Interdigitating Dendritic Cells Research Articles

Emergence of SARS‐CoV‐2 spike protein at the vaccination site

The anti-coronavirus disease 2019 (COVID-19) vaccines are of paramount importance in the fight against the COVID-19 pandemic. Both viral vector- and nucleic acid-based vaccines are known to effectively induce protection against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus by generating high antibody titers and effective T-cell responses to the spike protein they encode. Although these vaccines are being applied worldwide and have been extensively investigated, the immunomorphological events at the vaccination site with respect to SARS-CoV-2 spike protein expression have not yet been described. We had the opportunity to examine the deltoid muscles of three men who died shortly after vaccination for unrelated reasons. We examined the vaccination sites histologically and immunohistochemically with various antibodies. Furthermore we incubated two different cell lines with one vaccine and examined the expression of the spike protein. The vaccination sites show a dense lymphohistiocytic interstitial infiltrate which surrounds the small vessels and extends into the perimysium. The spike protein is expressed by histiocytic cells with a dendritic shape that are CD68-positive and CD207-negative, fibrocytes, and very rare S100-positive cells. Interestingly, the skeletal muscle, being constitutively human leukocyte antigen (HLA)-A,B,C-negative, is induced at different levels in each specimen. In a cell culture experiment, we confirmed the ability of fibroblasts and interdigitating dendritic sarcoma cells to express spike protein in vitro after incubation with the Comirnaty vaccine. Histiocytic cells and fibrocytes are the heralds of spike protein synthesis at the vaccination site. The underlying cause of this apparent cell specifity is unknown. This needs to be investigated in future experiments, for example in an animal model.

Two Sides of the Same Transdifferentiated Coin: A Case Vignette and Review of the Literature Exploring the Relationship between B Cell Non-Hodgkin Lymphoma, Histiocytic Sarcoma and Interdigitating Dendritic Cell Sarcoma

WHO classifies Histiocytic Sarcoma (HS) and Interdigitating Dendritic Cell Sarcoma (IDCS) as separate, unrelated, entities under histiocytic/dendritic cell neoplasms. We do not fully understand the pathogenesis of HS and IDCS, yet both have been shown to transdifferentiate from B cell non-Hodgkin lymphomas. Diagnosis is challenging and requires application of a wide variety of immunohistochemical studies, flow cytometry and molecular analysis. We present a case of HS which evolved from CLL/SLL and presented as a diagnostic challenge due to unusual features overlapping with what is typically seen in IDCS. An 82-year-old male with a history of CLL/SLL presented with right infiltrative tonsillar mass and cervical lymphadenopathy. Biopsy of the lymph node revealed two abnormal populations of cells : Twenty percent of cells were consistent with CD20+ kappa surface light chain restricted CLL/SLL cells. Eighty percent of cells were histiocytic cells with an abnormal immunophenotype showing expression of CD4, CD43, fascin, HLA-DR, PU.1, (weak) S100 and CD1a without CD163, lysozyme, CD34, CD117, CD21, CD23 or CD14. Expert consultation favored the diagnosis of HS with transdifferentiation from CLL/SLL. PCR for IgH gene rearrangement, performed on separate HS-rich and CLL-rich areas of the biopsy detected identical clonal peaks. Next generation sequencing detected pathogenic KRAS mutations (p.G12D, p.A146P) and likely pathogenic BCOR (p.K839fs*17) and FBXW7 (p.R465S) mutations. While HS was the favored diagnosis, some immunophenotypic features were unusual, including diffuse fascin immunoreactivity, weak S100, and CD1a immunoreactivity which raised the possibility of so-called IDCS. While clonal evolution of HS and IDCS from B cell Non-Hodgkin lymphomas has been reported, there is a paucity of literature on these entities. We suggest that there may be a pathogenic relationship between these two neoplasms that has yet to be elucidated due to their rarity and diagnostic challenge. Few clinical laboratories can perform the breadth of markers required for diagnosis. Both neoplasms have varied clinical presentations with nodal or extranodal involvement and portend poor prognosis. Review of the literature shows significant overlap in immunophenotypic and genomic characteristics of IDCS and HS, suggesting they may be related manifestations of the same neoplasm. A case report has described the initial presentation of IDCS that subsequently developed into HS, although sampling may have been an issue. We identified 11 cases, including our case in the literature presenting with positive histiocytic and dendritic cell markers referred as hybrid dendritic-histiocytic sarcomas or histiocytic sarcoma with interdigitating dendritic cell differentiation. Immunohistochemical analysis of these cases showed positivity rates of S100 (100%), lysozyme (82%) and CD1a (18%). One case in the literature described fascin immunoreactivity, as was observed in our case. Four of six cases had CD163 immunoreactivity. A hybrid neoplasm with overlapping features of follicular and interdigitating dendritic cells has also been reported, further confounding our understanding of these neoplasms. Large studies analyzing genomic features of these neoplasms have shown recurrent mutations in RAS-MAPK pathway, as was seen in our case. Further studies of the relationship between HS, IDCS should include gene expression profiling of these entities which may also yield therapy targets. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Development of a prognostic prediction model based on a combined multi-omics analysis of head and neck squamous cell carcinoma cell pyroptosis-related genes.

