Kaposi肉瘤组织内人类疱疹病毒8型的K15基因型研究

目的 了解Kaposi肉瘤组织中人类疱疹病毒8型(HHV-8)K15等位基因型分布情况,并初步探讨Kaposi肉瘤不同临床分型及临床表现与不同HHV-8 K15等位基因型的相关性.方法 采用酚-氯仿-异戊醇法对收集的27例Kaposi肉瘤石蜡包埋组织标本进行病毒DNA抽提,并使用巢式PCR扩增K15基因片段,然后测序并确定其等位基因型.结果 27例Kaposi肉瘤中有22例HHV-8感染为阳性,阳性率为81.48%,其中4例艾滋病-Kaposi肉瘤患者HHV-8感染均为阳性,感染率100%;在分析的22例HHV-8病毒株中,20例为P型,2例为M型;4例艾滋病-Kaposi肉瘤患者感染的均为P型HHV-8,2例M型感染者均为经典型Kaposi肉瘤患者.结论 Kaposi肉瘤组织内HHV-8的K15等位基因型主要是P型,也存在部分M型HHV-8感染者.4例艾滋病-Kaposi肉瘤患者感染的HHV-8均为P型.     

Kaposi肉瘤组织内人类疱疹病毒8型K1基因型的初步分析

A5和C7亚型,与非洲和欧洲来源毒株的同源性很高.     

Clinical exuberance of classic Kaposi's sarcoma and response to radiotherapy

Kaposi''s sarcoma (KS) is a multicentric vascular neoplasm, with cutaneous and extracutaneous involvement. Different clinical and epidemiological variants have been identified. The classic form is manifested mainly in elderly men with indolent and long-term evolution, with lesions localized primarily in the lower extremities. We present two cases of classic Kaposi''s sarcoma (CKS) in two female patients with extensive, exuberant skin involvement and rapid evolution, with good response to radiotherapy.     

人类疱疹病毒8型基因型的研究进展

人类疱疹病毒8型广泛存在于各种临床表型的Kaposi肉瘤中,其基因型分布呈现种族与地域特异性.了解Kaposi肉瘤患者中HHV-8基因型特征及分布情况,探讨其与Kaposi肉瘤临床可能的相关性和演变及传播等具有重要意义.并对HHV-8病毒体及其基因组特征,K1和K15基因位点的生物学功能.HHV-8基因型演变呈现地域与种族特异性进行概述.     

Asymmetrical transmission of human herpesvirus 8 among spouses of patients with Kaposi sarcoma

Background  Among heterosexuals, the sexual transmission of human herpesvirus 8 (HHV8) has not been established.
Objectives  To assess HHV8 seroprevalence in spouses of patients with classic and endemic Kaposi sarcoma (KS) and to suggest possible routes of transmission.
Methods  A case–control study was carried out in a teaching hospital among spouses of human immunodeficiency virus-negative patients with KS (cases – exposed subjects) and controls who did not have KS nor were related to patients with KS (nonexposed subjects). HHV8 seroprevalence in spouses of patients with KS was compared with HHV8 seroprevalence in controls matched for age, gender and place of birth. Other serology tests were compared between cases and controls. Among heterosexual couples, HHV8-seropositive and HHV8-seronegative spouses were compared for possible risk factors for virus transmission.
Results  HHV8 seroprevalence was significantly higher among spouses of patients with KS (13 of 22; 59%) than among matched controls (19 of 58; 33%; P  =   0·043). Among heterosexual couples, five of five (100%) male spouses were HHV8 positive vs. six of 15 (40%) female spouses ( P  =   0·04). There was no significant difference between HHV8-seropositive and HHV8-seronegative spouses for all other factors screened for among heterosexual couples.
Conclusions  Being a spouse of a patient with KS is a risk factor for HHV8 seropositivity. Our results suggest that female-to-male HHV8 transmission could be more efficient than male-to-female transmission among couples including a patient with KS. Transmission could involve distinctive behaviours, or currently unknown biological properties of HHV8.     

人类疱疹病毒8型ORF26基因亚型与Kaposi肉瘤的相关性研究

目的 明确Kaposi肉瘤患者感染的人类疱疹病毒8型（HHV-8）ORF26基因亚型分类，初步探讨其与Kaposi肉瘤不同临床分型及侵袭性的相关性。方法 对32例Kaposi肉瘤石蜡包埋组织进行HHV-8 DNA抽提、扩增、双向测序，使用DNAStar软件、Clustal W软件和PHYLIP软件包对测序结果进行系统发生学分析，从而确定HHV-8 ORF26基因亚型，最后运用Fisher确切概率法对结果进行统计学分析。结果 32例Kaposi肉瘤中有30例HHV-8阳性，阳性率为93.75%，其中6例艾滋病相关型患者HHV-8均阳性。30例HHV-8阳性患者中，17例为HHV-8 ORF26 A亚型，13例为C亚型。不同亚型间Kaposi肉瘤患者有无黏膜损害及临床分型的分布差异均无统计学意义（P > 0.05）。结论 Kaposi肉瘤患者感染HHV-8 ORF26亚型属于A亚型和C亚型，不同亚型与黏膜损害及临床分型无关。     

