Neoplastic Hematopoetic Disorders Flashcards

Question

Origin of lymphoid neoplasms. small cell lymphocytic lymphoma chronic lymphocytic leukemia

Answer 1

nbc - naïve b cell bone marrow

Answer 2

Pc cell in the bone marrow?

Answer 3

Mc - mantle b cell mantle of lymph noed

Answer 4

GC - germinal center b cell germinal center of lymph node

Answer 5

dn to dp dn- cd4cd8 double negative pro t cell dp cd4cd8 double positive pre t cell in thymus

Answer 6

ptc - peripheral t cell

Answer 7

mz- marginal zone b cell marginal zone of lymph node

Answer 8

B-cell acute lymphoblastic leukemia/lymphoma (B-ALL)

Answer 9

``` Chronic lymphocytic leukemia/small lymphocytic lymphoma B-cell prolymphocyticleukemia Lymphoplasmacyticlymphoma Splenicand nodal marginal zone lymphomas Extranodalmarginal zone lymphoma Mantle cell lymphoma Follicular lymphoma Marginal zone lymphoma Hairy cell leukemia Plasmacytoma/plasma cell myeloma Diffuse large B-cell lymphoma Burkittlymphoma ```

Answer 10

``` T-cell prolymphocyticleukemia Large granular lymphocytic leukemia Mycosis fungoides/Sézarysyndrome Peripheral T-cell lymphoma, unspecified Anaplastic large-cell lymphoma AngioimmunoblasticT-cell lymphoma Enteropathy-associated T-cell lymphoma Panniculitis-like T-cell lymphoma HepatosplenicγδT-cell lymphoma Adult T-cell leukemia/lymphoma Extranodal NK/T-cell lymphoma NK-cell leukemia ```

Answer 11

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL)

