Chapter 13-WBC, LNs, Spleen, And Thymus Flashcards
(344 cards)
1
Q
What is the clinical presentation of lymphocyte rich variant of Hodgkin lymphoma
A
Uncommon
- M>F
- Older adults
2
Q
What are the characteristics of myelodysplastic syndromes that are associated with worse outcomes
A
- Higher blast counts
- more sever cytopenias
- multiple clonal chromosomal abnormalities
3
Q
What are some clinical presentations seen with primary myelofibrosis
A
- Fatigue, splenomegaly, night sweats
- hyperuricemia and gout
4
Q
What is Fanconi anemia and what are they at an increased risk for
A
Familial decreased production of all blood cells. Higher risk of acute anemia
5
Q
What are the genetic abnormalities seen in Mantle cell lymphoma
A
- (11;14) translocation,
- IgH on 14
- cyclin D1 on 11
6
Q
What is the prognosis for AML with mutation in t(8;21)-RUNX1
A
Favorable
7
Q
What is the genetic abnormality in large granular lymphocytic leukemia
A
STAT3
8
Q
Which immunomarkers are present in the case of langerhans cell histiocytosis
A
- CCR6 and CCR7 (CCR7 is only present in the neoplastic forms)
- Binds to CCL19,20,21
9
Q
What is the most common plasma cell neoplasm and how does it commonly present
A
Multiple myeloma, presenting as bony destruction resulting in pain due to pathological fractures
10
Q
Which cells are the result from a hematopoietic stem cells
A
All blood cells, including the immune cells, RBCs, WBCs, platelets etc
11
Q
What are the clinical features of large granular lymphocytic leukemia
A
Dominated neutropenia and anemia
12
Q
Those patients with monoclonal gammopathy of uncertain significance (MGUS) are most likely to develop which condition
A
Symptomatic plasma cell neoplasm, usually multiple myeloma
13
Q
What is the prognosis of specified peripheral T cell lymphoma
A
Worse prognosis than even the most agressive B cell lymphomas
14
Q
Myeloid leukemias (cells with myeloid origin) originate in which locations and where do they tend to spread
A
Bone marrow that secondarily involve the spleen lymph nodes
15
Q
What are Auer rods
A
Needle like azuroohilic granules
16
Q
What are the common causes of neutrophilic leukocytosis
A
- Acute Bacterial infections (especially the pyogenic conditions)
- Sterile inflammation (such as tissue necrosis)
17
Q
Acute lymphadenitis of the mesenteric LN region is due to drainage of which area
A
Acute appendicitis
18
Q
What are the mechanisms that can cause the NFKB activation in Hodgkin’s lymphoma
A
EBV1 infection causing activation via:
- activation from latent membrane protein 1 (LMP1)
- loss of function mutation in IKB or A20 (aka TNF alpha-induced protein 3 or TNFAIP3)
19
Q
What are the clinical features of diffuse large B cell lymphoma
A
Rapidly growing mass at the nodal or Extranodal site, typically in the Waldeyet ring, which is the oralpharnyx that includes the tonisils and adenoids
20
Q
Splenic insufficiency causes increased susceptibility to which organisms
A
Pneumococci, meningococcal, Haemophilus influenza
21
Q
From the third month of embryogenesis until shortly before birth, what is the location of the chief site of blood cell formation
A
HSCs migrate to the liver and become the chief site
22
Q
Which forms of AML with t(8;21) and or inv(16) have a better prognosis
A
KIT negative mutations respond well to chemo
23
Q
What is the cell of origin for multiple myeloma
A
Plasma B cell
24
Q
What is the relation between smoking and leukemias
A
1.3 to 2 times higher risk of getting acute myeloid leukemia
25
What is the significance of plasma cell tumors and amyloid deposition
Light chains can be produced at such a rate that lambda light chains are deposited as amyloid
26
During leukocytosis, what other changes are commonly seen
Morphological changes:
- toxic granulations
- Dohle bodies
- cytoplasmic vacuoles
27
What condition do Myeloproliferative disorders have a high propensity to develop into
AML
28
What are the immunomarkers in unspecified peripheral T cell lymphoma
- CD2, CD3, CD5
| - Alpha/beta or gamma/delta TCR
29
What is the percentage of Jones Bence proteins in multiple myeloma
-99%
30
What is the most common trigger for hemophagocytic lymphohistiocytosis (HLH)
Infection, particularly EBV
31
What are the immunomarkers in Mycosis fungoides/Sezary syndrome
CLA (common leukocyte antigen)
-CCR4, CCR10
*All help with the homing of T cells to the skin
32
What is the clinical presentation of follicular lymphoma
- Painless, generalized lymphadenopathy
| - Extranodal site involvement such as testis, GI are rare
33
What is the clinical presentation of lymphocyte depleted variant of Hodgkin lymphoma
-Older adult males
-HIV infected
-Advanced disease
Weightloss, fever, night sweats
34
Lymphoid neoplasms are commonly associated with what
-Immune abnormalities with the loss of protective immunity and the breakdown of central tolerance
35
B-All appear in which patient population most often
3 year old Hispanic
36
What is the most common and most deadly neoplasm of plasma cells
-Multiple myeloma
37
Which stain is used to see iron ladened macrophages
Prussian blue ( can be used to see myelodysplastic syndromes)
38
Which parasite can cause cirrhosis of the liver and subsequent splenomegaly
-Shistosomiasis
39
What are the clinical features of acute myeloid leukemia
Replacement of marrow with blasts that cause marrow failure and:
- anemia
- Thrombocytopenia
- neutropenia
40
What is the classical definition of Myeloproliferative disorders
Increased production of one or more types of blood cells
41
What form of Reed stein burg cells are present in Nodular sclerosis variant of Hodgkin lymphoma
Lacunar RS cells
42
What is the state of cell infiltrate in Hodgkin’s lymphoma
Reactive cells as a result of the release of cytokines that are released from the Reed-Steinberg cells
-Reactive cells then further activate the RS cells via (CD30 and CD40)
43
How do multipotnent progenitors differ from HSCs
They are more readily able to proliferate, but have less capacity to self renew
44
What is the disease pattern seen in chronic Myeloproliferative leukemia (CML)
- Slow progressing, then enters an accelerated phase, which has increased anemia and thrombocytopenia
- The progressing into acute leukemia (aka blast crisis)
45
