[Clinicopathological and genetic features of thyroid tumors with PTEN mutations]

A retrospective analysis of clinicopathological features was conducted on 10 cases of thyroid tumors with PTEN mutations from Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Fujian Provincial Hospital, and the Affiliated Hospital of Qingdao University from 2020 to 2024. Histomorphological features were quantified using the Thyroid Histomorphological PTEN Hamartoma Syndrome (PHTS) scoring system(THiPS), immunophenotypic profiling and genetic features were examined via immunohistochemical staining and next-generation sequencing respectively. The cohort included 3 males and 7 females, with the age [M(Q₁,Q₃)] of 68.0(53.0, 74.0) years. Those 10 cases included papillary thyroid carcinomas (3 cases), oncocytic carcinoma of the thyroid (2 cases), follicular thyroid carcinoma (1 case), differentiated high-grade thyroid carcinoma (1 case), and thyroid low risk neoplasm (3 cases). The cases in this study had low THiPS scores [(1.0±1.15) scores], and all lacked the characteristic morphological features of PHTS. Immunohistochemical staining showed that loss of PTEN expression was confirmed in 7 cases, positive expression was found in 3 cases with non-sense PTEN mutation. Molecular analysis revealed co-mutations with PTEN in 80% of cases (8/10), including BRAF^V600E(3 cases), TERT promoter (4 cases), and TP53 mutations (2 cases), while 2 cases harbored PTEN-only mutations. Follow-up data were obtained for 6 cases, with a follow-up period of 15.0 (9.0, 20.0) months. Among them, 1 case was initially diagnosed with OCT pulmonary metastasis, while the remaining 5 cases showed no recurrence or metastatic lesions during the follow-up period. The THiPS score has limited diagnostic value for thyroid tumors with PTEN alteration. Negative PTEN immunohistochemical staining may suggest a PTEN mutation, but positive staining does not exclude a genetic alteration. PTEN gene mutations can be combined with BRAF, TERT, and TP53 alteration.