pathological subtypes: typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC). The latter three subtypes are highly aggressive with poor prognosis. There are limited reports on the optimal surgical strategies for Th-NENs. This study aims to report a case series of Th-NENs after surgical treatment and review the literatures.

Methods: We report a case series of five patients diagnosed with Th-NENs and summarize their clinical characteristics. Literatures related to surgical treatment of Th-NENs were reviewed.

Results: There were three males and two females, and mean age was 53.6 years. No myasthenia gravis or neuroendocrine symptoms were found. Three patients were diagnosed with AC and the other two were diagnosed with LCNEC. Two patients were stage II-b, one patient was stage III-a, and two patients were stage IV-b. One patient received preoperative chemotherapy, one patient received preoperative chemoradiotherapy, and three patients underwent surgery directly. Two patients underwent extended thymectomy via video-assisted thoracoscopic surgery (VATS), two patients underwent extended thymectomy via median sternotomy, and one patient underwent resection of anterior mediastinal tumor, sternal metastases, superior vena cava and partial right atrium via median sternotomy and cardiopulmonary bypass. R0 resection was achieved in 80% (4/5) of patients. There was no postoperative 90-day complication and death. One patient had no recurrence. One patient had lymph node metastases and was still alive after somatostatin analogue therapy. One patient had no recurrence of Th-NENs but died of other tumors. Two patients had distant metastases. Median overall survival (mOS) was 49 (range, 4-134) months. A total of 22 original studies related to surgical treatment of Th-NENs were retrieved.

Conclusions: Th-NENs is a very rare and extremely aggressive malignancy. Early diagnosis and surgical resection are the most important methods to improve prognosis. Radical resection and lymph node dissection are recommended for accurate staging and better prognosis. Currently, there are few clinical data on Th-NENs and several important surgical issues remain unresolved. In the future, multi-center, large-sample database and clinical studies are urgently needed to explore better treatment modality.

Keywords: Thymic neoplasms; case series; neuroendocrine tumors; prognosis; surgery.

Figure 1

Case 5, a 65-year-old female, was diagnosed with poorly differentiated LCNEC with concurrent ovarian cancer. The maximum diameter of the tumor was 84 mm. After 4 cycles of neoadjuvant chemotherapy with paclitaxel plus carboplatin, the patient underwent extended thymectomy via VATS. The pathological stage was Masaoka-Koga III-a (invasion of pericardium). (A-C) Images of thymic neoplasm before neoadjuvant chemotherapy; (D-F) images of thymic neoplasm after neoadjuvant chemotherapy. LCNEC, large cell neuroendocrine carcinoma; VATS, video-assisted thoracoscopic surgery.

Figure 2

Case 3, a 66-year-old female, was diagnosed with AC. The maximum diameter of the tumor was 50 mm. The patient underwent extended thymectomy via VATS. The pathological stage was Masaoka-Koga II-b (invasion of perithymic adipose tissue). (A-C) Images of thymic neoplasm. AC, atypical carcinoid; VATS, video-assisted thoracoscopic surgery.