Herpes Simplex Virus Type 2 Seroprevalence and Incidence and Growth of Ultrasound-Diagnosed Uterine Fibroids in a Large Population of Young African-American Women.

Reproductive tract infections have long been hypothesized to be risk factors for development of uterine fibroids, but few studies have investigated the issue. In our 2016 cross-sectional analysis from the Study of Environment, Lifestyle and Fibroids (2010-2018), a large Detroit, Michigan, community-based cohort study of 23- to 35-year-old African-American women with ultrasound fibroid screening, we found no association between a very prevalent reproductive tract infection, herpes simplex virus type 2 (HSV-2), and fibroids. With prospective data from the cohort (ultrasounds performed every 20 months over 5 years), we examined HSV-2's associations with fibroid incidence (among 1,208 women who were fibroid-free at baseline) and growth (among women with fibroids at baseline or diagnosed during the study). Using Cox proportional hazards models, we computed adjusted hazard ratios and 95% confidence intervals for fibroid incidence comparing HSV-2-seropositive women with HSV-2-seronegative women. The influence of HSV-2 infection on growth was assessed on the basis of the difference in fibroid size between successive ultrasounds (1,323 growth measures) using a linear mixed model, estimating the percent difference in growth scaled to 18 months. HSV-2 seropositivity was not associated with fibroid incidence (adjusted hazard ratio = 0.88, 95% confidence interval: 0.69, 1.12) or growth (estimated growth difference = 3.1%, 95% confidence interval: -5.8, 13.0). Women can be reassured that HSV-2 infection is unlikely to increase their risk of fibroid-related health problems, given these longitudinal measures.

Suspension of ulipristal acetate for uterine fibroids during ongoing EMA's review of liver injury risk: Unfortunate timing during the Covid-19 pandemic!

OBJECTIVE: EMA decided that with ulipristal acetate (UPA) treatment for uterine fibroids, should be discontinued due to the associated risk of hepatic failure, We analyzed whether the risk of recurrent symptoms due to fibroids may lead to an increased risk of Covid -19 infection and death, that would exceed the former risk of hepatic failure and transplantation. STUDY DESIGN, SIZE, DURATION: We used a Markov model to generate probabilities. PARTICIPANTS/MATERIALS, SETTING, METHODS: There are currently about 36,250 treated patients in Europe. We estimated bleeding probabilities, while using or discontinuing UPA, which may induce a need of medical or surgical management in symptomatic patients, and increase the risk of acquiring a Covid-19 infection, and die from it. We also estimated the risk of suffering a hepatic failure and hepatic transplantation. MAIN RESULTS AND THE ROLE OF CHANCE: Based on our assumptions, ceasing UPA during a Covid 19 pandemic may be associated with a fatality ratio between 4 and 18, due to the Pandemic, whereas pursuing UPA would be associated with a fatality rate due to the pandemic between 1-2, and an added fatality rate due to hepatic impairment of 1. The added risk of stopping UPA may range between 2 and 15 additional deaths. Our calculations suggest that the decision to stop UPA in the middle of the Covid- 19 pandemic may be untimely, since it may result in an increased risk of Covid-19 infection, due to the recurrence of symptoms and the need for medical and surgical treatment. WIDER IMPLICATIONS OF THE FINDINGS: A decision, like the one EMA took need to be taken in a wider health context of a population, than simply analyzing its role as regulating agent for medications.

Intracranial Leiomyoma Associated with Epstein-Barr Virus: A Cerebellopontine Angle Mass Presenting with Trigeminal Neuralgia.

