Oral Kaposi's Sarcoma Research Articles

Human Immunodeficiency Virus–Associated Kaposi Sarcoma as an Immune Reconstitution Inflammatory Syndrome: A Literature Review and Case Report

Kaposi sarcoma (KS) is the most common human immunodeficiency virus (HIV)-associated neoplasm (HIV-KS). Highly active antiretroviral therapy (HAART) results in a decrease in the incidence and prevalence of HIV-KS as well as in clinical improvement. However, in a subset of subjects who are HIV seropositive, KS may recrudesce early following the introduction of HAART as an immune reconstitution inflammatory syndrome (IRIS). The management of a patient who is HIV seropositive with rapid clinical worsening of oral KS lesions shortly after the initiation of HAART was documented. Repeated serologic testing for CD4(+) T-cell count and microscopic examination of two biopsy specimens of the oral lesion, one taken before and the other taken after cytotoxic chemotherapy, followed by surgical excision was the treatment modality used. Microscopic examination of the incisional biopsy specimen taken from the oral lesion at the time of the initial consultation confirmed the clinical diagnosis of KS. The sequential serological tests showed a progressive increase in CD4(+) T-cell counts that paralleled the rapid clinical worsening of the KS disease. This was consistent with the diagnosis of IRIS-associated HIV-KS. Subsequent cytotoxic chemotherapy brought about resolution of the IRIS and regression of the HIV-KS lesions. Microscopic examination of a biopsy specimen obtained after cytotoxic chemotherapy did not show any of the original KS. The residual palatal exophytic mass was excised. IRIS-associated HIV-KS is not a disease, but rather a temporary paradoxical immunoinflammatory reaction brought about by improvement in immune status following HAART. IRIS-associated HIV-KS can be controlled effectively by limited systemic cytotoxic chemotherapy in the setting of HAART.

Oral Health & HIV/AIDS

Oral lesions are common in women and children with HIV/AIDS and may decrease the overall quality of life in these patients because of pain, dry mouth, and difficulty in eating. An oral cavity screening is an easy, noninvasive, quick, and inexpensive procedure that provides nurses with invaluable information about the need for referral, treatment, and health education. Nurses can use the information obtained from a careful oral screening to decrease the symptoms experienced with oral lesions and optimize a patient's ability to chew and enjoy food. Common oral manifestations of HIV infection include fungal, viral, and bacterial infections, although neoplasms, periodontal disease, salivary gland disease, and lesions of uncertain origin are also seen. Oral lesions such as candidiasis, oral hairy leukoplakia, herpetic ulcers, and Kaposi's sarcoma are often among the first symptoms of HIV infection.

Oral Kaposi's sarcoma in Tanzania: Presentation, immunopathology and human herpesvirus-8 association

Oral Kaposi's sarcoma (OKS) from Tanzanian patients (78) at Muhimbili National Hospital/Muhimbili University College of Health Sciences corresponding to approximately 10% of KS registered during 1990-2005, were diagnosed (ELISA) as HIV-infected (OAKS) (74/78) and endemic KS (4/78). Females were 69.2% (54/78) with median age 31 and males 30.8% (24/78) with median age 38. More males (50%) had systemic KS than females (37%) and 4-times more multicentric OKS. All tested (34) oral KS patients sera had HHV-8 antibodies. Available (31/78) blood showed very low CD4+ T-lymphocyte counts. Most OKS (61.5%) had nodular histology. Immunostaining showed adult male nodular OAKS to have a significantly higher frequency of viral LANA+, endothelial CD34+ tumour spindle-cells (SC) and more Ki-67+ (median =24.1%) proliferating cells compared to females (17.2%). Juvenile nodular OAKS had more LANA+ and Ki-67+ cells than corresponding adult cases. Significantly more LANA+ and Ki-67+ cells were found in nodular OAKS compared to cutaneous HIV/AIDS Kaposi's sarcoma (CAKS). A positive correlation (60%) was found between the proliferation index (Ki-67+ cell frequency) and LANA+/CD34+ SC. OKS in Tanzania is since 1990, mostly seen in females, associated with HIV/AIDS and advanced (nodular) histopathology. Males have more systemic tumour burden while more females develop primary OAKS. HHV-8+ cells were more frequent in nodular male than female and in juvenile than adult nodular OAKS than cAKS. Higher tumoral HHV-8 content appeared to be correlated to proliferation index.

