Unit III Flashcards
1
Q
What condition presents with the following findings?
There is lymphopenia of both T and B cells, absent thymic shadow on X-ray, and tonsils are small; mitogen responses and serum immunoglobulins are low.
A
Severe Combined Immunodeficiency Disease (SCID)
2
Q
What defect causes SCID-X1?
A
a defect in the gene for the gamma chain that forms part of the receptors for IL-2 and other cytokines necessary for lymphoid development, or their signaling pathways.
3
Q
What causes autosomal recessive SCID diseases?
A
A lack of the enzyme adenosine deaminase (ADA); so
adenosine accumulates in all cells but impairs lymphocyte development selectively
4
Q
What is the most common SCID disorder in Navajo and Apache tribes?
A
V(D)J recombination
5
Q
What is X-linked (Bruton) Agammaglobulinemia?
A
When there are normal T cells but low to absent B cells
6
Q
What causes X-linked (Bruton) Agammaglobulinemia?
A
a defect in a protein tyrosine kinase gene, btk, normally expressed in preB and later B cells
7
Q
What are some of the symptoms associated with X-linked (Bruton) Agammaglobulinemia?
A
bacterial infections manifesting as pneumonia and chronic diarrhea
Enteroviruses which enter through the GI track are unprotected by IgA
8
Q
Which condition can fight against viral infections?
A
X-linked (Bruton) Agammaglobulinemia because this mostly affects B cells
9
Q
What would you diagnose a patient with high IgM with low IgG and IgA?
A
X-linked hyper IgM syndrome
10
Q
What causes X-linked hyper IgM syndrome?
A
The Tfh cell has an accessory molecule (CD154 or
CD40-ligand) that interacts with CD40 on B cells, signaling them to switch classes. If either is defective, the B cell gets no signal to make a switch.
11
Q
What condition is good a fighting bacterial infection but not good at infections that spread throughout the tissue?
A
This something that affect IgG… X-linked hyper IgM syndrome. Too big to get through to the tissues!
12
Q
What condition has a phenotype associated with recurrent bacterial conditions?
A
Common Variable Immunodeficiency (CVID)
13
Q
What disorder is caused by a deletion on chromosome 22?
A
DiGeorge Syndrome
14
Q
What leads to the symptoms associated with DiGeorge Syndrome?
A
The 3rd and 4th pharyngeal arches do not develop correctly therefore these children have no thymus or parathyroid gland.
T cells cannot mature and no calcium regulation = convulsions.
15
Q
What disease causes unexplained convulsions controllable by calcium?
A
DiGeorge Syndrome
16
Q
What disease leads to cell-mediated immunity being depressed; where viral and fungal infections are common.?
A
DiGeorge Syndrome
17
Q
What condition causes risk for lymphoma, enteropathy, or autoimmunity?
A
CVID
18
Q
What infections are associated with T deficiencies?
A
intracellular pathogens, including viruses, certain bacteria, and yeasts and fungi, especially Candida albicans and
Pneumocystis jirovecii
19
Q
What infections are associated with B cell deficiencies?
A
“high grade” bacterial pathogens such as Staphylococcus aureus, Haemophilus influenzae and Streptococcus pneumoniae.
20
Q
What is transient hypogammaglobulinemia of infancy?
A
infants slow to make their own IgG.
noticed about 6 months after birth and lasting up to 18 months
21
Q
What condition presents with mostly with recurrent and persistent Gram-positive bacterial infections?
A
transient hypogammaglobulinemia of infancy?
22
Q
What is CATCH-22?
A
symptoms of DiGeorge Syndrome
Calcium: parathyroid not developed so no regulation of calcium Appearance: low set ears, wide set eyes Thymus is not present Clefts Heart problems because
23
Q
What is the most common autoimmune deficiency?
A
Selective IgA deficiency
24
Q
What are symptoms of selective IgA deficiency?
A
usually asymptomatic, the patient may have diarrhea and sinopulmonary infections, or an increased frequency and severity of allergies.
25
What is the prevalence of IgA deficiency?
200 in 100,000
| 10-15 times more frequent no celiac disease
26
What does the nude mouse syndrome resemble?
Resembles DiGeorge
27
What is the enzyme which is absent in some cases of SCID?
ADA
28
How would you treat an ADA deficient SCID patient?
with IRRADIATED red blood cell transfusion
29
What is Ataxia Telangiectasia?
autosomal recessive disease characterized by sinus infections and pneumonia, ataxia (staggering) and telangiectasia (dilated abnormal blood vessels).
**IgA depressed
30
What type of genetic disease is ataxia telangiectasia?
autosomal recessive
31
Why is ataxia telangiectasia linked to tumors?
there is a defect in DNA repair
32
What is Wiskott-Aldrich?
comprised of platelet and B cell deficiency, eczema,
| and many bacterial infections.
33
What type of genetic disease is Wiskott-Aldrich?
X-linked
34
Does Type IV immunopathology require antibodies?
