Neoplasia/Hematology - Mechanisms of Disease - Lymphomas Flashcards
(133 cards)
1
Q
What are the three ‘B symptoms’ of lymphoma?
A
- Night sweats
- Fever
- Weight loss
2
Q
What does it mean for a lymphoma to be stage I?
And stage II?
A
Only 1 lymph node involved;
≥2 lymph nodes on the same side of the diaphragm
3
Q
What does it mean for a lymphoma to be stage III?
And stage IV?
A
≥2 lymph nodes involved with involvement on both sides of the diaphragm;
metastatic disease
4
Q
What does it mean if a lymphoma is stage Ib (or stage IIb or IIIb or IVb)?
(I.e. what does the ‘b’ mean?)
A
The stage + ‘B symptoms’
(B symptoms = night sweats + fever + weight loss)
5
Q
What chemo regimen is used for Hodgkin’s lymphomas?
A
ABVD + radiotherapy
6
Q
What chemo regimen is used for non-Hodgkin’s lymphomas?
A
R-CHOP
7
Q
Reed-Sternberg cells are positive for what two CD markers in particular?
A
CD15; CD30
8
Q
What marker would be an indicator that a population of leukocytes examined under flow cytometry are blasts (immature)?
A
CD34
9
Q
What is a smudge cell?
A
Lymphocytes squished during smear preparation
10
Q
What heuristic can be used to determine what a patient’s bone marrow cellularity should be?
A
100% - their age
(E.g. a 60 year old woman would have an expected cellularity of ~40%)
11
Q
Why might you order an echocardiogram on a patient being prepared for treatment for leukemia?
A
Many chemotherapeutic drugs are cardiotoxic
12
Q
In what way can flow cytometry of light chains be used to determine if there is a monoclonal lymphoproliferation?
A
The normal 3-to-1 kappa:lambda ratio is skewed nearly 100% in one direction
(i.e. all kappa or all lambda)
13
Q
What is the most common form of leukemia?
What is the median age of diagnosis?
A
CLL
70
14
Q
What is the most common leukemia seen in children?
And adults?
A
ALL;
CLL
15
Q
What mutation is common to follicular lymphomas?
What is overexpressed because of this mutation?
A
t(14 ; 18)
Bcl-2
16
Q
Name the diseases associated with each of the following translocations:
t(8 ; 14)
t(9 ; 22)
t(14 ; 18)
t(11 ; 14)
A
Burkitt lymphoma
CML
Follicular lymphoma
Mantle cell lymphoma
17
Q
You note that a proliferation of B cells is positive for t(11 ; 14), and it is Sox-11+.
What is the likely diagnosis?
Note: it is also CD5+, CD20+, and CD23-
A
Mantle cell lymphoma
(t(11 ; 14) leads to increased cyclin-D1 expression)
18
Q
Name a few translocations associated with marginal zone lymphomas.
A
t(11 ; 18)
t(11 ; 14)
t(1 ; 14)
19
Q
You note that a proliferation of B cells is positive for t(14 ; 18), and it is CD10+.
What is the likely diagnosis?
A
Follicular lymphoma
(increased expression of Bcl-2)
20
Q
Mantle cell lymphoma is associated with the t(11 ; 14) mutation which increases cyclin-D1 expression. What effect does cyclin-D1 have on the cell?
A
Increased progression of G1 to S
(increased activation of Rb and E2F)
21
Q
What are the two basic subtypes of acute lymphocytic leukemia?
A
B cell (more common);
T cell
22
Q
Which type of ALL typically involves the bone marrow?
Which typically presents as a lymphoma of the anterior mediastinum?
A
B-ALL (more common);
T-ALL
23
Q
How/where does T cell ALL typically present?
A
Lymphoma of the anterior mediastinum
24
Q
What is the hallmark sign of acute leukemias (ALL; AML) on blood smear examination?
A
Presence of blasts
25
A 16 year old male presents with easy brusing, pallor, weakness, and vomiting. A workup reveals thrombocytopenia, anemia, and a pronounced increase in WBCs.
You note the presence of many blasts on smear.
How do you quickly differentiate between ALL and AML?
