Lecture 16 - WBC Disorders Flashcards
What are malignant proliferations of cells native to lymphoid tissue - lymphocytes and their precursors and derivatives?
lymphomas
Lymphoma tumors usually arise in lymphoid tissue and can spread to invovle what other areas?
- solid tissue
- marrow
- blood
What are the two main types lymphomas are categorized into?
Hodgkin and non-Hodgkin lymphomas
what are malignant proliferations of cells native to the bone marrow, which often spillover into the blood?
Leukemias
leukemias can spread to involve solid organs, specifically which two?
liver and spleen
This distinction between lymphoma and the lymphocytic leukemias can be difficult sometimes, since in advanced states both can involve what?
both can involve lymphoid tissue at any site
what type of lymphoma has the characteristic morphologically of the presence of Reed-Sternberg cells admixed with variable inflammatory infiltrate?
hodgkin lymphoma
Is non-hodgkin lymphoma or hodgkin lymphoma accompanied by a fever?
hodgkin lymphoma is often accompanied by fever
Is non-HL or HL accompanied as arising in a single lymph node or chain of nodes?
Hodgkin lymphoma is accompanied as arising in a single lymph node or chain of nodes
Is HL more common in younger or older individuals and what is the averae age?
HL more common in young adults and the average age is 30 years
specifically why is staging so important in Hodgkin lymphoma?
because it is characterized by contiguous spread within lymph node groups
the cause of Hodgkin lymphoma is unknown, but what has been implicated in playing a role?
EBV (epstein barr virus)
what is the neoplastic cell associated with Hodgkin’s lymphoma?
Reed-Sternberg (RS) cell
Describe a Reed-Sternberg (RS) cell
A distinctive large cell with mirror image nuclei and prominent nucleoli
In HL are there usually small or large numbers of RS cells present in the involved node?
usually only SMALL numbers are present in the involved node
A diagnosis of Hodgkin lymphoma requires the presence of what?
RS cells in the appropriate histologic background: RS-like cells alone are NOT specific, and may be seen in non-neoplastic disorders like infectious mononucleosis
Where may RS cells arise?
RS cells may arise from specialized antigen-presenting cells in lymph nodes; the precise origin of the RS cell remains uncertain
*EBV genome can be identified in the RS cells in some cases
what does staging refer to?
the assessment of the amount of tumor burden and its distribution in the body
what does it mean to have low stage disease?
low stage disease denotes localized lymph node involvement, without systemic signs (fever weight loss) and has a better prognosis
what does it mean to have high stage disease?
Widespread disease, often with bone marrow involvement, has a worse prognosis
*More aggressive forms of disease typically present in higher stages
The choice of therapy (chemotherapy, radiotherapy, or both) and prognosis are based on what?
stage
What is the main treatment for HL and what treatment is used less today
chemotherapy is the main treatment and to a less extent radiotherapy
The stages of HL are further divided on the basis of absence or presence of systemic symptoms such as what?
- fever, night sweats, significant unexplained weight loss
* Example: stage IIIA
Most patients typically have what as the initial manifestation of disease in Hodgkin’s lymphoma?
-enlarged painless superficial lymph node involvement
involvement of other lymph nodes in the chest and abdomen can occur, but is less common at presentation, except in what type of HL?
lymphocyte-depleted type
Involvement of what two organs increase the stage?
spleen and liver
*Are assessed by MRI
What complications can occur in advanced disease of HL?
- infections (decrease cell-mediated immunity)
- anemia
- thrombocytopenia
what therapy has dramatically improved the survival in HD?
combination chemotherapy and to a lesser extent radiotherapy
There is a low, but definite risk for developing acute leukemia after treatment with chemotherapy and radiotherapy because of what?
bone marrow toxicites of the chemotherapeutic drugs used
where does Non-Hodgkin lymphomas (NHL) arise and where can it spread
arise in lymphoid tissue - either in lymph nodes or lymphoid tissue of solid organs - have the capacity to spread into other nodes, solid organs, bone marrow and blood
does NHL of HL have more morphologic diversity?
more morphologic diversity in NHL
How many different subtypes of NHL are recognized for purposes of determining prognosis and selecting therapy?
more than two dozen subtypes
How many subtypes comprise over 90% of the NHLs in the US?
only 8 of these subtypes
Do NHLs tend to have multiple or isolated node involvement?
