LN and WBC Disorders Flashcards
(178 cards)
1
Q
Another name for white blood cells
A
leukocytes
2
Q
how many main compartments of the body do leukocytes occupy?
A
4
(Disorders can begin in any of these locations and then spread to the others)
3
Q
what are the 4 main compartments of the body that leukocytes occupy? What is the relationship of each of these compartments to the WBC?
A
-bone marrow –> production of WBCs
-bloodstream –> transport
-lymph nodes –> immune activation
-site of infection or immune stimulation –> can be within any organ or soft tissue (what you see clinically)
4
Q
T/F PNMs only refer to neutrophils
A
false –> refer to all granulocytes
5
Q
what is leukopenia?
A
decreased serum level of leukocytes
6
Q
what is leukocytosis?
A
elevated serum levels of leukocytes, mostly neutrophils –> 15-20,000/mm3
7
Q
what is the normal expected value for WBCs in a CBC?
A
4 - 10,000/mm3 (or µl)
(elevates to 15-20,000/mm3)
8
Q
what is the main cause of neutrophilic leukocytosis? (2)
A
-bacterial infections
-tissue necrosis (burns, myocardial infarctions)
9
Q
what is the most common type of leukocytosis?
A
neutrophilic leukocytosis
10
Q
what is the main cause of lymphocytotic leukocytosis? (2)
A
-chronic infections
-some viral infections
11
Q
what is the main cause of monocytotic leukocytosis? (1)
A
-chronic infections
12
Q
what is the main cause of eosinophilic leukocytosis? (3)
A
-allergies (asthma, hay fever)
-parasitic infections
-drug reactions
13
Q
what is seen during a normal Lymph node (LN) evaluation?
A
LNs normally small (<0.5cm) and nonpalpable
14
Q
what is seen during a Lymph node (LN) evaluation where Lymphadenopathy (LAD) is present??
A
firm, enlarged LN (>1cm)
15
Q
where is painful LAD normally seen?
A
in the LN that is draining a region of infection (acute lymphadenitis)
16
Q
where is non-painful LAD normally seen?
A
with chronic inflammation (chronic lymphadenitis), metastatic cancer or lymphoma
17
Q
most cases of Lymphadenopathy (LAD) are ____ and ____, particularly in children
A
self-limited and benign (i.e. not malignancy/ cancer)
18
Q
does localized or generalized Lymphadenopathy (LAD) have more of a chance of underlying systemic disease?
A
generalized
19
Q
describe what is meant by “significance of duration” when it comes to Lymphadenopathy (LAD)
A
-if <2 weeks or >1 year without change in size = unlikely to be a tumor (neoplasm)
-if >6 weeks and not better by 12 weeks = risk for cancer
20
Q
what does an LAD workup consist of? (3)
A
serology (blood tests), imaging (ultrasound, CT) and possibly biopsy
21
Q
what is the MIAMI mnemonic for different etiologies of LAD?
A
-Malignancies
-Infections
-Autoimmune disorders
-Miscellaneous/unusual conditions
-Iatrogenic causes
22
Q
what are symptoms of a Malignancy-caused LAD?
A
- fever
- drenching night sweats
- unexplained weight loss of greater than 10% of body weight
- in supraclavicular LAD: intraabdominal malignancy (50%)
23
Q
what are symptoms of an Infection-caused LAD?
A
fever, chills, fatigue, and malaise
24
Q
what are symptoms of a Miscellaneous/unusual conditions-caused LAD?
A
other specific findings of each condition
25
what are symptoms of an Autoimmune disorder-caused LAD?
arthralgias, muscle weakness, and rash
26
what are symptoms of an Iatrogenic-caused LAD?
history of new medications
27
what LNs drain the oral cavity?
submandibular nodes
28
what is neutropenia?
decreased neutrophils in blood
29
what is Agranulocytosis?
decreased granulocytes (neutrophils, basophils an eosinophils) in blood
30
what are the major causes of neutropenia and Agranulocytosis? (2)
-Cancer chemotherapy
-Reaction to drugs
31
what is the most common sequellae of neutropenia and Agranulocytosis?
infection (particularly when below 500 cells/μl)
32
what are the major pathogenesises of neutropenia and Agranulocytosis?
