WBC Flashcards
Lymphomas are
malignant proliferations of cells native to lymphoid tissue – lymphocytes and their precursors and derivatives.
Lymphomas usually arise in
lymphoid tissue, and can spread to involve solid tissue, marrow, and blood.
Lymphomas are categorized into two main types–
Hodgkin and non-Hodgkin lymphomas.
Leukemias are malignant proliferations of cells native to the
bone marrow, which often spillover into the blood. Leukemias can spread to involve solid organs (usually liver and spleen).
Until 1973, ethnic pigmentation was
unhealthy - if it wasn’t pink, it’s bad. This has gone by.
The distinction between lymphoma and the lymphocytic leukemias can be difficult in some instances, since in advanced states both can involve
lymphoid tissue at any site.
Hodgkin lymphoma: This is a characteristic type of lymphoma defined morphologically by the presence of
Reed-Sternberg cells admixed with a variable inflammatory infiltrate.
Unlike non-Hodgkin lymphomas, Hodgkin lymphoma (HL) is often accompanied by
fever, arises in a single lymph node or chain of nodes, is more common in young adults (average age 30 years), and is characterized by contiguous spread within lymph node groups (for this reason, staging is particularly important in assessing prognosis).
The cause of Hodgkin lymphoma is unknown, but
EBV has been implicated in playing a role.
Hodgkin Lymphoma: Cell of Origin: The neoplastic cell is the
Reed-Sternberg (RS) cell, a distinctive large cell with mirror image nuclei and prominent nucleoli.
Usually only small numbers of RS cells are present in the
involved node.
A diagnosis of Hodgkin lymphoma requires the presence of 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.
RS cells may arise from specialized
antigen-presenting cells in lymph nodes; the precise origin of the RS cell remains uncertain. I
in some cases the Epstein-Barr virus genome can be identified in the
RS cells.
Hodgkins:
Classification (Grading):
Several variants of Hodgkin lymphoma are recognized each with their own common clinical presentations, histologic features, and (to a certain extent) prognosis. Spread of disease is predictable: lymph nodes,spleen
Liver, bone marrow.
Staging: Staging is used to determine treatment and prognosis
1.
I - Tumor in one anatomic region or two contiguous anatomic regions on the same side of the diaphragm
Staging: 2
II - Tumor in more than two anatomic regions or two non-contiguous regions on the same side of the diaphragm
Staging 3:
III - Tumor on both sides of the diaphragm not extending beyond lymph nodes, spleen or Waldeyer’s ring
Staging 4:
IV - Tumor in bone marrow, lung, etc.- any organ site outside of the lymph nodes, spleen or Waldeyer’s ring
“B” signs/symptoms:
Hodgkins
Fever, night sweats, and significant unexplained weight loss
Low-stage disease denotes
localized lymph node involvement, without systemic signs (fever, weight loss), and has a better prognosis.
High-stage disease indicates
widespread disease, often with bone marrow involvement, and has a worse prognosis.
Choice of therapy (chemotherapy, radiotherapy, or both) and prognosis are based on
stage.
More aggressive forms of disease typically present in
higher stages.
Treatment consists of a combination of
chemotherapy and, to a less extent today, radiotherapy.
All stages are further divided on the basis of
absence (A) or presence (B) of systemic symptoms, including fever, night sweats, and significant unexplained weight loss (terminology example: stage IIIA).
Hodgkins Bimodal age distribution:
20-30 years old and >50 years old, ~8,300 cases in 2017, Painless lymphadenopathy (often cervical, supraclavicular, mediastinal), Splenomegaly (detected by MRI)
Hodgkins: Most patients have
enlarged, painless, superficial lymph node in
ivolvement as the initial manifestation of disease. Involvement of other lymph nodes in the chest and abdomen can occur, but is less common at presentation, except in lymphocyte-depleted type.
Hodgkins: Involvement of the spleen and liver increase
the stage, and are assessed by MRI.
Hodgkins: Complications with
infections (decreased cell-mediated immunity), anemia, and thrombocytopenia can occur in advanced disease.