ALL --- **no Auer rods**
AML --- **Auer rods present** in blasts
26
**True/False**.
Some lymphoproliferative disorders such as CLL may be characterized by monoclonal B cells that are also found on flow cytometry to express some T cell receptors (e.g. CD5) with their B cell receptors.
True.
27
**True/False**.
CD markers below 10 are characteristic of B cells and CD markers above 10 are characteristic of T cells.
**False**.
CD markers below 10 are characteristic of **T** cells (e.g. CD1, 2, 3, 4, 5, 8) and CD markers above 10 are characteristic of **B** cells (e.g. CD19, 20, 21).
28
What are the differences between CLL, SLL, and MBL?
29
What is necessary for a diagnosis of CLL?
B cell count \> **5,000**
(lymphadenopathy / extranodal disease may or may not be present)
30
How are CLL and SLL (small lymphocytic leukemia) differentiated on blood analysis?
**CLL**: B cell count **\> 5,000** (mostly in blood and bone marrow)
**SLL**: B cell count **\<** **5,000** (mostly in lymph nodes)
31
What is necessary for a diagnosis of SLL?
B cell count \< **5,000**
+
**lymphadenopathy** / extranodal disease
32
What is necessary for a diagnosis of MBL (monoclonal B cell lymphocytosis)?
A largely elevated B cell count still **\< 5,000**
(with no lymphadenopathy or extranodal disease --- that would make it SLL)
33
Monoclonal B cell lymphocytosis is a potential precursor to what?
CLL
34
What system is used for classifying the severity of CLL?
The Rai system
35
What can cause thrombocytopenia, anemia, and an increased risk of infection in leukemia patients?
Bone marrow out-crowding by proliferating cells
36
CLL is most common in what age, race, and gender?
Older caucasian males
37
A patient is incidentally diagnosed with CLL. He is currently asymptomatic.
## Footnote
**How do you proceed?**
**Do not treat until S/Sy present**
(up to 1/3 of patients may not have significant S/Sy before death from other causes)
38
What are the two main categories of lymphoma?
Hodgkin's;
Non-Hodgkin's
39
Hodgkin's lymphoma is characterized by what cell type?
Reed-Sternberg cells
40
Lymphomas are all characterized by enlargement of what tissue type?
Lymphoid tissue
41
You suspect lymphoma in a patient with swollen lymph nodes.
What is the gold standard for diagnosis?
**Excisional biopsy**
42
How does a lymph node present when activated?
And when lymphoma is present?
**Reactive** (increase number of germinal centers);
**nodular/follicular pattern**
43
Name two methods by which malignant cells can be checked for specific surface molecules.
Flow cytometry;
immunohistochemistry
44
You identify a population of B cells on flow cytometry that are CD5+.
What condition is present?
CLL
(CD5 is normally a T cell CD marker)
45
What system is used for staging lymphomas?
The Ann Arbor system
46
What is the 5-year survival rate for Hodgkin's lymphoma?
87%
47
What is the most common type of Hodgkin's lymphoma?
How is its prognosis?
Nodular sclerosing;
good
48
What is the least common type of Hodgkin's lymphoma?
How is its prognosis?
Lymphocyte depleted;
poor
49
What CD markers are present in classical Hodgkin's lymphoma?
Which are absent?
CD**30**+ , CD**15**+
CD**20**- , CD**45**-
50
Classical Hodgkin's lymphoma makes up \_\_\_% of cases.
What type makes up the remainder?
Classical Hodgkin's lymphoma makes up **_95_**% of cases.
**nodular lymphocyte predominant** Hodgkin's lymphoma
51
Name the four main types of classical Hodgkin's lymphoma in decreasing order of frequency.
1. ________ \_\_\_\_\_\_\_\_
2. ________ \_\_\_\_\_\_\_\_
3. Lymphocyte-rich
4. Lymphocyte-depleted
1. **Nodular** **sclerosis**
2. **Mixed** **cellularity**
3. Lymphocyte-rich
4. Lymphocyte-depleted
52
Name the four main types of classical Hodgkin's lymphoma in decreasing order of frequency.
1. Nodular sclerosis
2. Mixed cellularity
3. \_\_\_\_\_\_\_\_-\_\_\_\_\_\_\_\_
4. \_\_\_\_\_\_\_\_-\_\_\_\_\_\_\_\_
1. Nodular sclerosis
2. Mixed cellularity
3. **Lymphocyte**-**rich**
4. **Lymphocyte**-**depleted**
53
Nodular lymphocyte predominant Hodgkin's lymphoma (responsible for 5% of cases) is characterized by what cell type?
