Kaposi's sarcoma-associated herpesvirus-like DNA sequences (KSHV/HHV-8) in oral AIDS-Kaposi's sarcoma: A PCR and clinicopathologic study

Recently, a new human herpesvirus (KSHV/HHV-8) has been identified in classic, transplant, endemic, and AIDS Kaposi's sarcoma that may be involved in the pathogenesis of Kaposi's sarcoma. The purpose of this study was to evaluate oral AIDS-Kaposi's sarcoma for detection of KSHV/HHV-8 DNA. DNA extracted from 54 oral AIDS-Kaposi's sarcoma lesions (47 initial, 7 postvinblastine treated), 5 non-Kaposi's sarcoma HIV-positive lesions, and 3 non-Kaposi's sarcoma HIV-negative lesions was evaluated by polymerase chain reaction (KS330_233bp amplicon) for KSHV/HHV-8. The AIDS-Kaposi's sarcoma study population consisted of 52 patients (51:1, men:woman; 92% men having sex with men, 8% heterosexual; mean age, 38 years; mean, CD4 59/mm³) Opportunistic infections occurred in 88% (candidiasis, 65%; Pneumocystis carinii pneumonia, 31%; nonoral Kaposi's sarcoma, 25%, mycobacterium avium-intracellulare (MAI), 16%; cytomegalovirus, 14%; herpes simplex virus, 14%). Sexually transmitted diseases occurred in 73% (gonorrhea, 37%; syphilis, 23%; condyloma, 22%; HSV, 16%). Most frequent lesion sites were palate (74%) and gingiva (17%). Most common lesion types were purple nodular (48%) and macular (42%). Histopathologic subtypes were nodular (71%), plaque (27%), and patch (2%). Polymerase chain reaction analysis detected KSHV/HHV-8 DNA in 53 of 54 AIDS-Kaposi's sarcoma lesions (47 of 47 initial, 6 of 7 postvinblastine treatment). KSHV/HHV-8 DNA was not detected in non-Kaposi's sarcoma lesions in HIV-positive or HIV-negative persons. KSHV/HHV-8 DNA sequence is present in a high proportion of oral AIDS-Kaposi's sarcoma lesions. Whether KSHV/HHV-8 is an etiologic agent or a cofactor in the development of this vascular neoplasm is uncertain and remains to be proven. Polymerase chain reaction analysis for KSHV/HHV-8 DNA sequence detection may be helpful in identifying Kaposi's sarcoma in early vascular proliferations, when the characteristic histopathologic features are not present.     

Overview: Kaposi's sarcoma,oral neoplasms

Since the last international workshop on the oral manifestations of HIV in 1993 there has been extremely rapid progress in our knowledge of the possible aetiology of Kaposi's sarcoma (KS) and this is reflected in this section which concentrates mainly on the epidemiology and molecular aspects of KS. Research continues in assessing potential links of oral neoplasms and especially in non-Hodgkin's lymphomas in patients with HIV/AIDS.     

Epstein-Barr virus infection and expression in oral lesions

OBJECTIVE: The prevalence of Epstein-Barr virus (EBV) and the recently discovered Kaposi's sarcoma associated herpes virus, human herpesvirus 8 (KSHV or HHV8), was determined within oral lesions common to HIV infection including OHL, pseudoOHL (PHL), oral lymphoma, oral aphthous ulcers, and an oral Kaposi's sarcoma. METHODS: DNA and RNA were extracted from oral lesions. EBV and HHV8 genomes were detected by Southern blot and polymerase chain reaction (PCR), and viral expression was analyzed using PCR amplification of cDNA. RESULTS: Multiple EBV strains were detected within OHL with recombination across repeat sequences generating new viral variants. EBV expression in OHL included expression of some viral genes, usually expressed in latent infections, that induce the EBV receptor. EBV replication was detected only within OHL lesions but not within adjacent Kaposi's tissue or oral aphthous ulcers while HHV8 was only detected within the Kaposi's lesions. CONCLUSIONS: These findings indicate that the OHL lesion is unique with viral replication and superinfection with additional EBV strains. Expression of the EBV receptor within the OHL lesion may promote superinfection which then activates EBV replication. The consistent detection of EBV replication only within OHL lesions and the detection of HHV8 only within Kaposi's sarcoma, strengthens the etiologic link between EBV and HHV8 infection to these specific pathologies.     