What is the rate that myelodysplastic syndrome (MDS) can transform into acute myeloid leukemia (AML)
10-40%
46
What is the prognosis for AML with mutation in NPM
Good
47
What is the immunomarkers in the case of the classic variants of Hodgkin lymphoma
Positive for PAX5, CD15,CD30
| Negative for CD 19, 20, 45
48
What is the morphological appearance of Dohle bodies and when are the commonly seen
Patches of dilated ER that appear as sky-blue cytoplasmic “puddles” seen during leukocytosis
49
Thrombosis of the splenic vein cause be caused by and can raise suspect of which conditions
-Carcinomas of the stomach or pancreas
50
What are the characteristics of the LNs in acute lymphadenitis
Enlarged and painful
51
What is the chromosome finding commonly seen in reed steinberg cells
Gain of function in the REL proto-oncogene on chromosome 2p
52
What are the contents of a thymoma
-rumors of thymic epithelial cells, contains benign immature T cells
53
What is a major complication of the BCR-ABL inhibitors
Resistance to it, which occurs in 50% of patients
54
Where do most Myeloproliferative disorders originate from
Multipotent myeloid progenitors
55
What are the clinical presentations of someone with splenomegaly
- dragging sensation in the LUQ, with pressure in the stomach,especially after eating
- Anemia
- leukopenia
- thrombocytopenia
56
What are the immnofactors involved in Burkitt’s lymphoma
CD10, CD19, CD20, BCL6
57
What is ataxia telangiectasias and what are they at an increased risk for
Caused by autosomal recessive of ATM gene
| -Neurodegenerative Disease that also carries an increased risk for acute leukemia
58
What are the markers that can be seen in the blood as the result of the tumor of a plasma cell
- M component aka, the Ig marker of the tumor
| - can be complete Ig, but commonly have excess light chains
59
What is the function of the MYC abnormality that allows for tumor development
Allows the Warburg effect, which allows shunting for aerobic glycolysis, allowing availability of glucose and glutamine
60
Which form of the diffuse large B cell lymphoma has a poorer prognosis
MYC translations
61
The proliferation and survival of multiple myeloma cells are dependent on which factor
IL6
62
What are the characteristics of the spent phase of polycythemia Vera (PCV)
Extensive fibrosis of the marrow that displaces the hematopoietic cells, usually resulting in extrameduallry hematopoiesis and organomegaly
63
What is the prognosis of mantle cell lymphoma
Poor, 3 to 4 years survival
64
What is the most common form of indolent NHL
Follicular lymphoma
65
Multifocal unisystem langerhans cell histiocytosis primarily affects which organs/factors
- Bone lesions that expand into the adjacent soft tissue
| * Develops diabetes insipidus in 50% of pts due to involvment of the posterior stalk of the hypothalamus
66
Chronic lymphocytic leukemia (CLL) signals are transduced through which pathway
Breton tyrosine kinase (BTK)
67
What is the clinical presentation of mantle cell lymphoma
- Painless lymphadenopathy
- involvement of the GI or spleen
- polyp like lesions in the gut or colon (lymphomatoid polyposis)
68
What are the histological findings in primary myelofibrosis
- atypical megakaryocytes (cloud like)
| - teardroped shaped red cells (dacryocytes)
69
Which AML has high number of Auer rods
T(15;17) aka acute promyelocytic leukemia
70
Which cell type tends to be increased in essential thrombocytosis (ET)
Megakaryocytes, usually with enlarged platlets
71
What are the histological findings in adult T cell lymphoma/leukemia
Multilobular nuclei in CD4 cells, usually in the shape of “flower or cloverleaf” shape
72
In AML that develops de novo in younger adults will have which translocations
Balance translocations of:
- t(8;21)
- t(15;17)
- inv(16)
73
What are the genetic abnormalities seen in essential thrombocytosis
- JAK2 (50% of cases)
- MPL (5-10%)
*most have mutations in calreticulin
74
What is the association between EBV and the modular sclerosing variant of Hodgkin lymphoma
None
75
What is leukocytosis
Increased number of white blood cells in the blood
76
In addition to adult T cell lymphoma/leukemia, what condition are patients with HTLV-1 at risk for
-progressive Demyelinating disease of the CNS and spinal cord
77
A patient with B-ALL will present with which clinical features
- lymphadenopathy
- Splenomegaly
- Bone pain
- hepatomegaly
- testicular enlargement
78
What are the complications that can be seen and fatal to a patient with primary myelofibrosis
- intercurrent infections
- thrombotic episodes
- bleeding with platlet abnormalities
- transformation to AML (5-20%)
79
Which cells are considered to be colony forming units
All cells from the myeloid lineage, which are all but NK, T and B cells
80
What are the most common genetic abnormalities in chronic lymphocytic leukemia (CLL)
```
*Translocations are rarem but
deletions of:
-13q14.3
-11q
-17p
Trisomy of 12q
Gain of fucntion in NOTCH 1
```
81
What are the immunofactors that are found on the cells in chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL)
Pan B cell markers, which are CD, 5, CD19, CD20, CD23
82
What are the clinical features of unspecified T cell lymphoma
-Lymphadenopathy with eosinophilic, pruritis, fever, weight loss
83
Which virus is implicated in the production of a malignancy that presents as a malignant infusion in the pleural cavity
HHV8
84
What are the factors that can cause the leukocytosis via the mechanism of decreased extravasation in tissues
-Glucocorticoids
85
What is the cell of origin in Mycosis fungoides/Sezary syndrome
CD4 cells that hone to the skin
86
Which more serious condition can PCV develop into
- ALL is very rare
| - AML in 2%
87
What is the prognosis of diffuse large B cell lymphoma
Aggressive tumors that are fatal without treatment:
| -intensive chemo has a 60-80% of complete remission with 40-50% cured
88
Which form of multiple myeloma is associated with a poorer prognosis
TP53
89
Which mutations in small amounts of MDS that are associated with a bad prognosis
TP53
90
IN normal adults, what is the ration of fat cells to the hematopoietic elements, and how does this ration change in disease states
Normal 1:1
Hypoplasia states: more fat cells
Tumors: less fat cells
91
