Fascin and the Differential Diagnosis of Childhood Histiocytic Lesions

1998 ◽  
Vol 1 (3) ◽  
pp. 216-221 ◽  
Author(s):  
Ronald Jaffe ◽  
Donna DeVaughn ◽  
Erik Langhoff
Keyword(s):  
Dendritic Cells ◽  
Differential Diagnosis ◽  
Dendritic Cell ◽  
Langerhans Cells ◽  
False Negative ◽  
Cell Lineage ◽  
Large Cell ◽  
Cell Types ◽  
Large Numbers ◽  
Spitz Nevi

This is a descriptive screening of 46 examples of childhood histiocytic lesions and some of their look-alikes using a monoclonal antibody, p55, to fascin. Fascin, an actin-bundling protein, identifies dendritic cells in the blood and in tissues. Our aim was to test the diagnostic utility of the antibody in various lesions at different sites and to see whether the staining patterns give insight into the cell types involved. Fascin intensely stained the cells of juvenile xanthogranulomas (JXG), Rosai-Dorfman lesions, and soft tissue dendrocytomas. Normal Langerhans' cells and the cells of Langerhans' cell histiocytosis were unreactive. Their lack of fascin staining may be relevant to fascin being maturation as well as lineage related. Epithelioid and palisading granulomas were unstained, though an example of Kikuchi lymphadenitis had large numbers of dendritic-type cells that stained strongly. A reticulohistiocytoma of the skin was also unstained and look-alike lesions, Spitz nevi, and mast cell lesions did not stain. Two of three large-cell lymphomas (both CD30+) also had fascin reactivity. Even though fascin is not specific to dendritic cells, staining other cell types as well (false positive), and not entirely sensitive, dendritic cells such as tissue Langerhans' cells are unstained (false negative), there seems to be a consistency of staining in childhood histiocytic lesions. This may be of diagnostic use when read in the context of the tissue differential diagnosis. Whether fascin can serve as a marker for the dendritic cell lineage, or at least for some phases of dendritic cell lifecycle, is not answered by this survey.

Dendritic cells of the human epidermis: immuno-electron microscopic studies of la antigen reactivity

1978 ◽  
Vol 36 (2) ◽  
pp. 644-645
Author(s):  
G. Rowden ◽  
M. G. Lewis ◽  
T. M. Phillips
Keyword(s):  
Dendritic Cells ◽  
Langerhans Cells ◽  
Cell Types ◽  
Cell Type ◽  
Electron Microscopic ◽  
La Antigen ◽  
Microscopic Studies ◽  
A Cell ◽  
C3 Receptors ◽  
Antigen Reactivity

Langerhans cells of mammalian stratified squamous epithelial have proven to be an enigma since their discovery in 1868. These dendritic suprabasal cells have been considered as related to melanocytes either as effete cells, or as post divisional products. Although grafting experiments seemed to demonstrate the independence of the cell types, much confusion still exists. The presence in the epidermis of a cell type with morphological features seemingly shared by melanocytes and Langerhans cells has been especially troublesome. This so called "indeterminate", or " -dendritic cell" lacks both Langerhans cells granules and melanosomes, yet it is clearly not a keratinocyte. Suggestions have been made that it is related to either Langerhans cells or melanocyte. Recent studies have unequivocally demonstrated that Langerhans cells are independent cells with immune function. They display Fc and C3 receptors on their surface as well as la (immune region associated) antigens.

scholarly journals Langerhans' cells, veiled cells, and interdigitating cells in the mouse recognized by a monoclonal antibody.

1986 ◽  
Vol 163 (4) ◽  
pp. 981-997 ◽  
Author(s):  
G Kraal ◽  
M Breel ◽  
M Janse ◽  
G Bruin
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Langerhans Cells ◽  
Precursor Cells ◽  
Peritoneal Exudate ◽  
Peritoneal Exudate Cells ◽  
Interdigitating Cells

An mAb, NLDC-145, is described that specifically reacts with a group of nonlymphoid dendritic cells including Langerhans cells (LC), veiled cells (VC), and interdigitating cells (IDC). The antibody does not react with precursor cells in bone marrow and blood. Macrophages are not stained by the antibody, but a subpopulation of Ia+ peritoneal exudate cells is recognized. Possible relationships of the various nonlymphoid dendritic cell (NLDC) types are discussed.

scholarly journals Neuroendocrine Carcinoma of the Uterine Cervix: A Clinicopathologic and Immunohistochemical Study with Focus on Novel Markers (Sst2–Sst5)

