Epstein-Barr Virus-associated Smooth Muscle Tumors Research Articles

Epstein-Barr Virus-Associated Smooth-Muscle Tumor of the Brain.

Epstein-Barr virus, a herpesvirus, has been associated with a variety of cancers, including Burkitt, Hodgkin, and non-Hodgkin lymphomas; posttransplant lymphoproliferative disorders; gastric carcinoma; and nasopharyngeal carcinoma, in both immunocompetent and immunocompromised individuals. Previous studies have established a connection between Epstein-Barr virus and the development of smooth-muscle tumors. Smooth-muscle tumors of the brain are very rare and are often misdiagnosed as meningiomas on imaging. To our knowledge, advanced imaging findings such as MR perfusion of smooth-muscle tumors of the brain have never been reported. We describe the radiologic and pathologic features of the Epstein-Barr virus-associated smooth-muscle tumors of the brain in a person with newly diagnosed advanced HIV.

EBV-Associated Smooth Muscle Tumors With Autoimmune Hemolytic Anemia and Hepatitis B Infection: Report of a Previously Undescribed Neoplasm With Review.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is rare in adults. The presence of intratumoral T lymphocytes and primitive rounded cells characterized this neoplasm. We report a 24-year-old Chinese man who developed EBV-SMT in the right adrenal gland with hepatitis B infection and autoimmune hemolytic anemia without a history of HIV infection, primary immune deficiency, organ transplantation, or malignant tumor. This patient had an unknown immunodeficient state. EBV-SMTs are commonly located in the liver, lung, and gastrointestinal tract but rarely in the adrenal gland. We reviewed 10 reported literature on EBV-SMT in the adrenal gland. It is imperative to distinguish EBV-SMT from conventional somatic smooth muscle tumors. The discovery of EBV-SMT forces the clinician to conduct a thorough evaluation of immune function and immune status surveillance, and these patients are vulnerable to subsequent malignant tumors.

Outcomes of children treated for multiple Epstein-Barr virus-associated post-transplant tumors.

After solid organ transplantation, children are at risk for Epstein-Barr virus-associated post-transplant lymphoproliferative disorder and smooth muscle tumors. Little is known about the clinical course, Epstein-Barr viral load variations, and optimal treatment for such patients. We set forth to understand the course of repeated episodes of post-transplant lymphoproliferative disorder and smooth muscle tumors. We performed a retrospective chart review of patients up to 21 years old with solid organ transplantation and post-transplant lymphoproliferative disorder at the Children's Hospital of Philadelphia from January 2003 through June 30, 2020. Six patients had multiple episodes of Epstein-Barr virus-associated post-transplant lymphoproliferative disorder and smooth muscle tumors. When the second episode was discovered, only one patient was symptomatic. Histology differed from diagnosis in four patients. Treatment included viral-specific T-lymphocytes (2), rituximab (3), reduction in immunosuppression alone (1). Five patients had complete response, and one had stable disease, but three patients developed a subsequent tumor. Two patients developed Epstein-Barr virus-associated smooth muscle tumors. Of these six patients, four are alive. The deaths were not related to their tumors. Despite a complete response to initial therapy, children are at risk for repeated episodes of Epstein-Barr virus-associated post-transplant lymphoproliferative disorder and smooth muscle tumors. Histology and location were not typically consistent with initial diagnosis, suggesting these are second primaries rather than recurrences. Disease may be managed with individualized treatment plans but EBV-specific T cells need further study in such tumors.

