Hematologic malignancies Flashcards
Characteristics of hematologic malignancies:
What do they share in common?
In regards to neoplasms of solid tissue, nearly all of neoplasms of hematpoietic cells are regarded as_________.
¨The common thread is the presence of a clonal malignant population of cells derived from a transformed cell of marrow derivation.
¨Different from neoplasms of solid tissues, nearly all neoplasms of hematopoietic cells are regarded as malignancies
¨The transforming event may occur anywhere, but most commonly occurs in:
- a hematopoietic stem cell or progenitor cell in the marrow (for acute leukemias and myeloid neoplasms)
- a lymphocyte in peripheral lymphoid tissues (for most lymphomas)
Neoplasms of what cells are considered hematologic malignancies?
As the transforming event often takes place in a multipotent progenitor cell, the clonal population in some hematologic malignancies may include cells of ________.
different lineages
What is leukemia?
In leukemia the chief manifestation is involvement of the _____ and _________, since these two are interconnected.
What is a lymphoma? It mainly manifests as a _______?
What are the two ways lymphoman can present?
Leukemia – literally “a condition of white blood,” refers to heme malignancies where the chief manifestation is involvement of the blood and marrow (these are interconnected compartments)
The many different leukemias include diseases of both lymphoid and myeloid cells, both 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.
Acute leukemia
What is it? Why do production of normal marrow cells fails?
Problems present with combination of what deficiencies?
Are they fatal?
¨Acute leukemia:
-A hematopoietic neoplasm with a rapidly progressive course, often with failed production of normal marrow cells due to the predominance of the leukemic cells, 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
Chronic leukemias
It refers to what two leukemias?
What do CLL and CML share in common?
¨The term 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:
- increased WBC count due to the accumulation of normal-appearing (but clonal) mature blood cells
- insidious onset, often with no symptoms at time of diagnosis (often diagnosed incidentally)
- natural course of disease is prolonged, with small risk of transformation to higher grade disease.
Grade in hematologic malignancies
1- When referring to leukemias, the term _______ is usually used for high grade leukemias, and the term _______ is used for low grade leukemias.
1- When referring to leukemias, the term acute is usually used for high grade leukemias, and the term chronic is used for low grade leukemias.
For lymphomas:
A high grade lymphoma may present as a rapidly enlarging mass.
A high grade, or acute, leukemia might present as a very high white blood cell count with near replacement of all normal cells in the marrow.
In contrast, a low grade lymphoma may come to attention as a mildly enlarged neck lymph node that has been present for years, or as a mild degree of lymphadenopathy (enlarged lymph nodes) noticed incidentally on an imaging study.
A low grade, or chronic, leukemia may have very subtle symptoms, but very often is noticed incidentally due to an elevated WBC count in the results of a CBC performed for some other reason.
Etiology of hematologic malignancies
¨Chromosomal abnormalities are detectable in a large majority of heme malignancies; recurrent abnormalities are most commonly ____________.
CHROMOSOMAL TRANSLOCATIONS:
Chromosomal abnormalities, most commonly translocations, are seen in the majority of hematologic malignancies. Some of these abnormalities are persistently found in certain diseases, such as the translocation t(9;22) seen in chronic myelogenous leukemia (CML). These types of persistent findings are important in that:
a) their persistent presence allows them to be used as diagnostic markers for certain hematologic malignancies
b) their persistent presence suggests they place a critical role in the development of the hematologic malignancy they are associated with
Translocations are found frequently both in lymphomas and myeloid neoplasms.
The reasons for frequent translocations in lymphoma is thought to be due to the natural susceptibility of the genome to translocations during normal periods of genomic instability, namely during the initial immunoglobulin / T‐cell receptor rearrangement during the maturation of B cells / T cells, and during the class recombination and somatic hypermutation process during the activation of B cells.
Etiology of hemologic malignancies
Oncogenic viruses
What are three common viruses that are involved in some lymphomas?
Which virus is implicated in primary effusion lymphoma?
Though the vast majority of heme malignancies are not associated with specific viruses, the are a few viruses known to be involved in the development of some lymphomas. These are:
1) Epstein-Barr virus (EBV) – implicated in the development of some cases of Hodgkin lymphoma, some cases of Burkitt lymphoma, and some other B-cell non-Hodgkin lymphomas
2) Human T cell leukemia virus-1 (HTLV-1) – implicated in the development of adult T cell leukemia/lymphoma
3) Kaposi sarcoma herpesvirus/Human herpesvirus 8
(KSHV/HHV-8) – implicated in primary effusion lymphoma
Predisposing conditions:
What are some conditions of genomic instability that predispose patients to hematologies malignancies?
