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Heme and Lymph Midterm > Chapter 13 Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus > Flashcards

Chapter 13 Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus Flashcards

1
Q

Name the formed elements of blood that originate from hematopoietic stem cells (HSCs)

A

red cells, granulocytes, monocytes, platelets, and lymphocytes

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2
Q

HSCs have two essential properties that are required for the maintenance of hematopoiesis. What are they?

A

1- pluripotency

2- capacity for self-renewal

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3
Q

Tumors of hematopoietic origin are often associated with mutations that block what?

A

Block progenitor cell maturation or abrogate their growth factor dependence

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4
Q

What are the two broad categories of white blood cell disorders?

A

1-Proliferative disorders

2-Leukopenias

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5
Q

Proliferative Disorders are what?

A

expansion of leukocytes that can be either reactive (infections and inflammations) or neoplastic (case of duh cancuh)

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6
Q

Leukopenias are what?

A

deficiency of leukocytes

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7
Q

Leukopenia is what?

A

abnormally low white cell count usually results from reduced numbers of neutrophils

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8
Q

Lymphopenia is seen when?

A

most commonly seen in advanced HIV infection, following glucocorticoids or cytotoxic drugs, autoimmune disorders, malnutrition, and certain acute viral infectiions

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9
Q

What is Lymphopenia?

A
  • more of a redistribution than a decrease in the number of lymphocytes in the body
  • acute viral illness cause sequestration of activated T cells in lymph nodes and increased adherence to endothelial cells
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10
Q

What is Granulocytopenia?

A

diminished granulocyte function

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11
Q

What is neutropenia?

A

reduction in number of neutrophils in the blood; alot of things cause this

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12
Q

What is agranulocytosis?

A

significant reduction in neutrophils having the SERIOUS consequence of leaving people open to bacterial and fungal infections

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13
Q

What can cause neutropenia?

A
  • inadequate or ineffective granulopoiesis

- increased destruction or sequestration of neutrophils in the periphery

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14
Q

When do you see inadequate or ineffective granulocytosis?

A

1- Supression of hematopoietic stem cells (i.e. Aplastic anemia) and infiltrative disorders (tumors, granulomatous DZ)

2- Supression of commited granulocytic precursors (exposure to certain drugs)

3- Ineffective hematopoiesis megaloblastic anemias and myelodysplastic syndromes causing precursors to die within the marrow

4- Congenital conditions (Kostmann Syndrome) in which inherited defects = impaired granulocytic differentiation

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15
Q

When do you see Accelerated destruction or sequestration of neutrophils?

A

1- immunologically mediated injury via lupus or drugs

2- Splenomegaly in which enlarged spleen = neutrophil sequestration and modest neutropenia

3-Increased peripheral utilization seen with overwhelming bacterial/fungal/rickettsial infections

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16
Q

What is the most common cause of agranulocytosis?

A

drug toxicity:
-alkylating agents and anti-metabolites in Cancer Txs

-Other drugs–>aminopyrine, chloramphenicol, sulfonamides, chlorpromazine, thiouracil, and phenylbutazone
THI CChAmPS
THIouracil
CHlorpromazine, Chloramphenicol, AminoPyrine, Sulfonamides

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17
Q

What is Chloramphenicol induced neutropenia?

A

toxic effect on granulocytic precursors in bone marrow

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18
Q

How do sulfonamides induced agranulocytosis?

A

antibody-mediated destruction of mature neutrophils

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19
Q

Patient presents with neutropenia. Autoantibodies directed agaisnt neutrophil-specific antigens are detected. What does the patient have?

A

Acquired Idiopathic Neutropenia

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20
Q

Patient presents with severe neutropenia in association with monoclonal proliferations of large granular lymphocytes ( LGL Leukemia). What is the possible cause?

A

Definite cause isnt clear. Perhaps caused by suppression of granulocytic progenitors by products of the neoplastic cell (usually CD8+ cytotoxic T cell)

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21
Q

Patient presents with malaise, chills, fever, often followed by marked weakness and fatigability. What might this patient have?

A

-Neutropenia

-Serious cases have neutrophil count < 500
infections usually fulminant = MUST give broad antibiotics when signs/symptoms appear

-in cases of post cancer TX patients are given G-CSF, a growth factor stimulating granulocyte production from marrow

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22
Q

What influences Leukocytosis?

A

1- size of myeloid and lymphoid precursor pool in bone marrow, thymus, circulation, and peripheral tissues
2-rate or release from storage pools
3-amount of adhesion to blood vessel walls
4-rate of extravasation of cells from blood into tissues

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23
Q

TNF and IL-1 stimulate macrophages, bone marrow stromal cells, and T cells to do what?

A

i. e. during the case of an infection

- produce increased increased amounts of hematopoietic growth factors–> full effect takes 7 days

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24
Q

Leukocytosis seen in the setting of neutrophils with toxic granulations, Doehle bodies, and cytoplasmic vacuoles indicates what?

A

Sepsis or severe inflammatory disorders (i.e. Kawasaki Disease)

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25
Q

What are toxic granules?

A

coarser and darker than normal neutrophilic granules representing abnormal azurophilic (primary) granules

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26
Q

What are Doehle bodies?

