Inhibitory KIR2DL2 Receptor and HHV-8 in Classic or Endemic Kaposi Sarcoma

KIR2DL2, an inhibitory Killer cell Immunoglobulin-like Receptor (KIR), has been shown to predispose to the development of several herpesvirus-associated diseases by inhibiting the efficiency of Natural Killer (NK) cells against virus-infected cells. The aim of this observational study was to assess the prevalence of KIR2DL2 and Human Herpes Virus 8 (HHV8) in patients affected with classical and endemic Kaposi sarcoma (KS), as well as in controls. Blood samples collected from 17 Caucasian, HIV-negative, immunocompetent patients affected with classical KS (c-KS), 12 African, HIV-negative patients with endemic KS (e-KS), 83 healthy subjects and 26 psoriatic patients were processed for genotypization by PCR for two KIR alleles, such as KIR2DL2 and KIR2DL3 and analyzed for HHV-8 presence. The totality of both c-KS and e-KS patients presented HHV-8 infection, whereas HHV8 was found in 26.9% of psoriatic subjects and 19.3% of healthy subjects. KIR2DL2 was found in the 76.5% of c-KS subjects, while the receptor was found in 41.7% of the e-KS group, 34.6% of psoriatic patients and 43.4% of healthy controls (p<0.0001). A significantly higher prevalence of KIR2DL2 in c-KS patients than in all the other subjects was also confirmed comparing age-matched groups. Based on these results, the inhibitory KIR2DL2 genotype appears to be a possible cofactor which increases the risk of developing c-KS in HHV8-positive, immunocompetent subjects, while it seems less relevant in e-KS pathogenesis.

Histopathological patterns and topographical distribution of Kaposi Sarcoma at Muhimbili National Hospital, Tanzania

Background: Kaposi sarcoma (KS) is derived from endothelial cell lineage; it is caused by Human Herpes Virus-8 (HHV-8) facilitated by immune suppression. KS remains one of the commonest sarcoma seen in Tanzania. The paucity of recent data makes monitoring the disease a challenge. This study describes the Histopathological Patterns and Topographical distribution of Kaposi Sarcoma at Muhimbili National Hospital, a tertiary care hospital in Tanzania. Methods: A hospital-based retrospective cross-sectional study was done to review biopsies sent to the Central Pathology Laboratory (CPL), Muhimbili National Hospital from 2010 to 2014. Results: A total of 818 cases representing 1.8 % of all malignancies during the study period were enrolled in the study. The age of patients at diagnosis ranged from 6 months to 94 years old, with the median age being 37 years. Male to female ratiowas 1.4:1.0. Females were younger than males (p < 0.001). The majority of the lesions were in the lower limbs, 352 (64.1%). Nodular KS accounted for 74.5% of all cases. Conclusion: Kaposi’s sarcoma remains a common malignancy. The patients present late at diagnosis. Early diagnosis and improved treatment protocols remain to be key steps towards reducing the burden of KS. Keywords: Kaposi's Sarcoma; Histopathological Patterns; Topographical distribution.

Rare, disseminated Kaposi sarcoma in advanced HIV with high-burden pulmonary and skeletal involvement

We describe the case of a 30-year-old man who presented to our institution with hypoxia and widespread pulmonary infiltrates managed initially as COVID-19 before receiving a new diagnosis of HIV-associated Kaposi sarcoma (KS) with widespread pulmonary and skeletal involvement. Initial differential diagnoses included Pneumocystis jirovecii pneumonia, disseminated mycobacterial infection and bacillary angiomatosis. A bone marrow biopsy showed heavy infiltration by spindle cells, staining strongly positive for human herpes virus-8 (HHV-8) and CD34, suggesting symptomatic, disseminated KS as the unifying diagnosis. The patient commenced cytotoxic therapy with weekly paclitaxel, with a clinical and radiological response. To our knowledge, this case is among the most severe described in the literature, which we discuss, along with how COVID-19 initially hindered developing a therapeutic allegiance with the patient.

Immunohistochemical characterization of KS cases seen in Nnewi Anambra state using HHV-8 LNA1 and HIV-1P24 antibodies

Introduction: Kaposi sarcoma (KS) is of public health significance in sub-Saharan Africa, including Nigeria, especially in the era of HIV/AIDS. Several works have been done on the prevalence and patterns of KS both in Nigeria and other parts of Africa, with a reported significant prevalence. We employed immunohistochemistry to characterise the morphologic KS cases seen in Nnewi. Materials and Methods: The Formalin Fixed, Paraffin Embedded (FFPE) tissue blocks of all haematoxylin and eosin (H&E) diagnosed cases of KS seen in the archives of histopathology facilities in Nnewi, Anambra State over 15 year period were retrieved. Fresh sections were made from the tissue blocks of the 82 cases that met the inclusion criteria for the study, and were subjected to immunohistochemistry using HHV-8 LNA1 (Human Herpes Virus-8 Latent nuclear antigen1) and HIV-1p24 antibodies and reviewed. Results: A total of 82 KS cases were studied, 69 of which were confirmed KS cases on immunohistochemistry. KS accounted for 1.20% and 14.47% of solid malignancies and sarcomas respectively. Nearly 80% of these were HIV/AIDS-associated, 59.3% of which occurred in females. KS occurred more in the third decade with an age range of 7-74years. Conclusion: KS is quite common in our environment and is largely HIV/AIDS associated. Reducing the burden of HIV/AIDS will invariably reduce KS burden.