-Decreased production in bone marrow
-Increased destruction of peripheral cells leads to hypercellular marrow
33
what are symptoms of neutropenia and Agranulocytosis?
Malaise, fever, chills, weakness, ulceration (oral, often gingival)- deep, punched out
34
35
36
37
what can cause decreased bone marrow and therefore decreased production of neutrophils and/or granulocytes? (3)
-Chemo tx can cause a transient marrow hypoplasia decreasing neutrophil production
-Pts with aplastic anemia have chronic marrow hypoplasia
-leukemia causes replacement of the normal marrow
38
what is the treatment for Neutropenia/Agranulocytosis? (3)
-Remove the offending agent
-Control infections (antibiotics, antifungals etc.)
-Give granulocyte colony-stimulating factor (G-CSF) to stimulate granulocyte production
38
what can cause the increased destruction of peripheral cells that leads to hypercellular marrow? (3)
-immune-mediated injury (drugs)
-overwhelming infection (using up peripheral cells)
-splenomegaly (can accelerate removal of granulocytes)
39
how are WBC Neoplasms classified?
based on morphologic and molecular criteria (lineage-specific protein markers and genetic changes)
40
what are the broad categories of WBC Neoplasms based on?
origin and differentiation
41
what are the 3 major broad categories of WBC Neoplasms?
Lymphoid neoplasms
-Myeloid neoplasms
-Histiocytic neoplasms (Langerhans cell histiocytosis)
42
what are 2 etiologies for lymphoid neoplasms? which is more common
-increased risk for translocations and transformation in B cells (more common)
-T cells are genomically stable (uncommon cause of lymphomas)
43
Lymphoid neoplasms can result due to increased risk for translocations and transformation in B cells because in germinal centers they undergo what 2 things?
-somatic hypermutation
-class switching
44
why do B cells undergo somatic hypermutation in the germinal center?
to increase antibody affinity
45
why do B cells undergo class switching in the germinal center?
to produce multiple antibody types
(i.e. from IgM to IgG, IgA, IgE) to the same antigen
46
Know what germinal centers look like in lymph nodes
germinal centers are the large circles in the image
47
what are the parts of the LN germinal center?
-Dark Zone
-Light Zone
-Mantle Zone
48
T/F lymphomas can develop at any step during the normal maturation of B-cells
true
49
what occurs in the LN's Dark Zone of the germinal center?
initial antigen stimulation
50
what occurs in the LN's light Zone of the germinal center?
apoptosis and class switching
51
Group of hematologic malignancies characterized by tumor cells that originate in the bone marrow and spill over into the blood
Leukemia
52
Tumor masses in lymph nodes or other tissues
Lymphoma
53
All lymphoid neoplasms can spread to ______ and _____
lymph nodes and other tissues
(liver, spleen, bone marrow and peripheral blood)
54
Because of the overlap in clinical behavior and location, classification of Lymphoid Neoplasms focuses on what?
the morphology (shape, size) and the molecular characteristics (surface markers) of the tumor cells
55
______ tumors come from cells arrested at or derived from a specific stage of normal lymphocyte differentiation.
B and T cell
56
T/F Lymphoid Neoplasms cells change morphology and surface markers as they progress through each stage of differentiation
true
57
what are the B-cell neoplasms that can occur in the bone marrow before the cell matures in the lymph node? (4)
-Precursor B lymphoblastic lymphoma/leukemia
-small lymphocytic lymphoma
-chronic lymphocytic leukemia
-multiple myeloma
58
what are the B-cell neoplasms that can occur in the mantle zone of the LN? (1)
mantle cell lymphoma
59
what are the B-cell neoplasms that can occur in the germinal center of the LN? (4)
-Follicular lymphoma
-Burkitt lymphoma
-Diffuse large B-cell lymphoma
-Hodgkin's lymphoma
60
what are the B-cell neoplasms that can occur in the marginal zone (post-germinal center) of the LN? (4)
-Diffuse large B-cell lymphoma
-marginal zone lymphoma
-small lymphocytic lymphoma
-chronic lymphocytic leukemia
61
what T-cell neoplasm occurs in the thymus before the T-cell reaches the LN?