No
35
What is the difference between the initiation and elicitation of a reaction?
Initiation is the response following first exposure to the antigen aka immunization phase
The elicitation phase is the reaction in a person who is already immunized aka effector phase
36
What do Th1 cells secrete
```
Interferon Gamma (M1 activation)
IL-2
```
37
What is type IV immunopathology?
“T cell-mediated” or “Type IV” mechanisms are just immune system events that can be harmful or great and involve T cells. . They are the only type of immunopathology (of Types I, II, III and IV) which do not require antibody or B cells (strictly speaking).
38
What are key differences in memory t cells?
There are more of them than in a naive person
| they have a lower activation threshold --> takes less antigen for elicitation of a reaction
39
What does PPD stand for?
purified protein derivative
40
What cell type would predominate if you had a cell mediated response in response to a TB test?
Macrophages. One activated Th1 cell can recruit 1000 macrophages!
41
Why don't TB skin tests immunize patients?
The dose of PPD needed to elicit a positive reaction in an immune person is far lower than would be required to immunize a person
42
Why is a cell mediated response to TB antigen considered delayed hypersensitivity?
inflammation begins to be visible in 6 to 12 hours, and peaks at 24 to 48 hours, thus earning the label delayed- type hypersensitivity.
43
why does a person usually have no observed symptoms when first exposed to poison ivy?
by the time t-cells have been activated and move into the periphery the antigen has been removed or washed from the skin and you have no reaction.
You became immunized without even knowing it!
44
What is anergy?
absence of the normal immune response to a particular antigen or allergen
45
What is QuantiFeron-TB Gold?
A test used to measure T cell mediated immunity
purified M. tuberculosis-specific (human, NOT cow like the PPD) proteins are added to sample of whole blood and after incubation the IFNgamma levels are measured in the medium with ELISA. The test will be negative in people vaccinated with BCG (attenuated bovine TB bacteria), allowing you to distinguish between infection and previous immunization. The test will be positive if you have sufficient T cells against human M. tuberculosis
46
Why are cytotoxic T cells less studies in delayed hypersensitivity reactions?
Remember that CTLs are part of intrinsic pathway and present proteins synthesized WITHIN a cell therefore, harder to get the antigen presented on MHC I
47
Discuss how a chemical or small peptide might not need to be processed through an antigen-presenting cell to be presented by that cell to T cells.
sometimes the antigen can be so small/epitope size that it can associate directly with MCH without having to be processed.
Antigens can also bind to a peptide which is then presented on an MHC.
48
Describe the problem that HLA-B*5701 people may have with the HIV drug abacavir.
Abacavir changes the conformation of HLA-B *5701 (MHC I) so that the it binds certain self peptides that are not normally presented and are now tagged as foreign and trigger an autoimmune response
49
How long does it take to trigger a response to a first set reaction graft host?
10-20 days
50
How long does it take to trigger a response to a second set reaction graft host?
5-10 days
**memory t-cells now in effect
51
What causes the first set reaction during a graft rejection?
5-10% of the recipient T cells recognize the graft MHCs as self MHC plus antigen, thus becoming activated
52
What is hyperacute or "white graft" reactions?
**antibody mediated
The graft is rejected before it even has time to “heal in.” This is sometimes called a “white graft” reaction because the graft stays white and bloodless.
Results from the development of antibodies against histocompatibility antigens. Hyperacute rejections are common in xenografts (from another species) because humans have a pre-existing antibody against ubiquitous carbohydrate epitopes present in many animal species, but not humans.
53
Discuss how autoimmunity can result from environmental exposure to tissues that cross-react with human organs.
We all have anti-brain t-cells but are often not exposed to eat. Meat packer example and researcher were exposed to brain in their system which activated their T-cells and they were able to cross the blood brain barrier to attack the brain. Called AUTOIMMUNE ENCEPHALITIS
54
What is Sjogren syndrome?
2nd most common autoimmune disease that attacks exocrine glands like those that secrete tears and saliva. Potentially related to CTL
55
What are the requirements for graft-versus-host disease to occur?
1) The graft must contain immunocompetent T-cells (bone marrow does)
2) There must be at least one antigen in the host which the graft’s T-cells can recognize
3) The host must be relatively immunoincompetent or unable for some other reason (possibly genetic) to recognize the graft’s MHC antigens. If the host recognized the graft MHCs, the graft would be rejected too quickly for a graft vs. host reaction to occur.
56
Define the graft-versus-leukemia phenomenon.
Studies have shown that patients who receive T-depleted allogenic marrow or marrow from themselves during a bone marrow transplant have the fewest GvH symptoms but higher rate of leukemia relapse than those who get allogenic bone marrow that still has T-cells. Thus, it is believed that graft-versus-leukemia reactions are somehow important for the success of a bone marrow transplant. The mechanisms underlying this phenomenon are not well understood.
**need T cells to prevent leukemia
57
What is the ideal balance between GvL and GvH
Want to optimize GvL and minimize GvH reaction
58
What is the CD marker for B cells?