Management of oral lesions in HIV-positive patients

HIV/AIDS is currently the leading cause of death in Africa and the fourth leading cause of death worldwide. This systematic review of the literature was conducted to evaluate the evidence for treatment of the most common oral lesions associated with HIV: oral candidiasis with or without oropharyngeal involvement (OPC), oral hairy leukoplakia (OHL), recurrent aphthous-like ulcerations (RAU), oral Kaposi's sarcoma (OKS), orolabial herpes simplex infection (HSV), oral herpes zoster infection (VZV), intraoral or perioral warts (HPV), and HIV-associated periodontal diseases. Treatment of HIV-associated salivary gland disease is addressed in a different section of this World Workshop. We found the largest body of evidence for treatment of OPC in HIV patients. Future trials will be needed to test drugs currently in development for treatment of Candida strains that are resistant to existing therapies. There were no double blind, placebo-controlled randomized clinical trials (RCT) for topical treatment of OHL, and only one RCT for systemic treatment of the lesion with desciclovir. Systemic thalidomide was the only drug tested in RCT for treatment or prevention of RAU. Only 1 double-blind RCT comparing vinblastine and sodium tetradecyl sulfate was identified for localized treatment of OKS. Three drugs (famciclovir, acyclovir, and valaciclovir) were shown to be effective in randomized, double-blind trials for treatment or suppression of mucocutaneous HSV lesions in HIV patients. In all 3 trials, the effects of these medications on orolabial HSV lesions were not reported separately. There were no double-blind, placebo-controlled RCT testing topical treatments for orolabial HSV lesions in HIV patients. No trials testing treatments of oral VZV were identified. There were no double-blind, placebo-controlled RCT for treatment of HIV-associated intraoral or perioral warts or periodontal diseases. In conclusion, there is a need for well-designed RCTs to assess the safety and efficacy of topical and systemic treatments of most oral mucosal and perioral lesions in HIV patients. There is also a need to develop newer drugs for treatment of resistant fungal and viral microorganisms. Finally, standardized outcome measures should be developed for future clinical trials to allow comparisons of studies using different populations.

Gingival Involvement in a Case Series of Patients With Acquired Immunodeficiency Syndrome‐Related Kaposi Sarcoma

This case series presents the polymorphic clinical characteristics of gingival acquired immunodeficieny syndrome (AIDS)-related Kaposi sarcoma (KS), a malignancy that is gradually becoming uncommon in developed nations. An up-to-date overview of the related epidemiology, etiopathogenesis, histopathology, and treatment is provided, along with a pictorial guide to ease clinical diagnosis. The oral/maxillofacial pathology records at Aristotle University and the University of Geneva were retrospectively reviewed. Thirty-two cases diagnosed with oral AIDS-related KS were retrieved between 1991 and 2004. KS diagnosis was established histologically by incisional biopsies from intraoral lesions. All charts contained clinical oral examination data, radiological images, and detailed photographic records. Thirteen patients (12 males and one female) presented with KS gingival involvement (40.6%). Eleven of the male patients were homosexual/bisexual men. The mean age of the patients at the time of intraoral KS diagnosis was 42.1 years, and the mean CD4 cell count was 103 (0 to 481). Gingival epidemic KS presented with various degrees of pigmentation and a wide range of clinical patterns, from relatively flat macules (early stage) to tumors with variable nodular morphology (advanced disease). Solitary or multiple gingival involvement may appear concomitantly with palatal and/or cutaneous lesions. Even though the incidence of intraoral KS had fallen precipitously in developed countries after the mid-1990s, gingival KS should be considered in the differential diagnosis of every pigmented gingival lesion. Periodontists are in a unique position to identify gingival involvement of intraoral KS and facilitate early diagnosis.

