Epstein-Barr Virus-associated Smooth Muscle Tumors Research Articles

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.

Epstein-Barr Virus-Associated Smooth Muscle Tumour: A Case Series with a Significant Proportion of Tumours Showing Proclivity for Cutaneous Soft Tissues

Background: Epstein-Barr virus-associated smooth muscle tumours (EBV-SMTs) are rare neoplasms of uncertain biological potential. They are seen in the setting of immune suppression from a variety of causes, including HIV infection and post-transplant immunosuppression. Most of the literature pertaining to these neoplasms comprises case reports and small case series, with a dearth of documented cases from South Africa. Objective: To expand on the literature of these rare neoplasms in the South African context, with an emphasis on a subset showing a predilection for the cutaneous soft tissues. Method: Twenty-one EBV-SMTs from 19 consecutive patients were retrieved from the archives of the Division of Anatomical Pathology in the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, and the National Health Laboratory Service. Clinical and pathological characteristics of each case were recorded, including patient age, tumour site, H&E morphology, immunophenotypic features and the tumoural EBV status. Results: The patients’ ages ranged from 12 to 63 years, with a mean of 36 years. Thirteen (68%) of the patients in whom the HIV status was known were HIV-positive. Two of the 19 patients each had 2 tumours, thus accounting for the total of 21 neoplasms studied. Although 12 of the 21 tumours (57.1%) were from a variety of visceral organs, 9 (42.9%) originated in the dermis and superficial subcutaneous tissues, making the cutaneous soft tissues the most commonly affected site. Morphologically, all of the neoplasms were characterised by fascicles of myoid cells, admixed rounder tumour cells, scattered intratumoural lymphocytes and variable immunohistochemical staining with markers of smooth muscle differentiation. All 21 neoplasms were proven to harbour EBV DNA. Conclusion: A significant proportion of EBV-SMTs may present in the cutaneous soft tissues. This neoplasm should, therefore, be included in the histopathological differential diagnosis of any cutaneous or superficial subcutaneous spindle cell tumour, especially in patients with a history of underlying immune suppression. Accurate diagnosis thereof and its distinction from other spindle cell neoplasms is important in view of management implications and the potential for multicentricity in some patients.

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

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.

Epstein-Barr virus-associated smooth muscle tumor involving the spine of an HIV-infected patient: Case report and review of the literature

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.

Long‐term follow‐up of post renal transplantation Epstein‐Barr virus‐associated smooth muscle tumors: Report of two cases and review of the literature

Epstein-Barr virus (EBV)-associated smooth muscle tumors (SMTs) following solid organ transplantation are very rare slow growing neoplasms. Most tumors present with non-specific symptoms mainly related to tumor location. Post-transplant EBV-associated small muscle tumors have been reported in various anatomical locations. The tumors have a predilection to unusual sites for SMTs and tend to be multifocal. The histologic appearance of these tumors generally does not predict their clinical behavior. Surgery and reduction in immunosuppression are the main stays of management. We herein report two cases of post renal transplant EBV-associated SMTs with over 6years of follow-up. A 33-year-old male patient presented with hepatic lesions and a 49-year-old female patient presented with multiple mesenteric and gluteal lesions. The tumors were diagnosed 6 and 10years after renal transplantation, respectively. Surgical resection and reduction/discontinuation of immunosuppression were successful in delaying progression of the disease; however, in both cases, the allografts failed during the course of management.

Concurrent Diffuse Large B-Cell Lymphoma and Epstein-Barr Virus-Associated Smooth Muscle Tumour in the Small Bowel of an HIV-Positive Adult—a Case Report and Review of the Literature

Concurrent Diffuse Large B-Cell Lymphoma and Epstein-Barr Virus-Associated Smooth Muscle Tumour in the Small Bowel of an HIV-Positive Adult—a Case Report and Review of the Literature

Rltpr Is a Central Scaffold Protein Regulating Human TCR Co-Signaling and Cytoskeletal Dynamics