What are the clinical causes of death in multiple myeloma
- Recurrent bacterial infections
| - Renal insufficiency
92
Which blasts ahve a delicate nuclear chromatin, two to four nucleoli, and more voluminous cytoplasm
Myeloblasts
93
Which conditions increase the risk for a splenic rupture
- infectious mononucleosis
- malaria
- typhoid fever
- lymphoid neoplasms
*due to the rapid increased size of spleen resulting in thinning of the capsule
94
What is the characteristic feature of follicular lymphomas
Devoid of any apoptotic B cells (due to the hover expression of the survival molecule BCL2
95
Where do marginal zone lymphomas arise from
LNs, spleen, or Extranodal tissues, usually in the case of chronic inflammation
96
What are the immunomarkers in the case of nonclassic Hodgkin lymphoma
Positive for CD19,20, BCL6
| Negative for CD15, 30,
97
What is the clinical presentation of nodular slcerosing variant of Hodgkin lymphoma
- stage 1 or 2 disease
- Mediastinal involvement
- most patients young adults, M=F
98
What is the common genetic even in all of Hodgkin’s lymphoma
Activation of the NFKB pathway
99
What is the characteristics of the lymphadenopathy seen in Hodgkin lymphoma
Painless
100
What is the peak age for acute myeloid leukemia (AML)
60 years old
101
What is the prognosis for AML with mutation in t(15;17)-RARA
Intermediate
102
What is the significance of increased number of light chains in the process of the plasma cell tumors
-Light chains, known as Bence-Jones proteins, are excreted in the urine
103
What is the most common plasma cell, especially occurring in older patients
Monoclonal gammopathy of uncertain significance (MGUS)
104
Most common AML in patients with Down syndrome and which morphology findings are common
AML with megakaryocytes maturation with detection of Abs against GIIb/IIa or vWF (megakaryocytes specific markers), commonly have marrow fibrosis
105
Which factors are upregulated in the cause of marginal zone lymphomas
BCL10 and MALT1
106
What is meant by the term pluripotency
Ability to become any of the mature cells in the blood
107
What is the clinical presentation of multiple myeloma
- Lytic bone lesions
- Hypercalcemia
- Renal failure
- immune abnormalities
108
What are the organisms patients with agranulocytosis are at a high risk of contracting
- Candida
| - Aspergillus
109
When do blood cell progenitors first appear and from which location
Yolk sac in the third week of gestation development
110
What is the true about anaplastic large cell lymphoma to have a poor prognosis
Lack of ALK gene, seen in older populations
111
What is the state of the capsule in a thymoma
Capsules are present, although can be penetrated in 25% of the time
112
Which genetic abnormality in follicular lymphoma is commonly seen
t(14;18), leading to overexpression of BCL2
- 14=IgH location
- 18= BCL2 location
113
What is the organ order of disease in Hodgkin lymphoma
1) Nodal Disease
2) Splenic disease
3) hepatic disease
4) marrow and other tissues
114
What is the condition of leukoerythroblasosis
Distortion of the marrow architecture that cause the immature release of precursors in to the blood
115
Which characteristic of chronic lymphocytic leukemia will follow a more aggressive course
-unmutated Ig segments
116
Which genetic abnormalities are associated with a better prognosis in multiple myeloma
-cyclin D1
117
What are the histological findings in the cause of Burkitt’s lymphoma
- High mitotic index, with numerous apoptotic cells
| - High rate of apoptotic cells leads to macrophage engulfment and the “starry sky” appearance
118
What is the time frame that drug induced MDS, myelodysplastic syndrome arise (also known as t-MDS)
2 to 8 years later
119
When might a marginal zone lymphoma regress
Upon removal of the pathogen or inflammation, as in the case of antibiotics to treat H pylori
120
Which form of AML as the best prognosis and what is the reasoning
T(11;15) because of treatment with all trans retinoic acid and arsenic salts
121
Adult T cell lymphoma/leukemia has what genetic abnormalities
Tax, which activates NFKB
122
What is the progression of disease in Mycosis fungoides/Sezary syndrome
1) Premycotic phase
2) plaque phase
3) tumor phase
123
Which from of myelodysplatic syndromes progresses to AML at the highest frequency
t-MDS, as drug induced MDS
124
What are the features of a reactive hyperplasia that is non neoplastic
1) Preservation of the LN architecture
2) Marked variation of the shape and size of the follicles
3) frequent mitotic figures, phagocytic macrophages with recognizable light and dark zones
125
What is the prognosis of Mycosis fungoides/Sezary syndrome and what is the usually the fatal event
Indolent tumors, with the progression to Agressive T cell lymphoma being the terminal event
126
What is the amino acid substitution in the case of polycythemia Vera (PCV)
Valine to phenylalanine at 617
127
What is the association between EBV and the lymphocytic depleted variant of Hodgkin lymphoma
90%
128
What is the general prognosis in the cause of Hodgkin’s lymphoma
Good
129
What is the prognosis of chronic lymphocytic leukemia (CLL)
Depends on the clinical stage of the disease
130
AMLs in older adults tend to have which genetic abnormalities as what is the prognosis
-deletions of 5q or 7q and are bad prognosis
131
What is the most common cancer of children
Acute lymphoblastic leukemias/lymphomas (ALLs)
132
What are the clinical features of an Extranodal NK/T cell lymphoma
- Destructive nasopharyngeal mass, with less commonly in testis and skin
- Causes ischemic necrosis
133
Which patient population is hairy cell leukemia seen
Middle aged white males (5:1)
134
In those patients that received alkylating agents for Hodgkin lymphoma were at higher risk to develop what conditions
Acute myeloid leukemia
135
What are the histological features of classic Reed-steinburg cells
-Large cells with multiple nuclei or single nucleus with multiple nuclear lobes. Each with a large inclusion like nucleolus about the size of a small lymphocytes
136
Univocal unsystematic Langerhans cell histiocytosis primarily affects which location
Skeletal system
137
What are tertiary lymphoid organs
Chronic immune reactions that cause the appearance of organized collections of immune cells in non lymphoid tissue