口蓋に発生したＡＩＤＳ関連カポジ肉腫の１例

A 46-year-old homosexual man was referred to our department on a certain day in February, 2005, by his home dentist because of a mass on the left side of the palate. He had been aware of this mass since the end of December 2004. This mass was dark purple, 10×18mm in size, elastic soft, and irregular in shape with clear margins. At presentation, a biopsy was performed, and the mass was diagnosed as Kaposi's sarcoma. On 8th day, laboratory tests revealed that he was HIV-1 positive. On 18th day, the patient was referred to the department of internal medicine. Highly active antiretroviral therapy (HAART) was initiated on 32th day. A complete remission of oral Kaposi's sarcoma was achieved on 130th day.

Disseminated oral Kaposi sarcoma lesion with extensive visceral involvement

Kaposi’s sarcoma (KS) has been considered the most common malignancy associated with human immunodeficiency virus (HIV) infection because of its propensity to develop in such individuals.This article, reports an unusual presentation of a disseminated oral KS lesion with extensive visceral involvement in an otherwise healthy young African-American male leading to a positive diagnosis of HIV.

Management of oral Kaposi’s sarcoma lesions on HIV-positive patient using highly active antiretroviral therapy: Case report and a review of the literature

This article reports an unusual presentation of an oral KS lesion in an HIV-positive HAART-naïve patient three years after diagnosis. The lesions gradually decreased in size subsequent to the initiation of HAART. KS lesions may regress after HAART begins, suggesting that the recovery of the immune system and a direct antiviral effect against human herpes virus 8 (HHV-8) may largely cause this improvement.

Oral Kaposi's sarcoma in a non-HIV homosexual White male

This paper reports the exceedingly rare occurrence of oral Kaposi's sarcoma in a non-HIV Caucasian White male. The lesion presented as a 8 mm vascular nodule on the buccal mucosa on the left. He was homosexual. The lesion was removed and histological examination confirmed Kaposi's sarcoma. The patient has been tested on 10 occasions for HIV from December 1998 to March 2004 and has been negative. The patient remains alive and well with no evidence of recurrence.

Oral Kaposi's sarcoma: a clinicopathologic study from South Africa

In this retrospective study, we defined the clinicopathologic characteristics of oral Kaposi's sarcoma (KS) and determined the presence of human herpesvirus 8 in the oral lesions in a group of South African patients. These results were compared with similar data from patients in developed countries. Eighty-one cases of oral KS were retrieved from the departmental archives. Fourteen patients with oral pyogenic granuloma served as control subjects. DNA was extracted by using a modified phenol chloroform extraction method and amplified by using polymerase chain reaction. If beta-globin DNA sequences could not be demonstrated, the patient was excluded from the study. Of the 81 patients included in the study, 68 (84%) had been diagnosed since 1997. Oral KS was often the first presenting sign of human immunodeficiency virus infection. Some of the lesions exceeded 4 cm in diameter. The most commonly affected site was the palate (37 patients), followed by the tongue and gingiva. Multiple oral sites were frequently involved. The mean age of the patients was 34.7 years (range, 2-58 years). The male-to-female ratio was 1.31 to 1. Most of the patients (94%) were black. Human herpesvirus 8 DNA sequences were detected in 44 of the 45 cases of oral KS in which the DNA was analyzed, and in 1 case of pyogenic granuloma. The only significant clinicopathologic differences in findings between our study and previous studies in developed countries were (1) the male-to-female ratio, (2) the preponderance of black patients, and (3) the more frequent involvement of the tongue. There are no studies reporting the clinicopathologic characteristics of oral KS in populations of developing countries.

Oral manifestations in HIV infection: fungal and bacterial infections, Kaposi's sarcoma.

Oral candidiasis (OC) is a frequent oral manifestation of HIV infection, is a marker disease and occurs as a pseudomembranous, erythematous or rarely hyperplastic variant; angular cheilitis is also seen. Candida albicans is frequently isolated but other species such as C. krusei and C. dublienensis are emerging. Resistance against fluconazole is common. Bacterial oral infections are comparatively rare and are predominantly localized to the gingiva and periodontium. Linear gingival erythema, necrotizing ulcerative gingivitis and necrotizing ulcerative periodontitis have been described in HIV-infected patients. Initially, these diseases were considered specific for HIV infection. In recent years, however, it has become apparent that gingivitis and periodontitis in HIV-infected patients do not differ from those in immunocompetent individuals. AIDS-associated Kaposi's sarcoma (KS) predominantly occurs at the palate, the gingiva and the dorsum of the tongue. Histopathologically, oral KS is identical to classical KS. Oral KS has been treated surgically, using laser, radiotherapy and intralesional injections with chemo- and immunotherapy. After introduction of highly active antiretroviral therapy (HAART) oral manifestations, such as OC, gingivo-periodontitis and KS are rarely seen.

