GI: WBC Disorders Flashcards Preview

• Absolute Leukocyte count usually >25,000 to 30,000 cells/mm³
• May involve neutrophils, Lymphocytes, or Eosinophils
• Normal Bone marrow response to Cytokines released by cells to infection or trauma
• Normal albeit exaggerated response to an infection

• Presence of Immature bone marrow WBCs and Nucleated RBCs in Peripheral blood ‘Peripheralization’ of the Bone marrow, irrespective of Total Leukocyte count
• Peripheral blood findings
  • Myeloblasts, Progranulocytes, and other Leukocyte precursors
  • Nucleated RBCs and Teardrop RBCs (if fibrosis is present)

• A low WBC count (< 5K)
• A/w advanced HIV
• Following therapy w/ Glucocorticoids or Cytotoxic drugs
• Autoimmune disorders
• Malnutrition
• Acute Viral Infections  --> Type I interferons --> T lymphocytes activation --> sequestration of activated T cells in Lymph nodes and increased adherence to Endothelial cells

• A high WBC count (> 10K)
• Increased Production in the Marrow
  • Chronic Infection or Inflammation
  • Paraneoplastic
  • Myeloproliferative disorders
• Increased Release from Marrow
  • Endotoxemia, Infection, Hypoxia
• Decreased Margination
  • Exercise, Catecholamines
• Decreased Extravasation into Tissues
  • Glococorticoids

• Decreased number of circulating neutrophils <1500 cells/mm³ (Serious if <500 cells/mm³)
• Aplastic anemia
• Immune destruction – SLE and Paroxysmal nocturnal Hemoglobinuria
• Septic shock
• Ticks, Viral, Bacterial, Fungal, XRT
• Drug toxicity (Chemo w/ alkylating agents)  - Dmg to stem cells results in decreased production of WBCs, especially neutrophils, anti-Metabolites for Chemo Tx.
• Severe Infection (gram-negative sepsis) – increased movement of neutrophils into tissues results in decreased circulating neutrophils
• As a Tx: GM-CSF or G-CSF may be used to Boost Granulocyte production, thereby decreasing risk of infection in Neutrophenic

• Decreased number of circulating lymphocytes
• Immunodeficiency (DiGeorge syndrome or HIV)
• High cortisol state (exogenous corticosteroids or Cushing syndrome) --> increased Cortisol --> Apoptosis
• Autoimmune destruction (SLE)
• Whole body radiation – Lymphocytes are highly sensitive to XRT – Lymphopenia is the earliest change to emerge after Whole Body XRT

• Increased circulating Neutrophils >7500 cells/mm³
• Bacterial infection or Tissue necrosis – induces release of Marginated pool and Bone marrow neutrophils, including immature forms (left shift)
• Immature cells are characterized by decreased Fc receptors (CD16)
• High cortisol state – impaires leukocyte adhesion, leading to release of Marginated pool of Neutrophils
• Chronic Infections and Chronic Inflammation (Lung abcesses) --> expansion of Myeloid precursor pool in Bone marrow

• Increased circulating monocytes >800 cells/mm³
• Chronic inflammatory states (autoimmune (RA) and infectious (TB, Subacute infective endocarditis, Cirrhosis))
• Malignancy (carcinomas and lymphomas)

• Hypercortisolism (Cushing syndrome, Coricosteroids)
• Corticosteroids sequester Eosinophils in Lymph noes and Trigger apoptosis

• Increased circulating eosinophils > 400 cells/mm³
• Allergic reactions (Type I Hypersensitivity – Mast cells)
• No sequestering of Eosinophils in Lymph nodes
• Parasitic infctions (Protozoa, Helminths)
• Polyarteritis nodosa, Churg-Strauss syndrome
• Job syndrome
• Addison disease (Cortisol deficiency)
• Hodgkin lymphoma (Tumor --> increased IL-5 production)
• Driven by increased Eosinophil chemotactic factor

• Increased ciruclating basophils >110 cells/mm³
• Classically seen in Chronic Myeloid Leukemia (CML)
• Chronic myeloproliferative disorders (Polycythemia vera)