Acroangiodermatitis (pseudo-Kaposi's sarcoma) in an HIV sero-positive patient with syphilis and hepatitis C virus coinfection: clinical and dermatopathological features

Acroangiodermatitis is an angioproliferative disease usually related to chronicvenous insufficiency, and it is considered a clinical and histological simulator ofKaposi''s sarcoma (KS). Immunohistochemistry is the suitable method to differentiatebetween these two entities. It reveals the following immunostaining profile:immunopositivity with anti-CD34 antibody is restricted to the vascular endothelium inacroangiodermatitis, and diffuse in the KS (endothelial cells and perivascularspindle cells); immunopositivity with anti-HHV-8 only in KS cases. We report the caseof an HIV seropositive patient without apparent vascular disease, who presentedviolaceous and brownish erythematous lesions on the feet, and whose histopathologyand immunohistochemistry indicated the diagnosis of acroangiodermatitis.     

人疱疹病毒8型ORF75基因亚型与Kaposi肉瘤的相关性研究

目的 探讨人类疱疹病毒8型(HHV-8)ORF75基因亚型,与Kaposi肉瘤不同临床分型及侵袭性的相关性.方法 对25例新疆Kaposi肉瘤石蜡包埋组织进行HHV-8 DNA抽提、扩增及双向测序,使用Clustal W软件和PHYLIP软件包对测序结果进行发生学分析,从而确定HHV-8 ORF75基因哑型.结果 25例Kaposi肉瘤中,21例HHV-8阳性,阳性率为84%,其中7例AIDS相关型Kaposi肉瘤患者HHV-8均阳性.21例HHV-8阳性患者中,18例为HHV-8 ORF75 A亚型,3例为C亚型;不同亚型间Kaposi肉瘤患者有无黏膜损害及临床分型的分布差异均无统计学意义(P＞0.05).结论 新疆Kaposi肉瘤患者感染HHV-8 ORF75亚型属于A亚型和C亚型,HHV-8 ORF75不同亚型可能与新疆Kaposi肉瘤黏膜损害及临床分型无关.     

The effects of human herpesvirus 8 infection and interferon-gamma response in cutaneous lesions of Kaposi sarcoma differ among human immunodeficiency virus-infected and uninfected individuals

Background Kaposi sarcoma (KS) is associated with human herpesvirus 8 (HHV‐8). The cutaneous immune response in this tumour is not well established and a better understanding is necessary. Objectives To evaluate the HHV‐8 expression and immune response in cutaneous lesions of classic KS (CKS) and AIDS‐associated KS (AIDS‐KS). Methods We performed a quantitative immunohistochemical study of cells expressing HHV‐8 latency‐associated nuclear antigen (LANA), CD4, CD8 and interferon (IFN)‐γ in skin lesions from patients with CKS and AIDS‐KS (with or without highly active antiretroviral therapy, HAART). Results CKS showed higher LANA expression compared with AIDS‐KS, regardless of HAART. We also found higher LANA expression in nodules compared with patch/plaque lesions. The tissue CD4+ cell proportion was lower in AIDS‐KS patients without HAART than in patients with CKS. In CKS lesions, CD4+ and CD8+ cells expressed IFN‐γ, as shown by double immunostaining. AIDS‐KS presented low numbers of IFN‐γ‐expressing cells. CD8+ cell numbers were similar in all groups, which appeared unrelated to the clinical or epidemiological type of KS. Conclusions Our quantitative data on the pattern of KS lesions in selected groups of patients, as shown by in situ immune response, demonstrated a CD4+ T‐cell involvement associated with IFN‐γ, an environment of immune response‐modified human immunodeficiency virus (HIV) infection. In our sample, the promotion of KS in patients without HIV appears to be related to higher HHV‐8 load or virulence than in those with AIDS. This higher resistance may be explained by a sustained immune response against this herpesvirus, that is only partially restored but effective after HAART.     

