DOCSLIB.ORG

Histiocytic and Dendritic Cell Lesions

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Histiocytic and Dendritic Cell Lesions Histiocytic and Dendritic Cell Lesions L. Jeffrey Medeiros, MD MD Anderson Cancer Center Outline 2016 classification of Histiocyte Society Langerhans cell histiocytosis / sarcoma Erdheim-Chester disease Juvenile xanthogranuloma Malignant histiocytosis Histiocytic sarcoma Interdigitating dendritic cell sarcoma Follicular dendritic cell sarcoma Rosai-Dorfman disease Hemophagocytic lymphohistiocytosis Writing Group of the Histiocyte Society Major Groups of Histiocytic Lesions Group Name L Langerhans-related C Cutaneous and mucocutaneous M Malignant histiocytosis R Rosai-Dorfman disease H Hemophagocytic lymphohistiocytosis Blood 127: 2672, 2016 L Group Langerhans cell histiocytosis Indeterminate cell tumor Erdheim-Chester disease S100 Normal Langerhans cells Langerhans Cell Histiocytosis “Old” Terminology Eosinophilic granuloma Single lesion of bone, LN, or skin Hand-Schuller-Christian disease Lytic lesions of skull, exopthalmos, and diabetes insipidus Sidney Farber Letterer-Siwe disease 1903-1973 Widespread visceral disease involving liver, spleen, bone marrow, and other sites Histiocytosis X Umbrella term proposed by Sidney Farber and then Lichtenstein in 1953 Louis Lichtenstein 1906-1977 Langerhans Cell Histiocytosis Incidence and Disease Distribution Incidence Children: 5-9 x 106 Adults: 1 x 106 Sites of Disease Poor Prognosis Bones 80% Skin 30% Liver Pituitary gland 25% Spleen Liver 15% Bone marrow Spleen 15% Bone Marrow 15% High-risk organs Lymph nodes 10% CNS <5% Blood 127: 2672, 2016 N Engl J Med 379: 856, 2018 Langerhans Cell Histiocytosis Solitary lesion of bone Eosinophilic Granuloma CD1a Langerhans Cell Histiocytosis Lungs Associated with smoking BRAF V600E CD207 Langerhans Cell Histiocytosis Lymph Nodes CD1a LNs can be localized or a part of disseminated disease This patient had generalized LNs and BRAF V600E mutation Langerhans Cell Histiocytosis Morphologic Features Frequency Feature 100% Langerhans cells (<5-75%) 92% Eosinophils 84% Multinucleated giant cells 75% Small lymphocytes 61% Necrosis 49% Neutrophils 29% Foamy histiocytes Mild atypia (reactive type) in ~50% of cases Mitotic rate: 0-23/10 high power fields Arch Pathol Lab Med 107: 59, 1983 Langerhans Cell Histiocytosis Immunophenotype and EM Immunophenotype S100+, CD1a+, CD207/langerin+ +/- BRAF V600E (mutation specific antibody) +/- CD4, CD11c, CD45/LCA, CD68, lysozyme+ Note: S100, CD1a, and CD207/langerin are not restricted to Langerhans cells Electron Microscopy Birbeck granules (aka Langerhans bodies) CD207 Am J Surg Pathol 41: 1390, 2017 Cyclin D1 Langerhans Cell Histiocytosis Birbeck Granules Also known as X bodies or Langerhans bodies Birbeck granules are characteristic (but not unique to) Langerhans cells Presence is a reflection of membrane activity; function debated Contain langerin = a type II transmembrane lectin receptor Francoise Basset, PhD J Invest Dermatol 37: 51, 1961 Michael S. C. Birbeck, PhD CR Acad Sci (Paris) 261:5719, 1965 1925-2005 Langerhans Cell Histiocytosis Mutations in BRAF/MAP2K1 Are Common Blood 116: 1919, 2010 BRAF V600E 18/40 (45%) MAP2K1 11/40 (27.5%) Blood 124: 1655, 2014 Extracellular MAPK/ ERK PATHWAY RTK VEGFR PDGFR EGFR Cytoplasm RAS GTP‐binding proteins: Proteins HRAS, KRAS and NRAS ARAF BRAF CRAF P Encoded by MAP2K1 gene MEK1/2 P ERK 1/2 Nucleus Transcription Regulation of proliferation, apoptosis, • MAPK: Mitogen‐activated protein kinase p90Rsk factors metabolism and immune response • ERK: Extracellular signal‐regulated kinase 85% of LCH cases have genetic abnormalities of the MAPK pathway They likely all do Blood 128: 2533, 2016 Langerhans Cell Histiocytosis Misguided Myeloid Dendritic Cell Model Model to explain the widely disparate