[Multifocal EBV-associated smooth muscle tumors: a clinicopathological analysis of seven cases].

Objective

To investigate the clinicopathological and prognostic features, immunophenotypic characteristics, and key points of differential diagnosis of multifocal EBV-associated smooth muscle tumors (EBV-SMT).

Methods

The clinicopathological data of 7 cases of EBV-SMT diagnosed in Sun Yat-sen University Cancer Center from June 2020 to March 2025 were retrospectively analyzed. Immunohistochemical staining, Epstein-Barr virus-encoded small RNAs (EBERs) in situ hybridization, and next-generation sequencing were performed, and the relevant literature was reviewed.

Results

All 7 patients were children or young adults, with a median age of 7 (2, 33) years. Five patients were immunocompromised due to congenital immune deficiency, autoimmune disease or post-transplant treatment. All the 7 cases presented with multifocal lesions, involving the brain, liver, lungs and adrenal glands. Histologically, 3 cases exhibited a classic spindle cell leiomyoma-like morphology, while the other 4 showed a more primitive round cell morphology resembling smooth muscle cells. All cases expressed smooth muscle markers, such as SMA, calponin, HHF35, h-caldesmon, and desmin, among others. The proliferation index of Ki-67 ranged from 1% to 30%. All cases were diffusely and strongly positive for EBERs by in situ hybridization. Next-generation sequencing identified an ITK gene deletion in one case (case 2). During a follow-up period of 1 to 44 months after diagnosis, 2 patients died, while the remaining 5 survived.

Conclusions

EBV-associated smooth muscle tumors are more likely to occur in children or young adults with immune deficiency, often manifesting as multifocal lesions in different organs. Accurate diagnosis relies on a comprehensive assessment incorporating clinical history, histopathological features, and findings of immunohistochemistry and EBERs in situ hybridization.