NHLs tend to have multiple node involvement, more frequent extanodal spread and peripheral blood involvemnt
(T/F) NHL affects mostly young individuals
FALSE
NHL affect all ages
Similar to HD what is required for diagnosis of NHL?
histologic examination of involved tissue
what percent of NHL are clonal neoplasms of B lymphocytes?
majority (85%) of NHL are clonal neoplasms of B lymphocytes
B lymphocytes are specialized for what?
antibody production
what percent of NHL are of T cell origin?
15% - the remainder of NHL is of T cell origin
B lymphocytes normally have to capacity to differentiate into what as part of the immune response, just as T-lymphocytes become activated as part of the normal immune response?
plasma cells (the most mature B cell)
when does a lymphoma develop
when there is monoclonal expansion of lymphocytes that have been “arrested” (or have acquired a genetic rearrangement that alters growth regulation) at a particular stage in transformation
(T/F) the clonal cells proliferate with normal regulatory mechanisms
FALSE
The clonal cells proliferate WITHOUT normal regulatory mechanisms
All lymphoid neoplasms are considered to arise from what?
a single transformed cell
Daughter cells synthesize antigen receptor proteins identical to the original cell that reflect a “frozen” state of what?
B cell maturation
NHL is a tumor of the immune system, do immune abnormalities occur frequently or infrequently?
immune abnormalities occur frequently
hypogammaglobulnemia - increased risk of infection
What is the classification of NHL?
moderately complicated
What is the principal reason for the classification system?
to facilitate communication and to obtain information on response to treatment and prognosis in similar histologic types
NHLs are classified on the basis of what four things?
- Morphology (microscopic appearance)
- Cell or origin (immunophenotype)
- Clinical features
- Genotype
What organization convenes panels of lymphoma experts to examine the accuracy and utility of the classification system
World health organization
T/F: There is less correlation between stage and prognosis in NHL than in HD
True
*Cell type and tumor proliferative index are better correlated with prognosis
Describe stage 1 distribution of disease
involves single lymph node region or extralyphatic organ or site
Describe stage 2 distribution of disease
involves two or more lymph node regions on side same of diaphragm along or with involvement of contiguous extrapyramidal organ or tissue
Describe stage 3 distribution of disease
Involves lymph node regions on both sides of diaphragm which may include spleen
Describe stage 4 distribution of disease
Multiple or disseminated foci of involvement of one or more extralymphatic organs or tissue with or without lymphatic involvement
in NHL is the clinical presentation painful or painless
usually painless
What area of the body is often enlarged with NHL and what two organs does it often spread?
enlarged lymph nodes, evidence of extranodal spread - enlarged liver or spleen
is more marrow involvement more common in HL of NHL
NHL
*And lymphoma cells may circulate in peripheral blood
Circulating lymphoma cells in the peripheral blood represent what phase of disease?
‘leukemic phase’ of the disease, in distinction to the group of diseases classified as leukemias
NHL can spread to involve solid organs, GI tract, bones, and what other system?
Nervous system
In NHL enlargement of lymph node groups can produce obstruction where?
can produce vascular and lymphatic obstruction
(T/F) in NHL complications with infections, anemia, and thrombocytopenia occur.
true
what is the treatment for NHL?
chemotherapy and less often radiotherapy
What treatment can be used for highly resistant disease, allowed higher doses of chemotherapy to be delivered with the hope of a cure?
bone marrow transplant
What is leukemia?