This study aimed to understand the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) and to develop and validate a prognostic model for HNSCC based on pyroptosis-associated genes (PAGs) in nasopharyngeal carcinoma. The Cancer Genome Atlas database was used to identify differentially expressed PAGs. These genes were analyzed using the Kyoto Encyclopedia of Genes and Genomes functional annotation analyses and Gene Ontology analyses. The NLR family pyrin domain containing 1 (NLRP1) gene, charged multivesicular body protein 7 (CHMP7) gene, and cytochrome C (CYCS) gene were used to create a prognostic model for HNSCC. The results of the Kaplan-Meier (K-M) and Cox regression analyses indicated that the developed model served as an independent risk factor for HNSCC. According to the K-M analysis, the overall survival of high-risk patients was lower than that of low-risk patients. The hazard ratios corresponding to the risk scores determined using the multivariate and univariate Cox regression analyses were 1.646 (95% confidence interval (CI): 1.189–2.278) and 1.724 (95% CI: 1.294–2.298), respectively, and the area under the receiver operator characteristic curve was 0.621. The potential mechanisms associated with the functions of the identified genes were then identified, and the tumor microenvironment and levels of immune cell infiltration achieved were analyzed. The immune infiltration analysis revealed differences in the distribution of Th cells, tumor-infiltrating lymphocytes, regulatory T cells, follicular helper T cells, adipose-derived cells, interdigitating dendritic cells, CD8+ T cells, and B cells. However, validating bioinformatics analyses through biological experiments is still recommended. This study developed a prognostic model for HNSCC that included NLRP1, CHMP7, and CYCS.

Lower Manic Fringe Expression as an Independent Prognostic Biomarker and Correlated with Immune Suppression of Tumor Microenvironment in Lung Adenocarcinoma

Non-small cell lung cancer is the leading cause of cancer-associated mortality worldwide and lung adenocarcinoma is its most common type. The fringe protein family can modulate the Notch receptors to regulate pathways and affect a variety of physiological processes, such as embryo development and tumor formation. To investigate the influence of manic fringe expression on the prognosis of lung adenocarcinoma patients and evaluate its correlation with immune suppression of tumor microenvironment is the objective of the study. Wilcoxon rank test and logistic regression were used to analyze the relationship between manic fringe expression and clinical characteristics of patients with lung adenocarcinoma. The influence of manic fringe expression on the prognosis of lung adenocarcinoma patients was analyzed using Kaplan- Meier plotter analysis and Cox regression, and a receiver operating characteristic curve and nomogram were constructed. Single sample gene set enrichment analysis was used to analyze the correlation between manic fringe expression and immune infiltration. The expression of manic fringe in lung adenocarcinoma was verified using the Oncomine and tumor immune estimation resource database. Manic fringe expression in lung adenocarcinoma patients was significantly lower than that in normal lung tissues. Kaplan-Meier plotter analysis revealed that the overall survival and disease-specific survival of lung adenocarcinoma patients with low manic fringe expression were shorter (p<0.05) than those of patients with high expression. Multivariate Cox analysis further confirmed that high manic fringe expression was an independent predictor of longer overall survival in patients with lung adenocarcinoma. Furthermore, the other clinicopathological features, such as tumour and lymph nodes classification and residual tumor R classification, were correlated with worse prognosis. Single sample gene set enrichment analysis showed that manic fringe expression was correlated with infiltration of interdigitating dendritic cells and tumor cells. Manic fringe may be used as an independent prognostic biomarker and is associated with immune infiltration in lung adenocarcinoma.

