Neutrophilia due to bacterial infection/tissue necrosis (release of marginated pool & bone marrow neutrophils including immature forms with decreased Fc receptors), high cortisol (impairs adhesion also causing release of marginated pool) Monocytosis due to chronic inflammatory states and malignancy Eosinophilia due to allergic reactions, parasitic infections and Hodgkins (via increased IL5); increased eosinophil chemotactic factor Basophilia due to CML Lymphocytic leukocytosis due to viral infections (hyperplasia of T cells) and Bordetella pertussis infection (bacteria produce a promoting factor which blocks lymphocutes from leaving blood to enter lymph node)

- neoplastic proliferation of mature CD4+ T-cells that infiltrate the skin causing rash, plaques and nodules - Pautrier microabscesses: aggregates of neoplastic cells in the epidermis Sezary Syndrome: when cells spread to involve the blood (Sezary cells= lymphocytes with cerebriform nuclei)

White Blood Cell Disorders Flashcards by Michelle Bernshteyn

Hematopoiesis Overview

stepwise maturation of CD34+ hematopoietic stem cells

* cells mature and are released from marrow to blood

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Leukopenia–> classifications and what causes them

Neutropenia due to drug toxicity (damages stem cells), severe infection (neutrophils migrate to tissues instead of staying in circulation); treatment: GM-CSF or G-CSF
Lymphopenia: due to immunodeficiency, high cortisol (apoptosis of lymphocytes), autoimmune destruction, radiation

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Leukocytosis

Neutrophilia due to bacterial infection/tissue necrosis (release of marginated pool & bone marrow neutrophils including immature forms with decreased Fc receptors), high cortisol (impairs adhesion also causing release of marginated pool)

Monocytosis due to chronic inflammatory states and malignancy

Eosinophilia due to allergic reactions, parasitic infections and Hodgkins (via increased IL5); increased eosinophil chemotactic factor

Basophilia due to CML

Lymphocytic leukocytosis due to viral infections (hyperplasia of T cells) and Bordetella pertussis infection (bacteria produce a promoting factor which blocks lymphocutes from leaving blood to enter lymph node)

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Infectious Mononucleosis (IM)–> cause, clinical features, mechanism, screening, complications

causes: EBV (CD8+) or CMV
EBV infects oropharynx, liver (causes hepatitis with hepatomegaly and elevated liver enzymes) and B-cells
CD8 T-cell response–> hyperplasia in paracortex & PALS–> lymphadenopathy & splenomegaly respectively
monospot test detects IgM Ab that cross-react with heterophile Ab turning (+) 1 wk post infection ((-) could mean CMV is the cause); serologic testing for EBV viral capsid antigen
Complications: splenic rupture (avoid contact sports), rash, risk of B-cell lymphoma

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Acute Leukemia Overview–> causes and types

neoplastic proliferation of blasts (large, immature, punched out nucleoli, little cytoplasm) >20%
crowds out normal hematopoiesis–> causes anemia, thrombocytopenia or neutropenia

Acute Leukemia = ALL & AML

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Acute Lymphoblastic Leukemia (ALL)–> causes, types

accumulation of lymphoblasts (immature) that stain (+) for TdT
common in Down Syndrome patients >5yo

B-ALL: CD10, CD19, CD20; prophylaxis to scrotum and CSF; t(12;21) in children & t(9;22) in adults

T-ALL: CD2-CD8 (NO CD10); presents as mediastinal (thymic) mass called acute lymphoblastic lymphoma

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Acute Myeloid Leukemia (AML)–> causes, types

accumulation of immature myeloid cells >20% in marrow that stain (+) for MPO
could arise from pre-exisiting dysplasia (myelodysplastic syndomes) from exposure to alkylating agents or radiotherapy

Acute Promyelocytic Leukmia (APL): t(15;17) translocation of retinoic acid receptor (RAR) on X17 to X15; RAR disruption blocks promyelocyte maturation; increased risk for DIC due to primary granules of abnormal promyelocytes; treatment: ATRA

Acute Monocytic Leukemia: monoblast proliferation infiltrating gums; lacks MPO

Acute Megakaryoblastic Leukemia: megakaryoblastic proliferation associated with Down Syndrome

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What do myelodysplatic syndromes usually present with?

