RESUMEN
BACKGROUND: Epstein-Barr virus-associated smooth muscle tumors (SMTs) are rare neoplasms that have been found to develop in immunocompromised patients. Three distinct groups of affected patients have been described: (1) human immunodeficiency virus-infected patients, (2) post-transplant patients, and (3) patients with congenital immunodeficiency. The tumors can develop anywhere in the body, with 17 reported cases occurring in the spinal canal, all in patients with human immunodeficiency virus infection. CASE DESCRIPTION: We report the first case of Epstein-Barr virus-associated SMT affecting the spinal canal in a post-bone marrow transplant adult patient. Interestingly, unlike other reported cases, the patient described here had not been receiving immunosuppressive therapy in the 2 years prior to diagnosis of the tumor. CONCLUSIONS: Despite the growing number of case reports, this diagnosis presents a challenge, as the pathophysiology and optimal treatment regimens are not well understood. Results of a literature review of Epstein-Barr virus-associated SMT of the spine as well as a discussion of the presentation, management, and prognosis of this condition is presented here.
Asunto(s)
Infecciones por Virus de Epstein-Barr/inmunología , Huésped Inmunocomprometido , Tumor de Músculo Liso/diagnóstico por imagen , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Descompresión Quirúrgica , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunosupresores/efectos adversos , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Neuritis Óptica/tratamiento farmacológico , Tumor de Músculo Liso/inmunología , Tumor de Músculo Liso/cirugía , Tumor de Músculo Liso/virología , Fusión Vertebral , Neoplasias de la Columna Vertebral/inmunología , Neoplasias de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/virología , Vértebras TorácicasRESUMEN
Immunotherapies targeting the PD-1/PD-L1 checkpoint axis are of growing interest for the treatment of mesenchymal neoplasms. However, PD-L1 expression and tumor-associated lymphocytes have not been well-investigated in uterine smooth muscle tumors. Forty-nine uterine smooth muscle tumors (23 leiomyosarcomas, 8 smooth muscle tumors of uncertain malignant potential [STUMP], 7 atypical leiomyomas, and 11 benign leiomyomas) were evaluated for tumoral and tumor-associated immune PD-L1 expression and tumor-associated T-cell infiltration. ALK immunohistochemistry was performed to exclude inflammatory myofibroblastic tumors. Tumor PD-L1 expression was seen in 70% of leiomyosarcomas and 14% of atypical leiomyomas; no cases of STUMP or benign leiomyoma demonstrated tumoral PD-L1. PD-L1 positivity was seen in tumor-associated immune cells in 78% of leiomyosarcomas, 25% of STUMP, no cases of atypical leiomyomas, and 9% of benign leiomyomas. Of the 23 leiomyosarcomas, 15 (65%) had a combined positive score ≥1, while of the 26 other uterine smooth muscle tumors, only 2 (8%) had a combined positive score ≥1. Tumor-associated CD8+ cells were highest among leiomyosarcomas (mean: 87/high-power fields vs. 17/high-power fields for nonleiomyosarcomas), and were significantly associated with PD-L1 expression. One PD-L1, CD8-enriched leiomyosarcoma showed an ALK overexpression suggesting possible classification as inflammatory myofibroblastic tumor, but otherwise lacked morphologic features of this entity. Leiomyosarcomas demonstrate significantly higher PD-L1 expression and cytotoxic T-cell infiltration when compared with other uterine smooth muscle tumors. These data suggest the possibility that treatment with targeted immunotherapy may be appropriate in a selected population of patients with leiomyosarcoma and, potentially, in related tumors bearing ALK rearrangements.
Asunto(s)
Antígeno B7-H1/análisis , Biomarcadores de Tumor/análisis , Leiomioma/inmunología , Leiomiosarcoma/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Tumor de Músculo Liso/inmunología , Linfocitos T Citotóxicos/inmunología , Neoplasias Uterinas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico/análisis , Antineoplásicos Inmunológicos/uso terapéutico , Femenino , Humanos , Inmunoterapia , Leiomioma/tratamiento farmacológico , Leiomioma/patología , Leiomiosarcoma/tratamiento farmacológico , Leiomiosarcoma/patología , Linfocitos Infiltrantes de Tumor/patología , Persona de Mediana Edad , Pronóstico , Tumor de Músculo Liso/tratamiento farmacológico , Tumor de Músculo Liso/patología , Linfocitos T Citotóxicos/patología , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/patología , Adulto JovenRESUMEN
Within the last two decades, there have been multiple reports of Epstein-Barr virus (EBV)-associated smooth muscle tumors in immunocompromised patients. This includes HIV-infected patients, post-transplant patients, and patients with congenital defects of their immune systems. Here we report the case of a 24-year-old African American female with congenital HIV presenting with progressive lower extremity weakness, constipation, aching pain in her shoulders, and subcostal anesthesia. Magnetic resonance imaging (MRI) revealed a large circumferential lesion extending from T1-T3 and a smaller left paraspinal lesion at C6-C7. The T1-T3 mass was excised via a right-sided costotransversectomy with laminectomy and fusion from T1-T3. Highly active antiretroviral therapy (HAART) was started postoperatively, and adjuvant radiotherapy was initiated but patient was lost to follow-up. Surgical pathology demonstrated a smooth muscle tumor diffuse nuclear positivity for EBV-encoded small RNA 1 by in situ hybridization. Although eight studies have reported HIV patients with EBV-associated smooth muscle tumors of the spine, to the author's knowledge, this is the first review comprised solely of patients with spinal involvement with the addition of our patient case.