Popcorn cells
54
**Reed-Sternberg cells**:
CD15\_\_ , CD20\_\_ , CD30\_\_ , CD45\_\_
**Popcorn cells**:
CD15\_\_ , CD20\_\_ , CD30\_\_ , CD45\_\_
**Reed-Sternberg cells**:
CD15**+** , CD20**-** , CD30**+** , CD45**-**
**Popcorn cells**:
CD15**-** , CD20**+** , CD30**-** , CD45**+**
55
Non-Hodgkin's lymphomas can first be divided into what two major categories?
B-cell derived;
T-cell derived
56
What are the two major categories of non-Hodgkin's B cell lymphomas?
Large cell (aggressive);
small cell (indolent)
57
Which form of leukemia can be classified as either a leukemia or a non-Hodgkin's B cell lymphoma?
CLL (/ SLL)
58
Describe the S/Sy of aggressive (large cell) Non-Hodgkin's B cell lymphomas:
\_\_\_\_\_\_\_\_\_\_ growing masses
\_\_\_\_\_\_\_\_\_\_ _____ symptoms
Elevated \_\_\_\_\_\_
\_\_\_\_\_\_\_\_\_\_ painful lymphadenopathy
Describe the S/Sy of aggressive (large cell) Non-Hodgkin's B cell lymphomas:
**_Rapidly_** growing masses
**_Systemic_** **_B_** symptoms
Elevated **_LDH_**
**_Sometimes_** painful lymphadenopathy
59
Describe the S/Sy of indolent (small cell) Non-Hodgkin's B cell lymphomas:
\_\_\_\_\_\_\_ growing masses, \_\_\_\_\_\_\_megaly, cyto\_\_\_\_\_
\_\_\_\_\_\_\_dious
pain\_\_\_ lymphadenopathy
Describe the S/Sy of indolent (small cell) Non-Hodgkin's B cell lymphomas:
**_Slowly_** growing masses, **_hepatospleno_**megaly, cyto**_penia_**
**_insi_**dious
pain**_less_** lymphadenopathy
60
These are the S/Sy of __________ (\_\_\_\_\_\_ cell) Non-Hodgkin's B cell lymphomas:
**Rapidly** growing masses
**Systemic B** symptoms
Elevated **LDH**
**Sometimes** painful lymphadenopathy
These are the S/Sy of **_aggressive_** (**_large_** cell) Non-Hodgkin's B cell lymphomas:
**Rapidly** growing masses
**Systemic B** symptoms
Elevated **LDH**
**Sometimes** painful lymphadenopathy
61
These are the S/Sy of _______ (\_\_\_\_\_\_ cell) Non-Hodgkin's B cell lymphomas:
**Slowly** growing masses, **hepatospleno**megaly, cyto**penia**
**insi**dious
pain**less** lymphadenopathy
These are the S/Sy of **_indolent_** (**_small_** cell) Non-Hodgkin's B cell lymphomas:
**Slowly** growing masses, **hepatospleno**megaly, cyto**penia**
**insi**dious
pain**less** lymphadenopathy
62
Identify which is more likely to be 'curable':
**Aggressive (large cell) non-Hodgkin's lymphomas**
or
**Indolent (small cell) non-Hodgkin's lymphomas**
**Aggressive (large cell) non-Hodgkin's lymphomas**
(presents much earlier and much more clearly)
63
Is the following an example of large cell (aggressive) or small cell (indolent) non-Hodgkin's B cell lymphoma?
**Mantle cell lymphoma**
**Small cell (indolent)** non-Hodgkin's B cell lymphoma
64
Is the following an example of large cell (aggressive) or small cell (indolent) non-Hodgkin's B cell lymphoma?
**Hairy cell leukemia**
**Small cell (indolent)** non-Hodgkin's B cell lymphoma
65
Is the following an example of large cell (aggressive) or small cell (indolent) non-Hodgkin's B cell lymphoma?
**Marginal zone lymphoma**
**Small cell (indolent)** non-Hodgkin's B cell lymphoma
66
Is the following an example of large cell (aggressive) or small cell (indolent) non-Hodgkin's B cell lymphoma?
