Patterns of Lymphoid Neoplasia in Peripheral Blood. Leon F. Baltrucki, M.D. Leon F. Baltrucki, M.D. Disclosure

Transcription

1 Patterns of Lymphoid Neoplasia in Peripheral Blood Leon F. Baltrucki, M.D. Leon F. Baltrucki, M.D. Disclosure Dr Baltrucki has received an honorarium for his participation as a faculty presenter in this educational activity. 1

2 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 Cytogenetics Detection, Recognition of Disease Progression & Complications Based on Patterns Reflecting Natural Hx 2

3 Problems with Disease Recognition Laboratory Requirements Concerted Cooperative Effort High Degree of Expertise in Cytology Oversight Disease Features Diversity a clinical-biological spectrum Variation - different forms of same entity Similarity Overlapping Features with subtle differences Rarity many entities rarely encountered Evolution from low-grade neoplasia or chronic reactive conditions Patterns of Lymphoid Neoplasia in Peripheral Blood Quantitative Lymphocytosis Lymphopenia +/- Anemia +/- Thrombocytopenia +/- Neutropenia Monocytosis Neutrophilia Eosinophilia Qualitative Scatterplots Diff IMI WBC IP Messages Atypical Lympho? Abn Lympho/L_Blasts? Monocytosis Blasts? Immature Gran? Cytology 3

4 Patterns of Lymphocytosis Analyzer Features Scatterplots IP Messages Atypical Lympho? Abn Lympho/L_Blasts? Monocytosis Hematological Features Magnitude Anemia / Cytopenias Monocytosis Neutrophilia Eosinophilia Clinical Features Historical Features Duration Doubling Time Cytological Features Degree of Variation Nuclear Irregularity Prominent Nucleoli Diagnostic Algorithms CBC + Automated WBC diff Cell Counts + IP messages Blood Smear Findings Abnormal Cytology Chart Review Clinical Context + Cumulative CBC Data Flow Cytometry FISH / Genetic Testing Molecular / Cellular Diagnosis 4

5 Flow Cytometry Cell Surface Antigens FITC Monoclonal Abs Lambda- PE CD23- PE CD20- FITC CD5- FITC Mature B-Cell Leukemias Flow Cytometry MCL HCL LPL MZL FL PLL PCL SIg +/ CyIg +++ CD / CD CD /+ -/+ -/+ - FMC7 -/ CD / CD CD38 -/+ - -/ /

6 Fluorescence In Situ Hybridization 11q13 region CCND1 IGH - JH Fusion Signals CCND1 14q32 region IGH - JH Normal Genes INTERPRETATION: Positive for a CCND1/IGH rearrangement Mature B-Cell Neoplasms - Leukemias Chronic Lymphocytic Leukemia Mantle Cell Leukemia B-Cell Prolymphocytic Leukemia * Splenic Marginal Zone Lymphoma Hairy Cell Leukemia Lymphoplasmacytic Lymphoma Plasma Cell Myeloma Plasma Cell Leukemia * Follicular Lymphoma (Leukemic) Burkitt s Leukemia * 6

7 Mature B-Cell Neoplasms Cytology B-PLL HCL MCL LPL MZL FL BL - Cytology Early Stage/ Chronic Phase Small Cells Uniform Population High N/C ratio Round Nucleus Clumped/Cracked to Condensed Chromatin Inconspicuous Nucleolus Pale Basophilic Cytoplasm 7

8 -Population Assessment Typical Chronic Phase Atypical or Advanced Prolymphocyte Genetic Risk-Stratification in 13q del Tri 12q Normal 17p del 11q del 8

9 - Natural History MZL MCL LPL Early MCL B-PLL Middle Late Date Range: All Results from 01/04/97 to 03/10/07 Disease Progression Prolymphocytoid Transformation 9

10 DDx: Atypical or Progressive MCL B-PLL vs. MCL MCL 10

11 Mantle Cell Leukemia Hyper-mutation Features like ALL B-Prolymphocytic Leukemia Peripheral Blood, Bone Marrow & Spleen WBC > 100 K Prolymphocytes > 55% Marked Anemia & Thrombocytopenia Massive Splenomegaly Complex Cytogenetics B Symptoms Rapidly Progressive 11

12 Splenic Marginal Zone Lymphoma Lymphocytosis mild Low-Grade Cytology / Villous Projections +/PB, Bone Marrow & Spleen Involvement MZL +/- Hepatitis C +/+/ Monoclonal Paraprotein +/- ITP, AIHA HCL Rare Transformations to High-Grade NHL HCL Bone Marrow Classic Pattern Reticulin Fibrosis Hypoplastic Marrow Spindle-Cell Pattern CD20 12

13 Classic Hairy Cell Leukemia - Cytology Pancytopenia Pattern Neutropenia Moderate to Marked Thrombocytopenia mild to moderate Anemia mild to absent Monocytopenia Circulating Hairy Cells may be very rare; fragile, & not in counting zone) Lymphoplasmacytic Lymphoma-WM +/ Lymphocytosis Rouleaux MCP often IgM type +/ Hyperviscosity Bleeding CNS Sx Blindness Hepatosplenomegaly 13

14 Anemia Thrombocytopenia Rouleaux Multiple Myeloma +/- Plasma Cells or Plasmacytoid Lymphs Primary PCL DDx = LPL Plasma Cell Leukemia Secondary PCL - Hx of MM 14

15 Mature T-Cell Neoplasms Cytology T-LGL SS/MF ATLL T-PLL PTCL 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 > to Detection in Peripheral Blood > to Molecular Diagnosis An Emerging Paradigm 15

16 QUESTIONS?? 16