• Increased circulating lymphocytes >5000 cells/mm³ in Adults and >8000 cells/mm³ in Children
• Viral infections – T lymphocytes undergo Hyperplasia in response to virally infected cells, Mononucleosis and Cytomegalovirus (CMV)
• Bordetella pertussis infection – Bacteria produce lymphocytosis – promoting factor, which blocks circulating lymphocytes from leaving the blood to enter the lymph node (Whooping cough) and Tuberculosis
• Drugs – Phenytoin and Tetracycline
• “Stuck in the blood” --> Increased [WBC]

• EBV infection that results in a Lymphocytic leukocytosis --> Increased [WBC]
• EBV is transmitted by Saliva “Kissing Disease” classically affects teenagers (15 – 24 y.o.), replicates in the epithelial cells in the Oropharynx
• Comprised of reactive CD8+ T cells --> MHC class I response
• CD8+ T cell response --> Generalized Lymphadenopathy (LAD) due to T-cell hyperplasia in Lymph node Paracortex
• A/w Splenomegaly due to T-cell Hyperplasia in the Periarterial lymphatic Sheath (PALS): White Pulp --> B-cells and T-cells
• High WBC count w/ Atypical Lumphocytes (Reactive CD8+ T cells) in the blood --> Dx w/ Heterophile Ab test (Monospot test)
• CVM is a less common cause
• EBV infects: Oropharynx --> Pharyngitis, Liver --> Hepatitis w/ Hepatomegaly and Elevated Liver enzymes, B-cells

• Detects IgM antibodies that cross-react w/ IgM Ab against Horse, Sheep, or Bovine RBCs (Heterophile Ab)
• Usually turns Positive w/in 1 week after Infection
• Negative Test suggests CMV as a possible cause or Test done too early
• Definitive diagnosis is made by Serologic testing for the EBV viral capsis antigen

• Increased risk of Splenic Rupture due to Splenomegaly --> Pts. are generally advised to avoid contact sports for One month – One year
• Rash if exposed to Ampicillin (PCN)
• Dormancy of Virus in B cells leads to Increased risk for both Recurrenc and B-cell Lymphoma, especially if Immunodeficiency (HIV) develops

• Absolute lymphocyte count <1500 cells/mm³ in Adults and <3000 cells/mm³ in Children
• HIV,
  DiGeorge syndrome (T-cell deficiency),
  SCID (B- and T-cell def.),
  Bruton agammaglobulinemia (B-cell def.),
  Immune destruction (SLE)
• Drugs
• XRT

• Neoplastic proliferation of Blasts – Accumulation of
  > 20% Blasts in the Bone Marrow
• Increased Blasts “crowd-out” Normal Hematopoiesis
  --> resuting in  “Acute” presentation w/ Anemia (Fatigue), Thrombocytopenia (Bleeding due to loss of Platelets), or Neutropenia (Infection)
• Blasts enter Blood stream --> increased [WBC] count
• Blasts are Large, Immature cells, often w/ Punched out Nucleoli
• Acute Leukemia is Subdivided: AML and ALL based on Blast Phenotype

Age Ranges for Common Leukemias

• Neoplastic accumulation of Lymphoblasts (>20%) in Bone Marrow
• 3x White : Blacks
• t(9;22) BCR-ABL - Tyrosine kinase --> Tx: Gleevec a Tyrosine kinase inhibitor
• t(4,11) MLL gene on Chrom. 11q23
• t(8;14)
• CNS manifistations: Headache, Vomiting, Nerve palsies resulting from Meningeal spread - Neoplastic infiltration
• Lymphoblasts are characterized by Positive Nuclear staining for TdT (DNA polymerase)
• TdT is absent in Myeloid blasts and Mature Lymphocytes
• A/w Children,  w/ Down Syndrome (> 5 y.o.)
• Subclassified into B-ALL and T-ALL based on Surface Markers

