Molecular and Clinicopathological Analysis of Epstein-Barr Virus–Associated Posttransplant Smooth Muscle Tumors

Jonigk, Danny; Laenger, Florian; Maegel, Lavinia; Izykowski, Nicole; Rische, Johanna; Tiede, Christina; Klein, Christoph; Maecker‐Kolhoff, Britta; Kreipe, Hans; Hussein, Kais

doi:10.1111/j.1600-6143.2012.04011.x

Cited by 85 publications

(187 citation statements)

References 52 publications

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“…While PTLD can occur in up to 10% of transplant patients, EBV-positive post-transplant smooth muscle tumours (PTSMT) are rare (<1% of patients) [1,2]. EBV-positive smooth muscle tumours (SMT) are not specific for transplant patients but are associated with any patients on long-term immunosuppression.…”

Section: Pathogenesis Risk Factors and Molecular Pathologymentioning

confidence: 99%

“…There is no gender-specific risk increase regarding any of the three tumour types [2,3,4,5,6,7,8,9,10,11]. In transplant patients, the type of immunosuppressive drug, the transplant organ and the manifestation of PTLD are not associated with PTSMT manifestation [2]. About 60% of PTSMT can be found in kidney-transplant patients but it has to be taken into account that this is the most frequently transplanted organ [2].…”

Section: Pathogenesis Risk Factors and Molecular Pathologymentioning

confidence: 99%

“…In transplant patients, the type of immunosuppressive drug, the transplant organ and the manifestation of PTLD are not associated with PTSMT manifestation [2]. About 60% of PTSMT can be found in kidney-transplant patients but it has to be taken into account that this is the most frequently transplanted organ [2]. In contrast to PTLD, PTSMT are late complications (median 48 months after transplantation, range 5-348 months), and early-onset tumours (<12 months after transplantation) occur in <5% of cases [2].…”

Section: Pathogenesis Risk Factors and Molecular Pathologymentioning

confidence: 99%

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Epstein-Barr Virus-Associated Smooth Muscle Tumours after Transplantation, Infection with Human Immunodeficiency Virus and Congenital Immunodeficiency Syndromes

Hussein¹,

Maecker‐Kolhoff

Donnerstag

et al. 2013

Pathobiology

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Smooth muscle tumours (SMT) after transplantation (PTSMT) or associated with congenital immunodeficiency syndromes (CI-SMT) and human immunodeficiency virus (HIV-SMT) are rare. The majority of PTSMT and CI-SMT are associated with Epstein-Barr virus (EBV), while some HIV-SMT can be EBV-negative. SMT in immunodeficient states may present with unspecific symptoms which are mainly related to tumour localisation. In PTSMT, >50% of tumours manifest in the liver/transplant liver, but in general PTSMT, HIV-SMT and CI-SMT can occur at any site as single or multiple tumours. Multiple tumour manifestations do not define metastatic disease as PTSMT can occur synchronously and/or metachronously. PTSMT can originate from the recipient as well as from the donor. Morphologically, most tumours, in particular PTSMT, lack marked histological atypia or tumour necrosis, while some HIV-SMT and CI-SMT can present as sarcoma-like variants, but histomorphology does not predict clinical aggressiveness or tumourbiological behaviour. In PTSMT, surgery and reduced immunosuppression show comparable overall survival rates, while poor prognosis is mainly associated with intracranial manifestation and non-resectable tumours. In HIV-SMT and CI-SMT, surgery should be performed. In all 3 tumour types, adverse prognosis is mainly related to comorbidities associated with immunosuppression but not with the extent of histological atypia or tumour size.

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Section: Pathogenesis Risk Factors and Molecular Pathologymentioning

confidence: 99%

Section: Pathogenesis Risk Factors and Molecular Pathologymentioning

confidence: 99%

Section: Pathogenesis Risk Factors and Molecular Pathologymentioning

confidence: 99%

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Epstein-Barr Virus-Associated Smooth Muscle Tumours after Transplantation, Infection with Human Immunodeficiency Virus and Congenital Immunodeficiency Syndromes

Hussein¹,

Maecker‐Kolhoff

Donnerstag

et al. 2013

Pathobiology

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“…The latent membrane proteins (LMP2A) of EBV have been shown to activate mTOR (14). Activation of AKT/mTOR pathway was demonstrated in post transplantation related SMTs (15).EBV-SMTs in pediatric patients appear earlier (interval between transplantation and tumor: mean, 42 months; range, 1.5-84 months) compared with adult patients (mean, 73-114 months) (14,16,17), and have a higher mortality rate. It has been hypothesized that the greater risk of EBV infection in children is related to the shorter interval from transplantation to the diagnosis of EBV-SMT.…”

mentioning

confidence: 99%

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

Liu

Chintalapati

Dietz

et al. 2017

J. Gastrointest. Oncol.

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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...

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“…Most tumors are smooth muscle neoplasms and are referred to as posttransplant smooth muscle tumors and thought to arise from mesenchymal/stromal cells. 2 Posttransplant lymphoproliferative disease may occur in up to 10% of patients receiving solid organ transplants but posttransplant smooth muscle tumors are rare and estimated to occur in less than 1%. Only rare cases of malignant sarcomatous proliferations have been reported in literature.…”

mentioning

confidence: 99%

A De Novo Unclassified Malignant Spindle Cell Neoplasm of Liver Allograft

Clevenger

Saxena

Idrees

2014

Archives of Pathology &Amp; Laboratory Medicine

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Spindle cell neoplasms are rarely reported in liver allografts; most are benign and associated with EpsteinBarr virus infection. We present a case of a malignant spindle cell neoplasm arising in a liver allograft. The patient underwent orthotopic liver transplant for cirrhosis secondary to nonalcoholic steatohepatitis. After 2 years, he presented with vague abdominal complaints. Imaging studies revealed a 10-cm right hepatic lobe mass. The patient underwent right-sided hepatectomy. The tumor displayed areas of broad, relatively hypocellular fascicles, whorls, and perivascular clustering; spindle cells with mild to moderate nuclear pleomorphism; and relatively abundant eosinophilic cytoplasm. Mitotic activity ranged from 2 to 4 mitotic figures per 20 high-power fields. Immunostaining displayed positivity for epithelial membrane antigen, vimentin, CD99, BCL2, cytokeratin, and human herpesvirus 8. Interphase fluorescence in situ hybridization findings were negative for a translocation involving the SS18 gene (18q11). We believe the tumor represents the first reported case of a novel unclassified spindle cell malignant neoplasm in a liver allograft.

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Molecular and Clinicopathological Analysis of Epstein-Barr Virus–Associated Posttransplant Smooth Muscle Tumors

Cited by 85 publications

References 52 publications

Epstein-Barr Virus-Associated Smooth Muscle Tumours after Transplantation, Infection with Human Immunodeficiency Virus and Congenital Immunodeficiency Syndromes

Epstein-Barr Virus-Associated Smooth Muscle Tumours after Transplantation, Infection with Human Immunodeficiency Virus and Congenital Immunodeficiency Syndromes

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

A De Novo Unclassified Malignant Spindle Cell Neoplasm of Liver Allograft

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