Flashcards in Module 1 Heme: Non-Hodgkin and Hodgkin's Lymphoma, CLL Deck (44):
The next lymphoid neoplasm that will be discussed is Burkitt's Lymphoma. Which is considered what kind of lymphoma?
Non-Hodgkin Lymphoma of medium B cells caused by EBV
--starts in the lymph nodes
What are the three types of Burkitt's Lymphoma?
1. African (Endemic)
--100% associated with EBV
--Cervical lymph node (submandibular) most commonly affected
--doubling time =24 hours
2. American (Sporadic)
--15% association with EBV
--mesenteric lymph node most commonly affected
3. Immunosuppression type (AIDS and post transplant patients): 25% EBV
In slide 11: pic of an African boy with what?
Extranodal sites in the jaw and it grows very fast!
--doubling time is 24 hours
---jaw mass is painless
What is the translocation is Burkitt's Lymphoma?
t(8.14): translocation between c-myc and heavy chain of Ig
--uncontrolled proliferation of b cells (hence why its a b cell lymphoma)
KI67 is positive in Burkitt's Lymphoma, why?
Marker for super fast cell proliferation
What is the presentation for Burkitt's Lymphoma?
African: fever, weight loss, and night sweats (called B symptoms)
American: obstruction due to the location of the ilial celical valve
What do you see on lymph node biopsy for a patient with Burkitt's Lymphoma?
1. Excisional Lymph Node Biopsy (good for all lymphomas): safe in that it wont spread
2. Lymph Node Biopsy: shows starry sky appearance (slide 11 blue dotted cell are the cancer cells and they are in sheets of malignant B cells) (Clear spaces are macrophages engulfing necrotic debris)
Why is there necrotic debris seen when a lymph node biopsy is done?
Because the nodes are growing so fast therefore they are outgrowing their blood supply
Apoptotic Bodies are seen in the lymph nodes of Burkitt's Lymphoma, why?
No expression of BCL2 (anti-apoptotic gene on Ch.18)
--so lots of apoptotic bodies
What is the other name for Burkitt's Lymphoma?
Small, non cleaved lymphoma
What do you see on flow cytometry for patients with Burkitt's Lymphoma?
CD 10, 19,20 (B cell markers)
What tumor marker is used for response to treatment in Burkitt's Lymphoma?
LDH (response to treatment because its a tumor maker)
What is the prognosis for Burkitt's Lymphoma?
--due to B symptoms
--extranodal spread to the blood (meningitis, brain, liver, spleen, bone marrow --results in pancytopenia)
What is the treatment for Burkitt's Lymphoma?
--very good response because of the rate of growth
Radiotherapy (be careful this can lead to development of myelodysplastic syndrome)
Remember that KI67 is positive and BCL2 is negative
The next lymphoid neoplasm we are going to speak about is Diffuse Large B cell lymphoma.. What are some features?
Most common type of lymphoma in adults, accounting for 50% of adult Non-Hodgkins Lymphoma's.
What are some morphological features of Diffuse Large B cell lymphoma?
---Neoplastic B cell are large (At least 3 to 4x the size of resting lymphocytes) and vary in appearance.
What is the pathogenesis for Diffuse B cell Lymphoma?
1/3rd of tumors have rearrangement of BCL6, located on 3q27, and even higher fraction of tumors have activating point mutations in the BCL6 promoter.
--increased BCL6 protein
Another 30% of tumors have a 14;18 translocation involving BCL2 genes and overexpression of this gene
Diffuse B cell lymphoma can be a primary (De novo) or secondary transformation of a previous low grade lymphoma. What is this called?
---chronic lymphocytic leukemia
Is diffuse Large B-cell lymphoma aggressive?
Yes, very high grade
How do patients present with diffuse Large B cell lymphoma?
Presents in late adulthood as an enlarging lymph node or an extranodal mass
Finally to end our discuss on non-hodgkin lymphoma, what are the common 5 and what are general features?
1. Small Lymphocytic lymphoma
2. Follicular Lymphoma
3. Diffuse Large B cell lymphoma
4. Small noncleaved (Burkitt's) Lymphoma
5. Lymphoblastic lymphoma
Always painless, no RS, extra-nodal spread, may skip nodes and tumor cells are in majority
Next topic to be discussed is Hodgkin Lymphomas which is associated with minimal change disease. There are classical and variant types. What are these types?
Classical: CD15+, CD30+
1.Nodular Sclerosis (classical)
2. Mixed Cellularity
3. Lymphocyte depleted
4. Lymphocyte Rich
Variant: CD20+, CD45+
1. Lymphocyte Predominant
Now, lets go through each one of these types and discuss. Starting with nodular sclerosis, what are the features of this classification?