Precursor T lymphoblastic lymphoma/leukemia
62
what T-cell neoplasm occurs in the the LN?
Peripheral T cell lymphomas
63
what are the WHO classification criteria for Lymphoid Neoplasms? (4)
-Morphology (H&E appearance)
-Cell origin (immunophenotyping by IHC and/or
flow cytometry)
-Clinical features
-Genotype (karyotype, presence of viral genomes)
64
______ and ______ account for the largest proportion of cancers in children by tumor type
- Leukemia
- lymphoma
65
Leukemias can have diffuse infiltration into what organs? what does this cause?
lymph nodes, spleen, liver and gingiva causing general enlargement
66
in general, what are Leukemias derived from?
a single transformed cell exhibiting clonal growth
67
T/F Typically the clonal population for a leukemia has different surface markers
false
Typically, the clonal cell population all have the same surface markers
68
what can be an etiology for Acute Leukemia? (4)
-Ionizing radiation (atomic bomb)
-Toxins (benzene and toluene)
-Antineoplastic chemotherapeutic drugs
(procarbazine, melphalan and other alkylating agents and etoposide)
-chromosomal abnormalities
69
what type of acute leukemia does Ionizing radiation most often lead to?
a myeloid leukemia
70
in the pathophysiology of Acute Leukemia there is myelophthisic anemia, which is the replacement of normal hematopoietic cells (myeloblasts, erythroblasts, and megakaryocytes) in bone marrow, causing what? (3)
-Neutropenia
-Thrombocytopenia
-anemia
71
when acute leukemia causes Neutropenia, what can this lead to?
bacterial, viral and fungal infections (oral ulcers, herpes, candida)
72
when acute leukemia causes Thrombocytopenia, what can this lead to?
bleeding and petechiae (gingival bleeding and palatal petechiae)
73
when acute leukemia causes Myelophthisic anemia, what can this lead to?
hypoxia
74
Acute Leukemia patients often present with signs and symptoms related to pathophysiology?
myelophthisic anemia
75
what are general symptoms of acute leukemia? (4)
-Fatigue, shortness of breath (SOB), pallor (decreased RBC's)
-Easy bruising (decreased platelets)
-Infection-bacterial and fungal mostly (due to decreased/dysfunctional WBC's)
-extramedullary hematopoiesis
76
what is the most common cancer in children?
Acute Lymphoblastic Leukemia (ALL)
77
what is Acute Lymphoblastic Leukemia (ALL) derived from?
immature B (pre-B) or T (pre-T) cells called lymphoblasts
78
90% of Acute Lymphoblastic Leukemia (ALL) patients show ____ and ____, creating an aberrant ____
show hyperdiploidy and a translocation creating an aberrant transcription factor
79
what is hyperdiploidy?
49-65 chromosomes/cell
80
What is a neoplasm of mature circulating lymphocytes (high WBC count), and can be either lymphocytic or myeloid
Chronic leukemia
81
Common symptoms of chronic leukemia slow onset in adult patients
-weakness/fatigue
-weight loss
-night sweats
-swollen abdomen (hepatosplenomegaly)
-infections
-easy bruising
82
For Chronic Leukemia:
CML - high WBC - ______
CLL - high WBC - ________
neutrophils
lymphocytes
83
what is the most common leukemia of adults in the Western world?
Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
84
are Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) the same?
no, they have different origins -- but they are grouped together because they are very similar otherwise
85
describe the tumor that occurs in Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) and why
Indolent, slow-growing tumor (due to increased BCL-2), often asymptomatic
(remember, BCL-2 is anti-apoptotic - gradual accumulation of cells)
86
how are Chromosomal translocations in Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) cured?
only achieved with hematopoietic stem cell transplant
BUT can only be treated once it reaches a certain threshold of division rate since therapies only target rapidly dividing cells and these tumors are slow
87
some Chromosomal translocations in Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) tumors transform to what?
more aggressive diffuse large B-cell lymphoma (Richter transformation)
(prognosis = death within a year)
88
What is a myeloproliferative disorder (neoplasm of mature cells of myeloid lineage) that particularly shows an increase in granulocytes
Chronic myeloid leukemia
89
What chromosome and translocation is involved in chronic myeloid leukemia? What does it cause?
