EBV-associated smooth muscle tumour: a clinicopathological and genetic study of nine cases revealing heterogeneous immune statuses and novel pathogenic mutations.

AIMS: EBV-associated smooth muscle tumour (EBV-SMT) is a rare neoplasm, primarily affecting patients with HIV, post-transplantation (PT), and congenital immunodeficiency (CI). Most EBV-SMT cases were reported by case reports, and genetic analyses are limited. Herein, we describe nine patients with EBV-SMTs to further expand the clinicopathological and genetic spectrum of EBV-SMT.

METHODS AND RESULTS: Nine patients with EBV-SMTs were identified from 2008 to 2024, and next-generation sequencing (NGS) was performed in six cases with available material. The study comprised four males and five females aged 9-60 years old, including two patients with HIV-SMTs, two with PT-SMTs, three with CI-SMTs, one post-immunosuppressive therapy patient, and one clinically immunocompetent patient. Tumours involved liver (n = 7), adrenal gland (n = 6), retroperitoneum (n = 1) and cervical spinal canal (n = 1). Histologically, eight cases showed characteristic interlacing fascicles of spindled cells with inflammatory cell infiltration. In one CI-SMT case, the tumour cells exhibited epithelioid morphology in a whorled pattern with obvious atypia. All cases showed SMA and EBER positivity. NGS detected recurrent mutations in PIEZO1(3/6), CYP2B6 (2/6), NQO1(2/6), NSMCE3(2/6), and PI4KA (2/6). Novel pathogenic mutations in MAGT1 and CARMIL2 were identified in two CI-SMTs, with the MAGT1 mutation linked to a rare immunodeficiency XMEN disease, reported here for the first time.

CONCLUSION: Our study reported nine EBV-SMT cases from heterogeneous immune statuses, with identification of recurrent mutations and pathogenic mutations in some of these tumours, further expanding its clinicopathological and genetic spectrum. Our findings suggest that EBV-SMT cannot be excluded in clinically immunocompetent patients, and further cytogenetic investigations are warranted.