Answer 12

``` Classical subtypes Nodular sclerosis Mixed cellularity Lymphocyte-rich Lymphocyte depletion ``` Lymphocyte predominance

Answer 13

15% | Rare

Answer 14

not on list

Answer 15

30+% | Rare

Answer 16

30+% | Rare

Answer 17

64% ``` Diffuse large B-cell lymphoma 18 1 Follicular lymphoma 8 4 Chronic lymphocytic leukemia/small lymphocytic lymphoma 12 3 Multiple Myeloma 13 2 Hodgkin lymphoma 7 5 B-celllymphoblastic leukemia/lymphoma 2 ```

Answer 18

T-cell lymphoblastic leukemia/lymphoma | 1

Answer 19

Myeloid leukemias 14 ``` Acute 10 1 Chronic (myeloproliferativedisorders) 4 2 ```

Answer 20

CD1Thymocytesand Langerhanscells CD3Thymocytes, mature T cells CD4Helper T cells, subset of thymocytes CD5T cells and a small subset of B cells CD8CytotoxicT cells, subset of thymocytes, and some NK cells

Answer 21

CD10Pre-B cells and germinal center B cells; also called CALLA CD19Pre-B cells and mature B cells but not plasma cells CD20Pre-B cells after CD19 and mature B cells but not plasma cells CD21EBV receptor; mature B cells and follicular dendriticcells CD23Activated mature B cells CD79aMarrow pre-B cells and mature B cells.

Answer 22

CD11cGranulocytes, monocytes, and macrophages; also expressed by hairy cell leukemias CD13Immature and mature monocytesand granulocytes CD14Monocytes CD15Granulocytes; Reed-Sternberg cells and variants inclassical Hodgkin lymphoma CD33Myeloid progenitors and monocytes CD64Mature myeloid cells

Answer 23

CD16NK cells and granulocytes CD56NK cells and a subset of T cells

Answer 24

CD34Pluripotenthematopoietic stem cells and progenitor cells of many lineages

Answer 25

CD30Activated B cells, T cells, and monocytes; Reed-Sternberg cells and variants in classical Hodgkin lymphoma

Answer 26

CD45All leukocytes; also known as leukocyte common antigen (LCA)

Answer 27

Thymocytesand Langerhanscells

Answer 28

Thymocytes, mature T cells

Answer 29

Helper T cells, subset of thymocytes

Answer 30

T cells and a small subset of B cells

Answer 31

CytotoxicT cells, subset of thymocytes, and some NK cells

Answer 32

PREB cells and germinal center B cells; also called CALLA

Answer 33

Pre-B cells and mature B cells but not plasma cells

Answer 34

Pre-B cells after CD19 and mature B cells but not plasma cells

Answer 35

EBV receptor; mature B cells and follicular dendriticcells

Answer 36

Activated mature B cells

Answer 37

Marrow pre-B cells and mature B cells.

Answer 38

Granulocytes, monocytes, and macrophages; also expressed by hairy cell leukemias

Answer 39

Immature and mature monocytesand granulocytes

Answer 40

Granulocytes; Reed-Sternberg cells and variants inclassical Hodgkin lymphoma

Answer 41

Myeloid progenitors and monocytes

Answer 42

Mature myeloid cells

Answer 43

NK cells and granulocytes

Answer 44

NK cells and a subset of T cells

Answer 45

Pluripotenthematopoietic stem cells and progenitor cells of many lineages

Answer 46

Activated B cells, T cells, and monocytes; Reed-Sternberg cells and variants in classical Hodgkin lymphoma

Answer 47

All l leukocytes; also known as leukocyte common antigen (LCA)

Answer 48

cell suspension tagged antibodies tagged antibodies attached to the cell listen to lecture and go through slides right now

Answer 49

b cel lymphoma

Answer 50

TdT, CD19, CD10, sIg-(usually CD20-)

Answer 51

CD19, CD20, CD22,sIg+

Answer 52

TdT, CD1a, CD2, CD5, CD7, CD4/CD8(usually surface CD3-)

Answer 53

CD2, sCD3, CD4, CD5, CD7, CD8 (TdT-, CD1a-)

Answer 54

Establish surface markers for lymphocytes From lymphocytes suspended from a lymph node or blood.

Answer 55

CD19+, lambda +

Answer 56

Bone marrow precursor B cell

Answer 57

Diverse chromosomal translocations; t(12;21) involvingRUNX1andETV6present in 25% of childhood ALL, t(9;22) / Bcr-Abl1is the most common in adult ALL

Answer 58

Predominantly children; symptoms relating to marrow replacement and pancytopenia; aggressive

Answer 59

Precursor T cell (often of thymic origin)

Answer 60

Diverse chromosomal translocations,NOTCH1 | mutations (50% to 70%)

Answer 61

Predominantly adolescent males; thymicmasses and variable bone marrow involvement; aggressive

Answer 62

Terminology:Neoplasms also known as “Acute Lymphoblastic Leukemia” US Epidemiology: Together 80 % of childhood leukemias Twice as common in Caucasians as in blacks Slightly more common in Hispanic population Slightly more common in males than females Most common acute leukemia associated with Down Syndrome !!!!

Answer 63

all represents 0.4% of all new cancers all is most requently diagnosed at age 14

Answer 64

B-cellprecursor neoplasms present in young kids (peak 3 y.o.) with extensive bone marrow involvement with peripheral blood “leukemic phase” Occasionally present as “lymphoma” with mass in lymph nodes

Answer 65

T-cellprecursor neoplasms tend to present in adolescent males as lymphoma with thymicinvolvement and possible leukemia

Answer 66

“lymphoblast”: Same morphologically for T-cell and B-cell precursor neoplasms Peripheral blast count usually > 20,000 and commonly > 50,000 May be aleukemic

Answer 67

Lymphoblastswith condensed nuclear chromatin, small nucleoli, and scant agranularcytoplasm. PAS+ / Myeloperoxidase -

Answer 68

•Specialized DNA polymerase present only in precursor B-or T-cells

Answer 69

•CD19, PAX5 (+/-CD10, CD20, cIgM)

Answer 70

* + CD1, CD2, CD5, CD7 | * CD3, CD4 & CD8 positive only in late pre-T-cell tumors

Answer 71

PAS+ /Myeloperoxidase -

Answer 72

* ~ 90% patients have structural changes in chromosomesof B-cell leukemic cells with hyperdiploidymost common, some hypodiploidyand some expressing Philadelphia chromosome (t9:22) bcr-ablprotein of 190 kDavs 210 kDaof CGL * ~ 70% T-ALLs have NOTCH1 gain of function mutations

Answer 73

Abrupt and stormy onset Classic Symptoms Leukemia: Depressed marrow function Fatigue(anemia) Infection & fever(neutropenia) Bleeding(thrombocytopenia) Generalized Lymphadenopathy Bone pain and tenderness Splenomegaly and Hepatomegaly CNS Symptoms-meningeal involvement (headache, vomiting) and nerve palsies Testicular involvement

Answer 74

95 % childhood B-cell ALL achieves remission & 3/4 considered cured In adults only 35-40% are cured

Answer 75

(1) Age 100,000 cells/ul (4) Presence of unfavorable cytogenetic aberrations •Philadelphia chromosome t(9;22) •Rearrangements of MLL (mixed lineage leukemia) gene

Answer 76

Marrow between pink bone trabeculae ~ 100% cellular. Malignant leukemic cells have replaced normal hematopoiesis. Explains infection (lack granulocytes), hemorrhage (lack of platelets), anemia (lack RBCs )

Answer 77

* Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma * Follicular Lymphoma * Diffuse Large B-cell Lymphoma * BurkittLymphoma * Mantle Cell Lymphoma * Marginal Zone Lymphoma * Hairy Cell Leukemia * Plasma Cell Neoplasms/Related Disorders (Myeloma) * Lymphoplasmacytic Lymphoma

Answer 78

Germinal-center B cell

Answer 79

Translocations involving c-MYCand lgloci, usually t(8;14); subset EBVassociated

Answer 80

Adolescents or young adults with extranodalmasses; uncommonly presents as "leukemia"; aggressive

Answer 81

Germinal-center or post-germinal-center B cell

Answer 82

Diverse chromosomal rearrangements, most often ofBCL6(30%),BCL2(10%), or c-MYC(5%)

Answer 83

All ages, but most common in adults; often appears as a rapidly growing mass; 30% extranodal; aggressive

Answer 84

Memory B cell

Answer 85

t(11;18), t(1;14), and t(14;18) creatingMALT1-IAP2,BCL10-IgH, andMALT1-IgHfusion genes, respectively

Answer 86

Arises at extranodal sites in adults with chronic inflammatory diseases; may remain localized; indolent

Answer 87

Germinal-center B cell

Answer 88

t(14;18) creatingBCL2-IgHfusion gene

Answer 89

Older adults with generalized lymphadenopathy and marrow involvement; indolent

Answer 90

Memory B cell

Answer 91

Activating BRAFmutations

Answer 92

Older males with pancytopenia and splenomegaly; indolent

Answer 93

Naive B cell

Answer 94

t(11;14) creatingCyclinD1-IgHfusion gene

Answer 95

Older males with disseminated disease; moderately aggressive

Answer 96

Post-germinal-center bone marrow homing plasma cell

Answer 97

Diverse rearrangements involvingIgH; 13q deletions

Answer 98

Myeloma: older adults with lytic bone lesions, pathologic fractures, hypercalcemia, and renal failure; moderately aggressivePlasmacytoma: isolated plasma cell masses in bone or soft tissue; indolent

Answer 99

Naive B cell or memory B cell

Answer 100

Trisomy 12, deletions of 11q, 13q, and 17p

Answer 101

Older adults with bone marrow, lymph node, spleen, and liver disease; autoimmune hemolysis and thrombocytopenia in a minority; indolent

Answer 102

* Same morphology and immunophenotypeof malignant cells but with two different clinical presentations * CLL if intiallypresents with >5000 abnormal B cells/uLblood * SLL if presents initially as malignant lymphadenopathy

Answer 103

Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Answer 104

•Diffusely effaced lymph node architecture * Proliferation centers -prominent mitotically active foci with prolymphocytes * Pathognomonic for SLL * Small (6-12 micron) lymphocytes with irregular nuclear chromatin * Variable numbers of prolymphocytes * Rare large immunoblasts * Leukemic phase in some patients and may involve bone marrow

Answer 105

* Peripheral blood and bone marrow lymphocytosis with small lymphocytes * Irregular nuclear chromatin * Smudge cells * Hemolytic anemia and/or thrombocytopenia in some patients * Infiltration and expansion of lymph node paracortex, spleen, and live

Answer 106

A, Low-power view shows diffuse effacement of nodal architecture. B, At high power the majority of the tumor cells are small round lymphocytes. A “prolymphocyte,” a larger cell with a centrally placed nucleolus, is also present in this field (arrow).

Answer 107

B, At high power the majority of the tumor cells are small round lymphocytes. A “prolymphocyte,” a larger cell with a centrally placed nucleolus, is also present in this field (arrow).

Answer 108

Small lymphocytes with condensed chromatin Smudge cells Coexistent autoimmune hemolytic anemia w/ spherocytesand nucleated erythroid cell

Answer 109

Lymphocytes have more cytoplasm.

Answer 110

typical periportallymphocytic infiltrate.

Answer 111

+ for pan B-cell markers CD19 and CD20 Additionally may have low level of surface Ig (kappa or lambda) expressed Classic finding is presence of T-cell marker CD5 on cells and also expresses CD23 (activation marker) SomeCD38+(worse prognosis)

Answer 112

Chromosomal translocations are rare but can have •Poor prognosis-trisomy 12q and deletions of 11q, 12q,17p •Good prognosis-deletion 13q (LUCKY 13) Some have NOTCH1 mutations (poor prognosis) Stimulation by transcription factor NF-κβ Bruton tyrosine kinase inhibitors can be used to inhibit CLL cell proliferation

Answer 113

Coexpressionof CD5 on CD19+ B cells

Answer 114

Onset > age 50 (median age 60) Male predominance 2:1 Often asymptomatic May have hypogammaglobulinemia(↑bacterial infections) May have small monoclonal Ig peak by electrophoresis CLL/SLL disrupts normal immune function (infections) 10-15% patients have autoantibodies produced by non-neoplastic cells to red cells and/or platelets

Answer 115

Extremely variable (average 15 years) 50-60% have mutated IGVH* (memory-post GC) –>24 years ZAP 70-, CD38- 40-50% have unmutatedIGVH (naive-pre GC) –7 years ZAP 70+, CD38+ Indolent clinical course Responds poorly to treatment Diffuse involvement of marrow and/or high serum Beta-2 microglobulin-worse prognosis

Answer 116

a rare transformation with worsening of cytopenias

Answer 117

into Diffuse Large B-cell Lymphoma (3%) or EVB+ Hodgkin Lymphoma (0.5%) with more aggressive course

Answer 118

~ 40% of adult non-Hodgkin lymphomas Onset after age 55 M=F “most common form of indolent lymphoma” = most common of the lymphomas that will not kill you quickly

Answer 119

Predominately in lymph nodes + ~ 85% marrow involvement 10% have peripheral blood lymphocytosis (

Answer 120

centroblasts(grade 3: >15 centroblasts/HPF)

Answer 121

Nodular aggregates of lymphoma cells are present throughout lymph node.

Answer 122

small lymphoid cells with condensed chromatin and irregular or cleaved nuclear outlines (centrocytes) are mixed with a population of larger cells with nucleoli (centroblasts).

Answer 123

reactive - just around the mantle? follicular lymphoma - in the whole follicle

Answer 124

+ for CD19, CD20, CD10 (CALLA)and sIg | + for BCL2 (apoptosis antagonist),BCL6

Answer 125

Hallmark is 14:18 translocation (90%)-BCL2 gene on 18 (antagonist of apoptotic cell death) with IgHon 14

Answer 126

Painless generalized adenopathy and bone marrow involvement (75%) Involvement extranodalsites uncommon Median survival 7 –9 years (incurable)

Answer 127

occurs in 30-50% of patients Usually to Diffuse Large B-Cell Lymphoma Sometimes c-MYC translocation leads to Burkitt-like lymphoma Following transformation, survival

Answer 128

Prominent nodules represent white pulp follicles expanded by follicular lymphoma cells. Other indolent B-cell lymphomas (small lymphocytic lymphoma, mantle cell lymphoma, marginal zone lymphoma) can produce an identical pattern of involvement

Answer 129