138
What are the common causes of eosinophilic leukocytosis
- Allergic disorders (asthma, hay fever, etc)
- Parasitic
- autoimmune
- Atheroembolic disease
139
What form of Reed stein burg cells are present in mixed cellularity variant of Hodgkin lymphoma
Mononuclear RS cells
140
Which cells are nonspecific esterase positive
Monoblasts
141
What is the most common cause of agranulocytosis
Drug toxicity
142
What are the two most common translocations in the cause of AML
1) t(8;22)- RUNX1
2) inv(16)- CBFB
*blocking the maturation of myeloid development
143
What is the prognosis of Burkitt’s lymphoma
Very agressive but responds well to treatment
144
What is the diagnosis in a patient that has LNs with:
-infiltrate of small lymphocytes with round to irregular nuclei, condensed chromatin, and scant cytoplasm with admired lymphocytes that batter in loose aggregates
Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL)
*What is described is a proliferation center, and is pathogonomic
145
What are the surface markers of hairy cell leukemia
- CD19,CD20
| - CD11c, CD25, CD103, annexin A1
146
What is the most common aneuploidy seen in myeloid cancers
MYC on chromosome 8
| RPS14 on chromosome 5q
147
What are patients with polycythemia Vera (PCV) at highest risk for
Hyperviscosity of blood
Thrombocytosis
Abnormal platlets
*all leading to thrombosis and bleeding
148
In Hodgkin’s lymphoma, what is the cell of origin
Germinal B cells
149
What is the hallmark of primary myelofibrosis
Development of obliterative marrow fibrosis
150
What is the causes of congestive splenomegaly
Chronic venous outflow obstruction, usually seen due to:
- Cirrhosis of the liver
- Portal or splenic vein thrombosis
- cardiac failure
*all lead to portal or splenic hypertension
151
What is the meaning of leukopenia
Deficiency of leukocytes
152
What is the lymphocyte count that is required to diagnose chronic lymphocytic leukemia (CLL)
>5000 per mm
153
What is the age group that myelodysplastic syndrome mostly affects
Older adults around 70 years old
154
Which histological stain is helpful in the distinction between lymphoblastic and myeloblast
Lymphoblasts are myeloperoxidase negative and contain periodic acid-Schaffer’s positive cytoplasmic material
155
What are the histological features of mononuclear variant Reed-steinburg cells
Large cells with a single nucleus with a large inclusion like nucleolus
156
What is the genetic abnormality seen in langerhans cell histiocytosis
-valine to glutamate substitution at the BRAF gene (commonly seen in hairy cell leukemia as well and seems to be present in this disease 55-60% of the time)
157
Mantle cell lymphoma are of which cell type
Mantle zone B cells
158
What are the factors that indicate a good prognosis with ALL
- 2-10 years of age
- low white count
- hyperdiploidy
- trisomy of 4,7,10,
- t(12;21)
- t(9;22)
159
T-ALLs have which genetic mutation
gain of function in NOTCH1 (70%)
160
What are the two cell types seen morphologically in follicular lymphoma and which is more common
1) Small cells with irregular or cleaved nuclear contours and scant cytoplasms known as centrocytes*** more common
2) Large cells with open nuclear chromatin, several nuclei, modest cytoplasm known as centroblasts
161
How does an acute viral infection result in lymphopenia
The production of type 1 interferons causes the sequestration of T cells into the LNs and increased adherence to vessel walls as a result of changes the adhesion molecules on the T cells
162
What are the clinical features of chronic lymphocytic leukemia (CLL)
Usually asymptomatic, but when they do present
- Lymphadenopathy, hepatosplenomegaly
- hypogammaglobulinemia
- Increased risk for infection
163
Chromosome 13 deletions in chronic lymphocytic leukemia (CLL) are indicated with changes in which factors
Micro-RNAs of miR-15a, miR-16-1
164
What is the characteristic histological feature in the cause of Langerhans histiocytosis
Birbeck granules, which are pentaluminal tubules, which often have a dilated end that looks like a tennis racket (contains langerin)
165
During the blast crisis of chronic Myeloproliferative leukemia (CML), what is the genetic abnormality
Mutations that mess up Ikaros, the transcription factors, similar to the B-ALL leukemias
166
Where do the majority of megakaryocytes reside and what do they produce
Resides next to sinusoids in bone marrow,and produce platelets
167
What are the clinal features of essential thrombocytosis
Elevated platlets, but no polycythemia or myelofibrosis
168
What are the immunofactors in multiple myeloma
- CD138, aka an Adhesion molecule known as syndicate-1
| - CD56
169
Polycythemia Vera (PCV) shows which clinical features
Increased marrow production of:
- RBCs
- Granulocytes
- Platlets
170
Which patients are seen to have chronic lymphocytic leukemia (CLL)
60 year old male
171
The genetic abnormality in anaplastic T large lymphoma results in what
ALK gene causes constitutively activated tyrosine kinase
172
How do 2/3 of non-Hodgkin lymphomas all of Hodgkin lymphomas present
Enlarged, nontender LNs
173
All cases of lymphoplasmacytic lymphoma involve mutations of which factor
MYD88
174
What are patients with hairy cell leukemia at a higher rate for
Infection, especially atypical mycobacterium
175
What is a serious side effect of the viscosity of the blood seen in PCV patients
- Plethoras and cyanosis due to the stagnation and deoxygenation of blood in the peripheral vessels
- Budd chiari syndrome (thrombosis of hepatic vein), portal vein and mesenteric vein, all leading to potential bowel ischemia
176
What is the association between EBV and the mixed cellularity variant of Hodgkin lymphoma
70%
177
What is the clinical presentation of lymphocyte predominant variant of Hodgkin lymphoma
Young males with cervical or axillary lymphadenopathy, mediastinal
178
What is the triad of felty syndrome and what condition is commonly seen to be the underlying cause
Triad:
RA, splenomegaly, neutropenia
-Usually have large granular lymphocytic leukemia as the underlining cause
179
What are the factors that can cause the leukocytosis via the mechanism of increased release from the marrow stores
- Endotoxemia
- infection
- Hypoxia
