Dr. Singh - Hematopathology : WBC, LN, Spleen, Thymus Flashcards
(129 cards)
1
Q
Leukocyte common Ag marker
A
CD45 (Basophils, N ,Eosinophil, Tcells, Bcells, NK cells, Moocytes)
2
Q
Early myeloblast marker
A
CD34
E, N, B
3
Q
Early Lymphblast marker
A
Tdt (T-cells, B-cells, NK cells)
4
Q
lymphocyte markers
A
CD19, CD20, Pax-5 (T-cell, B-cell)
5
Q
Natural Killer cell markers
A
CD56, CD16
6
Q
Helper T cells markers
CTL cells markers
A
CD4+
CD8+
7
Q
High myeloblast count can be a sign of
A
Acute Leukemia type
8
Q
Leukopenia
What
Most common
A
Low WBC
Neutropenia (extreme neutropenia = agranulocytosis)
9
Q
Absolute neutropenia is found how
WBC : 6.0x10^3
N : 4%
Bands : 2%
A
Absolute N Count = .06(6000) = 360
** anything under 500 is very serious
10
Q
what can cause neutropenia
A
- Toxic drugs for chemotherapy destroying bone marrow
- Aplastic anemia
- Megaloblastic anemia
- Ab mediated destruction
- Hypersplenism (spleen sequesters and destroys blood cells)
11
Q
What can happen when you have neutropenia
And how to TX
A
- Bacterial and Fungal infection
2. G-CSF (to recolonization)+ Abs
12
Q
Leukocytosis
A
Too much N
13
Q
Increased N marrow production caused by
A
Chronic infection or cancer
14
Q
Increased release of N form marrow stores
A
Acute inflammation
15
Q
Decreased Margination
A
Exercise (N unstick from vessels and enter circulation)
16
Q
Decreased extraversion into tissues
A
Glucocorticoids
17
Q
High N
High Lyphocytes
High E
High B
A
Acute bacterial infection, MI
Viral infection
Asthma, parasite, drug reactions
CML
18
Q
Germinal centers + medullary sinuses expand
A
During infection
19
Q
Acute supportive lymphadenitis
A
Painful puss filled LN usually from pyogenic infection, high neutrophils, abscess forms in LNs
20
Q
Follicular hyperplasia
A
Lymphadenitis
Many follicular areas that swell
The lymphocytes expand in the germinal center usually viral
21
Q
Organization in the LN
A
Germinal area or center and mantel area around it
22
Q
Sinus histocytosis
A
M are increased in the LN sinuses and seen usually in malignancy or drainage of foreign material - tattoo ink (they are histiocytes)
23
Q
Lymphoid neoplasia involves
A
B,T, NK, plasma cells
Hodgkin
24
Q
Myeloid neoplasia involves
A
AML
Myelodysplasia
Myeloproliferative neoplasia
25
Histiocytic neoplasia involves
Langerhans Cell Histiocytosis
26
3 things usually causing WBC neoplasia
- viral infection (HTLV, EBV, HHV-8)
- Chronic infection (H Pylori)
- Genetic mutation that’s acquired
27
Acute Lymphoblastic Leukemia/lymphoma
| SX
Fever - no Neutrophils so easy opportunistic infection
Fatigue - anemic
Bleeding and bruising - no platelets
Pain - expansion of BM from leukemic cells
N,V,Headache - meningis in brain can also have leukemic cells pack in there
28
ALL what happens
The lymphoid stem cell divide excessively into blasts and dont become mature WBCs (maturation arrest)
- BM is packed with myeloblast leukemia cells and can be hard to even draws out a BM sample
29
ALL under the microscope
Large purple cells that are lymphoblastic ($x size of RBCs)
30
How to DX ALL on peripheral smear looking at the cell markers
1. If there is TdT (prolymphocyte marker) = myeloid cells *SEEN*
2. If there is CD19, 20, 10, Pax-5 = B-cells involved *SEEN*
3. If there is CD 1-5, 7, 8 = T-cells are involved
31
How to TX ALL
Chemotherapy in CSF
Is usually very successful (age 2-10)
(12:21 transposition)
32
B-cell non-Hodgkin leukemia EXs
1. CLL
2. Follicular lymphoma
3. Diffuse large B-cell lymphoma (DLBCL)
4. Burkitt lymphoma
5. Mantel cell lymphoma
6. Marginal Zone lymphoma
7. Hairy Cell Leukemia
33
CLL/SLL
| Sx and blood smear
```
None really (usually older adults) however you can run a CBC and see some clone mature lymphocytes that are small (size of RBCs since they are mature)