``` ~ 25-50% of adult Non-Hodgkin Lymphomas (NHL) 2/3 of “aggressive lymphomas” Slight male predominance Median onset age 60 25% of childhood lymphomas ```

Answer 130

Large size neoplastic lymphocyte (2-5 times diameter of normal-sized lymphocyte) Diffuse pattern of growthwith effacement of node architecture

Answer 131

Tumor cells have large nuclei, open chromatin, and prominent nucleoli

Answer 132

+ for CD19, CD20, sIg | Variable expression germinal center markers (CD10, BCL6)

Answer 133

Heterogeneous cytogenetic changes >30 % dysregulation BCL6, a DNA-binding zinc-finger transcriptional regulator inhibits expression of factors that regulate differentiation inhibits p53 activity 10-20% contain t(14:18) (IgH-BCL2) present in follicular lymphomas preventing apoptosis 5% have c-MYC translocation and may resemble Burkittlymphoma

Answer 134

Typically present with rapidly enlarging often symptomatic mass at a single nodal or extranodalsite Oropharynx (Waldeyerring, tonsils, adenoids) common site

Answer 135

Mediastinal large B-cell lymphoma-young women with involvement of viscera and CNS Immunodeficiency-associated large B-cell lymphoma–occurs in end-stage HIV infection or bone marrow transplantation plus Epstein-Barr Virus Body cavity large cell lymphoma (Primary effusion lymphoma): associated with KSHV/HHV-8 in HIV patients

Answer 136

60-80% remission (~50% of these cured)

Answer 137

The isolated large mass is typical. In contrast, indolent B-cell lymphomas usually produce multifocal expansion of white pulp

Answer 138

30% childhood lymphomas in US | 2-3% of adult lymphomas

Answer 139

African(endemic) children & young adults –EBVpositive –Jaw and viscera involvement

Answer 140

–Most EBV negative –Abdominal masses (ileocecalinvolvement most frequent) –Bilateral breast, ovarie SporadicUS (nonendemic) children & young adults

Answer 141

–In association with HIV infection –May be initial manifestation of AIDS –Highly aggressive lymphoma

Answer 142

* Involved tissues effaced by diffuse infiltrate neoplastic lymphocytes * Intermediate-sized lymphocytes (10-25 micron in diameter) and moderate amount of amphophilicor basophilic cytoplasm * High mitotic rate (Warburg effect with aerobic glycolysis and high biosynthesis) * Apoptotic tumor cell death (“Starry Sky” pattern) * Marrow and blood rarely involved

Answer 143

Hypermutatedmature follicular center B-cells with surface IgM, kappa or lambda light chainsand + for IgM, BCL6, CD19, CD20and CD10

Answer 144

numerous pale tingiblebody macrophages are evident, producing a "starry sky" appearance.

Answer 145

tumor cells have multiple small nucleoli and high mitotic index. The lack of significant variation in nuclear shape and size lends a monotonous appearance.

