Multifocal Epstein-Barr Virus-Associated Smooth Muscle Tumor in Adults with AIDS: Case Report and Review of the Literature

Abstract

Objectives: The aim of this study was to provide a systematic review of Epstein-Barr virus-associated smooth muscle tumors (EBV-SMT) in human immunodeficiency virus (HIV)-infected adults, focusing on clinical and histopathologic features and outcome. Methods: A literature search was performed using Medline, Embase and the Cochrane Library. Results: We reviewed 35 cases including our case of a patient with a progressive multifocal EBV-SMT. Patients were mainly men (n = 24) with a mean age of 35.5 years. Median CD4 count was 21/mm³. Main locations were brain (n = 12), liver (n = 8), spinal cord (n = 7) and adrenal gland (n = 6). The tumors were multifocal in 34% of cases, whereas analysis of clonality showed different clones in tumors from different sites. Treatment included removal surgery in 17 cases and/or radiotherapy in 9 and therapeutic abstention in 4. Mean follow-up after diagnosis was 12.3 months. Nine patients died during this period essentially from opportunistic infection and only 2 from the disease. Conclusion: EBV-SMT should be added to the list of virally induced tumors in severely immunocompromised HIV-infected adults. Multifocality of independent tumor clones, especially in liver, brain, spinal cord and adrenal gland, and a slow disease progression seem to be the key features of these tumors, the treatment of which remains poorly defined.

Epstein-Barr Virus-associated Smooth Muscle Tumors in AIDS Patients: A Largest Case (Series)

“…This observation is consistent with recent reviews (6,9,10). In addition, our patients were relatively young, with a mean age of 34+9.2 years, also consistent with the previous reviews (6,9,10).…”

“…Only five and three patients with cranial and spinal epidura have been reported in the literature, and five of these patients were infected with HIV (11,18). In the present study, all SMTs in the brain were enhancing epidural masses located in the sellar and/or parasellar areas, consistent with other reports (6,(9)(10)(11)18). In addition, the majority of our patients with spinal SMTs presented with epidural masses in the neural foramina, mimicking nerve-sheath tumors.…”

“…It is likely that immunosuppression can predispose patients to the development of SMTs (7). The association became more evident as the number of AIDS patients and organ transplant recipients has significantly increased in the past few decades (4,5,(8)(9)(10).…”

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

“…Immunoperoxidase staining demonstrated positive vimetin, smooth muscle actin, and desmin, all specific findings in SMTs. 8 Lastly, in situ hybridization for EBV early RNAs produced strong and diffuse reactivity in addition to positive nuclear staining of EBV early RNAs. An initial tumor biopsy showed a translocation t(4;21) (q21:q11.2) but was not replicated in subsequent cytogenetic cultures and is of uncertain significance.…”

“…We speculate that the severe deficiency of NK cells in our patient, despite normal cytotoxic CD8 ϩ T cells, was sufficient to compromise the initial immune response, therefore contributing to the development of an EBV-SMT as seen in HIV, organ transplant, and congenital T-cell deficiency patients. [3][4][5][6][7][8]12 The NK cell deficiency appeared to be quantitative because the few cells present were phenotypically normal and low-level activity could be detected after IL-2 stimulation. It has been shown that EBV transformation can increase levels of indoleamine 2,3-dioxygenase in some cells, leading to down-modulation of NKG2D from NK cells.…”