Heme Pathology 3 Flashcards by Leimomi Kanagusuku

Myeloblast

Earliest precursor with large, rounder oval nucleus. Fine chromatin, evenly dispersed, few primary granules

How well did you know this?

Not at all

Perfectly

Promyelocyte

Nucleus about the same, but the cytoplasm starts to accumulate basophilic granules. Pale regions in nucleus = nucleoli

How well did you know this?

Not at all

Perfectly

Neutrophilic Myelocyte

Nucleus round, but chromatin more coarse. More cytoplasm

How well did you know this?

Not at all

Perfectly

Metamyelocyte

Kidney bean shaped nucleus

If indentation >1/2 = band

How well did you know this?

Not at all

Perfectly

Band

Not segmented into separate lobes yet

How well did you know this?

Not at all

Perfectly

Maure Neutrophil

3-5 Lobes

How well did you know this?

Not at all

Perfectly

Lymphocyte

Mononuclear cell

Nucleus is the same size as an RBC. Very little cytoplasm

How well did you know this?

Not at all

Perfectly

Lymphocyte

How well did you know this?

Not at all

Perfectly

Acute Myeloid Leukemia

Malignancy of Myeloblasts. Hypercellular

How well did you know this?

Not at all

Perfectly

Acute Myeloid Leukemia

Monoclonal population of -blasts

How well did you know this?

Not at all

Perfectly

Acute Myeloid Leukemia

-Blasts

How well did you know this?

Not at all

Perfectly

Acute Myeloid Leukemia

R-rod = linear configuration of granules

Only seen in neoplastic myeloblasts

How well did you know this?

Not at all

Perfectly

Acute Myeloid Leukemia

R-rods within myeloblasts

How well did you know this?

Not at all

Perfectly

Acute Myeloid Leukemia

Acute Promyelocytic leukemia (M3) - cytoplasm filled with granules and some R-rods

>20% blasts to diagnose leukemia

More procoag and fibrinolytic factors in cytoplasm - lead to problems with DIC

Translocation between ch. 15 & 17 T(15,17): PML gene (ch. 15) and Retinoic acid receptor alpha gene (ch. 17) switch –> fusion gene –> fusion protein –> prevents cell from maturing beyond promyelocyte stage. Can target with all-trans retinoic acid to aid maturation.

How well did you know this?

Not at all

Perfectly

Acute Myeloid Leukemia

Acute Promyelocytic leukemia (M3) - cytoplasm filled with granules and some R-rods

>20% blasts to diagnose leukemia

More procoag and fibrinolytic factors in cytoplasm - lead to problems with DIC

Translocation between ch. 15 & 17 T(15,17): PML gene (ch. 15) and Retinoic acid receptor alpha gene (ch. 17) switch –> fusion gene –> fusion protein –> prevents cell from maturing beyond promyelocyte stage. Can target with all-trans retinoic acid to aid maturation.

How well did you know this?

Not at all

Perfectly

AML

How well did you know this?

Not at all

Perfectly

AML (M4/5) Gingival infiltration by leukemia

How well did you know this?

Not at all

Perfectly

AML M4/M5

Leukemia Cutis

How well did you know this?

Not at all

Perfectly

Normal bone marrow

How well did you know this?

Not at all

Perfectly

Chronic Myelogneous Leukemia

Chronic leukemia of myeloid cells. Neoplasm of pluripotent stem cell -> leukocytosis, elevated platelets,

How well did you know this?

Not at all

Perfectly

Chronic Myelogneous Leukemia

Full spectrum of hematopoietic precursors

How well did you know this?

Not at all

Perfectly

Chronic Myelogneous Leukemia

How well did you know this?

Not at all

Perfectly

Chronic Myelogneous Leukemia

How well did you know this?

Not at all

Perfectly

Chronic Myelogneous Leukemia

How well did you know this?