Expression of CD86 on Circulating Monocytes in Patients with Vitiligo

CD86 is a 70-kDa glycoprotein made up of 329 amino acids, a transmembrane region and a longer cytoplasmic domain than CD80. It is expressed on interdigitating dendritic cells (DCs), Langerhans cells, peripheral blood DCs, memory B cells and germinal center B cells and macrophages. The majority of the intralesional APCs communicated the CD86 development marker Also co-localized for t cells, especially done punctual vitiligo lesions. Cytotoxic CD8+ t units bring been determinedly embroiled in the decimation from claiming melanocytes clinched alongside numerous investigations. The present investigation pointed to evaluate those outflow of CD86 looking into circle monocytes to vitiligo patients and on survey the correspondence between these expressions and the diverse infection contemplated parameters. Fourty patients torment from vitiligo, furthermore on twenty Obviously solid people about matched period Furthermore sex Similarly as a control bunch. Cd 86 might have been evaluated Eventually Tom's perusing utilizing flowcytometric dissection. Our discoveries recommend that, CD86 is connected with those defenselessness for improvement of vitiligo What's more might need a part in the infection pathogenesis Also its seriousness.

Clinical, histopathologic, and immunoarchitectural features of dermatopathic lymphadenopathy: an update.

Dermatopathic lymphadenopathy is a distinctive form of paracortical lymph node hyperplasia that usually occurs in the setting of chronic dermatologic disorders. The aim of this study is to update our understanding of the clinicopathologic and immunophenotypic features of dermatopathic lymphadenopathy. The study cohort was 50 lymph node samples from 42 patients diagnosed with dermatopathic lymphadenopathy. The patients included 29 women and 13 men with a median age of 49 years (range, 12-79). Twenty-two (52%) patients had a dermatologic disorder, including mycosis fungoides (n = 6), chronic inflammatory dermatoses (n = 13), melanoma (n = 1), squamous cell carcinoma (n = 1), and Kaposi sarcoma in the context of human immunodeficiency virus infection (n = 1). Twenty (48%) patients did not have dermatologic manifestations. Lymph node biopsy specimens were axillary (n = 22), inguinal (n = 21), cervical (n = 4), and intramammary (n = 3). All lymph nodes showed paracortical areas expanded by lymphocytes; dendritic cells, including interdigitating dendritic cells and Langerhans cells; and macrophages. Melanophages were detected in 48 (98%) lymph nodes. Immunohistochemical analysis provided results that are somewhat different from those previously reported in the literature. In the paracortical areas of lymph node, S100 protein was expressed in virtually all dendritic cells, and CD1a was expressed in a significantly greater percentage of cells than langerin (80 vs. 35%, p < 0.0001). These results suggest that the paracortical regions of dermatopathic lymphadenopathy harbor at least three immunophenotypic subsets of dendritic cells: Langerhans cells (S100+, CD1a+(high), langerin+), interdigitating dendritic cells (S100+, CD1a+(low), langerin-), and a third (S100+,CD1a-, langerin-) minor population of dendritic cells. Furthermore, in more than 60% of dermatopathic lymph nodes, langerin highlighted trabecular and medullary sinuses and cords, showing a linear and reticular staining pattern, which could be a pitfall in the differential diagnosis with Langerhans cell histiocytosis involving lymph nodes.