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1211
Author(s):  
Frediano Inzani ◽  
Angela Santoro ◽  
Giuseppe Angelico ◽  
Angela Feraco ◽  
Saveria Spadola ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Target Therapy ◽  
Somatostatin Receptors ◽  
Neuroendocrine Differentiation ◽  
Large Cell ◽  
Cell Types ◽  
Somatostatin Analogues ◽  
Small Cell ◽  
Neuroendocrine Neoplasms ◽  
Neuroendocrine Carcinomas

Background. Gynecological neuroendocrine neoplasms (NENs) are extremely rare, accounting for 1.2–2.4% of the NENs. The aim of this study was to test cervical NENs for novel markers of potential utility for differential diagnosis and target therapy. Methods. All cases of our center (n = 16) were retrieved and tested by immunohistochemistry (IHC) for 12 markers including markers of neuroendocrine differentiation (chromogranin A, synaptophysin, CD56), transcription factors (CDX2 and TTF1), proteins p40, p63, p16INK4a, and p53, somatostatin receptors subtypes (SST2-SST5) and the proliferation marker Ki67 (MIB1). Results. All cases were poorly differentiated neuroendocrine carcinomas (NECs), 10 small cell types (small cell–neuroendocrine carcinomas, SCNECs) and 6 large cell types (large cell–neuroendocrine carcinomas, LCNECs); in 3 cases a predominant associated adenocarcinoma component was observed. Neuroendocrine cancer cells expressed at least 2 of the 3 tested neuroendocrine markers; p16 was intensely expressed in 14 (87.5%) cases; SST5 in 11 (56.25%, score 2–3, in 9 cases); SST2 in 8 (50%, score 2–3 in 8), CDX2 in 8 (50%), TTF1 in 5 (31.25%), and p53 in 1 case (0.06%). P63 and p40 expressions were negative, with the exception of one case that showed moderate expression for p63. Conclusions. P40 is a more useful marker for the differential diagnosis compared to squamous cell carcinoma. Neither CDX2 nor TTF1 expression may help the differential diagnosis versus potential cervical metastasis. P16 expression may suggest a cervical origin of NEC; however, it must be always integrated by clinical and instrumental data. The expression of SST2 and SST5 could support a role for SSAs (Somatostatin Analogues) in the diagnosis and therapy of patients with cervical NECs.

scholarly journals Immunometabolism governs dendritic cell and macrophage function

2015 ◽  
Vol 213 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Luke A.J. O’Neill ◽  
Edward J. Pearce
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Metabolic Reprogramming ◽  
Environmental Cues ◽  
Direct Impact ◽  
Innate And Adaptive Immunity ◽  
Danger Signals ◽  
Intracellular Metabolism

Recent studies on intracellular metabolism in dendritic cells (DCs) and macrophages provide new insights on the functioning of these critical controllers of innate and adaptive immunity. Both cell types undergo profound metabolic reprogramming in response to environmental cues, such as hypoxia or nutrient alterations, but importantly also in response to danger signals and cytokines. Metabolites such as succinate and citrate have a direct impact on the functioning of macrophages. Immunogenicity and tolerogenicity of DCs is also determined by anabolic and catabolic processes, respectively. These findings provide new prospects for therapeutic manipulation in inflammatory diseases and cancer.

Eto2/MTG16 Regulates E-Protein Activity and Subset Specification in Dendritic Cell Development

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1229-1229
Author(s):  
Hiyaa Singhee Ghosh ◽  
Kang Liu ◽  
Scott Hiebert ◽  
Boris Reizis
Keyword(s):  
Dendritic Cells ◽  
Transcription Factors ◽  
T Cell ◽  
Dendritic Cell ◽  
Cell Fate ◽  
Cell Lineage ◽  
Transcriptional Regulators ◽  
E Proteins ◽  
E Protein