Combination chemotherapy and, to a lesser extent, radiotherapy have
dramatically improved the survival in HD.
There is a low, but definite risk for developing
acute leukemia after treatment with chemotherapy and radiotherapy because of the bone marrow toxicities of the chemotherapeutic drugs used.
Prognosis - hodgkins
5-year survival - Stage 1 and IIa
Stage I and IIA - almost 100%
Hodgkins: 5-year survival rate in Stage IV is
50%
“B” signs/symptoms associated with worse prognosis
Stage III and IV disease more likely to have
“B” symptoms (worse prognosis)
Non-Hodgkin lymphomas (NHL) arise in
lymphoid tissue – either in lymph nodes or lymphoid tissue of solid organs- and have the capacity to spread into other nodes, solid organs, bone marrow, and blood.
NHL: Over 2 dozen
types are currently recognized. Most (85%) are of B cell origin. Most of remainder are of T cell origin
Incidence rises steadily after age 40, approximately 72,000 cases in 2017.
NHL :There is more morphologic diversity in NHL than in
HD, and more than two dozen subtypes of NHL are recognized for purposes of determining prognosis and selecting therapy.
NHL: 8 of the subtypes comprise over
90% of the NHLs in the US.
In contrast to HD, NHLs tend to have
multiple node involvement, more frequent extranodal spread and peripheral blood involvement, and affect all ages.
Like HD, histologic examination of involved tissue is
required for diagnosis.
Cell of Origin: The majority (85%) of NHL are
clonal neoplasms of B lymphocytes.
B lymphocytes are those lymphocytes specialized for
antibody production.
The remainder of NHL are of
T cell origin (15%).
B-lymphocytes normally have the capacity to differentiate into
plasma cells (the most mature B cell) as part of the immune response, just as T-lymphocytes become activated as part of the normal immune response.
A lymphoma develops when there is a
monoclonal expansion of lymphocytes that have been “arrested” (or have acquired a genetic rearrangement that alters growth regulation) at a particular stage in transformation. The clonal cells proliferate without normal regulatory mechanisms.
Thus, all lymphoid neoplasms are considered to arise from a
single transformed cell. daughter cells synthesize antigen receptor proteins identical to the original cell that reflect a “frozen” state of B cell maturation.
(hypogammaglobulinemia,
increased risk of infection).
NHLs are classified on the basis of their
morphology (microscopic appearance), cell of origin (immunophenotype), clinical features, and genotype.
The World Health Organization convenes panels of lymphoma experts to examine the accuracy and utility of the classification system, and the most recent system, published in 2008, is based on the
Revised European-American Lymphoma classification that was first proposed in the mid-1990’s.
Staging: NHL: Similar to Hodgkin lymphoma. There is less correlation between
stage and prognosis in NHL than in HD. Cell type and tumor proliferative index are better correlated with prognosis.
NHL: • Localized disease indicates what stage-
low stage
• NHL - Numerous sites of involvement or bone marrow involvement indicates what stage-
high stage
• NHL - Prognosis often based more on which criteria?
sub-type of lymphoma than stage (exception to the general rule, “grading” or subtyping is critical with NHL)
NHL Clinical Features and Course: Presentation is usually with .
painless enlarged lymph nodes, or evidence of extranodal spread- enlarged liver or spleen.
Bone marrow involvement is more common in NHL than in
HD, and lymphoma cells may circulate in peripheral blood.
NHL - Circulating lymphoma cells in the peripheral blood represent a
‘leukemic phase’ of the disease, in distinction to the group of diseases classified as leukemias.
NHL - The disease can spread to involve
solid organs, GI tract, bones, and nervous system.
Enlargement of lymph node groups can produce
vascular and lymphatic obstruction. Complications with infections, anemia, and thrombocytopenia occur.
NHL Treatment involves
chemotherapy, and less often, radiotherapy. Bone marrow transplant may be used for highly resistant disease, allowing higher doses of chemotherapy to be delivered with the hope of a cure
Leukemias are 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.
Leukemias: There is often “spill over” of the proliferating cells into the
blood and other organs.