CD20, CD19, CD22
59
What is the CD marker for T cells?
CD3
60
What is the medullar sinus filled with?
histiocytes
61
What is the medullary cord filled with?
plasma cells and lymphocytes
62
What type of cells are found in the light zone of the germinal center?
mixed B-cells (centrocytes), T-cells, macrophages, and other cells
63
What type of cells are found in the dark zone of the germinal center?
mostly B cells called centroblasts
64
What are two markers specifically expressed in normal germinal B-cells and derived lymphomas
BCL6 and CD10
65
What do primary B cells secrete?
IgM
66
What do secondary B cells secrete?
IgG, IgD, IgA
67
What type of leukemia/lymphoma is associated with immature B cells?
B-cell acute lymphoblastic leukemia /lymphoblastic lymphoma (B-ALL/LBL)
68
What type of leukemia/lymphoma is associated with the mantle cells?
mantle cell lymphoma
69
What type of leukemia/lymphoma is associated with the Germinal center B-cells?
Follicular lymphoma
Burkitt Lymphoma
Hodgkin Lymphoma
70
What type of leukemia/lymphoma is associated with the pre or post germinal center B-cell?
chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL)
71
What type of leukemia/lymphoma is associated with plasma cells?
plasma cell myeloma (multiple myeloma)
72
What is the difference between chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL)?
When most of the cancer cells are located in the bloodstream and the bone marrow, the disease is referred to as CLL, although the lymph nodes and spleen are often involved. When the cancer cells are located mostly in the lymph nodes, the disease is called SLL.
73
What is the immunophenotype for CLL/SLL?
Positive: CD5 (aberrant expression of T cell marker on a B cell **always abnormal), CD23, and CD19
74
What is the diagnostic lymphocyte count for CLL?
Peripheral blood lymphocytosis ≥5 × 10^9/L for ≥ 3 months; monoclonal mature lymphocytes
75
What is the most common leukemia in the western world?
Chronic Lymphocytic Leukemia
76
What peripheral blood finding would you find for CLL/SLL
small monotonous lymphocytes
high nucleus to cytoplasm ratio
prolymphocytes present
**smudge cells
77
What are key morphologic findings for SLL?
pseudofollicles (proliferation centers): pale areas containing transformed larger cells
78
What is follicular lymphoma?
A lymphoma of germinal center B cells (centrocytes and centroblasts) with typically at least a partially follicular pattern.
79
What are morphologic features of follicular lymphoma?
You see neoplastic follicles distributed in the cortex and the medulla
follicles regular in size (should vary)
follicles are very close to one another
no mantle zone or poorly defined
no tingible body macrophages (areas eaten up)
80
What is the relationship between follicular lymphoma and BCL2?
BCL2 suppresses apoptosis and is POSITIVE in follicular lymphoma
**proto - oncogene
81
What is the mechanism for the BCL2 translocation?
BCL2 is located on chromosome 18 and translocated onto chromosome 14 downstream of the IGH promoter --> overexpression
82
What is the immunophenotype for follicular lymphoma?
BCL2 positive
positive B cell marker CD 19, CD20
Positive germinal B-cell marker CD10 and BCL6
83
Which one is more aggressive:
CLL/SLL, follicular lymphoma, mantle cell lymphoma
mantle cell lymphoma
84
What are the immunophenotypes for mantle cell lymphoma?
Positive B cell marker CD19, CD20
Positive CD5 (aberrant B cell expressing a t cell marker)
Positive cyclin D1 (BCL1) --> G1 S transition
85
What is the significance of cyclin D1?
cyclin binds to CDK which phosphorylates Rb and causes proliferation of cells by transitions from G1 --> S phase
86
What is the mechanism of the BCL1 gene translocation?
BCL1 gene on chromsome 11 to chromsome 14 IGH promoter
87
What type of Burkitt lymphoma is strongly associated with EBV?
Endemic Burkitt's Lymphoma
88
What are the cytologic findings in Burkitt's lymphoma?
medium sized lymphocytes with deeply basophilic cytoplasm with lipid vacuoles.
"starry sky" due to histiocytes trying to remove debree
89
What are the immunophenotypes for Burkitt's lymphoma?
positive B-cell markers CD19, CD20
Positive germinal B cell center CD10 and BCL6
Positive for MYC gene
90
What is diffuse large B-cell lymphoma?
a diffuse proliferation of medium to large-sized neoplastic B cells with a nuclear size greater than or equal to that of a histiocyte nucleus or more than twice the size of a small lymphocyte
91
What is the most common non-Hodgkins lymphoma?
diffuse large B- cell lymphoma 32% of all cases
92
Which lymphoma is typically in the malaria belt of equatorial Africa?
Endemic Burkitt's Lymphoma
93
Which lymphoma has a peak onset 4-7 years of age
Endemic Burkitt's Lymphoma
94
Which lymphoma is mostly in children and young adults?
Sporadic Burkitt's Lymphoma
95
Which lymphoma is primarily in HIV patients?
