Lecture - Module 6 Flashcards
Generally characterized by the presence of leukocytosis with an increased number of mature lymphocytes, lymphocytosis, on a peripheral blood film
CHRONIC LEUKEMIAS
characterized by an accumulation of lymphocytes.
Malignant lymphoproliferative disorders
Most common form of leukemia in adults in Western countries but it is very rare in far Eastern countries
CHRONIC LYMPHOCYTIC LEUKEMIA
SMALL LYMPHOCYTIC LYMPHOMA
Neoplasms composed of small B lymphocytes in the peripheral blood, bone marrow, spleen, and lymph nodes, mixed with prolymphocytes and paraimmunoblasts forming proliferation centers in tissue infiltrates.
CHRONIC LYMPHOCYTIC LEUKEMIA
SMALL LYMPHOCYTIC LYMPHOMA
Accounts for almost 7% of non-Hodgkin lymphomas (NHLs) in biopsies.
CHRONIC LYMPHOCYTIC LEUKEMIA
SMALL LYMPHOCYTIC LYMPHOMA
CHRONIC LYMPHOCYTIC LEUKEMIA / SMALL LYMPHOCYTIC LYMPHOMA median age of onset
65 years old
This form of leukemia is rare before age 20 and uncommon before age 50.
CHRONIC LYMPHOCYTIC LEUKEMIA / SMALL LYMPHOCYTIC LYMPHOMA
Classic CLL is usually a what type of disorder
B-cell disorder
a biologically and clinically heterogeneous hematologic malignancy characterized by a gradually progressive accumulation of morphologically mature B lymphocytes in the blood, bone marrow, and lymphatic tissues.
B-CLL
B-CLL characterized as
CD5+ CD19+ CD23+ monoclonal B cells
most consistent finding which is present in approximately 50% of patients in CLL and SLL
trisomy of chromosome 12
Chromosomal alterations in CLL/SLL
11q deletion
13q deletion
17p deletion
trisomy of chromosome 12 → most consistent finding which is present in approximately 50% of patients
translocation of chromosomes 8 and 14 → associated with B-CLL
translocation of chromosomes 9 and 22 → observed in non- T and non-B types
Chromosomal alterations in CLL/SLL associated with B-CLL
translocation of chromosomes 8 and 14
Chromosomal alterations in CLL/SLL most consistent finding which is present in approximately 50% of patients
trisomy of chromosome 12
Chromosomal alterations in CLL/SLL observed in non- T and non-B types
translocation of chromosomes 9 and 22
Displays the classic surface immunoglobulin (SIg) markers.
B-Cells
B-Cells displays the classic surface immunoglobulin (SIg) markers.
CD19
CD20
CD24
CD5
Abnormal findings discovered on a complete blood count (CBC)
Common symptoms include malaise, low-grade fever, and night sweats.
Hepatosplenomegaly is also frequently present.
CHRONIC LYMPHOCYTIC LEUKEMIA
SMALL LYMPHOCYTIC LYMPHOMA
CLL/SLL laboratory data
30 to 200 × 109/L
1/3 of patients, the total leukocyte count is greater than 100 × 109/L.
Absolute lymphocytosis, 80% or 90% small lymphocytes.
hypogammaglobulinemia.
Uncommon chronic lymphoproliferative disorder of the B-lymphocyte type.
More common in males than in females.
It has been suggested that a locus on the X chromosome might be involved in HCL
HAIRY CELL LEUKEMIA
appearance of fine, hair-like, irregular cytoplasmic projections that are characteristic of lymphocytes in this disease
HCL
The cytochemical features of HCL include a
strong acid phosphatase reaction
not inhibited by tartaric acid or tartrate-resistant acid phosphatase (TRAP) stain
Following ________, enzyme activity in the hairy cell may be TRAP negative
interferon therapy
cells display strong SIg. A. Hairy Cells Leukemia B. CLL/SLL C. Prolymphocytic leukemia D. Chronic leukemia
A
Immunological Markers for hairy cell leukemia
CD19+, CD20+, CD22+, CD24+, and CD25+
Immunological Markers for hairy cell leukemia recognizes what receptor
interleukin-2 (Tac) receptor
More aggressive type of HCL and has different morphological characteristics than typical HCL.
