8/11- Pathology of Leukemia and Lymphoma Flashcards
Name 2 things that distinguish acute from chronic leukemias
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Name 3 morphological characteristics seen in Hodgkin lymphomas distinguish them from non-Hodgkin lymphoma
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How is a lymphoma different from a leukemia
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How can you distinguish myeloid blasts form lymphoid blasts?
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What is the difference between a leukemoid reaction and leukemia?
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What cells/organs/tissue comprise the lymphoid system?
- B cells, T cells, NK cells
- Lymphoid organs: lymph nodes, thymus, spleen, tonsils, adenoids
- Less well organized tissue: MALT (GI Peyer’s patches), bone marrow, skin
What is this?
Lymph node
Describe the architecture of a lymph node
Cortex: B cell zone, follicles
Paracortex: T cell zone, T cells, histiocytes, high endothelial venules (HEVs)
Medulla
B cell Development Process (flowchart/picture)
T cell Development Process (flowchart/picture)
- Originate in bone marrow and move to thymus to mature
- Initially 4- and 8-
- Become either 4+ (Th) or 8+ (CTL)
What are some cell surface markers involved in lymphocyte development?
B cells:
- Very young: CD34 (SC marker)
- CD19 -> CD10 -> CD20 -> sIg
T cells:
- Very young: CD34
- CD2, CD7
- CD5
- CD4, CD8
- At then end, either: (CD3 + CD8) or (CD3 + CD4)
Overall, list the CDs of B cells and T cells
B-cells: think in the 20s
- CD19, 20, 22, 23 (and Ig)
T-cells: think single digits
- CD2, 3, 5, 7, 4, 8
What are characteristics of neoplastic conditions of the hematopoietic-lymphoid system?
- Clonal diseases of hematopoietic cells
- Usually resemble their benign counterparts in morphology and immunophenotype
- Many have recurrent cytogenetic abnormalities (often translocations)
What are a few names for hematopoietic tumors?
- Lymphomas
- Leukemias
What are a few names for solid tumors?
- Carcinomas
- Sarcomas
Key features of Hematopoietic tumors vs. Solid tumors
Hematopoeitic tumors:
- Systemic disease
- Replacement of normal marrow or LN elements
- Circulating tumor cells in the peripheral blood
Solid tumors:
- Localized growth
- Invasion
- Metastasis
What are main differences between leukemias and lymphomas?
Leukemia: marrow based; any Hp lineage
Lymphoma: LN based (or anything non-marrow); lymphoid lineage
Key characteristics of leukemias?
- Malignant marrow-based neoplasms
- Can be of any hematopoietic lineage (e.g. lymphoid, granulocytic, megakaryocytic, and erythroid)
- Acute or chronic
- Often involve the peripheral blood
Key characteristics of lymphomas?
- Malignancies of the immune system, arising in extramedullary sites (outside the BM)
- Arise from lymphocytes (B, T, or rarely NK cells)
- Arise from cells at different stages of maturation/development
- Cell of origin determines morphology and clinical course
- Diverse group clinically and morphologically
How to distinguish between a lymphoid leukemia vs. a lymphoma
- Lymphocytes normally reside in the bone marrow, peripheral blood, and lymphoid tissues
- Malignancies of these cells may have the same distribution
- The distinction is generally based on the predominant clinical manifestation (blood and bone marrow = leukemia, lymph node = lymphoma)
Example of differentiating lymphoid leukemia and lymphoma: Acute lymphoblastic leukemia vs. Lymphoblastic lymphoma
Acute lymphoblastic leukemia
- Blasts in teh blood and bone marrow
- Express immature markers
Lymphoblastic lymphoma
- Cells infiltrate thymus or lymph nodes
- Express immature markers
- “Blastic morphology”
Both have blasts, they’re just in different places!
How are lymphomas and leukemias classified (by WHO)?
Entities distinguished by:
- Clinical features
- Morphology
- Immunophenotype (markers or CDs the cells express)
- Genotype (cytogenetics, molecular diagnostics)
Based on specific clinicopathologic entities when possible
What features are used to classify leukemias as either acute or chronic?
- Cell maturity
- Clinical course
- Age of pt
What is seen in acute vs. chronic leukemia in regard to:
- Cell maturity
- Clinical course
- Age of patient
What cells are involved in acute leukemia?
BLASTS!
What is shown here?
BLASTS (Acute Leukemia)
- Medium to large
- High N/C ratio
- Fine chromatin
- +/- nucleoli
What cells are involved in chronic leukemia?
What is shown here?
More mature cells in chronic leukemia (CML)
Cells involved in Myeloid vs. Lymphoid cell lines?
Non-lymphoid:
- Granulocytic
- Monocytic
- Eosinophilic
- Basophilic
- Erythroid
- Megakaryocytic
Lymphoid
- B cell
- T cell
- NK cell
How to tell if blasts are lymphoid vs. myeloid?
Myeloid
- Larger
- More cytoplasm
- More prominent nucleoli
- +/- Auer rods
Lymphoid
- Smaller
- Scant cytoplasm
- Small to no nucleoli
What is this?
Lymphoid blasts
- Smaller
- Scant cytoplasm
- Small to no nucleoli
What is this?
Myeloid blasts
- Larger
- More cytoplasm
- More prominent nucleoli
- +/- Auer rods
What is the only 100% myeloid morphologic marker?
