Atypical Epstein–Barr virus (EBV) latent protein expression in EBV‐associated smooth muscle tumours occurring in paediatric transplant recipients

Rougemont, Anne‐Laure; Alfieri, Caroline; Fabrè, Monique; Gorska‐Flipot, Izabella; Papp, E.; Champagne, Josette; Phan, Véronique; Fournet, Jean‐Christophe; Sartelet, Hervé

doi:10.1111/j.1365-2559.2008.03086.x

Cited by 26 publications

(39 citation statements)

References 19 publications

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“…Polymorphic or monomorphic high grade B-cell PTLD manifestation occurred in a subgroup of patients with PTSMT (n = 12/68, 18%) (4,5,28,29,33,37,40,41). Except for one adult case (37), all of these patients were children (n = 11/12, 92%).…”

Section: Clinical Characteristicsmentioning

confidence: 99%

“…The femaleto-male ratio was 1:1.2 (no statistical significance) (2-41). The majority of PTSMT developed after kidney transplantation (n = 38/68, 60%) (2,4,6,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) and the site of tumor manifestation was mainly the liver/transplant liver (n = 38/68, 56%) (2,(5)(6)(7)10,11,15,(17)(18)(19)(20)(21)24,25,(27)(28)(29)(30)(31)(33)(34)(35)(36)38,41). PTSMT occurred in a total of 11 transplant Liver (n = 10/68, 15%) Heart (n = 9/68, 13%) Lung (n = 4/68, 6%) Heart + lung (n = 1/68, 2%) Bone marrow (n = 3/68, 4%)…”

Section: Clinical Characteristicsmentioning

confidence: 99%

“…Including our own five patients and data from 40 other case reports (2)(3)(4)(5)(7)(8)(9)(10)(11)(12)14,(17)(18)(19)(21)(22)(23)(26)(27)(28)(29)31,(34)(35)(36)(37)(38)40), we could analyze the morphological details. More than 50% of PTSMT were smaller than 5 cm (median diameter of unifocal tumor or the largest multifocal tumor 4 cm, range 0.8-15 cm).…”

Section: Tumor Morphology and Development Of Ebvmentioning

confidence: 99%

“…The EBV entry mechanism is not fully understood but might not be based on sustained CD21 (C3d/EBV receptor) protein expression in PTSMT (4). Corresponding to B cell latency types (Supplementary Table S1), EBNA2/EBNA3 expression of PTSMT indicates latency type III, which usually also includes latent membrane protein/LMP1 expression.…”

Section: Introductionmentioning

confidence: 99%

“…Corresponding to B cell latency types (Supplementary Table S1), EBNA2/EBNA3 expression of PTSMT indicates latency type III, which usually also includes latent membrane protein/LMP1 expression. However, LMP1 protein is rarely detectable in PTSMT, either due to very low LMP1 expression levels and/or limited technical sensitivity or a latency type III subtype which is typical for PTSMT (4)(5)(6). It has been shown that one EBV species with the same 30-bp deletion in the LMP1 gene was detectable in PTLD and subsequent PTSMT of one individual patient.…”

Section: Introductionmentioning

confidence: 99%

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

Jonigk

Laenger

Maegel

et al. 2012

American Journal of Transplantation

174

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Epstein-Barr virus (EBV)-associated posttransplant smooth muscle tumors (PTSMT)are very rare complications. We aimed to provide a clinicopathological characterization which is based on our own case series (n = 5) as well as previously reported PTSMT cases (n = 63). Meta-analysis of PTSMT and molecular analysis of tumor cells from our cohort was performed. Most PTSMT developed in kidney-transplanted patients (n = 41/68, 60%). Liver/transplant liver was the main site of manifestation (n = 38/68, 56%). Tumors occurred after a median interval of 48 months (range 5-348) and developed earlier in children than in adults. Most tumors showed no marked cellular atypia, low mitosis rate and no tumor necrosis. Gene expression analysis of 20 EBV-related genes, including two microRNAs, revealed overexpression of MYC (p = 0.0357). Therapy was mainly based on surgical resection or reduced immunosuppression but no significant differences in overall survival were evident. Lower overall survival was associated with multiorgan involvement (n = 33/68, 48.5%) and particularly with intracranial PTSMT manifestation (n = 7/68, 10%; p < 0.02), but not transplant involvement (n = 11/68, 16%). In summary, PTSMT differ from conventional leiomyosarcomas by their lack of marked atypia, unusual sites of involvement and defining EBV association. Surgery and reduced immunosuppression show comparable clinical results and prognosis is associated with intracranial manifestation.

