Hematological malignancy
Encyclopedia
Hematological malignancies are the types of cancer
that affect blood
, bone marrow
, and lymph node
s. As the three are intimately connected through the immune system
, a disease affecting one of the three will often affect the others as well: although lymphoma
is technically a disease of the lymph node
s, it often spreads to the bone marrow
, affecting the blood
and occasionally producing a paraprotein
.
While uncommon in solid tumors, chromosomal translocation
s are a common cause of these diseases. This commonly leads to a different approach in diagnosis and treatment of hematological malignancies.
Hematological malignancies are malignant neoplasms ("cancer"), and they are generally treated by specialists in hematology
and/or oncology
. In some centers "Hematology/oncology" is a single subspecialty of internal medicine
while in others they are considered separate divisions (there are also surgical and radiation oncologists). Not all hematological disorders are malignant ("cancerous"); these other blood conditions may also be managed by a hematologist.
Hematological malignancies may derive from either of the two major blood cell lineages
: myeloid
and lymphoid
cell lines. The myeloid cell line normally produces granulocytes, erythrocytes, thrombocytes, macrophages and mast cells; the lymphoid cell line produces B, T, NK and plasma cells. Lymphomas, lymphocytic leukemias, and myeloma are from the lymphoid line, while acute and chronic myelogenous leukemia, myelodysplastic syndromes and myeloproliferative diseases are myeloid in origin.
Historically, hematological malignancies have been most commonly divided by whether the malignancy is mainly located in the blood (leukemia
) or in lymph node
s (lymphoma
s).
However, the influential WHO Classification (published in 2001) emphasized a greater emphasis on cell lineage.
and blood film
are essential, as malignant cells can show in characteristic ways on light microscopy. When there is lymphadenopathy
, a biopsy
from a lymph node
is generally undertaken surgically
. In general, a bone marrow biopsy
is part of the "work up" for the analysis of these diseases. All specimens are examined microscopically to determine the nature of the malignancy. A number of these diseases can now be classified by cytogenetics
(AML, CML) or immunophenotyping
(lymphoma, myeloma, CLL) of the malignant cells.
) or symptomatic treatment (e.g. blood transfusion
s in MDS
). The more aggressive forms of disease require treatment with chemotherapy
, radiotherapy, immunotherapy
and - in some cases - a bone marrow transplant
. The use of rituximab has been established for the treatment of B-cell–derived hematologic malignancies, including follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL)
and radiotherapy regimens - the appearance of another form of cancer
). In the follow-up, which should be done at pre-determined regular intervals, general anamnesis
is combined with complete blood count
and determination of lactate dehydrogenase
or thymidine kinase
in serum.
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
that affect blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
, bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, and lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
s. As the three are intimately connected through the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
, a disease affecting one of the three will often affect the others as well: although lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
is technically a disease of the lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
s, it often spreads to the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, affecting the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
and occasionally producing a paraprotein
Paraprotein
A paraprotein is an immunoglobulin or immunoglobulin light-chain that is produced in excess by the clonal proliferation of plasma cells. Detection of paraproteins in the urine or blood is most often associated with benign MGUS , where they remain "silent", and multiple myeloma. An excess in the...
.
While uncommon in solid tumors, chromosomal translocation
Chromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
s are a common cause of these diseases. This commonly leads to a different approach in diagnosis and treatment of hematological malignancies.
Hematological malignancies are malignant neoplasms ("cancer"), and they are generally treated by specialists in hematology
Hematology
Hematology, also spelled haematology , is the branch of biology physiology, internal medicine, pathology, clinical laboratory work, and pediatrics that is concerned with the study of blood, the blood-forming organs, and blood diseases...
and/or oncology
Oncology
Oncology is a branch of medicine that deals with cancer...
. In some centers "Hematology/oncology" is a single subspecialty of internal medicine
Internal medicine
Internal medicine is the medical specialty dealing with the prevention, diagnosis, and treatment of adult diseases. Physicians specializing in internal medicine are called internists. They are especially skilled in the management of patients who have undifferentiated or multi-system disease processes...
while in others they are considered separate divisions (there are also surgical and radiation oncologists). Not all hematological disorders are malignant ("cancerous"); these other blood conditions may also be managed by a hematologist.
Hematological malignancies may derive from either of the two major blood cell lineages
Haematopoiesis
Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells...
: myeloid
Myeloid
The term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte...
and lymphoid
Lymphoid
Lymphoid is a term used to describe lymph or the lymphatic system.In the context of lymphoid leukemia, it refers specifically to lymphocytes Lymphoid leukemias and lymphomas are now considered to be tumors of the same type of cell lineage. They are called "leukemia" when in the blood or marrow and...
cell lines. The myeloid cell line normally produces granulocytes, erythrocytes, thrombocytes, macrophages and mast cells; the lymphoid cell line produces B, T, NK and plasma cells. Lymphomas, lymphocytic leukemias, and myeloma are from the lymphoid line, while acute and chronic myelogenous leukemia, myelodysplastic syndromes and myeloproliferative diseases are myeloid in origin.
Classification and incidence
Taken together, hematological malignancies account for 9.5% of new cancer diagnoses in the United States. Within this category, lymphomas are more common than leukemias.Historically, hematological malignancies have been most commonly divided by whether the malignancy is mainly located in the blood (leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
) or in lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
s (lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
s).
However, the influential WHO Classification (published in 2001) emphasized a greater emphasis on cell lineage.