Not at all

Perfectly

Chronic Myelogneous Leukemia

Chronic Myelogneous Leukemia Philadelphia Chromosome Characteristic **T(9,22) translocation** (90-95%). Others have a cryptic (microscopic) translocation

**Chronic Myelogenous Leukemia** ABL gene breaks off and translocates to BCR gene --\> **ABL-BCR** -\> tyrosine kinase gene product -\> always turned "On" -\> 2nd msnger pathways -\> cell proliferation/survival Can diagnose CML based on this translocation Can be used with a tyrosine kinase inhibitor

Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia Don't see R-rods. **TDT** - terminal deoxynucleotidal transferase (enzyme that is **only found in lymphoblasts)** so can stain just for that

Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia Better prognosis than AML (60-80% remission)

Chronic Lymphocytic leukemia Middle aged-elderly, M\>F, usually asymptomatic w/ leukocytosis and inverted differential (50% lymphocytes, 30% neutrophils)

CLL

CLL "Snickerdoodle"

Chronic Lymphocytic Leukemia

Hairy cell Malignancy of B-cells. Cytoplasm has projections that look like hair. Rare, indolent, curable

Hairy Cell Leukemia Usually also present with pancytopenia & **massive splenomegaly**

Bone marrow of Hairy Cell Leukemia Fried egg appearance

Hairy cell leukemia

TRAP stain - titrate resistant acid phosphatase for Hairy Cell Leukemia **2CDA** **cure** - few side effects, very effective.

Hairy Cell Leukemia

Hodgkin Lymphoma **Painless lymphadenopathy** Often localized to single axial group of nodes, orderly spread by contiguity, Mesenteric nodes and Waldeyer's ring rarely involved, Extranodal involvement uncommon

Hodgkin Lymphoma

Hodgkin Lymphoma **Reed-Sternberg cells** are characteristic, but are the minority of cells.

Hodgkin Lymphoma Reed-Sternberg Cells

Hodgkin Lymphoma Reed Sternberg Cells

Hodgkin's Lymphoma Nodular Sclerosis subtype Separated by Collagen bands

Hodgkin Lymphoma Nodular Sclerosis Subtype

Hodgkin Nodular Sclerosis subtype ## Footnote **Lacunar cell**

Normal Lymph node

Benign Lymphoid follicles

Follicular Lymphoma Follicles are all different sizes and scattered throughout lymph node **Characteristic translocation T(14,18)** 14 (immunoglobulin heavy chain); 18 (BCL2 - anti-apoptosis)

follicular lymphoma (Non-H)

Normal follicles BCL2 immunostain (Normal follicles don't stain)

Follicular lymphoma Non-Hodgkin BCL2 stain

Follicular lymphoma (non-H) Sometimes can end up in peripheral blood (Butt cells)

Diffuse large B-cell lymphoma Larger than normal lymphocytes Can develop from follicular lymphoma Aggressive high grade lymphoma, but can be treated

Burkitt Lymphoma "Starry sky" 1. Endemic form (from Africa) usually involves jaw/abdominal organs of children. Strongly associated with EBV. 2. Non-endemic (US) usually involves terminal ileum/ abdominal lymph nodes. 3. Immunodeficient patients.

Burkitt Lymphoma "Starry sky"

Burkitt Lymphoma Translocation T(8,14) c-myc (ch. 8) and Ig heavy chain (ch. 14)

Multiple Myeloma Malignancy of plasma cells. Usually affects middle-aged to older adults. Proliferate in bone marrow - so break down bone. CRAB - Hypercalcemia, Renal failure, Anemia, Bone (decreased density)

Multiple myeloma

Multiple myeloma Prominent pale-staining golgi (normal plasma cells)

Multiople myeloma Plasma cells

Multiple myeloma Lytic lesions (areas of decreased bone density)

Multiple myeloma Lytic lesions

Multiple myeloma Breakdown of bone in vertebrae

Rouleaux formation (RBCs) in multiple myeloma RBC normally have net-negative charge (zeta potential), but with all the protein, loss of negative charge that normally repel, so aggregate into stacks

1st group has good prognosis 2nd group has unfavorable prognosis 3rd group (variable)

Monoclonal protein immunoelectrophoresis

What are leukemias?

Malignant neoplasms of hematopoietic stem cells. Pathogenesis in most cases is unknown. Spill into blood, & may also infiltrate liver, spleen, lymph nodes & other tissues

What are the differences between acute and chronic leukemia?

Acute * Symptoms that result from suppression of normal marrow function: anemia (fatigue), fever (infection) and/or bleeding (thrombocytopenia) * Fatal w/in wks if untreated * Characterized by presence of immature blasts Chronic * Non-specific symptoms: fatigue, weight loss, anemia, or abonromal sensation in abdomen caused by splenomegaly * Longer survival * Associated with mature cells (but may have acute phase blast crisis)

Besides acute vs. chronic, how else can you classify leukemia?

Lymphoblastic (originate from precursor of B/T cells) vs. myeloid (precursor of granulocytes, monocytes, erythrocytes, or megakaryocytes)

What are the 4 types of leukemias?

