EBV-associated hepatic smooth muscle tumor of uncertain biologic behavior after heart transplantation in a pediatric patient: case report

Abstract

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare neoplasm recognized in immunocompromised patients. There are less than 30 cases of EBV-SMT reported in pediatric population following solid organ transplantation. Herein, we report a case of an 8-year-old female who was incidentally noted to have multiple lesions in the liver 8 years after heart transplantation. The tumor was composed of a cellular proliferation of spindle-shaped cells with low mitotic activity. The diagnosis of EBV-SMT was confirmed by in situ hybridization for EBV-encoded small RNA (EBER) transcripts. Multiple additional lesions were detected by whole body positron emission tomography-computed tomography (PET-CT) scan 4 months after the initial finding of the hepatic lesions. Immunosuppression was switched to a mechanistic target of rapamycin (mTOR) inhibitor. We conclude that EBV-SMT should be included in the differential diagnoses in post-transplantation patients and further investigations should be performed to evaluate additional lesions. transplantation. Serial testing for EBV DNA by quantitative polymerase chain reaction (PCR) was performed on peripheral blood starting 3 years after the heart transplant (she presented with cough and fever), which showed amplification with up to 131,600 copies/mL. Her EBV viral load has been consistent since then. She developed acute abdominal pain and an appendiceal perforation was diagnosed 8 years post-transplant. Two liver masses were incidentally identified in the left and right hepatic lobes by abdominal computed tomography (CT) scan. Both appeared hypoechoic and individually measured up to 2.5 cm. Whole body positron emission tomography (PET)-CT scan was performed thereafter with no evidence of lymphadenopathy or other lesions. The mass in the right lobe was excised and found to be well circumscribed, white, and firm on gross examination. The mass in the left lobe was not removed due to its deep location. KeywordsHistologically, the hepatic lesion was well demarcated from the adjacent liver parenchyma, and exhibited interlacing fascicles of spindle cells with eosinophilic cytoplasm and elongated, blunt-ended nuclei with stippled chromatin (Figure 1). Rare (less than 5%) primitive round cell component was identified. There was no evidence of necrosis or hemorrhage. Few small blood vessels were interspersed within the fascicles of spindle cells. Mitotic activity was less than 1 per 10 high power fields (HPF). Occasional lymphoid cells were seen at the junction between the tumor and adjacent liver parenchyma (Figure 2). Immunohistochemical (IHC) stains were performed to categorize the lesion. Smooth muscle actin ( Figure 3A) and HHF 35 ( Figure 3B) were positive, and desmin showed focal and weak equivocal staining consistent with smooth muscle origin. Ki67 showed only 1-2% of proliferative activity. EBV in situ hybridization was positive with a diffuse staining pattern (Figure 4), diagnostic of EBV infection. All these features were consistent with a diagnosis of EBV-SMT.W...

Epstein‐Barr virus associated smooth muscle tumors in solid organ transplant recipients: Incidence over 31 years at a single institution and review of the literature

“…The initial MedLine search strategy generated 238 references, of which 25 were included . The initial PubMed search strategy generated 133 results, of which 21 were unique and included . The secondary reference search yielded an additional 18 unique references that were included .…”

Treatment response with sirolimus for a pediatric patient with an EBV‐associated smooth‐muscle tumor after bone marrow transplantation

“…Few case reports on adults have demonstrated therapeutic responses with sirolimus alone or in combination with surgical resection in patients with EBV‐SMTs . In the case of a pediatric patient with an EBV‐SMT following heart transplant, partial surgical resection with the addition of sirolimus showed a short‐term partial response, with prevention of tumor growth for three months . Therapy with sirolimus is a promising treatment option for EBV‐SMTs that are not amenable to surgical resection.…”

“…Overall, EBV‐SMTs are rare in immunocompromised patients, with an estimated incidence of 1% to 5% . The majority of EBV‐SMTs have an association with solid organ transplantation and HIV infection . Cases related to congenital immunodeficiency or bone marrow transplantation (BMT) are rare, as described in only a few pediatric case reports .…”

“…8 The majority of EBV-SMTs Abbreviations: ALL, acute lymphoblastic leukemia; BMT, bone marrow transplant; EBNA, Epstein-Barr virus nuclear antigen; EBV, Epstein-Barr virus; EBV-SMT, Epstein-Barr virus smooth-muscle tumor; GVHD, graft-versus-host disease; HIV, human immunodeficiency virus; LMP, latent membrane protein; MTOR, mammalian target of rapamycin; PTLD, posttransplant lymphoproliferative disorder have an association with solid organ transplantation and HIV infection. [9][10][11][12] Cases related to congenital immunodeficiency or bone marrow transplantation (BMT) are rare, as described in only a few pediatric case reports. 8,[13][14][15][16][17] Development of EBV-SMTs appears soon after transplantation, and the tumors have higher mortality in pediatric patients.…”

Epstein Barr Virus-associated Pediatric Neoplasms

“…Therefore, SMT cells may express CD21 on their surfaces (38), except posttransplant subtype (PT-SMT) cells. The myc overexpression in some EBV-SMT tumors occurs and the result is cellular hyperplasia (39). The proliferation of SMT cells is promoted by the activation of the mTOR pathway and triggered by LMP2, an EBV latency membrane protein (40).…”