Relative proportions of hematological malignancies in the United States:
| Type of hematological malignancy | Percentage | Total |
|---|---|---|
| Leukemias | — | 30.4% |
| Acute lymphoblastic leukemia Acute lymphoblastic leukemia Acute lymphoblastic leukemia is a form of leukemia, or cancer of the white blood cells characterized by excess lymphoblasts.Malignant, immature white blood cells continuously multiply and are overproduced in the bone marrow. ALL causes damage and death by crowding out normal cells in the bone... (ALL) |
4.0% | |
| Acute myelogenous leukemia (AML) | 8.7% | |
| Chronic lymphocytic leukemia Chronic lymphocytic leukemia B-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by... (CLL) sorted under lymphomas according to current WHO classification; called small lymphocytic lymphoma (SLL) when leukemic cells are absent. |
10.2% | |
| Chronic myelogenous leukemia Chronic myelogenous leukemia Chronic myelogenous leukemia , also known as chronic granulocytic leukemia , is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood... (CML) |
3.7% | |
| Acute monocytic leukemia Acute monocytic leukemia Acute monocytic leukemia is considered a type of acute myeloid leukemia.-Diagnosis:In order to fulfill World Health Organization criteria for AML-5, a patient must have greater than 20% blasts in the bone marrow, and of these, greater than 80% must be of the monocytic lineage... (AMOL) |
0.7% | |
| Other leukemias | 3.1% | |
| Lymphoma Lymphoma Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage... s |
— | 55.6% |
| Hodgkin's lymphoma Hodgkin's lymphoma Hodgkin's lymphoma, previously known as Hodgkin's disease, is a type of lymphoma, which is a cancer originating from white blood cells called lymphocytes... s (all four subtypes) |
7.0% | |
| Non-Hodgkin's lymphomas (all subtypes) | 48.6% | |
| Myelomas | 14.0% | |
| Total | 100% |
By cell lineage
By cell lineage, hematological malignancies are classified according to their lineage in hematopoiesis:-
- Lymphoid leukemia
- LymphomaLymphomaLymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
- Myeloid leukemiaMyeloid leukemiaMyeloid leukemia is a type of leukemia affecting myeloid tissue.Types include:* Acute myeloid leukemia* Chronic myelogenous leukemia...
Diagnosis
For the analysis of a suspected hematological malignancy, a complete blood countComplete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
and blood film
Blood film
A blood film or peripheral blood smear is a thin layer of blood smeared on a microscope slide and then stained in such a way to allow the various blood cells to be examined microscopically...
are essential, as malignant cells can show in characteristic ways on light microscopy. When there is lymphadenopathy
Lymphadenopathy
Lymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....
, a biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
from a lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
is generally undertaken surgically
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
. In general, a bone marrow biopsy
Bone marrow biopsy
Bone marrow examination refers to the pathologic analysis of samples of bone marrow obtained by bone marrow biopsy and bone marrow aspiration. Bone marrow examination is used in the diagnosis of a number of conditions, including leukemia, multiple myeloma, lymphoma, anemia, and pancytopenia...
is part of the "work up" for the analysis of these diseases. All specimens are examined microscopically to determine the nature of the malignancy. A number of these diseases can now be classified by cytogenetics
Cytogenetics
Cytogenetics is a branch of genetics that is concerned with the study of the structure and function of the cell, especially the chromosomes. It includes routine analysis of G-Banded chromosomes, other cytogenetic banding techniques, as well as molecular cytogenetics such as fluorescent in situ...
(AML, CML) or immunophenotyping
Immunophenotyping
Immunophenotyping is a technique used to study the protein expressed by cells. This technique is commonly used in basic science research and laboratory diagnostic purpose. This can be done on tissue section , cell suspension, etc. An example is the detection of tumor marker, such as in the...
(lymphoma, myeloma, CLL) of the malignant cells.
Treatment
Treatment can occasionally consist of "watchful waiting" (e.g. in CLLChronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
) or symptomatic treatment (e.g. blood transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
s in MDS
Myelodysplastic syndrome
The myelodysplastic syndromes are a diverse collection of hematological medical conditions that involve ineffective production of the myeloid class of blood cells....
). The more aggressive forms of disease require treatment with chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, radiotherapy, immunotherapy
Immunotherapy
Immunotherapy is a medical term defined as the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. While immunotherapies that reduce or suppress are...
and - in some cases - a bone marrow transplant
Bone marrow transplant
Hematopoietic stem cell transplantation is the transplantation of multipotent hematopoietic stem cell or blood, usually derived from bone marrow, peripheral blood stem cells, or umbilical cord blood...
. The use of rituximab has been established for the treatment of B-cell–derived hematologic malignancies, including follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL)
Follow-up
If treatment has been successful ("complete" or "partial remission"), a patient is generally followed up at regular intervals to detect recurrence and monitor for "secondary malignancy" (an uncommon side-effect of some chemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
and radiotherapy regimens - the appearance of another form of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
). In the follow-up, which should be done at pre-determined regular intervals, general anamnesis
Medical history
The medical history or anamnesis of a patient is information gained by a physician by asking specific questions, either of the patient or of other people who know the person and can give suitable information , with the aim of obtaining information useful in formulating a diagnosis and providing...
is combined with complete blood count
Complete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
and determination of lactate dehydrogenase
Lactate dehydrogenase
Lactate dehydrogenase is an enzyme present in a wide variety of organisms, including plants and animals.Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes, each acting on either D-lactate or L-lactate...
or thymidine kinase
Thymidine kinase
Thymidine kinase is an enzyme, a phosphotransferase : 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, . It can be found in most living cells. It is present in two forms in mammalian cells, TK1 and TK2...
in serum.