**Follicular lymphoma**
**Small cell (indolent)** non-Hodgkin's B cell lymphoma
67
Is the following an example of large cell (aggressive) or small cell (indolent) non-Hodgkin's B cell lymphoma?
**Lymphoplasmacytic lymphoma**
**Small cell (indolent)** non-Hodgkin's B cell lymphoma
68
Is the following an example of large cell (aggressive) or small cell (indolent) non-Hodgkin's B cell lymphoma?
**Chronic lymphocytic leukemia / small lymphocytic leukemia**
**Small cell (indolent)** non-Hodgkin's B cell lymphoma
69
Describe the similar presentations for all small cell lymphomas according to age, gender, expansion of monoclonal cells (involved markers?), and bodily locations.
**Older males**;
monoclonal **Smlg+** (mature) **B** cells
Variably, **blood** and **bone marrow**
70
**True/False**.
Small cell lymphomas are proliferations of immature B cells.
**False**.
Small cell lymphomas are proliferations of ***mature*** B cells.
71
Name two proliferative diseases of B cells that express CD5.
CLL (/ SLL);
mantle cell lymphoma
72
Which is the most aggressive of the small cell non-Hodgkin's lymphomas that has a poor survival rate?
Mantle cell lymphoma
73
What are the two most common forms of non-Hodgkin's lymphoma?
1. Diffuse large B cell lymphoma
2. Follicular lymphoma
74
Small lymphocytes are similar in size to what?
RBCs
75
What disease is associated with the leukocytes in this image?
Follicular lymphoma
(known as cleaved cells or 'butt cells')
76
Hairy cell leukemia is typically seen in what patient population?
(Age --- race --- gender)
Middle-aged caucasian men
77
Hairy cell leukemia is relatively _______ (common/rare).
Hairy cell leukemia is relatively **_rare_**.
78
What mutation leads to hairy cell leukemia?
***BRAF***
(specifically, the V600E variant also seen in melanoma)
79
Hairy cell leukemia is positive for what distinguishing clusters of differentiation?
Are there any other distinguishing molecules that are expressed?
CD**11c**, CD**25**, CD**103**;
**TRAP**
80
A 49 year old caucasian male presents with splenomegaly and you note pancytopenia on lab results. A peripheral smear shows the cell type in the attached image.
Further testing reveals that these cells are positive for a *BRAF* mutation, and they are also CD5-, CD10-, CD11c+, CD25+, CD103+, and TRAP+.
**What is the likely diagnosis?**
Hairy cell leukemia
81
How will a bone marrow aspirate appear in a patient with hairy cell leukemia?
**Dry tap**
(reticulin fibrosis and diffuse infiltrate on biopsy)
82
Name the one lymphoma type that is associated with any of the following:
**Hashimoto's disease** (_thyroid_ lymphoma) (MALT)
***H. pylori*** (MALT)
**Sjogren's syndrome** (_salivary_ glands) (MALT)
Marginal zone lymphoma
83
**Marginal zone lymphomas** are a heterogenous group of proliferative disease that typically arise in the \_\_\_\_nodal ________ tissues (MALT); the \_\_\_\_\_\_\_\_; and _________ \_\_\_\_\_\_\_\_\_.
**Marginal zone lymphomas** are a heterogenous group of proliferative disease that typically arise in the **_extra_**nodal **_lymphoid_** tissues (MALT); the **_spleen_**; and **_lymph_** **_nodes_**.
84
**True/False**.
Marginal zone lymphomas (e.g. MALT) often remain localized and sometimes regress if the inciting agent (e.g. *H. pylori*) is removed.
True.
85
**True/False**.
Marginal zone lymphomas are typically CD5- and CD10-.
True.
86
What is lymphoplasmacytic lymphoma?
Malignant B cells differentiating into plasma cells
87
Lymphoplasmacytic lymphomas _that hypersecrete IgM_ (a type of macroglobulin) are known by what name?
This hypersecretion may lead to what?
Waldenstrom's macroglobulinemia;
hyperviscosity syndrome
88
**Waldenstrom's macroglobulinemia** is a particular type of __________ lymphoma where hypersecretion of ____ (a type of macroglobulin) leads to hyperviscosity.