-cytopenias, hypercellular bone marrow, abnormal maturation of cells, increased blasts (

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Chronic Leukemia Overview

neoplastic proliferation of mature circulating lymphocytes (high WBC count)
slow, asymptomatic, in adults

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Chronic Lymphocytic Leukemia (CLL)–> causes, complications

neoplastic proliferation of naive B-cells that co-express CD5 & CD20
increased lymphocytes and smudge cells
generalized lymphadenopathy

-complications: hypogammaglobulinemia (risk of infections), autoimmune hemolytic anemia, Richter transformation (to diffuse large B-cell lymphoma)

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Hairy Cell Leukemia–> cause, features, treatment

neoplastic proliferation of mature B-cells characterized by hairy cytoplasmic processes
(+) for TRAP
splenomegaly (accumulations in red pulp–> do not go to nodes), “Dry tap” on marrow aspiration due to fibrosis
responds to 2-CDA (adenosine deaminase inhibitor) since adenosine accumulates to toxic levels

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Adult T-Cell Leukemia/Lymphoma (ATLL)–> causes and features

-neoplastic proliferation of mature CD4+ T-cells associated with HTLV-1 (common in Japan & Caribbean)

-rash, generalized lymphadeopathy with hepatosplenomegaly & lytic bone lesions with hypercalcemia

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Mycosis Fungoides

neoplastic proliferation of mature CD4+ T-cells that infiltrate the skin causing rash, plaques and nodules
Pautrier microabscesses: aggregates of neoplastic cells in the epidermis

Sezary Syndrome: when cells spread to involve the blood (Sezary cells= lymphocytes with cerebriform nuclei)

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Myeloproliferative Disorders (MPD) Overview

neoplastic proliferation of mature cells of the myeloid lineage causing high WBC count
usually in older adults
complications: high turnover of cells increases risk of hyperuricemia/gout; progression to marrow fibrosis or transformation to acute leukemia

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Chronic Myeloid Leukemia (CML)–> cause, what it leads to

neoplastic proliferation of mature myeloid cells (especially granylocytes like basophils)
t(9;22)–>Philadelphia–>bcl-abl fusion
splenomegaly suggests accelerated phase
2/3 transform to AML, 1/3 to ALL

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CML vs. Leukemoid reaction (infection)

CML:
(-) LAP
-increased basophils
-t(9;22)

Leukemoid Reaction
(+) LAP
-no increase of basophils
-absent t(9;22)

Polycythemia Vera (PV)

neoplastic proliferation of mature myeloid cell (especially RBCs); granulocytes and platelets are also increased
JAK2 kinase mutation
symptoms due to hyperviscosity of blood (blurry vision, increased risk of venous thrombosis, flushing, itching)

-treatment: phlebotomy, hydroxyurea

Polycythemia Vera vs. Reactive Polycythemia

PV

decreased EPO
SaO2= normal

RP (high alt/lung disease)

increased EPO
SaO2= low

RP (ectopic EPO production from renal cell carcinoma)

increased EPO
SaO2= normal

Essential Thrombocytopenia (ET)

neoplastic proliferation of mature myeloid cells (especially platelets); RBCs and granulocytes are also increased
JAK2 kinase mutation
megakaryocytes–> excess PDGF–> marrow fibrosis

-splenomegaly (extramedullary hematopoiesis), leukoerythroblastic smear, increased risk of infection, thrombosis and bleeding (marrow can’t properly produce cells and spleen can’t compensate)

Lymphadenopathy (LAD) Overview

-enlarged lymph nodes

painless: nodes that are draining acute infection
painful: chronic inflammation, metastatic carcinoma or lymphoma
in inflammation, node enlargement is due to hyperplasia of particular regions
1. Follicular (rheumatoid arthritis, HIV)
2. Paracortex (viral infections)
3. Sinus Histiocytes (tissue with cancer- has become reactive)

Lymphoma Overview

neoplastic proliferation of lymphoid cells forming mass
non-Hodgkins & Hodgkins

-non-Hodgkins–> small B-cells (follicular, mantle cell, marginal zone, small lymphocytic), intermediate-sized B-cells (Burkitt lymphoma), large B-cells (B-cell lymphoma)

Hodgkins vs. non-Hodgkins

Hodgkins

40%
Reed-Sternberg cells
mass= reactive cells (inflammatory cells & fibrosis(
painless, B-symptoms
young adults
spread- contiguous; rarely extranodal
no leukemic phase

non-Hodgkins

60%
Lymphoid cells
mass= lymphoid cells
painless
late adulthood
spread- diffuse, extranodal
leukemic phase

Mantle Cell Lymphoma

neoplastic proliferation of small B-cells (CD20+) that expands the mantle zone
painless lymphadenopathy
t(11;14)–> cyclin D1 on X11 translocates to Ig heavy chain locus on X14 causing its overexpression promoting G1/S

