Retroperitoneal schwannomas (RSs) are rare benign neurogenic tumors with nonspecific imaging features and histological mimics, posing significant diagnostic challenges. To address this gap, we retrospectively analyzed 14 RS cases to delineate clinicopathological and immunohistochemical characteristics. Cases were retrieved from the pathology database of the First Affiliated Hospital of Guangzhou Medical University (2019–2024), with hematoxylin-eosin (H&E) and immunohistochemical (IHC) staining performed for evaluation. Among 14 patients, the male/female ratio was 2:5 and the average age was 47.3 years (range, 28 to 71 years). Patients with RSs generally did not have specific symptoms, and they were usually found during routine medical examinations (9/14). All underwent total tumor resection, with a mean tumor size of 5.5 cm (range, 2.5 to 9.5 cm). Microscopically, typical schwannoma features were observed alongside degenerative changes, including cyst formation (6/14), hemorrhage (8/14), calcification (3/14), ossification (3/14), ossification with bone marrow elements (1/14), and degenerative nuclear atypia (5/14). Immunohistochemically, tumors were strongly positive for S-100 (12/12) and SOX10 (12/12), with focal EMA (1/3) and SMA (2/10) reactivity. Over a mean follow-up of 26.4 months (range, 2 to 68 months), 13 patients remained recurrence-free, while one experienced local recurrence after 43 months. Our findings highlight that RS diagnosis requires integrating clinical, radiological, morphological, and immunohistochemical analyses to distinguish these tumors from mimics. Despite their benign nature, long-term surveillance is advised due to the potential for recurrence. This study underscores the importance of a multidisciplinary approach in diagnosing and managing RSs.
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