Case report of cutaneous histiocytic sarcoma: diagnostic and therapeutic dilemmas

Histiocytic sarcoma is a rare hematologic malignant neoplasia originating from histiocytic or dendritic cell clones. The lesions may be in nodal or extranodal sites, most commonly in the gastrointestinal tract. A small number of cases presents as unique cutaneous lesions. The definitive diagnosis is made by positivity for the immunohistochemical markers CD163, CD68, CD4 and lysozyme. The treatment is controversial, often with combined systemic chemotherapy. This is a case of cutaneous histiocytic sarcoma in an 82-year-old patient presenting two nodular lesions in the breast and right arm which were treated with simple excision and multidisciplinary follow-up, avoiding aggressive management and exhaustive investigations. Although most studies report aggressive evolution, the patient had good and stable clinical status during the twelve-month follow-up period.     

Serological and immunohistochemical detection of human herpesvirus 8 in Kaposi's sarcoma after immunosuppressive therapy for bullous pemphigoid

Kaposi's sarcoma (KS) developed in an 87-year-old human immunodeficiency virus-negative woman from Hokkaido island 4 months after oral administration of prednisolone for the treatment of bullous pemphigoid (BP), and rapidly disseminated to almost the entire body within 2 months. The open reading frame (ORF) 59 and ORF73 proteins encoded by human herpesvirus 8 (HHV-8) were detected immunohistochemically in the nuclei of the tumour cells of KS. The protein coded by ORF73, latent protein, was detected in most of the nuclei of the tumour cells, but only a few tumour nuclei were positive for the ORF59 protein, a lytic protein expressed during active infection. The antibodies against both lytic and latent proteins of HHV-8 were detected retrospectively in the serum 4 months before the appearance of KS and before prednisolone therapy had been started. Immunosuppression associated with the treatment for BP possibly activated latent HHV-8 infection and induced the development of KS.     

Detection of Epstein-Barr virus and human herpesvirus 7 and 8 genomes in primary cutaneous T- and B-cell lymphomas

BACKGROUND: Several studies have investigated the possible involvement of viral agents, particularly herpesviruses, in primary cutaneous lymphoma (PCL). OBJECTIVES: Our aim was to screen for the presence of human herpesvirus 7 (HHV-7) and 8 (HHV-8) genomes in samples of PCL, and to determine if their presence was independent of Epstein-Barr virus (EBV). METHODS: Screening was performed using polymerase chain reaction assay in 64 skin samples from historical lesional tissues with PCL. RESULTS: Only nine cases showed positivity for HHV-7: four of 29 mycosis fungoides (MF), two of four CD30-positive large-cell cutaneous T-cell lymphoma (CTCL), two of 12 follicle centre cutaneous B-cell lymphoma (CBCL) and one of nine marginal zone CBCL. Fifteen cases tested positive for EBV: seven of 29 MF, two of four pleomorphic small/medium sized CTCL, three of three angiocentric CTCL, one of 12 follicle centre CBCL and two of nine marginal zone CBCL. All cases were uniformly negative for HHV-8. No simultaneous positivity was found for EBV and HHV-7. Controls tested negative for all viruses. CONCLUSIONS: The findings indicate that EBV, HHV-7 and HHV-8 seem not to be involved in the pathogenesis of PCL.     

Detection of human herpesvirus 8 in Korean Kaposi's sarcoma cases by polymerase chain reaction and in situ polymerase chain reaction.

Several infectious agents, including herpesvirus-like particles, had been suggested as possible candidates for the development of Kaposi's sarcoma (KS), and a new herpesvirus, human herpesvirus 8 (HHV-8), was recently identified in the vast majority of KS lesions, irrespective of their association with human immunodeficiency virus (HIV) infection. However, the etiologic role of HHV-8 in KS remains controversial. We undertook this study to screen for and localize the presence of HHV-8 in KS in Korea. A total of 46 paraffin-embedded specimens were studied, including KS, hemangioproliferative disorders, and 10 non-KS lesions from HIV-positive patients. We performed nested polymerase chain reaction (PCR) and in situ PCR with HHV-8 specific primers. HHV-8 DNA sequences were detected in 8 of 11 KS specimens. All specimens of hemangioproliferative disorders, non-KS lesions from HIV-positive patients, and other skin samples were negative for HHV-8. When sequencing PCR products, the sequences were almost identical with the prototypic sequence for HHV-8. In PCR-positive tissues, in situ PCR staining of HHV-8 localized to nuclei of endothelial cells and perivascular spindle-shaped tumor cells. The results of this study suggest that HHV-8 is not widespread and has a certain causative role in the development of KS. Further studies, including serological and animal studies, will be helpful to appreciate an epidermiological link and pathogenetic mechanism between HHV-8 and KS.     