Clinicopathologic and Molecular Characteristics of Epstein-Barr Virus–Associated Smooth Muscle Tumor Compared With Those of Leiomyoma and Leiomyosarcoma

Epstein-Barr virus (EBV)–associated smooth muscle tumors (EBV-SMTs) are rare smooth muscle neoplasms exclusively associated with immunosuppression, such as in patients with HIV/AIDS, posttransplant, and congenital immunodeficiency. However, the genomic landscape of EBV-SMTs is poorly understood. Leiomyosarcomas harbor genomic instability and multiple recurrent DNA copy number alterations, whereas leiomyomas lack such changes. Thus, this study aimed to fill this knowledge gap by characterizing copy number alterations in EBV-SMTs and correlating this information with clinicopathologic characteristics. Our study investigated and compared the pathologic characteristics and copy number profiles of 9 EBV-SMTs (from 7 post-transplant and AIDS patients), 6 leiomyomas, and 7 leiomyosarcomas, using chromosomal microarray platforms. Our results showed a lower copy number alteration burden in EBV-SMTs and leiomyoma than in leiomyosarcoma. This contrast in the molecular profile between EBV-SMTs and leiomyosarcoma is concordant with the different clinical behaviors and pathologic characteristics exhibited by these tumors. Despite having an overall copy number alteration profile closer to leiomyoma, recurrent copy number gain of oncogenes, such as RUNX1, CCND2, and ETS2, was found in EBV-SMTs. Epigenetic alterations may play an important role in tumorigenesis as recurrent copy number gains were found in histone deacetylases. A gene enrichment analysis also demonstrated enrichment of genes involved in the host response to viral infection, suggesting that the tumor immune microenvironment may play an important role in EBV-SMT tumorigenesis.

Epstein-Barr Virus-Positive Leiomyosarcoma in Immunocompetent Patients.

Epstein-Barr Virus-Associated Smooth Muscle Tumor (EBV-SMT) is a rare tumor with a higher rate of occurrence in unusual locations in the setting of immunodeficiency. In this study, we evaluated a cohort of ordinary leiomyosarcomas (LMS) for the presence of EBV and described the clinicopathological features deviating from routinely diagnosed cases of EBV-SMT. The sections of tissue microarrays including 93 classical LMS occurring in various locations were hybridized with EBER and stained for LMP1 antibody using the Leica Bond Autostainer. EBV real-time PCR assay was performed in 2 EBER-positive cases. Among the 93 LMS cases, 2 non-uterine cases (2.2%) were positive for EBER and negative for LMP1, and were referred to as `EBV-positive LMS`. Both were females in their 6th decade without immunosuppression. EBV real-time PCR assay revealed the presence of EBV in one of the cases. Tumors were located in the pancreas and chest wall. Morphologically, tumors were rather myxoid, multinodular, and composed of long fascicles of spindle cells with intermediate- to high-grade features. High mitotic activity and focal necrosis were present, whereas no accompanying lymphocytes were detected. One of the patients developed metastatic disease after 3 years. EBV-positive LMS occurring in immunocompetent patients has features distinct from classical EBV-SMT seen in immunosuppressed patients.

Concurrent Epstein Barr virus-associated smooth muscle tumor and myeloid sarcoma of the liver and acute myeloid leukemia in a patient post kidney transplant: a case report and review of the literature

Epstein Barr virus-associated smooth muscle tumors (EBV-SMT) are rare neoplasms that can occur in immunocompromised individuals. The native or transplanted liver is the most commonly involved site in post transplant patients. Systemic therapies have been utilized in EBV-SMT with modest activity. We describe a 23-year-old female kidney transplant recipient who presented with acute myeloid leukemia (AML) and hepatic myeloid sarcoma (MS). Although it was not recognized initially, her liver biopsy revealing MS at diagnosis was posthumously found to have synchronous EBV-SMT. She underwent anthracycline based induction and achieved a complete remission of her AML by bone marrow biopsy. Due to a persistent hepatic mass, she was given salvage chemotherapy including fludarabine, etoposide, cytarabine, decitabine, and venetoclax for presumed refractory MS. Re-biopsy of the liver revealed the absence of MS and presence of EBV-SMT, which subsequently grew rapidly and precluded her from a liver tumor resection. The patient underwent sirolimus mammalian target of rapamycin (mTOR) therapy with palliative intent, but the patient's EBV-SMT progressed shortly after. At time of autopsy, the patient remained in complete remission from AML/MS, but was found to have multifocal progressive metastatic EBV-SMT. To our knowledge this is the first reported case of synchronous AML/MS and post transplant hepatic EBV-SMT that underwent treatment for AML/MS. Our report suggests that the chemotherapeutic agents utilized for AML/MS may have poor efficacy against EBV-SMT.