A

patches of dilated endoplasmic reticulum that appear sky-blue cytoplasmic “puddles”

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27
Q

What causes Neutrophilic Leukocytosis?

A
  • acute bacterial infections

- tissue necrosis from myocardial infarction, burns

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28
Q

What causes Eosinophilic Leukocytosis?

A 
allergic disorders like asthma
parasite infection
hodgkin and non hodgkin lymphoma
autoimmunee DZs: dermatitis herpetiformis
atheroembolic DZ
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29
Q

What causes Basophilic Leukocytosis?

A

Rare; indicates myeloproliferative DZ (chronic myelogenous leukemia)

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30
Q

What causes Monocytosis?

A

Chronic infections (Tuberculosis TB)
malaria
lupus ulcerative colitis

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31
Q

What causes Lymphocytosis?

A

accompanies monocytosis (TB)
bordetella pertussis infection
Hep A, CMV, EBV

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32
Q

Viral infections in kids show large numbers of activated lymphocytes mimicking what?

A

neoplastic leukocytosis but they only have reactive leukocytosis

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33
Q

Within several days of antigenic stimulation what changes are seen in the primary lymph node follicles?

A

Primary follicles enlarged and develop pale-staining germinal centers. The more intense the infection the more drastic the changes seen.

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34
Q

Histological changes seen in neutrophils with bacterial sepsis?

A

Upon peripheral blood smear Neutrophils containing coarse purple cytoplasmic granules (toxic granulations) and blue cytoplasmic patches of dilated endoplasmic reticulum (Doehle Bodies)

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35
Q

What are causes of acute nonspecific lymphadenitis in cervical region, axillary region, and inguinal region?

A 
Cervical = teeth or tonsil infxn
Axillary = extremity infection
Inguinal = extremity infxn
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36
Q

Where is chronic lymphadenitis commonly seen and why?

A

common in inguinal and axillary lymph nodes because they drain large portions of the body

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37
Q

Chronic immune reactions promote the appearance of what?

A

appearance of organized collections of immune cells in nonlymphoid tissues

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38
Q

What is Hemophagocytic Lymphohistiocytosis (HLH)?

A

reactive comdition marked by cytopenias and signs and symptoms of systemic inflammation related to macrophage activation

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39
Q

What is the common pathogenesis feature in all forms of HLH?

A

Systemic activation of macrophages and CD8+ cytotoxic T-cells

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40
Q

What role do macrophages have in HLH?

A

macrophages phagocytose blood cell progenitors in the marrow and formed elements in the peripheral tissues; while the “stew” of mediators released suppress hematopoiesis

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41
Q

What mutations are found in familial HLH and when does it typically present?

A

mutations impacting the ability of cytotoxic T cells and NK to properly form or deploy cytotoxic granules

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42
Q

What is a possible cause of HLH?

A

Cytotoxic T cells lose the ability to lyse antigen-bearing dendritic cells or activated macrophages

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43
Q

High levels of what inflammatory mediators are seen in HLH?

A

TNF-alpha, IL-6, and IL-12, and IL-2 receptor

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44
Q

What is the most common trigger for HLH?

A

EBV infection

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45
Q

How do HLH patients present?

A
  • acute febrile illness with splenomegaly and hepatomegaly

- hemophagocytosis seen on bone marrow biopsy

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46
Q

What labs do HLH patients have?

A
  • Anemia and thrombocytopenia
  • High liver enzymes (from hepatomegaly)
  • High IL-2 receptors
  • High plasma ferritin
  • intravascular coagulation
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47
Q

Prognosis of HLH?

A

W/o TX = death in 2 months

W/ TX = 50% die

TX= immunosuppressants and mild Chemotherapy

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48
Q

What are three categories of neoplastic proliferations?

A

1- Lymphoid Neoplasms
2- Myeloid Neoplasms
3- Histiocytoses

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49
Q

What are lymphoid Neoplasms?

A

Tumor group including B-cell, T-cell, and NK-cell origin.

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50
Q

What are Myeloid neoplasms?

A

Arise from early hematopoietic progenitors

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51
Q

What are three categories of Myeloid Neoplasms?

A

1- Acute Myeloid Leukemias
2- Myelodysplastic Syndromes
3- Chronic myeloproliferative disorders

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52
Q

What is Acute Myeloid Leukemia?

A

Immature progenitor cells accumulate in the bone marrow

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53
Q

What are Myelodysplastic Syndromes?

A

Associated with infective hematopoiesis and resultant peripheral cytopenias

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54
Q

What are Chronic Myeloproliferative disorders?

A

Increased production of one or more terminally differentiated myeloid elements (i.e. granulocytes)

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55
Q

What are Histiocytoses?

A

UNCOMMON proliferative lesions of macrophages and dendritic cells

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56
Q

What is Langerhans cell histiocytoses?

A

special type of immature Dendritic cell proliferation

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57
Q

What is present in the majority of white cell neoplasms?

A

Nonrandom Chromosomal abnormalities, most commonly translocations.

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58
Q

What drives cell growth and Warburg metabolism for oncoprotein mutations?