180
AML arising following treatment with topoisomerase inhibitors commonly have which genetic abnormalities
Translocation of MLL gene on 11q23
181
What are the typical protein findings in the case of multiple myeloma
- Increased IgG, Kappa light chain
| - Decreased lambda ligh chain levels
182
Which genetic abnormalities are commonly seen in MDS and tMDS
- monosomies 5 and 7
- deletions of 5q, 7q, 20q,
- trisomy 8
183
Stem cell leukemia is due to which mutation
FGFR1 fusions
184
Which infections are AML patients prone to
Pseudomomnas, fungi and commensal
185
What is the diagnostic feature of the Nodular sclerosing variant of Hodgkin lymphoma
-Collagen depositions in bands that divide the LNs into circumscribed nodules
186
What are the two variations of large granular lymphocytic leukemia and what are their immunomarkers
T cells variant: CD3 pos, CD56 neg
| NK variant: CD56 pos, CD3 neg
187
Other the LN involvment, what other locations are seen to be affected in follicular lymphoma and what pattern is seen there
- Bone marrow involvement, showing paratrabecular lymphoid aggregates
- splenic white and hepatic portal triads
188
How do the B and T cell acute lymphoblastic leukemias present
B cells: childhood acute leukemias
| T cells: adolescent male lymphomas
189
What is the result of MYC translocations
A progrowth mutation:
- Increased cell division
- Warburg effect
190
What are the factors that are present on the stem cells
CKIT+
Sac-1+
LIN-
191
What is the prognosis of adult T cell lymphoma
Very bad, fatal in a year despite chemo
192
What is the prognosis of multifocal multisystem langerhans cell histiocytosis
With intensive chemotherapy, 50% survive
193
Late stage and highly aggressive forms of multiple myeloma are associated with which genetic abnormality
MYC
194
What form of Reed stein burg cells are present in lymphocytic predominant variant of Hodgkin lymphoma
-L and H RS cells
195
In addition to BCL2, follicular lymphomas commonly express which gene
MLL2, which is a histone methyltransferase
196
What condition will have “smudge cells”, which are cells that were disrupted in the process of the smear
Chronic lymphocytic leukemia (CLL)/ Small lymphocytic lymphoma (SLL)
*looks like a cell exploded almost
197
What are the immunomarkers in the cause of langerhans cells histiocytosis
HLA-DR, S100, CD1a
198
What is the characteristic histiological finding in chronic Myeloproliferative leukemia
Presence of macrophages with abundant wrinkled, green-blue cytoplasm so called sea blue histiocytes
199
What is the prognosis of Extranodal NK/T cell lymphomas
aggressive and depends on the stage of the disease, as it responds well to ration but not to chemo
200
In those patients with hemophagocytic lymphohistiocytosis that survive, what other affects are seen
- Renal damage in adults
| - Growth and mental retardation in children
201
What are the major complications seen in the case of essential thrombocytosis
-Thrombosis and hemorrhage due to dysfunctional platelets
202
What is the histological finding in anaplastic large cel lymphoma
-hallmark “horseshoe cells” which are horseshoe nuclei with voluminous cytoplasms
203
What are the factors that can cause the leukocytosis via the mechanism of increased production in the marrow
- Chronic infection/inflammation
- Paraneoplastic
- Myeloproliferative disorders
204
Which immuno markers are present in follicular lymphomas
-CD10, CD19, CD20, BCL6
205
Acute lymoblastic leukemia/lymphoma are mainly composed of which cells
Premature B cells (85%) with the remainder of premature T cells
206
Invasive thymomas have which characteristic
- cytologically benign but locally invasive, with propensity to metastasize
* by definition, they penetrate the capsule
207
What factors correlate with a worse outcome in patients with chronic lymphocytic leukemia (CLL)
- deletions of 11q and 17p
- lack of somatic hypermutation
- ZAP-70
- NOTCH 1
208
What is the location of disease in Mycosis fungoides/Sezary syndrome
- epidermis and upper dermis in early disease
| - Bone marrow and LNs
209
Which patients are seen to have adult T cell leukemia/lymphoma
Only those with HTLV-1 (retrovirus that infects CD4 cells)
| -Commonly in southern Japan, West Africa, Caribbean basin
210
During the accelerated phase of chronic myeloproliferative leukemia (CML) which genetic abnormalities arise
- Trisomies 8
- Isochromosome 17q
- duplication of the Philadelphia translocation
211
What is the prognosis for AML with mutation in inv(16)-CBFB
Good
212
What cell origin in marginal zone lymphomas
Memory B cells
213
What are the common features of all forms of Hemophagocytic lymphohistiocytosis (HLH)
Reactive reaction:
1) Activation of macrophages and CD8 cytotoxic T cells
2) Proinflammatory cytokine “stew”
3) Suppression of hematopoiesis and cytopenias
4) Shock or cytokine storm
214
What is the prognosis of patients with unifocal or multifocal unisystem langerhans cell histiocytosis
Good, as there are tendencies to self regression
215
What is systemic mastiocytosis
The mass production of mast cells, which are located throughout the tissues
216
What are the clinical presentations of AML
Fatigue, fever, spontaneous mucosal, cutaneous bleeding:
- thrombocytopenia
- anemia
- neutropenia
217
What is the prognosis of ALL
Very good, with 95% remission and 75-85% cured
218
IN the cause of Burkitt’s lymphoma, what histological finding would indicate involvement of the bone marrow
-tumor cells with slightly clumped nuclear chromatin, 2-5 distinct nucleoli, royal blue cytoplasm containing clear cytoplasmic vacuoles
219
Most lymphoid neoplasms are of which origin
B cell origin (85-90%), with T cells making up the majority of the remainder
220
What is rouleaux formation and which condition is it present in
-High levels of M proteins in multiple myeloma causes red cells in peripheral blood smears to stick to one another in linear arrays
221
Where do the majority of red blood cell precursors reside
Surrounds macrophages (aka nurse cells) which provide the iron for the production of hemoglobin
222
B-ALLs have which genetic mutation
- Loss of function in PAX5, E2A, EBF
| - t(12;21), ETV6 and RUNX1
223
AMLs that arise due to DNA damaging agents, commonly used to treat myelodysplastic syndrome have which genetic abnormalities