presentations of LCH Distribution of disease depends on the cell in which mutation/ERK activation occurs Hematology Am Soc Hematol Educ Program 2015;2015:559-564 Immunity 44: 439, 2016 “Histiocytosis X (HX) has the advantage of widespread use, although it has been applied to other types of histiocytosis. The generally recognized Langerhans cell derivation of HX makes Langerhans cell histiocytosis an attractive alternative.” Arch Pathol Lab Med 107: 59, 1983 Langerhans Cell Histiocytosis (LCH) Rarely Associated with Lymphomas Mantle cell lymphoma LCH No BRAF V600E or MAP2K1 mutations Lymphomas 5 Classical Hodgkin lymphoma 1 Mantle cell lymphoma 1 Angioimmunoblastic T-cell CD1a LCH was <10%; incidental Sergio Pina Oviedo, MD Mod Pathol 30: 734, 2017 Langerhans Cell Histiocytosis Differential Diagnosis Dermatopathic lymphadenopathy Indeterminate dendritic cell tumor Langerhans cell sarcoma Dermatopathic Lymphadenopathy S100 Benign reaction pattern associated with skin disease CD1a Indeterminate Dendritic cell Tumor Thought to be derived from normal precursors of Langerhans cells (so-called indeterminate cells) Patients present with > nodules, papules or plaques on skin Dermis-based disease that can extend into subcutaneous fat Histologically looks like Langerhans cells histiocytosis But often no eosinophils Immunophenotype: CD1a+, S100+, CD207- Electron microscopy: No Birbeck granules Genetics: ETV3-NCOA2/t(1;8)(q23.1;8q13.3) reported in 3 cases Highly variable clinical course: Spontaneous regression or progression Indeterminate Dendritic Cell Tumor CD1a A negative langerin/CD207 is required to make this diagnosis CD207 Langerhans Cell Sarcoma Definition A high-grade neoplasm with overt malignant cytologic features and Langerhans cell phenotype History Rarely preceded by typical LCH (in my experience) Age and Sites of Disease Median 41 yrs (10-72yrs) Extranodal ~ 80% (most often skin); nodal ~ 20% Ancillary Support for Diagnosis Immunohistochemistry: S-100+, CD1a+, CD207/langerin+ Electron microscopy: Birbeck granules Genetics Rare cases with monoclonal IGH rearrangements Prognosis ~50% mortality as a result of progressive disease Langerhans Cell Sarcoma CD207 Erdheim-Chester Disease Definition “A clonal, systemic proliferation of histiocytes, commonly having a foamy (xanthomatous) component and containing Touton giants cells.” 2017 WHO book p. 481 Described by W. Chester in single author paper in German in 1930. J. Erdheim was mentor Renamed Erdheim-Chester disease in 1972 Jacob Erdheim, MD William Chester, MD Erdheim-Chester Disease Clinicopathologic Features Age and Sex Ratio Median 53 years (range, 20-74) Sex ratio: 3 to 1 male predominance Symptoms Can be asymptomatic or aggressive; related to sites Dull and deep bone pain common (especially knees) Histologic features Bland histiocytes infiltrate tissues Foamy or eosinophilic cytoplasm; Touton giant cells Fibrosis is common; +/- lymphocytes, plasma cells, eos No mitoses, necrosis, granulomas, emperipolesis Looks/phenotypes like juvenile xanthogranuloma Imaging Bilateral, symmetric cortical osteosclerosis of long bones Surrounds aorta (“coated”) or kidney (“hairy kidney”) Genetics BRAF V600E mutations in ~50%, ~4% NRAS, ~10% PI3KA Blood Advances 1:357, 2017 Erdheim-Chester Disease Positive CD14 CD68 CD163 Fascin Factor XIII Negative CD1a CD207 S100+ ~20% CD68 CD1a Erdheim-Chester Disease Radiologic Images Case courtesy of Dr Andrew Lawson Radiopaedia.org, rID: 29803 Case courtesy of Dr Andrew Dixon, Radiopaedia.org, rID: 9351 CGroup Many different lesions – most on skin Can subdivide into two broad groups Xanthogranuloma Non-xanthogranuloma Juvenile Xanthogranuloma Affects children >> adults Rare: < 1% of all pediatric tumors Single, few, or multiple lesions on skin: yellow papules 0.5-1 cm Often regress spontaneously Long bones are not