Abstract Abstract 1229 Eto-family proteins were first discovered as translocation fusion in AML1 (Runx1), a gene most frequently disrupted in human leukemia. Of the translocations that disrupt the AML1 gene in leukemia, Eto1(MTG8)/AML1 translocation accounts for ∼15% of Acute Myeloid Leukemia (AML). The Eto-family proteins function as transcriptional co-repressors that bind to DNA-binding transcription factors to regulate their target genes. Eto2 (MTG16) is an Eto-family member implicated in secondary or therapy-related AML, although recent reports provide evidence for Eto2/MTG16 translocations in de novo AML as well. Furthermore, recent studies have highlighted a role for MTG16 in HSC self renewal and T cell lineage specification, indicating its emerging role overall in hematopoiesis. The co-repressor function of Eto for E-proteins has been described previously in the context of Eto/AML1 fusion proteins. E-proteins are a class of basic-helix-loop-helix (bHLH) transcription factors that play an important role in hematopoiesis. Among the E-protein family, the role of E2A has been extensively studied in B and T cell development. Recently, our lab discovered the specific requirement of the E-protein E2-2 in the development of Plasmacytoid Dendritic Cells (pDC). pDC are the professional interferon producing (IPC) cells of our immune system important in anti-viral, anti-tumor and auto-immunity. pDC are a subtype of the antigen-presenting classical Dendritic Cells (cDC) with distinct structural and functional properties. Recently, we demonstrated that the putative cell fate plasticity of pDC was a direct manifestation of continuous E2-2 function. Using pDC-reporter mice in which E2-2 could be inducibly deleted from mature pDC we showed that the continuous expression of E2-2 was required to prevent the conversion of pDC to cDC. Here we report our current studies that investigate the molecular players underlying the E2-2 orchestrated genetic program for pDC cell fate decision and maintenance. Analyzing the transcriptome of the transitioning pDC, we have identified MTG16 as an important player in the fine regulation of DC lineage decisions. Using knock-out and chimeric mice, progenitor studies, promoter and biochemical analyses, we demonstrate MTG16 as an important E2-2 corepressor, promoting E2-2 mediated genetic program. We report that in order to facilitate the pDC cell fate, MTG16 enables E2-2 to suppress the cDC gene expression program, by negatively regulating the E-protein inhibitor Id2. The cell-fate conversion through deletion or overexpression of lineage-deciding transcriptional regulators has been described previously for B- and T cells. Theseh studies highlight the susceptibility of blood cells to aberrant functions of crucial transcriptional regulators, potentially leading to pathologic conditions. Therefore, understanding the interrelationship between the various genetic regulators that control lineage decisions and cell-fate plasticity is cardinal to accurate diagnosis and therapy for hematopoietic pathologies. Our study provides the first evidence for a physiological role of E-protein/Eto-protein interaction in dendritic cell lineage decision. Disclosures: No relevant conflicts of interest to declare.

Langerhans Cell Histiocytosis: Back to Histiocytosis X

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-8-SCI-8
Author(s):  
Carl E. Allen
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Langerhans Cells ◽  
Langerhans Cell Histiocytosis ◽  
Conflicts Of Interest ◽  
Langerhans Cell ◽  
Histiocytosis X ◽  
Specific Gene ◽  
Myeloid Dendritic Cell ◽  
Epidermal Langerhans Cells

Abstract Abstract SCI-8 Langerhans cell histiocytosis (LCH) is a disorder characterized by inflammatory lesions that include pathologic CD207+ dendritic cells. LCH has pleotropic clinical presentations ranging from single lesions cured by curettage to potentially fatal multisystem disease. The first descriptions of LCH, including Hand-Schüller-Christian disease and Letterer-Siwe disease, were based on anatomic location and extent of the lesions. Despite clinical heterogeneity, LCH lesions are generally indistinguishable by histology, which led to the notion that the spectrum of clinical manifestations represents a single disorder, histiocytosis X. The designation “Langerhans cell histiocytosis” was subsequently proposed with discovery of cytoplasmic Birbeck granules in the pathologic infiltrating dendritic cells in histiocytosis X lesions, a feature shared by epidermal Langerhans cells. The etiology of LCH remains elusive, and debate of LCH as an inflammatory versus malignant disorder remains unresolved. However, recent discoveries question the model of LCH arising from transformed or pathologically activated epidermal Langerhans cells. We found cell-specific gene expression signature in CD207+ dendritic cells within LCH lesions to be more consistent with immature myeloid dendritic cell precursors than epidermal Langerhans cells. Furthermore, recent mouse studies demonstrate that CD207+ is more promiscuous than previously appreciated. Langerin (CD207) expression can be induced in many dendritic cell lineages, supporting the plausibility of a spectrum of candidates for an LCH cell of origin, including circulating dendritic cell precursors. Finally, recurrent activating BRAF mutations in LCH lesions suggest a role for a hyperactive RAS pathway in LCH pathogenesis, and possibly in normal dendritic cell development. This presentation will discuss the historical background and recent advances in LCH biology, along with a proposal to reframe “histiocytosis X” as a myeloid neoplasia caused by aberrant maturation and migration of myeloid dendritic cell precursors. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Modular expression analysis reveals functional conservation between human Langerhans cells and mouse cross-priming dendritic cells

2015 ◽  
Vol 212 (5) ◽  
pp. 743-757 ◽  
Author(s):  
Maxim N. Artyomov ◽  
Adiel Munk ◽  
Laurent Gorvel ◽  
Daniel Korenfeld ◽  
Marina Cella ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Therapeutic Target ◽  
Langerhans Cells ◽  
Antigen Processing ◽  
Genome Project ◽  
Cross Presentation ◽  
Functional Conservation ◽  
Transcriptional Signature