deletions or monosomies of:
- 5q
- 7q
224
What is the risk factor in patients with follicular lymphoma
Development into diffuse Large B cell lymphoma (30-50%)
225
What is the clinical presentation of Burkitt’s lymphoma
Extranodal sites
- Endemic: mass in the mandible, the abdominal viscera, especially the kidneys, ovaries, adrenal gland
- Sporadic: illeocecum and peritoneum
226
What are the histological characteristics of the L and H variant of Reed Steinberg cells
“Popcorn cell” with multilobular nucleus
227
What is the level of neutropenia that puts a patient at a high risk of developing an infection
-500 per mm3
228
Which form of Hodgkin’s lymphoma is differently than the others
-Lymphocyte predominate has a abnormal Reed-Sternberg cells
229
Which blasts have folded or lobulated nuclei, Lack Auer rods, and are nonspecific esterase positive
Monoblasts
230
Which three viruses are implicated in the increased risk of lymphomas
- EBV
- human T cell leukemia virus (HTLV-1)
- Karposi (HHV-8)
231
What gene product is affected in AML with a translocation of t(11q23;v)
MLL
232
Which form of AML tends to exacerbate the bleeding tendencies
T(11;15)
233
What is the diagnosis of AML based on
Presence of at least 20% blasts in the bone marrow
234
Which age group is commonly seen to develop diffuse large B cell lymphoma
60 year old adults
235
How do patients with lymphoplasmacytic lymphoma present clinically
- lymphadenopathy
- Hepatomegaly
- Splenomegaly
236
What is the durability of CML
There is not one, the BCR inhibitors can help to reduce the load, but the “stem cell” is not hit, therefore incurable
237
What is the characteristic of marginal zone lymphomas on its ability to spread
Tend to stay localized from some time, spreading only late in the course
238
What is the prognosis of chronic lymphocytic leukemia where there is the development of a rapidly enlarging mass writhing the lymph node or spleen
Very bad (<1 year), and is due to the transformation into the large diffuse B cell lymphoma known as Richter syndrome
239
What genetic abnormalities are seen in hairy cell leukemia
BRAF serine/threonine kinase, particular a valine to glutamate a residue 600
240
In the case of polycythemia Vera (PCV) that has two mutated copies of JAK2, which clinical events are seen
- Higher white cell count
- More splenomegaly
- symptomatic pruritis
- Greater rate of progression to the spent phase
241
IN the case of large granular lymphocytic leukemia, what does the prognosis depend on
- T cells variant are more indolent
| - NK variant is more aggressive
242
IN the cause of diffuse Large B cell lymphoma, what is seen in pimrary effusion lymphoma and what is the cause
The cause is HV8 from Karposi sarcoma causing:
| -Malignant pleural or ascitic effusion
243
What do mutations in BCR-ABL cause
Proliferation of granulocytic and megakaryocytes progenitors, along with the release of immature ones from the marrow
244
What is the mutation seen in primary myelofibrosis
JAK2 (50%)
MPL (1-5%)
*mutations in calrectulin as well)
245
What increased cell is seen in during a boretella pertussis Infection
-Lymphocytosis
246
Which genetic abnormalities are associated with a worse prognosis in multiple myeloma
- deletions of 13q
- Deletions of 17p
- translocation of t(4;14)
247
What are the presenting features of hemophagocytic lymphohistiocytosis (HLH)
- Splenomegaly and hepatomegaly
- Anemia
- Thrombocytopenia
- High levels of plasma ferritin
- soluble IL-2
248
What age group is affected with eh multifocal multisystem Langerhand cell histiocytosis
Aka Letterer-Size disease
Children
249
What is the location of a tertiary organ in the cause of H. Pylori
-mucosal lymphcytes in the Payer’s patches
250
When and where hematopoietic stem cells first appear
Several weeks after the appearance of the cell progenitors, arising from the mesoderm of the intraembryonic aorta, gonad, mesonephric regions
251
What form of Reed stein burg cells are present in Lymohocytic depleted variant of Hodgkin lymphoma
Reticular/pleomorphic RS cells
252
What is the cell type present in noninvasive thymomas
Medullary like epithelial cells or a mixture of medulla and cortical cells
253
Acute lymphadenitis of the cervical region is due to drainage of which area
Infections of the teeth of tonsils
254
What are the immunomarkers in Extranodal NK/T cell lymphoma
- CD21 and CD3 neg (no TCR)
| - NK Type markers (CD56 positive)
255
What are the histological features of an invasive thymoma
- Cortical variety
- abundant cytoplasm
- rounded vesicular nuclei
256
How can a myeloblast be differentiated from lymphoblastic tumors
Lymphoblastic have:
- more condensed chromatin
- less clear nucleoli
- small amounts of cytoplasms that lack granules
257
What are the common causes of basophilic leukocytosis
-Rare, but commonly a sign on Myeloproliferative disease
258
What are the histological findings in myelodysplastic syndromes
- Ring sideroblasts (iron ladened macros)
- megaloblastoid maturation
- nuclear budding abnormalities (nuclei with misshapen and polyploid outlines
- Neutrophils with decreased granules (aka Dohle bodies)
- Pseudo-Pelger-Huey cells (neutrophils with two nuclear lobes
259
What is the histological finding of peripheral T cell lymphoma
Spectrum of small, intermediate, and large lymphoid cells, usually with irregular nuclear contours
260
What is the association between EBV and the lymphocytic dominant variant of Hodgkin lymphoma
None
261
What is the immunomarker in the cause of anaplastic large cell lymphoma
CD30
262
What is hand-Schuyler-Christian syndrome
- Calvarial bone defects
- diabetes insipidus
- exopthalamos
263
Acute lymphadenitis of the axillary region is due to drainage of which area
Infections of the extremities
264
A patient with T-ALL will present with which clinical features
- mediastinal thymic masses causing vessel compression
- lymphadenopathy
- Splenomegaly
- Bone pain
- hepatomegaly
- testicular enlargement
265
What are the immune receptors seen in diffuse large B cell lymphoma
CD19, CD20, Ig receptors
266
What is the morphological appearance of toxic granules and when are the commonly seen
-Seen in leukocytosis, and appear as coarser and darker than normal granules
