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Heme Path Exam 1 > Neoplastic Hematopoetic Disorders > Flashcards

Neoplastic Hematopoetic Disorders Flashcards

1
Q

Lymphoid Neoplasms basics

A

Possess phenotypes (surface markers) of various stages of lymphocyte maturation

Leukemia–involves bone marrow primarily

Lymphoma–forms discrete tissue masses

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2
Q

Myeloid Neoplasms basics

A

Neoplasms arise from hematopoietic stem cells of myeloid (erythroid, granulocytic or thrombocytic) linage

Acute myelogenous leukemias

Myeloid sarcoma (extramedullary myeloid tumor, granulocytic sarcoma, chloroma)

Myelodysplastic syndromes (cytopenias)

Chronic myeloproliferative neoplasms (cytoses)

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3
Q

Histiocytic Neoplasms basics

A

Uncommon proliferations of macrophages/dendritic cells

Langerhans cell histiocytosis

Histiocytic sarcoma

Interdigitating dendritic cell sarcoma

Follicular dendritic cell sarcoma

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4
Q

ALL is made of

A

lymphoid progenitors

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5
Q

CLL is made of

A

naïve b lymphocytes

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6
Q

Lymphomas are made of

A

B lymphocytes in germinal center

T-lymphocytes

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7
Q

Multiple Myeloma is made of

A

plasma cells

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8
Q

AML is made of

A

myeloid progenitors that go to:

neutrophils
eosinophils
basophils
monocytes
platelets
red cells
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9
Q

Myeloproliferative disorders are made of

A 
neutrophils
eosinophils
basophils
monocytes
platelets
red cells
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10
Q

epidemiology numbers

A 
71000 new cases
20000 deaths
4.3% of all new cancers cases are non-hodkins
0.5% of new cancer cases are hodgkins
leukemia is 3.3% of all new cancer cases
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11
Q

PathogeneticFactors in White Cell Neoplasia:

Chromosomal translocations and oncogenes

A
  • Dysregulationof normal differentiation/maturation/proliferation
  • Non-random chromosomal translocations
  • Oncoproteinscreated by genomic aberrations often block normal maturation
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12
Q

PathogeneticFactors in White Cell Neoplasia:

Inherited genetic factors:

A
  • Mutations that promote genomic instability (Bloom syndrome, Fanconianemia, ataxia telagiectasia)
  • Down Syndrome and type I neurofibromatosis have associated leukemias
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13
Q

Pathogenesis of white cell malignancies.

A

Various tumors harbor mutations that principally effect maturation or enhance self-renewal, drive growth, or prevent apoptosis. Exemplary examples of each type of mutation are listed; details are provided later under specific tumor types

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14
Q

Pathogenesis of white cell malignancies.

mutations in transcription factors that influence self renewal

A

mll translocation

pml-rar fusion gene

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15
Q

Pathogenesis of white cell malignancies.

pro survival mutation (decreases apoptosis)

A

bcl2 translocation

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16
Q

Pathogenesis of white cell malignancies.

progrowth mutations (increased clel division Warburg metabolism)

A

myc translocation

tyrosine kinase mutations

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17
Q

Etiologic and Pathogenetic Factors in White Cell Neoplasia

viruses

A

HTLV-1:Adult T-cell leukemia/lymphoma
Epstein-Barr Virus (EBV):BurkittLymphoma (30-40%),
Hodgkin lymphoma (3-40 %), and a few other B-cell and NK cell lymphomas
KSHV/HHV-8: Body cavity large cell lymphoma (B-cell) = Effusion lymphoma

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18
Q

Etiologic and Pathogenetic Factors in White Cell Neoplasia

Environmental

A

Helicobacter pylori: Gastric marginal zone lymphoma = MALT lymphoma

Gluten sensitive enteropathy: T-cell lymphoma

Insecticides & Chemical Agents: Predispose to leukemias

HIV: Clonal B-cell abnormalities

Smoking: Acute myeloid leukemia risk ↑1.3-2.0x

Breast implant with chronic peri-implant seroma: Anaplastic large cell lymphoma

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19
Q

Etiologic and Pathogenetic Factors in White Cell Neoplasia

iatrogenic

A

Radiation Therapy

Chemotherapy

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20
Q

Chromosomal Translocations and Acquired Mutations of lymphoid disorders

A
  • Genes that play a role in development, growth and survival of the normal counterpart of the tumor (BCL2, BCL10, MALT1)
  • Oncogenes that block normal maturation (requirement for bcl-6 to be turned off in order for germinal center B cells to mature to memory B cells)
  • Errorsoccurring during antigen receptor gene rearrangement or antibody diversification (IgHtranslocations)
    • Activation-induced cytosine deaminase → B-cell proliferation → mutations
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21
Q