Human herpesvirus type 8 and Epstein–Barr virus-associated cutaneous lymphoma taking anaplastic large cell morphology in a man with HIV infection

Human herpesvirus type 8 (HHV-8, Kaposi's sarcoma-associated herpesvirus)-positive lymphoma taking anaplastic large cell morphology in the skin is described in a 46-year-old man with AIDS. Multiple erythematous nodules appeared on the trunk and extremities during the treatment of AIDS. Histological examination of cutaneous nodules showed dense infiltration of CD30 + atypical lymphoid cells in the deep dermis. Immunoglobulin JH gene rearrangement was detected in these lymphoma cells. Both Epstein-Barr virus-encoded small RNA and HHV-8 mRNA (T1.1/nut-1) were detected in these lymphoma cells by in situ hybridization. Remarkable retention of the pericardial fluid was observed at the same time that cutaneous lesions grew, and lymphoma cells in the pericardial fluid showed the same phenotype as the cutaneous lymphoma. Chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone effectively reduced both the cutaneous nodules and pericardial fluid. However, the patient died 4 months after diagnosis because of cytomegalovirus infection. As far as we know, this is the first report of an HHV-8-positive cutaneous lymphoma taking anaplastic large cell morphology. This case suggests the association of AIDS-related anaplastic large cell lymphoma with HHV-8.     

Kaposi肉瘤患者血清人类疱疹病毒8型的检测

目的：了解干扰素治疗Kaposi肉瘤近期疗效及其对血清HHV-8 DNA检测的影响。方法：主要应用干扰素治疗4例无明显内脏损害的新疆经典型Kaposi肉瘤患者，同时在治疗前后采用PCR法检测血清HHV-8 DNA特异性片段。结果：4例患者经干扰素治疗45d后，均有不同程度的近期疗效，主要表现在皮损色泽变暗、结节和斑块变软、变平，部分小结节消退，且均无新皮损发生。但淋巴水肿无明显改观。血清HHV-8 DNA特异性片段经PCR检测，治疗后全部转阴。结论：干扰素治疗可有效地清除Kaposi肉瘤患者血清中HHV-8感染，能缓解病情，防止Kaposi肉瘤多灶病状的发生。     

No evidence for a role of human herpesvirus type 8 in sarcoidosis: molecular and serological analysis

The aim of this study was to analyse the association between human herpesvirus type 8 (HHV8) and sarcoidosis. Using nested polymerase chain reaction (PCR), we tested the presence of HHV8 DNA sequences in 13 skin specimens and peripheral blood mononuclear cells from eight patients suffering from sarcoidosis. We also looked for the presence of HHV8 antibodies in the sera of 28 patients with sarcoidosis using three techniques: two indirect immunofluorescence assays and an enzyme-linked immunosorbent assay with recombinant capsid protein fragment encoded by open-reading frame 65. HHV8 PCR analysis was negative while HHV8 serological studies showed an overall prevalence of 18% among patients suffering from sarcoidosis: 43% in patients from sub-Saharan Africa, 17% in patients from Northern Africa, 12.5% in patients from the French West Indies and 0% in French patients. In conclusion, our results do not indicate an association between HHV8 and sarcoidosis but reflect the seroepidemiology of this virus in different geographical regions.     

Immunohistochemical evidence of α-, β- and γ3-melanocyte stimulating hormone expression in cutaneous malignant melanoma of nodular type

Opiomelanocortins are formed after cleavage of the larger precursor molecule, proopiomelanocortin (POMC), which contains several peptide residues, sharing certain amino acid homology, including adrenocorticotrophic hormone (ACTH) and α-, β- and γ-melanocyte stimulating hormone (MSH). The expressions of α-, β- and γ3-MSH in human cutaneous malignant melanoma of nodular type are demonstrated. For the MSHs, the immunolabelling was concentrated mostly in the tumour cellular cytoplasm, with occasional cells displaying a nuclear staining. Labelled tumour cells were dispersed throughout the epidermis and dermis as individual cells or in so-called 'pearl-like nests', most of which consisted mainly of round or oval shaped cells as well as a few pleomorphic or spindle-shaped cells. The fluorescence intensity seemed to increase in accordance with the development of the tumours. All cases examined were clearly stained with protein S-100, which provided us with a definite diagnosis. Considering the overall MSHs-related staining intensity of each section, the general perception we got was that the closer to the centre of the tumour parenchyma, the stronger was the staining and, furthermore the larger/more poorly differentiated the cells, the stronger was the staining. We also found the MSHs expressions to appear in the peripheral part of the tumour and the perilesional tissues including epidermis, sweat glands, sebaceous glands as well as hair follicles. Neurohypertrophic features were encountered including increases in both the number of nerve fibres and their diameter. Our results presented here strongly support the viewpoint earlier proposed that MSH peptides, by an autocrine and/or paracrine production from melanoma cells, are engaged in the regulation of melanogenesis, growth and proliferation of the tumour cells. We also conclude that, although α-, β- and γ3-MSH peptides do not provide as high a sensitivity for diagnosis as protein S-100, they appear as useful markers for supportive diagnosis and assessment of malignant melanoma.