They are delicate and can smudge (smudge cells seen)
```
34
CLL/SLL markers seen
1. CD19, CD5 (B-cells)
CD20
2. Look at light chains that are all the same
35
CLL/SLL prognosis
Usually fine, however can become aggressive Richter Transformation (from MYC or TP53 mutation)
36
Follicular lymphoma DX
It looks the same as Follicular Hyperplasia so you look at the cells
1. 14:18 translocation (IgH next to BCL-2)
37
Follicular Lymphoma SX
Painless B-cell proliferation and generalized lymphadenopathy
38
How to stain and see difference in Follicular lymphoma and Follicular hyperplasia
Follicular Lymphoma : granular center is stained all brown (+ stain)
Follicular hyperplasia : granular center is stained brown in marginal area only granular center is white
39
Follicular lymphoma grading scale
Grade 1 : smaller cells (more mature cells)
Grade 2 : some larger cells
Grade 3 : all larger cells (mostly immature cells)
40
DLBCL is what
LARGE Masses in LN or other organ like the spleen
| Aggressive and fast growing
41
DLBCL special types
1. Immunodeficiency - related LCL (HIV, post-transplant, or something linked to EBV)
2. Primary effusion lymphoma (HHV-8)
42
DLBCL DX how
Cells muted in BCL-6 = over expressed B cells
| You see all other B- cell markers
43
Burkitt lymphoma
Looks like
And happens how
Starry sky pattern, 99% are dividing constantly
B-cells + MANY tingible (stainable) Ms = to eat a bunch of cells and debri
(Seen with the Ki-67 stain)
44
Burkitt lymphoma from what translocation
8: 14 (IgH next to MYC)
45
3 types of Burkitt Lymphomas
1. EBV associated (Endemic in Africa, causing mandibular growth)
2. Sporadic
3. HIV-related
= can be TX well if diagnosed early
46
Mantel Cell Lymphoma is what looks like what
B- cells resembling mantle cell layer
| Small, mature, and fast dividing and aggressive
47
Mantel Cell Lymphoma TX
Aggressively and BM transplant
48
Mantel Cell Lymphoma can cause
GI mucosal involvement
| Polyps (made of lymphocytes not intestinal mucosa = lymphomatoid polyposis)
49
Mantel Cell Lymphoma translocation
11: 14 (IgH next to Cyclin D1)
50
Marginal Zone Lymphoma looks like and where
In LN or extranodal sites (MALT-oma, GI, bronchial, thyroid) ——> chronic inflammation (H PYLORi INFECTION)
51
Marginal Zone Lymphoma can be seen in what organs
CHRONIC INFLAMMATION SITES :
1. Gastric MALToma (from H- pylori) - Tx the infection and can cause it to go away
2. Hashimoto’s thyroiditis can lead to MZL
3. Chronic Sialadenitis can cause Salivary gland MZL
52
Hairy Cell Leukemia looks like what
NEoplastic B-cells that are about 2X as big as RBCs with projections that look hairy on them (very few of them)
53
How to DX HCL
Drawing out BM you usually dont get anything due to the BM fibrosis
On blood smear you see some distance between each close packed cell due to hairy cytoplasm
54
HCL can cause what SX
Fatigue
Splenomegaly (to start make cells BM cant)
Pancytopenia (very low number of cells and hard to see a hairy cell in the blood)
Anemic (no WBCs, due to hairy BM cells)
55
HCL TX
Very good with chemotherapy
56
HCL markers involved
CD 25 and CD11c
57
How to DX any B -cell lymphoma
Run a flow cytometry
58
Plasma Cell Neoplasia
| 3 kinds of it
1. Myeloma
2. Monoclonal gammopathy of uncertain significance (Mgus)
3. Waldenström macroglubulinemia
59
Plasma cells look like
Central dark purple nucleus, light blue cytoplasm, and dark blue Perinuclear Hoff around the cytoplasm
60
Myeloma causes what things
Tumor in the BM
- Lytic Ben lesions
- Hypercalcemia
- Renal failure
- Immune abnormalities
61
Monoclonal gammopathy + myeloma is can be seen on a graph as what and is what
Too much gamma seen on electrophoresis
Gamma includes many immunoglobulins