involved Rarely patients have visceral involvement or disseminated disease Can cause symptoms or death due to local invasion Genetics Localized CGH: chromosomal abnormalities uncommon (~5%) Disseminated CGH: nonspecific chromosomal abnormalities described 1 case with MAPK1 mutation (Oncotarget 8: 46065, 2017) Mod Pathol 30:1234, 2017 Juvenile Xanthogranuloma Immunophenotype CD14+ CD68+ CD163+ Factor XIIIa +/- S-100+ ~20% Fascin+ ~20% CD1a- CD207/langerin - MAPK Pathway Mutations in Histiocytic Lesions A Unifying Feature in Pathogenesis LCH = Langerhans cell histiocytosis JXG = Juvenile xanthogranuloma ECD = Erdheim-Chester disease Hematology Am Soc Hematol Educ Program 2015; 2015:559-564 M Group Histiocytic sarcoma Interdigitating dendritic cell sarcoma Langerhans cell sarcoma “…we recommend reusing the old-term malignant histiocytosis, and refer to the phenotype as a subtype.” Blood 127: 2672, 2016 Histiocytic Sarcoma Definition and Clinicopathologic Features Definition A malignant proliferation of cells with morphologic and immunophenotypic features of mature tissue histiocytes Epidemiology Median age = 52 y; males = females Subset associated with B-cell lymphoma (transdifferentiation) Rare pts with mediastinal germ cell tumor and isochromosome 12p Presentation Often extranodal (GI tract, skin, soft tissues) Can be nodal or disseminated (“malignant histiocytosis”) Genetics Subset of cases with monoclonal Ig rearrangements Limited data on mutations (until recently) Outcome Clinically aggressive; poor response to therapy 60-80% of patients die of disease 2017 WHO book p. 468-470 Histiocytic Sarcoma CD11c CD163 Histiocytic Sarcoma Immunophenotype Positive Vimentin S100 (weak or focal), Ki-67 10-20% ZBTZ46 (Mod Pathol 31:1479, 2018) Variably Positive Fascin Weakly and variably positive CD45/LCA, CD68, lysozyme Negative CD1a, CD207/langerin CD21, CD23, CD35, clusterin CD34, myeloperoxidase EMA, keratins, melanoma-associated antigens B-cell and T-cell antigens 2017 WHO book p. 475 Methods 28 cases
Load more

Recommended publications
  • WSC 10-11 Conf 7 Layout Master
    The Armed Forces Institute of Pathology Department of Veterinary Pathology Conference Coordinator Matthew Wegner, DVM WEDNESDAY SLIDE CONFERENCE 2010-2011 Conference 7 29 September 2010 Conference Moderator: Thomas Lipscomb, DVM, Diplomate ACVP CASE I: 598-10 (AFIP 3165072). sometimes contain many PAS-positive granules which are thought to be phagocytic debris and possibly Signalment: 14-month-old , female, intact, Boxer dog phagocytized organisms that perhaps Boxers and (Canis familiaris). French bulldogs are not able to process due to a genetic lysosomal defect.1 In recent years, the condition has History: Intestine and colon biopsies were submitted been successfully treated with enrofloxacin2 and a new from a patient with chronic diarrhea. report indicates that this treatment correlates with eradication of intramucosal Escherichia coli, and the Gross Pathology: Not reported. few cases that don’t respond have an enrofloxacin- resistant strain of E. coli.3 Histopathologic Description: Colon: The small intestine is normal but the colonic submucosa is greatly The histiocytic influx is reportedly centered in the expanded by swollen, foamy/granular histiocytes that submucosa and into the deep mucosa and may expand occasionally contain a large clear vacuole. A few of through the muscular wall to the serosa and adjacent these histiocytes are in the deep mucosal lamina lymph nodes.1 Mucosal biopsies only may miss the propria as well, between the muscularis mucosa and lesions. Mucosal ulceration progresses with chronicity the crypts. Many scattered small lymphocytes with from superficial erosions to patchy ulcers that stop at plasma cells and neutrophils are also in the submucosa, the submucosa to only patchy intact islands of mucosa.