Useful histopathologic features for diagnosing focal liver lesions with spindle cell morphology: A clinicopathologic study

BackgroundFocal liver lesions with spindle cell morphology are rare in the daily practice of pathology. The differential diagnosis is broad, including both tumors and tumor-like lesions. Initial radiologic assessment is sometimes inaccurate. Histopathology is needed to arrive at the correct diagnosis. This study analyzed discrepancies between histopathology and radiologic findings of focal liver lesions with spindle cell morphology. MethodsA six-year retrospective analysis was conducted at a tertiary hospital in Thailand. All focal liver lesions with spindle cell morphology were retrieved. Clinicopathologic features of these cases were analyzed. The pathological diagnosis was rendered primarily based on routine histopathology, using other ancillary studies as an adjunct. Results287 biopsies and 151 resection specimens with focal liver lesions were identified. In 12 (2.7%) cases, tumors or tumor-like lesions with spindle cell morphology were retrieved. A total of five cases had discrepancies between histopathology and radiologic findings. These lesions encompassed primary liver tumors (EBV-associated smooth muscle tumor and leiomyosarcoma); metastatic tumors (gastrointestinal stromal tumor, small cell neuroendocrine carcinoma); and a tumor-like lesion (endometriosis). Several morphologic findings (i.e., cytologic grades, dense and loose areas, intratumoral lymphocytes, distinct perinuclear vacuoles, and hemosiderin) are important clues to diagnose these spindle cell lesions. ConclusionsPathologists play a critical role in diagnosing focal liver lesions with spindle cell morphology, particularly those with limited clinical data at the initial presentation. A thorough evaluation of histomorphology on routine hematoxylin and eosin-stained slides is essential for correct diagnosis.

ЗНАЧЕНИЕ ВРОЖДЕННЫХ ДЕФЕКТОВ ИММУНИТЕТА В ИЗУЧЕНИИ ЭПИДЕМИОЛОГИИ ИНФЕКЦИОННЫХ И НЕИНФЕКЦИОННЫХ ЗАБОЛЕВАНИЙ ЧЕЛОВЕКА

Primary immunodeficiencies (PID) are conditions caused by genetic defects in the immune system. Their main manifestation is an infectious syndrome (recurrent severe infections caused by common pathogens, with gross defects in immunity). However, as the PID study progressed, descriptions of patients with hypersensitivity to rare and opportunistic infections, mycobacterioses, including BCG infection, with severe/atypical course of common viral infections, including COVID-19, emerged. Due to the inability of the immune system of patients to control the oncogenic potential of various viruses, with defects in some immune mechanisms, these patients develop various tumors (Kaposi's sarcoma, EBV-associated smooth muscle tumor) or an increase in the frequency of, for example, EBV-associated lymphomas. The creation of the Russian register of PIDs makes it possible to predict the development of certain rare/opportunistic infectious and infectious diseases in the Russian Federation. The most important is the prevention of the development of rare/opportunistic infections by early detection of patients with PID and their pathogenetic treatment, including immunomodulatory, replacement therapy with human normal immunoglobulin preparations, as well as radical therapy – hematopoietic stem cell transplantation. In addition, an important epidemiological aspect of the study of PID is that patients are often unable to eliminate infectious pathogens for a long time and serve as a reservoir of various infections (vaccinal and wild strains of poliomyelitis, COVID-19).