Epstein–Barr virus and human immunodeficiency virus-negative oral plasmablastic lymphoma

Plasmablastic lymphoma (PBL) is an unusual subtype of human immunodeficiency virus (HIV)-related diffuse large B-cell lymphoma that was first described in the oral cavity. HIV-related lymphomas are frequently associated with Epstein-Barr virus (EBV). Recently, dual infection with EBV and human herpesvirus 8 (HHV8) has been demonstrated in PBL. So far, a few cases of PBL occurring in an HIV-negative patient have been documented and all of them were associated with immunosuppression status and/or EBV infection. Here we report a EBV and HHV8-negative oral PBL occurring in an immunocompetent HIV-negative male, which would be the first case.     

Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 and Kaposi sarcoma

Kaposi sarcoma-associated herpesvirus (KSHV) was discovered in 1994 and is now known to be a necessary but not sufficient causative agent of Kaposi sarcoma. While KSHV is likely also the causative agent of primary effusion lymphoma and multicentric Castleman's disease, its causal role has been refuted in the case of multiple myeloma, sarcoidosis, prostate cancer, and amyotrophic lateral sclerosis. The epidemiology of KSHV is both intriguing and challenging. Two epidemiologic findings are clear, but their explanation is unknown. The first is that KSHV is distributed disparately throughout the world, with the virus being common in the general population throughout Africa and the Middle East, but uncommon virtually everywhere else. The second is that even though the virus is uncommon in the general population in industrialized settings, it is disproportionately concentrated among homosexual men in these areas. KSHV has special importance to the dental profession because saliva is the body fluid that harbors it most commonly, although exactly in which ways saliva spreads the virus are not known.     

Pathogenesis of oral Kaposi's sarcoma in HIV-infection: Relevance of endogenous glucocorticoid excess in blood and saliva

Endogenous glucocorticoid excess with concomitant hypercortisolaemia and increased saliva level of the free active hormone, is a common feature of HIV-infected/AIDS patients. Exposure of the oral tissues to virtually uninterrupted high burden of glucocorticoids through saliva may contribute to the high frequency of oral Kaposi's sacoma (KS) in these patients. AIDS-KS cells contain unusually high levels of glucocorticoid receptor protein and recent studies indicate that growth of these cells in culture is significantly stimulated by glucocorticoids, particularly in the presence of growth factors, such as oncostatin-M. The suggestion that glucocorticoid excess may be important in the pathogenesis of KS in AIDS is not in conflict with the suspected aetiological role of newly reported KS-associated herpesviruses (KSHV), since steroid hormones may upregulate the expression of the viral gene. The latter is consistent with the observation that infection by specific oncogenic viruses does not necessarily result in cancers in the human, and does require the presence of other cellular factors or events.     