T cells are central players in adaptive immunity and T cell receptor (TCR) signaling and co-signaling govern immune defense, immune homeostasis and immune surveillance. Upon antigen encounter, the TCR becomes engaged and in concert with context-sensitive co-receptors, such as CD28, T cell activation, differentiation and function are achieved. Whereas TCR-dependent signaling has been subject to intense investigations, knowledge about CD28-dependent signal cascades is rather incomplete.In murine T cells, Rltpr was discovered to play an important role in CD28 co-signaling. We identified four patients from two consanguineous families presenting with generalized EBV-associated smooth muscle cell tumors and susceptibility to recurrent viral, bacterial, and fungal infections. All patients had homozygote loss-of-function mutations in RLTPR (c.489insG and c.871+1G>T respectively) and did not express RLTPR protein. Primary RLTPR-mutated T cells were characterized by deficiency to signal via CD28. In addition, the cells showed disturbed cytoskeletal microtubule network and defective migratory pattern with increased spontaneous motility in 2D and 3D, but reduced migratory persistence.To determine the protein interactome of human RLTPR, we designed CRISPR/Cas9 constructs and targeted the RLTPR locus in Jurkat cells. We derived five RLTPR-defective Jurkat clones, as determined by Western blot analysis and Sanger sequencing studies. Next, these clones were engineered via retroviral vectors to re-express a GFP-tagged human RLTPR protein. Jurkat T-cell clones expressing RLTPR with N-terminal-GFP, RLTPR with C-terminal-GFP or GFP only were stimulated with anti-CD3/CD28 or left unstimulated and lysed after 15 minutes. Upon pull-down using GFP-Trap, the RLTPR interactome was comprehensively investigated by nano liquid chromatography tandem mass spectrometry (LC-MS/MS) and analyzed using Maxquant. Confirmation by immunoprecipitation and western blotting was performed for selected proteins. In seven independent experiments, 903 different proteins were detected in total, 192 proteins repeatedly in at least half of the RLTPR-GFP samples. Quantitative analysis and statistical evaluation yielded 26 proteins significantly enriched in the RLTPR-GFP compared to the control samples (permutation-based q-values < 0.05).The interactome of RLTPR in genetically modified Jurkat cells primarily included cytoskeletal proteins such as capping proteins and (co)chaperones. In addition, RLTPR also interacted with a metabolic enzyme involved in nucleotide synthesis and with vesicle transport proteins involved in the initiation of TCR signaling. Known TCR or CD28 signaling molecules were not detected indicating an indirect contribution of RLTPR in these pathways.In summary, studying rare patients with EBV-associated smooth-muscle cell tumors has allowed us to define RLTPR-deficiency as a novel human primary immunodeficiency disorder and to define RLTPR as a central scaffolding molecule for CD28-mediated TCR co-signaling, cytoskeletal dynamics and metabolic signaling. DisclosuresNo relevant conflicts of interest to declare.

Epstein-Barr virus-associated smooth muscle tumors in AIDS patients: a largest case (series).

This study aimed to determine the outcomes of Epstein-Barr virus (EBV)-associated smooth muscle tumors (SMTs) in AIDS patients at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, treated from 2001-2011. Of the 17 patients, there were five men with a median CD4 count of 26 cells/μL. Eight and nine patients had single and multiple sites, respectively. The most common site was the cranial epidura (58.8%). All patients had EBV within the tumor. Seven patients underwent surgery. The median follow-up was one year. The mortality rate was 41.2%. All patients with undetectable HIV viremia survived. This is the largest case series regarding EBV-associated SMTs in AIDS patients with a long follow-up period.