A
  • Constitutively active tyrosine kinase
  • activates RAS
  • activates PI3K/AKT and MAPK downstream
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59
Q

What is the function of activation-induced cytosine deaminase (AID)?

A

DNA modifying enzyme used for immunoglobulin (Ig) modification class switching

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60
Q

When do you see activated the MYC proto-oncogene?

A

Seen activated in Germinal B-cell lymphomas by TRANSLOCATIONS to the transcriptionally active Ig

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61
Q

When do you see activated proto-oncogene BCL6?

A

Seen in activated germinal B-cell lymphomas by POINT MUTATION by mistargeted break induced by AID

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62
Q

List genetic diseases that promote genetic instability and potentially White Cell neoplasia

A
  • Bloom Syndrome
  • Fanconi Anemia
  • Ataxia Telangiectasia
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63
Q

List genetic diseases that increase incidence of childhood leukemia

A 
Down Syndrome (trisomy 21)
Type I Neurofibromatosis
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64
Q

What viruses might cause lymphomas?

A

HTLV-1 (human T-cell lymphoma virus-1)

EBV (Epstein-Barr virus)

KSHV/HHV-8 (Kaposi Sarcoma herpesvirus/ human herpes virus-8)

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65
Q

What is HTLV-1 associated with?

A

adult T-cell leukemia/lymphoma

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66
Q

What is EBV associated with?

A
  • Burkitt Lymphoma
  • 40% of Hodgkin Lymphoma
  • T-cell immunodifficiency B-cell lymphoma
  • Rare NK-cell lymphomas
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67
Q

Can chronic inflammation lead to T-cell lymphoma?

A
  • Yes, H. pylori (B-cell), gluten sensitivity (T-cell), and breast implants (T-cell) may cause a lymphomas
  • HIV may also cause lymphoma in any organ
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68
Q

Radiation therapy and some chemo cause what?

A

Some forms myeloid and lymphoid neoplasms due to the TX impact on hemato-lymphoid progenitor cells

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69
Q

Smoking causes an increase of what leukemia?

A
  • Acute myeloid leukemia
  • 1.3-2 fold increase in smokers
  • Benzene and other carcinogens are the cause
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70
Q

The term leukemia is used for what?

A

neoplasms that present with widespread involvement of the bone marrow and peripheral blood

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71
Q

The term lymphoma is used for what?

A

term used for proliferations that arise as discrete tissue masses

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72
Q

Plasma cell neoplasms arise from what?

A

arise from bone marrow

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73
Q

What is a hallmark of 2/3rds of NHLs and virtually all Hodgkin Lymphomas presents as?

A

enlarged nontender lymph nodes

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74
Q

The remaining 1/3 of NHLs present with symptoms related to the involvement of extranodal sites such as?

A

skin, stomach, or brain

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75
Q

Lymphocytic leukemias most often come to attention because of signs and symptoms related to the suppression of normal what?

A

normal hematopoiesis by tumor cells in the bone marrow

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76
Q

Plasma cell tumor symptoms are caused by?

A

proteins from plasma cell tumors and Igs from immune cells

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77
Q

Hodgkin Lymphoma is often associated with what? because why?

A

fever due to cytokines released from immune cells in response to tumor cells

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78
Q

What are the five broad categories of lymphoid neoplasms?

A

1- Precursor B-cell neoplasms (immature)
2- Peripheral B-cell neoplasms (mature)
3- Precursor T-cell neoplasms (immature)
4- Peripheral T-cell and NK-cell neoplasms (mature)
5- Hodgkin Lymphoma (Reed-Sternberg cells)

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79
Q

What is required for diagnosis of lymphoid neoplasia?

A

histologic exam of lymph nodes

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80
Q

All daughter cells from the malignant progenitor share the same what?

A

antigen receptor gene configuration and sequence, and synthesized identical antigen receptors proteins (Igs or T-cell receptors)

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81
Q

True or false: Most lymphoid neoplasms resemble some recognizable stage of B- or T-cell differentiation

A

True

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82
Q

What is the precentage breakdown of lymphoid neoplasms?

A

90% B-cell
9% T-cell
1% NK cell (RARE)

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83
Q

True or False: Lymphoid neoplasms are often assocaited with immune abnormalities?

A

True

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84
Q

How does Hodgkins vs NHL spread?

A
  • Hodgkins spreads in a predictable pattern

- NHL spreads widely early unpredictably

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85
Q

True or False: Acute lymphoblastic leukemia/lymphomas (ALLs) are neoplasms composed of immature B (pre-B) or T (pre-T) cells, which are call nymphblasts?

A

FALSE: they are called lymphoblasts, wake the fudge up homie

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86
Q

When do B-ALLs present? T-ALLs?

A
  • B-ALLs present as CHILDHOOD leukemias

- T-ALLs present as ADULT adolescent males as thymic “lymphomas”

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87
Q

What is the most common cancer of children?

A

Acute lymphoblastic leukemia/lymphoma (ALL)

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88
Q

What groups are at higher risk for ALL?

A

Hispanics > everyone
White 3x
boys > girls
Must be < 15 years of age

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89
Q

When do B-ALL and T-ALL peak in incidence?