Oral EBV and KSHV infection in HIV

The gamma herpesviruses, Kaposi's-sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are tightly associated with the development of AIDS-associated oral disease and malignancy during immune suppression. The objective of this investigation was to characterize oral infection and pathogenesis in healthy and immune-suppressed individuals. To characterize oral EBV and KSHV infection, we examined throat washings and oral epithelial cells from HIV-positive and HIV-negative individuals. Quantitative/real-time polymerase-chain-reaction (PCR) assays, transmission electronmicroscopy, immunostaining, and sequence analysis were used to identify viral infection. Virus was isolated from throat-wash samples and was used to infect epithelial and lymphoid cell lines. We detected EBV and KSHV in the oral cavity in healthy and immune-suppressed individuals. Viral strain analysis of KSHV K1 in multiple clones from the oral cavities of healthy persons and immunosuppressed patients detected several strains previously detected in KS lesions, with minor strain variation within individuals. Immunoelectron microscopy for multiple viral antigens detected consistent expression of viral proteins and oral epithelial specimens. In oral epithelial cells infected with wild-type KSHV in vitro, the K8.1 glycoprotein associated with lytic KSHV infection was detected in both primary and telomerase immortalized oral epithelial cultures by 24 hours post-infection. Virions were detected, subsequent to infection, by scanning electron microscopy. Oral epithelial cells were also infected in vitro with wild-type EBV originating from throat washes. Analysis of these data suggests that, like EBV, KSHV infection is present in the oropharynx of healthy individuals, is transmissible in vitro, and may be transmitted by saliva.     

Oral HIV‐associated Kaposi sarcoma

J Oral Pathol Med (2012) Kaposi sarcoma (KS), an AIDS defining condition, remains one of the most commonly HIV‐associated neoplasms. While the use of highly active antiretroviral therapy (HAART) has brought about a dramatic decrease in the prevalence and incidence of AIDS‐KS worldwide, this has not been the case in resource‐poor sub‐Saharan African countries, where HIV has reached epidemic proportions and human herpesvirus‐8 infection is endemic. Oral involvement is a common manifestation of AIDS‐associated KS and may be an early presenting finding of HIV infection. The clinical manifestation of oral KS can vary and may have an unpredictable course ranging from mild to fulminant. Rapidly progressive facial lymphoedema associated with extensive advanced oral KS portends a poor prognosis. Oral KS may regress with antiretroviral therapy or may flare up as part of the immune reconstitution inflammatory syndrome. The oral lesions of AIDS‐KS are best managed with HAART together with systemic chemotherapy. This article provides a review of contemporary knowledge of the biology, pathology, clinical features and management of oral AIDS‐KS.     

The Prevalence of EBV and KSHV in Odontogenic Lesions

ObjectivesOdontogenic lesions evolve as a result of altered dental development. This study aimed to evaluate the prevalence and the coinfection of Epstein-Barr virus (EBV) and Kaposi sarcoma–associated herpesvirus (KSHV) in radicular cysts, dentigerous cysts, odontogenic keratocysts, and ameloblastomas.MethodsPolymerase chain reaction (PCR) was used to analyse 66 cases of odontogenic lesions for the presence of EBV-DNA and KSHV-DNA. These lesions were 15 radicular cysts, 16 dentigerous cysts, 18 odontogenic keratocysts, and 17 ameloblastomas.ResultsEBV-DNA was detected in 24 (36.4%) of the studied samples as follows: 6 samples (40.0%) of radicular cysts, 4 (25.0%) of dentigerous cysts, 10 (55.6 %) of odontogenic keratocysts, and 4 (23.5%) of ameloblastomas (P = .168). KSHV-DNA was found in 16 (24.2%) of the studied samples as follows: 1 sample (6.7%) of radicular cysts, 6 (37.5%) of dentigerous cysts, 8 (44.4 %) of odontogenic keratocysts, and 1 (5.9%) of ameloblastomas (P = .001). Additionally, EBV and KSHV were positively correlated in all studied samples (P = .002).ConclusionsBoth EBV and KSHV are found in odontogenic cysts and ameloblastomas. KSHV and EBV are more prevalent in odontogenic keratocysts than in other studied odontogenic lesions. Further, there is a high prevalence of EBV and KSHV coinfection in odontogenic cysts and ameloblastomas.     