Smooth muscle tumors of soft tissue and non-uterine viscera: biology and prognosis

Smooth muscle tumors are here considered an essentially dichotomous group composed of benign leiomyomas and malignant leiomyosarcomas. Soft tissue smooth muscle tumors with both atypia and mitotic activity are generally diagnosed leiomyosarcomas acknowledging potential for metastasis. However, lesions exist that cannot be comfortably placed in either category, and in such cases the designation ‘smooth muscle tumor of uncertain biologic potential' is appropriate. The use of this category is often necessary with limited sampling, such as needle core biopsies. Benign smooth muscle tumors include smooth muscle hamartoma and angioleiomyoma. A specific category of leiomyomas are estrogen-receptor positive ones in women. These are similar to uterine leiomyomas and can occur anywhere in the abdomen and abdominal wall. Leiomyosarcomas can occur at any site, although are more frequent in the retroperitoneum and proximal extremities. They are recognized by likeness to smooth muscle cells but can undergo pleomorphic evolution (‘dedifferentiation'). Presence of smooth muscle actin is nearly uniform and desmin-positivity usual. This and the lack of KIT expression separate leiomyosarcoma from GIST, an important problem in abdominal soft tissues. EBV-associated smooth muscle tumors are a specific subcategory occurring in AIDS or post-transplant patients. These tumors can have incomplete smooth muscle differentiation but show nuclear EBER as a diagnostic feature. In contrast to many other soft tissue tumors, genetics of smooth muscle tumors are poorly understood and such diagnostic testing is not yet generally applicable in this histogenetic group. Leiomyosarcomas are known to be genetically complex, often showing ‘chaotic' karyotypes including aneuploidy or polyploidy, and no recurrent tumor-specific translocations have been detected.

Epstein–Barr virus‐associated smooth muscle tumors in a composite tissue allograft and a pediatric liver transplant recipient

Epstein-Barr virus (EBV) is known to establish latent infections in B-lymphocytes that can cause lymphoproliferative disorders particularly in immunocompromised patients. More recently, the development of rare EBV-associated smooth muscle tumors has been reported in transplant recipients. We herein describe 2 new cases of EBV-associated post-transplant smooth muscle tumors (EBV-PTSMT), including the first in a facial composite tissue graft recipient. Among the striking features shared by these 2 patients were their young ages, the fact that they were naïve for EBV before the transplantation, that they developed a post-transplant lymphoproliferative disorder before the diagnosis of EBV-PTSMT, and that they responded favorably to reduction of immunosuppression. Radiological and histologic features of EBV-PTSMT are shown. Finally, pathophysiology and therapeutic management of EBV-PTSMT are discussed based on a comprehensive review of the literature.

Multifocal Histologically Malignant Epstein–Barr Virus–Associated Smooth Muscle Tumor in a Pediatric Transplant Patient With an Indolent Course

Epstein-Barr virus-associated smooth muscle tumors (EBV-SMTs) are rare lesions that occur in immunocompromised patients. Dural involvement appears to be less common in organ transplant recipients than in HIV patients. Due to the paucity of reported cases following organ transplantation, the natural history of these lesions is unclear. We describe an 8-year-old female who presented with adrenal, small bowel, and intracranial tumors 6 years following renal transplantation. Histopathological analysis revealed a highly cellular, mitotically active, smooth muscle neoplasm without necrosis. The tumor stained diffusely for smooth muscle actin and myosin. In situ hybridization for EBV-encoded RNA was diffusely positive. Following gross total resection, antiviral therapy, and a reduction in immunosuppression, the patient is tumor-free at 3 years follow-up. In patients with compromised immune systems, it is important to recognize this unique form of SMT because, even when there are multiple lesions, the prognosis may be excellent.

Epstein–Barr virus‐associated smooth muscle tumors after kidney transplantation: treatment and outcomes in a single center

Epstein-Barr virus-associated smooth muscle tumors (EBV SMT) in adult kidney transplant recipients (KTR) are rare. The aims of this study are to document the clinical features, types of treatment given, and outcomes of KTR with EBV SMT in our institution. Sixteen patients were identified from our institution's databases. Patients' survival, tumor outcome, and graft survival were compared between patients who remained on cyclosporine-based immunosuppressant and those who converted to sirolimus-based therapy. The median time of diagnosis was 9.4 yr after kidney transplantation, and majority of the patients had multifocal disease at the time of diagnosis. Overall, the patient survival rate was 75% over a mean follow-up period of five yr. Two patients with non-functioning allograft at the time of diagnosis of EBV SMT were excluded from the treatment outcome analysis. Comparing the sirolimus (n = 7) vs. cyclosporine groups (n = 7), patient survival rate was 100% vs. 42.9% (p = 0.08), graft survival 71.4% vs. 28.7% (p = 0.53), and disease-free status 42.9% vs. 14.3% (p = 0.73), respectively. Surgical resection in combination with decreasing immunosuppression or conversion to sirolimus appears to be effective in the treatment of EBV SMT in KTR.