Lymphomas can be broadly distinguished by the mechanism that is used to ensure a survival advantage:

A
  • Lymphomas that are highly proliferative (Burkittlymphoma)
  • Lymphomas that evade apoptosis (Chronic lymphocytic leukemia)
  • Lymphomas with features of both(Mantle cell lymphoma)
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22
Q

Malignant Lymphomas numbers

A 
NON-HODGKIN LYMPHOMAS
•85% total
•2 major types; B –cell (80-85%) & T-cell/NK -cell
•many sub-types
HODGKIN’S LYMPHOMA
•15% of total
•5 or 6 subtypes
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23
Q

“The various lymphoid neoplasms can only be distinguished based on

A

appearance and molecular characteristics of the tumor cells”

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24
Q

Origin of lymphoid neoplasms.

precursor B
lympoblastic lymphoma/leukemias

A

BLB - pre b lymphoblast

bone marrow

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25
Q

Origin of lymphoid neoplasms.

small cell lymphocytic lymphoma
chronic lymphocytic leukemia

A

nbc - naïve b cell

bone marrow

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26
Q

Origin of lymphoid neoplasms.

multiple myeloma

A

Pc cell in the bone marrow?

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27
Q

Origin of lymphoid neoplasms.

mantle cell lymphoma

A

Mc - mantle b cell

mantle of lymph noed

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28
Q

Origin of lymphoid neoplasms.

follicular lymphoma
burkitt lymphoma
diffuse large b cell lymphoma
hodkins lymphoma

A

GC - germinal center b cell

germinal center of lymph node

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29
Q

Origin of lymphoid neoplasms.

precursor t lymphoblastic lymphoma/leukemia

A

dn to dp

dn- cd4cd8 double negative pro t cell

dp cd4cd8 double positive pre t cell

in thymus

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30
Q

Origin of lymphoid neoplasms.

peripheral t cell lymphomas

A

ptc - peripheral t cell

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31
Q

Origin of lymphoid neoplasms.

diffuse large b cell lymphoma
marginal zome lymphoma
small lymphocytic lymphoma
chronic lymphpcytic leukemia

A

mz- marginal zone b cell

marginal zone of lymph node

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32
Q

PRECURSORB-CELLNEOPLASMS

A

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

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33
Q

PERIPHERALB-CELLNEOPLASMS

A 
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
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34
Q

PERIPHERAL T-CELL AND NK-CELL NEOPLASMS

A 
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
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35
Q

PRECURSORT-CELLNEOPLASMS

A

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

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36
Q

HODGKIN LYMPHOMA

A 
Classical subtypes
   Nodular sclerosis
   Mixed cellularity
   Lymphocyte-rich
   Lymphocyte depletion

Lymphocyte predominance

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37
Q

Hodgkin Lymphoma

Adult
Child

A

15%

Rare

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38
Q

Non-Hodgkin
lymphomas

Adult
Child

A

not on list

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39
Q

B-Follicular center cell

Adult
Child

A

30+%

Rare

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40
Q

B-Burkitt(Burkitt-like)

Adult
Child

A
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41
Q

B-Small lymphocytic

Adult
Child

A
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42
Q

B-Diffuse large

Adult
Child

A

30+%

Rare

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43
Q

Lymphoblastic

Adult
Child

A
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44
Q

B-Lympho-Plasmacytoid

Adult
Child

A
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45
Q

U.S. Neoplasia Incidence 1992-2011

Lymphoid neoplasms -total

A

84%

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46
Q

U.S. Neoplasia Incidence 1992-2011

B-celllymphoid neoplasms

A

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
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47
Q

U.S. Neoplasia Incidence 1992-2011

T/NK-cell lymphoid neoplasms

A

T-cell lymphoblastic leukemia/lymphoma

1

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48
Q

U.S. Neoplasia Incidence 1992-2011

Non-lymphoidneoplasms -total

A

Myeloid leukemias
14

Acute
10
1
Chronic (myeloproliferativedisorders)
4
2
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49
Q

Immune Cell Antigens Detected by Monoclonal Antibodies

Primarily T-Cell Associated

A

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

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50
Q

Immune Cell Antigens Detected by Monoclonal Antibodies

Primarily B-Cell Associated

A

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.