BACKGROUND: Primary intracranial leiomyoma is a rare smooth muscle tumor often associated with Epstein-Barr virus (EBV), with <30 cases reported worldwide. These tumors commonly occur in patients with immunocompromised status, especially those with human immunodeficiency virus. In the present report, we have described the case of an EBV-associated leiomyoma at the cerebellopontine angle. The patient had presented with trigeminal neuralgia, which, to the best of our knowledge, is the first reported anatomical location and presentation for this tumor type. CASE DESCRIPTION: A 41-year-old male patient had presented with right-sided facial pain in the V1 and V2 dermatomes and previous workup and imaging studies. The patient had undergone treatment of a presumed right-side cerebellopontine angle meningioma as determined by the magnetic resonance imaging characteristics (no biopsy). The patient subsequently underwent right-sided retrosigmoid craniotomy and gross total resection of the tumor. The postoperative period was uneventful with resolution of the trigeminal neuralgia. Histopathologic examination revealed spindle cell neoplasm with histopathologic and immunohistochemical features consistent with leiomyoma. The tumor cells were positive for smooth muscle actin and desmin and were negative for S100, SOX-10, epithelial membrane antigen, glial fibrillary acidic protein, progesterone receptor, CD31, CD34, and E-cadherin. CONCLUSIONS: Primary intracranial leiomyomas are rare tumors associated with EBV infection that occur in immunocompromised patients. These lesions should be considered in the differential diagnosis for patients with known immunocompromised status (e.g., human immunodeficiency virus), and tissue biopsy should be considered.

Multifocal Epstein-Barr virus-associated miliary post-transplant smooth muscle tumors.

Epstein-Barr virus (EBV) promotes the development of undifferentiated carcinomas of the upper aerodigestive tract and different types of lymphomas. This ability of tumorigenesis is heightened in many immunocompromised patients who have an increased incidence of lymphoproliferative disorders. The virus also induces smooth muscle proliferation, and those occurring following transplantation are designated as EBV-associated post-transplant smooth muscle tumors. We report multifocal miliary-sized leiomyomas in the lungs in a renal transplant recipient as an incidental finding.

Novel mutation in DOCK8-HIES with severe phenotype and successful transplantation.

BACKGROUND: Hyper-IgE syndrome (HIES) due to DOCK8 deficiency is an autosomal recessive (AR) primary combined immunodeficiency which results in significant morbidity and mortality at a young age. Different mutations in the DOCK8 gene can lead to variable severity of the disease. OBJECTIVE: We evaluated the genetic mutations in three related patients with severe clinical manifestations suggestive of AR HIES. We also explored whether treatment with stem cell transplantation could lead to complete disease resolution. METHOD: We examined the clinical manifestations and immunological workup of these patients. Their DNA was also screened for causative mutation. Post transplantation, clinical and immunological data for the transplanted patient was also collected. RESULTS: All patients had a severe course of the disease with rarely reported severe complications in HIES. One patient died with lymphoma while another died with progressive multifocal leukoencephalopathy (PML) due to a slow virus. All our patients had two novel mutations in the DOCK8 gene. One of these mutations was a novel pathogenic mutation and explains the severity of the disease (homozygous splice site mutation at position 5 after the end of exon 45), while the other mutation was mostly non-pathogenic. Hematopoietic stem cell transplantation (HSCT) was performed in the youngest patient with excellent engraftment and full reversibility of the clinical manifestations. CONCLUSION: We report 3 patients from a consanguineous family diagnosed with AR-HIES due to a novel pathogenic mutation in DOCK8 gene leading to fatal outcome in 2 patients and complete resolution of the clinical and immunological features in the third patient by HSCT.

Epstein-Barr virus associated smooth muscle tumors in post transplant pediatric patients two cases of rare locations, and review of the literature.

Epstein-Barr virus (EBV) may present few or no symptoms in immunocompetent individuals; however, in immunocompromised patients as in the case of AIDS and post-transplant patients, the virus occasionally stimulates neoplastic transformations. Epstein-Barr virus may play a role in the development of smooth muscle tumors (SMT). In the case of Epstein-Barr associated smooth muscle tumors (EBV+SMT), the virus is thought to be the leading factor to the tumorigenic pathway. We report two pediatric patients (6 and 13 years old) who underwent liver transplantation and developed EBV+SMT in the colon and orbit. These two cases represent rare locations for this kind of lesion.

Bilateral Epstein-Barr virus-associated adrenal leiomyomas in a child without an established immunodeficiency.