A

B-ALL at age 3

T-ALL in adolescence

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90
Q

What is the pathogenesis of of B-ALL/T-ALL?

A

dysregulated expression and function of transcription factors required for normal B- and T-cell development

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91
Q

What is the mutation in T-ALL?

A
  • 70% of cases have GAIN of FUNCTION mutation in NOTCH1

- leads to disturbed differentiation of lymphoid precursors and promotes maturation arrest

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92
Q

What is the mutation in B-ALL?

A 
-LOSS of FUNCTION mutation in genes needed for B-cell development, PAX5, E2A, EBF
or t(12;21) ETV6 and RUNX1

-Leads to disturbed differentiation of lymphoid tissue precursors and promotes maturation arrest

93
Q

What is the most common chromosomal change of all ALLs?

A

hyperploidy

94
Q

What specialized DNA polymerase is expressed only in pre-B and pre-T lymphoblasts in 95% of cases?

A

Terminal deoxynucleotidyl transferase (TdT)

95
Q

B-ALL lymphoblasts express whan pan B-cell markers?

A

CD19
CD10
transcription factor PAX5

96
Q

What is negative in VERY immature B-ALLs?

A

CD10

97
Q

What do MATURE “late pre-B” ALLs express?

A 
CD10
CD19
CD20
IgM heavy chain 
Dysregulation of BCL 6 = too much or too little
98
Q

What are T-ALLs positive for in most cases?

A

CD1
CD2
CD5
CD7

99
Q

Immature T-ALLs are negative for what?

A

CD 3/4/8

100
Q

“late” pre-T-cell tumors are positive for what?

A

CD3/4/8

101
Q

What are the similar clinical features of ALL and AML?

A

accumulation of neoplastic “blasts” in the bone marrow suppressing normal hematopoiesis by physical crowding, competition for growth factors and they dont know what else (-_-)

102
Q

Common features characteristic of ALL are?

A
  • onset: days to weeks
  • anemia fatigue, infxn via neutropenia, bleeds via thrombocytopenia
  • bone pain, spleno/hepatomegaly, large vessel/airway compression in mediastinum
  • CNS:headache, puking, nerve palsies
103
Q

What is the prognosis of ALL?

A
  • pediatric: VERY GOOD. 95% get complete remission w/ agressive chemo. 75% are cured
  • pediatric: still leading cause of cancer deaths in kids
  • Adults: worse prognosis
104
Q

What factors worsen prognosis of ALL?

A
  • age < 2 years
  • adolescent and adult onset
  • peripheral blood count > 100,000
105
Q

What factors better prognosis of ALL?

A
  • age between 2 and 10
  • low white cell count
  • hyperdiploidy
  • trisomy of chromosomes 4, 7, and 10
  • presence of t(12;21)
106
Q

How do you treat t(9;22)-positve ALLs?

A

TX: with BCR-ABL kinase inhibitors along side chemo therapy

107
Q

What are two peripheral B-Cell Neoplasms?

A
  • Chronic Lymphocytic Leukemia

- Small Lymphocytic Lymphoma

108
Q

How do CLL and SLL differ?

A

in the degree of peripheral blood lymphocytosis (increase in lymphocytes)

109
Q

What is the most common adult leukemia in the western world?

A

CLL

110
Q

What is the pathogenesis of CLL/SLL?

A
  • most common genetic abnomalities are deletions of 13q14.3, 11q, 17q, and trisomy 12q
  • unmutated Ig segments indicates naive B-cell origin
111
Q

CLL/SLL need what two transcription factors to grow?

A

NK-kB and BTK

112
Q

What is the immunophenotype of CLL/SLL?

A

express pan B-cell markers: CD 19, 20, 23, 5 (sometimes) and IgM (sometimes also IgD)

113
Q

What are the clinical presentations of CLL/SLL?

A
  • asymptomatic at time of diagnosis
  • eventually get tired, anorexia, weight loss, Ig spike
  • leukopenia in SLL
  • High counts ( > 200,000) in CLL
114
Q

CLL and SLL disrupt ______ through uncertain mechanisms

A

immune function

- may cause Hypogammaglobulinemia, hemolytic anemia, or thrombocytopenia

115
Q

What is the prognosis of CLL/SLL?

A

poor: mean survival 6 years
worsening factors are: 11q and 7q deletions
no somatic hyperpigmentation, ZAP-70 expression, NOTCH1 mutations

may also transform to aggressive tumor

116
Q

What is Richter syndrome?

A

CLL/SLL tranformation to diffuse large B-cell lymphoma heralded by rapidly enlarged mass in lymph node or in spleen

117
Q

What is Follicular Lymphoma?

A

most common form of indolent NHL
middle age people
Males = females
< in Europe, Rare in Asians

118
Q

What is the pathogenesis of Follicular Lymphoma?

A

-arises from germinal center B cells and chromosomal translocations involving BCL2 on chromosome 18
IGH chromosome 14
-BCL2 is supposed to promote apoptosis
-MLL2 gene mutation

119
Q

What is the immunophenotype of follicular lymphoma?