Immunodeficiency associated Burkitt's Lymphoma
96
Which lymphoma is considered highly aggressive?
Burkitt's Lymphoma
97
What is a leukemia?
A malignancy of hematopoietic cells, where the chief manifestation is involvement of the blood and marrow
98
What is a lymphoma?
A malignancy of hematopoietic cells, derived from lymphocytes or their precursors, which presents primarily as a solid mass
99
What is extramedullary myeloid tumor (aka granulocytic sarcoma)?
A malignancy of hematopoietic cells, derived from myeloid cells or their precursors (granulocytes, monocytes, etc.), which presents primary as a solid mass
100
What is a synonymous term for high grade leukemia?
acute leukemia
101
What is a synonymous term for low grade leukemia?
chronic leukemia
102
What does a high grade lymphoma present with?
rapidly enlarging mass
103
What does a high grade/acute leukemia typically present with?
A very high white blood cell count with near replacement of all normal cells in the marrow
104
What is lymphadenopathy?
enlarged lymph nodes
105
What is the thought to the reason that lymphomas have frequent translocations?
a natural susceptibility of genome translocations during normal period of genomic instability, during the initial immunoglobulin/ T- cell receptor rearrangement during the maturation of B cells/ T cells, and during the class recombination and somatic hypermutations process during the activation of B cells.
106
What chromosomal translocations are seen with chronic myelogenous leukemia (CML)?
translocations t(9;22)
107
What lymphomas are associated with the Epstein-Barr Virus (EBV)?
Classical Hodgkin Lymphoma
Brukitt Lymphoma
B cell non-Hodgkin Lymphoma
108
What lymphomas are associated with the Human T cell leukemia virus-1(HTLV-1)
causative factor in adult t cell leukemia/lymphoma (ATLL)
109
What lymphomas are associated with the Kaposi sarcoma herpes virus / Human herpes virus-8 (KSV/HHV-8)?
primary effusion lymphoma
110
What childhood cancer is most common?
Leukemia
111
What are myeloid malignancies?
those arising from mature or immature members of granulocytic, monocytic, erythroid, megakaryocytic, and mast cell lineages
112
What are lymphoid malignancies?
those arising from mature or immatures members of the B cell, T cell, and NK cell lineages
113
What translocation is seen in mantle cell lymphoma?
t(11;14) involving IGH and CCND1 genes
114
What test do you use to immunophenotype?
flow cytometry
| immunohistochemistry
115
What is myelodysplastic syndrome?
a group of conditions where a clonal population derived from a neoplastic hematopoietic stem cell takes over the marrow and is NOT capable for making normal blood cells in one or more lineages.
Usually a precursor to acute myeloid leukemia
116
What is myeloproliferative neoplasms?
neoplastic clonal proliferations of the marrow where the clone makes NORMAL functioning cells, usually in multiple lineages, but makes too many of them in on or more lineage.
tendency to progress into acute leukemia
117
What is non-hodgkin lymphoma?
any malignancy derived from mature B cells (excluding CHL or plasma cell neoplasms), T cells, or NK cells. Majority derived from B cells.
118
What are lab findings with acute leukemia?
decreased number of normal peripheral blood cells due to marrow infiltration by leukemic cells
119
What are risk factors for acute leukemia? (even though most patients don't have these risk factors?
previous chemotherapy, DNA alkylating agents and topoisomerase II inhibitors
Tobacco smoke
Ionization radiation
Benzene exposure
Genetic syndromes including Down Syndrome, Fanconi anemia, Ataxia-telangiectasia
120
What symptoms are associated with acute leukemia?
fatigue, malaise, dyspnea
easy bruisability, weight loss
bone pain or abdominal pain
neurologica symptoms
121
What are signs of acute leukemia?
```
anemia and pallor
thrombocytopenia, hemorrhage, ecchymoses, petechiae, fundal hemorrhage
fever and infection
adenopathy, hepatosplenomegaly
gum or skin infiltration
renal enlargement
cranial neuropathy
```
122
What is the significance of the leukemic stem cell in acute leukemia?
you have the presence of leukemic stem cells that have the potential for self-renewal. Thus, patients with acute leukemia have a population of cells that have an inexhaustible source of leukemic cells that replace the bone marrow.
123
What is the incidence ALL?
1-5 cases per 100,000
124
What percent of cases ALL cases occur in children 6 years and under?
75% MAJORITY!
125
What marker is expressed by immature lymphoblasts or myeloblasts?
CD34
126
What marker is expressed specific to lymphoblast?
Tdt is a nuclear enzyme specific to lymphoblasts
127
B-ALL accounts for what percentage of ALL?
80-85%
128
Name the B-lineage antigens
CD19
CD22
CD79a
129
What type of ALL has the worst prognosis?
Ph+ ALL
130
What is the prognosis for B- ALL with translocation 11q23 MLL?
poor prognosis
| typically seen in neonates and young infants
131
What percent of cases are B-ALL with t(9;22)
25% of ADULT B-ALL CASES
132
What percent of cases are B-ALL with t(12;21)(p13;q22); ETV6-RUNXI?