Azacitidine in Pediatric Hematologic Myeloid Malignancies: A Retrospective Study

Purpose: Hypomethylating agents are approved in adults with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS). By contrast, data in pediatric hematologic malignancies are scarce. Herein, we report the off-label administration of Azacitidine (Aza) in a cohort of children, adolescents and young adults (AYA). Methods: Patients from Robert-Debré, Saint-Louis and Armand-Trousseau University Hospitals (Assistance Publique-Hôpitaux de Paris), 25 year-old or younger at initiation of treatment and who received Aza between 2009 and 2019 were included. Data on indication, efficacy and toxicity of the treatment were retrospectively collected. Results: As 3 patients (pts) were treated twice with Aza at different stages of their disease, 35 treatments in 32 patients were analyzed. Median age at diagnosis was 11.7 y (range 0.1-22.4). Diagnosis were: 16 Acute Myeloid Leukemias (AML), 6 Juvenile Myelomonocytic Leukemias (JMML), 7 Myelodysplastic Syndromes (MDS), 2 Mixed Phenotype Acute Leukemias (MPAL) and 1 Interdigitating Dendritic Cells Sarcoma. Aza was administrated after a median of 2 lines of treatment (range 0-6) and front line in 5 out of 32 pts (16%; MDS = 4, JMML = 1). Concomitant therapy was administrated in 15/35 treatments (43%) (Sorafenib = 6, Gemtuzumab Ozogamicin = 2, donor lymphocyte infusions = 2, other = 5). Fourteen out of 35 treatments (40%) were delivered in patients with a history of hematopoietic stem cell transplantation (HSCT). Aza was administrated either intravenously (n = 11) or subcutaneously (n = 24) at a dose of 75mg/m² for 7 (20/35, 57%) or 5 (6/35, 17%) consecutive days every 28 days, i.e. same daily dose as in adults; at reduced doses (≤ 50mg/m²) in 3/35 patients; at a dosing scheme varying from one cycle to another in 6/35 patients. Patients received a median of 3 cycles of Aza per treatment (range 1-31). A total of 137 cycles was delivered. Aza was well tolerated with only 5/137 cycles delayed due to hematological (n = 3) or non-hematological (n = 2) toxicity. Aza was discontinued due to toxicity in 2/137 cycles (1 rectal bleeding, 1 severe sepsis). Anemia was noted in 68/130 cycles (52%), thrombocytopenia in 68/128 cycles (53%), neutropenia in 84/127 cycles (66%) and febrile neutropenia in 25/131 cycles (19%). Two grade 5 side effects were observed: 1 patient died from cerebral hemorrhage in a context of anti-platelet poly-immunization, another from septic shock in a context of neutropenia. Most common non-hematological side effects included: nausea, vomiting, diarrhea, subcutaneous injections lesions (local inflammation or hematoma) and infections. Responses to Aza are detailed in the attached table. Best responses to Aza included: 2 complete remissions (CR) both after 3 cycles, 3 CR with incomplete hematologic recovery (CRi) after a median of 2 cycles (range 1-2), 2 partial remissions (PR) after 2 and 3 cycles, 6 stable diseases (SD) during a median of 2 cycles (range 2-12) and 2 hematologic improvements. Overall response rate (sum of CR, CRi, PRs), was 19% (6/32) (3 non evaluable responses). Three out of the 6 patients treated with Aza combined with Sorafenib (AML = 4, MPAL = 2) obtained a response (CR: 2, CRi: 1). The association led to HSCT for 2 of them; the third patient had a CR maintained almost 3 years without HSCT, before relapsing on therapy. One patient with MDS had a SD for 12 months after palliative treatment with Aza. Overall, Aza treatment allowed to proceed to HSCT in 8 out of 32 patients (25%), 7 out of 8 proceeding to a first HSCT [CR: 1 patient, CRi: 3 patients, PR: 2 patients, SD: 1 patient, progressive disease: 1 patient]. These 8 pts included: 4 pts with AML, alive in CR after a median follow-up of 29.5 months (2 of them received concomitant targeted therapy); 2 pts with JMML (1 alive in CR after a follow-up of 25 months); 2 pts with MDS (both died, 7 and 30 months after Aza initiation). Finally, 24 out of 32 patients died and overall survival at 5 years was 23% (IC95% [11;48]) with no difference according to diagnosis. Conclusion: In a cohort of pediatric and AYA patients with heavily pretreated myeloid malignancies, Aza was well tolerated, and allowed to bridge 25% of patients to HSCT. Further prospective studies are needed to explore combination of Aza with targeted therapy in pediatric patients. Disclosures Boissel: NOVARTIS: Consultancy.

Dimorphism and Dissemination of Histoplasma capsulatum in the Upper Respiratory Tract after Intranasal Infection of Bats and Mice with Mycelial Propagules.