    [Show full text]
  • An Electron Microscope Study of Histiocyte Response to Ascites Tumor Homografts*
    An Electron Microscope Study of Histiocyte Response to Ascites Tumor Homografts* L. J. JOURNEYANDD. B. Aiviosf (Experimental Biology Department, Roswell Park Memorial Institute, fíujfaln.New York) SUMMARY When the ascites forms of the DBA/2 lymphoma L1210 or the C57BL E.L. 4 lymphoma are injected into C3H mice, host histiocytes (macrophages) accumulate and are responsible for the destruction of a large number of tumor cells. Many of the tumor cells, often apparently intact, are ingested. The ingestion process is rapid and depends upon invagination of an area of the histiocyte with simultaneous projection of cytoplasmic fimbriae which complete the encirclement. The earliest change seen in the enclosed cell is shrinkage; digestion of the cell wall and cytoplasmic elements fol lows. Phagocytosis accounts for only a proportion of the cells destroyed by histiocytes. Other cells are probably destroyed when their cell membrane is broken down in an area in contact with a histiocyte, apparently permitting fusion of the two cytoplasms. Weaver and his colleagues (13) observed that cytes and details some of the concomitant changes host cells were frequently found in close associa occurring in the histiocytes themselves. tion with tumor cells and described death of both host and incompatible tumor cell after a period of MATERIALS AND METHODS contact. Gorer (9) found that the predominant In a series of experiments 20 X IO7 cells from host cell in the ascites fluid during tumor rejection rapidly growing ascites populations of the lympho- was the histiocyte. This finding was confirmed, and mas E. L. 4 or L1210 native to C57BL and DBA/ some quantitative measurements were made by 2, respectively, were injected into the peritoneal one of us (1) and later by Weiser and his col cavity of young adult male C3H/He mice.
    [Show full text]
  • Histiocytic and Dendritic Cell Lesions
    1/18/2019 Histiocytic and Dendritic Cell Lesions L. Jeffrey Medeiros, MD MD Anderson Cancer Center Outline 2016 classification of Histiocyte Society Langerhans cell histiocytosis / sarcoma Erdheim-Chester disease Juvenile xanthogranuloma Malignant histiocytosis Histiocytic sarcoma Interdigitating dendritic cell sarcoma Follicular dendritic cell sarcoma Rosai-Dorfman disease Hemophagocytic lymphohistiocytosis Writing Group of the Histiocyte Society 1 1/18/2019 Major Groups of Histiocytic Lesions Group Name L Langerhans-related C Cutaneous and mucocutaneous M Malignant histiocytosis R Rosai-Dorfman disease H Hemophagocytic lymphohistiocytosis Blood 127: 2672, 2016 L Group Langerhans cell histiocytosis Indeterminate cell tumor Erdheim-Chester disease S100 Normal Langerhans cells Langerhans Cell Histiocytosis “Old” Terminology Eosinophilic granuloma Single lesion of bone, LN, or skin Hand-Schuller-Christian disease Lytic lesions of skull, exopthalmos, and diabetes insipidus Sidney Farber Letterer-Siwe disease 1903-1973 Widespread visceral disease involving liver, spleen, bone marrow, and other sites Histiocytosis X Umbrella term proposed by Sidney Farber and then Lichtenstein in 1953 Louis Lichtenstein 1906-1977 2 1/18/2019 Langerhans Cell Histiocytosis Incidence and Disease Distribution Incidence Children: 5-9 x 106 Adults: 1 x 106 Sites of Disease Poor Prognosis Bones 80% Skin 30% Liver Pituitary gland 25% Spleen Liver 15% Bone marrow Spleen 15% Bone Marrow 15% High-risk organs Lymph nodes 10% CNS <5% Blood 127: 2672, 2016 N Engl J Med
    [Show full text]
  • Progress in Understanding the Pathogenesis of Langerhans Cell Histiocytosis: Back to Histiocytosis X?