267
In the case of multiple myeloma secreting IgA and IgG, what complications arise
Increased viscosity
268
The familial forms of hemophagocytic lymphhistiocytosis (HLH) are associated with which central defect
Dysfunction in the ability of cytotoxic T cells and NK cells to form or deploy cytotoxic granules
269
What is the first symptom commonly seen in chronic Myeloproliferative leukemia (CML)
Dragging sensation in the abdomen, commonly due to splenomegaly or acute onset of pain in the upper right quadrant due to splenic infarct
270
What is the effect of splenomegaly on the neutrophil count
Results in neutropenia as a result of increased sequestration
271
Hairy cell leukemia is of which cell origin
Memory B cell
272
What are the most common locations for there to be an emboli lodging
Spleen, kidney, brain
273
What is the prognosis of hemophagocytic lymphohistiocytosis
Grim without treatment, particularly if they have the familial form
274
Which two common conditions place patients at an increased risk of childhood leukemia
- Down syndrome (trisomy 21)
| - Type 1 neurofibromatosis
275
What is the result of result of sulfonamides on neutrophils and what is the mechanism of actions
-Agranulocytosis as a result of antibody mediated destructions of the mature neutrophils
276
What is the clinical presentation of mixed cellularity variant of Hodgkin lymphoma
- Stage 3 or 4
- M>F
- peaks in young adults and older than 55
- Weightloss, night sweats, fever
277
IN the cause of diffuse large B cell lymphomas, what are two pathogens that can cause it
- EBV in the case of immunodefiecncy
| - HHV8 (Karposi) that causes primary effusion lymphoma,
278
In those patients that received radiation for Hodgkin lymphoma were at higher risk to develop what conditions
- Lung cancer
- Melanoma
- breast cancer
279
Which patient population is seen to develop mantle cell lymphoma
50-60 year old males
280
What pathogenesis is associated with Extranodal NK/T cell lymphoma
EBV
281
What is true about anaplastic large cell lymphoma to have a good prognosis
ALK positive, usually seen in children and young adults
282
Where does anaplastic large cell lymphoma congregate
Around venules and infiltrate lymphoid sinuses, which can mimic metastatic carcinoma
283
What is the dominant clinical feature in the cause of multifocal multisystem langerhand cell histiocytosis
- Cutaneous lesions that resemble a seborrheic rupture, which are infiltrates of langerhans cells over the front of the back trunk and scalp
- anemia, thrombocytopenia, recurrent infections, otitis media, mastoiditis
284
How does the characteristic of hairy cell leukemia affect its ability to be aspirated
-Stuck in a extracellular matrix of reticulin fibers, so produces a “dry tap”
285
What is the prognosis for AML with mutation in t(11q23;v)-MLL
Poor
286
What is the cellularity in the cause of agranulocytosis in the cause of the drugs that suppress or destroy the granulocyte precursors
Hypocellularity
287
What are the factors that can cause the leukocytosis via the mechanism of decreased margination
- Exercise
| - Catecholamines
288
What are the common morphological features of diffuse large B cell lymphoma
Large cell size with a diffuse pattern of growth
| -Large nuclei, open chromatin, Prominent nucleoli
289
Paracortical hyperplasia is the result of which immune response
T cell mediated
290
What is the genetic abnormality that is seen in Burkitt Lymphoma
-MYC
291
Which LNs tend to be involved in the modular sclerosing variant of Hodgkin lymphoma
Lower cervical, supraclavicular, and mediastinal LNs
292
What is the most common NHL
Diffuse large B cell lymphomas (DLBCL)
293
What is Waldenstrom macroglobulinemia
Syndrome where the high levels of IgM leads to the high viscosity of blood
294
What are the features of solitary myeloma
-almost inevitably progresses to multiple myeloma in 10-20 years
295
What is usually the level or erythropoietin in polycythemia Vera (PCV)
Low, because the levels of RBCs are high
296
What is the cell of origin in adult T cell leukemia/lymphoma
CD4 cells
297
The “stary sky” appearance is indicative of which kind of general conditions
-rapidly growing lymphoid tissues as macrophages ingest apoptotic tumor cells
298
What is the morphology of the multiple myeloma tumors
-Soft, gelatinous, red mass with bone lesions with punched out defects
299
What is the genetic abnormality seen in polycythemia Vera
JAK2
300
What is the chromosomal abnormality in anaplastic large cell lymphoma
ALK gene on 2p23
301
What is the blood count finding that is indicative of chronic Myeloproliferative leukemia (CML)
Leukocytosis with >100,000 cells/mm3
302
What is the pattern of disease in Hodgkin’s lymphoma
- Starts in a single or chain of LNs
| - Spreads contiguous fashion, going to the anatomically next LN
303
What is the classical definition of an acute myeloid leukemia
-Accumulation of Immature myeloid cells (blasts) in the bone marrow that suppresses normal hematopoiesis
304
Lymphoplasmacytic lymphoma has which immune markers
-CD20 and surface Ig
305
What are the clinical features seen in primary myelofibrosis
-Marrow is replaced by fibrosis, leading to cytopenias and extramedulary hematopoiesis
306
What is the result of chlorpromazine and phenothiazines on neutrophil counts, and what is the mechanism of action
Agranulocytosis due to a toxic effect on the granulocytic precursors in the bone marrow
307
What is the age group commonly seen to be infected with chronic Myeloproliferative leukemia (CML)
Adults
308
What is the underlying pathology of Burkitt’s lymphoma with regards to pathogens
EBV
309
Which condition is commonly seen to have erythromelalgia
Essential thrombosis (ET), and polycythemia Vera
*which is a burning feeling in the hands and feet due to occlusion of the small arteries by pellet aggregations
310
What are the morphology changes seen in mantle cell lymphoma
- deeply cleave nuclear contours
| - irregular nuclear outlines, condensed chromatin, scant cytoplasm
311
What is the gene product affected in AML translocation t(15;17)
RARA (retinoic Acid receptor alpha) fuses with PML
*Commonly has a mutation in FLT3 as well
312
Pulmonary langerhans cell histiocytosis develops in which patients.
