Answer: C - EBV-associated smooth muscle tumor (EBV-SMT)

This morphologic and immunohistochemical patterns are in keeping with a smooth muscle tumor; considering the patient’s history of transplant, further evaluation of tumor by in situ hybridization for Epstein-Barr virus RNA is advisable (see above image).

Considering all the above, option c is the most accurate answer. This is a case of Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT). EBV-SMT is rare and often develops in context of secondary immunodeficiency caused by HIV infection or by immunosuppressive treatment after solid organ transplantation. Less commonly, EBV-SMT is reported in context of primary/ congenital immunodeficiency disorders.

EBV-SMT is a well-differentiated tumor with spindle cells, variable (but often mild) atypia and generally low mitotic activity. This tumor is noted to display primitive round cell areas and prominent intratumoral lymphocytes. EBV-SMT is positive for alpha-smooth muscle actin and is often positive for Desmin; it is characteristically positive by situ hybridization for early EBV RNAs (EBER). This tumor is distinct from classic soft tissue smooth muscle tumors and is not evaluated by conventional histologic criteria. Its morphologic patterns often overlap with leiomyoma and occasionally with leiomyosarcoma; hence, assessment of smooth muscle tumors by EBER-ISH, specially in immunocompromised patients, is paramount to reach the appropriate diagnosis.

While reports on EBV-SMT indicate variable aggressiveness of tumor, features such as cellular atypia, mitotic activity, and necrosis have no definitive correlation its clinical behavior. In liver, EBV-SMT must be differentiated from other spindle lesions with similar morphologic appearance including Kaposi sarcoma, myopericytoma, fat-poor angiomyolipoma and gastrointestinal stromal cell tumors, amongst others. Immunostaining and in situ hybridization studies, as described above, are of essential diagnostic utility.

Without definitive reconstitution of immunity, long-term survival can be poor in a subset of patients. In secondary immunodeficiencies and when the underlying condition is not curable, treatment of EBV-SMT consists of surgery in combination with antiretroviral pharmacotherapy and reduction or alteration of immunosuppressive regimen.

References:

1. Arva NC, Schafernak KT. Rare Presentations of Epstein-Barr Virus--Associated Smooth Muscle Tumor in Children. Pediatr Dev Pathol. 2016;19(2):132-138. doi:10.2350/15-05-1627-CR.1

2. Coletta D, Parrino C, Nicosia S, et al. Primary leiomyoma of the liver in an immunocompetent patient. Intractable Rare Dis Res. 2020;9(4):251-255.

3. Dekate J, Chetty R. Epstein-Barr Virus-Associated Smooth Muscle Tumor. Arch Pathol Lab Med. 2016;140(7):718-722. 

4. Deyrup AT, Lee VK, Hill CE, et al. Epstein-Barr virus-associated smooth muscle tumors are distinctive mesenchymal tumors reflecting multiple infection events: a clinicopathologic and molecular analysis of 29 tumors from 19 patients. Am J Surg Pathol. 2006;30(1):75-82. 

5. Magg T, Schober T, Walz C, et al. Epstein-Barr Virus+ Smooth Muscle Tumors as Manifestation of Primary Immunodeficiency Disorders. Front Immunol. 2018;9:368. Published 2018 Feb 27.

6. Shen Q, Feng W, Long MS, et al. Multicentric hepatic EBV-associated smooth muscle tumors in an AIDS patient: a case report, investigation of mTOR activation and review of the literature. Int J Clin Exp Pathol. 2011;4(4):421-429.

7. Zhou Q, Wu F, Guo Y, Zhu B. Epstein-Barr virus associated hepatic smooth muscle tumor in a patient with acquired immunodeficiency syndrome: A case report. Medicine (Baltimore). 2020;99(18):e19930.