    review Progress in understanding the pathogenesis of Langerhans cell histiocytosis: back to Histiocytosis X? Marie-Luise Berres,1,2,3,4 Miriam Merad1,2,3 and Carl E. Allen5,6 1Department of Oncological Sciences, Mount Sinai School of Medicine, 2Tisch Cancer Institute, Mount Sinai School of Medicine, 3Immunology Institute, Mount Sinai School of Medicine, New York, NY, USA, 4Department of Internal Medicine III, University Hospital, RWTH Aachen, Aachen, Germany, 5Texas Children’s Cancer Center, and 6Baylor College of Medicine, Houston, TX, USA Summary Langerhans cell histiocytosis (LCH) is the most common his- tiocytic disorder, arising in approximately five children per Langerhans cell histiocytosis (LCH), the most common million, similar in frequency to paediatric Hodgkin lym- histiocytic disorder, is characterized by the accumulation of phoma and acute myeloid leukaemia (AML) (Guyot-Goubin CD1A+/CD207+ mononuclear phagocytes within granuloma- et al, 2008; Stalemark et al, 2008; Salotti et al, 2009). The tous lesions that can affect nearly all organ systems. Histori- median age of presentation is 30 months, though LCH is cally, LCH has been presumed to arise from transformed or reported in adults in approximately one adult per million, pathologically activated epidermal dendritic cells called Lan- both as unrecognized chronic paediatric disease and de novo gerhans cells. However, new evidence supports a model in disease (Baumgartner et al, 1997). There are occasional which LCH occurs as a consequence of a misguided differen- reports of affected non-twin siblings and multiple cases in tiation programme of myeloid dendritic cell precursors. one family, though it is not clear if this is significantly more Genetic, molecular and functional data implicate activation frequent than one would expect by chance (Arico et al, of the ERK signalling pathway at critical stages in myeloid 2005).
    [Show full text]
  • Histiocyte Society LCH Treatment Guidelines
    LANGERHANS CELL HISTIOCYTOSIS Histiocyte Society Evaluation and Treatment Guidelines April 2009 Contributors: Milen Minkov Vienna, Austria Nicole Grois Vienna, Austria Kenneth McClain Houston, USA Vasanta Nanduri Watford, UK Carlos Rodriguez-Galindo Memphis, USA Ingrid Simonitsch-Klupp Vienna, Austria Johann Visser Leicester, UK Sheila Weitzman Toronto, Canada James Whitlock Nashville, USA Kevin Windebank Newcastle upon Tyne, UK Disclaimer: These clinical guidelines have been developed by expert members of the Histiocyte Society and are intended to provide an overview of currently recommended treatment strategies for LCH. The usage and application of these clinical guidelines will take place at the sole discretion of treating clinicians who retain professional responsibility for their actions and treatment decisions. The following recommendations are based on current best practices in the treatment of LCH and are not necessarily based on strategies that will be used in any upcoming clinical trials. The Histiocyte Society does not sponsor, nor does it provide financial support for, the treatment detailed herein. 1 Table of Contents INTRODUCTION...................................................................................................... 3 DIAGNOSTIC CRITERIA......................................................................................... 3 PRETREATMENT CLINICAL EVALUATION ......................................................... 3 1. Complete History........................................................................................