.This article describes, for the first time, the role of the nasal mucosa (NM) as the initial site for the Histoplasma capsulatum mycelial-to-yeast transition. The results highlight that yeasts may arrive to the cervical lymph nodes (CLN) via phagocytes. Bats and mice were intranasally infected with H. capsulatum mycelial propagules and they were killed 10, 20, and 40 minutes and 1, 2, and 3 hours after infection. The NM and the CLN were monitored for fungal presence. Yeasts compatible with H. capsulatum were detected within the NM and the CLN dendritic cells (DCs) 2–3 hours postinfection, using immunohistochemistry. Histoplasma capsulatum was re-isolated by culturing at 28°C from the CLN of both mammalian hosts 2–3 hours postinfection. Reverse transcription-polymerase chain reaction assays were designed to identify fungal dimorphism, using mycelial-specific (MS8) and yeast-specific (YPS3) gene expression. This strategy supported fast fungal dimorphism in vivo, which began in the NM 1 hour postinfection (a time point when MS8 and YPS3 genes were expressed) and it was completed at 3 hours (a time point when only the YPS3 transcripts were detected) in both bats and mice. The presence of intracellular yeasts in the nasal-associated lymphoid tissue (NALT), in the NM nonassociated with the NALT, and within the interdigitating DCs of the CLN suggests early fungal dissemination via the lymph vessels.

Fibroblastic reticular cell tumour in axilla- A rare entity

Primary sarcomas arising in lymph node are few and far between. They are believed to arise from either follicular dendritic cells, indeterminate dendritic cells, interdigitating dendritic cells and seldom from fibroblastic reticular cells which are said to have mesenchymal origin and are involved in cytokine transport. A 37-year-old female patient reported with painless mass in axilla without any breast lump. On histopathology a diagnosis of NHL was made which on immunohistochemistry with CK8, CK18 and SMA positivity was diagnosed as fibroblastic reticulum cell tumour. The case is being reported because of its rarity. Keywords: Fibroblastic reticular cells, Immunohistochemistry, Lymph node, Stromal cells, Sarcoma.

Avian coronavirus infection induces mannose-binding lectin production in dendritic cell precursors of chicken lymphoid organs.

The aim of this immunocytochemical study was to compare mannose-binding lectin (MBL) production induced by avian coronavirus in the spleen and caecal tonsil (CT). One-day-old specific-pathogen-free (SPF) chickens were experimentally infected with six QX field isolates and the H120 vaccine strain. In the negative control birds, the spleen was MBL negative, while the CT showed scattered MBL-positive cells in close proximity and within the surface epithelium and germinal centre (GC)-like cell clusters. MBL was detectable in the ellipsoid-associated cells (EACs) and cell clusters in the periarterial lymphoid sheath (PALS) by 7 days post infection (dpi). In both organs, the MBL-positive cells occupy antigen-exposed areas, indicating that GC formation depends on resident precursors of dendritic cells. The majority of MBL-positive EACs express the CD83 antigen, providing evidence that coronavirus infection facilitated the maturation of dendritic cell precursors. Surprisingly, co-localisation of MBL and CD83 was not detectable in the CT. In the spleen (associated with circulation), the EACs producing MBL and expressing CD83 are a common precursor of both follicular (FDC) and interdigitating dendritic cells (IDC). In the CT (gut-associated lymphoid tissue, GALT) the precursors of FDC and IDC are MBL-producing cells and CD83-positive cells, respectively. In the CT the two separate precursors of lymphoid dendritic cells provide some 'autonomy' for the GALT.

Diffuse lesion and necrosis tied to poorer prognosis of interdigitating dendritic cell sarcoma: cases report and a pooled analysis

Interdigitating dendritic cell sarcoma is a neoplastic proliferation of interdigitating dendritic cells and no therapeutic consensus exists. This study aimed to investigate the prognostic impacts of tumor lesion, cellular atypia, mitosis and necrosis on the interdigitating dendritic cell sarcoma. Case reports and pooled analyses were designed to explore the relationships. One case was a 40-years old man with localized lesion, moderate to notable cellular atypia, 30 mitoses per 10 high-power fields and no necrosis and the progression-free survival was longer than 20 months. The other case was a 62-years old woman with diffuse lesion, notable cellular atypia, less than one mitosis per 10 high-power fields and diffuse necrosis and the progression-free survival was shorter than 1 month. Cellular atypia and mitosis had not any relationship with survival. Compared with localized lesion, diffuse lesion presented a 2.92-fold risk of progression (HR = 2.92, 95% CI 1.01, 8.51) and an 8.79-fold risk of death (HR = 8.79, 95% CI 1.86, 41.64). Diffuse necrosis presented a 4.39-fold higher progression risk (HR = 5.39, 95% CI 1.78, 16.29) and a 5.37-fold higher death risk (HR = 6.37, 95% CI 1.46, 27.86) than focal or no necrosis. Diffuse lesion and diffuse necrosis were indicators of poorer prognosis and the clinical application should be warranted in further studies.