Answer 146

cytoplasmic vacuoles

Answer 147

All have translocations of the c-MYCgene, Chromosome 8 t(8;14) (IgHlocus) common t(8;2) (kappa) or t(8;22) (lambda) less common INCREASED c-MYC EXPRESSION May have mutations inactivating p53 All endemictumors are latently infected with EBV 15-20% sporadic and 25% of HIV have associated EBV

Answer 148

Aggressive neoplasm, but sensitive to chemotherapy. “Most children and young adults can be cured”

Answer 149

46, XY, t(8;14) shows typical translocation for Burkittlymphoma, one of the most common lymphomas in Africa children. In U.S., commonly in young adults as intra-abdominal mass.

Answer 150

2.5% of Non Hodgkin Lymphoma (NHL) in US Onset 5thto 6thdecade M>F

Answer 151

Homogenous population small cleaved lymphocytes resembling the normal mantle B-cells that surround the follicular center

Answer 152

Associated with an t(11:14)translocation involving the Cyclin D1 (cell cycle regulator promoting G1→S phase) locus on 11 and IgHlocus on chromosome 14 Naive cell with no somatic hypermutation

Answer 153

Cyclin D1, CD5, CD19, CD20,BCL2, and moderately high levels of surface immunoglobulin (IgM or IgD), but CD23-, CD10-

Answer 154

Presents with painless lymphadenopathy +/-peripheral blood involvement (20-40%) Signs/symptoms of splenomegaly (50%) ExtranodalGI involvement commonly seen Sometimes presents as lymphomatoidpolyposis)

Answer 155

Aggressive, Median survival only 3-4 years

Answer 156

neoplastic lymphoid cells surround a small, atrophic germinal center, producing a mantle zone pattern of growth.

Answer 157

shows a homogeneous population of small lymphoid cells with somewhat irregular nuclear outlines, condensed chromatin, and scant cytoplasm. Large cells resembling prolymphocytes(seen in chronic lymphocytic leukemia) and centroblasts(seen in follicular lymphoma) are absent

Answer 158

Initially recognized in mucosal sites and referred to as MALTomasor mucosal-associated lymphoid tissue lymphomas

Answer 159

Extranodal(GI & Spleen) and/or lymph nodes

Answer 160

Arise in tissues involved by chronic inflammatory disorders of autoimmune or infectious etiology (Helicobacter pylori, Campylobacter jejuni, Sjogrensyndrome, Hashimoto thyroiditis) Remain localized for long periods, spreading systemically only late in course If gastric, may regress if inciting agent (H. pylori) is removed T-helper cell driven

Answer 161

Positive CD19, CD79a, BCL2 | Negative CD5, CD10, CD23, cyclin D1

Answer 162

``` No translocations initially but later can develop; t(1;14) BCL10; IgH t(11;18) MALT1;IAP2 t(14;18) IgH;IAP2 BCL10 and MALT1 activate NF-κB ```

Answer 163

Excellent if inciting agent removed (80% 15 year survival) If translocations occur then tumor does not regress with antibiotic treatment May transform into diffuse large B-cell lymphoma

Answer 164

Rare, 2% of all leukemias | Predominately a disease of middle-aged Caucasian males (M:F 5:1)

Answer 165

Characteristic “hairy cells” in peripheralblood

Answer 166

CD19, CD20, CD79a, sIg, CD22, CD25, PAX5, CD11c , CD103, DBA.44, TRAP (tartrate resistant acid phosphatase) also CD123, HC2, FMC7 and annexinA1

Answer 167

High incidence somatic hypermutation(post germinal center) | BRAF mutations

Answer 168

Infiltration bone marrow, liver & spleen by neoplastic cells Massive splenomegalycommon Pancytopeniawith increased susceptibility to infection Increased atypical mycobacterial infections Leukocytosis only in 15-20%

Answer 169

Indolent course Tumor cells “exceptionally sensitive”to chemotherapy Long-lasting remission in majority of patients

Answer 170

A,Phase-contrast microscopy shows tumor cells with fine hairlikecytoplasmic projections. B,In stained smears, these cells have round or folded nuclei and modest amounts of pale blue, agranularcytoplasm

Answer 171

B-cell clone that usually synthesizes and usually secrets a single homogeneous immunoglobulin or its fragments Often referred to as plasma cell dyscrasia Cause 15% of deaths from white cell neoplasms Monoclonal Ig in the blood is referred to as “M component”, monoclonal protein, dysproteinemia or paraproteinemia Rouleauxin peripheral blood smear

Answer 172

Neoplastic plasma cells often synthesize excess light or heavy chains along with complete immunoglobulins •Free L (light) chainsare known as Bence Jones proteinthat are primarily detected in the urine since blood levels are quickly eliminated in urine

Answer 173

multiple myeloma plasmacytoma smoldering myeloma heave light chain disease waldenstrom macroglobulinemia primary or immunocyte associated amyloidosis monoclonal gammopathy of undetermined significance

Answer 174

plasma cell meyeloma

Answer 175

(single mass) Intraosseous –most eventually progress to multiple myeloma Soft tissue –may be cured by local resection

Answer 176

(asymptomatic with high plasma M component > 3gm/dL) | ~75% per progress to multiple myeloma within 15 years

Answer 177

Secretes free H (L) chain fragments

Answer 178

High levels of IgM

Answer 179

free L chains leading to AL type amylodosis

Answer 180

M components

Answer 181

* Incidence begins to increase substantially between ages 50 and 60 and peaks in 8thand 9thdecade * 1% US deaths caused by malignancy * ~ 15% WBC malignancy deaths * 10,000-12,000 cases of multiple myeloma/ year in U.S. * Incidence varies by race; slightly higher incidence in males * 9/100,000 Blacks * 4/100,000 Caucasians * 2.5/100,000 Chinese * 1.5/100,000 Japanese

Answer 182

median age at diagnosis is 69

Answer 183

t14q32 (IgHgene) to 11q13 (cyclin D1) or 6p21(cyclin D3) & del17p (TP53) Rarely develop plasma cell leukemia (MYC mutations) IL-6 drives proliferation Tumor M1P1αupregulates RANKL and inhibits of osteoblasts (Wntpathway) Radiographic punched-out lytic defects, usually 1-4 cm in diameter

Answer 184

Express CD38, CD138, CD79a and cytoplasmic immunoglobulins (+/-CD56) Do not usually express CD19

Answer 185

The sharply punched-out bone lesions are most obvious in the calvarium

Answer 186