    [Show full text]
  • Download PDF (3467K)
    Studies on Phagocytosis and Fate of Histiocyte in Subcutaneous Connective Tissue A Study of Histiocyte with Electron Microscope By Michio Kunichika Department of Anatomy, Yamaguchi University School of Medicine (Director : Prof. Gako Jimbo) Chapter I. Introduction So far the phagocyte has been studied with only the light microscope and the details of the ultramicroscopic structure, which exceeds the limitation of the resolution power of 0.2p, has not been clarified. In 1938, the electron microscope was invented by B or r i es and R u s k a and, in 1948, the ultra-microtom method was established by Peas e, Baker and others. Thus, in these several years, cytomor- phology has made a great progress. By means of the electron microscope (abbreviated as EM hereafter) the finer structure of the cell has gradually been clarified and it is generally accepted that the cell membrane is a real membrane of a definite thickness. At present the assumption that, when a foreign body is attached, the cell membrane once disappears allowing the invasion of the foreign body into the cytoplasm is untenable. Pal a d e also reported that the endplasmic reticulum was communicated with the pericellular space and, presumably, was the apparatus the function of which was exchange of substance with the medium around the cell. U c h i n o (1957) studied the phagocyte in the subcutaneous connective tissue and stated that foreign body particles were carried to the so-called food vacuole via E.R. and were filled in it when they were numer- ous and were distributed on the inner surface of the limiting membrane of the vacuole when they were rare, and that indian ink and sepia melanin granules were chemically stable and did not seem to have been influenced by the digesting action in food vacuole though phagocytized substance was usually digested in it.
    [Show full text]
  • Heterogeneity of HLA-DR-Positive Histiocytes in Human Intestinal Lamina Propria: a Combined Histochemical and Immunohistological Analysis
    J Clin Pathol: first published as 10.1136/jcp.36.4.379 on 1 April 1983. Downloaded from J Clin Pathol 1983;36:379-384 Heterogeneity of HLA-DR-positive histiocytes in human intestinal lamina propria: a combined histochemical and immunohistological analysis WS SELBY, LW POULTER, S HOBBS, DP JEWELL, G JANOSSY From the Department ofGastroenterology, John Radcliffe Hospital, Oxford, and Department of Immunology, Royal Free Hospital School of Medicine, London SUMMARY HLA-DR-positive histiocytes in the lamina propria of the human intestine have been characterised using combined histochemical and immunohistological techniques. In the small intestine, 80-90% of the HLA-DR+ histiocytes had irregular surfaces with stellate processes, and exhibited strong membrane adenosine triphosphatase (ATPase) activity, but weak acid phos- phatase (ACP) and non-specific esterase (NSE) activities (HLA-DR+ ACP+'- NSA+'- ATP++; type 1 cell). In contrast, in the lamina propria of the colon the majority (60-70%) of HLA-DR+ cells were large, round cells with strong ACP and NSE activities but no detectable ATPase activity (HLA-DR+ ACP++ NSE++ ATP+'-; type 2 cell). The colon also contained a population of type 1 cells (30-40%). In active inflammatory bowel disease affecting the colon a third population of HLA-DR+ histiocytes was seen. These cells were irregular in outline, with many processes, and were ACP++ NSE+ ATP+'- (type 3 cell). The type 3 cells appeared to replace type 2 cells. After treatment, the appearances returned to normal. These findings suggest that the different populations of HLA-DR+ histiocytes in the human intestine may have several functions, reflecting the different forms of antigen present in the intestine.
