Inflow Occlusion Combined With Bleomycin Sclerotherapy for Management of Macro/Mixed Cystic Lymphatic Malformation in Children

Background: The link between cystic lymphatic malformation (cLM) and normal lymphatic system has become the focus of research. This study aimed to assess the outcomes of indocyanine green (ICG) lymphography-guided inflow occlusion combined with bleomycin sclerotherapy for the management of macro or mixed cLM in children.Methods: Between June 2018 and October 2020, inflow occlusion combined with bleomycin sclerotherapy was performed in 81 cLM patients (age range from 6 months to 8 years). All cases were evaluated by the following parameters: cLM location, histological typing, number of afferent lymph vessels, dermal backflow, curative effects, treatment frequency, and postoperative complications. The duration of postoperative follow-up was from 10 to 16 months.Results: All cLM cases could be found with at least one lymphatic inflow. Excellent outcomes were observed in 68 cases (84.0%), 11 cases (13.6%) experienced good outcomes, and two (2.5%) cases had fair outcome. No case experienced repeated treatment for more than three times. Wound infection, fever, and scar hyperplasia were the independent adverse events, which were managed by symptomatic treatment.Conclusion: Inflow occlusion combined with bleomycin sclerotherapy renders a safe and efficient approach for the management of macro or mixed cLM.

The conduit system exports locally secreted IgM from lymph nodes

Immunoglobulin M (IgM) is the first type of antibody produced during acute infections and thus provides an early line of specific defense against pathogens. Being produced in secondary lymphoid organs, IgM must rapidly be exported to the blood circulation. However, it is currently unknown how such large pentameric molecules are released from lymph nodes (LNs). Here, we show that upon immunization, IgM transiently gains access to the luminal side of the conduit system, a reticular infrastructure enabling fast delivery of tissue-derived soluble substances to the LN parenchyma. Using microinjections of purified IgM, we demonstrate that conduit-associated IgM is delivered by neither the afferent lymph nor the blood, but is locally conveyed by conduits. Exploiting in vivo models, we further demonstrate that conduit-associated IgM is locally and transiently produced by activated, antigen-specific B cells migrating in the T cell zone. Thus, our study reveals that the conduit system is coopted by B cells to rapidly export secreted IgM out of LNs.

Type I Interferons and NK Cells Restrict Gammaherpesvirus Lymph Node Infection

ABSTRACTGammaherpesviruses establish persistent, systemic infections and cause cancers. Murid herpesvirus 4 (MuHV-4) provides a unique window into the early events of host colonization. It spreads via lymph nodes. While dendritic cells (DC) pass MuHV-4 to lymph node B cells, subcapsular sinus macrophages (SSM), which capture virions from the afferent lymph, restrict its spread. Understanding how this restriction works offers potential clues to a more comprehensive defense. Type I interferon (IFN-I) blocked SSM lytic infection and reduced lytic cycle-independent viral reporter gene expression. Plasmacytoid DC were not required, but neither were SSM the only source of IFN-I, as IFN-I blockade increased infection in both intact and SSM-depleted mice. NK cells restricted lytic SSM infection independently of IFN-I, and SSM-derived virions spread to the spleen only when both IFN-I responses and NK cells were lacking. Thus, multiple innate defenses allowed SSM to adsorb virions from the afferent lymph with relative impunity. Enhancing IFN-I and NK cell recruitment could potentially also restrict DC infection and thus improve infection control.IMPORTANCEHuman gammaherpesviruses cause cancers by infecting B cells. However, vaccines designed to block virus binding to B cells have not stopped infection. Using a related gammaherpesvirus of mice, we have shown that B cells are infected not via cell-free virus but via infected myeloid cells. This suggests a different strategy to stop B cell infection: stop virus production by myeloid cells. Not all myeloid infection is productive. We show that subcapsular sinus macrophages, which do not pass infection to B cells, restrict gammaherpesvirus production by recruiting type I interferons and natural killer cells. Therefore, a vaccine that speeds the recruitment of these defenses might stop B cell infection.

Isolated Splenic Metastases of Her2+++ Gastroesophageal Junction Adenocarcinoma

Isolated metastases from gastric adenocarcinoma to the spleen are very infrequent. Usually, there are multiple metastases from gastric cancer, and isolated splenic metastases are very rare [Lam and Tang: Arch Pathol Lab Med 2000;124:526-530] because of certain anatomical and physiological characteristics (e.g., angulation between the splenic artery and celiac trunk, paucity of afferent lymph flow toward the spleen, contractility of the spleen and major immune content). Here, we report 2 cases of isolated splenic metastases from an adenocarcinoma of the gastroesophageal junction, both with long-term survival outcome and overexpression of Her2.

The HIV-1 envelope protein gp120 is captured and displayed for B cell recognition by SIGN-R1+ lymph node macrophages

The HIV-1 envelope protein gp120 is both the target of neutralizing antibodies and a major focus of vaccine efforts; however how it is delivered to B cells to elicit an antibody response is unknown. Here, we show that following local gp120 injection lymph node (LN) SIGN-R1+ sinus macrophages located in interfollicular pockets and underlying SIGN-R1+ macrophages form a cellular network that rapidly captures gp120 from the afferent lymph. In contrast, two other antigens, phycoerythrin and hen egg lysozyme, were not captured by these cells. Intravital imaging of mouse LNs revealed persistent, but transient interactions between gp120 bearing interfollicular network cells and both trafficking and LN follicle resident gp120 specific B cells. The gp120 specific, but not the control B cells repetitively extracted gp120 from the network cells. Our findings reveal a specialized LN antigen delivery system poised to deliver gp120 and likely other pathogen derived glycoproteins to B cells.