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Patients with hematological malignancies in Belarus (adults) (2007).
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Limphoproliferative diseases
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T-cell differen-tiation stages
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Lymphopoiesis in lymph nodes.
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Acute leukemia.
Originated from bone marrow (>25% blasts).
Usually monoclonal
disease.
Lineage committed morphology (FAB classif.)
B and T
or myeloid malignant cells are estimated by immunophenotyping (FAB classif. 1996 classif.)
Cytogenetic abnormalities (WHO classif. 2001,2008).
Fusion genes as markers of disease diagnosis and prognosis.
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Acute leukemia
(WHO classification, 2008).
Mixed phenotype acute leukemia
(T or B- myeloid, NK-cell…)
B lymphoblastic leukemia/lymphoma with t(9:22)(q34;q11.2);
BCR-ABL1.
B lymphoblastic leukemia/lymphoma with t (v;11q23); MLL rearranged.
B lymphoblastic leukemia/lymphoma with t(12;21)(p13;q22) TEL-AML1 (ETV6-RUNX1)
B lymphoblastic leukemia/lymphoma with hyperdiploidy.
B lymphoblastic leukemia/lymphoma with hypodiploidy.
B lymphoblastic leukemia/lymphoma with t(5;14)(q31;q32); IL-3-IgH
B lymphoblastic leukemia/lymphoma with t (1;19)(q23;p13.3); TCF-PBX1
T lymphoblastic leukemia/lymphoma.
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Cytogenetic and genetic features of ALL.
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Chronic lymphocytic leukemia
(WHO classification, 2008).
Mature B-cell neoplasms
Chronic
lymphocytic leukemia/small lymphocytic lymphoma,
B-cell prolymphocytic leukemia,
Splenic marginal zone lymphoma,
Hairy
cell leukemia,
Lymphoplasmacytic lymphoma,
Waldenstrom macroglobulinemia,
Heavy chain diseases,
Plasma cell myeloma,
-MALT lymphoma,
Follicular lymphoma,
Diffuse large B-cell lymphoma,
Plasmablastic lymphoma,
Burkitt lymphoma.
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Chronic lymphocytic leukemia
(WHO classification, 2008).
Mature T-cell and
NK-cell neoplasms:
T-cell prolymphocytic leukemia,
T-cell large granular lymphocytic leukemia,
Aggressive NK-cell
leukemia,
Adult T-cell leukemia/lymphoma,
Mycosis fungoides,
Sezary syndrome,
Primary cutaneous CD30+ T cell lymphoproliferative disorders,
Peripheral T-cell lymphoma,
Anaplastic large cell lymphoma…
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Adverse prognostic factors of CLL
Diffuse infiltration of bone
marrow by lymphocytes;
Advanced age;
Male gender;
Deletions in chr.17p (p53!) or
11q (ATM !) (5-10% of pts for each) ;
High serum level of beta-2 – microglobulin;
Increased fraction of prolymphocytes in PB;
>20% of ZAP-70-positive cells, >30% CD38+ cells;
No rearangement in IgH V region.
Favorable prognostic factors
No diffuse infiltration of bone marrow by lymphocytes;
Deletion in chr.13 q (50% of pts);
<20% of ZAP-70-positive cells, <30% CD38+ cells;
Mutations in IgH V region.
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Typical B cell phenotype in CLL
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Strategy for CLL therapy.
First line of therapy:
Fludarabine, Cyclophosphamine, Rituximabe (FCR).
Chemotherapy, MABs such as alemtuzumab (directed against
CD52) and ofatumumab (directed against CD20) are also used.
Stem cell transplantation – rare.
Survival:
Subclinical “disease” can be identified in 3,5% of normal adults and up to 7% of individuals over the age of 70.
Survival rate depends on subtypes (6-8 years to 22 years).
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Hodgkin Lymphoma et al. (WHO, 2008).
Hodgkin lymphoma:
- classical
Hodgkin lymphoma,
- Lymphocyte-rich classical Hodgkin lymphoma, …
Histiocytic and
dendritic cell neoplasms:
- histiocytic sarcoma,
- Langerhans cell histiocytic,
- Follicular dendritic cell sarcoma,…
Posttranplantation lymphoproliferative disorders:
-plasmacytic hyperplasia,
-Infectious mononucleous-like PTLD,
-polymorphic PTLD,
- monomorphic PTLD (B- and T/NK-cell types),…
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Histological diagnosis of HD.
The Reed–Sternberg cells are identified
as large often bi-nucleated cells with prominent nucleoli and
an unusual CD45-, CD30+, CD15+/- immunophenotype. In approximately 50% of cases, the Reed–Sternberg cells are infected by the Epstein–Barr virus.
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The adverse prognostic factors for HD
Age ≥ 45
years
Stage IV disease
Hemoglobin < 105 g/l
Lymphocyte count < 600/µl
or < 8%
Male gender
Albumin < 40 g/l
White blood count ≥ 15,000/µl
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Stages and Therapy of HD
Therapy strategy: radiation therapy
+/- chemotherapy.