**** on looking at serum levels, there is a narrow spike in gamma region and Alb region, normal results would show only a spike at Alb = M SPIKE
62
In gammaopathy + myeloma which immunoglobulins are usually involved in excess
IgG and IgA (with K or L light chains)
63
How do we know if something is myeloma or Mgus
1. More then 60% plasmacytosis in BM = Multiple Myeloma DONE
| 2. if over 10% = you need more information (CRAB Criteria)
64
CRAB criteria
C : Calcium elevated
R : Impaired REnal function
A : Anemia
B : Bone Lesions
65
Elevated Calcium presents as and due to what
Due to osteolysis (from many plasma cells in the BM)
- altered mental status
- seizures
- cardiac rhythmic disturbances (Short QT)
- N,V, C
66
Renal Insufficiency presents as and due to what
1. From immunoglobulins that are being filtered through (Ig attach to glycoproteins Tamm Horsfall = BENCE JONES PROTEINS* in tubules) = clog tubules + damage
2. Proteinuria + light chain in urine
3. Amyloidosis : Congo red stain + apple green in glomerulus = AL amyloid in myeloma
67
Anemia presents as and due to what
From plasma cells in BM not able to make WBC
- also from IL-6 production = suppression cytokines
- renal disease = low erythropoietin made
68
Bone Lesions presents as and due to what
Can break bone and spontaneous fracture or holes in bone like skull
69
When is hyperviscosity seen
Hen you have too much immunoglobulins
70
Where can you see hyperviscosisty
Myeloma , Mgus = high IgG (monomer) or IgA (diner)= viscous
| Waldenström macroglubulinemia = high IgM a pentomer = extremely viscous
71
Hyperviscosity can cause what
| And what does it look like
Thromboembolic complications due to sticky blood
| Looks like Rouleaux formation (RBCs are sticking like coins)
72
What is another name for Waldenström macroglubulinemia
Lymphoplamacytic Lymphoma , due to this disease involves mature B cells that are wanting to differentiate to plasma cells
73
Waldenström macroglubulinemia an cause what
1. Hyperviscosity = visual impairments, stroke, embolic conditions, Cryoglobulinemia (ischemia to fingers)
2. High IgM
3. Reynolds phenomenal + Reaulux formation
74
Hodgkin lymphoma vs non-Hodgkin lymphoma
H : localized not really spreading,
| NH : many different nodes, Waldeyer ring + mesenteric nodes involved, Extranodal presentation
75
Classic Hodgkin Lymphoma you see and markers in it
1. Reed- Sternberg cells (owl eye cells) = CD 15, CD30, Pax-5 + IgH rearrangement
76
How does Classical Hodgkin lymphoma present
Localized in one area one LN and then later can spread to another area
1. Nodular sclerosis : had nodules and fibrosis around it in the LN
2. Multicellulaity : has many different cells in the LN
77
Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLP HL)
| SX
Similar to HL however histologically extremely different
78
Nodular LP HL histologically looks like and markers
Lymphohistocytic HL cells = Popcorn cells
- YES CD20
- NO CD15, CD30
79
NLP HL can transform to
DLBCL
80
How to DX HL
You have to stain and look at the cells because the Reed- Stanberg cells are very dilute and very few in the many colonal B- cells
+ CD15 and + CD30
OR
+ Popcorn cells + CD20
81
Peripheral NK/T-cell lymphomas : Anaplastic Large Cell Lymphoma
Aggressive T cell tumor form ALK tyrosine kinase gene translocation *
- usually younger patients (ALK + and good prognosis)
- some are ALK negative and older (worse prognosis)
82
Peripheral NK/T-cell lymphomas : Adult T- cell leukemia/lymphoma
Aggressive CD4+ tumor from a HTLV-1 infection
| - Cloverleaf cells in blood ****, usually seen on skin as lesions and nodules
83
Peripheral NK/T-cell lymphomas : Large granular lymphocytic leukemia
CTL T cell tumor or NK cell tumor associated with a STAT3 TF mutation + cytopenias + autoimmune phenomena
84