What do we know about the structure of human thymic Hassall’s corpuscles? A histochemical, immunohistochemical, and electron microscopic study

Hassall’s corpuscles are the most prominent structures in the human thymus. However, relatively few analyses have been performed to determine their function and cellular origins during development. In this study, we evaluated the cellular microenvironment of human thymic Hassall’s corpuscles using histochemistry, immunohistochemistry, and transmission electron microscopy. We examined 95 human thymic tissue samples, which were perioperatively obtained from children undergoing cardiac surgery. To characterize the complex cellular microenvironment of human thymic corpuscles, we used a panel of 14 different antibodies to identify discrete cell types. We also utilized various histochemical methods (PAS reaction, alcian blue staining, alkaline phosphatase and acid phosphatase activity staining, von Kossa staining of calcified particles) and transmission electron microscopy to visualize these structures. Considerable variation in the sizes, shapes, and numbers of Hassall’s corpuscles was observed, even amongst children of the same age. Inside the largest Hassall’s corpuscles, cystic dilatation with an accumulation of cellular debris was found. These morphological observations might be associated with disruptions in the formation, migration, or differentiation of cardiac neural crest cells, which are essential for heart and thymus development. Immunohistochemical staining and electron microscopy revealed that Hassall’s corpuscles resemble other types of stratified squamous epithelia. Most Hassall’s corpuscles are heterocellular, consisting of thymic epithelial cells, macrophages, interdigitating dendritic cells, myoid cells, and, occasionally, mast cells and lymphocytes. To explore the potential functions of Hassall’s corpuscles, we found that the concentrations of B-lymphocytes and BCL2-positive lymphocytes suggested a role in regulation of lymphopoiesis. We also found that these structures do not originate from the perivascular epithelium as previously proposed, nor could we identify blood or lymph endothelial cells in close proximity. This leaves the origins of Hassall’s corpuscles an open question.

Expression of Programmed Cell Death 1 Ligands (PD-L1 and PD-L2) in Histiocytic and Dendritic Cell Disorders.

Programmed cell death 1 ligands 1 and 2 (PD-L1 and PD-L2) are cell surface proteins expressed by activated antigen-presenting cells and by select malignancies that bind PD-1 on T cells to inhibit immune responses. Antibodies targeting PD-1 or PD-L1 elicit antitumor immunity in a subset of patients, and clinical response correlates with PD-1 ligand expression by malignant or immune cells within the tumor microenvironment. We examined the expression of PD-1 ligands on subsets of antigen-presenting cells and 87 histiocytic and dendritic cell disorders including those that are benign, borderline, and malignant. Within reactive lymphoid tissue, strong PD-L1 is detected on most macrophages, subsets of interdigitating dendritic cells, and plasmacytoid dendritic cells, but not on follicular dendritic cells or Langerhans cells. Macrophage/dendritic cell subsets do not express discernible PD-L2. Seven of 7 cases of sarcoidosis (100%), 6 of 6 cases of histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) (100%), 2 of 11 cases of Rosai-Dorfman disease (18%), and 3 of 15 cases of Langerhans cell histiocytosis (20%) exhibited positivity for PD-L1. All cases of sarcoidosis were also positive for PD-L2. Seven of 14 histiocytic sarcomas (50%), 2 of 5 interdigitating dendritic cell sarcomas (40%), 10 of 20 follicular dendritic cell sarcomas (50%), and none of 9 blastic plasmacytoid dendritic cell neoplasms were positive for PD-L1. Eleven of 20 (55%) follicular dendritic cell sarcomas were also positive for PD-L2. PD-L1 and PD-L2 are useful new markers for identifying select histiocyte and dendritic cell disorders and reveal novel patient populations as rational candidates for immunotherapy.