Smokers, usually with BRAF mutations
313
What conditions do patients with myelodysplastic syndromes show and what is the reasoning
Shows peripheral blood cytopenias, due to the abnormal cells remaining in the bone marrow
314
Emboli that lodge in the spleen are most often coming from which source
The heart, commonly due to endocarditis of the mitral or aortic valves
315
Which of the factors that cause leukocytosis via increased production in the marrow are growth factor independent
-Myeloproliferative disorders
316
What is the treatment of ALL with the t(9;22) and what is the prognosis
- chemo in addition of TK inhibitor, as (9;22) creates a BCR-ABL tyrosine kinase that is overly active
- An Increased effectiveness in treatment
317
What are the typical characteristics of lesions seen due to infection in a patients with agranulocytosis
- Ulcerating necrotizing lesions of the gingeva, mouth (floor, roof, buccal, pharynx)
- Deep undermined lesions covered by grey to green-black necrotic membranes
318
Which factors of ALL imply a poorer outcome
- Younger than age two, because associated with MLL gene
- Adolescentas and adulthood presentation
- blast count in the blood >100,000
319
What is the best method for the assessment of the morphology of the hematopoietic cells
Marrow aspirate smears
320
What is the relation in timing of antigen receptor rearrangements and malignancy
-Rearrangement generally precedes the malignancy, so all daughter cells share the same antigen receptor gene configuration
321
What is the most common from of Hodgkin lymphoma
Nodular Sclerosing Type
322
Which condition can increase the risk of chronic lymphocytic leukemia
congenital X linked agammaglobulinemia, as both has dysfunction in the BTK proteins
323
What is the fastest growing tumor
Burkitt’s lymphoma
324
What is the most common leukemia of adults in the western world
Chronic lymphocytic leukemia (CLL)
325
What is the association between EBV and the lymphocytic rich variant of Hodgkin lymphoma
40%
326
What are the clinical manifestations of hairy cell leukemia
- Splenomegaly
- Hepatomegaly
- pancytopenia (due to splenic sequestration)
327
What form of Reed stein burg cells are present in lymohocytic risk variant of Hodgkin lymphoma
Mononuclear RS cells
328
What is the clinical features of Sezary syndrome
-skin involvment as generalized exfoliating erythroderma, rarely forming a tumor, but can have the leukemia
329
What are the Extranodal sites in diffuse large B cell lymphoma that are seen
-GI, skin, bone, brain
330
What treatment does stem cell leukemia respond to
PKC412 therapy
331
What clinical feature can be seen lymphoplasmacytic lymphoma
- IgM production leading to hyperviscosity which is known as Waldenstrom macroglobulinemia
- secretion of red light chains and bone destruction are rare
332
What are variations in the morphology of the plasma cells in multiple myeloma
- Flame cells (red cytoplasms)
- Mott cells (multiple grapelike cytoplasmic droplets)
- Russell or Dutcher bodies (globular inclusions)
333
What are the common causes of monocytosis
- Chronic infections
- Bacterial endocarditis
- rickettsiois
- malaria
- IBD
334
What are the histological features of the lacunar Reed-steinburg cells
Delicate, folded or multilobate nuclei and abundant pale cytoplasm that is disrupted during the cuttin of sections, leaving a nucleolus in an empty hole
335
What are the genetic abnormalities seen in diffuse large B cell lymphomas (DLRBL)
- BCL6 at 13q27 (30%)
- BCL2 at t(14;18) (10%)
- MYC (5%)
336
In those patients that survive polycythemia Vera (PCV) for extended amounts of time end up showing which feature
Primary myelofibrosis with the appearance of obliterative fibrosis and extensive extra-medullary hematopoiesis (mainly the spleen)
337
What are the genetic abnormalities seen with multiple myelomas
Translation of IgH on chromosome 14 with:
- cyclin D1 on 11q13
- Cyclin D3 on 6p21
338
What is seen in the bone marrow cellularity in the case of megaloblastic anemia’s and myelodysplastic syndromes
Hypercellularity due to ineffective granulopoiesis
339
What is the mutation seen in systemic mastocytosis
KIT
340
What are the two properties of the HSC that are required
- Pluripotency
| - Sell renewal
341
What is the classical definition of myelodysplastic syndromes
Defective maturation of myeloid progenitors that gives rise to ineffective hematopoiesis, leading to cytopenias
342
What are the clinical presentations of hyperviscosity syndromes
- Visual impairment (due to venous congestion, retinal hemorrhages)
- Neurological problems (sluggish blood flow leading to headaches/dizzy)
- Bleeding (formation of complexes between macroglobulins and clotting factors that interfere with platelets
- Cyroglobulinemia (precipitation of macroglobulin at low temps leading to Raynaud)
343
What is the genetic abnormality seen in chronic myelogenous leukemia (CML)
BCR-ABL (BCR on 22, ABL on 9) resulting in constructive ABL kinase aka, the Philadelphia translocation
344
What is Bloom syndrome and which conditions are they at risk for
- Genomic instability at a higher risk for cancers and acute leukemia
- Tend to have a short stature
