Diffuse intrathyroidal dissemination of papillary thyroid carcinoma with no stromal fibrosis at presentation: A pattern of aggressive differentiated thyroid carcinoma

Multifocal Papillary thyroid carcinoma (PTC) is a very common condition. In certain cases, it is possible to find tens to hundreds of foci with a diffuse intrathyroidal spread in the whole thyroid with no stromal fibrosis. Herein, PTC with such features was nominated as diffuse disseminate variant (DDV) PTC. The aim of the present study was to investigate the histopathological characteristics, molecular features, and biological behavior of DDV and compare the characteristics of DDV to diffuse sclerosing variant (DSV) PTC.Thirty-four DDV and 23 DSV cases were identified from consecutive surgical specimens diagnosed with PTC between 2014 and 2019. Targeted next-generation sequencing (NGS) was applied to investigate the mutation spectrum of DDV and DSV.DDV was commonly diagnosed in young patients and exhibited high rates of LNM (100 %), ETE (61.8 %), and LVI (44.1 %); however, they did not differ from DSV (P > 0.05). Male patients were more frequently diagnosed with DDV than with DSV (P < 0.001). The size of the largest tumor was significantly greater in DDV than in DSV patients (P = 0.008). In addition, BRAFV600E mutation was significantly higher in the DDV than in the DSV group (P < 0.001). The RET/PTC rearrangement was more frequent in DSV than in DDV patients; however, the difference was not statistically significant (P = 0.106). Moreover, DDV had a higher rate of recurrence compared to DSV treated with the same protocol (total thyroidectomy followed by radioactive iodine (RAI) treatment) (47.1 % and 8.7 %, P = 0.002).DDV should be regarded as a novel aggressive variant of PTC with distinct clinicopathological characteristics, aggressive biological behaviors, and a high recurrence.