25% of childhood B-ALL
133
What is the prognosis of B-ALL with t(12;21)(p13;q22); ETV6-RUNXI?
very favorable
134
T-ALL more frequently occurs in what population?
adolescents and young adults
135
T-ALL frequently presents with...?
a component of lymphoblastic lymphoma (T-LBL), often manifesting as a large mediastinal mass
136
Do males or females typically get T-ALL / T-LBL?
males
137
What are T-lineage antigens?
CD2, CD3, CD7, CD4, CD8
138
What are T-lineage antigens seen in immature T cells?
CD99 and CD1a
139
Does T or B ALL have worse prognosis?
T-ALL
140
Which leukemia has better prognosis for hyperdiploidy?
ALL
141
What is the average age diagnose for acute myeloid leukemia?
65 years old
142
What lab results indicate AML diagnosis?
increase myeloblasts accounting for 20% or more of nucleated cells in the marrow or peripheral blood
143
What morphologic finding indicates the presence of a myeloblast under the microscope?
auer rod
144
What is a generic marker of an immature myeloblast?
CD34 ** can also be seen in lymphoblasts
145
What are myeloblast antigens?
CD117
myeloperoxidase
CD64
CD14
146
What type of leukemia can express megakaryocytic antigens?
AML
147
What cytogenetic abnormalities are consistent with AML?
balanced translocations
148
What causes AML with t(8;21) (q22;22)
fusion blocks the transcription of CBF dependent genes which blocks differentiation
149
What is the prognosis for AML with t(8;21) (q22;22)?
relatively good prognosis
150
What is notable for AML with inv(16)(p12.1;q22); CBFB-MYH11?
frequent presence in marrow of immature eosinophils with abnormal basophilic granules called base eos
see a mixture of increased myeloblasts and monocytes
151
What is the prognosis fo AML with inv(16)(p12.1;q22); CBFB-MYH11?
same as AML t(8;21) has relatively good prognosis
152
What is acute promyelocytic leukemia (APL)?
has abnormal promyelocytes predominate instead of blassts
153
What are laboratory findings for promyelocytic leukemia?
t(15;17)
| hypergranular cells
154
What is the cause of APL?
gene fusion blocks the RAR gene which is needed for differentiation of promyelocytes
155
How can you treat APL?
supra physiologic doses of all trans retinoic acid (ATRA)
156
What are some complication with APL to be on the look out for?
disseminated intravascular coagulation (DIC)
157
What type of leukemia usually show megakaryoblastic differentiation and seen in infants with Down Syndrome?
AML with t(1;22)(p12;q13)
**relatively good prognosis
158
What is the prognosis for AmL with abnormalities of 11q23; MLL?
poor prognosis
159
What lab findings diagnose t-AML secondary to alkylating agents or radiation?
a complex karyotype that includes whole or partial loss of chromosome 5 and/or 7
160
What is the clinical significance of monocytic differentiation?
they infiltrate the skin and gums, resulting in many small lesions
161
What presents with marrow fibrosis?
megakaryoblastic
162
What is the prognosis for t-AML in general? (therapy related AML)
A VERY poor prognosis
163
What are the three molecular markers currently used to predict prognosis in patients with AML with normal karyotype?
1. ** FLT3 ITD - positivity for internal tandem duplications (ITD) is POOR PROGNOSTIC FACTOR
2. NPMI - positivity for a mutation in NPM1 is GOOD PROGNOSTIC FACTOR (only if negative for first)
3. CEBPA - positivity for mutation in CEBPA gene is a GOOD PROGNOSTIC FACTOR (only if negative for first)
164
Who is most likely to get AML?
risk increases with age (median age = 65)
| MEN more likely than women
165
Where are the leukemic cells often found for acute monocytic leukemia? (Not otherwise specified, NOS)
In the gums
166
What is megakaryoblasic AML NOS often associated with?
marrow fibrosis
167
What are morphologic changes associated with myelodysplastic syndrome (MD)?
Dyserythropoiesis - RBC with nuclear budding and increased ring sideroblasts
Dysgranulopoiesis - neutrophils with bilobed nuclei called pseudo-Pelger-Huet cells, cytoplasmic hypogranularity
Dysmegakaryopoiesis -Megakaryocytes with hypolobated or non-lobated nuclei, often hyperchromatic nuclei, megakaryocytes often of small size
168
What are the two main features that characterize myelodysplastic syndrome (MDS)?
a) ineffective hematopoiesis
| b) increased risk of transformation to acute myeloid leukemia
169
What are the two clinical scenarios of MDS?
1) Primary / Idiopathic - old folks 70 years or older
2) Secondary / Therapy-Related (t-MDS) - Usually occurs 2-8 years after use of alkylating agents or exposure of fields of active marrow to ionizing radiation. Usually contains whole or **partial deletions of chromosomes 5 and/or 7.