Acute myeloid leukemia (AML) Chronic myelogenous leukemia (CML) Acute lymphoblastic leukemia (ALL) Chronic lymphocytic leukemia (CLL)

AML accounts for \_\_\_% of acute leukemias and is more commonly seen in \_\_\_\_\_\_\_\_

AML 90% of acute leukemias More commonly seen in adults

How to AML patients present?

Anemia, thrombocytopenia, leukocytosis/leukopenia

How do we diagnose AML? (amount of blasts?)

\>20% myeloblasts in bone marrow OR peripheral blood

On what factors was the French-American-British (FAB) classification based?

Based on type of myeloid precursor (neutrophilic, monocytic, erythroid, or megakaryocytic) and degree of differentiation/maturation (FAB M0-M7)

What is the acute myeloid leukemia in which neoplastic promyelocytes predominate?

AML - FAB M3 Acute Promyelocytic Leukemia t(15,17) translocation found affecting APL gene and retinoic acid receptor gene (functions in cell maturation) Also mutations FLT3 gene (tyrosine kinase promoting cell proliferation and survival)

What is a common complication of AML?

DIC - as cells release progcoagulants and fibrinolytic factors contained in abnormal granules

What is the treatment for AML?

Retinoic acid induces cell maturation, reducing risk for DIC

Describe the myelobasts in AML

1. Uniform in appearance 2. 25-30 um 3. Fine chromatin and 1-3 prominent nucleoli 4. Scanty blue cytoplasm may or may not have azurophilic granules 5. Auer rods (abnormal linear arrangement of azurophilic granules) may be present 6. Usu. myeloperoxidase +, Tdt negative

Describe the pathophysiology of AML

Blasts accumulate in marrow, displacing normal progenitors with immature, neoplastic nonfunctional cells Untreated, AML is lethal within weeks to months

WHO Classification

I: AML with genetic abberations II: AML with MDS-like features III: AML Therapy Related IV: Other

What is CML?

Chronic myeloproliferative disorder Characterized by effective hematopoiesis & massively large spleen (extramedullary hematopoiesis) Thought to be due to proliferation of pluripotent myeloid stem cell without maturation arrest Presentation: leukocytosis, anemia, thrombocytopenia/cytosis

What do you see in the peripheral blood in CML? Bone marrow?

Peripheral blood: 1. Increased # leukocytes with left shift 2. Increased # basophils/eosinophils Bone marrow 1. Hypercellular with increased # morphologically normal precursors 2. Varying degrees of marrow fibrosis

How do you diagnose CML?

Based on combo of clinical, morphologic, and cytogenetic findings Characteristic translocation t(9,22) ABL-BCR - fusion results in protein with tyrosine kinase activity (Philadelphia Chromosome)

What are some other chronic myeloproliferative disorders?

1. Polycythemia vera (increased RBC count; JAK2 mutation in 95%) 2. Primary myelofibrosis (marrow fibrosis with extramedullary hematopoiesis & massive splenomegaly; JAK2 mutation in 50%) 3. Essential thrombocythemia (Marked thrombocytosis; JAK2 mutation in 40-50%)

What is ALL? S/Sx Diagnosis

Acute Lymphoblastic Leukemia/Lymphoma Arises from neoplastic stem cell committed to lymphoid lineage. Blasts accumulate in marrow, crowd out normal progenitors, and spill into peripheral blood. S/Sx: anemia/thrombocytopenia with high WBC and circulating blasts Dx: Lymphoblasts must comprise at least 20% of nucleated marrow cells or blood leukocytes

What is the morphology of lymphoblasts in ALL?

1. Typically 20-30um 2. Bland, finely reticulated chromatin 3. Nucleoli indistinct 4. Cytoplasm sparse and lacks granules 5. Usually express TdT (terminal deoxynucleotidyl transferase), CD10, but negative for myeloperoxidase

What is CLL? Who does it affect? S/sx

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Chronic, usually indolent neoplasm of mature lymphocytes Affects middle age to older adults; M:F = 2:1 S/Sx: Elevated lymphocyte count (10K-150K/ul);anemia; thrombocytopenia; usu asymptomatic

What is the morphology of CLL?

1. Lymphoid cells in CLL are slightly larger than the normal lymphocyte 2. Tend to have "blocky" chromatin and sparse cytoplasm

What causes CLL?

Most cases due to monoclonal B cell population Expression of pan-B-cell markers CD19/20 with co-expression of CD5 and CD23 Surface immunoglobulin weakly expressed and light chain restriction is present

What is the natural course of CLL?