The Changing Clinical Spectrum of Human Immunodeficiency Virus (HIV)-Related Oral Lesions in 1,000 Consecutive Patients: A 12-Year Study in a Referral Center in Mexico.

In developing countries, the variations in the clinical spectrum of human immunodeficiency virus (HIV)-related oral lesions over time, and the possible effects of antiretroviral therapy, have not been described. In this study we evaluate the clinical spectrum of oral lesions in a series of HIV-infected patients when first examined at the acquired immunodeficiency syndrome (AIDS) clinic of a tertiary care institution in Mexico City, Mexico, and the changes observed over 12 years. All HIV-infected adult patients had an oral examination performed by specialists in oral pathology and medicine who used established clinical diagnostic criteria for oral lesions. Four periods were defined according to the evolving pattern of antiretroviral use: the first 2 were before the introduction of highly active antiretroviral therapy (HAART) and the last 2 were during more established use of HAART. For the statistical analysis the chi-square test for contingency tables and the chi-square test for trend were utilized. For dimensional variables, except age, the Kruskal-Wallis or Mann-Whitney rank sum tests were used when applicable and trend was tested with the Spearman correlation coefficient. Age was tested through analysis of variance (ANOVA) and linear regression analysis. Alpha value was set at p = 0.05 for each test. In the 12-year study, 1,000 HIV-infected patients were included (87.9% male). At the baseline examination, oral lesions strongly associated with HIV were present in 47.1% of HIV-infected patients. Oral candidosis (31.6%), hairy leukoplakia (22.6%), erythematous candidosis (21.0%), and pseudomembranous candidosis (15.8%) were the most frequent lesions. Oral Kaposi sarcoma (2.3%), HIV-associated periodontal disease (1.7%), and oral non-Hodgkin lymphoma (0.1%) were less frequent. HIV-related oral lesions decreased systematically-by half during the course of the 4 study periods (p < 0.001). Except for Kaposi sarcoma, all oral lesions strongly associated with HIV showed a trend to decrease significantly during the study period. No apparent variation in the occurrence of salivary gland disease or human papillomavirus-associated oral lesions was found. A significant trend to a lower prevalence was observed in the group of patients who were already taking antiretroviral therapy, non-HAART and HAART (p < 0.001 and p = 0.004, respectively). Only a discrete reduction, barely significant, was noted among untreated patients (p = 0.060). By Period IV (1999-2001), those who received HAART showed the lowest prevalence of oral lesions strongly associated with HIV (p < 0.001). Patients with oral lesions strongly associated with HIV had significantly lower median CD4+ counts and higher viral loads than those without oral lesions strongly associated with HIV (p < 0.001 and p = 0.005, respectively). When CD4+ counts were correlated with prevalence of oral candidosis, a consistently negative association was found; this association prevailed even after the study group was partitioned according to period. In this selected cohort of 1,000 patients with HIV infection, the clinical spectrum of HIV-related oral lesions has changed over the 12-year study, with a decreased prevalence of most oral lesions. Our findings probably represent improvements in medical care of HIV-infected persons, earlier detection of HIV-infected patients at the AIDS clinic, the increasing use of prophylactic drugs to prevent secondary AIDS-related opportunistic infections, and, perhaps most important, the availability of potent antiretroviral therapy in recent years, since the introduction of HAART.

Viral infections in the mouth

Oral hairy leukoplakia (OHL) and Kaposi's sarcoma (KS) are commonly encountered in the HIV-infected patient. A unique feature of OHL is non-cytolytic high level of replication of Epstein-Barr virus (EBV) in the glossal epithelium. The expression of viral-encoded anti-apoptotic proteins concomitant to replicative proteins probably underlies this phenomenon. The question of whether OHL arises from activation of EBV latent in the tongue, or from superinfection by endogenous EBV shed via nonglossal sites or by exogenous EBV remains unresolved. Human herpesvirus 8 (HHV8) is now seen as necessary but not sufficient cause of KS. Expression of HHV8-encoded oncogenic proteins in endothelial cells probably explains the aberrant proliferation of these cells in KS lesions. Studies into why KS is so commonly observed at the palate in HIV-infected patients may provide important clues to its pathogenesis.

