[Clinicopathological analysis of 28 cases of micronodular thymic tumours with lymphoid stromal hyperplasia]

Objective: To investigate the density, distribution and clinicopathological significance of S100⁺ dendritic cells, FoxP3⁺ regulatory T cells and mature tertiary lymphoid structures (TLS) in micronodular thymic tumors with lymphoid stromal hyperplasia (MNN). Methods: The clinicopathological data of 28 patients with MNN admitted to Nanjing Chest Hospital, Jiangsu Province Hospital and Jiangsu Cancer Hospital from August 2016 to August 2024 were retrospectively collected. The clinical and imaging features, pathological characteristics, immunophenotype, immune microenvironment and molecular characteristics of the patients were analyzed. Result: Among the 28 cases of MNN, 18 were micronodular thymoma with lymphoid stromal hyperplasia (MNT), and 10 were micronodular thymic carcinoma with lymphoid stromal hyperplasia (MNC). Both exhibited characteristic lymphoid stromal surrounding the tumor with a nodular growth pattern. Immunohistochemistry showed that MNT was characterized by CD5-/CD117-/Glut1-/TdT+/low Ki-67 expression while MNC was characterized by CD5+/CD117+/Glut1+/TdT- (or occasional TdT+), and high Ki-67 expression. The expression level of S100⁺ dendritic cells in MNT [(1 765±733) cells/mm²] was higher than that in MNC [(693±129) cells/mm², P＜0.05], whereas the number of FoxP3⁺ regulatory T cells in MNT [(285±100) cells/mm²] was lower than that in MNC [(711±177) cells/mm², P＜0.05]. The density of mature TLS in MNC [(28±17)/10 low-power field (LPF)] was significantly higher than that in MNT [(3.4±2.6)/10 LFP, P＜0.001)]. First-generation sequencing results revealed GTF2I mutations in two MNT cases, whereas no such mutations were detected in seven MNC cases. All 28 cases of MNN underwent resection of mediastinal tumors, and four received postoperative radiotherapy. The follow-up period ranged from 6 to 96 months (one patient was lost to follow-up), with a median follow-up of 48 months. None of the 27 patients experienced recurrence or metastasis. Conclusions: Both MNT and MNC share similar morphological characteristics. The immunophenotype CD5+/CD117+/Glut1+/TdT- and high Ki-67 index can effectively distinguish MNC. The overall prognosis of MNN is favorable. S100⁺ dendritic cells, FoxP3⁺ regulatory T cells, mature TLS, and GTF2I genes alterations are associated with the prognosis of this disease and hold significant value in its diagnosis and differential diagnosis.