Philadelphia chromosome:
BCR-ABL t(9:22) translocation causing a fusion protein
90
What is a blast crisis in chronic myeloid leukemia?
Some cases undergo transformation into an acute leukemia
91
What is treatment for chronic myeloid leukemia?
Tyrosine kinase inhibitors (e.g. imatinib (Gleevec)) induce sustained remissions and prevent progression to blast crisis
92
What does MDS stand for?
Myelodysplastic syndrome
93
What happens in Myelodysplastic syndrome
Disordered maturation defect where bone marrow replaced by clonal, multipotent stem cells with capacity for differentiation into red cells (erythroid precursors), granulocytes and platelets
94
T/F Myelodysplastic syndrome is usually idiopathic but can develop after chemotx or exposure to ionizing radiation
True
95
In Myelodysplastic syndrome (MDS) the marrow is hypercellular/normocellular but the peripheral blood shows _______
cytopenias
96
Myelodysplastic syndromehas a high risk of transformation to what?
transformation to AML (acute myeloid leukemia)
97
What are some examples of B cell lymphomas?
- Hodgkin Lymphoma
- Non-Hodgkin Lymphomas
- Plasma cell disorders: multiple myeloma
98
What are some examples of Non Hodgkin lymphomas?
- Follicular lymphoma
- Marginal zone lymphoma
- Diffuse Large B cell lymphoma
- Burkitt lymphoma
99
What type of cell often classifies Hodgkin lymphoma histologically?
- Typified by the Reed-Sternberg (RS) cell which is a germinal center B cell
- Some have EBV infection
100
describe the histological appearance of Reed-Sternberg (RS) cell (B-cell)
Large cell with a multilobated nucleus, prominent nucleoli and which sometimes can be binucleated forming "owl eye" appearance
101
What age is affected most by Hodgkin Lymphoma
Adolescents/young adults or patients >50 yrs
102
what are the common signs/symptoms of Hodgkin Lymphoma?
-Painless lymphadenopathy (LAD)
-"B symptoms" - fever, weight loss, night sweats, pruritis, anemia
(underlined are associated with advanced disease)
103
describe the classic Painless lymphadenopathy of Hodgkin Lymphoma?
arises in a single lymph node (lower cervical, supraclavicular, mediastinal LNs) → spreads to contiguous nodes
104
what is Tx for for Hodgkin Lymphoma?
-Chemotherapy
-advanced disease also receives radiotherapy
-Immunotherapy (anti-PD-1 antibodies for refractory disease
105
what is prognosis for Hodgkin Lymphoma?
high survival rate --> Five-year survival: >90%
106
most Follicular lymphomas have what genetic characteristic?
t(14;18) translocation causing overexpression of BCL-2 protein
107
what population are Follicular lymphomas seen in?
Adults >50 years
108
what are the signs/symptoms of Follicular lymphomas? (1)
Painless, generalized lymphadenopathy
109
how does the tumor of Follicular lymphomas appear?
Incurable, indolent lymphoma
110
Treatment for Follicular lymphomas is reserved for ______ or symptomatic disease
bulky
111
30-40% of Follicular lymphomas progress to what?
diffuse large B-cell lymphoma
112
how will Follicular lymphomas appear histologically?
no discrete dark or light zones --> normal pattern/architecture destroyed due to tumor
113
where do Extranodal marginal zone lymphomas arise from? what do they cause?
mucosa with lymphoid tissue (MALT) associated with epithelium (stomach, salivary glands etc.) → can cause swelling
114
what sustains extranodal marginal zone lymphomas? (2)
- chronic inflammation triggered by autoimmune disorders (Sjogren syndrome in salivary glands, or Hashimoto thyroiditis)
- sites of chronic infection (H. pylori gastritis)
115
how to treat H. pylori caused Extranodal marginal zone lymphomas and why?
-Kill the bug = kill the tumor
-bacteria allows specific T cells to drive growth and the survival of B cells
-BUT: polyclonal B cell growth can evolve into monoclonal change and spread to distant sites.