CD 15+, CD30 + ; EBV: rare
RS cells = Lacunar with collagen bands
68% (most common)
F is greater than male
Lower cervical, supraclavicular mediastinal LN and young patients
more common in teens
The next classification is Mixed cellularity, what are some features?
CD 15+, CD30+ ; EBV: 70%
RS cells = abundant with EOS, PC and histiocytes
23% (second most common)
May be disseminated
May have B symptoms
Most frequent in patients older than 50 years
The next classification is Lymphocyte depleted, what are some features?
CD 15+, CD30+; EBV: most
RS cells = Abundant with few lymphs
B symptoms in older patients
Associated with AIDS patient and oral hairy leukopenia
The next classification is Lymphocyte Rich, what are some features?
CD 15+, CD30+; EBV: 40%
RS cells abundant with T lymphocytes
Rare and best prognosis
The last classification is lymphocyte predominance, what are some features?
CD15-, CD30-, EBV -, CD20+
RS cells = popcorn with mature lymphs
Large nodules (but no collagen band fibrosis)
less than 35 years old
What is the presentation for patients with Hodgkin lymphoma?
Cervical and Axillary lymphadenopathy (pain after alcohol consumption)
--B symptoms (fever, weight loss and night sweats)
What investigative tests are done for Hodgkin Lymphoma?
Excisional LN biopsy:
--Reed Sternberg Cell (malignant B cells)
What are some features of Reed Sternburg Cells?
Secrete Cytokines: attract inflammatory cells
Have an owl's eye appearance
What is a poor prognosis for Hodgkin Lymphoma?
Increased RS cells (more the worse prognosis)
--best prognostic factor is stage
What is a good prognosis for Hodgkin Lymphoma?
More lymphocytes the better
Less RS cells
No extranodal spread (liver, spleen, bone marrow)
--generally not as aggressive an non-hodgkins lymphoma
To end our discussion on Hodgkin lymphoma what are the common features?
Painful after alcohol
Extra-nodal spread (less common)
Spreads along chain of Lymph nodes (respects anatomy) (gets in the blood slower so therefore better prognosis)
Tumor cells in minority (non neoplastic inflammatory cells in majority)
The next topic for discussion is Chronic Lymphocytic Leukemia. This is a malignant B cell tumor What is the main difference between small and chronic?
Small Lymphocytic Lymphoma (SLL): restricted to lymph node; lymphocyte count is less than 4,000
Chronic Lymphocytic Leukemia (CLL): Bone marrow to blood; lymphocyte count is greater than 4000
Whom in the population tend to get chronic lymphocytic leukemia?
Older men (over 50)
--most common adult leukemia
What is the pathogenesis for chronic lymphocytic leukemia?
Mature, non functional malignant B cells that co-express CD20 and CD5
What is the presentation for Chronic Lymphocytic Leukemia?
-Usually asymptomatic and incidental finding on blood smear
--Pancytopenia (fatigue, recurrent infections and bleeding)
--Develop warm autoimmune hemolytic anemia after time due to the malignant B cells activate normal B lymphocytes to form IgG and causing extravascular hemolysis
---Activate normal lymphocytes to produce IgG (attacks own red cells)
--Hypogammaglobulinemia :no plasma cells being formed
--Heptaosplenomegaly (due to extramedullary hematopoiesis)
What do you see on Peripheral blood smear in patients with CLL?
Peripheral Blood Smear: most accurate
--Smudge Cells (malignant B cells that are crushed during preparation due to fragile membranes)
--malignant B cells
---Spherocytes (autoimmune hemolytic anemia, Coombs positive)
What do you see on Flow Cytometry for patients with CLL?
What do you see on Bone Marrow Aspirate and Lymph Node Biopsy for patient with CLL?
BM: Less than 5-10% blasts
Lymph Node Biopsy: Proliferation center (Well developed germinal centers) where the B cells are located
-less than 5-10% blasts because they are mature lymphocytes
What are the complications in CLL?
1. Recurrent Infections: (S. pneumoniae) most common cause of death
2. Heart Failure (anemia)
3. Bilirubin gallstones (hemolytic anemia)
4. CLL ----DLBL (diffuse large B cell lymphoma): high grade lymphoma: Richter's transformation
5. CLL --- AML: Blast transformation/crisis; blasts greater than 20-25% in bone marrow aspirate
6. Warm autoimmune hemolytic anemia (warm because IgG binds at normal body temp)
7. Thrombocytopenia = bleeding
What is Evan's Syndrome?
CLL + H. pylori + ITP