| Aim To analyze the clinicopathologic features of patients with thymic neuroendocrine tumors in a single center and to analyze the prognostic factors in real world studies.Methods A retrospective evaluation and analysis of a consecutive series of patients diagnosed with thymic neuroendocrine tumors in Peking Union Medical College Hospital from 1983 to 2022 were carried out.Survival analysis was performed to investigate prognostic factors.Results A total of 129 patients with thymic neuroendocrine tumors were eligible,of which 64.34%were males and the median age of diagnosis was 46.0 years old(36.157.0).The cases diagnosed before 2000 accounted for 8.52%and 61.24%after 2010.The median tumor maximum size was 6.0cm(3.9～8.9).12.40%of the patients had multiple endocrine neoplasia type 1 and 24.03%had ectopic adreno-cortico-tropichormone syndrome.112 cases(86.82%)underwent surgical resection,of which 86 cases(66.67%)were radical resection and 26 cases(20.16%)were palliative resection.Lymph node resection was performed in 50 cases(38.76%)and pericardial/vascular resection was performed in 23 cases(17.83%).According to the pathological findings,91 cases(70.54%)were low-to-intermediate grade thymic neuroendocrine tumors,and 38 cases(29.46%)were high-grade neuroendocrine tumors.Eighteen patients received puncture biopsy,and the puncture pathology of 12 patients was consistent with that of paraffin pathology.The results of intraoperative freezing pathology were consistent with those of paraffin pathology in 17 of 36 patients.Masaoka-Koga stages Ⅰ,Ⅱ,Ⅲ andⅣ accounted for 17.83%,13.18%,31.01%and 37.98%,respectively.The 1-year,3year and 5-year overall survival rates were 89.9%,75.19%and 68.21%,respectively.Univariate analysis showed that the year of diagnosis(p<0.001),the presence of complications(p=0.048),the surgical resection(radical resection vs palliative resection/no surgery)(p=0.004),pathological grade(p<0.001),and Masaoka-Koga stage(p<0.001)were significantly different in overall survival analysis.Multivariate analysis showed that the year of diagnosis(HR 0.442,95%CI 0.294-0.663,p<0.001),pathological grade(HR 2.911,95%CI 1.591-4.967,p<0.001),Masaoka-Koga stage(HR 2.239,95%CI 1.559～3.215,p<0.001)were independent factors of overall survival in thymic neuroendocrine tumors.Among surgical patients,the year of diagnosis(HR=0.551,95%CI 0.344-0.883,p=0.013),pathological grade(HR=2.135,95%CI 1.136-4.013,p=0.019),Masaoka-Koga stage(HR=2.620,95%CI 1.722-3.986,p<0.001)and surgical resection(HR=2.434,95%CI 1.219-4.858,p=0.012)were independent influencing factors of overall survival.Neoadjuvant therapy was a potentially protective factor for prognosis(HR=0.275,95%CI 0.079-0.957,p=0.042).The overall survival of Masaoka-Koga stage Ⅲ to Ⅳ patients with ectopic ACTH syndrome was lower(p=0.012).Conclusions The gold standard for the diagnosis of thymic neuroendocrine neoplasms is paraffin pathology of surgically resected specimens.Pathological grade and Masaoka-Koga stage were independent factors affecting overall survival of thymic neuroendocrine tumors.Additionally,surgical resection was another independent influencing factors for overall survival in surgical patients,and neoadjuvant therapy was a potential protective factor.Removal of metastatic lymph nodes may lead to radical removal and delay the onset of death.Aim To explore the expression of PD-L1 and VISTA,and the distribution of CD4+T cells,CD8+T cells and CD68+macrophages in thymic neuroendocrine tumors and its microenvironment.The correlation between immune microenvironment and prognosis was also analyzed.Methods The tumor tissue samples of patients diagnosed as thymic neuroendocrine tumor were obtained from the tissue bank of Peking Union Medical College Hospital.Immunohistochemical staining was implemented,and the correlation between biomarker expression and prognosis was investigated via survival analysis.Results A total of 26 patients with thymic neuroendocrine tumor were collected,including 1 typical carcinoid,19 atypical carcinoid,3 large cell neuroendocrine carcinoma and 3 small-cell carcinoma.There were 7,3,10 and 6 cases in Masaoka-Koga stage Ⅰ,Ⅱ,Ⅲ and Ⅳ,respectively.Immunohistochemical results showed that the number of CD4+T cells,CD8+T cells and CD68+macrophages were 51(18-199),69(25-339)and 79(60-104)respectively at 20 times of field.CD4+T cells were mainly distributed in lymphocyte nests near tumor foci.CD8+T cells and CD68+macrophages were more distributed in the tumor mesenchyma.PD-L1 expression was present in 11 cases(42.3%),of which 3 cases were only expressed in tumor cells,5 cases were only expressed in immune cells,and 3 cases were expressed in both tumor cells and immune cells.VISTA was expressed in 17 cases(65.4%),of which 14 cases were only expressed in immune cells,and 3 cases were expressed in tumor cells and immune cells.The positive expression of PD-L1 and CD68 showed fusion regions,and VISTA showed fusion regions with the expression of CD4 or CD8.In thymic carcinoid,high expression of CD4+T cells(p=0.005)and CD8+T cells(p=0.011)were significantly correlated with longer progress-free survival.Macrophages with high expression of CD68+showed a tendency of potentially shorter PFS(p=0.332).The tumor with positive expression of PD-L1(p=0.546)and negative expression of VISTA(p=0.385)exhibited shorter PFS.Conclusion CD4+,CD8+and CD68+immune cells were present in thymic neuroendocrine tumors and the adjacent.PD-L1 and VISTA were mainly expressed in immune cells.PD-L1 was co-expressed with CD68,while VISTA was co-expressed with CD4 or CD8.Among thymic carcinoid,the enrichment of CD4+T cells and CD8+T cells was associated with the longer PFS of patients,while the positive expression of PD-L1 and negative expression of VISTA in tumor,and the enrichment of CD68+macrophages had potential for shorten PFS. |
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