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51
Q

Immune Cell Antigens Detected by Monoclonal Antibodies

Primarily Monocyteor Macrophage Associated

A

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

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52
Q

Immune Cell Antigens Detected by Monoclonal Antibodies

Primarily NK-Cell Associated

A

CD16NK cells and granulocytes

CD56NK cells and a subset of T cells

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53
Q

Immune Cell Antigens Detected by Monoclonal Antibodies

Primarily Stem Cell and Progenitor Cell Associated

A

CD34Pluripotenthematopoietic stem cells and progenitor cells of many lineages

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54
Q

Immune Cell Antigens Detected by Monoclonal Antibodies

Activation Markers

A

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

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55
Q

Immune Cell Antigens Detected by Monoclonal Antibodies

Present on All Leukocytes

A

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

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56
Q

CD1

A

Thymocytesand Langerhanscells

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57
Q

CD3

A

Thymocytes, mature T cells

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58
Q

CD4

A

Helper T cells, subset of thymocytes

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59
Q

CD5

A

T cells and a small subset of B cells

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60
Q

CD8

A

CytotoxicT cells, subset of thymocytes, and some NK cells

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61
Q

CD10

A

PREB cells and germinal center B cells; also called CALLA

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62
Q

CD19

A

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

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63
Q

CD20

A

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

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64
Q

CD21

A

EBV receptor; mature B cells and follicular dendriticcells

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65
Q

CD23

A

Activated mature B cells

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66
Q

CD79A

A

Marrow pre-B cells and mature B cells.

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67
Q

CD11C

A

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

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68
Q

CD13

A

Immature and mature monocytesand granulocytes

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69
Q

CD14

A

Monocytes

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70
Q

CD15

A

Granulocytes; Reed-Sternberg cells and variants inclassical Hodgkin lymphoma

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71
Q

CD33

A

Myeloid progenitors and monocytes

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72
Q

CD64

A

Mature myeloid cells

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73
Q

CD16

A

NK cells and granulocytes

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74
Q

CD56

A

NK cells and a subset of T cells

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75
Q

CD34

A

Pluripotenthematopoietic stem cells and progenitor cells of many lineages

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76
Q

CD30

A

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

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77
Q

CD45

A

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

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78
Q

Flow Cytometry Principles Immunophenotyping

A

cell suspension

tagged antibodies

tagged antibodies attached to the cell

listen to lecture and go through slides right now

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79
Q

b cells are cd20, cd10 positive, kappa light chain restricted=

A

b cel lymphoma

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80
Q

Immature B-cells

A

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

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81
Q

Mature B-cell

A

CD19, CD20, CD22,sIg+

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82
Q

Immature T-cells

A

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

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83
Q

Mature T-cells

A

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

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84
Q

Flow cytometry

A

Establish surface markers for lymphocytes

From lymphocytes suspended from a lymph node or blood.

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85
Q

Population of Large Lymphocytes

A

CD19+, lambda +

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86
Q

B-cell acute lymphoblastic leukemia/lymphoma

Cell of origin

A

Bone marrow precursor B cell

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87
Q

B-cell acute lymphoblastic leukemia/lymphoma

genotype

A

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

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88
Q

B-cell acute lymphoblastic leukemia/lymphoma

salient clinical features

A

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

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89
Q

T-cell acute lymphoblastic leukemia/lymphoma

cell of origin

A

Precursor T cell (often of thymic origin)

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90
Q

T-cell acute lymphoblastic leukemia/lymphoma

genotype

A

Diverse chromosomal translocations,NOTCH1

mutations (50% to 70%)

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91
Q

T-cell acute lymphoblastic leukemia/lymphoma

salient clinical features

A

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

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92
Q

Precursor B-cell/T-cell Neoplasms overview

A

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 !!!!

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93
Q

Precursor B-cell/T-cell Neoplasms

numberse

A

all represents 0.4% of all new cancers

all is most requently diagnosed at age 14

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94
Q

Precursor B-cell/T-cell Neoplasms

B cell

A

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

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95
Q

Precursor B-cell/T-cell Neoplasms

T cell

A

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

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96
Q

Precursor B-cell/T-cell Neoplasms

Major diagnostic cell is

A

“lymphoblast”: Same morphologically for T-cell and B-cell precursor neoplasms

Peripheral blast count usually > 20,000 and commonly > 50,000

May be aleukemic

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97
Q

Acute lymphoblastic leukemia/lymphoma.

slide

A

Lymphoblastswith condensed nuclear chromatin, small nucleoli, and scant agranularcytoplasm.

