Clinicopathological analysis of seven cases of papillary thyroid carcinoma with ETV6::NTRK3 gene fusion

Papillary thyroid carcinoma (PTC) is the most prevalent subtype of thyroid carcinoma, with its incidence increasing globally. However, large-scale research data on the morphological characteristics of PTC accompanied by ETV6::NTRK3 gene rearrangement remain limited. We collected seven PTC samples with ETV6::NTRK3 gene fusion, all of which underwent both histopathological and cytopathological examinations. The morphological and clinicopathological features of these cases were further analyzed and characterized. The mean age in this study was 33 years, with a female-to-male ratio of 6:1. Lesions were more frequently located in the right lobe (71.43%). Histologically, all cases exhibited a multinodular infiltrative growth pattern. Five cases (71.43%) predominantly featured follicular architectures, accompanied by papillary, solid, or hobnail structures. Case 4 showed a purely follicular-like growth pattern. Multifocal lymph node metastases were observed in four cases (57.14%), with the largest diameter of metastatic foci ranging from 0.9 to 1.3 cm. In the background thyroid, five cases (71.43%) demonstrated chronic lymphocytic thyroiditis, while two cases (28.57%) exhibited nodular goiter. Cytopathological features showed the tumor cells are distributed in small sheets or clusters. All cases exhibited nuclear elongation, thickening, or irregularity of the nuclear membrane. Intranuclear pseudoinclusions were observed in six cases (85.71%), while nuclear grooves were present in five cases (71.43%). Four cases (57.14%) showed abundant cytoplasmic content in the cells, three of which displayed eosinophilic cytoplasm. The remaining three cases (42.86%) demonstrated an increased nuclear-to-cytoplasmic ratio. Follicular-like structures and papillary-like structures were identified in the cell-embedded paraffin sections of Case 1 (14.29%) and Case 2 (14.29%), respectively. This study uncovered the histological and cytopathological features of PTC with ETV6::NTRK3 gene fusion. While this subset of PTC shares some morphological characteristics with classic PTC, it also exhibits distinct morphological alterations. Therefore, further analysis with larger sample sizes is warranted to enhance diagnostic accuracy and differentiation, thereby reducing the risk of misdiagnosis or missed diagnosis.