``` Common Locations: Vertebrae 66% Ribs 44% Skull 41% Pelvis 28% Clavicle 10% Scapula 10% ```

Answer 187

80-90% PCD 59 30-80 1.5:1 multiple bone marrow lesions positive 99%

Answer 188

5-10% pcd 56 80 2-3:1 any bone >50% in vertebrae single lesion 43% (22-77)

Answer 189

80 4:1 80-90% upper airway negative 27% (0-86%)

Answer 190

Normal marrow cells are largely replaced by plasma cells, including forms with multiple nuclei, prominent nucleoli, and cytoplasmic droplets containing Ig.

Answer 191

flame cell mott cell ditcher body Russell body

Answer 192

marrow. | Sheets of atypical plasma cells (plasmablasts)

Answer 193

Lytic bone lesions → pathologic fractures and substantial bone pain Hypercalcemia (metastatic calcification) Suppression of humoral immunity recurrent infections Renal insufficiency Second only to infection as cause of death Due to toxicity of hypercalcemia and Bence-Jones proteins Increased immunoglobulins (AL amyloidosis) and Bence-Jones proteins Monoclonal gammopathy: IgG (60%)>IgA>IgM/IgD/IgE (15-20% produce only light chains) Hyperviscositywith IgA, IgG3and IgM subtypes Visual impairment, neurologic symptoms, bleeding, cryoglobulinemia 1% produce no monoclonal protein

Answer 194

Untreated survival is 6 –12 months from diagnosis With chemotherapy, median survival is 4-6 years Cyclin D1 translocations good prognosis

Answer 195

median age at death is 75 Note: Mirrors incidence with only a shift to the right of 5-6 years Only lymphoid neoplasm with much higher incidence and death rate in African-Americans than Caucasians

Answer 196

B-cell neoplasm of older adults; presents in 6th& 7thdecade Common cause of WaldenstromMacroglobulinemia(IgM) but can also produce IgG or IgA

Answer 197

lymphocytes, plasma cells, and intermediate forms; Immunoglobulin inclusions (Russell bodies –cytoplasm; Dutcher bodies-nucleus)

Answer 198

MYD88mutations leading to NF-κB activation

Answer 199

Positive for CD19, CD79a, surface and cytoplasmic immunoglobulins (IgM, IgD, IgG or IgA); also variable CD20, and CD38

Answer 200

Lymphadenopathy, hepatomegaly and splenomegaly 10% have RBC hemolysis ~50%have HyperviscositySyndrome from high levels IgM Visual Impairment Neurologic problems: dizziness, deafness & stupor Bleeding Cryoglobulinemia No lytic bone lesions Usually no Bence-Jones proteinuria or amyloidosis

Answer 201

Incurable with median survival 4-6 years from time of diagnosis

Answer 202

* Peripheral T-cell Lymphoma, unspecified * Anaplastic Large Cell Lymphoma * Adult T-cell Leukemia/Lymphoma * Mycosis Fungoides/SezarySyndrome * Large Granular Lymphocytic Leukemia * ExtranodalNK/T-cell Lymphoma

Answer 203

5-10% of Non Hodgkin Lymphoma in US Higher % in Asia Much more aggressive neoplasms than B-cell neoplasms Much worse prognosis than B-cell neoplasms Occur Predominately in ExtranodalSites Diagnosis completely on flow cytometry marker studies Exhibit T-cell surface CD markers Lack TDT May or may not express CD4 or CD8