PAS+ / Myeloperoxidase -

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98
Q

Precursor B-cell/T-cell Neoplasms
Immunophenotype:

•+ TdT(terminal deoxynucleotidyltransferase

A

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

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99
Q

Precursor B-cell/T-cell Neoplasms
Immunophenotype:

B-cell type(Maturation arrested before surface expression of Ig)

A

•CD19, PAX5 (+/-CD10, CD20, cIgM)

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100
Q

Precursor B-cell/T-cell Neoplasms
Immunophenotype:

T-cell type (arrested at early stages of development)

A
    • CD1, CD2, CD5, CD7

* CD3, CD4 & CD8 positive only in late pre-T-cell tumors

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101
Q

Precursor B-cell/T-cell Neoplasms

special stains

A

PAS+ /Myeloperoxidase -

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102
Q

Precursor B-cell/T-cell Neoplasms

cytogenigs and molecular genetics

A
  • ~ 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
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103
Q

lymphoblastsrepresented by the red dots express terminal deoxynucleotidyl-transferase (TdT) and the B-cell marker CD22.
C, The same cells are positive for two other markers, CD10 and CD19, commonly expressed on pre-B lymphoblasts

A

b-all

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104
Q

Precursor B-cell/T-cell Neoplasms

Clinical Features

A

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

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105
Q

Precursor B-cell/T-cell Neoplasms

Prognosis:

A

95 % childhood B-cell ALL achieves remission & 3/4 considered cured

In adults only 35-40% are cured

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106
Q

Precursor B-cell/T-cell Neoplasms

Bad Prognosis factors:

A

(1) Age 100,000 cells/ul

(4) Presence of unfavorable cytogenetic aberrations
•Philadelphia chromosome t(9;22)
•Rearrangements of MLL (mixed lineage leukemia) gene

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107
Q

“Packed Marrow Acute Lymphoblastic Leukemia;

A

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 )

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108
Q

Peripheral B-Cell Neoplasms

A
  • 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
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109
Q

Burkitt Lymphoma

cell of origin

A

Germinal-center B cell

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110
Q

burkitt lymphoma

genotype

A

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

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111
Q

burkitt lymphoma

salient clinical features

A

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

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112
Q

diffuse large b cell lymphoma

cell of origin

A

Germinal-center or post-germinal-center B cell

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113
Q

diffuse large b cell lymphoma

genotype

A

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

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114
Q

diffuse large b cell lymphoma

salient clinical features

A

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

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115
Q

Extranodalmarginal zone lymphoma

cell of origin

A

Memory B cell

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116
Q

Extranodalmarginal zone lymphoma

genotype

A

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

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117
Q

Extranodalmarginal zone lymphoma

salient clinical features

A

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

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118
Q

follicular lymphoma

cell of origin

A

Germinal-center B cell

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119
Q

follicular lymphoma

genotype

A

t(14;18) creatingBCL2-IgHfusion gene

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120
Q

follicular lymphoma

salient clinical features

A

Older adults with generalized lymphadenopathy and marrow involvement; indolent

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121
Q

Hairy cell leukemia

cell of origin

A

Memory B cell

122
Q

Hairy cell leukemia

genotype

A

Activating BRAFmutations

123
Q

Hairy cell leukemia

salient clinical features

A

Older males with pancytopenia and splenomegaly; indolent

124
Q

Mantle cell lymphoma

cell of origin

A

Naive B cell

125
Q

Mantle cell lymphoma

genotype

A

t(11;14) creatingCyclinD1-IgHfusion gene

126
Q

Mantle cell lymphoma

salient clnical features

A

Older males with disseminated disease; moderately aggressive

127
Q

Multiple myeloma/solitary plasmacytoma

cell of origin

A

Post-germinal-center bone marrow homing plasma cell

128
Q

Multiple myeloma/solitary plasmacytoma

genotype

A

Diverse rearrangements involvingIgH; 13q deletions

129
Q

Multiple myeloma/solitary plasmacytoma

salient clnical features

A

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

130
Q

Small lymphocytic lymphoma/chronic lymphocytic leukemia

cell of origin

A

Naive B cell or memory B cell

131
Q

Small lymphocytic lymphoma/chronic lymphocytic leukemia

genotype

A

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

132
Q

Small lymphocytic lymphoma/chronic lymphocytic leukemia

salient clinical features

A

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

133
Q

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

Terminology & Epidemiology

A
  • 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
134
Q

Most common leukemia of adults in western world

A

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

135
Q

Small Lymphocytic Lymphoma

A

•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
136
Q

Chronic Lymphocytic Leukemia

A
  • 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
137
Q

Small lymphocytic lymphoma/chronic lymphocytic leukemia (lymph node).

slide

A

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).