Indolent (survival from 5-10 Years) and most don't need treatment at time of Dx Eventually, cytopenias occur, leading to infection or bleeding complications Autoimmune disorders common (esp. autoimmune hemolytic anemia, thrombocytopenia, neutropenia)

What is Hairy Cell Leukemia? Who does it affect?

Rare (2% of all leukemias), Low grade neoplasm of mature B cells Older adult males (median age=55; M:F = 5:1) Usu present with enlarged spleen and pancytopneia with absolute neutropenia and monocytopenia Usu only a few "hairy cells" found in peripheral blood smear

What is the morphology of Hairy Cell Leukemia?

1. Medium sized with round or oval nucleus 2. Moderate amount of cytoplasm with fuzzy border 3. Tartrate-resistant acid phosphatase (TRAP stain)

Course, prognosis, and treatment of hairy cell leukemia?

Indolent course Good prognosis Treat with 2CDA (2 chlorodeoxyadenosine)

What is Hodgkin Lymphoma? Who gets it?

~40% of all adult lymphomas Adults, slightly more common in men (except nodular sclerosis type)

How do you diagnose Hodgkin lymphoma?

1. Presence of Reed-Sternberg cells (binucleated with prominent nucleoli) 2. Mononuclear Hodgkin cells in background of reactive eosinophils, plasma cells, and histiocytes

What are the 5 types of Hodgkin Lymphoma?

1. Nodular Sclerosis 2. Mixed cellularity 3. Lymphocyte-rich 4. Lymphocyte depletion 5. Lymphocyte predominance

How do you stage Hodgkin Lymphoma?

Ann Arbor System 1. Involves single lymph node or extranodal site 2. Involves 1+ lymph nodes on same side of diaphragm 3. Involves lymph node regions on both sides of diaphragm 4. Multiple disseminated foci of 1+ extralymphatic organs

What are the differences between Hodgkin and Non-Hodgkin lymphoma?

What is follicular lymphoma? What mutation is it associated with? How does it present?

A non-Hodgkin lymphoma (indolent but incurable) 40% of adults with non-Hodgkin lymphoma Derives from germinal center t(14,18) causes overexpression of bcl-2, interfering with apoptosis Presents with painless generalized lymphadenoptahy and frequent marrow involvement 30-50% tranform to higher grade lymphoma over time

What is diffuse large B-cell lymphoma? What is it derived from? How does it present?

50% of adults with non-Hodgkin lymphoma Wide age range (children to elderly) Derives from germinal center or post-germinal center B cell Rapidly enlarging lymphadenopathy, extranodal disease (30%), GI tract, CNS Fatal if untreated, but potentially curable (40-50%)

What is Burkitt's lymphoma? What are the differences between the 2 types? What is it associated with? What is its morphology?

30% of non-Hodgkin lymphoma American type: GI tract, para-aortic lymph nodes African (endemic) type: Jaw involvement (100% latently infected with EBV) Bone marrow and peripheral blood involvement is common Association with EBV and t(8,14) translocation involving c-myc Morphology = "starry sky" with many lymphoma cells and tingible-body macrophages

What is a multiple myeloma? Who does it affect? What is the clinical presentation?

Monoclonal proliferation of neoplastic plasma cells with involvement of the bone marrow @ multiple sites Affects middle aged to elderly Clinical presentation: 1. Heme: Normocytic anemia, occasional thrombocytopenia/leukopenia, Rouleaux formation due to increased serum Ig 2. Bone: pain/pathologic fractures (lytic lesions in skull, vertebrae, ribs, pelvis) 3. Hypercalcemia 4. Renal failure 5. Infection

What are some complications of multiple myeloma?

M (monoclonal) protein: serum protein electrophoresis detects monoclonal immunoglobulin or light chains produced by neoplastic plasma cells Bence-Jones protein: free light chains in urine, which contribute to renal failure Amyloidosis: Ig or light chains may form amyloid (beta-pleated sheet conformation) and may result in organ dysfunction Plasmacytoma: solitary focus of neoplastic plasma cells

Translocations: - CML - Burkitt lymphoma - Follicular lymphoma - M3 type of AML

- CML: t(9;22) (bcr-abl hybrid) - Burkitt lymphoma t(8,14) (c-myc activation) - Follicular lymphoma t(14;18) (bcl-2 activation) - M3 type of AML: t(15;17) (responsive to all-trans retinoic acid)