Comparison of apoptosis and apoptosis-related gene products between extranodal oral B-cell lymphoma and maxillofacial nodal B - cell lymphoma

Twenty-seven cases of primary extranodal oral B-cell lymphoma and 22 cases of primary maxillofacial nodal B-cell lymphoma were investigated for the presence of apoptotic cells and the expression of apoptosis-related gene products by terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL) and immunohistochemistry. The majority of extranodal oral diffuse large B-cell lymphomas (17/25, 68%) and maxillofacial nodal diffuse large B-cell lymphomas (14/16, 88%) contained no or less than 10% apoptotic cells. Whereas the majority of extranodal oral diffuse large B-cell lymphomas (18/25, 72%) and maxillofacial nodal diffuse large B-cell lymphomas (13/16, 81%) contained more than 10% of Ki-67-positive cells. Bcl-2-, Bax-, p53- and Ki-67-positive rates were higher in maxillofacial nodal diffuse large B-cell lymphomas than in extranodal oral diffuse large B-cell lymphomas, but only Bax (chi2 test, 0.01相似文献   

Evaluation of fine needle aspiration cytology in the diagnosis of cervical lymph node lymphomas

Purpose

Surgical biopsy examination is the gold standard for the diagnosis of lymph node lymphomas. Fine-needle aspiration cytology (FNAC) is a quick and safe method in the management of cervical lymph nodes. Its value in confirming recurrent or residual lymphoma is well established. However, its role in the primary diagnosis of lymph node lymphoma remains controversial. The aim of this study was to assess, in our experience, the reliability of FNAC in the diagnosis of cervical lymph node lymphomas.

Characteristics of oral and paraoral malignant lymphoma: a population-based review of 361 cases.

BACKGROUND: Lymphoma is the second most common neoplasm of the head and neck; almost 50% of all lymphomas occur in this region. Waldeyer's ring is the most common site of lymphomas involving the oral region. The purpose of this study was to review the characteristics of a large series of malignant lymphoma of the oral region. METHODS: Three hundred sixty-one consecutive cases of malignant lymphoma of the oral region were identified in the Tumor Registry between 1969 and 1998. RESULTS: The 361 cases (200 males and 161 females) of malignant lymphoma of the oral region accounted for 3.5% of all oral malignancies. The mean age was 62.5 years and the most prevalent site of involvement was the tonsil (32.7%), followed by the parotid gland (16.1%). Sixty-five percent of the lesions were diagnosed as large-cell (38%) or small-cell (27%) lymphoma. One quarter of the patients died of the disease in a mean of 2.78 years after diagnosis. Of a total 26 patients who died from other causes, 12 died because of other cancers, including 7 (27%) with leukemia and 5 (19%) with oral carcinoma. The prognosis is based, at least partially, on the histologic grading (low, intermediate, or high) and the anatomic stage of the disease. Localized low-grade lymphomas have a more favorable prognosis compared with those that are disseminated and/or have high-grade cellular changes. CONCLUSION: Lymphoma is the second most common malignant oral disease. Thorough head and neck and oral examination is necessary to identify lesions that may represent lymphoma.     

Primary extranodal non-Hodgkin''s lymphoma of the oral region

Seventy cases (47M, 23F) of primary extranodal non-Hodgkin's lymphoma of the oral region were studied to determine tumor characteristics. The most frequent disease sites were the palate (21 cases), gingiva (17 cases) and parotid gland (13 cases). Each lymphoma was classified according to the criteria of the Working Formulation for Clinical Usage. Only 5.7% of cases were follicular lymphomas while diffuse lymphomas had a high incidence. Histologic subtypes included small lymphocytic (1%), small cleaved cell (7%), mixed small and large cell (20%), large cell (43%), large cell, immunoblastic (17%), lymphoblastic (9%) and small non-cleaved cell lymphoma (3%). Immunologic study utilizing the avidin-biotinylated horseradish peroxidase complex (ABC) technique demonstrated the presence of intracytoplasmic monoclonal immunoglobulin in 24 (34%) of the suggested B-cell lymphoma cases; 20 tumors (28%) were classified as T-cell lymphoma based on a positive reaction for mouse monoclonal antibody (UCHL-1) to T-cell related membrane antigen; 11 tumors (16%) contained intracytoplasmic alpha 1-antitrypsin, suggesting true histiocytic lymphoma; 15 tumors (22%) did not contain immunoglobulin, UCHL-1 or alpha 1-antitrypsin positive cells and showed no definite characteristics.     

