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* Context.--Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with poor outcome. BPDCN diagnostically overlaps with entities such as acute myeloid leukemia, histiocytic/dendritic cell neoplasms, and natural killer/T-cell lymphomas. Unfortunately, large, patient-centered studies that comprehensively analyze clinical, pathologic, and other diagnostic features are lacking. As such, there is an incomplete understanding of this disease. Objective.--To better characterize BPDCN, a multicenter working group consisting of hematopathologists and dermatopathologists gathered in person and remotely to review the current understanding of BPDCN, discuss specific issues regarding the diagnosis and differential diagnosis, and perform a retrospective analysis of the literature. Data Sources.--The working group curated a database of published BPDCN patient cases (BPDCN Network literature database), and following careful discussion and review, 361 articles were identified, comprising a total of 1513 individually annotated patients. Conclusions.--By conducting an in-depth analysis, not only did we confirm known findings such as frequent skin involvement (84% of patients; 861 of 1028) and a male predominance among older patients (>60 years old; male to female ratio of 3.5:1; 617:177), but we also identified a number of underrecognized features, such as significant central nervous system involvement (38% of cases; 24 of 64), and a more equal male to female prevalence among patients younger than 40 years (male to female ratio of 1.25:1; 167:134). Furthermore, we were able to accurately summarize the immunophenotypic, cytogenetic, and molecular features of this disease. BPDCN is a complex disease with distinct morphologic, immunophenotypic, and molecular findings. Continual updates of the literature database generated here and further analysis can allow for prospective refinement of our understanding of this orphan disease. (Arch Pathol Lab Med. 2023;147:837-846; doi: 10.5858/ arpa.2021-0612-RA), Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and clinically aggressive hematologic malignancy. Although BPDCN has long been recognized as a distinct clinical entity, the nomenclature for this disease [...]

* Context.--Although rare in everyday practice, the initial presentation of hematopoietic neoplasms other than lymphoma in the musculoskeletal system and other extranodal sites can generate challenging diagnostic problems for surgical pathologists. Objective.--To review the morphologic and immunophenotypic features of various nonlymphoid hematopoietic diseases presenting at extranodal sites, with emphasis on the inherent diagnostic pitfalls and differential diagnoses of these entities to aid surgical pathologists in their accurate recognition. Data Sources.--Cases reviewed herein represent both in-house and consult cases seen at our institution between 2010 and 2021. Conclusions.--Entities that present in this way include myeloid neoplasms and histiocytic/dendritic cell neoplasms. These tumors commonly cause nonspecific symptoms, and their histologic appearance can overlap with a variety of benign neoplasms and reactive processes. This can lead to delay in diagnosis and intervention with potentially lifesaving therapy; thus, accurate and expedient recognition is of paramount importance. (Arch Pathol Lab Med. 2022;146:1144-1159; doi: 10.5858/arpa.2021-0229-RA), Nonlymphoid hematopoietic neoplasms presenting in the musculoskeletal system and other nonnodal sites have long presented diagnostic challenges for pathologists owing to their infrequent nature and nonspecific morphologic features that not [...]

Conventional type 1 dendritic cells (cDC1).sup.1 are thought to perform antigen cross-presentation, which is required to prime CD8.sup.+ T cells.sup.2,3, whereas cDC2 are specialized for priming CD4.sup.+ T cells.sup.4,5. CD4.sup.+ T cells are also considered to help CD8.sup.+ T cell responses through a variety of mechanisms.sup.6-11, including a process whereby CD4.sup.+ T cells 'license' cDC1 for CD8.sup.+ T cell priming.sup.12. However, this model has not been directly tested in vivo or in the setting of help-dependent tumour rejection. Here we generated an Xcr1.sup.Cre mouse strain to evaluate the cellular interactions that mediate tumour rejection in a model requiring CD4.sup.+ and CD8.sup.+ T cells. As expected, tumour rejection required cDC1 and CD8.sup.+ T cell priming required the expression of major histocompatibility class I molecules by cDC1. Unexpectedly, early priming of CD4.sup.+ T cells against tumour-derived antigens also required cDC1, and this was not simply because they transport antigens to lymph nodes for processing by cDC2, as selective deletion of major histocompatibility class II molecules in cDC1 also prevented early CD4.sup.+ T cell priming. Furthermore, deletion of either major histocompatibility class II or CD40 in cDC1 impaired tumour rejection, consistent with a role for cognate CD4.sup.+ T cell interactions and CD40 signalling in cDC1 licensing. Finally, CD40 signalling in cDC1 was critical not only for CD8.sup.+ T cell priming, but also for initial CD4.sup.+ T cell activation. Thus, in the setting of tumour-derived antigens, cDC1 function as an autonomous platform capable of antigen processing and priming for both CD4.sup.+ and CD8.sup.+ T cells and of the direct orchestration of their cross-talk that is required for optimal anti-tumour immunity. Conventional type 1 dendritic cells perform antigen processing and priming of CD4.sup.+ and CD8.sup.+ T cells against tumour antigens, orchestrating their cross-talk to effect anti-tumour immunity., Author(s): Stephen T. Ferris [sup.1] , Vivek Durai [sup.1] [sup.10] , Renee Wu [sup.1] , Derek J. Theisen [sup.1] , Jeffrey P. Ward [sup.1] [sup.2] , Michael D. Bern [sup.3] [...]