Peripheral NK/T-cell lymphomas : Extranodal NK/T cell lymphoma
Aggressive tumor from NK cells and linked to EBV infection
85
EBV is liked to
1. Burkitt lymphoma
2. DLBCL
3. Extra nodular NK/T cell lymphoma
86
Peripheral NK/T-cell lymphomas : Mycosis Fungoides
T-cell lymphoma presenting with skin plaque lesions that are saddle and if biopsied can be mistaken as inflammation, however is t-cell clones
NO HTLV-1 association
87
Peripheral NK/T-cell lymphomas : Sézary Syndrome
T-cell lymphoma with erythroderma (Red all over body skin rash, red man syndrome) and leukemia in blood (cerebraform cells in blood)
NO HTLV-1 association
88
Myeloid neoplasms 3 types
AML
Myelodysplastic syndromes
Myeloproliferative neoplasms
89
AML
Leukemic stem cell which makes only a bunch of blasts and prevents maturation of cells = a bunch of myeloblasts
90
AML is DX how
1. Having 20% or more BLASTS (any WBC) in the BM****
2. You can see granules in the cytoplasm at times in the blasts
3. Fever, fatigue, bleeding, bruising, PANCYOPENIA (no blasts in peripheral blood)****
91
AML with genetic aberrations
Translocation of 8:21 or 15:17
| Good prognosis
92
AML with MDS like features
First the patient has myeloid dysplasia and it becomes AML
| Poor prognosis
93
AML therapy related
Getting AML from therapy such as chemotherapy
| Poor prognosis
94
AML not otherwise specified
Other types of differentiated blasts like erythroid blasts, Megakaryocytic blasts, Monocytic blast
95
AML 8:21
| What happens
Usually younger patients
CBF makes mature cells however in this type of translocation a ETO protein + RUNX1-RUNX1T1 blocks the CBF and there is no maturation of the myoblasts
96
AML with 15:17
Is also called Acute Promelocytic Leukemia ***8
| YOU SEE AUER RODS
97
AML with 15:17 happens how
Usually RAR bind to RA and = allows differentiation to N
| In this RAR is bound by a PML protein and makes it not want RA, no differentiation to Ns
98
AML 15:17 TX
Gleevec or ALL TRANS RA which overrides the PML protein bound to the RXR
99
AML 15: 17 SX and Why when you dont have leukocytosis and panocytopenia sx
- NO leukocytosis, panocytosis at times
- YOU see HYPERCOAGABILITY (bruising and bleeding and coagulation of blood due to the myloblasts having Annexin = plasminogen -> plasmin AND activated and TF to make F10a)
100
Other unusual AML SX not involving hypercoagability or leukemia or panocytopenia
1. Extra nodular involvement of gingiva (black and red infiltration of myloblasts), and Leukemia cutis (myloblasts to skin)
2. Soft tissue masses stained +CD34 (in any part of the body)
101
Myelodysplastic Syndrome
Clonal disorder in many cell types (not one identical clone)
Usually from therapy
Can come before AML
102
Myelodysplastic Syndrome SX
Cytopenia (anemia usually)
103
Myelodysplastic Syndrome DX how
1. Which lineages are effected
2. Chromosomal translocation
3. Blast count : increased a bit (are higher risk for AML transformation)
4. You can see Dyserythropoiesis (multinucleated RBCs), Ring sideroblasts (Fe deposits), Pseudo Pelger-Huet cells (Bilobed N), Dysmegakaryopoiesis (small MK with separate lobes)
104
Looking for excess blasts in Myelodysplastic Syndrome
More then 20% = AML
| If above 10% : RAEB 2 (refractory anemia excess blast 2) , higher RAEB are more likely to become AML
105
Myelodysplastic Syndrome happen from what mutations
1. Epigenetic mutations
2. RNA splicing factor mutation
3. TF mutation
106
Myeloproliferative neoplasms mutation is what
Any kinase = proliferation
107
Myeloproliferative neoplasms SX
BM proliferated with something
The cells travel to extramedullary areas
AML or ALL can happen
108
CML SX
1. peripheral leukocytosis of mature myeloid cells high number of cells in BM
2. Splenomegaly (extrameduallary hematopoiesis)
3. Higher Buffy coat
4.