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Section: Clinical Characteristicsmentioning

confidence: 99%

Section: Clinical Characteristicsmentioning

confidence: 99%

Section: Tumor Morphology and Development Of Ebvmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Jonigk

Laenger

Maegel

et al. 2012

American Journal of Transplantation

174

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

Penney

Bishop

Howell

2019

Pediatric Blood & Cancer

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Epstein–Barr virus–associated smooth‐muscle tumors (EBV‐SMTs) are unique and rare neoplasms described in immunocompromised patients. The case describes a nine‐year‐old female with a history of acute lymphoblastic leukemia with relapse and subsequent allogeneic bone marrow transplantation who presented with multiple EBV‐SMTs of the liver. EBV utilizes the mammalian target of rapamycin (mTOR) pathway for tumor growth, and sirolimus, a mTOR inhibitor, has shown to result in a short‐term response. We now report an extended treatment response with sirolimus in a pediatric patient with an EBV‐SMT.

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Aberrierender reparativer Gewebeumbau

Jonigk

2014

Pathologe

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Not only tumorous infiltrations can lead to destruction of parenchymal organs but also the aberrant proliferation and matrix production of mesenchymal cells and vessels during a dysregulated repair attempt. This fibrogenesis is the result of a complex pathogenesis, which can be investigated in animal models but also in situ to harvest new biomarkers. This article deals particularly with the second method and summarizes molecular pathological findings in various model diseases for aberrant reparative tissue reconstruction. These model diseases include plexiform vasculopathy in pulmonary arterial hypertension (PAH), Quilty lesions in heart transplantation, bronchiolitis obliterans (BO), inflammatory airway remodeling and Epstein-Barr virus (EBV) induced smooth muscle proliferation (posttransplantation smooth muscle tumor, PTSMT).Using in situ molecular pathology, we were able to dismiss an assumed involvement of myofibroblastic cells in vessel reconstruction of the lung in PAH. We could also for the first time perform a comprehensive molecular characterization of the vascular remodeling and prove that plexiform vasculopathy represents a complex-regulated epiphenomenon of excessive pulmonary hypertension. This method also allowed us to describe for the first time the miRNA expression in PAH in a compartment-specific manner and to draw conclusions regarding the damaged overriding regulatory mechanisms. In the same way, we were also able to describe the chimeric character of the complex neoangiogenesis in the donor organ after heart transplantation.After lung transplantation, we identified for the first time a group of tissue-based molecular markers, which can predict later occurrence of BO even in morphologically normal transbronchial biopsies. In addition, we have documented for the first time the molecular characteristics of the morphologically analogous airway reconstruction in lung-transplanted and non-transplanted patients. We could further elucidate the role of matrix metalloproteinases (MMP) and their antagonists in inflammatory airway reconstruction and deduce from this the resulting therapeutic implications. Accordingly, we were able to further clarify the origin, pathogenesis and the malignant potential of EBV-induced PTSMT and for the first time provide an evidence-based therapy recommendation and risk assessment.In summary, this article documents that in situ diagnostics can meet the requirements of the challenging parameters and issues of life sciences. It is to be expected that the technical possibilities will develop analogously to the increasing demands and the in situ method will move further into the focus of molecular pathology.

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Atypical Epstein–Barr virus (EBV) latent protein expression in EBV‐associated smooth muscle tumours occurring in paediatric transplant recipients

Cited by 26 publications

References 19 publications

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

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

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

Aberrierender reparativer Gewebeumbau

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