138
Q

Small lymphocytic lymphoma/CLL (lymph node).

slide

A

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).

139
Q

Chronic lymphocytic leukemia.

slide

A

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

140
Q

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

A

Lymphocytes have more cytoplasm.

141
Q

Small lymphocytic lymphoma/chronic lymphocytic leukemia

involving the liver

A

typical periportallymphocytic infiltrate.

142
Q

typical periportal lymphocytic infiltrate.

immunophenotype

A

+ 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)

143
Q

typical periportal lymphocytic infiltrate.

cytogenetics/molecular genetics

A

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

144
Q

Flow cytometry of chronic lymphocytic leukemia / small lymphocytic lymphoma

A

Coexpressionof CD5 on CD19+ B cells

145
Q

Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma
Clinical Features

A

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

146
Q

Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma

Prognosis

A

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

147
Q

Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma

Prolymphocytic Transformation (Leukemia)

A

a rare transformation with worsening of cytopenias

148
Q

Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma

Richter Transformation (Syndrome)

A

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

149
Q

Follicular Lymphoma

Epidemiology

A

~ 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

150
Q

Follicular Lymphoma

Body Location and Morphology

A

Predominately in lymph nodes + ~ 85% marrow involvement

10% have peripheral blood lymphocytosis (

151
Q

Follicular Lymphoma

Grade given based on number of

A

centroblasts(grade 3: >15 centroblasts/HPF)

152
Q

Follicular lymphoma (lymph node

slide

A

Nodular aggregates of lymphoma cells are present throughout lymph node.

153
Q

Follicular lymphoma (lymph node). ,At high magnification

slide

A

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

154
Q

BCL2 expression in reactive and neoplastic follicles.

A

reactive - just around the mantle?

follicular lymphoma - in the whole follicle

155
Q

Follicular Lymphoma

Immunophenotype:

A

+ for CD19, CD20, CD10 (CALLA)and sIg

+ for BCL2 (apoptosis antagonist),BCL6

156
Q

Follicular Lymphoma

cytogenetics

A

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

157
Q

Follicular Lymphoma

Clinical Features/Prognosis

A

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

158
Q

Follicular Lymphoma

Transformation

A

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

159
Q

Follicular lymphoma (spleen).

gross

A

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

160
Q

Diffuse Large B-cell Lymphoma

epidemiology

A 
~ 25-50% of adult Non-Hodgkin Lymphomas (NHL)
2/3 of “aggressive lymphomas”
Slight male predominance
Median onset age 60
25% of childhood lymphomas
161
Q

Diffuse Large B-cell Lymphoma

morphology

A

Large size neoplastic lymphocyte
(2-5 times diameter of normal-sized lymphocyte)

Diffuse pattern of growthwith effacement of node architecture

162
Q

Diffuse large B-cell lymphoma

slide

A

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

163
Q

Diffuse Large B-cell Lymphoma

immunophenotype

A

+ for CD19, CD20, sIg

Variable expression germinal center markers (CD10, BCL6)

164
Q

Diffuse Large B-cell Lymphoma

Cytogenetics and Molecular Genetics

A

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

165
Q

Diffuse Large B-cell Lymphoma

Clinical Features

A

Typically present with rapidly enlarging often symptomatic mass at a single nodal or extranodalsite

Oropharynx (Waldeyerring, tonsils, adenoids) common site

166
Q

Diffuse Large B-cell Lymphoma

Important Clinical Subtypes

A

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

167
Q

Diffuse Large B-cell Lymphoma

Prognosis:

A

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

168
Q

Diffuse large B-cell lymphoma involving the spleen.

gross

A

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

169
Q

BurkittLymphoma

epidemiology

A

30% childhood lymphomas in US

2-3% of adult lymphomas

170
Q

BurkittLymphoma

african

A

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

171
Q

BurkittLymphoma

sporadic

A

–Most EBV negative
–Abdominal masses (ileocecalinvolvement most frequent)
–Bilateral breast, ovarie

SporadicUS (nonendemic) children & young adults

172
Q

BurkittLymphoma

immunodefficiency

A

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

173
Q

BurkittLymphoma

morphology

A
  • 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
174
Q

BurkittLymphoma

immunophenotype

A

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

175
Q

BurkittLymphoma

slide

A

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

176
Q

BurkittLymphoma

slide high power

A

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

177
Q

BurkittLymphoma

bone marrow aspiration

A

cytoplasmic vacuoles

178
Q

BurkittLymphoma

cytogenetics and molecular genetics

A

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

179
Q

BurkittLymphoma

prognosis

A

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

180
Q

BurkittLymphoma

karyotype

A

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.

