Introduction to the Hematopoietic Neoplasms
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Transcript Introduction to the Hematopoietic Neoplasms
MLAB 1415- Hematology
Keri Brophy-Martinez
Chapter 21:
Introduction to Hematopoietic Neoplasms
Terms
Neoplasm or tumor: “New growth”
Results from a dysregular prolieferation of a single transformed cell
Can be malignant or benign
Malignant
“Deadly”
Clone of abnormal , proliferating cells, without function or
differentiation
Have the potential to metastasize or get bigger
“Cancer”
Benign
Premalignant
Originate from highly organized, differentiated cells
Do not spread or invade surrounding tissues
Classification of Neoplasms in Bone Marrow
Lymphoid
Myeloid
Only lymphocytic cells affected
Granulocytes, monocytes, megakaryocytes,
erythrocytes affected
Both Lymphoid and Myeloid lines can
include benign and malignant neoplasms
Further Classifications
Premalignant myeloid neoplasm
Myeloproliferative disorders (MPD)
Myelodysplastic syndromes (MDS)
Premalignant lymphoid disorders
Chronic lymphoproliferative disorders
Plasma cell disorders
Lymphoid and myeloid malignant bone marrow neoplasms
Leukemia
More Terms
Leukemia
A malignant disease of hematopoietic tissue characterized
by replacement of normal bone marrow elements with
abnormal (neoplastic) blood cells. Abnormal cells are also
seen in peripheral blood
Lymphoma
Abnormal proliferation of lymphoid cells within the
lymphatic tissue or lymph nodes, results in a solid tumor
Leukemias
General Classification
Acute
Chronic
Age
All ages
Adults
Clinical onset
Sudden
Gradual
Course of disease
Weeks to months
Months to years
Predominant cell
Blasts
Some mature forms
Mature forms
Anemia
Mild-severe
Mild
Thrombocytopenia
Mild-severe
Mild
WBC
Variable
Increased
Organomegaly
Mild
Prominent
Blood Picture
Acute
Chronic
How Do Leukemias Arise?
Somatic mutation of a single
hematopoietic stem or progenitor
cell
Unlimited self-renewal of the
cancer-initiating cell
As the mutant cell line
predominates, normal
hematopoiesis is inhibited
causing leukemic cells to spill
into peripheral blood
Proto-oncogenes and Oncogenes
Proto-Oncogene—normal unaltered gene that has the
potential to become an oncogene
Oncogene–Altered cell genes that cause tumors
Located at breakpoints of chromosomal aberrations, such as
translocations
Oncogene Activation
Factors
Genetic susceptibility
Fanconi’s anemia
Down’s syndrome (18-20 fold increased incidence)
Somatic mutation
Ionizing radiation, nuclear weapons
Chemicals and drugs
Benzene,Chloramphenicol, phenylbutazone
Certain chemotherapy drugs that are cytotoxic, especially when used in
conjuction with therapeutic radiation
Viral infection
Retrovirus-HIV-1, HTLVI, II
Immunologic dysfunction
Ataxia-telangiectasia - lymphoid leukemia or lymphoma
Sex-linked agammaglobulinemia
Epidemiology
Most new cases found in older adults ( > 67 yrs old)
50% of leukemias are acute
More common in whites
Age groups
ALL: children 2-5 years old: lymphoid
CLL: Adults> 50: lymphoid
AML: adults: myeloid
CML: adults: myeloid
Clinical Findings
Anemia
Due to erythropenia
Infection
Due to neutropenia
Bleeding Episodes
Due to thrombocytopenia
Bone pain
Due to marrow expansion
Weight loss
Evaluation of Leukemia
Note onset of symptoms
Analyzing CBC
Observe cell lineage
Thrombocytopenia?
RBC level/ anemia?
Lymphoid or Myeloid?
Assess maturity of predominating cells
Lab Features
Normochromic,normocytic anemia
Thrombocytopenia
Platelet morphology and function can be abnormal
Leukocyte count can be increased, decreased or normal
Immature leukocyte precursors seen
Bone marrow hypercellular
Maturation abnormalities in all cell lines
Uric acid increased
Official Hematopoietic Neoplasm Classification
Two systems
French-American British(FAB)
Historical
World Health Organization (WHO)**
Widely accepted
Important because..