Answer 204

Helper T cell

Answer 205

HTLV-1provirus present in tumor cells

Answer 206

Adults with cutaneous lesions, marrow involvement, and hypercalcemia; occurs mainly in Japan, West Africa, and the Caribbean; aggressive

Answer 207

Helper or cytotoxic T cell

Answer 208

No specific chromosomal abnormality

Answer 209

Mainly older adults; usually presents with lymphadenopathy; aggressive

Answer 210

Cytotoxic T cell

Answer 211

Rearrangements ofALK in a subset

Answer 212

Children and young adults, usually with lymph node and soft-tissue disease; aggressive

Answer 213

NK-cell (common) or cytotoxic T cell (rare)

Answer 214

EBV-associated; no specific chromosomal abnormality

Answer 215

Adults with destructive extranodal masses, most commonly sinonasal; aggressive

Answer 216

Helper T cell

Answer 217

No specific chromosomal abnormality

Answer 218

Adult patients with cutaneous patches, plaques, nodules, or generalized erythema; indolent

Answer 219

Two types: cytotoxic T cell and NK cell

Answer 220

Point mutations in STAT3

Answer 221

Adult patients with splenomegaly, neutropenia, and anemia, sometimes, accompanied by autoimmune disease

Answer 222

* Present with lymphadenopathy and sometimes systemic signs (pruritis, fever, and weight loss) * T-cell lymphomas associated with lymph nodes * Significantly worse prognosis than comparable B-cell * Survival

Answer 223

spectrum of small, intermediate, and large lymphoid cells, many with irregular nuclear contours, is visible

Answer 224

Approximately 10-20% of childhood lymphoma and

Answer 225

* Rearrangement present more in children & young adults * results in fusion protein which activates tyrosine kinase (JAK/STAT) * Most common t(2;5) ALKand nucleophosmin(NPM)on chromosome 5 * Excellent response to treatment when ALK+ (75% cured)

Answer 226

* Usually in older adults | * poor prognosis ~other peripheral T-cell lymphomas

Answer 227

CD30, CD2, CD4, CD45, CD25, +/-CD25, +/-ALK

Answer 228

A, Several “hallmark” cells with horseshoe-like or “embryoid” nuclei and abundant cytoplasm lie near the center of the field. B, Immunohistochemicalstain demonstrating the presence of ALK fusion protein.

Answer 229

* Only in adults infected with human T-cell leukemia virus Type 1 (HTLV-1) * Virus encodes Tax protein activating NF-κβ * Endemic in Southern Japan, West Africa & Caribbean * Hepatosplenomegaly, lymphadenopathy, skin lesions, lymphocytosis, hypercalcemia * Rapidly progressive; fatal within months * Median survival 8 months * Characteristic cloverleaf nucleii * High levels of CD 25

Answer 230

CD4+ T-cell lymphoma of the skin CLA, CCR4 & CCR10 expression leads to skin infiltration Lymphoma cells with ceribriformnuclei

Answer 231

Inflammatory (erythrodermic) pre-mycotic patch, plaque, & tumor phases Aggressive neoplasm with median survival 8-9 years (M>F)

Answer 232

Sezarysyndromeis variant in which skin involvement is manifest as a generalized exfoliativeerythroderma

Answer 233

Leukemic phase with Sezarycell (cerebriformnuclei) seen in Sezarysyndrome and 25% of plaque →Survival

Answer 234

•P.K.A. Tϒ-lymphoproliferative disorder •Lymphocytes with abundant blue cytoplasm containing scattered azurophilicgranules •Rare disorder •Variants •CD3+ T-cell (indolent) •CD56+ NK cell (aggressive) •Neutropenia & anemia despite scant marrow involvement •Involves splenic red pulp and hepatic sinusoids (hepatomegaly) •Associated with rheumatologic disorders •Feltysyndrome in some (rheumatoid arthritis, splenomegaly and neutropenia)

Answer 235

•P.K.A. lethal midline granuloma, midline malignant reticulocytosisand angiocentriclymphoma •Tumor cells typically surround and invade small vessels •Clinically presents as sinonasallymphoma…..aggressive neoplasm poorly responsive to chemotherapy •EBV related •Most CD56+ NK cell •Sometimes midline skin or testes involved

Answer 236

* Classical Hodgkin lymphoma(95%) * Nodular sclerosis (65-70%) * Mixed cellularity (20-25%) * Lymphocyte-rich (

Answer 237

hodkins disease

Answer 238

* Germinal center or post germinal center B-cell with V(D)J recombination and somatic hypermutation * Aneuploid * Activated transcription factor NF-κβ * Some EBVlatent membrane protein driven * Some eosinophil and T-cell driven via activation of RS cell CD30& CD40receptors * Increased copies of c-REL proto-oncogene * LOF mutations in NF-κβinhibitor proteins (Iκβor A20)