109
CML translocation
Philadelphia chr (9:22) = activated a kinase BCR-ABL
110
What can you see when testing for CML
**** Increased buff coat in blood that is centrifuged (higher WBCs)
111
Higher Buffy coat in blood means
Leukemia
112
Wha happens to CML over time
If there is a lot of leukocytosis then viscosity can increase and mutations can happen and cause increased blasts = AML or ALL
113
4 types of Myeloproliferative neoplasms
1. CML : WBCs
2. Polycythemia Vera : RBCs
3. Essential thrombocythemia : platelets
4. Primary myelofibrosis : stroma fibroblasts
2-4 are increased in JAK2 Kinase**
114
What happens during myelofibrosis
Can happen as the end stage of Myeloproliferative neoplasms 2-4
- low BM elements due to fibrosis
= SPLENOMEGALY (JAKofy)
115
Langerhans cell histocytosis 3 types
Multi focal multisystem
Unisystem
Pulmonary (smokers
116
Langerhans cell histocytosis SX
The Langerhans cells (dendritic cells) eat away the bone = lytic lesions
2. Cleaved nuclei many of them
3. **** electronmicroscopy showed Birbeck granules (tennis-racket shaped)
4. ** many E like being there in the blood smears
117
Birbeck granules are found when
For Langerhans cell histocytosis (tennis racket shaped)
| When looking at electronmicroscopy
118
How to stain for Langerhans cell histocytosis
1. CD1a and S100 (Langerhans cells)
| 2. Many eosinophils as well
119
Important anatomy of spleen
1. Splenic A goes to it and 1 single splenic vein drains it
2. Blood opens up to the open circulation pockets
3. Germinal center (white pulp) = lymphocytes
120
Spleen function
1. Phagocytosis
2. Sequester RBCs
3. Ab production
4. Fetal and adult (if condition) hematopoiesis
121
Splenomegally what and how
1. Follicular hyperplasia in the germinal center = expands Spleen
- usually from viral infection
2. Congestive Splenomegaly from hepatic dysfunction (the 1 splenic V is blocked as it goes to the liver)
122
Hypersplenism what and how
Enlargement of spleen due to cytopenia
(Blood or spleen problem)
- Hereditary spherocytosis (stiff RBCs)
- Sickle Cell
- Idiopathic thrombocytopenia purpura : platelets are covered by opsonizing Abs
- splenomegally can cause that type of spleen dysfunction to take more RBCs
123
Splenic rupture from what and how
ABD trauma
Rapid splenomegaly (Infections Mononucleosis)
- causes Hypotension
124
Splenic Neoplasia
Usually vessel neoplasm
| Other leukemia’s can involve the spleen make nodules
125
Splenic infarcts
It grows so fast it outgrows its vascular supple it needs
| Clogged Spenic A (Sickle Cell)
126
Thymus
Very cellular in babies
| Adults is mostly fat (some squamous Hassle Corpuscle cells)
127
Thymus Hyperplasia
Increased cells start to proliferate in the thymus as an adult
Can cause MG
128
Thymoma
A tumor is in the thymus as a clonal neoplasm
- obstruct airway or esophagus is possible
- MYASTHERNIA GRAVIS
129
Myasthenia Gravis (MG)
AutoAbs from thymine hyperplasia or thyoma
| AB——> post-synaptic R for ACH = progressive weakness especially as the day goes on , SOB
