[Clinicopathological and molecular genetic features of micronodular thymic neoplasms with lymphoid stroma: a study of seventeen cases].

Objective: To investigate the clinicopathological and molecular genetic features of micronodular thymoma (MNT) and micronodular thymic carcinoma (MNC) with lymphoid stroma. Methods: Seventeen cases of micronodular neoplasms with lymphoid stroma diagnosed at the Third Affiliated Hospital of Soochow University, Changzhou, China from March 2017 to October 2024 were collected (16 cases of MNT and 1 case of MNC). Their clinicopathological data were reviewed, and their paraffin-embedded sections were stained with immunohistochemistry (IHC). Three cases of MNT and one case of MNC were also examined using next generation sequencing (NGS). Results: Of the 17 patients with MNT or MNC, 7 were male and 10 were female, age 66 (63, 72)years old. Microscopically, tumor cells were scattered in the lymphoid stroma as solid epithelioid nests. The tumor nests were relatively regular in 16 cases, and the tumor cells were mainly short spindle or oval, with bland morphology. Tumor cells of MNC showed marked cytological atypia, conspicuous nucleoli, frequent mitotic figures, and fibrous stroma. IHC showed that tumor cells of all 17 cases diffusely expressed CKpan, CK19 and CK5/6. CD5, CD117 and Glut1 were diffusely positive in the MNC case, but negative in any of the 16 MNT cases. In contrast, there were a considerable number of immature T lymphocytes positive for CD99, TdT and CD1a in the lymphoid stroma around MNT tumor nodules, but not in the MNC. Among the 3 MNT cases subjected to NGS testing, 2 cases had missense mutations in GTF2I (p.L424H), and 1 had missense mutations in HRAS (p.G13V and p.L120P). In the MNC case subjected to NGS testing, gene alterations such as a frameshift mutation in BRCA2 (p.D1451Ifs*12) and a missense mutation in TP53 (p.I195T) were detected, but not GTF2I gene mutations. Conclusions: MNC cells are more atypical than MNT cells. CD5, CD117 and Glut1 are diffusely expressed in MNC, but not in MNT. The genetic alterations in MNC are more diverse than those of MNT, but MNC lacks the characteristic GTF2I mutation of MNT.