**Waldenstrom's macroglobulinemia** is a particular type of **_lymphoplasmacytic_** lymphoma where hypersecretion of **_IgM_** (a type of macroglobulin) leads to hyperviscosity.
89
Lymphoplasmacytic lymphomas are associated with what infectious agent?
Hepatitis C
90
**True/False**.
The hypoviscosity in some lymphoplasmacytic lymphomas (Waldenstrom's macroglobulinemia) can lead to blindness, bleeding, neurological issues, and thermoglobulinemia (where IgM precipitates at warm temperatures, leading to Raynaud's phenomenon and urticaria).
**False**.
The ***hype***rviscosity in some lymphoplasmacytic lymphomas (Waldenstrom's macroglobulinemia) can lead to blindness, bleeding, neurological issues, and ***cryo***globulinemia (where IgM precipitates at ***cold*** temperatures, leading to Raynaud's phenomenon and urticaria).
91
How can monoclonal antibody production (e.g. in Waldenstrom's macroglobulinemia or multiple myeloma) be easily diagnosed?
Serum protein electrophoresis
(clear M spike)
| (SPEP)
92
What is the most common type of non-Hodgkin's lymphoma?
Diffuse large B cell lymphoma
93
**True/False**.
Diffuse large B cell lymphomas are often associated with *MYC* or *Bcl-2* mutations.
True.
94
**True/False**.
Diffuse large B cell lymphoma often follows a fairly standard course with little variability.
**False**.
Many presentations (e.g. primary mediastinal, intravascular, primary effusion, primary cutaneous,
95
What are the two main categories of diffuse large B cell lymphoma?
1. _______ B-cell-like
2. _______ B-cell-like
1. **Germinal center** B-cell-like
2. **Activated** B-cell-like
96
Burkitt lymphoma is typically a(n) ______ aggressive, \_\_\_\_\_\_-grade malignancy.
Burkitt lymphoma is typically an **_extremely_** aggressive, **_high_**-grade malignancy.
97
Where is Burkitt lymphoma endemic?
Equatorial Africa
98
Where do most Burkitt lymphoma tumors typically arise on the body?
The jaw / face
99
What lymphoma is associated with EBV?
Burkitt lymphoma
100
**True/False**.
Burkitt lymphoma is basically a mature version of ALL.
True.
101
A man presents with large masses in his jaw and face. The cells in the masses are large lymphocytes with plentiful vacuoles (image attached below), and nearly all (~99%) are positive for **Ki-67** (a marker of active cell proliferation). The cells are **CD10+** and a **t(8 ; 14)** mutation is present.
The histology from the biopsies will appear with what general characteristic appearance?
'**Starry sky**' appearance
| (Burkitt lymphoma)
102
What translocation is associated with Burkitt lymphoma?
The cells will be CD5\_\_\_
The cells will be CD10\_\_\_
**t(8 ; 14)**
The cells will be CD5**-**
The cells will be CD10**+**
103
The t(8 ; 14) mutation seen in Burkitt lymphoma leads to creation of what oncogene?
*C-MYC*
104
An unclassifiable lymphoma with characteristics of **Hodgkin's** and **diffuse large B cell** lymphomas is known as what?
A gray zone lymphoma
105
A 'triple-hit' lymphoma is a highly aggressive, high-grade B cell lymphoma with what mutations?
* MYC*
* Bcl-2*
* Bcl-6*
106
What immunodeficiency-related lymphoproliferative disorder develops as a result of immunosuppression following transplant (solid organ, bone marrow, or stem cells) + infection with EBV?
**Post-transplant lymphoproliferative disorder**
(begins as mononucleosis-like lesions --\> leads to B and T cell lymphomas)
107
The S/Sy of T cell large granular lymphocytic leukemias often present as:
A\_\_\_\_\_\_\_\_\_tic / ________ course
\_\_\_\_\_\_megaly
\_\_\_\_\_\_\_cytosis
\_\_\_\_\_\_\_penia
The S/Sy of T cell large granular lymphomas often present as:
A**_symptoma_**tic / **_indolent_** course
**_Spleno_**megaly
**_Lympho_**cytosis
**_Neutro_**penia (may also be anemic)
108
Rheumatoid arthritis is associated with what lymphoma?