Prevalence and classification of HIV-associated oral lesions.

An International Workshop addressed the prevalence and classification of HIV/ AIDS associated oral lesions. Five questions provided the framework for discussion and literature review. What is the prevalence of oral lesions in children and adults? Should the accepted classification of HIV-related oral lesions be modified in the light of recent findings? Why is there a gender difference in the prevalence of oral lesions in developed and developing countries? Are there unusual lesions present in developing countries? Is there any association between modes of transmission and the prevalence of oral lesions? Workshop discussion emphasized the urgent need for assistance in the development of expertise to obtain accurate global prevalence data for HIV-associated oral lesions. Oral candidiasis has been consistently reported as the most prevalent HIV-associated oral lesion in all ages. Penicilliosis marneffei, a newly described fungal infection, has emerged in South-east Asia. Oral hairy leukoplakia and Kaposi's sarcoma appear to be associated with male gender and male-to-male HIV transmission risk behaviours. These lesions occur only rarely in children. Additional prevalence data are needed from developing countries prior to substantially altering the 1993 ECC/WHO Classification of oral lesions associated with adult HIV infection. The workshop confirmed current oral disease diagnostic criteria.

Mechanisms of expression of HHV8, EBV and HPV in selected HIV-associated oral lesions.

Opportunistic DNA viruses, particularly members of the herpesvirus family, are frequently the aetiological agents of HIV-associated oral lesions. Oral lesions common to the early phase of the AIDS epidemic, including Kaposi's sarcoma (KS), oral aphthous ulceration, AIDS-associated oral lymphoma, and oral hairy leukoplakia (OHL), have been tested for the prevalence of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV). While EBV DNA is detected by PCR in all of these lesions, abundant viral replication can only be detected in OHL. In OHL, a novel state of EBV infection has been discovered with concurrent expression of replicative and transforming proteins, with all of these proteins contributing to the development of the lesion. Activation of signalling pathways and up-regulation of the viral receptor, proliferative and antiapoptotic genes by these proteins induce several of the histological features common to OHL, such as acanthosis and hyperproliferation. In contrast to other permissive herpesvirus infections, expression of EBV transforming proteins within the permissively infected OHL tissue enables epithelial cell survival and may enhance viral replication. Detection of KSHV in these HIV-infected individuals has been localized only to their saliva. Replicative and latent KSHV gene products have been detected in association with the development of oral KS lesions. EBV, but not human cytomegalovirus (HCMV), has been detected by PCR in minor salivary gland biopsies of HIV-associated salivary gland disease. Human papillomaviruses (HPV) are associated with oral warts in HIV-positive individuals; a diagnosis that appears to be increasing in frequency in the era of highly active antiretroviral therapy. To date, there appears to be little increase in the incidence of HPV-associated oral cancer. The mechanisms of interaction between HIV and HPV are not fully understood. Expression of viral gene products is clearly important and necessary for the development of multiple AIDS-associated oral lesions.

Oral tumours in Tanzanian children based on biopsy materials examined over a 15-year period from 1982 to 1997

To provide information on the types and distribution of oral tumours and tumour-like lesions occurring in a Tanzanian child population aged 0-16 years. Retrospective study of biopsy results from hospital records from 1982-1997. Department of Histopathology, the Muhimbili Medical Centre (MMC) in Dar es Salaam. INTERVENTION/ METHODS: A total of 158 biopsy results, from 75 girls and 83 boys, were retrieved and studied. Malignant tumours were the most frequent (43.0%) followed by benign tumours (30.4%) and tumour-like lesions (26.6%). Burkitt's lymphoma was the most frequent malignant tumour accounting for 88.2% of all malignancies followed by squamous cell carcinoma (4.4%) and oral Kaposi's sarcoma (2.9%). Fibroma, papilloma and haemangioma were the most frequent benign tumours constituting 27.1%, 14.6% and 12.5%, respectively. Odontogenic cysts were the most frequent tumour-like lesions (28.6%) followed by fibrous dysplasia (19%) and giant cell granuloma (16.7%). The six most common oral lesions were Burkitt's lymphoma, fibroma, odontogenic cysts, fibrous dysplasia, papilloma and giant cell granuloma.