A
  • normal germinal center B cells

- normal Germinal Center B cells are BCL2-negative

120
Q

How common is Diffuse Large B-Cell Lymphoma?

A
  • DLBCL is the most common form of NHL
  • men > women
  • > 60 years of age
121
Q

What is the pathogenesis of of DLBCL?

A
  • Dysregulated BCL6
  • oncogene mutation MYC
  • p300 and CREBP mutations as well
122
Q

What is the immunophenotype of DLBCL?

A

Mature B-cell tumors express CD 10/19/20 and BCL6

123
Q

What are two subtypes of DLBCL?

A
  • Immunodeficiency-associated Large B-cell lymphoma which is seen in the setting of severe T-cell immunodeficiency (HIV infxn and bone marrow transplant). EBV infxn is common
  • Primary Effusion Lymphoma presents as a malignant pleural effusion. Older people or HIV. fail to express B-cell markers. Clonal IgH. Infxn w/ KSHV/HHV-8 is common
124
Q

What are the clinical features of DLBCL?

A

-enlarging node anywhere in the body
-Waldeyer ring– oropharyngeal lymphoid tissue that includes the tonsils and adenoids
-Liver and spleen masses
-Bone marrow involved in late course
-

125
Q

What is the prognosis of DLBCL?

A
  • fatal if not treated immediately
  • TX leads to 80% remission and 50% cured
  • DLBCL w/ MYC mutation = worse prognosis
126
Q

What is Burkitt Lymphoma?

A
  • Very aggressive mature B-cell tumor typically in extranodal sites
  • MYC Chr 8 proto-oncogene mutation
  • Latent EBV infxn is common
127
Q

What is the pathogenesis of Burkitt Lymphoma?

A
  • Warburg effect
  • fastest growing human tumor
  • MYC Chr 8 mutation
128
Q

What is the immunophenotype of Burkitt Lymphoma?

A
  • tumors of mature B-cells express surface IgM, CD10/19/20, and BCL6
  • almost always fails to express BCL2
129
Q

What are the clinical features of endemic Burkitt Lymphoma?

A
  • children and young adults
  • mass in mandible
  • involves adominal vicera (ovaries, kidneys, adrenals)
130
Q

What are the clinical features of sporadic Burkitt Lymphoma?

A
  • mass in ileocecum or peritoneum

- RARE bone marrow and peripheral blood involvement

131
Q

What is the prognosis of Burkitt Lymphoma?

A
  • good prognosis with TX
  • aggressive w/o TX
  • Adult have slightly worse prognosis
132
Q

Plasma Cell Neoplasms and related disorders may be described as what?

A
  • B-cell proliferation containing neoplastic plasma cells that virtually always secrete a monoclonal Ig or Ig fragment, which serve as tumor markers and often have pathologic consequences
  • most common and deadly = multiple myeloma
133
Q

Can neoplastic cells usually synthesize excess light chains along with complete Igs?

A

yes

134
Q

What is multiple myeloma (plasma cell myeloma)?

A
  • tumors scattered throughout skeletal system
  • Solitary myeloma = single mass in bone
  • Smoldering myeloma = no symptoms w/ high plasma M component
135
Q

What is Waldenstrom macroglobulinemia?

A
  • high IgM leads to hyperviscosity of blood
  • associated w/ lymphoplasmacytic lymphoma
  • older adults
136
Q

What is heavy chain disease?

A
  • synthesis and secretion of free heavy-chain fragments

- associated w/ Mediterranean lymphoma

137
Q

What is primary or immunocyte-associated amyloidosis?

A

-monocolonal proliferation of plasma cells secreting light chains deposited as amyloids

138
Q

What is monoclonal gammopathy of undetermined significance (MGUS)?

A
  • patients w/o SX but have large M component in blood
  • adults
  • may progress to multiple myeloma
139
Q

What are the clinicopathologic entities of multiple myeloma?

A
  • lyitic bone lesions
  • high IL-6 in blood
  • hypercalcemia (via MIP1a activated osteoclasts)
  • renal failure
  • kappa light tubular deposits
  • acquried immune abnormalities
140
Q

What is the pathogenesis of Multiple Myeloma?

A
  • IgH locus proto-oncogene rearrangement
  • Chr 14, Chr 11, Chr 17p (P53 tumor suppressor mutation)
  • MYC mutation = late stage highly aggressive
141
Q

Immunophenotype of Multiple Myeloma is what?

A

plasma tumor cells are positive for CD138, adhesion molecule syndecan-1, CD56

142
Q

What are the clinical features are:

A

1- plasma cell growth in bones
2- production of excessive Igs
3- suppression of normal humoral immunity
4- chronic pain from bone resorption
5- hypercalcemia
6- Recurrent bacterial infxns
7- BENCE-JONES-Proteinuria (most important)

143
Q

How do you recognize Solitary Myeloma (Plasmacytoma)?

A
  • bone lesions
  • lungs, oronasophraynx, nasal sinus lesions
  • modest elevation of M protein
144
Q

How do you recognize Smoldering Myeloma?