181
Q

Mantle Cell Lymphoma

epidemiology

A

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

182
Q

Mantle Cell Lymphoma

morphology

A

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

183
Q

Mantle Cell Lymphoma

cytogenetics and molecular genetics

A

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

184
Q

Mantle Cell Lymphoma

immunophenotype

A

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

185
Q

Mantle Cell Lymphoma

clnical features

A

Presents with painless lymphadenopathy +/-peripheral

blood involvement (20-40%)

Signs/symptoms of splenomegaly (50%)

ExtranodalGI involvement commonly seen
Sometimes presents as lymphomatoidpolyposis)

186
Q

Mantle Cell Lymphoma

pronosis

A

Aggressive, Median survival only 3-4 years

187
Q

Mantle Cell Lymphoma

slide low power

A

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

188
Q

Mantle Cell Lymphoma

slide high power

A

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

189
Q

Marginal Zone Lymphoma (MALT Lymphoma)

terminology

A

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

190
Q

Marginal Zone Lymphoma (MALT Lymphoma)

body location and mophorlogy

A

Extranodal(GI & Spleen) and/or lymph nodes

191
Q

Marginal Zone Lymphoma (MALT Lymphoma)

pathogenesis

A

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

192
Q

Marginal Zone Lymphoma (MALT Lymphoma)

immunophenotype

A

Positive CD19, CD79a, BCL2

Negative CD5, CD10, CD23, cyclin D1

193
Q

Marginal Zone Lymphoma (MALT Lymphoma)

genetics

A 
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
194
Q

Marginal Zone Lymphoma (MALT Lymphoma)

prognosis

A

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

195
Q

Hairy Cell Leukemia

Epidemiology

A

Rare, 2% of all leukemias

Predominately a disease of middle-aged Caucasian males (M:F 5:1)

196
Q

Hairy Cell Leukemia

morphology

A

Characteristic “hairy cells” in peripheralblood

197
Q

Hairy Cell Leukemia

immunophenotype

A

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

198
Q

Hairy Cell Leukemia

cytogenetics and molecular gneteics

A

High incidence somatic hypermutation(post germinal center)

BRAF mutations

199
Q

Hairy Cell Leukemia

clinical features

A

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

200
Q

Hairy Cell Leukemia

prognosis

A

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

201
Q

Hairy Cell Leukemia

peripheral blood smear

A

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

202
Q

Plasma Cell Neoplasms (Dyscrasias) and Related Disorders

A

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

203
Q

Plasma Cell Neoplasms Bence Jones protein

A

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

204
Q

Clinicopathologic Entities Associated with Monoclonal Gammopathy

A

multiple myeloma

plasmacytoma

smoldering myeloma

heave light chain disease

waldenstrom macroglobulinemia

primary or immunocyte associated amyloidosis

monoclonal gammopathy of undetermined significance

205
Q

mm

quick

A

plasma cell meyeloma

206
Q

plasmacytoma

quick

A

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

207
Q

Smoldering myeloma

quick

A

(asymptomatic with high plasma M component > 3gm/dL)

~75% per progress to multiple myeloma within 15 years

208
Q

heavy light chain diease

quick

A

Secretes free H (L) chain fragments

209
Q

Waldenstom Macroglobulinemia

quick

A

High levels of IgM

210
Q

Primary or immunocyte-associated amyloidosis

quick

A

free L chains leading to AL type amylodosis

211
Q

Monoclonal gammopathyof undetermined significance(MGUS):

quick

A

M components

212
Q

Multiple Myeloma

epidemiology

A
  • 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
213
Q

Myeloma Incidence

A

median age at diagnosis is 69

214
Q

multiple myeloma

mutations

A

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

215
Q

multiple myeloma express

A

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

216
Q

Multiple myeloma of the skull (radiograph

A

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

217
Q

Multiple myeloma (radiograph

A 
Common Locations:
Vertebrae 66%
Ribs 44%
Skull 41%
Pelvis 28%
Clavicle 10%
Scapula 10%
218
Q

Multiple Myeloma

prevalence% plasma cell dyscrasias

average age onset

age range

m:f ration

primary locations

skeletal survey

monoclonal protein

A

80-90% PCD

59

30-80

1.5:1

multiple bone marrow lesions

positive

99%

219
Q

Solitary plasmacytoma

prevalence% plasma cell dyscrasias

average age onset

age range

m:f ration

primary locations

skeletal survey

monoclonal protein

A

5-10% pcd

56

80

2-3:1

any bone >50% in vertebrae

single lesion

43% (22-77)

220
Q

Extramdullary plasmacytoma

prevalence% plasma cell dyscrasias

average age onset

age range

m:f ration

primary locations

skeletal survey

monoclonal protein

A

80

4:1

80-90% upper airway

negative

27% (0-86%)

221
Q

Multiple myeloma (bone marrow aspirate).

slide

A

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

222
Q

Plasma Cell Variants in

Plasma Cell Dyscrasias

A

flame cell

mott cell

ditcher body

Russell body

223
Q

Neoplastic dysmorphic multiple myeloma plasma cells fill the

A

marrow.