    [Show full text]
  • Histiocytic Disorders Amir H
    PHC15 12/06/2006 04:24PM Page 340 15 Histiocytic disorders Amir H. Shahlaee and Robert J. Arceci of phagocytosis of foreign material, antigen processing, and Introduction antigen presentation to lymphocytes. This system, recog- nized in part through the work of Metchnikoff, was originally The histiocytoses are a diverse group of hematologic dis- termed the reticuloendothelial system by Ludwig Aschoff orders defined by the pathologic infiltration of normal tissues in the early part of the twentieth century.3,4 The central cell by cells of the mononuclear phagocyte system (MPS). The of this system, the mononuclear phagocyte or histiocyte, heterogeneity of this family of disorders, a direct result of the represents a group of anatomically and functionally distinct biologic variability of the cells of the MPS and the tissues they cells arising from a common precursor, the hematopoietic inhabit, makes the study of these diseases one of the most stem cell. intriguing yet complex areas of modern hematology. Cells of the MPS have a wide range of morphologic, anatomic Advances in basic hematology and immunology over the and functional characteristics that make classification of this last two decades have significantly enhanced our under- system difficult. Our ability to identify and classify the cells standing of the histiocytic disorders. It is now accepted that of the MPS has advanced in parallel with developments in the pathogenic cells central to the development of the histio- basic hematology and immunology. As our knowledge of the cytoses arise from a common hematopoietic progenitor. More molecular biology regulating hematopoiesis has improved, specifically, the ability to molecularly identify the hemato- we have been able to identify specific characteristics that poietic cells has enabled us to classify the histiocytoses based have enabled us to classify the cells of the MPS.
    [Show full text]
  • Hematopathology
    320A ANNUAL MEETING ABSTRACTS expression of ALDH1 was analyzed using mouse monoclonal ALDH1 antibody (BD Conclusions: Based on the present results we conclude that miR29ab1 ko’s have Biosciences, San Jose, CA). Correlations between ALDH1 expression and clinical and decreased hematopoietic stem cell population compared to the wild types and that histological parameters were assessed by Pearson’s Chi-square and M-L Chi-square miR29ab1 might have an important role in the maintenance of this cell population. tests. Survival curves were generated using the Kaplan-Meier method and statistical Also, miR29 genes might regulate immunity and life span, since both miR29ab1 and differences by log rank test. miR29ab1/b2c ko’s seem to have markedly decreased life spans. Results: Majority of the tumors (116, 63%) showed stromal staining only, 21 (11%) tumors showed both epithelial and stromal expression, 47 (26%) tumors did not show 1347 The Majority of Immunohistochemically BCL2 Negative FL Grade either epithelial or stromal staining. The normal salivary gland showed epithelial I/II Carry A t(14;18) with Mutations in Exon 1 of the BCL2 Gene and Can expression only. Statistical analyses did not show any correlation between tumor pattern, Be Identifi ed with the BCL2 E17 Antibody tumor size, the presence of perineural invasion and the patterns of ALDH1 expression. P Adam, R Baumann, I Bonzheim, F Fend, L Quintanilla-Martinez. Eberhard-Karls- The survival analysis using Kaplan-Meier method and log rank test did not show any University, Tubingen, Baden-Wurttemberg, Germany. signifi cant differences among the three patterns of ALDH1 expression with survival.
    [Show full text]
  • I M M U N O L O G Y Core Notes
    II MM MM UU NN OO LL OO GG YY CCOORREE NNOOTTEESS MEDICAL IMMUNOLOGY 544 FALL 2011 Dr. George A. Gutman SCHOOL OF MEDICINE UNIVERSITY OF CALIFORNIA, IRVINE (Copyright) 2011 Regents of the University of California TABLE OF CONTENTS CHAPTER 1 INTRODUCTION...................................................................................... 3 CHAPTER 2 ANTIGEN/ANTIBODY INTERACTIONS ..............................................9 CHAPTER 3 ANTIBODY STRUCTURE I..................................................................17 CHAPTER 4 ANTIBODY STRUCTURE II.................................................................23 CHAPTER 5 COMPLEMENT...................................................................................... 