Simultaneous onset of primary cutaneous B-cell lymphoma and human herpesvirus 8-associated Kaposi's sarcoma

We report the simultaneous occurrence of Kaposi's sarcoma (KS) and primary cutaneous B-cell lymphoma (CBCL) of the leg in a 79-year-old woman, seronegative for HIV-1, HTLV-1 and HTLV-2. The CBCL underwent complete clinical remission after local radiotherapy, whilst the KS became disseminated within a year following diagnosis. However, 2 years after the diagnosis of KS, the patient died with neurological symptoms. These were presumed to be due to involvement of the central nervous system by lymphoma, although in the absence of an autopsy, this could not be proven. Skin biopsies from the original KS and CBCL lesions, as well as short-term culture of spindle cells from the KS lesion and peripheral blood mononuclear cells (PBMC), were studied by semiquantitative polymerase chain reaction (PCR) using primers specific for DNA sequences of a novel γ-herpesvirus-8 (HHV-8). PCR studies were strongly positive for the virus on KS cells and PBMC; conversely, a low viral load was found on CBCL cells. A high titre of serum IgG antibodies reacting with the nuclei of the HHV-8 positive cell line BCP-1 was found. These data suggest that reactivation of latent infection with HHV-8 had occurred in this patient, and that HHV-8 is directly involved in KS, but not in CBCL of the leg, an aggressive variant of CBCL.     

KSHV/HHV8-associated primary cutaneous plasmablastic lymphoma in a patient with Castleman's disease and Kaposi's sarcoma

Abstract:  We report a unique case of Kaposi's sarcoma (KS)-associated herpesvirus (KSHV)/human herpesvirus (HHV)8-associated lymphoma in a 56-year-old man with a history of acquired immune deficiency syndrome, Castleman's disease, KS, and idiopathic thrombocytopenic purpura. Three months following the diagnosis of KS affecting a left cervical lymph node and Castleman's disease with bone marrow involvement, he presented with a subcutaneous, tender lesion on his left arm. A skin biopsy demonstrated a superficial and deep, interstitial-nodular infiltrate of severely atypical lymphoid cells showing plasmacytoid features, numerous mitotic figures, and frequent individual apoptotic tumor cells. The morphologic features were those of plasmablastic lymphoma (PBL). Immunohistochemical study showed that the lymphoma cells strongly expressed CD45, CD30, and KSHV/HHV8 latency-associated nuclear antigen. KSHV/HHV8 was also detected in the biopsy sections of the patient's KS and Castleman's disease. Epstein–Barr virus in situ hybridization was diffusely positive. In situ hybridization demonstrated κ-light chain restriction. Although KSHV/HHV8 has been individually associated with KS, Castleman's disease, and PBL, this appears to be the first reported case in which all three entities were present simultaneously in one person, suggesting a critical role of KSHV/HHV8 as a common denominator in the pathogenesis of these diseases.     

Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection

Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation.     

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.     

Absence of human herpesvirus 8 and Epstein-Barr virus genome sequences in cutaneous epithelial neoplasms arising in immunosuppressed organ-transplant patients

Recent studies have implicated herpesvirus 8 and Epstein-Barr virus in the development of cutaneous malignancies in immunosuppressed patients. In order to examine the strength of this association, we examined 37 malignant, pre-malignant and benign cutaneous epithelial neoplasms removed from immunosuppressed organ recipients for the presence of human herpesvirus 8 and Epstein-Barr viral genome sequences using polymerase chain reaction (PCR) and in situ hybridization. We examined 2 actinic keratoses, 1 benign keratosis, 11 invasive squamous cell carcinomas, 17 squamous cell carcinomas in situ and 6 basal cell carcinomas. We also examined 4 basal cell carcinomas, 1 invasive squamous cell carcinoma and 3 squamous cell carcinomas in immunocompetent hosts. In contrast to findings reported by other investigators, we were unable to detect viral genome sequences in any of the biopsies examined. Our findings suggest that human herpesvirus 8 and Epstein-Barr virus likely do not play an etiologic cogenesis in immunocompromised patients.     