Sheets of atypical plasma cells (plasmablasts)

224
Q

Multiple Myeloma

clinical features

A

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

225
Q

multiple myeloma

prognosis

A

Untreated survival is 6 –12 months from diagnosis

With chemotherapy, median survival is 4-6 years

Cyclin D1 translocations good prognosis

226
Q

Myeloma Mortality

A

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

227
Q

Lymphoplasmacytic Lymphoma

terminology and epidemiology

A

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

228
Q

Lymphoplasmacytic Lymphoma

morphology

A

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

229
Q

Lymphoplasmacytic Lymphoma

genetics

A

MYD88mutations leading to NF-κB activation

230
Q

Lymphoplasmacytic Lymphoma

immunophenotype

A

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

231
Q

Lymphoplasmacytic Lymphoma

clinical features

A

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

232
Q

Lymphoplasmacytic Lymphoma

prognosis

A

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

233
Q

Peripheral T-Cell Neoplasms

list of conditions

A
  • 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
234
Q

Peripheral T-cell and NK-cell Neoplasms

overview

A

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

235
Q

Adult t cell leukemia/lymphoma

cell of origin

A

Helper T cell

236
Q

Adult t cell leukemia/lymphoma

genotype

A

HTLV-1provirus present in tumor cells

237
Q

Adult t cell leukemia/lymphoma

salient clinical features

A

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

238
Q

peripheral t cell lymphoma unspecified

dell of origin

A

Helper or cytotoxic T cell

239
Q

peripheral t cell lymphoma unspecified

genotype

A

No specific chromosomal abnormality

240
Q

peripheral t cell lymphoma unspecified

salient clinical features

A

Mainly older adults; usually presents with lymphadenopathy; aggressive

241
Q

anaplastic large cell lymphoma

cell of origin

A

Cytotoxic T cell

242
Q

anaplastic large cell lymphoma

genotype

A

Rearrangements ofALK in a subset

243
Q

anaplastic large cell lymphoma

salient clinical features

A

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

244
Q

extranodal nk/tcell lymphoma

cell of origin

A

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

245
Q

extranodal nk/tcell lymphoma

genotype

A

EBV-associated; no specific chromosomal abnormality

246
Q

extranodal nk/tcell lymphoma

salient clinical features

A

Adults with destructive extranodal masses, most commonly sinonasal; aggressive

247
Q

mycosis fungoides/sezary syndrome

cell of origin

A

Helper T cell

248
Q

mycosis fungoides/sezary syndrome

genotype

A

No specific chromosomal abnormality

249
Q

mycosis fungoides/sezary syndrome

salient clnical features

A

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

250
Q

large granular lymphocytic leukemia

cell of origin

A

Two types: cytotoxic T cell and NK cell

251
Q

large granular lymphocytic leukemia

genotype

A

Point mutations in STAT3

252
Q

large granular lymphocytic leukemia

salient clinical features

A

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

253
Q

Peripheral T-cell Lymphoma, Unspecified

A
  • 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
254
Q

Peripheral T-cell lymphoma, unspecified (lymph node).

slide

A

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

255
Q

Anaplastic Large Cell Lymphoma

numbers

A

Approximately 10-20% of childhood lymphoma and

256
Q

Anaplastic Large Cell Lymphoma

ALK+ [anaplastic lymphoma kinase (ALK)gene(2p23) ]

A
  • 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)
257
Q

Anaplastic Large Cell Lymphoma

ALK-

A
  • Usually in older adults

* poor prognosis ~other peripheral T-cell lymphomas

258
Q

Anaplastic Large Cell Lymphoma

markers

A

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

259
Q

Anaplastic Large Cell Lymphoma

slide

A

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.

