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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 ??