Molecular Detection and Genotyping of Human Herpes Virus 8 in a sample of Iraqi Blood Donors

Human herpes virus-8 (HHV-8) infection has increased recently in Arabic countries. HHV-8 in healthy persons does not necessarily cause life-threatening infection, and however, it causes a more severe infection among immunocompromised patients. The distribution of HHV-8 genotypes varies according to ethnicity and depends on the geographic region prior rapid development of global travel. A cross sectional prospective study included a hundred healthy blood donor samples with a mean age of (36.60±10.381), 81% were positive for molecular detection of HHV-8 DNA. PCR results for HHV-8 were strongly related with risk factors such as the number of sexual relations, previous surgeries, blood transfusion, dental operation, and the number of blood donations. In this study, genotypes (A, B, C and D) were detected, largely associated with blood donors residences and distributed to areas of Iraq through a map. Genotype A comprised 28 (34.6%) of blood donors and for genotype C it was 16 (19.8%) and both genotypes were found to be the predominant genotypes, followed by genotype B of 7 (8.7%) and D of 2 (2.5%), the latter is included into Mixed genotypes of 8 (9.9%), whereas, 22 (27.2%) were undetermined genotypes. Efforts should focus on these findings, which may indicate that Iraq is an endemic region of HHV-8 infection.

Multicentric Castleman Disease in a DOCK8 Deficient Patient with Orf Virus Infection

Castleman disease is a rare, heterogeneous disorder that driven by proinflammatory responses. Human herpes virus-8 has a major role in pathogenesis of multicentric Castleman disease. There is also a subgroup of cases, human herpes virus-8 negative, idiopathic multicentric Castleman disease. The role of primary immunodeficiencies in idiopathic Castleman disease are poorly described. DOCK8 deficiency is a combined primary immunodeficiency. It has a broad clinic spectrum including atopy, autoimmunity and cancer. We present a 10-year-old, DOCK8 deficient patient. He had giant lobular capillary hemangiomas on his neck, iliac and gluteal regions and multiple lymphadenopathies. Abdominal lymph node pathology revealed hyaline vascular type Castleman disease and human herpes virus-8 staining was negative. His lesions were shown to be infected with orf virus. Our case is the first case to relate idiopathic multicentric Castleman disease and DOCK8 deficiency; also, very unusual presentation of orf virus infection in humans.

Primary effusion lymphoma occurring in the setting of transplanted patients: a systematic review of a rare, life-threatening post-transplantation occurrence

Background Primary effusion lymphoma is a rare, aggressive large B-cell lymphoma strictly linked to infection by Human Herpes virus 8/Kaposi sarcoma-associated herpes virus. In its classic form, it is characterized by body cavities neoplastic effusions without detectable tumor masses. It often occurs in immunocompromised patients, such as HIV-positive individuals. Primary effusion lymphoma may affect HIV-negative elderly patients from Human Herpes virus 8 endemic regions. So far, rare cases have been reported in transplanted patients. The purpose of our systematic review is to improve our understanding of this type of aggressive lymphoma in the setting of transplantation, focusing on epidemiology, clinical presentation, pathological features, differential diagnosis, treatment and outcome. The role of assessing the viral serological status in donors and recipients is also discussed. Methods We performed a systematic review adhering to the PRISMA guidelines. The literature search was conducted on PubMed/MEDLINE, Web of Science, Scopus, EMBASE and Cochrane Library, using the search terms “primary effusion lymphoma” and “post-transplant”. Results Our search identified 13 cases of post-transplant primary effusion lymphoma, predominantly in solid organ transplant recipients (6 kidney, 3 heart, 2 liver and 1 intestine), with only one case after allogenic bone marrow transplantation. Long-term immunosuppression is important in post-transplant primary effusion lymphoma commonly developing several years after transplantation. Kaposi Sarcoma occurred in association with lymphoma in 4 cases of solid organ recipients. The lymphoma showed the classical presentation with body cavity effusions in absence of tumor masses in 10 cases; 2 cases presented as solid masses, lacking effusions and one case as effusions associated with multiple organ involvement. Primary effusion lymphoma occurring in the setting of transplantation was more often Epstein Barr-virus negative. The prognosis was poor. In addition to chemotherapy, reduction of immunosuppressive treatment, was generally attempted. Conclusions Primary effusion lymphoma is a rare, but often fatal post-transplant complication. Its rarity and the difficulty in achieving the diagnosis may lead to miss this complication. Clinicians should suspect primary effusion lymphoma in transplanted patients, presenting generally with unexplained body cavity effusions, although rare cases with solid masses are described.

A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease

Castleman disease (CD) is a rare lymphoproliferative disorder known to represent at least four distinct clinicopathologic subtypes. Large advancements in our clinical and histopathologic description of these diverse diseases have been made, resulting in subtyping based on number of enlarged lymph nodes (unicentric versus multicentric), according to viral infection by human herpes virus 8 (HHV-8) and human immunodeficiency virus (HIV), and with relation to clonal plasma cells (POEMS). In recent years, significant molecular and genetic abnormalities associated with CD have been described. However, we continue to lack a foundational understanding of the biological mechanisms driving this disease process. Here, we review all cases of CD with molecular abnormalities described in the literature to date, and correlate cytogenetic, molecular, and genetic abnormalities with disease subtypes and phenotypes. Our review notes complex karyotypes in subsets of cases, specific mutations in PDGFRB N666S in 10% of unicentric CD (UCD) and NCOA4 L261F in 23% of idiopathic multicentric CD (iMCD) cases. Genes affecting chromatin organization and abnormalities in methylation are seen more commonly in iMCD while abnormalities within the mitogen-activated protein kinase (MAPK) and interleukin signaling pathways are more frequent in UCD. Interestingly, there is a paucity of genetic studies evaluating HHV-8 positive multicentric CD (HHV-8+ MCD) and POEMS-associated CD. Our comprehensive review of genetic and molecular abnormalities in CD identifies subtype-specific and novel pathways which may allow for more targeted treatment options and unique biologic therapies.