Avian dendritic cells: Phenotype and ontogeny in lymphoid organs

Dendritic cells (DC) are critically important accessory cells in the innate and adaptive immune systems. Avian DCs were originally identified in primary and secondary lymphoid organs by their typical morphology, displaying long cell processes with cytoplasmic granules. Several subtypes are known. Bursal secretory dendritic cells (BSDC) are elongated cells which express vimentin intermediate filaments, MHC II molecules, macrophage colony-stimulating factor 1 receptor (CSF1R), and produce 74.3+ secretory granules. Avian follicular dendritic cells (FDC) highly resemble BSDC, express the CD83, 74.3 and CSF1R molecules, and present antigen in germinal centers. Thymic dendritic cells (TDC), which express 74.3 and CD83, are concentrated in thymic medulla while interdigitating DC are found in T cell-rich areas of secondary lymphoid organs. Avian Langerhans cells are a specialized 74.3−/MHC II+ cell population found in stratified squamous epithelium and are capable of differentiating into 74.3+ migratory DCs. During organogenesis hematopoietic precursors of DC colonize the developing lymphoid organ primordia prior to immigration of lymphoid precursor cells. This review summarizes our current understanding of the ontogeny, cytoarchitecture, and immunophenotype of avian DC, and offers an antibody panel for the in vitro and in vivo identification of these heterogeneous cell types.

Dietary rice bran supplementation prevents Salmonella colonization differentially across varieties and by priming intestinal immunity

The global burden of enteric dysfunction and diarrhoeal disease remains a formidable problem that requires novel interventions. This study investigated the immune-modulatory capacity of bran across rice varieties with phytochemical differences. 129SvEvTac mice were fed a 10% rice bran or control diet followed by infection with Salmonella enterica. Faecal shedding titres were quantified and flow cytometry was used to investigate intestinal immunity. The largest protection against Salmonella colonization was observed with IAC600 variety. Reduced faecal shedding correlated with increased levels of boron, soluble fibre, vitamin E isomers, and fatty acids. IAC600 and Red Wells rice bran modulated small intestinal neutrophils, macrophages, interdigitating dendritic cells, CD8+, γδ, and regulatory T cells, as well as CD8+ and γδ T cells in the mesenteric lymph nodes. Rice bran is a promising functional food and merits evaluation for the prevention of Salmonella colonization and regulation of intestinal immunity in people.

Dermatopathic Lymphadenopathy With Increased IgG4-Positive Plasma Cells.

Both dermatopathic lymphadenopathy (DL) and immunoglobulin G4-related disease (IgG4-RD) are frequently complicated with allergic diseases. However, the relationship between DL and IgG4-RD is not well known. To clarify this relationship on the basis of clinical and pathological findings, including IgG4-positive (IgG4+) plasma cell infiltration in lymph nodes (LNs) of DL patients, we analyzed LNs of 11 DL patients using immunostaining of IgG, IgG4, forkhead box P3 (FOXP3), transforming growth factor (TGF)-β, interferon (IFN)-γ, and matrix metalloproteinase (MMP)-1, MMP-8, and MMP-13. Toluidine blue staining was also performed to identify mast cells. Of 3 patients with a high ratio of IgG4+/IgG+ cells (>40%) and elevated serum IgG4 levels, 2 developed IgG4-RD, whereas the other patient did not. Of 8 patients with a low ratio of IgG4+/IgG+ cells (<40%) or no infiltration of IgG4+ cells, 5 who could be followed did not develop IgG4-RD. The numbers of mast cells were similar to those of TGF-β-positive cells, and serial sections showed that mast cells possibly produce TGF-β. LNs of DL patients with a high ratio of IgG4+/IgG+ cells had significantly more mast cells and TGF-β-positive cells than those of patients with a low ratio of IgG4+/IgG+ cells or no infiltration of IgG4+ cells. However, no fibrosis was observed in LNs of both groups. IFN-γ was positive in interdigitating dendritic cells, Langerhans cells, and macrophages. MMP-1, MMP-8, or MMP-13 was expressed in macrophages. The lack of fibrosis in LNs may have been due to the production of IFN-γ, MMP-1, MMP-8, or MMP-13. Thus, DL with increased IgG4+ cells seems to be a phenotype of IgG4-RD in LNs.