HAIRY CELL LEUKEMIA VARIANT
Cells are smaller than the typical HCL cell with a central round nucleus, prominent nucleoli, a larger nuclear cytoplasmic ratio, and basophilic cytoplasm with occasional cytoplasmic projections.
HAIRY CELL LEUKEMIA VARIANT
Differential diagnosis of vHCL from typical HCL can be made by
cytochemical staining (TRAP) and immunophenotyping
Malignancy of B prolymphocytes affecting blood, bone marrow, and spleen.
Characterized by a large number of small lymphocytes with scant cytoplasm and the immature features of prolymphocytes in the peripheral blood.
Leukocytosis can exceed 100 × 109/L.
PROLYMPHOCYTIC LEUKEMIA
In PROLYMPHOCYTIC LEUKEMIA, prolymphocytes must exceed _______ of lymphoid cells in the peripheral blood.
55%
Immunological Markers for PROLYMPHOCYTIC LEUKEMIA
CD19+ CD20+ CD24+ CD22+ Cells display strong SIg.
a malignant bone marrow– based, plasma cell neoplasm associated with abnormal protein production.
Multiple myeloma
an increased number of plasma cells in the peripheral blood and should be considered a form of multiple myeloma and not a separate entity
Plasma cell leukemia
Usually evolves from an asymptomatic premalignant stage of clonal plasma cell proliferation called “monoclonal gammopathy of undetermined significance (MGUS).
MULTIPLE MYELOMA (PLASMA CELL MYELOMA)
MULTIPLE MYELOMA (PLASMA CELL MYELOMA) onset of disorder
ages of 40 and 70 years
Bone pain, weakness, fatigue
Abnormal bleeding - may be a prominent feature
In some patients: major symptoms result from acute infection, renal insufficiency, hypercalcemia, or amyloidosis.
Approximately 90% of patients suffer from broadly disseminated destruction of the skeleton
MULTIPLE MYELOMA (PLASMA CELL MYELOMA)
Leads to a compensatory decrease in synthesis and increase in catabolism of normal immunoglobulins.
MULTIPLE MYELOMA (PLASMA CELL MYELOMA)
In MULTIPLE MYELOMA (PLASMA CELL MYELOMA) this may develop as a result of bone marrow failure
Granulocytopenia
In MM, increased plasma volume caused by monoclonal protein commonly produces
hypervolemia
Laboratory data of MM
Increased plasma cells Rouleaux formation Relative lymphocytosis Bleeding overproduction of IgM (19S) antibodies monoclonal serum protein is detected
In MM, what type of antibody is present in majority of the patients
IgG
In MM, what are the antibodies that is less frequently seen and rarely seen?
IgA and IgD
It is a B-cell neoplasm characterized by lymphoplasmo-proliferative disorder with infiltration of the bone marrow and a monoclonal immunoglobulin M (IgM) protein.
WALDENSTRÖM PRIMARY MACROGLOBULINEMIA
LYMPHOPLASMACYTIC LYMPHOMA
Associated with the production of abnormally large amounts of gamma globulin of the 19S or IgM type.
Basic abnormality in this macroglobulinemia is uncontrolled proliferation of lymphocyte and plasma cells.
WALDENSTRÖM PRIMARY MACROGLOBULINEMIA
LYMPHOPLASMACYTIC LYMPHOMA
→ includes the various forms of leukemias and malignant lymphomas that are of lymphoreticular origin.
LYMPHOMAS
includes the various forms of leukemias and malignant lymphomas that are of lymphoreticular origin.
Lymphoproliferative disorder
group of closely related disorders that are characterized by the overproliferation of one or more types of cells of the lymphoid system such as lymphoreticular stem cells, lymphocytes, reticulum cells, and histiocytes
Lymphomas
Reed-Sternberg cells function as:
stimulatory cells in lymphocyte reaction
accessory cells in mitogen-induced T-cell proliferation
antigen presenting in HLA-DR restricted, antigen specific in T-cell activation
Characterized by a persistent defect in the cellular immunity with abnormalities in T lymphocytes, IL-2 production, and increased sensitivity to suppressor monocytes and normal T suppressor cells.