33 CHAPTER 6 ANTIBODY GENETICS, ISOTYPES, ALLOTYPES, IDIOTYPES.....45 CHAPTER 7 CELLULAR BASIS OF ANTIBODY DIVERSITY: CLONAL SELECTION..................................................................53 CHAPTER 8 GENETIC BASIS OF ANTIBODY DIVERSITY...................................61 CHAPTER 9 IMMUNOGLOBULIN BIOSYNTHESIS ...............................................69 CHAPTER 10 BLOOD GROUPS: ABO AND Rh .........................................................77 CHAPTER 11 CELL-MEDIATED IMMUNITY AND MHC ........................................83 CHAPTER 12 CELL INTERACTIONS IN CELL MEDIATED IMMUNITY ..............91 CHAPTER 13 T-CELL/B-CELL COOPERATION IN HUMORAL IMMUNITY......105 CHAPTER 14 CELL SURFACE MARKERS OF T-CELLS, B-CELLS AND MACROPHAGES...............................................................111
    [Show full text]
  • Mast Cell Sarcoma: a Rare and Potentially Under
    Modern Pathology (2013) 26, 533–543 & 2013 USCAP, Inc. All rights reserved 0893-3952/13 $32.00 533 Mast cell sarcoma: a rare and potentially under-recognized diagnostic entity with specific therapeutic implications Russell JH Ryan1, Cem Akin2,3, Mariana Castells2,3, Marcia Wills4, Martin K Selig1, G Petur Nielsen1, Judith A Ferry1 and Jason L Hornick2,5 1Pathology Service, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA; 2Mastocytosis Center, Harvard Medical School, Boston, MA, USA; 3Department of Medicine, Harvard Medical School, Boston, MA, USA; 4Seacoast Pathology / Aurora Diagnostics, Exeter, NH and 5Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA Mast cell sarcoma is a rare, aggressive neoplasm composed of cytologically malignant mast cells presenting as a solitary mass. Previous descriptions of mast cell sarcoma have been limited to single case reports, and the pathologic features of this entity are not well known. Here, we report three new cases of mast cell sarcoma and review previously reported cases. Mast cell sarcoma has a characteristic morphology of medium-sized to large epithelioid cells, including bizarre multinucleated cells, and does not closely resemble either normal mast cells or the spindle cells of systemic mastocytosis. One of our three cases arose in a patient with a remote history of infantile cutaneous mastocytosis, an association also noted in one previous case report. None of our three cases were correctly diagnosed as mast cell neoplasms on initial pathological evaluation, suggesting that this entity may be under-recognized. Molecular testing of mast cell sarcoma has not thus far detected the imatinib- resistant KIT D816V mutation, suggesting that recognition of these cases may facilitate specific targeted therapy.
    [Show full text]
  • Histiocytosis an Introduction
    Br. J. Cancer SI -S3 '." Macmillan Press Ltd., 1994 Br. J. Cancer (1994), 70, (Suppl. XXIII) SI-S3 1994 Histiocytosis An Introduction Jon Pritchard FRCP' & Valerie Broadbent FRCP2 'Department of Haematology/Oncology, Hospitalfor Sick Children, Great Ormond Street, London, WCIN 3JH, England. 2Consultant Paediatric Oncologist, Paediatric Oncology Unit, Box No 181, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, England. Summary The Histiocytoses are a group of rare and puzzling multisystem disorders, currently regarded as non-malignant but often treated with 'cancer chemotherapy'. In this article, the origins of histiocytes and of the Histiocyte Society's classification of the Histiocytoses are described with suggested minor modifications to the classification. The current nomenclature for the 2 principal diseases, now named 'Langerhans cell histiocytosis' and 'Haemophagocytic Lymphohistiocytosis', is less confusing than the terms originally chosen. The article sets the scene for the succeeding papers, which focus on 'Langerhans cell histiocytosis'. Histiocytosis Histiocytes (Gk = iatos = tissue, ic(6TTapo = cell) are formed three disorders known as "eosinophilic granuloma", "Hand- in the bone marrow (Figure 1) from a pluripotential self- Schuller-Christian Disease" and "Letterer-Siwe Disease" renewing haemopoietic stem cell via a colony-forming cell were actually part of a spectrum of one disease process, for (the CFU-GM) capable of differentiation only into granu- which he coined the term "Histiocytosis X" (Lichtenstein, locytes and cells of the monocyte lineage. Histiocytes are of 1953). Nezelof et al., identified a Langerhans-like cell as two types (a) mononuclear phagocytes and (b) 'professional' diagnostic of the process (Nezelof et al., 1973) and the desig- antigen-presenting cells.
    [Show full text]