Epstein-Barr Virus-Associated Smooth Muscle Tumor and Its Correlation With CD4 Levels in a Patient With HIV Infection.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare tumor found in immunocompromised patients, and its treatment is not well-established. A role for antiretroviral therapy in human immunodeficiency virus (HIV)-related EBV-SMT has been proposed; however, the relevance of tumor size, CD4 levels, and immune reconstitution inflammatory syndrome (IRIS) has not been previously reported. We present the first case, to our knowledge, of a tumor that shrank in association with elevated CD4 counts. IRIS occurred in this case following antiretroviral therapy. This finding highlights the importance of the immune response in HIV-related EBV-SMT.

Multifocal EBV-associated smooth muscle tumors in a patient with cytomegalovirus infection after liver transplantation: a case report from Shiraz, Iran

IntroductionImmunodeficient patients, including the recipients of solid organs, exhibit an increase in the incidence of neoplasms. Post-transplant smooth muscle tumor (PTSMT) is a distinct and infrequent entity of these groups of neoplasms. Epstein–Barr virus (EBV) is considered to be involved in the etiology of this neoplasm.Case reportA 28-year-old man who underwent liver transplantation presented with abdominal pain and diarrhea for several months. He had a history of resistant systemic cytomegalovirus (CMV) infection after transplantation. Radiologic evaluation and colonoscopy revealed multiple liver, spleen, lung, and colon lesions. Microscopic assessment of colon and liver lesions using IHC study were in favor of spindle cell proliferation with mild atypia and a mild increase in mitotic rate without any necrosis, with features of smooth muscle tumor. Considering the transplantation history, EBER chromogenic in situ hybridization (CISH) study on paraffin blocks was requested, which demonstrated EBV RNA in tumor cell nuclei, suggesting EBV-associated smooth muscle tumor. In addition, PCR for CMV on paraffin blocks was positive. PCR for EBV and CMV viremia were negative. The dosage of immunosuppressive agents was reduced, and currently, he is being followed, with slow expansion in the size of the lesions.ConclusionAlthough the incidence of post-transplant smooth muscle tumors (PTSMTs) is low, it should be remained in the differential diagnosis in post-transplantation patients, especially dealing with multifocal tumors. As strong stimulant for smooth muscle tumors, close follow-up and screening for EBV and CMV infection and early treatment at the time of diagnosis are recommended to avoid these virus-induced tumors.

CARMIL2 Immunodeficiency with Epstein Barr Virus Associated Smooth Muscle Tumor (EBV-SMT). Report of a Case with Comprehensive Review of Literature

Background: Primary immunodeficiency (PID) having defects related to lymphocyte cytotoxic pathway or T-cell dysfunction are well known for developing opportunistic infections and Epstein-Barr virus (EBV)-associated diseases. CARMIL2 deficiency is a recently described combined immunodeficiency (CID) disorder characterized by defective CD28-mediated T cell co-stimulation, altered cytoskeletal dynamics, susceptibility to various infections and Epstein Barr Virus smooth muscle tumor (EBV-SMT). Case report: We report a homozygous CARMIL2 pathogenic variant presenting with recurrent infections and EBV associated smooth muscle tumor (SMT) in a child. Conclusion: The present study reports that EBV SMT may occur in a child with CARMIL2 deficiency.

M189 DOCK8 DEFICIENCY PRESENTING AS MULTIFOCAL EBV-ASSOCIATED SMOOTH MUSCLE TUMORS

DOCK8 deficiency is a combined primary immunodeficiency (PID) that causes autosomal recessive hyper-IgE syndrome and is characterized by recurrent infections, atopy, and risk of autoimmunity and malignancy.[1] We report a case of EBV-associated smooth muscle tumors secondary to DOCK8 deficiency requiring allogeneic bone marrow transplant.

Combined surgery and radiofrequency ablation for the treatment of EBV-associated smooth muscle tumors after liver transplantation in a child

EBV-associated post-transplant smooth muscle tumors (EBV-PTSMTs) is a rare complication following solid organ transplantation and has been observed more frequently in pediatric and young adult populations. This manuscript reports a 10-month-old female child who developed multicentric EBV-PTSMTs in a liver graft and in the distal ileum 2 years after living donor liver transplantation. The patient was successfully treated with resection and radiofrequency ablation of a liver nodule in a central position in the graft parenchyma.