Detection of human herpesvirus 8 sequences in cutaneous cherry angiomas

Cherry angiomas (CAs) are common vascular benign skin tumors, characterized by abnormal angiogenesis, whose etiology is still unclear and poorly studied. We investigated the presence of HHV8 in CAs due to virus ability of inducing neoangiogenesis in endothelial cells. A total of 29 patients were enrolled in a randomized, controlled, blinded analysis of skin specimens including various vascular lesions. All clinical samples were anonymized and analyzed by three different biomolecular assays to minimize the risk of false positive/negative results. Results showed that 53 % of eruptive CAs harbor HHV8 sequences, with the highest viral loads in samples derived from immunosuppressed patients. By contrast, no paucilesional CAs were positive for HHV8. Considering HHV8 prevalence in the Mediterranean population (10–15 %), results obtained in eruptive CAs are significant and suggest for the first time a possible involvement of HHV8 in eruptive cherry angiomas development, particularly in the context of immunosuppression, similar to that recognized for major HHV8-induced pathologies.     

A report of Epstein-Barr virus-positive primary cutaneous natural killer-/T-cell lymphoma

We describe a patient who presented with Epstein-Barr virus-positive tumor-stage primary cutaneous lymphoma. Our patient had previously been treated with oral methotrexate for long-standing rheumatoid arthritis. Tissue analysis revealed large tumor cells that were surface CD2- and CD3-positive; T-cell-restricted intracellular antigen-positive; CD56-, CD20-, and CD30-negative; and stained positively for Epstein-Barr virus. Our case is noteworthy for several reasons. Although the presence of rheumatoid arthritis and therapy with methotrexate are putative risk factors for the development of immune suppression-related and Epstein-Barr virus-related lymphomas, the vast majority of lymphomas in this setting are of B-cell origin, and rarely are these primary cutaneous in nature. In addition, our patient's tumor displayed an unusual phenotype, with immunophenotypic features suggestive of an atypical natural killer-/T-cell lymphoma. Methotrexate was withdrawn, and our patient was successfully treated with local radiotherapy. She has remained in complete remission 28 months since diagnosis.     

原发于皮肤的老年人EB病毒阳性弥漫大B细胞淋巴瘤一例

患者男,88岁。双下肢多发结节、溃疡6个月。皮肤科检查：双下肢多个暗紫色结节,触之较硬,中央溃疡、结痂。组织病理检查：真皮内及皮下组织淋巴样细胞弥漫浸润,细胞核大、深染,异形性明显,可见核分裂象,部分区域可见小灶状坏死。大淋巴样细胞表达CD20、CD79a、Bcl?2,EB病毒编码RNA原位杂交阳性。诊断：EB病毒阳性弥漫大B细胞淋巴瘤。患者放弃系统化疗,确诊6个月后死亡。     

皮肤CD8+亲表皮性T细胞淋巴瘤一例

75岁男性患者,躯干、四肢出现瘙痒性红斑、斑块和苔藓样皮疹5年.皮肤科检查:颈部、躯干和四肢泛发暗红、灰黑色浸润性斑片和斑块,以背部为甚.全身浅表淋巴结无肿大,未发现系统受累情况.组织病理显示:表皮不规则增生,棘层肥厚,表皮内可见核深染的异形淋巴细胞浸润,形成Pautrier微脓肿.真皮浅层有片状和团块状淋巴样细胞浸润,细胞有异形性.免疫组化标记:肿瘤细胞CD3、CD8、GrB、LCA和TIA-1阳性,CD4和CD5阴性.符合原发性皮肤CD8+亲表皮性T细胞淋巴瘤诊断.口服维胺酯治疗病情有所好转.     

Detection of Epstein-Barr virus in primary cutaneous amyloidosis

To determine the association of Epstein-Barr virus (EBV) with primary cutaneous amyloidosis (PCA), a retrospective study was conducted on skin tissue from 27 Chinese patients with lichen amyloidosus and macular amyloidosis. In situ hybridization with oligonucleotide probes was used to detect the expression of EBV-encoded RNAs (EBERs). Eleven of 27 cases (40.7%) were found to contain the EBV genome. No EBV genome was detected in the skin of the control groups, including three cases of secondary cutaneous amyloidosis, two cases of primary systemic amyloidosis, and four cases of lichen simplex chronicus. Our study showed no correlation between the presence of EBV in PCA patients and the patients'age, sex, clinical type or severity of the skin lesions. Although our results suggest that EBV may be associated with some cases of PCA, the true aetiological role of EBV in PCA remains unknown.     

