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1

Describe Hematologic malignancies

Presence of a CLONAL malignant population of cells derived from a TRANSFORMED CELL that came from the MARROW

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3 main manners of malignant hematologic manifestation:

1. Leukemia
2. Lymphoma
3. Extramedullary myeloid tumor (granulocytic sarcoma)

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Leukemia

hematopoietic malignancy derived from stem cell or progenity in blood and marrow.

-ie: granulocytic, monocytic, erythroid, megakaryocytic, and mast cell lineages.

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Lymphoma

hematopoietic malignancy derived from lymphocytes or their precursors

ie: B cell,T cell, and NK cells lineages

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Extramedullary myeloid tumor

(aka granulocytic sarcoma) -

hematopoietic malignancy derived from myeloid cells or their precursors which presents primarily as a solid mass.

ie (granulocytes, monocytes, myeloblasts etc.),

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What is the difference between Chronic Lymphocytic Leukemia (CLL) + Small lymphocytic Lymphoma (SLL) ?

They are the same disease, but where the disease is more involved differs

Blood and marrow - CLL
Solid growths → enlarged lymph nodes - SLL

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Grade

how much has the tumor cells differentiated? - Clinical aggressiveness of a malignancy, growth rate

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Difference between High vs Low grade lymphoma

High grade Lymphomas:
- Rapidly enlarging mass

Low grade lymphomas:
- Mild degree of lymphadenopathy
- Present for years
- Incidentally noticed on imaging study

*If you see lymphoma: think hard mass

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Difference between High vs Low grade Leukemia

High grade "acute" Leukemia:
- Very high WBC w. replacement of most normal cells in marrow

Low grade "chronic" Leukemia:
- Subtle symptoms
- Incidentally noticed on CBC for different ailment

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Why do Hematologic malignancies love chromosomal translocations?

Due to natural susceptibility of genome to translocate during normal periods of genomic instability

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Examples of genomic instability leading to lymphomas containing balanced translocations

1. Initial immunoglobulin/T-cell receptor rearrangement during maturation of B cells/T cells

2. Class recombination and somatic hypermutation process during activation of B cells

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Class recombination

aka isotype switching (ie: IgG to IgM)

- Examples of genomic instability leading to lymphomas containing balanced translocations

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Somatic hypermutation:

immune sys. adapts to new microbe → diversify B cell receptors → respond to new threats

-Examples of genomic instability leading to lymphomas containing balanced translocations

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List 3 viruses known to have oncogenic roles in some cases of lymphoma.

1. Epstein-Barr virus (EBV):

2. Human T cell leukemia virus-1 (HTLV-1):

3. Kaposi sarcoma herpesvirus / Human herpesvirus-8 (KSV/HHV-8):

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Epstein-Barr virus (EBV):

Causes: Some cases of
- classical Hodgkin lymphoma
- Burkitt lymphoma
- B cell non-Hodgkin lymphomas

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Human T cell leukemia virus-1 (HTLV-1)

Causes adult T cell leukemia/lymphoma (ATLL)

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Kaposi sarcoma herpesvirus / Human herpesvirus-8 (KSV/HHV-8)

Causes:
Primary effusion lymphoma
Kaposi sarcoma (cancer common in pts w AIDS)

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incidences of leukemia and lymphoma in adult populations

Age adjusted incidence rates for all ages: (# new cases per population in given time)
○ #7 - Non-hodgkin lymphoma
○ #10 - Leukemia
__________________________
Age adjusted cancer death for all races:
○ #6 - Leukemia
○ #7 - non-Hodgkin lymphoma
○ #15 - Myeloma

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incidences of leukemia and lymphoma in childhood populations

○ #1 - Leukemia
37% of all childhood cancers
(○ #2 - Brain/CNS tumors)
○ #3 - Lymphoma
24% of all childhood cancers

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WHO Multiparameter Classification System of malignancies

1. Microscopic appearance of the malignant cells

2. Histologic growth patterns of the malignant cells in the marrow, lymph node, or other tissue

3. Presence or absence of specific cytogenetic findings or molecular findings

4. Relative amount of malignant cells present in the marrow or blood

5. Presence or absence of certain cell surface markers, cytoplasmic markers, and/or nuclear markers

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Current Basic Functional Categories for Hematologic Malignancies

• ACUTE LEUKEMIAS
• MYELODYSPLASTIC SYNDROME (MDS)
• MYELOPROLIFERATIVE NEOPLASMS (MPNs)
• CLASSICAL HODGKIN LYMPHOMA (CHL)
• NON-HODGKIN LYMPHOMA (NHL)
• PLASMA CELL NEOPLASMS

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General overview of: ACUTE LEUKEMIAS

Due to the rapid accumulation of immature cells in the marrow → Immature cells replace many of the normal marrow cells → cytopenias (of some marrow lineages)

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General overview of: MYELODYSPLASTIC SYNDROME (MDS)

Neoplastic clonal population→ takes over the marrow →
cant make normal blood cells in one or more myeloid lineages (dysplasia). →
low blood cell counts

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General overview of: MYELOPROLIFERATIVE NEOPLASMS (MPNs)

Neoplastic clonal population → take over marrow →
makes too many normal functioning myeloid cells (in multiple lineages) →
increased blood counts

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General overview of: CLASSICAL HODGKIN LYMPHOMA (CHL)

neoplastic cells derived from B cells

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General overview of: NON-HODGKIN LYMPHOMA (NHL)

malignancy derived from mature lymphocytes (B cells , T cells, or NK cells), excluding CHL or plasma cell neoplasms.

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General overview of: PLASMA CELL NEOPLASMS

Neoplasms derived from plasma cells, including MGUS, plasmacytoma, and multiple myeloma.