Asunto(s)
Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por VIH/complicaciones , Huésped Inmunocomprometido , Tumor de Músculo Liso/inmunología , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Infecciones por VIH/congénito , Herpesvirus Humano 4 , Humanos , Imagen por Resonancia Magnética , Músculos Paraespinales/patología , Tumor de Músculo Liso/patología , Tumor de Músculo Liso/virología , Adulto JovenRESUMEN
Epstein-Barr virus positive (EBV+) smooth muscle tumors (SMTs) constitute a very rare oncological entity. They usually develop in the context of secondary immunodeficiency caused by human immunodeficiency virus infection or immunosuppressive treatment after solid organ transplantation. However, in a small fraction of predominantly pediatric patients, EBV+ SMTs may occur in patients with primary immunodeficiency disorders (PIDs), such as GATA2 and CARMIL2 deficiency. In secondary immunodeficiencies and when the underlying condition can not be cured, the treatment of EBV+ SMTs is based on surgery in combination with antiretroviral and reduced or altered immunosuppressive pharmacotherapy, respectively. Importantly, without definitive reconstitution of cellular immunity, long-term survival is poor. This is particularly relevant for patients with EBV+ SMTs on the basis of PIDs. Recently, allogeneic hematopoietic stem cell transplantation resulted in cure of immunodeficiency and EBV+ SMTs in a GATA2-deficient patient. We propose that in the absence of secondary immunodeficiency disorders patients presenting with EBV+ SMTs should be thoroughly evaluated for PIDs. Allogeneic hematopoietic stem cell transplantation should be taken into consideration, ideally in the setting of a prospective clinical trial.
Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por Virus de Epstein-Barr/inmunología , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 4/fisiología , Síndromes de Inmunodeficiencia/inmunología , Músculo Liso/patología , Tumor de Músculo Liso/inmunología , Animales , Humanos , Síndromes de Inmunodeficiencia/terapia , Inmunosupresores/uso terapéutico , Tumor de Músculo Liso/terapiaRESUMEN
Epstein-Barr Virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor typically seen in immunocompromised patients. Here, we report a case of EBV-SMT and associated granulomatous inflammation in the liver of a 32-year-old man with history of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). To our knowledge, an association of these two lesions has not been previously reported. We review the literature and discuss pathogenesis, differential diagnosis and immunohistochemical (IHC) stains helpful for the diagnosis of this rare entity. Finally, we consider possible explanations for the concomitant presence of these lesions.
Asunto(s)
Infecciones por Virus de Epstein-Barr/virología , Granuloma/virología , Hepatitis/virología , Tumor de Músculo Liso/virología , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/virología , Adulto , Biopsia con Aguja Gruesa , Diagnóstico Diferencial , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/inmunología , Granuloma/diagnóstico , Granuloma/inmunología , Hepatitis/diagnóstico , Hepatitis/inmunología , Humanos , Huésped Inmunocomprometido , Inmunohistoquímica , Masculino , Valor Predictivo de las Pruebas , Tumor de Músculo Liso/diagnóstico , Tumor de Músculo Liso/inmunologíaRESUMEN
Epstein-Barr virus (EBV) has oncogenic potential and has been implicated in the etiology of a wide range of malignancies. Certain EBV-driven neoplasms, such as smooth muscle tumors (SMTs), manifest typically in immunocompromised patients. In children, these neoplasms have been encountered in the setting of primary immune disorders, specifically severe combined and common variable immunodeficiency syndromes. Human immunodeficiency virus infection and posttransplant immunosuppression, in particular liver and kidney transplantation, likewise increase the risk in the pediatric population. The location of these neoplasms appears related to the type of immunodeficiency: in acquired immunodeficiency syndrome they are frequently located intracranially or intraspinally, whereas after transplant they usually involve the liver or lung. We report 2 distinct cases of EBV-related SMT, unique through their coassociated immunosuppressive state or location: the 1st occurred in a patient with immunodeficiency secondary to NEMO gene mutation following hematopoietic stem cell transplantation; the 2nd developed in the orbit after heart transplant.