Leukemias: Classification: This group of diseases can be roughly conceptualized both in terms of
onset and of cell type involved. Disease onset can be acute (rapid) or chronic (indolent), and cell types include myelogenous (myeloid and monocytic) and lymphoid.
What are the types of leukemias we need to know?
acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (CML).
Leukemia classification becomes increasingly complex as a
greater number of tests become available to evaluate specific morphologic, enzymatic, immunologic, and genetic aspects of the malignant cells.
Acute leukemias:
Rapid, usually fatal in months
Mostly blasts (immature cells)
WBC increased normally, 30% show decrease
Bone marrow: >20% blasts
Chronic Leukemias
Indolent, often long survival
Mostly mature cells
Often increased WBC
Blasts not increased in Bone marrow
• Acute lymphoblastic leukemia (ALL): The proliferating cell is a
primitive lymphoid cell. This type of leukemia accounts for about 40% of the acute leukemias, and is the most frequent type in children <15 years old.
ALL: It is the principal cause of cancer deaths in
childhood, with a peak incidence at age 4, but ALL can affect persons of all ages.
ALL: Five subtypes
(early B precursor, pre-B, mature B, and T cell) are recognized immunologically.
ALL: Cytogenetic analysis has
prognostic significance, with hyperdiploidy (>50 chromosomes per leukemic cell) being the subtype with best prognosis (most are children)
ALL: Prognosis related to cytogenetics,
Adults often have bad prognosis, Chemotherapy is mainstay of treatment with bone marrow transplantation considered at relapse
Enlargement of lymph nodes, liver and spleen is more common in ALL than
AML.
ALL often involves the
central nervous system.
ALL: The best prognosis group is
children aged 2-10 with pre-B cell type.
Acute myelogenous leukemia (AML): The proliferating cell is a
primitive myeloid cell.
AML: Several subtypes exist based on
morphology, cytochemistry, immunophenotype and cytogenetics.
AML: Increased WBC count often accompanied by
anemia and thrombocytopenia.
AML: More common in
adults
AML: Cytoplasmic evidence of myeloid differentiation includes the
presence of several types of granules (myeloperoxidase) found in more mature myeloid cells.
AML: Cytoplasmic inclusions called Auer rods, when present, are
diagnostic.
Many subtypes of AML can be recognized based on
morphology, cytochemistry, immunophenotype and karyotype.
AML - The karyotype is most predictive of
prognosis.
AML usually affects an older adult population, with a median age of
50 years.
AML - Sometimes the lesional cells will proliferate in
soft tissue (including the gingivae), producing what is termed granulocytic sarcoma.
AML = Although many patients can obtain remission of disease after chemotherapy, the duration of remission is often
transient.
—————- transplant is the current therapy undergoing evaluation/trial for treatment of refractory patients as well as those in first remission from standard chemotherapy, and is a potentially curative procedure.
Bone marrow
• Chronic Lymphocytic Leukemia (CLL): The proliferating cell is a
mature-appearing, but immunologically incompetent, lymphocyte.
Immunologically CLL cells can be proven to be
monoclonal (derived from the same precursor cell) and within a given patient all have identical cell surface phenotype.
CLL: More than 95% are of
B cell type, and most commonly express IgM kappa surface immunoglobulin.
CLL cells have
High expression of BCL2
• CLL accounts for about 2/3 of
chronic leukemias, and is most common in adults over 60, with a male:female ratio of 2:1.
The course of the disease of CLL is
indolent, and patients may not require treatment during the early stages.
CLL: As the monoclonal lymphocytes proliferate and migrate to other lymphoid sites there can be involvement of
spleen, liver, and lymph nodes.
Peripheral leukocytosis is common in
CLL, , and can be 5-10x normal.
Eventually cytopenias may develop (anemia and thrombocytopenia)
in CLL as the marrow is overrun by leukemic cells.
CLL: Because the neoplastic lymphocytes do not respond to antigenic stimuli,
hypogammaglobulinemia develops in most patients.
CLL: Chemotherapy is the basis of treatment. Median survival is
4-6 years.
Chronic Myelogenous Leukemia (CML): The proliferating cell is an
immature hematopoietic cell, a stem cell from which all other hematopoietic cells arise.