116
how is localized Extranodal marginal zone lymphomas treated?
cured by simple excision followed by radiotherapy
117
what is the most common type of lymphoma in adults?
Diffuse large B-cell lymphoma
118
what are the genetic causes of Diffuse large B-cell lymphoma? (2)
-t(14;18) translocation of BCL-2
-translocations of MYC
119
How does Diffuse large B-cell lymphoma often appear?
symptomatic, rapidly enlarging mass either within a lymph node or extranodal in virtually any organ or tissue
120
Does the tumor of Diffuse large B-cell lymphoma grow slowly or quickly?
Aggressive tumor
121
how to treat Diffuse large B-cell lymphoma?
intensive combination chemotherapy and anti-CD20 drugs (retuximab) with 60-80% complete remission
122
how does Diffuse large B-cell lymphoma appear histologically?
diffuse wall to wall large cells with a lot of mitotic activity
123
what is the Fastest growing human tumor?
Burkitt lymphoma
124
what is the genetic cause of Burkitt lymphoma?
t(8;14) translocation of MYC and IgH (heavy chain)
125
what populations is Burkitt lymphoma found in?
Effects mainly children and young adults usually at extranodal sites
126
Where are jaw masses associated with EBV found?
- African cases and about 20% of other cases associated with EBV
127
what is a major symptoms of Burkitt lymphoma in north america?
-Abdominal masses
128
describe treatment for Burkitt lymphoma
although the tumor is highly aggressive, with intensive chemotherapy most patients can be cured
129
how does Burkitt lymphoma appear histologically?
"starry sky"
130
pathologically, what occurs during Plasma cell neoplasms?
Neoplastic plasma cells secrete a monoclonal immunoglobulin (M protein) or immunoglobulin fragment which is a tumor marker and has pathologic consequences
131
T/F M proteins are small and restricted to plasma
false
M proteins are large and restricted to plasma
132
If immunoglobulin light chains are also made by Plasma cell neoplasms, they can be detected in what?
the urine and blood
133
what is Dysproteinemia?
Abnormal protein content in the blood, usually related to immunoglobulins
134
what is Monoclonal gammopathy (paraproteinemia, M component, M protein)?
an increase in a single immunoglobulin type as a result of a clone of plasma cells
135
how are Abnormal immunoglobulins detected?
serum protein electrophoresis
136
how does serum protein electrophoresis help to detect Abnormal immunoglobulins?
separates proteins based on charge, size and shape
137
what are the 2 major types of protein in the serum?
albumin and globulin proteins (alpha-1, alpha-2, beta-1, beta-2 and gamma)
138
what is increased serum albumin associated with? decreased?
-increased: severe dehydration
-decreased: malnutrition, cachexia, liver dz, nephrotic syndrome, protein-losing enteropathies, severe burns
139
what is increased serum alpha-1 globulin associated with? decreased?
-increased: inflammatory states, pregnancy
-decreased: alpha-1 antitrypsin deficiency
140
what is increased serum alpha-2 globulin associated with? decreased?
-increased: inflammatory states, nephrotic syndromes, oral contraceptive use, steroid use, hyperthyroidism
-decreased: hemolysis, liver disease
141
what is increased serum gamma globulin associated with? decreased?
-increased: polyclonal and monoclonal gammopathies
-decreased: agammaglobulinemia, hypogammaglobulinemia
142
what are Conditions with Abnormal Igs? (4)
-Multiple myeloma
-Monoclonal gammopathy of undetermined
significance (MGUS)
-Amyloidosis (light chain deposition with or without multiple myeloma)
-Waldenström’s macroglobulinemia (increased IgM blood levels in association with lymphoplasmacytic lymphoma)
143
A common lymphoid malignancy with a Median age = 70 years (older adults)
Multiple myeloma
144
what does Multiple myeloma involve in the body? what are symptoms?
bone marrow with associated lytic lesions (often 'punched out' radiolucenies) throughout the skeleton (vertebral column, ribs, skull etc.)
145
what is the most frequent M protein seen in Multiple myeloma?
IgG
146
what are Bence-Jones proteins?
kappa or lambda light chains that can be produced in Multiple myeloma -- their small size allows excretion in the urine
147
what is often the genetic cause of Multiple myeloma?
