Epstein-Barr Virus-Associated Leiomyosarcoma of the Thyroid in a Child With Congenital Immunodeficiency

Abstract

We report an unusual case of multifocal leiomyosarcoma involving the thyroid gland, liver, and right lung in a child with congenital immunodeficiency disease. The smooth muscle nature of these neoplasms was confirmed by immunohistochemistry and electron microscopic studies. In situ hybridization showed large amounts of Epstein-Barr virus messenger RNA within the tumor cells. Although Epstein-Barr virus-associated smooth muscle tumors have been reported in children with AIDS and after organ transplantation, we are unaware of any case report in congenital immunodeficiency disease.

Epstein-Barr Virus-Associated Smooth Muscle Tumours after Transplantation, Infection with Human Immunodeficiency Virus and Congenital Immunodeficiency Syndromes

“…EBV-positive smooth muscle tumours (SMT) are not specific for transplant patients but are associated with any patients on long-term immunosuppression. Similar tumours can manifest in patients who suffer from human immunodeficiency virus (HIV) infection (HIV-SMT) or congenital immunodeficiency syndromes (CI-SMT) [3,4,5,6,7,8,9,10,11]. Among HIV patients and patients with rare congenital defects, the exact frequency of tumour manifestation is not known, but is most likely <5%.…”

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

“…7,[10][11][12]14,15 Congenital immunodeficiency, such as ataxia telangiectasia and T-cell deficiency, have been linked to EBV-SMT; however, these cases are extremely rare. [3][4][5] Our case demonstrates that a broader range of immunodeficiency syndromes may be associated with the development of EBV-SMTs and highlights the utility of immune defenses outside of the adaptive system. Adrenal gland involvement in EBV-SMTs is surprising given the limited smooth muscle present.…”

“…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.…”

“…EBV has never been linked to an isolated NK cell deficiency. [3][4][5][6] Classic NK deficiency is defined as a deficiency in NK cell numbers and function with normal NKT cell (CD56 ϩ /CD3 ϩ ) numbers in the presence of otherwise intact immunity. 1 We report, to our knowledge, the first case of classic NK deficiency discovered in the presence of bilateral EBV ϩ adrenal SMTs.…”

Epithelioid Leiomyosarcoma in a Non-Immunocompromised Infant: Additional Differential Diagnosis of Pediatric “Round Cell Tumors”

“…Leiomyosarcoma (LMS) has become the second leading malignancy of children with human immunodeficiency virus (HIV) infection or other immunodeficiency diseases, and is often associated with Epstein-Barr virus (EBV) infection (1,2). However, LMS is rare in non-immunocompromised children and accounts for only 2 to 4% of childhood soft tissue sarcomas (3,4).…”