GI: WBC Disorders Flashcards Preview

Pathology > GI: WBC Disorders > Flashcards

Flashcards in GI: WBC Disorders Deck (63):
1

  • 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

Leukemoid Reaction

2

  • 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)

Leukoerythroblastosis

3

  • 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

Leukopenia

4

  • 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

Leukocytosis

5

  • 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

Neutropenia

(Agranulocytosis)

6

  • 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

Lymphopenia

7

  • 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

Neutrophilic Leukocytosis

8

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

Monocytosis

9

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

Eosinopenia

10

  • 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

Eosinohilia

11

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

Basophilia

12

  • 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]

Lymphocytic Leukocytosis

13

  • 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

Infectious Mononucleosis

14

  • 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

Monospot Test for Infectious Mononucleosis (IM)

15

  • 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

Complications of Infectious Mononucleosis (IM)

16

  • 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

Lymphopenia

17

  • 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

Acute Leukemia Basics

18

Age Ranges for Common Leukemias

  • More common in Adults than in Children
     
  • Newborn to 14 years old
    • ALL is most common
    • ALL is most common overall cancer in Children
  • 40 – 60 y.o.
    • AML – Acute Myeloblastic Leukemia
    • CML – Chronic Myelogenous Leukemia
  • > 60 y.o.
    • CLL – Chronic Lymphocytic Leukemia
    • CML – Chronic Myelogenous Leukemia

19

  • 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

Acute Lymphoblastic Leukemia (ALL)

20

  • 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)

B cell Acute Lymphoblastic Leukemia (B-ALL)

21

  • 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

T cell Acute Lymphoblastic Leukemia (T-ALL)

22

  • 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

Acute Myeloid Leukemia (AML)

23

  • 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

Acute Promyelocytic Leukemia (APL)(Subclass of AML)

24

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

Acute Monocytic Leukemia (Subclass of AML)

25

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

Acute Megakaryoblastic Leukemia

26

  • 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”

AML arising from pre-existing dysplasia (Myelodysplastic syndromes)

27

  • Neoplastic proliferation of naïve B cells that co-express CD5, CD 19CD20, and CD2313q14.3, 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

Chronic Lymphocytic Leukemia (CLL)

28

  • 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)

Hariy Cell Leukemia

29

  • 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

Adult T-cell Leukemia / Lymphoma (ATLL)

30

  • 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

Mycosis Fungoides

Sezary syndrome

31

  • 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

Myeloproliferative Disorders – Basics

32

  • 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)

Chronic Myeloid Leukemia (CML)

33

  • 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: 1st Phlebotomy, 2nd 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.

Polycythemia Vera (PV)

34

  • 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

Essential Thrombocythemia (ET)

35

  • 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)

Myelofibrosis

36

  • 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

Lymphadenopathy – Basics

37

  • 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

Lymphoma – Basics

38

  • 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

Hodgkin Lymphoma

39

  • 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

Non-Hodgkin Lymphoma

40

  • 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

Follicular Lymphoma (NHL)

41

  • 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

Mantle Cell Lymphoma (NHL)

42

  • 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

Marginal Zone Lymphoma (NHL)

43

  • 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

Burkitt Lymphoma (NHL)

44

  • 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

Diffuse Large B-cell Lymphoma (NHL)

(DLBCL)

45

  • 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

Hodgkin Lymphoma – Basics

46

  • 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

Nodular Sclerosis (HL)

47

  • Best prognosis of HL subtypes

Lymphocyte-rich (HL)

48

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

Mixed Cellularity (HL)

49

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

Lymphocyte-depleted (HL)

50

  • 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 smearincreased 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)

Multiple Myeloma (Plasma Cell Disorder – Dyscrasias)

Solitary Plasmacytoma

51

  • 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

Monoclonal Gammopathy of Undetermined Significance (MGUS) (Dyscrasias)

52

  • 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

Waldenstrom Macroglobulinemia (Dyscrasias)

(Can occur w/ Monoclonal Myeloma,
but stronger a/w Lympoplasmacytic lymphoma)

53

  • 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

Langerhans Cell Histiocytosis – Basics

54

  • 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

Letterer-Siwe Disease

55

  • 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

Eosinophilic Granuloma

56

  • 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

Hand-Schuller-Christian Disease

57

  • 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

Primary T cell Associations

58

  • 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

Primary B cell Associations

59

  • 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

Primary Monocyte and Macrophage Association

60

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

Primary NK Association

61

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

Primary Stem Cell Association

62

  • CD 30 - Activation Marker

Activation Markers;
B-cell
T-cell
Monocytes
Reed Sternberg

63

  • CD - 45 - Leukocyte Common Antigen

Common on All Leukocytes
(Leukocyte Common Antigen)