Oral manifestations of HIV/AIDS in a Kenyan provincial hospital.

In Kenya many patients exposed to the HIV infection present with orofacial lesions as the primary manifestations of the disease and only a few studies have been performed to document this observation. To clinically evaluate and document the range and pattern of oral lesions in a group of hospitalised patients with HIV-infection. A prospective study. Coast Province General Hospital in Mombasa, Kenya, which is the main referral institution serving a population of approximately two million people. Examination of all the cases included in the study was performed according to the WHO criteria. Both male and female patients aged 16 years and above were selected. The criterion of recruitment was based on a suspicion of immunosuppression, the presence of oral manifestations and the willingness to participate in the study. Prior to the examination each patient had undergone counselling followed by two consecutive screening tests using the ELISA technique. Where indicated incisional biopsy was performed to confirm the clinical diagnosis of the relevant lesions. In collaboration with the medical team, treatment was administered as per the needs of the patient in terms of anti-fungals, antivirals or topical cortisteroids. Of the 61 cases, 25(41%) were males and 36(59%) females with an age range of 19 to 65 years (mean = 34.7 years). While all the cases had periodontal disease, over 80% had candidiasis of the hyperplastic, erythematous and pseudomembraneous types. Lymphadenopathy and angular cheilitis were each diagnosed in 27.9% of the cases; while oral Kaposi's sarcoma was seen in 13% of the patients. Other conditions seen included persistent oral ulceration (11.5%), oral hairy leukopLakia and herpes zoster each constituting 4.9%; herpes simplex, mucosal hyperpigmentation, parotomegaly and facial palsy each comprised six per cent and oral warts seen in one case. In accordance with the pattern and prevalence of oral manifestations in our study, the results were largely consistent with those documented elsewhere. For the alleviation of the morbidity arising from the commonly occurring lesions, early detection is mandatory. Furthermore, documentation of the varied regional patterns of occurrence of these lesions may aid in the rational application of the emerging treatments.

Effect of highly active antiretroviral therapy on frequency of oral warts

To investigate changes in the pattern of oral disease associated with highly active antiretroviral therapy (HAART), we assessed the frequency of these lesions in our clinic over 9 years. We retrospectively studied 1280 patients seen between July, 1990, and June, 1999, and related oral findings to medication use, immune function, and viral load. We found significant decreases in oral candidosis, hairy leucoplakia, and Kaposi's sarcoma over time, but no change in the occurrence of aphthous ulcers. There was an increase in salivary-gland disease and a striking increase in warts: three-fold for patients on antiretroviral therapy and six-fold for those on HAART (p=0.01). This pattern of oral disease in a referral clinic suggests that an increase in oral warts could be occurring as a complication of HAART.

当初エプーリスと診断された口腔内カポジ肉腫の１例

Kaposi's sarcoma is one of the most common diseases in patients with AIDS, but it is rare in Japan. We describe a case of oral Kaposi's sarcoma diagnosed as epulis on the basis of clinical and pathological findings. Chang (1994) reported that Kaposi's sarcoma is associated with human herpesvirus 8 (HHV-8). We confirmed the presence of HHV-8 in this case by the nested PCR method. Moreover, the oral Kaposi's sarcoma indicated that this patient had AIDS.

Outlook in oral and cutaneous Kaposi's sarcoma

We looked at survival of 138 patients with HIV-1-associated Kaposi's sarcoma. Patients with lesions of the oral mucosa had a higher death rate (risk ratio 3.4 [95% CI 1.6-7.1]; p=0.001) than those having exclusively cutaneous manifestations of the disease. Patients with oral Kaposi's sarcoma and a CD4 cell count of at least 150/microL had a similar mortality risk to patients with the cutaneous disease but CD4 cell concentration of no more than 150/microL. Thus, oral Kaposi's sarcoma is an important prognostic marker, at least for patients who do not receive triple antiretroviral therapy.