170
What are the three different types of tests that could be performed to make a diagnosis of MDS?
dyserythropoiesis
dysgranulogpoiesis
dysmegakaryopoiesis
171
What are pseudo-Pelger-Huet cells?
Neutorphils with bilobed nuclei. One of the cytopenias seen in myelodysplastic syndrome.
172
What are four possibe causes of secondary myelodysplasia that might mimic MDS
- Certain drugs, including many chemotherapeutic drugs
- Deficiencies of vitamin B12, folic acid, or certain essential elements
- Viral infection
- Toxin exposure, especially heavy metals such as arsenic
173
What is the diagnostic criteria for low grade MDS?
Myeloblasts account for less than 5% of marrow cells, and less than 2% of peripheral blood cells.
174
What is the diagnostic criteria for high grade MDS?
Myeloblasts account for more than 5% of marrow cells and/or more than 2% of peripheral blood cells
175
Explain Refractory Cytopenia with Unilineage Dysplasia (RC-UD)
low grade MDS relatively good prognosis. Refractory Anemia has a median survival from diagnosis of over 5 years, with a rate of transformation to AML of only 2% at 5 years.
176
What is the prognosis for high grade MDS?
dismal; even if patients don't progress to AML they frequently die secondary to their bone marrow failure
177
What is Refractory Cytopenia with Multilineage Dysplasia (RC-MD)
low grade MDS with evidence of dysplasia in 2 or more lineages
Worse prognosis than RC-UD, with median survival of 2.5 years, and rate of transformation to AML of 10% at 2 years
178
What is MDS with isolated deletion 5q?
Unique type of low grade MDS, associated with anemia, often with increased platelets, and marrow showing distinctive megakaryocytes with small, round, non-lobated nuclei
179
What is Refractory Anemia with Excess Blasts-1 (RAEB-1): ?
5-9% blasts in marrow or 2-4% blasts in the peripheral blood.
median survival of 16 months, and 25% of patients transform to AML.
180
What is Refractory Anemia with Excess Blasts-2 (RAEB-2): ?
10-19% blasts in marrow or 5-19% blasts in the peripheral blood
median survival of 9 months, and 33% of patients transform to AML.
181
Why does myeloproliferative neoplasms often result in splenomegaly and hepatomegaly?
- sequestration of excess blood
| - extramedullay hematopoiesis
182
What are three possible negative end points for MPN?
- transformation to acute leukemia (usually AML, but sometimes ALL)
- development of myelodysplasia with ineffective hematopoiesis (transform to MDS)
- excessive marrow fibrosis with resultant bone marrow failure
183
What WBC findings are consistent with CML?
WBC anywhere from 12,000 - 1,000,000
increased neutrophils
increased basophils
sometimes platelets are increased
184
What is the initial phase for CML?
The chronic phase
185
what marrow findings are consistent with CML?
hypercellularity
small megakaryocytes with round, NON-lobated nuclei.
No dysplasia seen in the marrow or blood.
186
What is the blast phase for CML?
When it progresses to acute leukemia >20% blasts in marrow or blood
187
What is the intermediate phase for CML called?
accelerated phase
188
What is the second generation PTKI for CML?
dasatinib
189
What is polycythemia vera?
predominant proliferation of red blood cells
| also granulocytes and platelets
190
What mutations cause polycythemia vera?
JAK2 kinase mutation
| V617F point mutation
191
What causes secondary polycythemia?
smoking, chronic hypoxia, certain hemoglobin disorders, and others.
192
What is the most serious complication of polycythemia vera?
venous or arterial thrombosis
also possible marrow fibrosis
193
If you see a patient with thrombosis of the mesenteric vein, portal vein, or splenic vein, what diagnosis should you always consider?
polycythemia vera
194
What is the prognosis and treatment for polycythemia vera?
very good prognosis
| phlebotomy (blood letting) and aspirin therapy
195
What is primary myelofibrosis?
predominant proliferation of megakaryocytes and granulocytes that can progress to myelofibrosis
196
What mutation is associated with myelofibrosis?
JAK 2 kinase mutation found in 50% of cases
197
what is the prognosis for primary myelofibrosis?
Most PMF patients are not diagnosed until they have reached the fibrotic stage, at which time they have median survivals of around 5 years.
Survival times are much longer if diagnosed in the prefibrotic stage.
Most deaths due to PMF result from bone marrow failure secondary to fibrosis.
198
What is essential thrombocythemia?
sustained marked thrombocytosis. It differs from PMF in that there is no granulocytic hyperplasia in the marrow (the marrow is usually normocellular in ET), and the clustered atypical megakaryocytes in the marrow are even larger and more bizarre than in PMF.
199
What are Signs/symptoms of Essential Thrombocythemia?