A
  • patients asymptomatic
  • serum M protein >3
  • Plasma cells make up 30%
145
Q

How do you recognize Monoclonal Gammopathy of Uncertain Significance?

A
  • MGUS >50 years old
  • asymptomatic
  • serum M protein <3
  • 1% of these patients in 1yr get multiple myeloma
146
Q

How do you recognize Lymphoplasmacytic Lymphoma?

A
  • 6th or 7th decade of life
  • plasma cells secrete IgM
  • high IgM = hyperviscosity = Waldenstroms
147
Q

What is the pathogenesis of Lymphoplasmacytic lymphoma?

A

MYD88 mutations = NK-kB active = cell grow and proliferation

148
Q

What is the immunophenotype of Lymphoplasmacytic Lymphoma?

A

-B-cell markers CD20 and surface Ig (usually IgM)

149
Q

How does Lymphoplasmacytic Lymphoma present?

A

weakness, fatigue, weight loss,
1/2 get hepato/splenomegaly
autoimmune hemolyisis via cold agglutinins

150
Q

IgM increases viscosity of the blood causing hyperviscosity syndrome. What is this characterized by?

A

Visual impairment
Neurologic problems- deaf, headache, sluggish blood
Bleeding
Cryoglobulinemia

151
Q

What is Mantle Cell Lymphoma?

A
  • type of NHL lymphoid neoplasm
  • 5th or 6th decade of life
  • M>F
152
Q

Pathogenesis of mantle cell lymphoma is:

A

IgH locus mutation on Chr 14

D1 locus mutation on Chr 11

153
Q

Immunophenotype of Mantle cell lymphoma is?

A
  • express high lvls cyclin D1
  • CD19/20
  • CD5+ and CD23 negative which helps to distinguish it from CLL/SLL
154
Q

how does Mantle Cell Lymphoma present?

A
  • painless lymphadenopathy
  • Prognosis: POOR w/ survival 3-4 years
  • may involve gut
155
Q

What are marginal cell lymphomas?

A

B-cell tumors arising in the lymph nodes, spleen, or extranodal tissues
-associated with Sjogrens, Hashimotos, and Helicobacter gastritis

156
Q

Under what conditions do marginal cell lymphomas arise

A

chronic inflammtion

157
Q

What mutations do marginal cell lymphomas have?

A

MALT1 and BCL10

158
Q

What is Hairy Cell leukemia?

A
  • slowly growing B-cell cancer
  • rare
  • B-cells look hairy
159
Q

What is the pathegenesis of Hairy Cell Leukemia?

A

serine/threonine kinase BRAF mutation

160
Q

What is the immunophenotype of Hairy Cell Leukemia?

A

CD19/20, surface Ig (usually IgG)

CD11c, CD25, CD103, and annexin A1

161
Q

How does hairy cell leukemia present?

A
  • splenomegaly (MOST common and sometime only physical sign)
  • hepatomegaly
  • pancytopenia
162
Q

What is the prognosis of Hairy Cell Leukemia?

A

prognosis is good
needs light chemo
5 year avg relapses (easily treated again)

163
Q

Peripheral T-Cell and NK-Cell Neoplasms are indentified how?

A
  • presence of eosinophils and macrophages in lymph nodes
  • brisk neoangiogenesis
  • CD2/3/5/8 positive
  • DNA analysis confirming clonal T-cell receptor rearrangements
164
Q

Anaplastic Large-Cell Lymphoma (ALK Positive) has the presence of what?

A

Chr 23 ALK gene mutation

165
Q

How can anaplastic Large-cell lymphoma be identified?

A
  • large anaplastic cells containing HORSESHOE nuclei
  • voluminous cytoplasm
  • ALK detected in tumor cells (not in normal cells)
  • some express CD30
166
Q

What is the prognosis of anaplastic Large-cell lymphoma?

A

Good prognosis

80% cure rate

167
Q

Adult T-cell Leukemia/Lymphoma is only found in ______ infected with ________

A

Adults infected with HTLV-1

HTLV is found in japan, mediterranian, and west africa

168
Q

What are common findings in Adult T-cell Leukemia?

A
  • skin lesions
  • hypercalcemia
  • peripheral blood lymphocytosis
  • hepato/splenomegaly
169
Q

What is the prognosis of Adult T-cell Leukemia?

A

POOR, dead in a year

170
Q

What are Mycosis Fungoides and Sezary Syndrome?

A

they are different manifestations of a tumor of CD4+ helper T-cells that home to the skin; dermis and epidermis

171
Q

What are the skin lesion phases of Mycosis Fungoides

A

premycotic phase = inflammatory phase
plaque phase
tumor phase

172
Q

How are Mycosis Fungoides and Sezary Syndrome different? What is their prognosis?

A

skin lesions in Sezary Syndrome rarely turn into tumors

Prognosis is 8-9 year survival rate

173
Q

Large Granular Lymphocytic Leukemia can be defined by?

A
  • tumor of cytotoxic T and NK cells w/ transcription factor STAT3 mutation
  • autoimmune phenomena
  • cytopenias
174
Q

What dominates the clinical picture of Large Granular Lymphocytic Leukemia?

A

Neutropenia and anemia

175
Q

What is extranodal NK/T-cell lymphoma highly associated with?

