Thymic NEN are rare tumours. Among Asian/Pacific islanders, their annual incidence has been reported to be approximately 0.04/100,000 population[8]. They account for 2% of all mediastinal tumours and 5% of all thymic tumours. The ratio of prevalence between male and female is 3:1[9]. Consequently, the rarity of thymic neuroendocrine neoplasms has resulted in few clear consensus statements or guidelines for optimal treatment. Howerer, the current evidence consistently suggests that thymic NEN behave in a more aggressive manner compared to NEN in other organs.
Thymic NEN are currently classified based on their histopathologic features as low-grade, intermediate-grade, high-grade neoplasms[10]. High-grade neuroendocrine carcinoma is different in mitoses per 10 HPF and necrotic degree compared with low-grade[11]. So, the reasons of differences in the morphologic and immunohistochemical features between the tumor in the biopsy and in the resection specimen were diversified. We guess the biopsy might have sampled a better-differentiated area which causes to degree of differentiation. The classification of thymus neuroendocrine tumors varies from that of gastrointestinal neuroendocrine tumors in some classification systems, and in particular does not include Ki-67 and includes the assessment of necrosis. It is worth noting that neoadjuvant chemotherapy can increase the necrosis of lesions, which may affect the pathological diagnosis of thymic NEN and the choice of follow-up treatment. Therefore, it is a question whether the pathological reclassification after neoadjuvant chemotherapy is meaningful for patients with thymic NEN treated with neoadjuvant chemotherapy.
As an autoimmune disease, SS is often accompanied by thymic lesion, such as thymic hyperplasia, multilocular thymic cyst, thymoma, as is reported. However, our patient was diagnosed as high-grade neuroendocrine carcinoma accompanied with pSS, as first presentation of thymic NEN. The mechanism we infer may be interaction between endocrine system and immune system which leads to destruction of acinar cells and the pathology contains thymic lymphoid hyperplasia which isn’t detected.
Neuroendocrine tumors are highly heterogeneous and all elements need to be considered (eg, histopathology, concomitant disease, symptoms). To date, no single currently available biomarker is sufficient as a diagnostic, prognostic, or predictive marker in patients with neuroendocrine tumors[12]. According to the relevant articles, the only unanimous prognostic factor is the completeness of surgical resection[2]. So, after multidisciplinary discussion, two cycles of neoadjuvant chemotherapy is preferred considering imaging features of lesions. Based on NCCN Guidelines of Neuroendocrine and Adrenal Tumors, cisplatin and etoposide are preferred regimens of adjuvant therapy.. Therefore, we chose EP neoadjuvant chemotherapy regimen. Fairly, after two courses of neoadjuvant chemotherapy, the symptoms of SS were partial relieved and RF turned negative. More importantly, the patient underwent R0 resection. Although literature data regarding the role of neoadjuvant chemotherapy in patients with potentially resectable NEN are not well defined[13], we think that it is an attemptable way for radical resection and relieving the symptoms of related complications. According to NCCN guidelines, after potentially curative surgery, surveillance is recommended for at least 10 years for most patients. Due to the loss of follow-up, our case was followed up for only one year, which is our deficiency.
For SS patients, fatigue is their most important symptom and the one most difficult to cope with, which is also the first symptom of our patient[14]. Previously, there is no ideal therapeutic drug for SS, mainly for local replacement therapy and systemic immunotherapy. And for related constitutional symptoms, there is currently no evidence to support pharmacological treatment. In our case, the symptoms of SS were relieved after two courses of chemotherapy and SS was clinically cured after one year of follow-up. So, we guess SS may benefit from neoadjuvant chemotherapy which aims to resectability of the tumor. Although the mechanism of association between thymic NEN and SS hasn’t been explored, this provides a new treatment option for SS.