Allows clinicians a way to compare therapeutic regimens
System for ID and comparison of clinical features & lab findings
Permit associations of cytogenetic abnormalities with disease
FAB classification
Consists of three groups
Myeloproliferative Disorders(MPD)
Myelodysplastic Syndromes(MDS)
Acute leukemia (AL)
Based on morphological characteristic of
Wright-stained cells in peripheral blood or
bone marrow with supplementary
cytochemical stains
WHO Classification
Classification system uses morphology, cytochemistry and
immunophenotyping to determine cell lineage and degree of
maturation(similar to FAB)
Additionally uses genetic and clinical features prior to therapy and history
of MDS to define subgroups
Consists of four groups
Myeloid
Lymphoid
Further classified as MPD, MDS/MPD, MDS, AML
Further classified as B cell, T/NK cell, Hodgkin’s Disease
Mast cell
Histiocytic
Lab Techniques for Diagnosis and classification of
neoplasms
Cytochemical analysis
In vitro staining of cells to look at cells’ chemical
composition
Evaluation of positivity in these stains must be determined
on the leukemic blast stage of the cell
Usually performed on bone marrow slides
Helpful in differentiating lymphoid or myeloid lineage of
blasts in AL
Reactions are either enzymatic or nonenzymatic
Cytochemical stains
Types
Myeloperoxidase (MPO)
Activity is present in the primary granules and Auer rods of
myeloid cells
Separates myeloid and lymphoid blasts
Stains late myeloblasts, granulocytes, monocytes less intensely
Differentiates AML from ALL
Granules stain reddish-brown
Smears must be fresh
Cytochemical stains: con’t
Sudan Black B
Activity is present in phospholipids in the membrane of 1̊ (nonspecific)
and 2̊ granules (specific)
Parallels myeloperoxidase but smears do not have to be fresh
Granules stain black
Periodic Acid Schiff (PAS)
Activity is in glycogen and related substances
Stains lymphocytes, granulocytes, megakaryocytes
Helpful in diagnosing erythroleukemia where there is strong reactivity
in normoblasts
Stains red-purple in blocks in cytoplasm
Cytochemical stains: con’t
Esterases
Specific Esterase (Naphthol AS-D Chloroacetate)
Activity is in cytoplasm
Stains neutrophilic granulocytes, differentiates monoblasts and
myeloblasts
Granules of myeloblasts stain blue-black
Nonspecific Esterase (Alpha-Naphthyl Acetate)
Activity is in cytoplasm
Stains monocytes and also megakaryocytes
Differentiates myeloblasts from monoblasts (can use a double staining
technique to view both specific and nonspecific stains on one smear)
Addition of Na fluoride to this stain inhibits activity in monocytes
Granules stain orange red
Cytochemical stains: con’t
Leukocyte Alkaline Phosphatase (LAP)
Enzyme within the 2O or specific granules of
maturing granulocytes
Distinguishes leukemoid reactions ( ) from
chronic myelogenous leukemia ( )
Acid Phosphatase
Present in lysosomes in normal leukocytes
Helpful in diagnosing hairy cell leukemia because
they are NOT inhibited by TRAP
Cytochemical stains: con’t
Terminal Deoxynucleotidy transferase (TdT)
Primitive cell marker found in cell nuclei
Distinguishes ALL from malignant lymphoma
Toluidine Blue
Positive marker for basophils and mast cells
Lab Techniques for Diagnosis and classification of
neoplasms
Immunologic marker studies
Cell surface markers
Monoclonal or polyclonal antisera is added to
cell suspensions of fresh peripheral blood or
bone marrow and an immunofluorescent
method is used in a flow cytometry instrument
to analyze the markers which are expressed as
cluster designations (CD). CD’s identify
antibodies that are specific for certain cells
and allow for a positive identification.
Lab Techniques for Diagnosis and classification of
neoplasms
Molecular Genetics
This newer method of diagnosing leukemia consists of DNA probes and
polymerase chain reaction (PCR)-based studies. They are rapid and precise
and are used to confirm chromosomal abnormalities that are not detected by
conventional studies. They are also used to monitor residual disease
following therapy.
FISH (Fluorescence in situ hybridization)
Cytogenetics (Chromosome studies)
Identifies chromosome translocations which are specific for
certain leukemias
Philadelphia chromosome (t[9:22]) is associated with CML
t[15:17] is associated with acute promyelocytic leukemia
Treatment
Cures are not common except in childhood
leukemia. The best hope for a cure in adults
lies in bone marrow transplantation.
Cytoreductive chemotherapy
Reduces the leukemic cell mass
Block DNA synthesis
Block RNA synthesis
Complications arise from marrow hypoplasia and
resulting cytopenia
Treatment
Radiotherapy (radiation)
Kills focalized leukemic cells
Usually used in addition to chemotherapy and for CNS
prophylaxis
Bone marrow transplantation
Bone marrow is eradicated with chemo and radiation.
Compatible donor cells are transfused and they travel to the
empty marrow where they engraft and repopulate the marrow
with healthy cells.
Complications include graft vs host (GVH) disease which can be
fatal.
References
McKenzie, Shirlyn B., and J. Lynne.
Williams. "Chapter 21." Introduction. Clinical
Laboratory Hematology. Boston: Pearson,
2010. Print.