Epstein- Barr Virus Related Malignant and Non-Malignant Transformation in Two Paediatric Liver Transplant Patients

Introduction: Epstein-Barr virus (EBV)-associated smooth muscle tumors (EBV-SMT) are a distinctive group of mesenchymal tumors that develop exclusively in patients with clinical immunosuppression, predominantly in HIV and recipients of solid organ transplantation, particularly paediatric patients. The incidence of developing neoplastic disorders after solid organ transplantation is highly dependent on the intensity of the prophylactic anti-viral regimen, the induction therapy, as well as high levels of calcineurin inhibitors. Recently 2 of our liver transplant patients have been diagnosed with both benign and malignant EBV- related smooth muscle tumours presenting as significant gastrointestinal bleeds. Since the 1970‘s, there have been a small number of cases of leiomyomas in immunosuppressed patients post transplant. Case Presentation: Patient ZH underwent a liver transplant for missed biliary atresia at one year five months of age. Her course was complicated by portal vein thrombosis and a failed Meso-Rex shunt two months post transplant. Despite this, her liver remained well perfused on hepatic arterial blood supply with no problems with rejection. A meso-caval shunt was done at six years of age when she continued having significant gastrointestinal bleeds. A mesenteric lymph node removed incidentally during surgery was consistent with leiomyosarcoma on histology. Further imaging showed lung metastatic lesions and at a subsequent laparotomy a primary ileal lesion was resected. She completed chemotherapy and six weeks later had another gastrointestinal bleed which revealed a leiomyoma on histology from a rectal biopsy. She was commenced on IVI gancyclovir and tacrolimus was changed to sirolimus. Despite the above management, a repeat colonic biopsy following another gastrointestinal bleed confirmed the presence of a leiomyoma. Patient AJG underwent a liver transplant at four years of age for biliary atresia. He had an uncomplicated course post transplant except for raised EBV levels initially treated with three months of intravenous gancyclovir and then oral valgancyclovir. He had a massive gastrointestinal bleed two years later which revealed features consistent with post transplant lymphoproliferative disorder of terminal ileum and leiomyoma in the sigmoid colon. Discussion: Smooth muscle EBV induced tumours after organ transplantation are rare, occurring more often in the paediatric population. These tumours are generally insidious and their prognosis depends on the size, site and surgical options. There is no standard treatment. Although the benign variant carries a good prognosis, leiomyosarcoma carries a poor prognosis. We are highlighting these two cases to emphasise the need for ongoing vigilance to detect EBV-associated malignancies with regular EBV PCR monitoring and adjustment of immunosuppression if EBV PCR titres rise. Management involves an interdisciplinary approach with input from transplant physicians, surgeons and oncologists. Management involves surgical resection of all lesions if possible, reduction of immunosuppression and possibly changing from a calcineurin inhibitor to a MTOR inhibitor. Once malignant transformation has occurred, the prognosis is poor.

Epstein-Barr virus–associated smooth muscle tumor—report of 3 tumors including 1 intracerebral case with a prominent intratumoral B-lymphocytic component and plasma cells

Three Epstein-Barr virus-associated smooth muscle tumors (intracranial, endobronchial, and paraspinal) in 2 patients are presented. The patient with the intracranial tumor had no concurrent or previous manifestation of this neoplasm and was immunosuppressed because of a renal transplant. The other patient had AIDS and radiologic evidence of involvement of multiple other sites. Although mitotic activity was present, none of the tumors displayed any high-grade malignant histologic features. All tumors were strongly positive for smooth muscle actin and variably expressed h-caldesmon. Desmin was negative in all 3 tumors. The intracranial tumor was associated with prominent intracerebral edema and displayed, in addition to a prominent intratumoral T-cell component, a hitherto unreported component of prominent intratumoral B cells and plasma cells.

