Intro to Hematologic Malignancies Flashcards
Hematologic Malignancies
diverse, but common thread is the presence of a clonal malignany population of cells derived from a transformed cell of marrow derivations.
Transforming events occur…
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
Leukemia
“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.
Lymphoma
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
Extramedullary myeloid tumor / granulocytic sarcoma
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.
Useful concept
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.
Acute Leukemia
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
Leukemic Cells (in acute leukemia)
are often, but not always, blasts, which are often accumulating due to a block in maturation.
Chronic Leukemia
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
High Grade Hematologic Malignancies
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.
Low Grade
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
Etiology of hematologic malignancies
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
Chromosomal abnormalities
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.
Oncogenic viruses
Though vast majority of heme malignancies are NOT associated with specific viruses, there are a few viruses known to be involved in some lymphomas
Epstein-Barr virus (EBV)
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
Human T cell leukemia virus-1
Implicated in development of adult T cell leukemia/lymphoma. Geographically isolated to jamaica and islands of Japan.
Kaposi sarcoma herpesvirus/Huma herpes virus 8
Implicated in primary effusion of lymphoma. Will mainly see in immunocompromised Pts.
Other predisposing conditions for hematologic malignancies
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
Childhood cancers
Leukemia is the MOST common childhood cancer type. Lymphoma is the 3rd most common cancer type. Brains and central nervous system is 2nd.
Classification of hematologic malignancies
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
Functional categorization: Acute Leukemias
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.
Functional categorization: Myelodysplastic syndrome
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
Functional categorization: myeloproliferative neoplasms
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.
Functional categorization: classical hodgkin lymphoma
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