Asunto(s)
Neoplasias del Ojo/virología , Herpesvirus Humano 4/aislamiento & purificación , Tumor de Músculo Liso/virología , Neoplasias del Bazo/virología , Actinas/análisis , Adulto , Autopsia , Biomarcadores de Tumor/análisis , Biopsia , Displasia Ectodérmica/genética , Displasia Ectodérmica/inmunología , Displasia Ectodérmica/cirugía , Neoplasias del Ojo/inmunología , Neoplasias del Ojo/patología , Neoplasias del Ojo/terapia , Resultado Fatal , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/cirugía , Trasplante de Corazón/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/inmunología , Humanos , Huésped Inmunocomprometido , Inmunohistoquímica , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/cirugía , Inmunosupresores/efectos adversos , Hibridación in Situ , Lactante , Masculino , Enfermedades de Inmunodeficiencia Primaria , ARN Viral/genética , Factores de Riesgo , Tumor de Músculo Liso/inmunología , Tumor de Músculo Liso/patología , Tumor de Músculo Liso/terapia , Neoplasias del Bazo/inmunología , Neoplasias del Bazo/patología , Neoplasias del Bazo/terapiaRESUMEN
Rare Epstein-Barr virus (EBV)+ smooth muscle tumours (SMT) manifest typically under immunosuppression. Three major subtypes are known: human immunodeficiency virus-associated (HIV-SMT), after transplantation (PTSMT) or associated with congenital immunodeficiency syndromes (CI-SMT). So far, there are no analyses which compare the clinico-pathological characteristics of all three subtypes. Case reports and case series on these three tumour types were collected (1990-2012). Meta-data analysis was performed for identification of similarities and differences. A total of 73 HIV-SMT, 66 PTSMT and 9 CI-SMT were evaluated. There was a slight female predominance (55-67%). Children were affected nearly equally in HIV-SMT (33%) and PTSMT (35%), while all CI-SMT occurred in children. HIV-SMT manifested preferentially in the central nervous system, gut/liver, skin, lungs/larynx/pharynx and adrenal glands. PTSMT were predominantly found in the liver, lungs/larynx/pharynx, gut/spleen and brain. CI-SMT were often found in lungs/larynx, brain, liver, adrenal glands and spleen. Antecedent EBV+ lymphoproliferations manifested more often in PTSMT. In all three tumour subtypes, survival analyses did not show any significant differences regarding surgical therapeutic approaches, the occurrence of multiple tumours, tumour size or sarcoma-like histological features. HIV-SMT had the poorest overall survival, which might be attributed to HIV-associated infectious complications.
Asunto(s)
VIH/aislamiento & purificación , Tumor de Músculo Liso/patología , Estudios de Cohortes , Inmunodeficiencia Variable Común/inmunología , Inmunodeficiencia Variable Común/patología , Inmunodeficiencia Variable Común/virología , Infecciones por Virus de Epstein-Barr/patología , Humanos , Pronóstico , Tumor de Músculo Liso/inmunología , Tumor de Músculo Liso/virologíaAsunto(s)
Infecciones por Virus de Epstein-Barr/virología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Neoplasias Hepáticas/virología , Infecciones Oportunistas/virología , Tumor de Músculo Liso/virología , Biomarcadores de Tumor/análisis , Biopsia con Aguja , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/inmunología , Resultado Fatal , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/inmunología , Persona de Mediana Edad , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/inmunología , ARN Viral/genética , Tumor de Músculo Liso/química , Tumor de Músculo Liso/diagnóstico , Tumor de Músculo Liso/inmunología , Tomografía Computarizada por Rayos XRESUMEN
Epstein-Barr virus (EBV) - associated smooth muscle tumors (EBV-SMT) are a rare, recently recognized distinct group of mesenchymal tumors that develop exclusively in patients with immunosuppression. It is believed that tumorigenesis is, at least in part, through the activation of the Akt/mammalian target of rapamycin (mTOR) signal pathway. We describe the clinicopathologic and immunohistochemical features of a multifocal hepatic EBV-SMT in a 34-year-old acquired immunodeficiency syndrome (AIDS) patient and investigate the activation status of the mTOR signal pathway in this tumor. In addition, we provide a review of the literature on the clinicopathologic findings of hepatic EBV-SMT in adult AIDS patients, and discuss their biologies and possible therapeutic strategies.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Infecciones por Virus de Epstein-Barr/complicaciones , Neoplasias Hepáticas/virología , Tumor de Músculo Liso/virología , Serina-Treonina Quinasas TOR/metabolismo , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/virología , Adulto , Terapia Antirretroviral Altamente Activa , Antivirales/uso terapéutico , Biopsia , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/inmunología , VIH-1/genética , Herpesvirus Humano 4/genética , Humanos , Inmunohistoquímica , Hibridación in Situ , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Masculino , ARN Viral/análisis , ARN Viral/sangre , ARN Viral/genética , Transducción de Señal , Tumor de Músculo Liso/diagnóstico , Tumor de Músculo Liso/inmunología , Tumor de Músculo Liso/metabolismo , Tomografía Computarizada por Rayos XRESUMEN
EBV is associated with various malignancies in patients with acquired or induced immune impairment. EBV-SMT is very uncommon in immunocompromised patients, and a kidney localization has been described only anecdotally. We report the case of a 17-yr-old kidney transplant recipient diagnosed as having an EBV-SMT inside the renal graft, which was successfully managed by minimizing isolated immunosuppression.
