This case report describes an HIV-1-infected patient presenting brain localization of KS, despite previously administered chemoterapy and cART treatment. Disease localization was documented by accurate histological, virological and radiological examination with MRI and DWI. At first evaluation of the patient, absence of cutaneous neoplastic lesions, immunological status with CD4+ cell count stably above 200/mm3, HIV-1 RNA of 68 copies/mL, negative HHV8 PCR in the peripheral blood, and diagnosis of concurrent gingival carcinoma made the diagnosis of KS unlikely.
In the pre-cART era, HIV-1-infected patients with KS typically had a low CD4 cell count and a high HIV viral load. Since the introduction of cART, the incidence of KS has decreased
 and survival improved
[15, 16]. Further, it is well documented that cART, especially HIV protease inhibitors, can improve KS lesions with or without use of liposomal anthracycline
[15, 17]. However, unusual cases of cutaneous HIV-associated KS occurring even during stable immunologic rescue and HIV-RNA suppression in plasma are reported
Our patient was cART-experienced, with genotypic multi-drug resistance in HIV. Despite the high-level resistance, re-optimized cART allowed to obtain stable low-level viremia in plasma close to 50 copies/mL cut-off. Biopsy of the lymph node revealed histologic KS and allowed starting chemotherapy with improvement of visceral lesions. At the onset of neurological symptoms, brain mass lesions at MRI were detected. Radiologic features of intracranial KS have only rarely been described; intracranial masses of the patient had a vascular component, and appeared as a inhomogeneous mass with hyperintense signal on T1- and on T2-weighted images, with surrounding edema, minimal mass effect and with faintly ring enhancement. The hyperintensity on T1-weighted images probably was due to abnormally increased blood vessels with slow intra-lesional flow. The low ADC value of KS lesions might be due to its histological architecture made of high tumor cellularity and relatively large vascular spaces. Although no studies have elucidated the direct relationship between blood flow velocity and vascular spaces size we hypothesise that blood velocity in KS lesions is low because of the large vascular spaces, and that this may determine the increased signal strengths and lower ADCs on DWI. FDG-PET of the body only showed the suspicion of neoplastic disease in various tissues, but FDG-PET of the brain unfortunately was not performed. Only autopsy specimens allowed obtaining the diagnosis of KS, that was confirmed by the detection of HHV8-DNA in the brain tissues. In HIV-infected patients, differential diagnosis of mass lesions is required. Mass algorithms in the pre-cART era were well defined, but in the cART era, when the epidemiology of opportunistic infections changed, are lacking. Brain biopsy, if feasible, is no longer mandatory for the diagnosis of mass lesions in HIV-patients
, however histological examination in some cases is still the only way to obtain a definitive diagnosis.
Only few histologically proven cases of KS metastatic to the brain in HIV-1 patients have been described: up to now Gorin et al. reported two cases at the beginning of the AIDS era
, and Buttner et al. described in 1997 a patient who had never taken cART
. Two more cases were published by Levy et al. and one was observed by Post et al. in CNS diseases studies performed in the 80’s
. In a morphological analysis of brains from 100 AIDS patients observed in the course of 1987–1995 years, Mossakowski et al. found one case of cerebral KS
, so did Jellinger et al. in a retrospective study on 450 consecutive autoptical AIDS cases between 1984 and 1999, only in the cohort of 1984–1992
. Most of these cases were observed in advanced patients with other concomitant AIDS-related events and none occurred during antiretroviral treatment. Moreover, in our patient cART was mainly effective, with low plasma viral copies and partial immune recovery.
The cause of brain involvement in this patient despite an initial improvement of visceral lesions with the appropriate treatment
, is difficult to explain. Furthermore, it is well documented that positive HHV8 DNA on peripheral blood or a CD4 level below 200/mm3 are risk factors of poor evolution of KS
, but the patient had a stable immunity and a persistent negative blood HHV8 DNA. Despite incomplete suppression of HIV-1 replication, cART was effective to prevent the development of opportunistic infections in all the clinical history of the patient. We know that HIV-1 plays a role on the KS diffusion through the production and the release of the HIV-1 Tat protein, a KS progression factor, and that cART has a documented direct anti-angiogenetic effect
[23, 24]. In this case, independently of the CD4 cell count, the incomplete suppression of HIV-1 could have enhanced the diffusion of KS, producing an increased release of the HIV-1 Tat protein.
This case describes a rare complication of KS, never reported in the cART era, and raises a question about the diagnosis and the treatment suggesting that KS should be considered for the differential diagnosis with other intracranial mass lesions that can occur in HIV patients and focusing on the problem of appropriate treatment for CNS involvement.
The case described was approved by an internal revision group at the Direction of Clinical Department.
Written informed consent was obtained from the wife of the patient for publication of this case report and any accompanying images. A copy of the consent form is available for review by the Editor of this journal.