leukopoiesis normal and abnormal
DESCRIPTION
Leukopoiesis Normal and abnormal. Barrett W. Dick, M.D. Director, Hematology Laboratories Memorial Medical Center Springfield. IL Clinical Professor, Pathology and Medicine Southern Illinois School of Medicine June, 2000. Evolution of White Cells. Stem cell vs. Progenitor Cell. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/1.jpg)
LEUKOPOIESISNORMAL AND ABNORMAL
Barrett W. Dick, M.D.Director, Hematology Laboratories
Memorial Medical CenterSpringfield. IL
Clinical Professor, Pathology and Medicine
Southern Illinois School of Medicine
June, 2000
![Page 2: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/2.jpg)
Evolution of White Cells
![Page 3: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/3.jpg)
Stem 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
![Page 4: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/4.jpg)
Evidence 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.
![Page 5: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/5.jpg)
Granulopoiesis
![Page 6: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/6.jpg)
Myeloblast
![Page 7: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/7.jpg)
Promyelocyte
![Page 8: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/8.jpg)
Neutrophil Myelocyte
![Page 9: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/9.jpg)
Neutrophil Metamyelocyte
![Page 10: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/10.jpg)
Neutrophil band form - "band"
![Page 11: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/11.jpg)
Neutrophil 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.
![Page 12: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/12.jpg)
Neutrophil 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.
![Page 13: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/13.jpg)
Lymphocyte Transformation
![Page 14: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/14.jpg)
Small Lymphocyte
![Page 15: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/15.jpg)
Transformed lymphocytes aka:"Reactive", "Large", "Variant" or "Atypical"
![Page 16: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/16.jpg)
Blood Smear Examination
![Page 17: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/17.jpg)
Performance of a White Cell Differential
![Page 18: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/18.jpg)
Smear Examination
Thin Area
Feather Edge
![Page 19: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/19.jpg)
Performance of a White Cell Differential - General Principles
• Scan at low power:o Identify appropriate thin areao Evaluate quality of smear
• High power oil- 50X or 100X:o Scan for abnormal cells and make a qualitative
assessmento Perform 200 cell differentialo Rescan to confirm that differential is an accurate
representation
![Page 20: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/20.jpg)
Confidence Interval for Manual Differentials
• On a 1-200 cell manual differential, if a cell type is reported as:o "50%", the 95% C.I. is ~40% - 60% .o ‘1%’, the C.I. is ~0-8% .
• A statistically meaningful differential - 1000 cell differential required but not practical
• Conclusions:o Scanning the smear for abnormalities is more
important than the diffo Absolute counts from the machine are more accurate
![Page 21: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/21.jpg)
Exceptions 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 situations
o Agranuloctosis/neutropenia- Monocytosis frequently
predicts bone marrow recovery
o Relative or absolute monocytosis is a frequent finding
in myelodysplastic syndromes
![Page 22: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/22.jpg)
Absolute Counts Define Cytoses or Cytopenias
![Page 23: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/23.jpg)
Wbc Normal Ranges (cells/cumm)
• Neutrophils: 1500-6500 (Caucasians)
800-1200 (African subpopulation
• Lymphocytes: 1500-3000
• Monocytes: <1000
• Eosinophils: <700
• Basophils: <200
• Seg/Band Ratio: 5-6:1
• Relative Monocytes: <10%
![Page 24: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/24.jpg)
Principles 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 population
• When 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 seen
• In practice, because of forced cutbacks in staffing, this currently is unlikely to be the case in most institutions
• Conclusion: You better learn to examine blood smears
![Page 25: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/25.jpg)
Normal Wbc Found in Peripheral Blood
![Page 26: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/26.jpg)
Segmented Neutrophil
![Page 27: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/27.jpg)
Neutrophil Segmented Form
![Page 28: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/28.jpg)
Eosinophil
![Page 29: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/29.jpg)
Basophil
![Page 30: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/30.jpg)
Basophil
Basophil 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
![Page 31: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/31.jpg)
Small Lymphocyte
![Page 32: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/32.jpg)
Large Transformed Lymphocyte
In a normal blood smear, 15-17% of the lymphocytes may be large lymphocytes.
![Page 33: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/33.jpg)
Large Granular Lymphocyte
Frequently, but arbitrarily included as reactive lymphocytes. The granules identify them as "killer" cells.,
![Page 34: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/34.jpg)
Large granular lymphocytes- "LGL’s"
• There are at least two distinct subclasses of killer cells
o ADCC: antibody dependent cytotoxic cells; a subclass of CD8 cells. Require the presence of an antibody to be functional
o Natural killer cells: do not require the presence of an antibody
![Page 35: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/35.jpg)
Monocyte
![Page 36: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/36.jpg)
Monocyte
Reactive Lymphocyte Vs. Monocyte
• Bluish cytoplasm • Granules few and
larger • Indistinct
chromatin, more intensely stained
• Muddy blue-gray cytoplasm
• Many small azurophilic granules, barely visible
• "Ropy" chromatin
![Page 37: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/37.jpg)
Variations in Normal Wbc
![Page 38: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/38.jpg)
Neutrophil with Toxic Granules
![Page 39: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/39.jpg)
Neutrophil band with Toxic Granules
![Page 40: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/40.jpg)
Neutrophil with Dohle Body
Dohle Bodies are condensations of cytoplasmic RNA, stain blue-gray, and have the same significance as toxic granulation.
![Page 41: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/41.jpg)
Neutrophil with Dohle Body
![Page 42: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/42.jpg)
Hypersegmented 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.
![Page 43: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/43.jpg)
Hypersegmented Neutrophil in Megaloblastic Anemia
![Page 44: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/44.jpg)
Transformed lymphocytes aka:"Reactive", "Large", "Variant" or
"Atypical"
![Page 45: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/45.jpg)
Abnormal WBC
![Page 46: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/46.jpg)
Myeloblasts, Auer Rod
![Page 47: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/47.jpg)
Lymphoblasts, Acute Lymphocytic Leukemia
Lymphoblasts are usually smaller than myeloblasts and frequently have little or no visible cytoplasm.
![Page 48: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/48.jpg)
Myelocyte - 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.
![Page 49: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/49.jpg)
Pelger-Huet Anomaly
The 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.
![Page 50: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/50.jpg)
Pseudo Pelger-Huet Anomaly
Cells that look metamyelocytes are almost never found in the hereditary form.
![Page 51: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/51.jpg)
Hypogranular 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.
![Page 52: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/52.jpg)
Sezary's Syndrome Cutaneous T-cell Lymphoma
The "cerebriform" nucleus is characteristic of some T cellleukemia/lymphomas
![Page 53: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/53.jpg)
Hairy Cell Leukemia
![Page 54: Leukopoiesis Normal and abnormal](https://reader038.vdocuments.net/reader038/viewer/2022103101/568143b3550346895db03d05/html5/thumbnails/54.jpg)
Infectious Organisms
Intracellular organisms in HIV patients, Histoplasma on the left,suspected Cryptosporidium on right.