Malignant neoplasms of hematopoietic tissue that arise in the bone marrow
- The malignant cells proliferate in the bone marrow, commonly producing a pattern of diffuse infiltration
- There is often “spill over” of the proliferating cells into the blood and other groups
The cell types of acute and chronic leukemias include what?
myelogenous (myeloid and monocytic) and lymphoid
What are the basic classification of leukemias (4 of them)
Acute lymphoblastic leukemia (ALL)
Chronic lymphhocytic leukemia (CLL)
Acute myelogenous leukemia (AML)
Chronic myelogenous leukemia (CML)
Is acute of chronic leukemia described: indolent, often long survival; survival in years
chronic leukemia
Is acute or chronic leukemia described: rapid, usually fatal, survival in months
acute leukemia
Is acute or chronic leukemia described: in the peripheral blood mostly blasts (immature cells)
acute leukemia
Is acute or chronic leukemia described: in the peripheral blood mostly mature cells
chronic leukemia
Is acute or chronic leukemia described: White cell count often increased
both acute and chronic leukemia - but acute leukemia is decreased in 30%
Is acute or chronic leukemia described: more than 20% blasts in the bone marrow
acute leukemia
Is acute or chronic leukemia described: blasts usually not increased in the bone marrow
chronic leukemia
In acute lymphoblastic leukemia (ALL) the proliferating cell is what?
A primitive lymphoid cell
Which type of leukemia accounts for 40% of the acute leukemias and is the most frequent type in children less than 15 years old
acute lymphoblastis leukemia (ALL)
which type of leukemia is the principal cause of cancer deaths in childhood, with peak incidence at age 4, but can affect persons of all ages?
acute lymphoblastic leukemia (ALL)
what are the four subtypes that are recognized immunologically in acute lymphoblastic leukemia (ALL)?
- early B precursor
- Pre-B
- Mature B
- T cell
cytogenetic analysis has prognostic significance and what is the subtype with the best prognosis (most are children)
hyperdiploidy ( more than 50 chromosomes per leukemic cell)
in enlargement of lymph nodes, liver and spleen more common in AML or ALL?
enlargemnt of lymphnodes, liver and spleen is more common in ALL
*ALL also often involves the central nervous system
what is the best prognosis group for acute lymphatic leukemia (ALL)?
children aged 2-10 with pre-B cell type
What is the proliferating cell in acute myelogenous leukemias (AML)?
primitive myeloid cell
what is the cytoplasmic evidence of myeloid differentiation in acute myelogenous leukemia (AML)?
includes the presence of several types of granules (myeloperoxidase) found in more mature myeloid cells
What are Auer rods in acute myelogenous leukemia (AML)?
cytoplasmic inclusions that when present are diagnostic
How can many subtypes of AML be recognized?
Based on morphology, cytochemistry, immunophenotype and karyotype
*KARYOTYPE IS MOST PREDICTIVE OF PROGNOSIS
AML affects what population and what is the median age?
usually affects an older adult population, with a median age of 50 years
What is granulocytic sarcoma?
in AML sometimes the lesional cells will proliferate in soft tissue (including the gingivae)
what is the current therapy for AML undergoing evaluation/ trial for treatment of refractory patient as well as those in first remission from standard chemotherapy, as is a potentially curative procedure?
Bone marrow transplant
What is the proliferating cell in chronic lymphocytic leukemia (CLL)?
the proliferating cell is a mature-appearing, but immunologically incompetent, lymphocyte
*Immunologically these cells can be proven to be monoclonal (derived from the same precursor cell) and within a given patient all have identical cell surface phenotype
In CLL what percentage are B cell type?
more than 95%
In CLL what immunoglobulin is commonly expressed?
IgM kappa surface immunoglobulin
Chronic Lymphocytic Leukemia (CLL) accounts for what percent of chronic leukemias and is most common in adults older than what age?
2/3 or 66% of chronic leukemias and is most common in adults over 60
what is the male: female ratio in CLL?