Adrenal leiomyomas are rare, bilateral ones being rarer. Literature available on these rare tumors documents only 4 cases in children less than 12 years of age. Each case has been associated with acquired immune deficiency syndrome or some other immunodeficiency state. Here we present a rare case of large, bilateral, adrenal leiomyomas in a child with no known immunodeficiency. An 11-year-old girl with a past history of herpes zoster (1 year before the present complaints) was admitted with abdominal pain of 2 months' duration. Radiology revealed bilateral adrenal neoplasms, probably bilateral pheochromocytoma. Histology showed bilateral adrenal leiomyomas that were Epstein-Barr virus associated. We report this case to draw attention to the occurrence of a common pathologic entity at an uncommon site in a setting of no definite known immunodeficiency.

Epstein-Barr virus associated primary intracranial leiomyoma in organ transplant recipient: case report and review of the literature.

INTRODUCTION: A 45 year old female renal transplant recipient presented with headaches of 3 months duration. Clinical and radiological evaluation revealed an approximately 4x4 cm rounded, enhancing mass at the left temporal pole. At surgery, the mass had dural attachment and clinically, radiographically, and macroscopically resembled a meningioma. Histopathological analysis revealed a leiomyoma. Epstein-Barr virus (EBV) DNA was demonstrated within the tumour cell nuclei by the in situ hybridisation technique. DISCUSSION: This is the first documentation of an EBV-associated primary intracranial leiomyoma in an organ transplant recipient and provides additional evidence of a possible relation between EBV infection and development of smooth-muscle tumours (SMT). CONCLUSION: With increasing numbers of individuals being on long-term immuno-suppression, EBV-associated SMTs may be encountered more frequently in the future.

Toward gene therapy of uterine fibroids: targeting modified adenovirus to human leiomyoma cells.

BACKGROUND: To circumvent the paucity of the primary adenovirus (Ad5) receptor and the non-specific Ad5 tropism in the context of uterine leiomyoma cells, Ad5 modification strategies would be beneficial. METHODS: We screened several modified adenoviruses to identify the most efficient and selective virus toward human leiomyoma cells to be used as candidate for delivering therapeutic genes. We propagated: wild-type Ad5-luc, fiber-modified viruses: ad5 RGD-luc, Ad5-Sigma-luc, Ad5/3-luc and Ad5-CAV2-luc, as well as transcriptional targeted viruses: ad5 survivin-luc, Ad5-heparanase-luc, Ad5-MSLN-CRAD-luc and Ad5-SLPI-luc, on 293 cells and purified them by double CsCL density centrifugation. Then we transfected primary cultures of human leiomyoma cells derived from fibroids of four different patients, telomerase-immortalized human leiomyoma cell line (huLM), telomerase-immortalized normal human myometrial cell line (HM9) and immortalized normal human liver cells (THLE3) with the viruses at 5, 10 and 50 plaque-forming units (PFU)/cell. After 48 h, luciferase activities were measured and normalized to the total cellular protein content. RESULTS: Ad5-RGD-luc and Ad5-CAV2-luc, Ad5-SLPI-luc and Ad5-MSLN-CRAD-luc at 5, 10 and 50 pfu/cell showed significantly higher expression levels of luciferase activity in both primary and immortalized human leiomyoma cells when compared with Ad5-Luc. Additionally, these modified viruses demonstrated selectivity toward leiomyoma cells, compared with myometrial cells and exhibited lower liver cell transduction, compared with Ad5-luc, at the same dose levels. CONCLUSIONS: Ad5-CAV2-luc, Ad5-RGD-luc, Ad5-SLPI-luc and Ad5-MSLN-CRAD-luc are promising delivery vehicles in the context of leiomyoma gene therapy.

Epstein-Barr virus-associated bronchial leiomyoma in a boy with cellular immunodeficiency.

Bronchial leiomyoma is a rare disease in children. Recently, the association of leiomyoma and HIV infection was reported. We describe a boy with a cellular immunodeficiency, who had endobronchial leiomyoma. The tumor cells were positive for Epstein-Barr virus-encoded RNA-1 (EBER-1) and Epstein-Barr virus-determined nuclear antigen-2, suggesting a role of Epstein-Barr virus in the pathogenesis of leiomyoma.

