Multi-Organ Failure as the Initial Presentation of Lymphocyte-Depleted Hodgkin Lymphoma in Two Patients with Human Immunodeficiency Virus.

Patients with HIV-associated lymphocyte-depleted Hodgkin lymphoma (HIV-HL) often present with advanced, extranodal disease and aggressive clinical features, limiting definitive therapeutic intervention. Here we report two patients with HIV-HL who presented with multi-organ dysfunction as an initial manifestation of their malignancy. Both were initially treated with brentuximab vedotin (BV), which led only to a temporary partial response, highlighting the challenges of treatment. One patient was eventually started on nivolumab and responded very well to the immune checkpoint inhibitor. To our knowledge, this is the first case to describe successful use of nivolumab in a patient with relapsed lymphocyte-depleted HIV-HL. Prompt recognition of multi-organ dysfunction as an initial presentation of lymphocyte-depleted HIV-HL is essential to ensure rapid provision of therapy. While use of BV remains a reasonable option, earlier introduction of immunotherapy in the treatment of HL may provide an additional option in critically ill patients with lymphocyte-depleted HIV-HL.

The search for an optimal DNA, RNA, and protein detection by in situ hybridization, immunohistochemistry, and solution-based methods.

Clinical trials and correlative laboratory research are increasingly reliant upon archived paraffin-embedded samples. Therefore, the proper processing of biological samples is an important step to sample preservation and for downstream analyses like the detection of a wide variety of targets including micro RNA, DNA and proteins. This paper analyzed the question whether routine fixation of cells and tissues in 10% buffered formalin is optimal for in situ and solution phase analyses by comparing this fixative to a variety of cross linking and alcohol (denaturing) fixatives. We examined the ability of nine commonly used fixative regimens to preserve cell morphology and DNA/RNA/protein quality for these applications. Epstein-Barr virus (EBV) and bovine papillomavirus (BPV)-infected tissues and cells were used as our model systems. Our evaluation showed that the optimal fixative in cell preparations for molecular hybridization techniques was "gentle" fixative with a cross-linker such as paraformaldehyde or a short incubation in 10% buffered formalin. The optimal fixatives for tissue were either paraformaldehyde or low concentration of formalin (5% of formalin). Methanol was the best of the non cross-linking fixatives for in situ hybridization and immunohistochemistry. For PCR-based detection of DNA or RNA, some denaturing fixatives like acetone and methanol as well as "gentle" cross-linking fixatives like paraformaldehyde out-performed other fixatives. Long term fixation was not proposed for DNA/RNA-based assays. The typical long-term fixation of cells and tissues in 10% buffered formalin is not optimal for combined analyses by in situ hybridization, immunohistochemistry, or--if one does not have unfixed tissues--solution phase PCR. Rather, we recommend short term less intense cross linking fixation if one wishes to use the same cells/tissue for in situ hybridization, immunohistochemistry, and solution phase PCR.