2:1
In CLL is the course of the disease is indolent, and patients may not require treatment when?
they may not require treatment in the early stages
In CLL as the monoclonal lymphocytes proliferate and migrate to other lymphoid sites there can be involvement of ____, _____, and ____ _____
spleen, liver and lymph nodes
In CLL, Peripheral leukocytosis is common and can be how many time normal?
5-10X normal
In CLL, as the marrow is overrun by leukemic cell eventually what may develop?
cytopenias (anemia and thrombocytopenia)
In CLL, because the neoplastic lymphocytes do not respond to antigenic stimuli, what develops in most patients?
hypogammagobulinemia
What is the median survival for chronic lymphocytic leukemia (CLL)
4-6 years
What is the proliferating cell in chronic myelogenous leukemia (CML)?
an immature hematopoietic cell, a stem cell from which all other hematopoietic cells arise
In CML the stem cell pool is increased how many time normal?
10-20 X normal, and although the cell can mature, there is failure to respond to normal regulators of growth
In CML, there is a marked increase in peripheral white cell count, with all myeloid ell types present especially which ones?
myelocytes, eosinophils, and basophils
what is the specific chromosomal abnormality is found in chronic myelogenous leukemia (CML) that occurs in all the proliferating cells?
Philadelphia chromosome [t(9;22)]
The chromosomal abnormality results in fusion of what genes, which mimic the effects of growth factor activation, driving the proliferation of CML
BCR-ABL genes
*While this fusion gene is ALWAYS present in CML, it is not unique to this disorder
what percent of chronic leukemias does CML account for and what the the age range for the adults it effects?
1/3 of chronic leukemia
adults from 25-60 years of age
In CML, enlargement of what organ to the due to proliferation of abnormal cells is almost always present?
the spleen
the terminal phase of CML is also known as what and characterized by what?
Blast crisis
marked by relative increase in immature cells in peripheral blood and bone marrow, and decreased response to treatment
the terminal phase of CML is equivalent to an acute leukemia, and is what fraction of myeloid linage and what fraction of lymphoid lineage?
myeloid lineage (2/3) and lymphoid lineage (1/3)
what is the initial therapy of CML?
targeted inhibitors of the BCR-ABL tyrosine kinase, which induce complete remission in a high percentage of patients
*With relapsed or resistant disease, bone marrow transplant may be performed, although this is risky in older patients
In leukemia, the clinical features result from:
- impairment of marrow function as abnormal cells suppress growth of normal cells
- infiltration of body organs due to proliferation of the abnormal cells
anemia is manifest as what three things?
pallor, weakness, and fatigue
what is thrombocytopenia and what does it produce?
decreased platelets and it produces bleeding and bruises
Why do infections result in leukemia?
infectiosn result from decreased production of mature granulocytes and production of non-functional granulocytes and/or lymphocytes
in leukemia, what can result due to infection or increased metabolism of proliferating cells?
fever
In leukemia, organ enlargement int he lymph nodes, spleen, and liver occurs because of what?
the abnormal cells proliferate in these sites
In leukemia, abnormal pain or obstrauction of vascular and lymphatic channels can result. Infiltration of the gingiva is a feature commonly associated with which type of leukemia?
acute myelo-monocytic leukemias
Plasma cell disorders result from what?
clonal expansion of immunoglobulin-secreting cells
In plasma cell disorders, the secreted immunoglobulin (or portion of immunoglobulin) results in increases in serum monoclonal protein (M component) which may have adverse effects of what two functions?
renal and neurologic function
what is the proliferating cell in multiple myeloma?
plasma cell that produces immunoglobulin
In multiple myeloma, because this is a clonal disorder, only one immunoglobulin type is produced by the which cells and what immunoglobulin type is produced in most cases?
neoplastic cells * In 60% this is IgG In 20-25% IgA remainder it is only kappa or lamba light chain Rarely is it IgM, IgD, or IgE
*In some patients complete monoclonal immunoglobulin is present as well as excess light chains
what is Bence Jones proteinuria?
