Endemic Kaposi sarcoma in HIV-negative children and adolescents: an evaluation of overlapping and distinct clinical features in comparison with HIV-related disease

Abstract Background Endemic Kaposi sarcoma (KS) was first described in African children over fifty years ago, but has recently been overshadowed by HIV-related disease. We aimed to evaluate the similarities and differences between endemic HIV-negative and epidemic HIV-positive pediatric KS in a KS-associated herpesvirus-endemic region of Africa. Methods We describe clinical characteristics of 20 HIV-negative children with endemic KS over a six-year period and compare findings with a historical control—an HIV-related pediatric KS cohort from Lilongwe, Malawi. Results The HIV-negative endemic KS cohort was 70% male with a median age of 9.3 years. Lymph node involvement was present in 50%, hyperpigmented skin lesions in 45%, and woody edema in 40%. One patient (5%) presented with oral KS involvement and no patients presented initially with visceral KS. Significant anemia (hemoglobin < 8 g/dL) and thrombocytopenia (platelet count < 100 × 109/L) were found at time of original KS diagnosis in 45 and 40% respectively. In both HIV-negative and HIV-positive cohorts, lymphadenopathy was the most common presentation, prototypical skin lesions were often absent, severe cytopenias were a common clinical feature, and treatment outcomes were similar. Patients with endemic KS demonstrated less frequent oral involvement (5% versus 29%, P = 0.03) and a lower proportion of patients with visceral involvement (0% versus 16%, P = 0.06). Conclusions These data suggest clinical overlap between epidemiological variants. Treatment protocols for pediatric KS in sub-Saharan Africa should be devised to include both endemic HIV-negative and epidemic HIV-related disease to better define the clinical and biological comparison

Update on pathology laboratory development and research in advancing regional cancer care in Malawi

The pathology laboratory at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi was established in 2011. We published our initial experiences in laboratory development and telepathology in 2013 and 2016, respectively. The purpose of this paper is to provide an update on our work by highlighting the positive role laboratory development has played in improving regional cancer care and research. In addition, we provide a summary of the adult pathology data from specimens received between July 1, 2011, and May 31, 2019, with an emphasis on malignant diagnoses. We compare these summaries to estimates of cancer incidence in this region to identify gaps and future needs

Genetic errors of immunity distinguish pediatric non-malignant lymphoproliferative disorders

Background Pediatric non-malignant lymphoproliferative disorders (PLPD) are clinically and genetically heterogeneous. Long-standing immune dysregulation and lymphoproliferation in children may be life-threatening, and a paucity of data exists to guide evaluation and treatment of children with PLPD. Objective The primary objective of this study was to ascertain the spectrum of genomic immunologic defects in PLPD. Secondary objectives included characterization of clinical outcomes and associations between genetic diagnoses and those outcomes. Methods PLPD was defined by persistent lymphadenopathy, lymph organ involvement, or lymphocytic infiltration for more than 3 months, with or without chronic or significant EBV infection. Fifty-one subjects from 47 different families with PLPD were analyzed using whole exome sequencing (WES). Results WES identified likely genetic errors of immunity in 51% to 62% of families (53% to 65% of affected children). Presence of a genetic etiology was associated with younger age and hemophagocytic lymphohistiocytosis. Ten-year survival for the cohort was 72.4%, and patients with viable genetic diagnoses had a higher survival rate (82%) compared to children without a genetic explanation (48%, p = 0.03). Survival outcomes for individuals with EBV-associated disease and no genetic explanation were particularly worse than outcomes for subjects with EBV-associated disease and a genetic explanation (17% vs. 90%; p = 0.002). Ascertainment of a molecular diagnosis provided targetable treatment options for up to 18 individuals and led to active management changes for 12 patients. Conclusion PLPD therefore defines children with high risk for mortality, and WES informs clinical risks and therapeutic opportunities for this diagnosis

Endemic Kaposi sarcoma in HIV-negative children and adolescents: an evaluation of overlapping and distinct clinical features in comparison with HIV-related disease

Abstract Background Endemic Kaposi sarcoma (KS) was first described in African children over fifty years ago, but has recently been overshadowed by HIV-related disease. We aimed to evaluate the similarities and differences between endemic HIV-negative and epidemic HIV-positive pediatric KS in a KS-associated herpesvirus-endemic region of Africa. Methods We describe clinical characteristics of 20 HIV-negative children with endemic KS over a six-year period and compare findings with a historical control—an HIV-related pediatric KS cohort from Lilongwe, Malawi. Results The HIV-negative endemic KS cohort was 70% male with a median age of 9.3 years. Lymph node involvement was present in 50%, hyperpigmented skin lesions in 45%, and woody edema in 40%. One patient (5%) presented with oral KS involvement and no patients presented initially with visceral KS. Significant anemia (hemoglobin < 8 g/dL) and thrombocytopenia (platelet count < 100 × 109/L) were found at time of original KS diagnosis in 45 and 40% respectively. In both HIV-negative and HIV-positive cohorts, lymphadenopathy was the most common presentation, prototypical skin lesions were often absent, severe cytopenias were a common clinical feature, and treatment outcomes were similar. Patients with endemic KS demonstrated less frequent oral involvement (5% versus 29%, P = 0.03) and a lower proportion of patients with visceral involvement (0% versus 16%, P = 0.06). Conclusions These data suggest clinical overlap between epidemiological variants. Treatment protocols for pediatric KS in sub-Saharan Africa should be devised to include both endemic HIV-negative and epidemic HIV-related disease to better define the clinical and biological comparison

Defining the Inflammatory Plasma Proteome in Pediatric Hodgkin Lymphoma.

Hodgkin lymphoma (HL) histopathology is characterized by rare malignant Reed&ndash;Sternberg cells among an inflammatory infiltrate. We hypothesized that characteristics of inflammation in pediatric HL lesions would be reflected by the levels of inflammatory cytokines or chemokines in pre-therapy plasma of children with HL. The study objectives were to better define the inflammatory pre-therapy plasma proteome and identify plasma biomarkers associated with extent of disease and clinical outcomes in pediatric HL. Pre-therapy plasma samples were obtained from pediatric subjects with newly diagnosed HL and healthy pediatric controls. Plasma concentrations of 135 cytokines/chemokines were measured with the Luminex platform. Associations between protein concentration and disease characteristics were determined using multivariate permutation tests with false discovery control. Fifty-six subjects with HL (mean age: 13 years, range 3&ndash;18) and 47 controls were analyzed. The cytokine/chemokine profiles of subjects with HL were distinct from controls, and unique cytokines/chemokines were associated with high-risk disease (IL-10, TNF-&alpha;, IFN-&gamma;, IL-8) and slow early response (CCL13, IFN-&lambda;1, IL-8). TNFSF10 was significantly elevated among those who ultimately relapsed and was significantly associated with worse event-free survival. These biomarkers could be incorporated into biologically based risk stratification to optimize outcomes and minimize toxicities in pediatric HL