The Solitary Fibrous Tumor, the Chameleon of the Head and Neck Region—Clinical, Epidemiological, and Histopathological Aspects

<b>Background/Objectives:</b> The solitary fibrous tumor is an uncommon benign mesenchymal neoplasm with relatively indolent and rarely metastasizing behavior. This retrospective study includes 26 cases of head and neck solitary fibrous tumors diagnosed between 2017 and 2024. <b>Methods:</b> The morphological examination with Hematoxylin-Eosin staining was completed via immunohistochemical reactions with specific antibodies. <b>Results:</b> The Ki-67 proliferation index had a median of 11.2%, with an interquartile range of 5% to 15%. CD20-positive B-cells had a score of 0 in 50% of cases (<i>n</i> = 26), while CD3 and CD5 T-cells had a score of 3 in 81% of cases (<i>n</i> = 21). CD4-positive T-cells had a majority score of 1 (81%, <i>n</i> = 21). CD8-positive T-cells had a broader distribution: 65% (<i>n</i> = 17) of cases presented a score of 1, 27% (<i>n</i> = 7) a score of 2, and 8% (<i>n</i> = 8) a score of 0. Antigen-presenting dendritic cells and mast cells presented a majority score of 0 in the entire cohort, being undetectable in 85% (<i>n</i> = 22) and 88% (<i>n</i> = 23) of cases, respectively. CD20-positive B-lymphocytes demonstrated moderately strong correlations with the Ki-67 cell proliferation index (r = 0.77). The time to recurrence was most strongly associated with the Ki-67 mitotic index (r = 0.81), CD4-positive (r = 0.85), and CD5-positive T-lymphocytes (r = 0.55), and CD20-positive B-lymphocyte expression (r = 0.68). <b>Conclusions:</b> This research illustrates our experience with head and neck solitary fibrous tumors, the surgical decisions, and the morphological and immunohistochemical features, while reviewing the cases published in English in the specialized literature.