Characterization of functionally distinct dendritic cell (DC) subsets in mice has fueled interest in whether analogous counterparts exist in humans. Transcriptional modules of coordinately expressed genes were used for defining shared functions between the species. Comparing modules derived from four human skin DC subsets and modules derived from the Immunological Genome Project database for all mouse DC subsets revealed that human Langerhans cells (LCs) and the mouse XCR1+CD8α+CD103+ DCs shared the class I–mediated antigen processing and cross-presentation transcriptional modules that were not seen in mouse LCs. Furthermore, human LCs were enriched in a transcriptional signature specific to the blood cross-presenting CD141/BDCA-3+ DCs, the proposed equivalent to mouse CD8α+ DCs. Consistent with our analysis, LCs were highly adept at inducing primary CTL responses. Thus, our study suggests that the function of LCs may not be conserved between mouse and human and supports human LCs as an especially relevant therapeutic target.

scholarly journals The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency

2011 ◽  
Vol 208 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Venetia Bigley ◽  
Muzlifah Haniffa ◽  
Sergei Doulatov ◽  
Xiao-Nong Wang ◽  
Rachel Dickinson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Peripheral Blood ◽  
Langerhans Cells ◽  
Elevated Serum ◽  
Blood Compartment ◽  
Hla Dr ◽  
Epidermal Langerhans Cells

Congenital or acquired cellular deficiencies in humans have the potential to reveal much about normal hematopoiesis and immune function. We show that a recently described syndrome of monocytopenia, B and NK lymphoid deficiency additionally includes the near absence of dendritic cells. Four subjects showed severe depletion of the peripheral blood HLA-DR+ lineage− compartment, with virtually no CD123+ or CD11c+ dendritic cells (DCs) and very few CD14+ or CD16+ monocytes. The only remaining HLA-DR+ lineage− cells were circulating CD34+ progenitor cells. Dermal CD14+ and CD1a+ DC were also absent, consistent with their dependence on blood-derived precursors. In contrast, epidermal Langerhans cells and tissue macrophages were largely preserved. Combined loss of peripheral DCs, monocytes, and B and NK lymphocytes was mirrored in the bone marrow by complete absence of multilymphoid progenitors and depletion of granulocyte-macrophage progenitors. Depletion of the HLA-DR+ peripheral blood compartment was associated with elevated serum fms-like tyrosine kinase ligand and reduced circulating CD4+CD25hiFoxP3+ T cells, supporting a role for DC in T reg cell homeostasis.

TCL1 expression in plasmacytoid dendritic cells (DC2s) and the related CD4+ CD56+ blastic tumors of skin

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 5007-5009 ◽  
Author(s):  
Marco Herling ◽  
Michael A. Teitell ◽  
Rhine R. Shen ◽  
L. Jeffrey Medeiros ◽  
Dan Jones
Keyword(s):  
Dendritic Cells ◽  
Lymph Node ◽  
Dendritic Cell ◽  
De Novo ◽  
Nk Cell ◽  
Cell Lineage ◽  
Plasmacytoid Dendritic Cells ◽  
Prolymphocytic Leukemia ◽  
T Cell Malignancies ◽  
Myelomonocytic Leukemia

AbstractInitially considered to be of natural killer (NK)–cell origin, CD4+ CD56+ blastic tumors (BTs) of skin have recently been proposed to be of dendritic cell lineage. We have previously described BTs with transformation to myelomonocytic leukemia. Here we report expression of the lymphoid proto-oncogene TCL1 in 10 (83%) of 12 BTs and in lymph node plasmacytoid dendritic cells (DC2s). TCL1 was also expressed in myelomonocytic blasts of 3 transformed BT cases but not in true NK-cell tumors (n = 18), de novo acute myelomonocytic leukemias (1 of 14, 7%), or mature T-cell malignancies (1 of 112, < 1%), with the exception of T-prolymphocytic leukemia (T-PLL). All BT cases were also positive for the DC2-associated marker CD123. These results further support derivation of BTs from DC2s, and demonstrate that TCL1 expression in this tumor is common to the immature blastoid, lymphoid-appearing, and subsequent myelomonocytic phases of this disease.

scholarly journals The Dendritic Cell Lineage: Ontogeny and Function of Dendritic Cells and Their Subsets in the Steady State and the Inflamed Setting

2013 ◽  
Vol 31 (1) ◽  
pp. 563-604 ◽  
Author(s):  
Miriam Merad ◽  
Priyanka Sathe ◽  
Julie Helft ◽  
Jennifer Miller ◽  
Arthur Mortha
Keyword(s):  
Dendritic Cells ◽  
Steady State ◽  
Dendritic Cell ◽  
Cell Lineage ◽  
And Function
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