• Lymphoblasts (TdT+) that express CD10, CD19, and CD20
• Loss of Function Mutations: PAX5, E2A, and EBF
• Excellent response to Chemo
• Mass in the Skin or a Bone
• Requires prophylaxis to Scrotom and CSF
• t(12;21) --> 25% have ETV6 and RUNX1  - Marrow replacement and Pancytopenia, Good prognosis – more commonly seen in Children "Childhood Acute Leukemia"
• t(9;22) --> Poor prognosis – more commonly seen in Adults (Phil+ALL)

• Lymphoblasts (TdT+) that express markers from CD2 to CD8, but NO CD10
• 70% have NOTCH1 - T cell development
• Typically evolve to  Leukemic picture
• Usually presents in Teenagers as a Mediastinal (Thymic) mass ("Adolescent Males w/ Thympic Lymphomas")
• Called Acute Lymphoblastic Lymphoma because the Malignant cells form a Mass

• Neoplastic accumulation of Immature Myeloid cells (>20%) in the Bone marrow
• Positive Cytoplasmic staining for Myeloperoxidase (MPO)
• Crystal aggregates of MPO may be seen as Auer Rods
• Older adults (Average age is 50 – 60 y.o.)
• Subclassified based on Cytogenic abnormalities, Lineage of Immature myeloid cells, and Surface markes
• Treatment-related AML a/w which prior therapies
  • Aklylating agents
  • Topoisomerase II inhibitors
  • XRT

• t(15;17) – translocation of the Chimeric protein w/ Retinoic acid receptor (RARα) fused to Promyelocytic leukemia protein (PML) --> Chrom 17 to Chrom 15; RAR disruption blocks maturation/differentiation on myeloid cells at the Promyelocytes (blasts) stage
  --> Promyelocytes and Myeloblasts accumulate
• Abnormal promyelocytes contain numerous Primary granules that increase risk for DIC
• Tx: all-trans-retinoic acid (ATRA) (Vit. A der.)
  --> binds the altered receptor and causes the blasts to mature and differentiate --> and die

• Proliferation of monoblasts; usually lack MPO
• Blasts characteristically Infiltrate the Skin and Gums (Gingival infiltrations)

• Proliferation of megakaryoblasts; usually lack MPO
• A/w Down Syndrome (< 5 y.o.)

• Exposure to Alkylating agents or XRT
• Myelodysplastic syndromes --> present w/ Cytopenias, Hypercellular Bone marrow, Abnormal maturation of cells, and Increased blasts (<20%)
• Pts. die from Infection or Bleeding, some progress to Acute leukemia
• If Blasts are > 20% --> “AML has arisen in a background of dysplasia”

• Neoplastic proliferation of naïve B cells that co-express CD5, CD 19, CD20, and CD23 - 13q14.3, 11q, and 17p, and Trisomy 12q
• Most common leukemia overall, esp. Western World
• Increased Lymphocytes and Smudge cells are seen on Blood smear - 10% NOTCH1 and NF-kB and ZAP-70
• Involvement of Lymph nodes --> Generalized lymphadenopathy and is called Small lymphocytic lymphoma (SLL)(mass ‘-oma’)
• Hypogammaglobulinemia – Infection most common cause of Death in CLL
• Autoimmune hemolytic anemia – antibodies against RBCs
• Transformation to Diffuse large B-cell lymphoma (Richter transformation) – marked clinically by an enlarging Lymph node or Spleen --> Aggressive enlarging Tumor

• Neoplastic proliferation of Mature B cells w/ Hairy cytoplasmic processes --> cells are positive for TRAP (tartate-resistant acid phosphatase)
• CD 11c, CD 25, CD103
• Memory B cell w/ Activating BRAF mutations
• Older Males w/ Splenomegaly (due to accumulation of Hairy cells in Red pulp) and “dry tap” on Bone marrow aspiration (due to Marrow fibrosis)
• Lymphadenopathy is usually absent
• Excellent response to 2-CDA (cladribine), an Adenosine deaminase inhibitor: Adenosine accumulates to toxic levels in Neoplastic B cells (Purine degradation pathway --> death of neoplastic B cells)