A

EBV infection

176
Q

What is the overall prognosis of Large Granular Lymphocytic Leukemia?

A

POOR; chemo resistant but radiation responds well

177
Q

What does Hodgkin lymphoma have that NHL doesnt?

A

1-localized to single axial group of nodes
2-orderly spread by contiguity
3-mesenteric nodes and Waldeyer ring rarely involved
4-Extranodal presentation rare

178
Q

What does Nonhodgkins Lymphoma have that NL doesnt?

A

1-involvement of multiple peripheral nodes
2-noncontiguous spread
3-Waldeyer ring and mesenteric nodes involved
4-extranodal presentation common

179
Q

What are the 5 WHO types of Hodgkins Lymphoma?

Which ones have similar Reed Sternberg cells and are considered classic?

A 
1- Nodular Sclerosis
2-Mixed Cellularity
3-Lymphocyte-rich
4-Lymphocyte depletion
5-Lymphocyte predominance
Subtypes 1-4 are considered classic
180
Q

What is a common event in classical HL?

A

activation of transcription factor NF-kB (EBV or some mutation does this)

181
Q

What is TNFAIP3?

A

loss of function mutation in EBV tumor

182
Q

How does HL most commonly present as?

A

Painless lymphadenopathy

183
Q

What are the three major groups of myeloid neoplasms?

A

1- Acute Myeloid Leukemias (AMLs)
2- Myeloproliferative Disorders
3- Myelodysplastic Syndromes

184
Q

Acute Myeloid Leukemias are described as?

A
  • aggressive
  • blasts replace marrow = suppressed hematopoiesis
  • RUNX1/ETO and CBFB/MYH11 mutations = favorable
  • RARA/PML (bad) and MLL (bad) and NPM (good)
185
Q

How is diagnosis of AML confirmed?

A

performing stains for myeloid-specific antigens

186
Q

What chromosomes are affected in AML?

A

Chr 8 in kids and Chr 5 and 7 in adults

MLL gene mutatuions if happens after TX

187
Q

How does Acute Myeloid Leukemia (AML) present?

A
  • Anemia, neutropenia, and thrombocytopenia
  • Fatigue, fever
  • Spontaneous Bleeding of skin and mucosa
  • Cutaneous petechiae and bruising
  • Gingival Bleeding
  • Pseudomonas infection
  • Occasional soft tissue masses
188
Q

What is the prognosis of AML?

A

variable
no KIT mutation = good
KIT involvement = bad

189
Q

What might Myelodysplastic Syndromes progress to?

A

t-MDS (post radiation) and primary (idiopathic) 40% of case progress into AML

190
Q

What are Myelodysplastic Syndromes (MDS)?

A

clonal stem cel disorders characterized maturation defects w/ ineffective hematopoiesis accompanied by a high risk of transformation to AML

191
Q

What is MDS?

A

bone marrow replaced by ineffective hematopoiesis cells

192
Q

What is the pathogenesis of MDS?

A

loss-of-function mutation of P53 is suspected

Chr 5 and 7 and 20 mutations

193
Q

What are the clinical features of MDS?

A
  • older adults around 70
  • 50% found on accident w/ other blood tests
  • 50% weak, tired, bleeds, infxs (all b/c pancytopenia)
194
Q

What are Myeloproliferative Disorders?

A

tumors leading to high blood cell counts and extramedullary hematopoiesis
overly activated Tyrosine kinase

195
Q

What are the overlapping common features among proliferative disorders?

A
  • increased Proliferative drive
  • extramedullary Hematopoiesis
  • marrow fibrosis
  • peripheral cytopenias
  • variable transformation to acute leukemia
196
Q

How is Chronic Myelogenous Leukemia (CML) differentiated from other myeloproliferative disorders?

A

presence of chimeric BCR-ABL gene on BCR Chr 22 and ABL Chr 9

197
Q

What is the pathogenesis of Chronic Myelogenous Leukemia?

A
  • BCR-ABL dimerization = overactive ABL tyrosine kinase
  • causes abnormal release of immature granulocytic forms from the marrow into the blood
  • active tyrosine kinase = active Ras = active JAK/STAT
198
Q

What are the clinical features of Chronic Myelogenous Leukemia?

A
  • adults mainly
  • insidious onset w/ mild anemia
  • hypermetabolism from cell turnover = tired
  • 1st symptom is draggin abdomen b/c of spleen
  • detected byOCR test for BCR-ABL fusion gene
199
Q

What is the prognosis for Chronic Myelogenous Leukemia?

A

Good: hematopoietic stem cell transplant in young 75% cured
Poor: once accelerated or blast crisis phase hits

200
Q

What is the blast crisis stage of Chronic Myelogenous Leukemia?

A

mutations that interfere with the activity of IKAROS transcription factor

201
Q

What is Polycythemia Vera (PCV)?

A
  • marrow makes too many cells leading to thick blood and potential clots
  • overactive tyrosine kinase JAK2
202
Q

What is the pathogenesis of PCV?

