Reactive nodular fibrous pseudotumor presents with distinct immunohistochemical profiles and no progression in patientsIdentifying Reactive Nodular Fibrous Pseudotumor to Avoid Overtreatment

Reactive nodular fibrous pseudotumor (RNFP) is a rare benign fibrocollagenous lesion that often poses diagnostic challenges because of its nonspecific clinical and radiological features, particularly at unusual sites such as the lung. This study aimed to characterize the clinicopathological, immunohistochemical, and prognostic features of RNFP and summarize the literature. We retrospectively analyzed four pathologically confirmed RNFP cases, including a rare pulmonary case, and combined them with 40 reported cases (n = 44). RNFP occurred at multiple anatomical sites, most commonly in the abdomen, followed by the extremities and chest. The pulmonary lesion presented as a solitary nodule mimicking malignancy. Histologically, all lesions showed low cellularity, abundant hyalinized collagen, and scattered bland spindle cells without cytologic atypia or mitoses. Immunohistochemically, all cases were positive for vimentin; 50% expressed SMA and 25% showed focal CD34 expression, whereas STAT6, β-catenin, S-100, and desmin were consistently negative. All molecular detection results were uniformly negative. During follow-up (6–60 months), no recurrence or progression was observed. RNFP is a benign reactive lesion with characteristic histological and immunophenotypic features. Diagnosis relies on morphological assessment and immunohistochemical exclusion of mimics. Awareness of its anatomical distribution, including rare pulmonary involvement, is essential to avoid misdiagnosis and overtreatment.