Answer 239

Frequent lacunar cells and occasional diagnostic RS cells; background infiltrate composed of T lymphocytes, eosinophils, macrophages, and plasma cells; fibrous bands dividing cellular areas into nodules. RS cells PAX5+,CD15+, CD30+; 33% EBV+*

Answer 240

Most common subtype; usually stage I or II disease; frequent mediastinalinvolvement; equal occurrence in males and females (F = M), most patients young adults

Answer 241

Frequent mononuclear and diagnostic RS cells; background infiltrate rich in T lymphocytes, eosinophils, macrophages, plasma cells; RS cells PAX5+, CD15+, CD30+; 75% EBV+

Answer 242

More than 50% present as stage III or IV disease; M > F; biphasic incidence, peaking in young adults and again in adults older than 55 MOST COMMON FORM OF HODGKIN LYMPHOMA IN PATIENTS>50

Answer 243

Frequent mononuclear and diagnostic RS cells; background infiltrate rich in T lymphocytes; RS cells PAX5+, CD15+, CD30+; EBV-(1 case)

Answer 244

Uncommon; M greater than F; tends to be seen in older adults

Answer 245

Reticular variant: Frequent diagnostic RS cells and variants and a paucity of background reactive cells; RS cellsPAX5+, CD15+, CD30+; 50% EBV+

Answer 246

Uncommon; more common in older males, HIV-infected individuals, and in developing countries;

Answer 247

Frequent L&H (popcorn cell) variants in a background of follicular dendritic cells and reactive B cells; RS cells CD20+, CD15-, C30-; EBV-, BCL6+

Answer 248

Uncommon; young males with cervical or axillarylymphadenopathy; mediastinal*

Answer 249

A, Diagnostic Reed-Sternberg cell, with two nuclear lobes, large inclusion-like nucleoli, and abundant cytoplasm, surrounded by lymphocytes, macrophages, and an eosinophil. B,Reed-Sternberg cell, mononuclear variant Hodgkin lymphoma diagnostic? CD30+, CD15+, CD20-, CD45-, PAX5+, +/-EBV

Answer 250

A low-power view shows well-defined bands of pink, acellular collagen that subdivide the tumor into nodules.

Answer 251

This variant has a folded or multilobatednucleus and lies within a open space, which is an artifact created by disruption of the cytoplasm during tissue sectioning

Answer 252

A diagnostic, binucleateReed-Sternberg cell is surrounded by reactive cells, including eosinophils (bright red cytoplasm), lymphocytes, and histiocytes

Answer 253

Negative CD45 staining of RS cells and Variants

Answer 254

membrane and paranuclearstaining of RS cells and Variants

Answer 255

Positive CD15 staining of RS cells and Variants

Answer 256

lymphocyte-predominance

Answer 257

Numerous mature-looking lymphocytes surround scattered, large, pale-staining lymphohistiocyticvariants (“popcorn” cells).

Answer 258

Several such variants with multiply infoldednuclear membranes, small nucleoli, fine chromatin, and abundant pale cytoplasm are present. CD20+, CD 45+, BCL6+, CD15-, CD30-, EBV-

Answer 259

* Lymphadenopathy at first * Classical Hodgkin lymphoma * Cervical, mediastinal, axillary, para-aortic * Bimodal age distribution * Nodular lymphocyte predominance Hodgkin lymphoma * Cervical, axillary, inguinal * Young males

Answer 260

Involvement of a single lymph node region (I) or a single extra-lymphatic organ or site (IE).

Answer 261

Involvement of two or more lymph node regions on the same side of the diaphragm alone (II) or localized involvement of an extra-lymphatic organ or site (IIE).

Answer 262

Involvement of lymph node regions on both sides of the diaphragm without (III) or with (IIIE) localized involvement of an extra-lymphatic organ or site.

Answer 263

Diffuse involvement of one or more extra-lymphatic organs or sites with or without lymphatic involvement.

Answer 264

of the following symptoms: unexplained fever, drenching night sweats, and/or unexplained weight loss of greater than 10% of normal body weight

Answer 265

Stage I/IIA almost 90%; Stage IV 5 year survival 60-70%

Answer 266

Bimodal Age Distribution (mostly young adults) More often localized to a single axial group of nodes (cervical, mediastinal, para-aortic) Orderly spread by contiguity Mesenteric nodes and Waldeyer ring rarely involved Extra-nodal presentation rare Excellent Response to therapy

Answer 267

Marked Increase after age 50 (elderly) More frequent involvement of multiple peripheral nodes Noncontiguous spread Waldeyerring and mesenteric nodes commonly involved Extra-nodal presentation common Poor response to therapy

Answer 268

“Bi-Modal Peaks”??? 20-29 years > 70 years?

Answer 269

Large majority | after age 50

Answer 270

0.5% of all new cancers 300000 new cases/year 100000 people di each year

Answer 271

4.3% of all new cancers 2000000 new cases/year 500000 people die each year

Neoplastic Hematopoetic Disorders Flashcards

(302 cards)