Asunto(s)
Infecciones por Virus de Epstein-Barr/inmunología , Huésped Inmunocomprometido , Neoplasias Renales/terapia , Neoplasias Renales/virología , Trasplante de Riñón/inmunología , Tumor de Músculo Liso/terapia , Tumor de Músculo Liso/virología , Adolescente , Humanos , Inmunosupresores/uso terapéutico , Neoplasias Renales/diagnóstico , Neoplasias Renales/inmunología , Masculino , Tumor de Músculo Liso/diagnóstico , Tumor de Músculo Liso/inmunologíaRESUMEN
Epstein-Barr virus (EBV) associated smooth muscle tumors (SMTs) have been described in patients with acquired immune deficiency syndrome (AIDS) and, more recently, in association with immunosuppression after solid-organ transplantation. We present the autopsy findings of multiple leiomyosarcomas (LMSs) in a 24-year old man who died 18 months after undergoing orthotopic cardiac transplantation for idiopathic cardiomyopathy. The recognition of EBV-driven LMS developing in cardiac transplant recipients in multiple unusual sites is crucial for the management of these patients and should include complete surgical removal anti-viral therapy and modulation of immunosuppression.
Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Trasplante de Corazón , Herpesvirus Humano 4 , Terapia de Inmunosupresión/efectos adversos , Leiomiosarcoma/virología , Neoplasias Primarias Múltiples/virología , Adulto , Trasplante de Corazón/inmunología , Humanos , Leiomiosarcoma/inmunología , Leiomiosarcoma/patología , Masculino , Neoplasias Primarias Múltiples/inmunología , Neoplasias Primarias Múltiples/patología , Tumor de Músculo Liso/inmunología , Tumor de Músculo Liso/patología , Tumor de Músculo Liso/virologíaRESUMEN
immunosuppressed patients are predisposed to the development of smooth muscle tumours which show near consistent association with Epstein-Barr virus (EBV). This report describes a 37-year-old patient with acquired immunodeficiency syndrome who initially presented with two masses in the liver. Image-guided core biopsy revealed a spindle cell tumour with histological and immunological features of smooth muscle neoplasm which was shown by in situ hybridisation for EBV early RNAs to be EBV-associated. The literature on this uncommon entity is critically reviewed and the differential diagnosis is also discussed.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/inmunología , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/aislamiento & purificación , Huésped Inmunocomprometido , Neoplasias Hepáticas/virología , Tumor de Músculo Liso/virología , Adulto , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/patología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/patogenicidad , Humanos , Hibridación in Situ , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Masculino , ARN Viral/análisis , Tumor de Músculo Liso/inmunología , Tumor de Músculo Liso/patologíaRESUMEN
AIMS AND METHODS: Digestive stromal tumors are the most frequent undifferentiated mesenchymal tumors. The prognosis of these tumors is difficult to predict and the histogenesis is still subject to controversy. However, the frequent and specific expression of CD117 (c-kit) by these tumors could suggest an origin from interstitial cells of Cajal. The aim of this study was to analyse the histological and immunohistochemical characteristics of 46 digestive stromal tumors surgically resected, with comparaison of CD34 and CD117 expression in these tumors. Sixteen tumors were analyzed on electron microscopy. RESULTS: Sixty three and 74% of the stromal tumors were positive for CD117 and CD34 respectively. While CD117 expression was similar in all locations, on the contrary, there was a decreasing gradient of CD34 expression between gastric (87%) and jejunal (33%) tumors. All tumors with skeinoid fibers expressed CD117. Focal expression of smooth muscle actin was noted in 43% of the cases. The ultrastructural study showed no correlation with the immunohistochemical results. CONCLUSION: Digestive stromal tumors show an immunophenotypic and ultrastructural heterogeneity. CD117 expression is frequent, but not constant.