Epstein-Barr virus-associated smooth muscle tumor in a girl

A girl, aged 7 years, was admitted due to pain in both lower limbs for more than one year. Lumbar MRI showed soft tissue masses in the paravertebral region. Cerebral MRI showed nodular masses in the cavernous sinus at both sides. Chest CT showed high-density nodules in the outer basal segment of the right inferior lobe and the anterior segment of the left upper lobe of the lung. Biopsy of lumbar lesions showed Epstein-Barr (EB) virus-related smooth muscle tumor. Genetic testing showed a de novo mutation, c.725_730delAGAGTA (p.K242_S243del), in the ITK gene. The masses in the lumbar vertebra were removed by surgery, and then the pain in both lower limbs disappeared. This article reports a case of EB virus-related smooth muscle tumor with a deletion mutation in the ITK gene, which provides experience for the diagnosis and treatment of this disease.

Role of surgery in treating epstein-barr virus-associated smooth muscle tumor (EBV-SMT) with central nervous system invasion: A systemic review from 1997 to 2019.

Epstein‐Barr virus‐associated smooth muscle tumor (EBV‐SMT) is a rare mesenchymal tumor occurred almost exclusively in immunocompromised hosts. This article provides a systematic review of literature under PRISMA guideline on clinical features, treatment modalities, roles of surgical intervention, and outcomes of all 65 reported EBV‐SMTs with central nervous system (CNS) invasion. Over 95% of reported cases were immunocompromised, while human immunodeficiency virus infection and post‐organ transplantation were the most commonly associated underlying causes (near 90%). Despite a heterogeneous follow‐up period, a 1‐year survival rate of 76.0% and 5‐year survival rate of 59.6% may support the indolent and non‐deadly nature of EBV‐SMT even with CNS invasion. Immune survey and reconstruction should be conducted for every patient with CNS EBV‐SMT. Surgical resection is mostly adopted as primary treatment to obtain diagnosis and relieve compressive effect. A total resection of tumor may be beneficial if tumor was symptomatic and had intracranial invasion.

Epstein–Barr virus-associated smooth muscle tumors in patients with primary immunodeficiencies

Epstein–Barr virus-associated smooth muscle tumors (EBV-SMTs) are rare soft tissue neoplasms that typically occur in conditions of secondary immunodeficiency due to human immunodeficiency virus or immunosuppression after organ transplantation. Beyond that, EBV-SMTs occur in patients with primary immunodeficiencies (PIDs). EBV-SMTs pathogenesis is still unclear but it was shown that the key mechanism of the tumor development is T- and NK-cell defect. Treatment strategy depends not only on tumor localization and resectability, but also on immunodeficiency etiology and its correction possibility. Here we report literature review and two patients with combined PIDs (CARMIL2- and ATM-genes deficiency) who developed EBV-SMT. In each case, the parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

Heck’s disease occurring after Epstein‐Barr virus‐associated smooth muscle tumors in an immunosuppressed child

A 10-year-old Guatemalan girl with past medical history of Epstein-Barr virus-associated smooth muscle tumors (EBV-SMT) and combined immunodeficiency presented for evaluation of painful intraoral lesions. On examination, she was noted to have multiple, white to flesh-colored, soft, flat-topped papules, and plaques on the buccal and labial mucosa. Human papillomavirus type 13 was detected on PCR with PGMY primers of previously biopsied buccal tissue, confirming a diagnosis of Heck's disease (multifocal epithelial hyperplasia). We present an immunosuppressed, pediatric patient with two rare, virus-associated neoplastic disorders that have not been previously reported to occur in the same individual.

Epstein-Barr virus-associated smooth muscle tumor in a kidney transplant recipient: A case-report and review of the literature.