Unlikely role of Epstein-Barr virus in the pathogenesis of primary cutaneous CD30+ anaplastic large cell lymphoma

BACKGROUND: Primary cutaneous CD30+ anaplastic large cell lymphoma (ALCL) is a rare subset of cutaneous lymphoma, with a much better prognosis than its nodal counterpart. The pathogenesis of both nodal and primary cutaneous CD30+ ALCL is largely unknown but experimental data support the hypothesis that the Epstein-Barr virus could play a role in the nodal subset. OBJECTIVE: To evaluate the involvement of Epstein-Barr Virus (EBV) in primary cutaneous CD30+ ALCL by searching for both nucleic acids and EBV proteins in cutaneous lesions. SETTING: Two University Hospitals in Southern France (secondary referral hospitals). PATIENTS: Eight consecutive patients with typical primary cutaneous CD30+ anaplastic large cell lymphoma were studied. METHODS: Search for the presence of DNA, RNA and EBV proteins in cutaneous lesions by PCR, in situ hybridization and immunohistochemistry. RESULTS: EBV DNA and RNA was identified in only one lesion of primary cutaneous CD30+ ALCL and in none of the normal adjacent skin samples. In situ hybridization and immunohistological studies were consistently negative in all samples. Conclusion: These results do not support an early role of EBV in the oncogenetic pathogenesis of primary cutaneous CD30+ ALCL.     

牛痘样水疱病样原发性皮肤CD8阳性T细胞淋巴瘤一例

一例13岁女孩面部和四肢为主反复出现红斑、丘疹、水疱样皮损9年,皮疹形态与牛痘水疱病相似(hydroa vacciniforme,HV)。在病情急性进展期,伴高热,体温39℃以上。皮肤科检查:面部水肿,面部和四肢较多的萎缩性圆形和椭网形痘疮样瘢痕,散在红斑、丘疹、坏死和结痂;四肢数个水肿性红色斑块,中心有圆形破溃面。组织学上,在真皮的血管和附属器周围,可见大量表达CD8异形淋巴细胞浸润,诊断CD8⁺皮肤T细胞淋巴瘤。糖皮质激素和免疫抑制剂可使病情缓解,随诊至今,无系统受累情况。     

Evidence for polyclonal infection of Epstein-Barr virus in a patient with primary cutaneous anaplastic large cell lymphoma

We report a case of CD30 + primary cutaneous anaplastic large cell lymphoma. The lymphoma cells were shown to express the Epstein-Barr virus (EBV)-encoded small RNAs by in situ hybridization and to have EBV genomes by PCR, whereas no monoclonal band was detected by Southern blot analysis using the EBV terminal repeat probe. These data suggested polyclonal infection by EBV, which provides evidence that EBV plays little part in the pathogenesis of this tumour even in the infected cases.     

A rare case of primary cutaneous plasmacytoma-like lymphoproliferative disorder following renal transplantation

Post-transplant lymphoproliferative disorder (PTLD) is a lymphoid proliferation that develops as a complication of solid organ or bone marrow transplants. PTLD limited to the skin is very rare. Plasmacytoma-like PTLD is an uncommon variant of monomorphic PTLD. Its presentation in the skin is extraordinary with very few cases reported in the literature. We report a new case of plasmacytoma-like PTLD presenting as multiple skin nodules on the leg of a 74-year-old kidney transplant recipient. Histopathologic and immunohistochemical examination of one nodule revealed atypical plasmacytoid and plasmablastic cells that showed kappa light chain restriction and stained positive for CD138. Staging investigations excluded extracutaneous manifestations of the disease. This case is unusual for several reasons including involvement limited to the skin, plasmacytoid phenotype of the tumor, presentation 18 years following transplantation and Epstein-Barr virus negativity.     

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.