• Neoplastic proliferation of mature CD4+ T cells
• Helper T cells - Adults w/ cutaneous Lesions
• A/w HTLV-1; most commonly seen in Japan and Caribbean (Human T-cell Leukemia Virus 1)
• Rash (skin infiltration)
• Generalized lymphadenopathy w/ Hepatomegaly (Mature lymphocytes like to go to Lymph node and Spleen)
• Lytic (punched-out) bone lesions w/ Hypercalcemia
• Leads to Multiple myeloma and Adult T-cell Leukemia

• Neoplastic proliferation of Mature CD4+ T cells that Infiltrate the skin --> localized Skin rash, Plaques, and Nodules
• Helper T cells - Adulta w/ destructive extranodal patches, plaques, nodules, or generalized erythema
• Aggregates of neoplastic cells in the Epidermis (“Pautrier microabscesses”)
• Cells can spread to involve the blood --> Sezary syndrome (lobish nuclei)
• Characteristic lymphocytes w/ Cerebriform nuclei (Sezary cells) are seen on Blood smear

• Neoplastic proliferation of Mature cells of Myeloid lineage
• Disease of Late adulthood: 50 – 60 y.o.
• High WBC count w/ Hypercellular Bone marrow (increased granulocyte production --> incrased [WBC])
• Cells of ALL myeloid lineages are increased BUT classified based on the Dominant Myeloid cell produced
• Increased risk for Hyperuricemia and Gout due to High turnover of cells
• A/w Post-therapy myelodysplasia
• Ringed sideroblasts, Megaloblasts, Abnormal megakaryocytes, and Myeloblasts in the Marrow
• Progression to Marrow fibrosis --> ‘Spent phase’ or ‘Burnt-out phase’) of Transformation to Acute leukemia

• Neoplastic proliferation of Mature Myeloid cells: esp. Granulocytes and precursors; Basophils are characteristically increased
• t(9;22) (Phili+ chromosome) which generates a BCR-ABL fusion protien w/ increased Tyrosine kinase activity --> overproduction of neoplastic cells
• Tx: Imatinib – blocks Tyrosine Kinase activity
• Splenomegaly – suggests progression to accelerated phase of disease, (3) Phases: Chronic, Accelerated (enlarging), and Transformation
• Transformation to acute leukemia usually follows shortly therafter
• Can transform to AML (2/3) or ALL (1/3) since mutation is in a Pluripotent stem cell
• Distingusing factors:
  • Negative Leukocyte alkaline phosphate (LAP) stain (Granulocytes in Leukemoid rxn are LAP positive)
  • Increased Basophils (absent in Leukemoid rxn)
  • t(9;22) (absent in Leukemoid rxn)

• Neoplastic proliferation of Mature Myeloid cells, especially RBCs
• Granulocytes and Platelets are also increased
• A/w JAK2 kinase mutation (Granulocytosis and Thrombocytosis)
• Symptoms mostly due to Hyperviscosity of Blood --> Super-thick
• Blurry vision and Headache
• Increased risk of Venous Thrombosis (Hepatic vein, Portal vein, Dural sinus)(a/w Budd-chiari syndrome --> Hepatic vein thrombosis)
• Flushed face due to congestion (Plethora)
• Itching, especially after Bathing (Histamine release from increased # mast cells --> Pruritis)
• Tx: 1^st Phlebotomy, 2^nd Hydroxyurea and w/out Tx: Death w/in 1 year
• PV vs. Reacitve Polycythemia
• PV, Erythropoietin (EPO) lvls decreased and SaO₂ are normal
• Reactive Polycythemia due to High altitude or Lund disease; increased EPO SaO₂ is low
• Ractive Polycthemia: Renal cell carcinoma --> increased [EPO] w/ normal Oxygen sat.