when only light chains are produced, patients can excrete the lower molecular weight light chains in the urine
What characterizes myeloma?
multifocal destructive bone lesions
Bone resorption results from secretion of _____ activating factors by the myeloma cells
osteoclast
Proteinaceous casts may for in what part of the body
the kidneys (myeloma kidney)
Hypercalcemia is often present and _______ may form from the monoclonal protein
amyloid
how many cases of multiple myeloma are projected to be diagnosed in 2015 in the US, and what is the average age of the patient
24,000
average patient is 70 years old
What do patients often present with in multiple myeloma?
bone pain, hypercalcemia, and renal disease
As the tumor cells proliferate, complications with recurrent infections, anemia, and thrombocytopenia develop due to what?
destruction of normal marrow by the tumor
What makes the diagnosis in multiple myeloma?
documenting monoclonal protein and skeletal lesions
the terminal phase of CML is equivalent to an acute leukemia, and is what fraction of myeloid linage and what fraction of lymphoid lineage?
myeloid lineage (2/3) and lymphoid lineage (1/3)
what is the initial therapy of CML?
targeted inhibitors of the BCR-ABL tyrosine kinase, which induce complete remission in a high percentage of patients
*With relapsed or resistant disease, bone marrow transplant may be performed, although this is risky in older patients
In leukemia, the clinical features result from:
- impairment of marrow function as abnormal cells suppress growth of normal cells
- infiltration of body organs due to proliferation of the abnormal cells
anemia is manifest as what three things?
pallor, weakness, and fatigue
what is thrombocytopenia and what does it produce?
decreased platelets and it produces bleeding and bruises
Why do infections result in leukemia?
infectiosn result from decreased production of mature granulocytes and production of non-functional granulocytes and/or lymphocytes
in leukemia, what can result due to infection or increased metabolism of proliferating cells?
fever
In leukemia, organ enlargement int he lymph nodes, spleen, and liver occurs because of what?
the abnormal cells proliferate in these sites
In leukemia, abnormal pain or obstrauction of vascular and lymphatic channels can result. Infiltration of the gingiva is a feature commonly associated with which type of leukemia?
acute myelo-monocytic leukemias
Plasma cell disorders result from what?
clonal expansion of immunoglobulin-secreting cells
In plasma cell disorders, the secreted immunoglobulin (or portion of immunoglobulin) results in increases in serum monoclonal protein (M component) which may have adverse effects of what two functions?
renal and neurologic function
what is the proliferating cell in multiple myeloma?
plasma cell that produces immunoglobulin
In multiple myeloma, because this is a clonal disorder, only one immunoglobulin type is produced by the which cells and what immunoglobulin type is produced in most cases?
neoplastic cells * In 60% this is IgG In 20-25% IgA remainder it is only kappa or lamba light chain Rarely is it IgM, IgD, or IgE
*In some patients complete monoclonal immunoglobulin is present as well as excess light chains
what is Bence Jones proteinuria?
when only light chains are produced, patients can excrete the lower molecular weight light chains in the urine
What characterizes myeloma?
multifocal destructive bone lesions
Bone resorption results from secretion of _____ activating factors by the myeloma cells
osteoclast
Proteinaceous casts may for in what part of the body
the kidneys (myeloma kidney)
Hypercalcemia is often present and _______ may form from the monoclonal protein
amyloid
how many cases of multiple myeloma are projected to be diagnosed in 2015 in the US, and what is the average age of the patient
24,000
average patient is 70 years old
What do patients often present with in multiple myeloma?
bone pain, hypercalcemia, and renal disease
As the tumor cells proliferate, complications with recurrent infections, anemia, and thrombocytopenia develop due to what?
destruction of normal marrow by the tumor
What makes the diagnosis in multiple myeloma?
documenting monoclonal protein and skeletal lesions