Background: Polysaccharides, considered as immunomodulators with the capacity to activate immunity against microbial pathogens and tumors, have been employed for their dietary and medical benefits. Purpose: This study investigated the immunomodulatory effect of polysaccharide such as type II arabinogalactan from Anoectochilus formosanus (AGAF) on dendritic cell (DC) maturation and the underlying molecular mechanisms. Methods and results: Exposing DCs to AGAF induces cell maturation, which is characterized by the upregulation of CD86, CD83, CD80, CD40, and MHC class I and class II expression through flow cytometry analysis and morphological change without cytotoxicity. In addition, AGAF-triggered DC2.4 cells were involved in priming T-cell activation in vitro and in vivo. Transfection of toll-like receptor (TLR) 2 proteins and TLR4 siRNA suppressed DC maturation, suggesting that AGAF induced DC maturation through TLR2 and TLR4. Conclusion: These findings indicate that AGAF may be a potentially effective immunomodulator in stimulating DC maturation. Keywords: Polysaccharides Arabinogalactan Anoectochilus formosanus D.C2.4 cells DC maturation T cell activation, Introduction Various plants that contain major active compounds such as polysaccharides are used in traditional medicine to prevent several diseases. Polysaccharides offer numerous benefits including antioxidant (Liu et al. 2013; [...]

The mammalian hippocampus is crucial for episodic memory formation (1) and transiently retains information for about 3-4 weeks in adult mice and longer in humans (2). Although neuroscientists widely believe that neural synapses are elemental sites of information storage (3), there has been no direct evidence that hippocampal synapses persist for time intervals commensurate with the duration of hippocampal-dependent memory. Here we tested the prediction that the lifetimes of hippocampal synapses match the longevity of hippocampal memory. By using time-lapse two-photon microendoscopy (4) in the CA1 hippocampal area of live mice, we monitored the turnover dynamics of the pyramidal neurons' basal dendritic spines, postsynaptic structures whose turnover dynamics are thought to reflect those of excitatory synaptic connections (5, 6). Strikingly, CA1 spine turnover dynamics differed sharply from those seen previously in the neocortex (7-9). Mathematical modelling revealed that the data best matched kinetic models with a single population of spines with a mean lifetime of approximately 1-2 weeks. This implies 100% turnover in ~2-3 times this interval, a near full erasure of the synaptic connectivity pattern. Although N-methyl-D-aspartate (NMDA) receptor blockade stabilizes spines in the neocortex (10, 11), in CA1 it transiently increased the rate of spine loss and thus lowered spine density. These results reveal that adult neocortical and hippocampal pyramidal neurons have divergent patterns of spine regulation and quantitatively support the idea that the transience of hippocampal-dependent memory directly reflects the turnover dynamics of hippocampal synapses., The hypothesis that synaptic connectivity patterns encode information has profoundly shaped research on long-term memory. In the hippocampus, synapses in basal CA1 mainly receive inputs from hippocampal area CA3, and [...]

Learning how immune cells target tumours is crucial for cancer immunotherapy. The finding that a type of dendritic cell activates two sorts of T cell and coordinates their crosstalk sheds light on immune responses to tumours. Type 1 dendritic cells activate both CD4 and CD8 T cells., Author(s): Marianne Burbage, Sebastian Amigorena Author Affiliations: A dendritic cell multitasks to tackle cancer The generation of an efficient immune response against cancer is a multifaceted, multistep process. https://www.nature.com/articles/s41586-020-2611-3 , [...]