Auer rods!!!
Provide leukemia names based on their status as either myeloid/lymphoid and acute/chronic
What cells are seen in:
- Acute myeloid leukemia (AML)
- Acute lymphoblastic leukemia (ALL)
- Chronic myelogenous leukemia (CML)
- Chronic lymphocytic leukemia (CLL)
- AML: myeloblasts
- ALL: lymphoblsats
- CML: neutrophils and myeloid precursors
- CLL: mature B lymphocytes
AML Immunophenotype: myeloid markers
(think of the 3s)
- CD13
- CD33
- May express other markers depending on the lineage and differentiation of the blasts
AML Immunophenotype: immature markers (blasts)
- CD34 (stem cell marker)
- TdT (terminal deoxynucleotidal transferase)
Can be myeloid or lymphoid; just tells you that cells are immature!
What is this? Don’t need to know genotype
AML with t(8;21)
What is this? Key features?
Acute promyelocytic leukemia (APL) with t(15;17)
- Granules!!
- Auer rods (“faggot cell”; lots of Auer rods)
- Bi-lobed nucleus Tend to present with DIC (coagulopathic)
What is this? Key features?
AML with inv(16)
- Eos with funny granules!)
What is this? Key features?
AML with monocytic differentiation
- Lobular, folded nucleus
What is this? Key features?
AMkL (megakaryoblastic leukemia)
AMkL (megakaryoblastic leukemia) is often associated with what?
Reticulin fibrosis
- When megs are up to no good, fibrosis often follows
Chronic myeloid leukemias = myeloproliferative neoplasms (disorders)
THEY’RE THE SAME THING
What conditions are included among chronic myeloid leukemias (myeloproliferative neoplasms (disorders))?
- Chronic myelogenous leukemia
- Essential thrombocytopenia
- Polycythemia vera
- Primary myelofibrosis (Chronic idiopathic myelofibrosis)
Describe hematopoiesis in myeloproliferative neoplasms?
Effective but abnormal
- Hypocellular marrow
- High PB counts
Describe hematopoiesis in myelodysplastic syndromes?
Ineffective
- Hypercellular marrow
- Cytopenias in PB
What is seen here?
Multilineage dysplasis
- Funny looking cells of all types
Describe myeloproliferative and myelodysplastic disorders in terms of:
- Clonal
- PB counts
- Marrow cellularity
- Dysplastic features
- Potential for AML
What is a main division in the classification of lymphomas?
Non-Hodgkin lymphomas
Hodgkin lymphoma
What are characteristics of Non-Hodgkin vs. Hodgkin lymphomas?
Non-Hodgkin:
- More common
- Usually have a monomorphic growth pattern
- Neoplastic cell = predominant cell
Hodgkin Lymphoma:
- Less common
- Pleomorphic growth pattern
- Neoplastic cell is rare
- Predominant cells are reactive
What cells are involved in Non Hodgkin lymphomas? Classified how? Characteristics?
B, T, and NK-cell lymphomas
- Classified in part based on maturity of the cells: lymphoblasts versus mature B and T cells
- Some have characteristic patterns of cell marker expression (those CD’s again)
- Some have characteristic genetic abnormalities: translocations – similar to the way some leukemias have recurrent genetic abnormalities Many types, corresponding to different classes of lymphocytes
Where in the lymphoid tissue are B cell lymphomas likely to arise?
The germinal center is a hazardous place where B cells engage in risky behavior; muck about with their genes (somatic mutations and class switching)
Is Follicular lymphoma Hodgkins or NHL?
NHL (It’s a peripheral B cell lymphoma)
Characteristics of Follicular Lymphoma
- Non-Hodgkins Lymphoma (NHL)
- Peripheral B cell lymphoma
- Morphology and immunophenotype reminsicent of germinal center B cells
— Nodule follicular architecture
— Small cleaved lymphocytes
— Looks like there are too many follicles!
What is shown here?
Describe Hodgkin Lymphoma
- Malignant cell = Reed Sternberg cell (RS cell)
— Recent studies have shown RS cells are actually post germinal center B-cells
— They have forgotten a lot of their “B-ness”
- Morphology: few RS cells in a background of lymphocytes, histiocytes, eosinophils, plasma cells, fibrosis
- Prognosis and therapy determined by stage (extent of involvement)
- Unlike NHL, has pattern of spread is orderly and contiguous
What is the hallmark of Hodgkin Lymphoma?
Reed-Sternberg Cell
- Very large compared to other surrounding lymphocytes
- Huge nucleoli (like owl eyes)
What is this?
Nodular Sclerosing Hodgkin Lymphoma
What are the arrows pointing to?
Reed-Sternberg cells
What are features of plasma cell neoplasms?
Have features of leukemia:
- Involve the bone marrow
Have some features of lymphoma:
- Usually doesn’t involve the peripheral blood
- Cells like to stick together and can cause more localized lesions (plasmacytomas)
Cause a lot of systemic symptoms and laboratory abnormalities
- Produce a monoclonal immunoglobulin
- Anemia, kidney problems, bone lesions, high calcium Morphology: sheets of plasma cells in the bone marrow
What is seen here?
WAY too many plasma cells (usually less than 5%)
What is this?
Plasma cells (again, way too many)