Epstein-Barr virus (EBV) is a herpesvirus linked to pre-malignant lymphoproliferative diseases and up to nine distinct human tumors. The most frequent EBV-associated malignancies are lymphomas and nasopharyngeal carcinoma. By promoting smooth muscle proliferation, EBV can induce EBV-associated smooth muscle tumors (SMT) which remain a very rare oncological entity. This study reports one case report of SMT and aims to offer the largest review of literature on post-transplantation-SMT (PT-SMT) in kidney transplant recipients, with a focus on therapeutic management and evolution of graft function. Case reports and case series of PT-SMT in kidney transplant recipients were collected from 1996 to 2019. A total of 59 PT-SMT were evaluated. The median time at diagnosis was 74.6months after kidney transplantation. The most frequent localizations were liver and lung. EBV seroconversion was notified in all six patients with previously negative status. Preferred therapeutic option was surgery (65.9%), associated with a reduction in immunosuppression (77.2%), which includes switch to mTOR inhibitors (29.5%), and discontinuation of MMF (32%). In our review, 13% of patients experienced rejection, 8.7% lost their graft and went back on hemodialysis; 8.8% of patients died of PT-SMT. PT-SMT is a rare but serious condition in kidney transplant recipients. EBV seroconversion following transplantation appears as a risk factor in developing PT-SMT in solid-organ recipients. In the absence of guidelines, therapeutic management for PT-SMT is challenging and exposes the patient to high risk of graft loss.

Epstein Barr virus associated smooth muscle tumors in the central nervous system: a case report and systematic review of the literature

Epstein Barr virus (EBV)-associated smooth muscle tumors (SMT) in the central nervous system are rare tumors. EBV-associated SMT mainly occur in patient with compromised immune status. We report on a case of a HIV positive patient, who developed multiple EBV-SMTs, intracranially and in the spine. We systematically review the literature on the topic. A 46years old female with HIV was imaged for complaints of headaches for 2years, when an intracranial lesion was found. The patient was followed with sequential MRI scans before an excision was performed 5years later. Pathology revealed an EBV-associated SMT. Multiple other lesions appearing in the brain and in the spine over years were treated by stereotactic radiosurgery or by surgery. At the time of this report, the patient is alive under HARRT treatment without recurrence. A systematic PRISMA guided literature research was conducted on the topic reviewing multiple databases for EBV-associated SMT located in brain or spine. We identified 52 patients from the literature and performed a pooled analysis. All patients in this cohort except one were immuno-suppressed from HIV, post-transplant therapy or because of CIS. Female predominance and a median age of 35years was identified as was frequent multifocality. Therapeutic strategies varied but were mostly multidisciplinary with surgery. Based on our results, EBV-associated SMT should be included in the differential diagnosis of intracranial lesions mimicking meningiomas in immuno-suppressed patients. Stereotactic radiosurgery can be offered as an alternate treatment option for suitable lesions. Long-term surveillance via MRI scanning is recommended for follow up.

An unusual cause of a multifocal bone lesion: Epstein–Barr Virus-Associated Smooth Muscle Tumour (EBV-SMT) involving bone

Epstein–Barr virus-associated smooth muscle tumours (EBV-SMTs) are rare neoplasms of uncertain biological potential, which occur in the setting of immunodeficiency of a variety of causes, including HIV infection and post-transplant immunosuppression. The association between SMTs and immunosuppression was first described by Pritzker et al. in 1970. They have a male predominance and occur at unusual sites in adults. The CNS is the most common site in the setting of HIV while post transplantation cases are more likely to occur in liver, lungs and GIT. Other sites have also been reported including bone. We report a case of an EBV-SMT presenting as multifocal, lucent lesions of proximal tibia, proximal fibula and distal femur in a 45-year-old female patient with previous lung transplantation. A biopsy of the tibial lesion showed a smooth muscle tumour with positive staining for EBER (EBV ISH) supporting a diagnosis of EBV-SMT. EBV-SMTs of bone are rare and to our knowledge this is the first example of multifocal EBV-SMT confined to bone.