• Neoplastic proliferation of Mature Myeloid cells, Especially Platelets from myeloid stem cells
• RBCs and Granulocytes are also increased
• A/w JAK2 kinase mutation
• Increased risk of Bleeding and/or Thrombosis
• Rarely progresses to Marrow fibrosis or Acute leukemia
• No significant risk for Hyperuricemia or Gout

• Neoplastic proliferation of Mature Myeloid cells, Especially Megakaryoytes
• A/w JAK2 kinase mutation (50% of cases)
• Megakaryocytes produce excess platelet-derived growth factor (PDGF) causing Marrow fibrosis
• Splenomegaly due to Extramedullary hematopoiesis
• Leukoerythroblastic smear (tear-drop RBCs, nucleated RBCs, and Immature Granulocytes --> Reticuline gaits prevent immature cells to exit into the Blood; Big cells must divide to pass through
• Increased risk of Infection, Thrombosis, and Bleeding (Bone Marrow is no longer producing WBCs, RBCs, and Platelets)

• Enlarged lymph nodes
• Painful LAD: Lymph nodes that are draining a region of Acute infection (Acute lymphadenitis)
• Painless LAD: Chronic inflammation (chronic lymphadenitis), metastatic carcinoma, or Lymphoma
• Inflammation: Lymph node enlargement is due to Hyperplasia of Particular regions of the Lymph nodes
• Follicular Hyperplasia (B-cell region) seen w/ Rheumatoid arthritis and early stages of HIV infection (B-cell – Cortex) (CD4+ T cells + Follicular cells)
• Paracortex Hyperplasia (T-cell region) seen w/ Viral infections (IM)
• Hyperplasia of Sinus Histiocytes seen in Lymph nodes that are draining a tissue that has Cancer --> Reactive due to increased draining of an area that has Cancer

• Neoplastic proliferation of Lymphoid cells that forms a Mass
• May arise in a Lymph node or in Extranodal tissue
• Hodgkin Lymphoma (HL) and non-Hodgkin Lymphoma (NHL)
• NHL is futher classified based on Cell type (B vs. T), Cell size, Pattern of Cell growth, Expression of Surface markers, and Cytogenetic translocations
• (4) Small B cells
  • Follicular lymphoma
  • Mantle cell Lymphoma
  • Marginal zone lymphoma
  • Small Lymphocytic Lymphoma (CLL cells that involve tissue)
• Intermediate-sized B cells – Burkitt Lymphoma
• Large B cells – Diffuse Large B-cell Lymphoma

• 40%
• Malignant cells are Reed-Sternberg cells
• Mass Composition is Predominantly Reactive cells (inflammatory cells and Fibrose)
• Painless Lymphadenopathy occasionally w/ ‘B’ symptoms (younger adults)
• Contiguous spread (Orderly Fasion); rarely extranodal
• Staging guides therapy; XRT is mainstay of Tx
• Leukemic phase DOES NOT occur

• 60%
• Malignant cells are Lymphoid cells
• Mass Composition is Lymphoid cells
• Painless Lymphadenopathy, usually arises in Late adulthood
• Diffuse spread (Less predictable); often Extranodal
• Leukemic phase occurs

• Neoplastic proliferation of Small B cells (CD20) that form Follicle like nodules
• Presents in Late adulthood w/ Painless Lymphadenopathy and Marrow involvement (NHL)
• t(14;18) --> BCL2-IgH fusion gene on Chrom. 18 translocates to the Ig Heavy chain locus on Chrom 14 --> Overexpression of BCL2 --> Inhibits apoptosis
• MLL2 encodes Histone methyltransferase that regulates gene expression --> epigenetic abnormalities
• Tx: Reserved for pts. who are symptomatic and involves Low-dose Chemo or Rituximab (anti-CD20 Ab)
• Enlarging Lymph node --> Progression to Diffuse Large B-cell lymphoma --> indicates additional mutations

• Neoplastic proliferation of Small B cells (CD20) that expands the Mantle zone or ‘Expands the region immediately adjacent to Follicle zone’ - Older Males
• Late adulthood w/ Painless Lymphadenopathy (NHL)
• Naive B cell w/ t(11;14) – Cyclin D1-IgH gene on Chrom 11 translocates to Ig Heavy chain locus on Chrom 14
• Overexpression of Cyclin D1 promotes G₁ --> S phase transition in the Cell cycle --> Facilitating neoplastic proliferation

