Intro to Hematologic Malignancies

Question 1

Hematologic Malignancies

Answer 1

diverse, but common thread is the presence of a clonal malignany population of cells derived from a transformed cell of marrow derivations.

Question 2

Transforming events occur…

Answer 2

anywhere, but most commonly in 1) a stem cell or progenitor cell in the marrow for acute leukemias and myeloid neoplams. 2) A lymphocyte in peripheral lymphoid tissues for most lymphomas

Question 3

Leukemia

Answer 3

“a condition of white blood,” refers to heme malignancies where the chief manifestation is involvement of the blood and marrow. Cells can be mature and immature.

Question 4

Lymphoma

Answer 4

refers to a heme malignancy, derived from lymphocytes or their precursors, which chiefly manifests as a solid mass. — Lymphomas may be nodal (presenting as enlarged lymph node(s)) or extranodal (presenting at sites such as skin, brain, or GI tract), or both

Question 5

Extramedullary myeloid tumor / granulocytic sarcoma

Answer 5

a heme mailgnancy, composed of myeloid cells or their precursors (e.g. granulocytes, monocytes, myeloblasts) which presents primarily as a solid mass. Less common than leukemia and lymphoma.

Question 6

Useful concept

Answer 6

Many hematopoietic neoplasms contain BOTH a leukemic and a lymphomatous component
When this happens, the neoplasm may be called by different names depending on which component PREDOMINATES, even though both names refer to the same disease. Example Chronic Lymphocytic Leukemia + Small Lymphocytic Lymphoma. In WHO classifications it is CLL/SLL.

Question 7

Acute Leukemia

Answer 7

A hemopoietic neoplasm with a rapidly progressive course, often with failed production of normal marrow cells due to the predominance of leukemic cells (fill up the marrow space), and thus often presenting due to problems associated with any combination of these: Low platelets (bleeding, bruises, hemorrhagic stroke), Low neutrophils (fever, infections, malaise), Low RBC (fatigue)
ACUTE LEUKEMIAS ARE RAPIDLY FATAL WITHOUT THERAPY

Question 8

Leukemic Cells (in acute leukemia)

Answer 8

are often, but not always, blasts, which are often accumulating due to a block in maturation.

Question 9

Chronic Leukemia

Answer 9

is used in reference to either chronic lymphocytic leukemia (CLL) or chronic myelogenous leukemia (CML). While these two disease are different in many ways, they share in common: 1) increased WBC count due to the accumulation of normal mature blood cells 2) insidious onset, often with no symptoms at time of diagnosis (often diagnosed incidentally) 3) natural course of disease is prolonged, with small risk of transformation to higher grade disease

Question 10

High Grade Hematologic Malignancies

Answer 10

Lymphoma often present as RAPIDLY enlarging mass.
Leukemia (acute) may often present as a VERY high white blood cell count with near replacement of the normal cells in the marrow and blood.

Question 11

Low Grade

Answer 11

lymphoma may present as MILDLY enlarged lymph nodes on an imaging study. Leukemia (chronic) is often noted incidentally by an increased WBC count on a CBC

Question 12

Etiology of hematologic malignancies

Answer 12

Require multiple genomic insults. Can be IDed by cytogenetic studies, sch as karytyping and/or FISH. Point mutations, tandem duplications require molecular testing like PCR

Question 13

Chromosomal abnormalities

Answer 13

detectable in large majority of heme malignancies. recurreny abnormalities are most commonly BALANCED TRANSLOCATION. Ex t(9;22) in CML). Translocations are found frequently in both lymphoid and myeloid malignancies. Can use as genetic markers.

Question 14

Oncogenic viruses

Answer 14

Though vast majority of heme malignancies are NOT associated with specific viruses, there are a few viruses known to be involved in some lymphomas

Question 15

Epstein-Barr virus (EBV)

Answer 15

Most common virus related cause. Implicated in the development of some cases of hodgkin lymphoma, some cases of burkitt lymphoma, and some other b-cell non-hodgkin lymphomas

Question 16

Human T cell leukemia virus-1

Answer 16

Implicated in development of adult T cell leukemia/lymphoma. Geographically isolated to jamaica and islands of Japan.