A
  • low serum erythropoietin
  • elevated hematocrit = blood sludge/viscosity = clots
  • marrow fibrosis
  • growth factor independent hematopoietic cells
203
Q

How does PCV present clinically?

A
  • middle age adults
  • insidious
  • increased blood volume, red cell mass and hematocrit
  • cyanotic from stagnation of blood
  • headaches, dizziness, hypertension
  • Clotting and Bleeding and DVT stroke
204
Q

What is the prognosis of PCV?

A
  • death w/o TX in months from bleeding

- moderate: 10 year survival rate

205
Q

What is essential thrombocytosis (ET)?

A
  • rare chronic blood disorder
  • overproduction of platelets by megakaryocytes in marrow
  • rarely develops into acute myeloid leukaemia or myelofibrosis
206
Q

What are the mutations of ET?

A

point mutations in JAK2 and MPL

207
Q

How does ET present clinically?

A
  • elevated platelet counts
  • absence of polycythemia and marrow fibrosis
  • MILD bone marrow cell increase
  • increased megakaryotcytes (also abnormally shaped)
208
Q

What risks are there with ET?

A
  • Erythromelalgia = throbbing/burning of hands and feet caused by smal arteriole occulsion by platelets
  • others are same as PCV such as bleeding and clotting
209
Q

What is Primary Myelofibrosis?

A
  • normal bone marrow tissue is gradually replaced with a fibrous scar-like material.
  • Eventually leads to progressive bone marrow failure
210
Q

What is the chief pathologic feature of primary myelofibrosis?

A

extensive deposition of collagen in the marrow by non-neoplastic fibroblasts

211
Q

What are the mutations in primary myelofibrosis?

A
  • Calreticulin mutations = active JAK-STAT
  • JAK2
  • MPL
  • over active TGF-B
212
Q

How does primary myelofibrosis present clinically?

A
  • over 60yrs old
  • sensation of fullness in LUQ (from enlarged spleen)
  • progressive anemia
  • tired, fever, night sweats
  • normochromic normocytic anemia w/ leukoerythroblastosis
213
Q

What is the prognosis of primary myelofibrosis?

A

Poor: 3-5 years

214
Q

Langerhans Cell Histiocytosis is what?

A

-Rare
-CCR6 expressed by normal skin Langerhans
CCR7 expressed by neoplasstic Langerhans
-clonal proliferation of dendritic cells and macrophages (Langerhans cells) deriving from bone marrow
-capable of migrating from skin to lymph nodes.

215
Q

What is the most common mutation for langerhans cell histiocytosis?

A
  • BRAF mutation

- less common = TP53, RAS, tyrosine kinase MET

216
Q

Birbeck granules in the cytoplasm are characteristic of what?

A
  • Langerhans Cell Histiocytosis

- they are tennis racket in appearance containing langerin protein

217
Q

Describe Multifocal Multisystem Langerhans Cell Histiocytosis (Letterer-Siwe Disease):

A
  • Onset: before age 2
  • Clinical: Scalp and Trunk skin lesions and seborrheic eruption
  • Symptoms: Otitis media and mastoiditis
  • Prognosis: awful. rapid death. 5 yrs w/ TX
218
Q

Describe Unifocal and Multifocal Unisystem Langerhans Cell histiocytosis (eosinophilic granuloma):

A
  • Characterized by: langerhans cells mixed with eosinophils, lymphocytes, plasma cells, and neutrophils
  • unifocal lesion affect older kids and adults. Unifocal is indolent and may heal spontaneously or cured by radiation or cured by local excision

-Multifocal affects young kids.diabetes in 50% b/c of hypothalamus involvement and pituitary.
calvarial bone defect, diabetes insipidus, and exopthalmos —– Hand-Sculler-Christian triad

219
Q

What is Hand-Schuller-Christian tirad?

A

Calvarial Bone defect + diabetes insipidus + exopthalmos

220
Q

What is Pulmonary Langerhans cell histiocytosis?

A
  • adult smokers
  • BRAF mutation in 40% mutations
  • Langerhans cell proliferations
221
Q

What is the main cause of massive congestive splenomegaly?

A

Cirrhosis of the liver

222
Q

Emboli commonly lodge in what artery of the spleen?

A

Splenic artery

-common in endocarditis of mitral and aortic valves

223
Q

Neoplasms of the Spleen of the spleen are rare but what two are most common?

A

Lymphangiomas of cavernous type

hemangiomas of cavernous type

224
Q

Thymic Hypoplasia or aplasia is seen in what syndrome?

A

DiGeorge Syndrome

225
Q

Thymic Hyperplasia is seen in what?

A

Graves Disease, Rheumatoid arthritis

226
Q

Thymomas are what?

A

tumors of thymic epithelial glands

  • adults > 40
  • mostly found in anterior superior mediastinum
227
Q

Clinical presentation of Thymomas is what?

A
  • symptoms of impingement on mediastinal structures
  • 45% detected when evaluating Myasthenia Gravis ptx
  • devlopment of diverse autoimmune disorders
228
Q

C-MYC+
Biopsy of distal small bowel in ileum
Starry sky appearance on biopsy

A

Burkitt Lymphoma

Heme and Lymph Midterm (8 decks)

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