Lymphoproliferative Neoplasms With Plasmablastic Morphology: An Overview and Diagnostic Approach

Context.— Plasmablastic morphology can be seen in several uncommon lymphoproliferative neoplasms. Sometimes it is difficult to distinguish these neoplasms from each other. Objective.— To review the current understanding of major lymphoproliferative neoplasms with plasmablastic morphology; summarize the clinical, morphologic, immunophenotypic, cytogenetic, and molecular characteristics of each disease entity; and highlight a practical approach for differential diagnosis. Data Sources.— Peer-reviewed medical literature and the authors' personal experience. Conclusions.— Plasmablastic lymphoma; plasmablastic myeloma; primary effusion lymphoma; human herpesvirus 8–positive diffuse large B-cell lymphoma, not otherwise specified; and anaplastic lymphoma kinase (ALK)–positive large B-cell lymphoma are major lymphoproliferative neoplasms with plasmablastic morphology. These neoplasms share many common morphologic and immunophenotypic characteristics. Definitive diagnosis requires a thorough understanding of disease phenotype and diagnostic criteria of each category. Recognition of expression pattern of Epstein-Barr virus–encoded small RNA, human herpesvirus 8, and ALK in these neoplasms is critical for diagnosis in cases with typical presentation. Additional ancillary studies and clinical findings may help in difficult cases.

Human herpesvirus 8 molecular mimicry of ephrin ligands facilitates cell entry and triggers EphA2 signaling

Human herpesvirus 8 (HHV-8) is an oncogenic virus that enters cells by fusion of the viral and endosomal cellular membranes in a process mediated by viral surface glycoproteins. One of the cellular receptors hijacked by HHV-8 to gain access to cells is the EphA2 tyrosine kinase receptor, and the mechanistic basis of EphA2-mediated viral entry remains unclear. Using X-ray structure analysis, targeted mutagenesis, and binding studies, we here show that the HHV-8 envelope glycoprotein complex H and L (gH/gL) binds with subnanomolar affinity to EphA2 via molecular mimicry of the receptor’s cellular ligands, ephrins (Eph family receptor interacting proteins), revealing a pivotal role for the conserved gH residue E52 and the amino-terminal peptide of gL. Using FSI-FRET and cell contraction assays, we further demonstrate that the gH/gL complex also functionally mimics ephrin ligand by inducing EphA2 receptor association via its dimerization interface, thus triggering receptor signaling for cytoskeleton remodeling. These results now provide novel insight into the entry mechanism of HHV-8, opening avenues for the search of therapeutic agents that could interfere with HHV-8–related diseases.

Seroprevalence and molecular diversity of Human Herpesvirus 8 among people living with HIV in Brazzaville, Congo

Human herpesvirus 8 (HHV8) is endemic in Africa, although studies of this infection are rare in Congo. We evaluated seroprevalence and HHV-8 diversity among people living with HIV. We included 353 patients receiving highly active antiretroviral therapy. Antibodies against HHV-8 latency-associated nuclear antigen were detected by indirect immunofluorescence. In HHV-8 positive patients, we performed HHV-8 quantification in blood and saliva by real-time PCR and typing by Sanger sequencing of K1 open reading frame. HHV-8 seroprevalence was 19%, being male (odd ratio [OR] = 1.741, [95% Confidence interval {CI}, 0.97–3.07]; p = 0.0581) and having multiple sex partners before HIV diagnosis (OR = 1.682, [CI 95%, 0.97–2.92]; p = 0.0629) tended to be associated with HHV-8 seropositivity. Of the 64 HHV-8 seropositive patients, HHV-8 DNA was detected in 10 (16%) in saliva, 6 (9%) in whole-blood and in 2 (3%) in both whole-blood and saliva. Three out of 6 HHV-8 strains were subtypes A5, 2 subtype B1 and 1 subtype C. HHV-8 seroprevalence was relatively low with more frequent carriage in men, associated with asymptomatic oral excretion and a predominance of subtype A5. These data tend to support the hypothesis of horizontal transmission in people living with HIV in Brazzaville.

Viruses and Skin Cancer

Advances in virology and skin cancer over recent decades have produced achievements that have been recognized not only in the field of dermatology, but also in other areas of medicine. They have modified the therapeutic and preventive solutions that can be offered to some patients and represent a significant step forward in our knowledge of the biology of skin cancer. In this paper, we review the viral agents responsible for different types of skin cancer, especially for solid skin tumors. We focus on human papillomavirus and squamous cell cancers, Merkel cell polyomavirus and Merkel cell carcinoma, and human herpesvirus 8 and Kaposi’s sarcoma.