- transient ischemic attacks (TIAs) (these are essentially small strokes causing no permanent damage)
- digital ischemia with paresthesias
- thrombosis of major arteries or veins (less common than in PV)
- splenomegaly is not common in PV, and is more suggestive of another MPN
200
What is leukoerythroblastosis?
increased immature granulocytes (myelocytes, metamyelocytes) and increased immature nucleated red blood cells present
201
What myeloproliferative disorder is associated with leukoerythroblastosis?
myelofibrosis
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What myeloproliferative disorder leads to extramedullary hematopoiesis?
myelofibrosis
203
What are smudge cell findings consistent with?
CLL/SLL
204
Which is the only lymphoma that affects men and women equally?
follicular lymphoma
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What is plasma cell myeloma or multiple myeloma?
malignant proliferation of plasma cells in bone marrow
plasma cells release osteoclast activating factor --> eats away at bone and causes "punched out lesions" usually in the vertebrae or skull
plasma cells produce immunoglobulin mostly IgG or IgA
decreased charge in RBC causing rouleaux formation
increased free light chains --> deposits in the tissue and forms primary AL amyloid also leads to bence jones proteins in the urine also deposits in kidney tubules and increases renal failure
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What is the diagnostic criteria for plasma cell myeloma?
No minimal level of M protein is included, but in most cases it is >30g/L of IgG, >25g/L of IgA, or >1g/24 hours of urine light chain
207
What are related organ/tissue impairments associated with plasma cell myeloma?
```
CRAB
hyperCalacemia
Renal failure
Anemia
Bone Lesions
```
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What is solitary plasmacytoma of bone?
a localized tumor of the bone, which is composed of clonal plasma cells that are cytologically, immunophenotypically, and genetically similar to those of plasma cell myeloma.
209
What is the diagnostic criteria for solitary plasmacytoma of bone?
- Single bone lesion consisting of monoclonal plasma cells
- No evidence of other bone lesions
- Absence of renal failure, hypercalcemia, and anemia that could be attributable to myeloma
- Absent or low serum or urine M protein
- Normal levels of uninvolved polyclonal immunoglobulins
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What is extraosseous plasmacytoma?
localized plasma cell tumors that arise in tissues outside of the bone marrow. They appear to be biologically distinct from solitary plasmacytoma of bone and plasma cell myeloma
211
Where do you typically find extraosseous plasmacytoma?
About 75% of them occur in the upper respiratory tract, including nasal passages, sinuses, oropharynx, and larynx.
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What is the diagnostic criteria for classic Hodgkin lymphoma?
presence of Reed sternberg cell = multi-lobed B cells
positive CD15 and CD30
lacks the common leukocyte antigen CD45
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What is the most frequent subtype of classic hodgkin lymphoma?
Nodular sclerosis variant
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What population is most at risk for nodular sclerosis variant?
Typically seen in young adults, and females
215
What is the morphology of nodular sclerosis?
Broad thick bands of fibrosis/collagen
| lacunar cells - reed sternberg cells that have large cytoplasm surrounding them an artifact of "formalin fixation"
216
What percent of nodular sclerosis cases are associated with EBV?
10-25%
217
What is the second most frequent subtype of classic hodgkin lymphoma?
mixed cellularity variant
218
What population is mixed cellularity variant often seen in?
children and older patients
219
What percent of mixed variant cases are associated with EBV?
75%
220
What morphologic findings are associated with mixed cellularity variant?
reed sternberg cells with abundant eosinophils (recruited by IL-5)
221
What are the three factors that immunopatholgy depends on?
genetics, environment, and bad luck
222
What is type I immunopatholgy?
symptoms or pathology due to IgE antibody
T2 mediated events are often seen here too
223
What is Type II immunopatholgy?
pathology due to IgG, IgM, or IgA antibody causing harm to self
224
What is Type V immunopathology and what other mechanism is it grouped with?
auto-reactive antibodies against surface receptors which STIMULATES (rather than harms) the cell
225
What is Type III immunopathology?
pathology caused by formation of immune complexes trapped in the basement of membranes of blood vessels and activates complement, leading to vasculitic inflammation.
226
What is Type IV inmmunopathology?
Pathologic outcomes of normal or abnormal T cell responses, including both helper and cytotoxic cells
227
What is Myasthenia Gravis?
a disease of progressive muscle weakness because patients are making antibody to the acetylcholine receptor
228
How does the antibody against AChR get made in myasthenia gravis (only in some patients)?
Aire transcription factor drives the thymic expression of CHRNA1, a gene for the AChR alpha subunit. Patients won't have the CHRNA1 promoter interacting with Aire so the protein is not expressed in the thymus (or displayed in the thymus) and Th clones reactive with the AChR are not deleted by negative selection.
229
What is one way to treat myasthenia gravis?
thymectomy often yields dramatic improvement
230
What is goodpasture syndrome?
uncommon conditions that involves the formation of autoantibodies to lung and kidney basement membranes
231
What do lung and kidney basement membranes share?
an epitope on the antigen (Type IV collagen)
232
What is Dressler Syndrome?
immune response to pericaridal or myocaridal antigens that causes cardiac pain, fever, malaise, and pericardial effusion seen after heart attack
233
What is rheumatic heart disease?
heart disease occurring after streptococcal infection due to a CROSS REACTION between group A streptococcus M-protein antigen and a structure on the heart's endothelial lining (probably laminin on heart valves) followed by neutrophil-mediated destruction.