T cell large granular lymphocytic leukemia
109
Adult T cell leukemia/lymphoma is most common in what geographic regions?
Japan;
West Africa;
the Caribbean
110
**True/False**.
Adult T cell leukemia/lymphoma follows a relatively benign course and has no cutaneous lesions.
**False**.
Adult T cell leukemia/lymphoma follows a relatively ***aggressive*** course and ***has*** ***cutaneous*** lesions.
111
Adult T cell leukemia/lymphoma often causes what bone or skin or serum abnormalities?
Osteolytic lesions;
cutaneous lesions;
hypercalcemia
112
Adult T cell leukemia/lymphoma is associated with what infectious agent?
HTLV-1
113
Nasopharyngeal NK or T cell lymphomas are most common in what geographic region(s)?
How does they typically present?
Asia;
aggressive, destructive nasopharyngeal mass (often midline)
114
**True/False**.
T cell lymphomas are often aggressive and difficult to treat.
True.
115
What is mycoses fungoides (/ Sézary syndrome)?
What _specific_ cell type is involved?
A T cell lymphoma that causes cutaneous lesions;
**CD4+ cells**
116
What is the basic progression of the lesions seen in mycosis fungoides?
Patch --\> Plaque --\> Tumor
117
The T cells in mycosis fungoides are unique in that they are CD\_\_+ and CD\_\_-.
The T cells in mycosis fungoides are unique in that they are CD**4**+ and CD**7**-.
118
**True/False**.
Mycosis fungoides is typically indolent but progressive.
True.
119
What is the most common form of T cell lymphoma?
In what gender is it more common?
**Peripheral** T cell lymphoma;
**males** (2:1)
120
Anaplastic large cell lymphomas are rare and typically CD\_\_\_+.
They are often characterized by a t(\_\_ ; \_\_) mutation.
Anaplastic large cell lymphomas are rare and typically CD**_30_**+.
They are often characterized by a t(**_2_** ; **_5_**) mutation.
121
**True/False**.
Anaplastic cell lymphomas are often aggressive, ALK+, present in older adults, and they typically respond poorly to chemotherapy.
**False**.
Anaplastic cell lymphomas are often aggressive, ALK+, present in **_children/young adults_**, and they typically respond **_well_** to chemotherapy.
122
Multiple myeloma is a neoplasm of what cell type?
Plasma cells
123
What are the main S/Sy of multiple myeloma?
**CRAB**
Hyper**C**alcemia
**R**enal dysfunction
**A**nemia
**B**one pain
124
Where are the proliferating plasma cells of multiple myeloma typically found?
Colonizing the **bone marrow**
125
The immunoglobulins secreted by multiple myeloma cells are referred to as what?
The **M** component
126
**True/False**.
The M component of multiple myeloma is mostly associated with elevated _IgG_ levels, but it can be any of the following: IgG, IgA, IgM, or just light chains.
(Note: the M component is a homogenous secretion --- i.e. a particular case of MM will only produce one of the options listed above at a time.)
True.
127
What is the most common cause of death in multiple myeloma?
Infection
128
How does the bone marrow appear in multiple myeloma?
What is seen on peripheral smear?
Punched-out, lytic lesions;
roleaux formation
129
In the attached image of multiple myeloma cells, what is the lighter shaded area of the cell adjacent to the nucleus (note: this is seen in several lymphomas)?
The enlarged Golgi apparati
(highlighted below)
130
How is the M component of multiple myeloma measured and classified?
**Serum protein electrophoresis**
+
**Immunofixation** (e.g. checking gamma vs. lambda monoclonal production)
131
In an asymptomatic patient, you identify that they have a proliferation of plasma cells in their bone marrow replacing \< 10% of the bone marrow cellularity. Upon further investigation, you identify a small M spike (\<3 g/dL) .
What is the diagnosis?
Monoclonal gammopathy of undetermined significance
(MGUS)
132
How often does monoclonal gammopathy of undetermined significance progress to multiple myeloma?
**Rarely**
| (typically follows benign course)
133
What malignancy is strongly associated with EBV infection and the appearance in this micrograph?
(Clear vacuoles within leukocytes in peripheral smear)
Burkitt lymphoma
(**B**urkitt has **b**ubbles)