CML: Clonal proliferation of
immature granulocytes - a stem cell disorder. Marked increase in white blood cell count with eosinophilia and or basophilia, left-shifted granulocytes
CML: May have
thrombocytosis and anemia. Splenomegaly is typically present.
IN CML: The stem cell pool is increased
10-20x normal, and although the cells can mature, there is failure to respond to normal regulators of growth.
CML: Typically there is a marked increase in
peripheral white cell count, with all myeloid cell types present (especially myelocytes, eosinophils, and basophils).
CML: A specific chromosomal abnormality, the Philadelphia chromosome [t(9;22)], occurs in
all the proliferating cells. The chromosomal abnormality results in fusion of the BCR-ABL genes, which mimic the effects of growth factor activation, driving the proliferation of CML.
While this fusion gene is always present in CML, it is not
unique to this disorder.
CML accounts for about 1/3 of
chronic leukemias, and usually occurs in adults from 25-60 years of age.
Enlargement of the spleen due to proliferation of abnormal cells is almost always present with
CML
CML: The terminal phase of the disease marked by a relative increase in
immature cells in peripheral blood and bone marrow, and decreased response to treatment, is known as blast crisis. This stage is equivalent to an acute leukemia, and is of myeloid lineage in 2/3 and of lymphoid lineage in 1/3.
CML: Initial therapy is with targeted inhibitors of the
BCR-ABL tyrosine kinase, which induce complete remission in a high percentage of patients.
CML: With relapsed or resistant disease,
bone marrow transplant may be performed, although this is risky in older patients.
Clinical Features of Leukemia: Clinical features result from:
(1) impairment of marrow function as abnormal cells suppress growth of normal cells, and (2) infiltration of body organs due to proliferation of the abnormal cells.
Leukemia: Anemia is manifest as
pallor, weakness, and fatigue.
Leukemia: Thrombocytopenia
(decreased platelets) produces bleeding and bruises.
Leukemia: Infections result from decreased production of mature
granulocytes and production of non-functional granulocytes and/or lymphocytes.
Leukemia: Fever can be due to
infection or increased metabolism of proliferating cells.
Leukemia: Organ enlargement (lymph nodes, spleen, liver) occurs as the
abnormal cells proliferate in these sites.
Leukemia: Infiltration of the gingivae is a feature commonly associated with
acute myelo-monocytic leukemias.
Plasma cell disorders result from clonal expansion of
immunoglobulin-secreting cells.
The secreted immunoglobulin (or portion of immunoglobulin) results in increases in
serum monoclonal protein (M component) which may have adverse effects on renal and neurologic function.
Multiple Myeloma: The proliferating cell is a
plasma cell that produces immunoglobulin. Because this is a clonal disorder, only one immunoglobulin type is produced by the neoplastic cells. In 60% this is IgG; in 20-25%, IgA; in the remainder it is only kappa or lambda light chain; rarely it is IgM, IgD, or IgE.
Multiple myeloma: When only light chains are produced, patients can excrete the
low molecular weight light chains in the urine (Bence Jones proteinuria).
Multiple myeloma: In some patients, complete monoclonal immunoglobulin is present as well as
excess light chains in urine.
Multiple Myeloma: Multifocal destructive bone lesions characterize
myeloma.
Multiple Myeloma: Bone resorption results from secretion of
osteoclast activating factors by the myeloma cells.
Multiple Myeloma: Proteinaceous casts may form in the
kidneys (myeloma kidney).
Multiple Myeloma: ——— is often present, and ——— may form from the monoclonal protein.
Hypercalcemia, amyloid
Mutliple Myeloma 30,000 cases are projected to be diagnosed in 2016 in the US, with an average patient being
70 years old.
Multiple Myeloma: Patients often present with
bone pain, hypercalcemia, and renal disease.
Multiple myeloma: As the tumor cells proliferate, complications with recurrent infections, anemia, and thrombocytopenia develop due to
destruction of normal marrow by the tumor.
Multiple myeloma: Documenting monoclonal protein and skeletal lesions makes the .
diagnosis