HODGKIN DISEASE
Aneuploidy, or a deviation from the diploid number of chromosomes, resulting from the gain or loss of chromosomes or from polyploids
HODGKIN DISEASE
In HODGKIN DISEASE there is a gain of chromosome ________________
1, 2, 5, 12, and 21
Most frequent type of NHL is
diffuse large B-cell lymphoma
Three different types of diffuse large B-cell lymphomas
Germinal center, B cell like lymphoma
Activated B cell like lymphoma
New subtype, type 3 diffuse large B-cell lymphoma
Type of diffuse large B-cell lymphomas that expresses high levels of genes characteristic of germinal center, B-cell–like lymal germinal center B cells
Germinal center, B-cell–like lymphoma
Type of diffuse large B-cell lymphomas that expresses genes characteristic of mitogenically activated blood B cells
Activated B-cell–like lymphoma
Type of diffuse large B-cell lymphomas which has a heterogeneous gene expression that suggests it includes more than one subtype of lymphoma
New subgroup, type 3 diffuse large B-cell lymphoma
leukemic phase of cutaneous T- cell lymphoma, mycosis fungoides.
Sezary Syndrome
Typically the size of a small lymphocyte and has a dark-staining, clumped, nuclear chromatin pattern
Sézary cell
derived from mature or post thymic T cells
Mature T-Cell & NK-Cell Neoplasms
Consistently associated with the BCR-ABL 1 fusion gene located in the Philadelphia chromosome.
CHRONIC MYELOGENOUS LEUKEMIA
reciprocal translocation of DNA between chromosomes 9 and 22
Ph1 chromosome
Stains ALP present in most neutrophil
Leukocyte Alkaline Phosphatase Stain (LAP)
Leukocyte Alkaline Phosphatase Stain (LAP) differentiate
CML (↓) from leukemoid reaction or polycythemia vera
In Leukocyte Alkaline Phosphatase Stain (LAP), what anticoagulant must be used and what anticoagulant results to falsely decreased
Heparin
EDTA
Leukocyte Alkaline Phosphatase Stain (LAP) is increased in
polycythemia vera
Leukemoid Reaction
3rd Trimester of Pregnancy
Leukocyte Alkaline Phosphatase Stain (LAP) is decreased in
(↓) CML, IM, PA, PNH
Clinical description was that of a patient with engorged veins, plethora, and an elevated red blood cell count.
Leukocytosis and thrombocythemia were recognized as additional features
Polycythemia Rubra Vera
Added PV to the classification of MPNs
Main differential diagnosis is that of reactive erythrocytosis due to hypoxia
Dameshek
Clonal stem cell disorder characterized by hyperproliferation of the erythroid, myeloid, and megakaryocytic lineages
POLYCYTHEMIA VERA
Northern blot analysis showed that PV-1 is highly expressed in _________________ and to a much lesser degree in fetal liver
normal human bone marrow
a common complication of PV and often is unrecognized
Thrombophlebitis with pulmonary embolism
characterized by systemic bone marrow fibrosis and extramedullary hematopoiesis.
Primary Myelofibrosis
caused by infiltrative disorders, including malignancies and infections, or exposure to chemical toxins or irradiation.
Secondary Myelofibrosis
Characterized by a significant increase in circulating platelets, usually in excess of 1,000 × 109/L.
ESSENTIAL THROMBOCYTOSIS/ESSENTIAL THROMBOCYTHEMIA
Exhibits features of both myelodysplastic and myeloproliferative disorders at the time of diagnosis.
Characterized by leukocytosis with a majority of neutrophils.
Multilineage dysplasia is common
Atypical chronic myeloid leukemia
BCR-ABL1negative
Disorder of childhood
Proliferation of granulocytic and monocytic lineages
Blasts and promonocytes account for less than 20% of peripheral blood cells and bone marrow aspirates.
Erythroid and megakaryocytic abnormalities are frequently preset
BCR-ABL1 mutation is absent but mutations of genes of the RAS/MAPK pathway are characteristic.
Juvenile myelomonocytic leukemia
JMML
Neoplasm meets the definition of MDS/MPN but does not meet the criteria for CMML or the other classification in this category
Myelodysplastic/myeloproliferative neoplasm, unclassifiable