260
Q

Adult T-cell Leukemia/Lymphoma

all of it

A
  • 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
261
Q

Mycosis Fungoides

overview

A

CD4+ T-cell lymphoma of the skin

CLA, CCR4 & CCR10 expression leads to skin infiltration
Lymphoma cells with ceribriformnuclei

262
Q

Mycosis Fungoides

clinical

A

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

263
Q

Mycosis Fungoides

sezary syndrome

A

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

264
Q

Mycosis Fungoides

leukemic phase

A

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

265
Q

Large Granular Lymphocytic Leukemia all of it

A

•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)

266
Q

ExtranodalNK/T-cell Lymphoma all of it

A

•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

267
Q

WHO Classification Hodgkin Lymphoma Subtypes

A
  • Classical Hodgkin lymphoma(95%)
    • Nodular sclerosis (65-70%)
    • Mixed cellularity (20-25%)
    • Lymphocyte-rich (
268
Q

5 cm lymph node (obviously from a patient with lymphadenopathy). The node should normally be soft, pink-tan &

A

hodkins disease

269
Q

Hodgkin lymphoma molecular pathogenesis

A
  • 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)
270
Q

Hodkin lymphoma nodular sclerosis (65-70%)

morphology and immunophenotype

A

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+*

271
Q

Hodkin lymphoma nodular sclerosis (65-70%)

typical clinical features

A

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

272
Q

Hodgkin lymphoma mixed celluarity (20-25%)

morphology and immunopheontye

A

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

273
Q

Hodgkin lymphoma mixed celluarity (20-25%)

typical clinical features

A

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

274
Q

Hodgkin lymphoma lymphocyte rick (

A

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

275
Q

Hodgkin lymphoma lymphocyte rick (

A

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

276
Q

Hodgkin lymphoma lymphocyte depletion (

A

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

277
Q

Hodgkin lymphoma lymphocyte depletion (

A

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

278
Q

Hodgkin lymphoma lymphocyte predominance (5%)

morphology and immunophenotype

A

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

279
Q

Hodgkin lymphoma lymphocyte predominance (5%)

typical clinical features

A

Uncommon; young males with cervical or axillarylymphadenopathy; mediastinal*

280
Q

Reed-Sternberg cells and variants

A

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

281
Q

Hodgkin lymphoma, nodular sclerosis type.

A

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

282
Q

Reed-Sternberg cell, lacunar variant (Nodular Sclerosis).

A

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

283
Q

Hodgkin lymphoma, mixed-cellularity type

slide

A

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

284
Q

Classical HL: cd45 slide

A

Negative CD45 staining of RS cells and Variants

285
Q

Classical HL: CD30

A

membrane and paranuclearstaining of RS cells and Variants

286
Q

Classical HL: cd15

A

Positive CD15 staining of RS cells and Variants

287
Q

Hodgkin disease, nodular

A

lymphocyte-predominance

288
Q

Hodgkin lymphoma, lymphocyte predominance type.

A

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

289
Q

Reed-Sternberg cell, lymphohistiocyticvariant.

“Popcorn cell” of nodular lymphocyte predominance subtype !

A

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

290
Q

Clinical Features of Hodgkin Lymphoma

A
  • Lymphadenopathy at first
    • Classical Hodgkin lymphoma
      • Cervical, mediastinal, axillary, para-aortic
      • Bimodal age distribution
    • Nodular lymphocyte predominance Hodgkin lymphoma
      • Cervical, axillary, inguinal
      • Young males
291
Q

Clinical Staging of Hodgkin
and Non-Hodgkin Lymphomas

1

A

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

292
Q

Clinical Staging of Hodgkin
and Non-Hodgkin Lymphomas

2

A

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).

293
Q

Clinical Staging of Hodgkin
and Non-Hodgkin Lymphomas

3

A

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.

294
Q

Clinical Staging of Hodgkin
and Non-Hodgkin Lymphomas

4

A

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

295
Q

Hodgkin and non hodgkins staging

All stages are further divided on the basis of the absence (A) or presence (B)

A

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

296
Q

Hodgkin Disease Cure Rate

A

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

297
Q

Hodgkin basics

A

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

298
Q

Non-Hodgkin lymphoma basics

A

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

299
Q

Age of Initial Diagnosis

Hodgkin Lymphoma

A

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

300
Q

Age of Initial Diagnosis

non-Hodgkin Lymphoma

A

Large majority

after age 50

301
Q

Incidence and Mortality Rates

Hodgkin Lymphoma

A

0.5% of all new cancers

300000 new cases/year

100000 people di each year

302
Q

Incidence and Mortality Rates

non-Hodgkin Lymphoma

A

4.3% of all new cancers

2000000 new cases/year

500000 people die each year

Heme Path Exam 1 (7 decks)

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