Prognosis: The 5-year survival rate for those patients
with a favorable prognosis was 98%, while that for patients with worse outlooks was at least 85%
Stage I is involvement of a single lymph node region (I) (mostly the cervical region) or single extralymphatic site (IIe);
Stage II is involvement of two or more lymph node regions on the same side of the diaphragm (II) or of one lymph node region and a contiguous extralymphatic site (IIe);
Stage III is involvement of lymph node regions on both sides of the diaphragm, which may include the spleen (IIIs) and/or limited contiguous extralymphatic organ or site (IIIe, IIIes);
Stage IV is disseminated involvement of one or more extralymphatic organs
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Non-Hodgkin lymphoma
Causes
The many different forms of lymphoma likely
have different causes. These possible causes and associations with
at least some forms of NHL include:
Infectious agents like Epstein-Barr virus, Human T-cell leukemia virus, Helicobacter pylori, HHV-8 and HIV infection.
Chemicals, like diphenylhydantion, dioxin, and phenoxyherbicides.
Medical treatments like radiation therapy and chemotherapy. Genetic diseases, like Klinefelter ‘s syndrome, Chediak-Higashi syndrome, ataxia-telangiectasia syndrome
Autoimmune diseases, like Sjogren’s syndrome, celiac sprue, rheumatoid arthritis and systemic lupus erythematosis
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Cytogenetic analysis for B-cell malignancies
t(11;14) is mainly
found in mantle cell lymphoma, but also in B-prolymphocytic
leukaemia, in plasma cell leukaemia, in splenic lymphoma with villous lymphocytes, in chronic lymphocytic leukaemia, and in multiple myeloma, herein briefly described; all these diseases involve a B-lineage lymphocyte
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Diagnosis of DLBCL by MicroArray technique:
Germinal center
B cell DLBCL vs activated (post-germinal center) B
cell DLBCL
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Burkitt’s lymphoma (rare type of NHL)
(endemic= EBV
positive)
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Immunophenotypic diagnosis of Burkitt’s lymphoma
The cells of BL
typically express monotypic surface IgM, CD19, CD20, CD22, CD10,
Bcl-6, and CD79a, and are negative for CD5, CD23, Bcl-2, and nuclear terminal deoxyribonucleotide transferase (TdT).Lack of surface immunoglobulin has been reported in a few cases. The presence of CD10 and Bcl-6 expression supports the germinal center-cell stage of differentiation.
A remarkable feature of BL is the high growth fraction (> 95%) as demonstrated by Ki-67. The leukemic cells of BL express a mature immunophenotype that distinguishes it from precursor B-cell acute lymphoblastic leukemia (ALL).
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Path from Normal plasma cells through Monoclonal Gammopathy
of Undetermined Significance to
Multiple Myeloma.
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Morphology of malignant plasma cells in blood (H&E
staining)
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Immunophenotyping of Plasma Cells
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Multiple Myeloma diagnosis and therapy.
Diagnosis: Roentgen + BM
biopsy+..
Therapy: chemotherapy, BMT.
Survival: 5-8 years.
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M-protein and diseases.
More than 50% of patients with
serum M protein have an initial clinical diagnosis of
MGUS ( M protein <30g/l in serum, +10% plasma cells in BM). The prevalence of MGUS increases with age, from approximately 1% in patients 50 to 60 years old to greater than 5% in those older than 70 years. The age-adjusted prevalence is higher in males than in females and is twice as high in patients of African descent as in patients of European descent
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Waldenstrom macroglobulinemia: pathogenesis
Immunophenotype of
BM cells in WM
Ig light chain - Positive
CD19
- Positive
CD20 - Positive
CD52 - Positive
Surface IgM - Positive
CD79b - Positive
CD11c - Usually negative
CD25 - Positive
CD23 - Usually negative
CD38 - Dim positive
FMC7 - Usually dim positive
CD22 - May be positive
CD5 - Negative
CD10 - Negative
CD27 - Dim positive
CD75 - Usually negative
CD138 - Usually negative
Bcl2 - Dim positive
Bcl6 - Usually absent
PAX5+ - Dim positive
CD45 (RA) - Usually positive
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Light chain Disease
(Bence-Jones proteins).
A Bence Jones protein is a
monoclonal globulion protein or immunoglobulin light chain found in
the urine, with a molecular weight of 22-24 kDa. Detection of Bence Jones protein may be suggestive of Multiple Myeloma or Waldenstrom’s macroglobulinemia.
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(Bence-Jones protein in serum/urine (up) and serum (down))
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HEAVY CHAIN DISEASE
Heavy chain disease is a form of paraproteinemia with
a proliferation of cells producing immunoglobulin heavy chains
There are
four forms:
alpha chain disease (Seligmann's disease)
gamma chain disease (Franklin's disease)
mu chain disease
delta chain disease
