HIV and prior exposure to antiretroviral therapy alter tumour composition and tumour: T-cell associations in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma worldwide, accounting for up to 40% of new non-Hodgkin Lymphoma (NHL) globally. People living with HIV are up to 17 times more likely to develop NHL, and as such, DLBCL is the leading cause of cancer death in this high-risk population. While histologically indistinguishable, HIV-associated (HIV+) and HIV-negative (HIV-) DLBCL are molecularly distinct, and biological differences may have implications for the development of future therapeutic interventions. Further, the impact of immunologic differences in people with HIV, including preceding ART, remains largely unknown. Here, we investigate the impact of HIV infection and ART exposure on the clinical features of DLBCL and T-cell immune response by performing imaging mass cytometry on our unique patient cohort in Malawi. In this cohort, HIV infection is positively prognostic, and HIV+/ART-naïve patients have the best outcomes. No established biomarkers other than Ki67 are associated with HIV or ART status, and the only tumour-intrinsic biomarkers that remain prognostic are MYC and MYC/BCL2 protein co-expression. Finally, TCR clonality is associated with distinct tumour-T cell interactions by HIV/ART status, indicating differential anti-tumour immune responses. We demonstrate previously undescribed HIV and ART-related differences in the DLBCL tumour microenvironment.

Oropharyngeal Mixed Neuroendocrine-Nonneuroendocrine Neoplasm (MiNEN): A Case Report and Literature Review.

Mixed neuroendocrine-nonneuroendocrine (MiNEN) neoplasms in the head and neck are exceptionally rare biphasic tumors with unclear pathogenesis and an aggressive clinical behavior. This is the first reported case of an oropharyngeal MiNEN with the nonneuroendocrine component being an HPV-associated adenocarcinoma. The tumor arose in a 56 year-old male with history of long-term cigarette smoking and was composed of an adenocarcinoma intermixed with a small cell neuroendocrine carcinoma. P16 immunohistochemical stain and HPV16/18 in-situ hybridization were strongly and diffusely expressed in both components.

HIV infection and ART exposure affect tumor TCR repertoire of diffuse large B cell lymphoma.

The most common subtype of lymphoma globally, diffuse large B cell lymphoma (DLBCL), is a leading cause of cancer death in people with HIV. The restructuring of the T cell compartment because of HIV infection and antiretroviral therapy (ART) may have implications for modern treatment selection, but current understanding of these dynamic interactions is limited. Here, we investigated the T cell response to DLBCL by sequencing the T cell receptor (TCR) repertoire in a cohort of HIV-negative (HIV-), HIV+/ART-experienced, and HIV+/ART-naive patients with DLBCL. HIV+/ART-naive tumor TCR repertoires were more clonal and more distinct from each other than HIV- and HIV+/ART-experienced ones. Further, increased overlap between tumor and blood TCR repertoires was associated with improved survival and HIV/ART status. Our study describes TCR repertoire characteristics for the first time to our knowledge in an African DLBCL cohort and demonstrates contributions of HIV infection and ART exposure to the DLBCL TCR repertoire.

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.