¨Primary or acquired immunodeficiencies
¨Inherited conditions of genomic instability, such as Fanconi anemia and ataxia-telangiectasia
¨Ionizing radiation exposure
¨Exposure to certain DNA-damaging chemotherapies
Epidemiology:
Non-Hodkin lymphoma is #7 in terms of cancer sites
Leukemia is # 10
Epidemiology:
In terms of death rate leukemia is more deadly than Non-Hodgkin.
Although hematologic malignancies are relatively uncommon, they are not rare.
In the National Cancer Insititute’s list of frequency of U.S. cancers by site for all ages/races, non‐Hodgkin lymphoma is 7th most frequent, and the generic category “leukemia” is 10th most frequent. To put this in more tangible terms, non‐Hodgkin lymphoma and leukemia occur at rates that are about four to five times lower than the rates of the most common cancers, such as prostate cancer and breast cancer.
In the National Cancer Insitute’s list of age‐adjusted cancer death rates by site for all races, “leukemia” now surpasses “lymphoma,” due largely to the fact that many adults with acute leukemia will eventually die of their disease. Myeloma, which is was not in the top 15 for incidence, now appears as number 15 for cancer death rates, due to the fact the currently myeloma is essentially incurable (though it frequently has a long disease course.)
Regarding childhood cancers (age <20), leukemia is the most common type, representing 37% of childhood cancers. Lymphoma is the 3rd most common type, representing 24% of childhood cancers. (Second place belongs to brain/CNS tumors). If one were to merge leukemia and lymphoma together as ‘hematologic malignancies,’ that new category would easily rank as the most common type of malignancy in children.
In terms of childhood cancers:
In regards to childhood cancers…
Leukemia is the most common childhood cancer by type.
Lymphoma is the third most common childhood cancer by type.
(brain/CNS tumors are second most common type)
Classification of hematologic malignancies
Myeloid – Resemble cells of the granulocytic, monocytic, erythroid, megakaryocytic, and/or mast cell lineages
Lymphoid – Resemble cells of the B cell, T cell, and NK cell lineages
Other – Resemble histiocytes, dendritic cells, Langerhans cells
WHO multiparameter classification system:
The WHO classification system draws from various different sources of information to diagnostically define entities. This information used for any one entity might include some or all of the following:
‐ microscopic appearance of the malignant cells
‐ histologic growth pattern of the malignant cells in the marrow, lymph node, or other tissue
‐ presence or absence of specific cytogenetic findings or molecular findings
‐ relative amount of malignant cells present in the blood or marrow
‐ presence or absence of certain cell surface markers / cytoplasmic markers / nuclear markers
***For some diagnostic entities, a piece of data from only one of these categories may be sufficient to make the diagnosis, while for another entity, data from that category may not have much of a bearing.
-For example, mantle cell lymphoma is defined by the presence of a translocation t(11;14) involving the IGH and CCND1 genes. In the absence of having some type of evidence that this translocation is present, it is very difficult to diagnose mantle cell lymphoma. However, one can easily diagnose diffuse large B cell lymphoma (DLBCL) without knowing any of the cytogenetic findings.
The goal of the WHO is thus to allow the recognition of as many distinct clinical entities (meaning entities that are worth separating from each other due to known differences in clinical behavior, responses to treatment, etc.) as possible by the pathologist using available techniques.
Acute leukemias
Accumulation of immature cells in the _______.
-Rapidly growing malignancy, usually with a block in maturation resulting in the accumulation of immature cells in the marrow, often replacing normal marrow cells, and often accumulating in the blood as well.
The immature cells are often, but not always, blasts; they can be myeloid or lymphoid.
Myelodysplastic syndrome
Bone marrow is overtaken by who?
Characterized by persistently _______ in one or more lineages.
-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 (dysplasia).
Usually characterized by persistently low blood cell counts in one or more lineages.
¨NON-HODGKIN LYMPHOMA
NHL refers to all the different lymphomas of mature-appearing lymphocytes, excluding classical Hodgkin lymphoma and malignancies of plasma cells.
NHL is subdivided into:
- B cell NHLs (large majority if NHLs)
- T cell / NK cell NHLs (less than 5% of NHLs).
Therapeutic principles
Therapeutic principles for aggresive leukemia:
Is surgery used very often?