US1HIV – changing patterns in HAART era,patients’ quality of life and occupational risks

Oral manifestations are early and important indicators of HIV‐infection. Several lesions with strong association to HIV infection have been described: oral candidiasis (OC), oral hairy leukoplakia (OHL), Kaposi's sarcoma (KS), Non‐Hodgkin‐Lymphoma (NHL), necrotising ulcerative gingivitis and periodontitis. These lesions may be present in up to 50% of patients with HIV‐infection and up to 80% of those with AIDS. Changing patterns in HAART era: With the advent of highly active antiretroviral therapy (HAART) the prevalence of OC, OHL and HIV – associated periodontal disease has decreased in adults. The prevalence of KS has not changed. However, there has been an increase in HPV‐associated oral lesions (papillomas, condylomas and focal epithelial hyperplasia) and HIV‐related salivary gland disease. In children receiving HAART no change in the prevalence of HIV‐related oral lesions has been found. Quality of life: The presence of oral lesions has a marked impact on health related quality of life. HIV‐associated orofacial lesions may lead to facial disfigurement (KS, NHL) or may impair speech and swallowing. Consequently, weight loss and pain may be result. Studies have shown that patients with OC, angular cheilitis and OHL have a high score of decayed teeth (DMFT). Xerostomia and taste disturbances may also be factors with impact on quality of life. Occupational risks: Occupational exposure to HIV has resulted in 57 documented cases of HIV sero‐conversion among healthcare workers in the US (December 2001). Exposure to HBV and HCV carries a much higher risk of occupational infection than that for HIV‐exposure.     

Plasmablastic lymphoma: a case report.

Plasmablastic lymphoma is a rare subcategory of non-Hodgkin lymphoma frequently associated with human immunodeficiency virus. It is a large B-cell lymphoma that has a predilection for the oral cavity. Clinically, plasmablastic lymphoma may mislead to a diagnosis of Kaposi's sarcoma. When infected, plasmablastic lymphoma may mimic an odontogenic cellulitis. Epstein-Barr virus and human herpesvirus 8 are very often associated. Awareness of this entity can prevent misdiagnosis with nonlymphoid malignancies, notably Kaposi's sarcoma, because this lesion does not express the conventional B-cell markers. Unfortunately, as for other high-grade lymphomas in patients with acquired immunodeficiency syndrome (AIDS), the prognosis is poor. The case of a heterosexual 42-year-old man referred for a right hemifacial neoplasm is reported.     

HIV-associated Kaposi sarcoma: pathogenic mechanisms

Kaposi sarcoma (KS) is a multicentric angioproliferative disorder characterized by spindle cell proliferation, neo-angiogenesis, inflammation, and edema. Human herpesvirus (HHV)-8, a gamma-herpesvirus, is a critical factor, but is not alone sufficient for the initiation of KS. Other cofactors such as human immunodeficiency virus (HIV), host-derived cytokines, chemokines, and growth factors are required for the development of KS. Whether HIV-associated KS is a reactive hyperplastic inflammatory lesion or a true neoplasm is still controversial. It is likely that HIV-associated KS begins as a reactive disorder that in some cases progresses to a monoclonal, an oligoclonal, and a polyclonal neoplasm.     

Hodgkin's disease involving the Gingiva in AIDS

Non-Hodgkin lymphomas are a recognised complication of AIDS and may involve the oral cavity. However, no case of Hodgkin's disease affecting the oral cavity in AIDS appears to have been recorded. We report a male homosexual with AIDS and Hodgkin's lymphoma, who presented with gingival involvement.     

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 non-glossal 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.     

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

OBJECTIVES: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.