• Neoplastic proliferation of Small B cells (CD20) that expands the Marginal zone
• Memory B cell
• t(11;18), t(1;14), and t(14;18) creating MALT1-IAP2,
  BCL 10-IgH and MALT1-IgH Fusion genes
• A/w Chronic inflammatory states, Hashimoto thyroiditis, Sjogren syndrome, H pylori gastris
• The marginal zone is formed by Post-germinal center B cells --> mucosal enlargment of parotid
• MALToma is a Marginal Zone Lymphoma in mucosal sites
• Gastric MALToma may regress w/ treatment of H pylori

• Neoplastic proliferation of Intermediate-sized B cells (CD20) - Germinal-center B-cells;
  IgM, CD 10, CD 19, CD 20 and A/w EBV
• High mitotic index and ‘Starry-sky’ appearance on Histo
• Extranodal mass in a Child or Young adult
• African form --> involves the Jaw
• Sporadic form --> involves the Abdomen
• 46,XY, t(8,14) is most common "Warburg effect"
  --> Translocation of c-MYC - aerobic glycolysis (Chrom 8) to the Ig Heavy chain locus on Chrom 14
• Overexpression of c-myc­ oncogene promotes cell growth

• Neoplastic proliferation of Large B cells
  (CD 19 and CD20) that grow diffusely in Sheets, particularly of the Waldeyer ring
• Germinal-center or Post-Germinal center B-cells
• Dysregulation of BCL6 at 3q27 (30%),
  BCL2 at t(14;18) (10%), MYC (5%) and p300 and CREBP
• Most common form of NHL - Older Adults
• "Rapidly Growing Mass" - Aggressive (High-grade), Not well differentiated
• Arises sporadically or from Transformation of Low-grade Lymphoma (e.g. Follicular lymphoma)
• Late adulthood as an enlarging Lymph noed or an Extranodal mass

• Neoplastis proliferation of Reed-Sternberg (RS) cells
• Large B cells w/ Multilobed nuclei and Prominent Nucleoli (‘owl-eyed nuclei’)
• Positive for CD15 and CD30 – NO CD20 expression
• RS cells secrete Cytokines
• ‘B’ symptoms (Fever, Chills, Weight loss, Night sweats)
• Attract reactive Lymphocytes, Plasma cells, Macrophages, and Eosinophils
• May lead to Fibrosis
• Reactive inflammatory cells make up a bulk of the Tumor and form basis of classification (4) Subtypes

• 70% cases
• Enlarging Cervical or Mediatinal Lymph node in a Young adult, usually Female
• Lymph node is divided by Bands of Sclerosis
• RS cells are present in ‘Lake-like spaces’ – Lacunar cells

• Best prognosis of HL subtypes

• A/w Abundant Eosinophils
• RS cells produce IL-5 --> Draws in Eosinophils
• Worst subtype

• Most aggressive HL subtype
• Usually seen in Elderly and HIV positive pts

• Malignant proliferation of Plasma cells in the Bone marrow - Diverese rearrangement w/ IgH and 13q del.
• Post-Germinal-Center Bone marrow homing Plasma cell
• Most common Primary malignancy of the Bone
• High serum IL-6 – stimulates Plasma cell growth and Ig production
• "C-R-A-B" "hyperCalcemia, Renal insufficiency (light chain nepthropathy), Anemia normocytic normochromatic, and Bone lesions" 
• Bone pain w/ Hypercalcemia and Alkaline Phosphatase – plasma cells activate RANKL receptor on Osetoclasts --> Bone destruction --> Lytic ‘punched-out’ skeletal lesions on x-ray, Vertebrae and Skull --> Increased risk of Fracture --> Destruction mediatiated by RANKL, Dx w/ IL-6 for Plasma cells
• Elevated serum protein – plasma cells produce Ig – M-'Spike' is present on Serum Protein Electrophoresis (SPEP), commonly IgG or IgA
• Increased risk of Infection – Monoclonal Ab lacks antigenic diversity; Inf. Is most common cause of Death in Multiple Myeloma
• Rouleux formation of RBC on Blood smear – increased serum protein decreases Charge Between RBCs
• Primary AL amyloidosis – Free light chains circulate in Serum and Deposit in Tissues
• Proteinuria – Free light chain is excreted in the Urine as Bence Jones protein; Deposition in Kidney tubules leads to risk for Renal failure (Myeloma Kidney)