Often translocations fusing IgH locus (14, heavy chain) to cyclin D1 (11) and cyclin D3 genes
148
What causes proliferation of cells in Multiple myeloma?
MM cells bind to bone marrow stromal cells causing them to make IL-6 which causes osteoclast precursor cells to proliferate
149
In MM cells, up-regulation of ______ by bone marrow stromal cells activates osteoclasts → bone _____ → hypercalcemia, pathologic fracture
- RANKL
- resorption
150
what is the mechanism that causes the following symptoms in Multiple myeloma?
-recurring bacterial infections
Defective production of normal B cells→ high risk for bacterial infections
151
what is the mechanism that causes the following symptoms in Multiple myeloma?
-renal dysfunction
-obstructive proteinaceous casts (Bence-Jones proteins, complete immunoglobulin, albumin etc.)
-Light chain deposition in the glomerulus or
interstitial
-Hypercalcemia leads to dehydration and renal stones
-Bacterial pyelonephritis due to hypogammaglobulinemia
152
how does pathologic fracture appear radiographically in Multiple myeloma?
"punched out" radiolucencies
153
what can hypercalcemia lead to in Multiple myeloma?
-confusion, weakness, lethargy
154
T/F renal failure can occur in up
to 50% of Multiple myeloma patient
true
155
a definitive diagnosis of Multiple myeloma requires what?
bone marrow exam
156
how does Multiple myeloma appear histologically?
note the plasma cells
157
how is Multiple myeloma treated?
-proteasome inhibitors (Chemotx)
-Bisphosphonates
158
what are Bisphosphonates and what do they play in treating Multiple myeloma?
drugs that inhibit bone resorption --> reduce fractures and hypercalcemia
159
without treatment, what is the prognosis for Multiple myeloma?
death within a year
160
with treatment, what is the prognosis for Multiple myeloma?
Median survival: 4-7 years
161
Some Multiple myeloma patients have this form that may be asymptomatic for many years
"smoldering myeloma"
162
what is another name for Mycosis fungoides?
Cutaneous T-cell lymphoma
163
what are symptoms of Mycosis fungoides?
-Erythematous rash progressing to a plaque and then to a tumor phase.
-Can spread to lymph nodes and viscera
164
when Mycosis fungoides becomes systemic, how does it present?
-tumor cells in peripheral blood = Sezary syndrome - 1-3 yr survival
165
what causes Adult T-cell leukemia/lymphoma?
human T-cell leukemia virus type I (HTLV-1)
166
where is Adult T-cell leukemia/ lymphoma edemic?
southern Japan, Caribbean, West Africa
167
what is prognosis for Adult T-cell leukemia/lymphoma?
very aggressive with median survival time -- approx. 8 months
168
what is Histiocytosis?
a variety of proliferative disorders of dendritic cells or macrophages
169
what do Histiocytic neoplasms range from? what is between these two extemes
-highly malignant rare neoplasms to benign/reactive proliferations in lymph nodes
-Between these extremes is Langerhans cell histiocytosis (histiocytosis X)
170
what are Langerhans cells? what do they do?
-Immature dendritic cells found in the epidermis with similar cells found in many other organs.
-capture antigens and present them through MHC class II to T cells
171
Proliferating cells in Langerhans cell histiocytosis (LCH) appear how?
- more like tissue macrophages (histiocytes) rather than dendritic cells.
- Eosinophils also present
172
What is the pathogenesis of Langerhans cell histiocytosis?
BRAF mutation (component of RAS signaling pathway
173
Langerhans cell histiocytosis is acute/chronic presentations that affect what?
skin, viscera and/or bone
174
What is the most common clinical manifestation of langerhans cell histiocytosis?
bone involvement (eosinophilic granuloma of bone)
175
Which bones are most affected from langerhans cell histiocytosis?
Skull, ribs, vertebrae and mandible are commonly affected (similar locations as multiple myeloma)
176
What are symptoms of bone involvement in langerhans cell histiocytosis?
- Dull pain and tenderness often present
- Punched-out or ill-defined radiolucency
177
