Epstein-Barr virus associated with smooth-muscle tumours in HIV patients

HIV-positive individuals who develop smooth-muscle tumours typically develop these cancers in multiple and unusual sites, according to a Thai study published in the May 15^th edition of Clinical Infectious Diseases. The investigators also established an association between infection with Epstein-Barr virus and the development of smooth-muscle tumours in HIV-positive individuals.

Kaposi’s sarcoma, lymphoma and cervical cancer occur with increased frequency in HIV-positive patients and are used to diagnose an individual’s progression to AIDS. However, there have been case reports indicating an increased incidence of smooth-muscle tumours in HIV-positive children, and in rare instances, adults. Earlier studies suggest that smooth-muscle tumours in individuals with immune suppression, such as HIV-negative transplant patients are associated with infection with Epstein-Barr virus.

Investigators from Chulalongkorn University in Bangkok wished to describe clinical manifestation of smooth-muscle tumours in HIV-positive patients and to demonstrate an association between smooth muscle tissues and Epstein-Barr virus using a variety of testing methods, including immunohistochemical analysis, in situ hybridization and Epstein-Barr virus PCR testing.

Samples of tumours were obtained for immunohistochemical analaysis and in situ hybridization. HIV and Epstein-Barr virus viral load were also measured and data on individuals’ CD4 cell count were obtained.

A total of nine HIV-positive patients with smooth muscle tumours were identified during the study period (late 2001 – late 2003). Eight were adults (age range 26 – 39-years) infected with HIV through heterosexual sex, the other patient being a vertically infected four-year-old child. By the end of the study period, six patients were alive and three had died. All the patients had a CD4 cell count below 200 cells/mm³ (range 3 – 150 cells/mm³) when their smooth muscle tumours were diagnosed, two were coinfected with hepatitis B virus, and five individuals had already been diagnosed with at least one AIDS-defining illness.

All but two patients developed smooth-muscle tumours in multiple sites. In HIV-negative individuals smooth-muscle tissue tumours tend only to develop in one site, usually affecting the genitourinary or gastrointestinal tract. None of the smooth muscle tissue tumours seen in this study affected these sites. Nine cases of smooth muscle tissue affecting the epidura were diagnosed. In addition cases affecting the vocal cords (two instances), adrenal glands (two instances) abdominal wall (two instances), iris (one case), liver (one case), lung (once case), orbit (one case) and thigh (one case) were also diagnosed..

In situ hybridisation using samples obtained from tumour sites provided results positive for Epstein-Barr virus for all nine patients. Seriological anaylsis indicated past Epstein-Barr virus infection in seven patients and Epstein-Barr virus PCR testing was positive for two patients.

“Our series, which is, to our knowledge the largest case series published, provides additional evidence of the association between smooth-muscle tumours with Epstein-Barr virus in patients with AIDS”, write the investigators.

Removal of tumours followed by HAART was associated with a good prognosis for six patients. However, three individuals died. All three of these patients had smooth-muscle tumours in multiple sites, had been diagnosed with an AIDS-defining illness and had low CD4 cell counts (range 5 – 150 cells/mm³.

“Smooth-muscle tumours in patients with AIDS typically arise in multiple and very unusual sites” conclude the investigators, adding “our series also suggests an association between Epstein-Barr virus infection and the development of smooth-muscle tumours.”