• Increased Serum protein w/ M spike on SPEP
• No lytic Bone lesions
• No Hypercalcemia
• No AL amyloid
• No Bence Jones proteinuria
• Commonly in Elderly (5% of 70 y.o.)
• 1% Pts develop Multiple Myeloma each year

• B-cell Lymphoma w/ Monoclonal IgM production (Pentamer – Big Globulin)
• Generalized Lymphadenopathy w/out Lytic Bone lesions 
• Increased serum Protein w/ IgM spike (comprised of IgM)
• Visual and Neurologic deficits (Retinal hemorrhage or Stroke) – IgM (large pentamer) causes Serum Hypersensitivity --> Increased viscosity of RBCs
• Bleeding – Viscous serum results in defective Platelet aggregation --> Cold agglutinin disease --> Cryoglobulinemia --> Raynaud phenoomenon
• Acute complications are treated w/ Plasmapheresis --> removes IgM from the serum

• Langerhans cells are specialized Dendritic cells – in the Skin mostly, organomegaly
• Derived from Bone marrow monocytes
• Present antigen to Naïve T cells
• Langerhans cell Histiocytosis is Neoplastic proliferation of Langerhans cells – characteristic Birbeck (Tennis racket) granules are seen on Electron microscopey – cells are CD1a+ and S100+ by immunochemistry

• Malignant proliferation of Langerhans cells
  --> Histiocytosis
• Birbeck granules are a distinctive feature, identified by EM are found in the Cytoplasm
• Classically presentation is Skin rash and Cystic skeletal defect in an Infant (< 2 y.o.)
• Multiple organs may be involved --> rapidly fatal

• Benign proliferation of Langerhans cells in Bones
• Classic presentation is Pathologic Fracture in an adolescent
• Skin is not involved
• Biopsy shows Langerhans cells w/ mixed Inflammatory cells, Including numberous Eosinophils

• Malignant proliferation of Dendritic (Langerhans) cells from Monocyte lineage
• Classic Child presentation is Scalp Rash, Lytic Skull defects "big holes in the the cranium", Diabetes Insipidus, and Exophthalmos
• Also presents as Recurrent Otitis media w/ Mass involving the Mastoid bone
• Immature cells --> do not stimulate primary T Lymphocytes via antigen presentation
• CD 1a and S-100 cellular expression (mesodermal origin)
• Birbck granules "tennis rackets" on EM

• CD 1- Thymocytes and Langerhans cells
• CD 3 - Thymocytes, Mature T cells
• CD 4 - Helper T cells, subset of Thymocytes
• CD 5 - T cells and small subset of B cells

• CD 8 - Cytotoxic T cells, subset Thymocytes and NK cells

• CD 10 - Pre B-cell and Germinal center B-cell
• CD 19 - Pre B-cell and Mature B-cell
• CD 20 - Pre B-cell after CD 19 and Mature B, Not Plasma
• CD 21 - EBV receptor, Mature B-cell, Follicular Dendritic c.
• CD 23 - Activated Mature B-cell
• CD 79a - Marrow Pre-B-Cell

• CD 11c - Granulocyte, Monocyte, Macrophage, Hairy cell
• CD 13 - Immature and Mature Monocyte and Granulocyte
• CD 14 - Monocytes
• CD 15 - Granulocytes; Reed-Sterberg and Varients
• CD 33 - Myeloid progenitor
• CD 64 - Mature Myeloid cells

• CD 16 - NK cells and Granulocytes
• CD 56 - NK cells and subset of T cells

• CD 34 - Pluripotent Hematopoietic Stem cell and Progeniotr cells of Many Lineages

• CD 30 - Activation Marker

• CD - 45 - Leukocyte Common Antigen