Question 17

Kaposi sarcoma herpesvirus/Huma herpes virus 8

Answer 17

Implicated in primary effusion of lymphoma. Will mainly see in immunocompromised Pts.

Question 18

Other predisposing conditions for hematologic malignancies

Answer 18

1) Primary or acquired (ex- HIV) immunodeficiencies. 2) Inherited conditions of genomic instability such as fanconi anemia and ataxia-telangiestasia. 3) ionization radiation exposure. 4) exposure to certain DNA-damaging chemotherapies

Question 19

Childhood cancers

Answer 19

Leukemia is the MOST common childhood cancer type. Lymphoma is the 3rd most common cancer type. Brains and central nervous system is 2nd.

Question 20

Classification of hematologic malignancies

Answer 20

WHO classification (2008) changed. The below is the HIGH level, older way. 
1) Myeloid - resemble cells of the granulocytic, monocytic, erythroid, megakaryocytic, and/or mast cell lineage. 2) Lymphoid resemble cells of the B cell, T cell, and NK cell lineages. 3) Other - Resemble histiocytes, dendritic cells, langerhans cells

Question 21

Functional categorization: Acute Leukemias

Answer 21

Rapidly growing malignancy, usually with a block in maturation resulting in accumulation of immature cells in the marrow, often replacing normal marrow cells, and often accumulating in the blood as well. Often immature cells are BLASTS. they can be myeloid or lymphoid.

Question 22

Functional categorization: Myelodysplastic syndrome

Answer 22

group of conditions where the marrow is OVERTAKEN by a neoplastic clone that is incapable of making normal effective blood cells in one or more myeloid lineages. Usually characterized by persistently low blood cell counts in one or more lineages. Generally a slow progression. ONLY MYELOID

Question 23

Functional categorization: myeloproliferative neoplasms

Answer 23

Marrow is overtaken by a neoplastic clone that MAKES normal functioning myeloid cells, usually in multiple lineages, but makes TOO many of them. Get increased blood counts. Only MYELOID.

Question 24

Functional categorization: classical hodgkin lymphoma

Answer 24

neoplastic cells in hodkins lymphoma are now known to be derived from B CELLS. But still unique that it is its own category of heme malignancy

Question 25

Functional categorization: Non-hodgkin lyphoma

Answer 25

Refers to different malignancies of mature lymphocyes. Excluding classical hodgkin lymphoma and malignancies of plasma cells. SUBDIVIDED into B Cells NHLs, and T cell / NK cells NHLs

Question 26

Functional Categorization: Plasma Cell Neoplasms

Answer 26

includes MGUS, plasmacytoma, and multiple myeloma.

Question 27

Functional categorization: other

Answer 27

histiocytoses, dendritic cell tumors, and other rare entitues.

Question 28

for many low grade malignancies treatment might include

Answer 28

no therapy, treating symptoms, surveillance for significant disease progression (such as transformation to high grade disease). Most Pts die WITH their disease vs. DUE to their disease.

Question 29

for high grade malignancies treatments might include

Answer 29

• chemotherapy alone (kids are sensitive to this), chemotherapy with radiation therapy, stem cell transplant (w/ conditioning chemotherapy, maybe from umblical cord), palliative treatments. Need to consider Pts age, how healthy they are, and stage of disease. Also note, ONLY IN VERY RARE SITUATIONS IS SURGERY AN APPROPRIATE HEMATOLOGIC MALIGNANCIES.

Question 30

Incidence rates and death rates

Answer 30

Non hodgkin lymphoma is 7, Leukemia is 10 for incidence. For death rates non-hodgkin lymphoma is 7, Leukemia is 6.

Question 31

WHO Classifications

Answer 31

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