Marginal Zone Lymphoma

-neoplastic proliferation of small B-cells (CD20+) that expands the marginal zone (which is formed by post-germinal center B-cells)
associated with chronic inflammatory states (Hashimoto thyroiditis, Sjorden syndrome, H. pylori gastritis

-MALToma is in mucosal sites

Follicular Lymphoma

- neoplastic proliferation of small B-cells (CD20+) that form follicle-like nodules - late adulthood with painless lymphadenopathy - t(14;18)= BCL2 on X18 translocates to Ig heavy chain locus on X14--> BCL2 overexpression inhibiting apoptosis

Follicular Lymphoma vs. Reactive Follicular Hyperplasia

Follicular Lymphoma - disruption of normal lymph node architecture - lack of tingible body macrophages in germinal centers - Bcl2 expression - monoclonality Reactive Follicular Hyperplasia - no disruption of normal lymph node architecture - presence of tingible body macrophages in germinal centers - no Bcl2 expression - polyclonality

Burkitt Lymphoma

- neoplastic proliferation of intermediate-sized B-cells (CD20+) - associated with EBV - extranodal mass (African- jaw, Sporatic- abdomen) - translocations of myc- t(8;14) high mitotic index and "starry-sky" appearance on microscopy

Diffuse Large B-Cell Lymphoma

- neoplastic proliferation of large B-cells (CD20+) growing in sheets - aggressive - arises sporatically or from transformation of a low-grade lymphoma - presents in late adulthood as an enlarging lymph node or extranodal mass

Hodgkin Lymphoma (HL)

- proliferation of Reed-Sternberg cells (large B cells with multilobed nuclei and prominent nucleoli (+) for CD15 & CD30) - secretion of cytokines causing B-symptoms, attraction of reactive cells and possible fibrosis Subtypes: 1. Nodular Sclerosis: most common, enlarging cervical/mediastinal lymph node with bands of sclerosis in young female 2. Lymphocyte-Rich: best prognosis 3. Mixed Cellularity: lots of eosinophils (RS produce IL5) 4. Lymphocyte-Depleted: most aggressive in elderly & HIV positive patients

Name the 4 plasma disorders (Dyscrasias)

1. Multiple Myeloma 2. Monoclonal Gammopathy of Undetermined Significance (MGUS) 3. Waldenstrom Macroglobulinemia

Multiple Myeloma--> cause, clinical features

- malignant proliferation of plasma cells in the marrow that is the most common primary malignancy of bone - high IL6 stimulating plasma cells and Ig - Clinical features: - bone pain (with hypercalcemia since plasma cells activate RANK receptor causing lytic lesions) - elevated serum protein (plasma cells produce Ig; M spike due to IgG or IgA) - increased risk of infection (monoclonal Ab lacks antigenic diversity) - Rouleaux formation (increased serum protein decreases charge between RBCs) - primary AL amyloidosis (increased free light chains circulate and deposit in tissues) - proteinuria (free light chain excreted as Bence Jones protein depositing in tubules- possible renal failure)

Monoclonal Gammopathy of Undetermined Significance (MGUS)

-increased serum protein with M spike -other features of Multiple Myeloma are absent -common in elderly -1% will develop multiple myeloma

Waldenstrom Macroglobulinemia--> cause, clinical features, treatment

-B-cell lymphoma with monoclonal IgM production - Clinical features: - generalized lymphadenopathy (no lytic bone lesions) - increased serum protein with M spike (IgM) - visual/neurologic deficits (IgM causes hyperviscosity) - bleeding (defective platelet aggregation) *treatment: plasmapheresis (removed IgM)

Langerhans Cells & Langerhans Cell Histocytosis Overview

- Langerhans cells: specialized dendritic cells in the skin that present antigen to naive T cells (derived from bone marrow monocytes) - Langerhans Cell Histocytosis: neoplastic proliferation of Langerhans cells characterized by Birbeck (tennis racket) granules; CD1+a and S100+

Letterer-Siwe Disease

- malignant proliferation of Langerhans Cells | - skin rash, cystic skeletal defects in infant (

Eosinophilic Granuloma

- benign proliferation of Langerhans Cells in bone - in adolescents, presents as fracture (skin not involved) - biopsy: Langerhans cells with mixed inflammatory cells with many eosinophils

Hand-Schuller-Christian Disease

- malignant proliferation of Langerhans cells | - scalp rash, lytic skull defects, diabetes insipidus, exophthalmos in child (>3yo)