Presentation on theme: "Leukopoiesis Normal and abnormal"— Presentation transcript:
1Leukopoiesis Normal and abnormal Barrett W. Dick, M.D.Director, Hematology LaboratoriesMemorial Medical CenterSpringfield. ILClinical Professor, Pathology and Medicine Southern Illinois School of MedicineJune, 2000
3Stem cell vs. Progenitor Cell Stem cell: a primitive cell that is capable of both self renewal and differentiation. Upon differentiation, it can develop into myeloid or lymphoid lineages. Progenitor cell: a primitive cell beyond the stem cell stage that is committed to lineage differentiation
4Evidence for Separate Common Progenitor Cell for B Lymphocytes and Myeloid Progenitor Philadelphia chromosome is found in CML and a significant fraction of ALL, common B cell type.Blast crisis in CML is frequently lymphoblastic, almost always B cell type.
11Neutrophil segmented form - "seg" To be considered a segmented form, there must be at least one point where the the nucleus is segmented into two lobes with the connection between the containing no visible DNA (1). If there is visible DNA (2), it is not considered a segment.
12Neutrophil Maturation When a differential count is performed, traditionally, the device used for tallying the cells is arranged with the least mature cells on the left. This is the historic origin of the term "shift to the left" describing a relative increase in immature forms.
19Performance of a White Cell Differential - General Principles Scan at low power:Identify appropriate thin areaEvaluate quality of smearHigh power oil- 50X or 100X:Scan for abnormal cells and make a qualitative assessmentPerform 200 cell differentialRescan to confirm that differential is an accurate representation
20Confidence Interval for Manual Differentials On a cell manual differential, if a cell type is reported as:"50%", the 95% C.I. is ~40% - 60% .‘1%’, the C.I. is ~0-8% .A statistically meaningful differential cell differential required but not practicalConclusions:Scanning the smear for abnormalities is more important than the diffAbsolute counts from the machine are more accurate
21Exceptions to the Absolute Counts "Rule" % Segs compared % Bands - Ratio of the two defines a "left shift"% Mono’s - Relative monocytosis is important in some clinical situationsAgranuloctosis/neutropenia- Monocytosis frequently predicts bone marrow recoveryRelative or absolute monocytosis is a frequent finding in myelodysplastic syndromes
24Principles of Blood Smear Examination A 200 cell differential is a semi-quantitative estimate of the actual diff because the sampling error is very high - you are looking at a very small sample of a very large populationWhen a differential is reported, what it should mean is that an experienced individual has examined that smear and, other than what was reported, no significant abnormalities were seenIn practice, because of forced cutbacks in staffing, this currently is unlikely to be the case in most institutionsConclusion: You better learn to examine blood smears
30BasophilBasophil granules are very soluble. In this example they are partially dissolved and are easily mistaken for toxic granules in a neutrophil. The background cytoplasm in a basophil is gray in contrast to the salmon-pink color in a neutrophil
32Large Transformed Lymphocyte In a normal blood smear, 15-17% of the lymphocytes may be large lymphocytes.
33Large Granular Lymphocyte Frequently, but arbitrarily included as reactive lymphocytes. The granules identify them as "killer" cells.,
34Large granular lymphocytes- "LGL’s" There are at least two distinct subclasses of killer cellsADCC: antibody dependent cytotoxic cells; a subclass of CD8 cells. Require the presence of an antibody to be functionalNatural killer cells: do not require the presence of an antibody
42Hypersegmented Neutrophil Hypersegmented neutrophils are classically associated with megaloblastic processes. However, they are commonly present when there is a neutrophilia. Rarely, it is a hereditary abnormality.
43Hypersegmented Neutrophil in Megaloblastic Anemia
44Transformed lymphocytes aka: "Reactive", "Large", "Variant" or "Atypical"
47Lymphoblasts, Acute Lymphocytic Leukemia Lymphoblasts are usually smaller than myeloblasts and frequently have little or no visible cytoplasm.
48Myelocyte - Eo/Baso?Abnormal myelocyte frequently interpreted as having both eosinophil and basophil granules. Most likely this is a normal eosinophil myelocyte with primary granules. In either case the significance is they are virtually only seen in the blood in chronic myeloproliferative disorders.
49Pelger-Huet AnomalyThe Pelger-Huet anomaly can be either hereditary or acquired. The main features are exaggerated nuclear clumping and hyposegmetation. The latter manifests itself as "increased " band counts.
50Pseudo Pelger-Huet Anomaly Cells that look metamyelocytes are almost never found in the hereditary form.
51Hypogranular Neutrophils The color of normal neutrophils is due to their granules. When they are poorly granulated they appear gray which is the normal cytoplasmic color.
52Sezary's Syndrome Cutaneous T-cell Lymphoma The "cerebriform" nucleus is characteristic of some T cellleukemia/lymphomas