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Patterns of Lymphoid Neoplasia in Peripheral Blood
Leon F. Baltrucki, M.D.Leon F. Baltrucki, M.D.
D B l ki h i d h i
Disclosure
• Dr Baltrucki has received an honorarium for his participation as a faculty presenter in this educational activity.
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Patterns of Lymphoid Neoplasia in Peripheral Blood
Leon F. Baltrucki, M.D.Leon F. Baltrucki, M.D.
Lymphoid Neoplasia - Overview
Broad Variety of Diseases
Clinically Indolent > Life Threatening
Many Rarely Encountered
Disease Detection Requires Correlation of Analyzer Data and Blood Smear Findings, with
Cumulative Hematological Data and
Clinical Findings
Flow Cytometry & FISH CytogeneticsFlow Cytometry & FISH Cytogenetics
Detection, Recognition of Disease Progression
& Complications
Based on Patterns Reflecting Natural Hx
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Problems with Disease Recognition
Laboratory RequirementsConcerted Cooperative EffortHigh Degree of Expertise in Cytologyg g p y gyOversight
Disease FeaturesDiversity – a clinical-biological spectrumVariation - different forms of same entitySimilarity – Overlapping Features with subtle
differencesdifferencesRarity – many entities rarely encounteredEvolution from low-grade neoplasia or chronic
reactive conditions
Patterns of Lymphoid Neoplasia in Peripheral Blood
Lymphocytosis Scatterplots
Quantitative Qualitative
Lymphocytosis
Lymphopenia
+/- Anemia
+/- Thrombocytopenia
+/- Neutropenia
Monocytosis
ScatterplotsDiffIMI
WBC IP MessagesAtypical Lympho?Abn Lympho/L_Blasts?Monocytosisy
Neutrophilia
Eosinophilia
yBlasts?Immature Gran?
Cytology
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Patterns of Lymphocytosis
Analyzer FeaturesScatterplotsIP MessagesAtypical Lympho?
Hematological FeaturesMagnitudeAnemia / CytopeniasMonocytosis
Clinical Features
Atypical Lympho?Abn Lympho/L_Blasts?Monocytosis
MonocytosisNeutrophiliaEosinophilia
Historical FeaturesDuration Doubling Time
Cytological FeaturesDegree of VariationNuclear IrregularityProminent Nucleoli
Diagnostic Algorithms
Cell Counts + IP messages
CBC + Automated WBC diff Blood Smear Findings
Abnormal Cytology
Chart Review
Clinical Context +Cumulative CBC Data
Flow Cytometry FISH / Genetic Testing
Molecular / Cellular Diagnosis
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Flow Cytometry
FITC
Cell Surface Antigens
PE
E
Monoclonal Abs
CD20- FITC CD5- FITC
Lam
bd
a-P
CD
23-
PE
Mature B-Cell Leukemias – Flow Cytometry
CLL MCL HCL LPL MZL FL PLL PCL
SIg +/- ++ +++ +++ ++ + ++CyIg +++
CD5 + + - -/+ - - - -CD20 + ++ +++ ++ ++ + ++ -CD23 + - - - -/+ -/+ -/+ -FMC7 -/+ + + + + + + -CD25 - - ++ - -/+ - - -CD103 - - ++ ++ - - - -CD38 -/+ - -/+ + - -/+ - +++
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Fluorescence In Situ Hybridization
11q13 region CCND1 IGH - JH
Fusion Signals
14q32 region
CCND1
INTERPRETATION: Positive for a CCND1/IGH rearrangement
IGH - JH Normal Genes
Mature B-Cell Neoplasms - Leukemias
Chronic Lymphocytic LeukemiaMantle Cell LeukemiaB-Cell Prolymphocytic Leukemia *B-Cell Prolymphocytic LeukemiaSplenic Marginal Zone LymphomaHairy Cell Leukemia
Lymphoplasmacytic LymphomaPlasma Cell MyelomayPlasma Cell Leukemia *
Follicular Lymphoma (Leukemic)Burkitt’s Leukemia *
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Mature B-Cell Neoplasms –CytologyB-PLL
MZL
HCL
CLL
MCL
LPL
CLL
FL BL
LPL
CLL - Cytology
Early Stage/ Chronic Phase CLL
Small Cells – Uniform Population
High N/C ratio
Round Nucleus
Clumped/Cracked to Condensed Chromatin
Inconspicuous NucleolusInconspicuous Nucleolus
Pale Basophilic Cytoplasm
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CLL-Population Assessment
Typical Chronic Phase CLL
“Atypical” or Advanced CLL
Prolymphocyte
Genetic Risk-Stratification in CLL
13q del Tri 12qNormal
17p del 11q del
Normal
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CLL - Natural History
CLLMZL
CLLMCLB-PLL
MCLLPL
B-PLL
Early
Middle
Late
Date Range: All Results from 01/04/97 to 03/10/07
CLL – Disease Progression
“Prolymphocytoid” TransformationTransformation
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DDx: Atypical or Progressive CLL
MCL CLL B-PLL
CLL vs. MCL
CLL
MCL
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Mantle Cell Leukemia
Hyper-mutation
Features like ALL
CLL
B-Prolymphocytic Leukemia
Peripheral Blood, Bone Marrow & Spleen
WBC > 100 KWBC > 100 K“Prolymphocytes” > 55%
Marked Anemia & Thrombocytopenia
Massive Splenomegaly
CLL Complex Cytogenetics
“B Symptoms” Rapidly Progressive
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Splenic Marginal Zone Lymphoma
Lymphocytosis – mild
Low-Grade Cytology /
CLL
+/- Villous Projections
PB, Bone Marrow & Spleen Involvement
+/- Hepatitis C+/ Monoclonal Paraprotein
MZL
HCL
+/- Monoclonal Paraprotein+/- ITP, AIHA
Rare Transformations to High-Grade NHL
HCL –Bone Marrow
Reticulin Fibrosis“Classic” Pattern
Spindle-Cell PatternHypoplastic Marrow
CD20CD20
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Classic Hairy Cell Leukemia - Cytology
Pancytopenia PatternNeutropenia – Moderate to MarkedThrombocytopenia – mild to moderateAnemia – mild to absent
Monocytopenia
Ci l ti H i C llCirculating Hairy Cells –may be very rare; fragile, &
not in counting zone)
Lymphoplasmacytic Lymphoma-WM
+/‐ Lymphocytosis
Rouleaux
MCP often IgM‐type
+/‐ Hyperviscosity
Bleeding
CNS Sx
CLL
Blindness
Hepatosplenomegaly
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Multiple Myeloma
AnemiaThrombocytopeniaRouleaux
+/- Plasma Cells or“Plasmacytoid Lymphs”
Plasma Cell Leukemia
Primary PCL – DDx = LPL
S dSecondary PCL -Hx of MM
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Mature T-Cell Neoplasms –Cytology
SS/MFT-LGL ATLL
PTCL
T-PLL
Patterns of Lymphoid Neoplasia in PB
Patterns of Lymphoid Neoplasia Emerge when we correlate ALL available data
Detection of these Diseases is Primarily OUR Responsibility
Detection in Peripheral Blood > toDetection in Peripheral Blood > to Molecular Diagnosis – An Emerging Paradigm
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QUESTIONS ??