Epstein-Barr virus-associated smooth muscle tumour presenting as a parasagittal brain tumour

Dural-based brain tumours, apart from meningiomas, are rare. Epstein-Barr virus (EBV)-associated smooth muscle tumor (SMT) is a documented but rare disease that occurs in immunocompromized patients. These tumours may be located at unusual sites including the brain. We present a 37-year-old patient, positive for the human immunodeficiency virus (HIV), who was admitted after generalized tonic–clonic seizures. MRI and CT scan revealed a dural-based brain tumour, intraoperatively thought to be a meningioma, but with an eventual histological diagnosis of EBV–SMT. Clinically the patient was well postoperatively with a Glasgow coma scale score of 15/15 and no focal neurologic deficit. This case confirms the association between EBV and SMT in patients with HIV/acquired immunodeficiency syndrome (AIDS). It also highlights the need to include EBV-SMT in the differential diagnosis of intracranial mass lesions in patients with HIV/AIDS.

Bilateral adrenal EBV-associated smooth muscle tumors in a child with a natural killer cell deficiency

AbstractEBV-associated smooth muscle tumors are found in immunocompromised patients, most commonly HIV/AIDS. We present a 12-year-old girl with the first documented case of EBV-related smooth muscle tumors in the presence of a rare classic NK cell deficiency. This sheds light on the role of NK cells in controlling EBV-related smooth muscle tumors.

Epstein-Barr virus-associated smooth muscle tumor of the tonsil

Smooth muscle tumors of the tonsil are rare. Recently, the occurrence of Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) has been increasingly recognized in immunocompromised patients, mainly post-transplantation and AIDS patients. The clinicopathologic features of EBV-SMT are different from conventional smooth muscle tumors. To the best of our knowledge, EBV-SMT involving the tonsil in an AIDS patient has not been reported. A 27-year-old man presented with a 2.2cm right tonsillar mass six months after AIDS diagnosis. The tumor was composed of a cellular proliferation of oval to spindle-shaped cells with mitotic count up to 10 in 10 high-power fields. The diagnosis of EBV-SMT was confirmed by in situ hybridization for EBV-encoded RNA (EBER) transcripts. Synchronous lesions were also detected in the liver and peritoneum by an abdominal computed tomographic scan. EBV-SMT should be included in the differential diagnoses of a mesenchymal tumor in immunocompromised patients, and in the differential diagnoses of a smooth muscle tumor occurring in uncommon sites including the tonsil.

Dermal Epstein Barr Virus–Associated Leiomyosarcoma: Tocsin of Acquired Immunodeficiency Syndrome in Two Children

Although rare in childhood, a relatively high incidence of smooth muscle tumors are recognized in patients with AIDS, mainly in association with Epstein Barr virus (EBV) infection. Although EBV-associated smooth muscle tumors have been documented rarely in the subcutis of AIDS patients, dermal involvement has not been described to date. This report describes dermal EBV-associated leiomyosarcomas (EBV-LMS) with a nodular but superficial plaque-like appearance on the lower limbs of 2 males, 9 and 12 years old. Histopathological assessment of the excised lesions demonstrated hypercellular mitotically active dermal tumors with hyperchromatic spindle and round cells, arranged in short fascicles and sheets, with microfoci of necrosis. A smooth muscle immunophenotype, including prominent desmin immunopositivity, and positive EBV-encoded RNA in situ hybridization investigation confirmed a diagnosis of EBV-LMS. Subsequent HIV seropositivity and AIDS were confirmed in both patients. Both patients also had pulmonary tuberculosis and received antituberculous therapy. Patient 1 had a 3 cm re-excision of the prior tumor site. He received highly active antiretroviral therapy, completed 6 months of antituberculous therapy, achieved immune reconstitution and viral suppression and is tumor-free 2 years after tumor excision. Patient 2 died before further therapy. The immune status, presence, and appropriate therapy of co-existent systemic infection and highly active antiretroviral therapy in AIDS patients with EBV-LMS are crucial to a favorable outcome.