Renal leiomyoma associated with Epstein-Barr virus in a pediatric transplant patient.

Renal leiomyoma is a rare smooth muscle tumor of the kidney. An association between Epstein-Barr virus and smooth muscle tumors in immunocompromised patients recently has been recognized. We describe a pediatric renal transplant patient who developed an Epstein-Barr virus-associated renal leiomyoma in his transplant kidney 5 years posttransplantation. Possible factors involved in the tumor pathogenesis in our patient are discussed, including immunosuppression, growth hormone therapy, and Epstein-Barr virus induction.

CD5+ Epstein-Barr virus-positive intravascular large B-cell lymphoma in the uterus co-existing with huge myoma.

A 42-year-old female underwent hysterectomy because of a huge uterine mass. Histologically, she was diagnosed as having intravascular lymphoma co-existing with myoma uteri. Lymphoma cells were large in size and were positive for CD5, CD20, CD45, CD79a, lambda light chain, and EBV but were negative for CD3 and cyclin D1. No other organs except for the adjoining bilateral ovaries seemed to be affected by the lymphoma cells. She received the combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) together with rituximab and has been well without definite disease progression. So far, this is the first case of CD5+ EBV+ intravascular large B-cell lymphoma (CD5+ EBV+ IVLBL) in the uterus of a patient who was incidentally diagnosed and successfully treated.

Smooth muscle tumors of soft tissue.

This paper presents an overview of smooth muscle tumors occurring in deep soft tissue. Although the existence of leiomyomas of soft tissue has been questioned in the past, it appears that they do exist but are rare, and must be diagnosed using stringent histologic criteria that include no atypia and minimal or no mitotic activity. They segregate into two distinct clinicopathologic groups, one group occurring in patients of either sex in deep somatic soft tissue and the second occurring primarily in women in the pelvic retroperitoneum. The latter bear a histologic similarity to uterine leiomyomas. Leiomyosarcomas occur in retroperitoneum followed by deep somatic soft tissue and are diagnosed by the presence of nuclear atypia and essentially any level of mitotic activity. Leiomyosarcomas of deep somatic tissue commonly arise from small veins and their behavior can be predicted by a number of factors including age, grade, and "disruption" of tumor. Conversely, few factors have proved to be prognostically useful for leiomyosarcomas of the retroperitoneum, as nearly all prove fatal. Epstein Barr virus (EBV)-associated smooth muscle tumors are a recently emerging entity that occur in the setting of immunocompromise. Their behavior is closely tied to the immune status of the patient rather than to specific histologic features.

Metachronous Epstein-Barr virus-related smooth muscle tumors in a child after heart transplantation: case report and review of the literature.

Soft tissue tumors are uncommon manifestations of Epstein-Barr virus (EBV) infection in patients who have had transplants. The authors report 2 metachronous EBV-containing smooth muscle tumors in a child who had a heart transplant, and review the literature on posttransplant soft tissue tumors.

Primary leiomyoma of the liver.

This case report describes a primary hepatic leiomyoma presenting as a mass lesion detected on ultrasonography of the abdomen in an asymptomatic hepatitis B carrier on routine surveillance. Primary leiomyomata of the liver are rare occurrences, with only 9 cases reported in the literature. The presenting features of primary hepatic leiomyomata and diagnostic approach towards such lesions are discussed. The significance of such tumours in the immunocompromised is also mentioned.

Hepatic leiomyomatous neoplasm associated with Epstein Barr virus infection in an adult with acquired immunodeficiency syndrome.

Focal lesions in the liver in patients with acquired immunodeficiency syndrome (AIDS) pose an important clinical problem. Hepatic smooth-muscle tumor is rare in AIDS patients and has been reported mostly in children. We describe a 32-year-old male AIDS patient, with previous disseminated tuberculosis, who developed a small tumor in the liver. Liver biopsy disclosed an unusual hepatic leiomyomatous neoplasm that was associated with Epstein Barr virus infection. It differed from the more common Kaposi's sarcoma and presented a relatively benign course.