**Classic type II
234
What is autoimmune thrombocytopenic purpura?
platelets are opsonized and their destruction, mainly in the spleen, is rapid.
Destruction of platelets by autoantibodies
235
When does autoimmune throbocytopenic purpura typically occur?
in young people some weeks after a viral infection, in older people, in association with many other autoantibodies
236
What is autoimmune hemolytic anemia?
may follow a viral infection, be associated with another autoiimmune syndrome, or cancer
drugs such as penicillin, methyldopa, chlorpormazine and quinidine can induce
237
What are the three mechanisms of Type II tissue damage?
neutralization
complement mediated damage
stimulatory hypersensitivity
238
What is Graves disease?
stimulatory autoimmunity to the TSH receptor on thyroid cells
239
What is Hashimoto disease?
Leading cause of hypothyroidism. Antigens include thyroglobulin (molecule in which iodine is stored), thyroid peroxidase, and pathological process is inflammatory and destructive
240
Explain the hybrid (foreign + self) antigen formation.
anti self B cells wont get you in trouble if the self antigens were T dependent and you dont have a antiself follicular helper T cell to trigger a reaction
If you have an anti self B cell that binds to the self part and ingests a foreign antigen that was tagging along. Then it can present this to a Tfh cell and trigger a reaction.
241
What is the idea behind the forbidden clone?
A t cell somehow escapes the normal thymic clonal deltion mechanism and encounters antigens that stimulate a response
242
Describe cross reactivity.
the tendency of one antibody to react with more than one
| antigen
243
Which cancers have lymphadenopathy?
CLL, follicular lymphoma, mantle cell lymphoma
244
What is a rash fever headache associated with?
tick borne disease
245
What disease causes increased pigmentation (from increased ACTH, with MSH-like
effect) including diffusely on skin, especially on palmar creases?
Addisons disease
246
What are the symptoms associated with Cushing's disease?
Round face, moon facies, “buffalo hump”, increased fat in arms, legs and waistline, skin thinning, increased bruising(ecchymosis and purpura), striae, delayed wound healing
247
proximal superficial fungal infection on the nail bed would be a clue for what disease?
HIV
248
acanthosis nigrans is associated with what conditions?
glucose metabolism, prediabetic, diabetic, metabolic syndromes
rare cases Family history
249
What would be a red flag that acanthosis nigrans is associated with cancer?
rapid onset and weight loss
250
What is the most common cancer associated with acnathosis nigrans?
adenocarcinoma of stomach
251
What are findings associated with diabetes?
yellow skin
rash on skin
mal perforans (foot ulcers)
disseminated granuloma annular
252
What are findings associated with infective endocarditis?
Skin findings include splinter hemorrhages, purpura, nail
| fold changes, Janeway lesions (bruises, and septic bacteria found here), Osler's nodes (vascular, painful)
253
What is scleroderma?
Skin findings of thickened skin over fingers and hands, skin
tightening around mouth, Raynaud’s
i. Commonly develop pulmonary hypertension, however pericarditis has poor prognosis
254
bilateral hilar lymphadenopathy is a clue for what conditions?
sarcoidosis
Skin findings can be protean including hyperpigmented
plaques, erosive and ulcerated plaques, granulomatous reactions in
tattoos
255
What disease is associated with lichen planus?
heptatitis C **European
purple, polygonal, pruritic papules
256
What is porhyria cutanea tarda?
associated with hepatitis
deficiency in uroporhyrinogen decarboxylase
blistering lesions on hands with sun exposure, hypertrichosis and atrophic scars with milia
257
What is osler weber rendlu?
minor vascular blebs all over body. Can be in GI where they bleed out or the lungs
258
What is Pyoderma Gangrenosum?
Punched out ulcers that can rapidly enlarge
Associated with inflammatory bowel disease as much as 30% of the time
NEVER DEBRIDE, will only enlarge
neutrophils attack skin
259
Hair loss and nail changes (spoon shaped) is associated with what condition?
Koilonychia
260
red distal nail beds associated with what?
renal failure
261
What is a bright red band at the tip of the nail bed associated with?
cirrhosis
262
What are four skin findings used to diagnose lupus?
malar rash (butterfly), discoid rash, oral ulcers, photosensitivity
263
Renal cancer tends to metastasize where?
face
264
What is leser traulat sign?
eruptive seborrheic keratosis
265
What is dermatomyostitis?
shawl like rash on upper torso
usually women
purple eyelids
can be associated with pulmonary fibrosis and genitourinary cancer, especially in women with rapid onset of severe symptoms
266
What is Erythema Gyratum Repens?
wood grain rash
| lung cancer!
267
What is hypertrichosis lanuginosa acquisita associated with?
lung cancer!