Histopathological atlas and proposed classification for melanocytic lesions in Tyr::NRasQ61K; Cdkn2a−/− transgenic mice

Reference EPFL-ARTICLE-188431doi:10.1111/pcmr.12115View record in Web of Science Record created on 2013-09-09, modified on 2017-05-12

Interdigitating dendritic cell sarcoma presenting simultaneously with acute myelomonocytic leukemia: report of a rare case and literature review

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare tumor derived from interdigitating dendritic cells. We report the first case of a 64-year-old Chinese woman who was diagnosed with simultaneous IDCS and acute myelomonocytic leukemia (AML-M4). The patient had undergone chemotherapy for breast cancer 6years previously. Based on the laboratory results, both the IDCS and the AML-M4 in this patient were determined to be of myelogenous origination. Furthermore, a review of 62 IDCS cases (Medline database, key word: IDCS) reported to date revealed that as many as 17% of the patients had malignant disease and received radiotherapy and/or chemotherapy prior to developing IDCS, and that this group of patients showed worse prognosis compared with counterparts. The patient in the present report showed poor response to four cycles of sequential chemotherapy, and died 6months after the initial diagnosis.

Aberrant Expression of the Dendritic Cell Marker TNFAIP2 by the Malignant Cells of Hodgkin Lymphoma and Primary Mediastinal Large B-Cell Lymphoma Distinguishes These Tumor Types From Morphologically and Phenotypically Similar Lymphomas

Tumor necrosis factor-α-inducible protein-2 (TNFAIP2) is a protein upregulated in cultured cells treated with tumor necrosis factor α (TNF), but its expression in normal and neoplastic tissues remains largely unknown. Here, we use standard immunohistochemical techniques to demonstrate that TNFAIP2 is normally expressed by follicular dendritic cells, interdigitating dendritic cells, and macrophages but not by lymphoid cells in secondary lymphoid tissues. Consistent with this expression pattern, we found strong TNFAIP2 staining of tumor cells in 4 of 4 cases (100%) of follicular dendritic cell sarcoma and in 3 of 3 cases (100%) of histiocytic sarcoma. Although TNFAIP2 is not expressed by the small and intermediate-sized neoplastic B cells comprising follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, or marginal zone lymphoma, we observed strong TNFAIP2 staining of the large, neoplastic cells in 31 of 31 cases (100%) of classical Hodgkin lymphoma, in 12 of 12 cases (100%) of nodular lymphocyte-predominant Hodgkin lymphoma, and in 27 of 31 cases (87%) of primary mediastinal (thymic) large B-cell lymphoma. In contrast, TNFAIP2 was expressed by malignant cells in only 2 of 45 cases (4%) of diffuse large B-cell lymphoma, not otherwise specified, in 2 of 18 cases (11%) of Burkitt lymphoma, and in 1 of 19 cases (5%) of anaplastic large cell lymphoma. Further analysis indicates that TNFAIP2, as a single diagnostic marker, is more sensitive (sensitivity=87%) and specific (specificity=96%) than TRAF1, nuclear cRel, or CD23 for distinguishing the malignant B cells of primary mediastinal (thymic) large B-cell lymphoma from those of its morphologic and immunophenotypic mimic, diffuse large B-cell lymphoma, not otherwise specified. Thus, TNFAIP2 may serve as a useful new marker of dendritic and histiocytic sarcomas, the aberrant expression of which in the malignant cells of classical Hodgkin lymphoma and primary mediastinal (thymic) large B-cell lymphoma serves to distinguish these tumors from other large cell lymphomas in routine clinical practice.

BCL2 Chromosomal Translocation Is Not a General Feature of the Interdigitating Dendritic Cell Sarcoma

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasia of interdigitating dendritic cells. Two single case reports documenting IDCS harboring t(14;18) translocation involving immunoglobulin heavy chain (IGH) and BCL2 have been reported recently; however, one of the 2 IDCS has a synchronous follicular lymphoma, the absence or presence of a follicular lymphoma in the remaining case is not mentioned. In this study, by using polymerase chain reaction and fluorescence in situ hybridization techniques, we have showed that there is neither t(14;18)/IGH-BCL2 nor IGH gene rearrangement in 4 de novo IDCS without a concurrent or known history of a B-cell lymphoma, including follicular lymphoma, indicating that BCL2 chromosomal translocation is not a general feature of de novo IDCS.