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Myeloid tissue histology

Dennis Ivan Bravo, M.D.


Outline

Review of bone and BM histology

Erythropoiesis

Granulopoiesis

Platelet formation

Clinical correlation
Review of bone and BM
histology
Function of bone

Support for soft tissues and provides attachment points for


tendons.

Protection for soft internal organs.

Assists movement in combination with skeletal muscle.

The bones store minerals (calcium and phosphate) and


releases these minerals when needed.

Blood cell production. Red bone marrow produces red


blood cells, white blood cells, and platelets

Triglyceride storage in yellow bone marrow.


Review of bone histology
x100 Scanner
Trabecular bone
with marrow
Trabecular bone
Histology of bone
marrow

Active hematopoietic marrow contains


stem cells, progenitor cells, and developing
erythroblasts, myeloblasts, and
megakaryoblasts (red marrow)

Adipose cells, various with age and activity


(yellow marrow)

Marrow sinuses and capillary network


Bone marrow
Normal marrow
Fat
Red marrow
Yellow marrow
Yellow marrow

Located on long bones of adults

Highly inltrated with fat

NOT hematopoietic, although has potential


to become one if necessary
Yellow marrow
Yellow marrow
Yellow marrow
bone trabeculae
adipose tissue
Yellow marrow
Yellow marrow
Red marrow

Located in epiphyses of long bone, at,


irregular and short bones

Highly vascular with large venous sinusoids


and many islands of hematopoietic cells
Red marrow
granulopoietic cells
venous sinus
Red marrow
x400
granulopoietic cells
venous sinus
adipocyte
erythropoietic cells
Section of Active Marrow
Red marrow
erythropoietic cells
venous sinus
megakaryocyte
Normal marrow
Fat
Red marrow
megakaryocyte
adipocyte
Red marrow

Amount of red marrow varies with age of


patient

Childhood: Red marrow is 100% of BM and


present in virtually every bone

Adults: Red marrow is ~50% of BM and


present in sternum, ribs, pelvis, and skull

~70 years: Red marrow reduced to ~ 30% of


the BM
Erythropoiesis
Pluripotent
stem cell
Unipotent
stem cells
Unipotent
stem cells
Unipotent stem cell
(granulocyte-monocyte colony forming unit)
Unipotent
stem cell
Proerythroblast Lymphoblast
Myeloblast Monoblast
Megakaryocyte
Basophilic
erythroblast
Neutrophil
promyelocyte
Eosinophil
promyelocyte
Basophil
promyelocyte
Promonocyte
Polychromatophilic
erythroblast
Prolymphocyte
Neutrophil
myelocyte
Eosinophil
myelocyte
Basophil
myelocyte
Megakaryoblast
Orthochromatic
eryhtroblast
Neutrophil
metamyelocyte
Eosinophil
metamyelocyte
Basophil
metamyelocyte
Reticulocyte
Neutrophil
stab cell
Eosinophil
stab cell
Basophil
stab cell
Erythrocyte
Lymphocyte
Neutrophil Eosinophil Basophil Monocyte Platelet
Pluripotent
stem cell
Unipotent
stem cells
Unipotent
stem cells
Unipotent stem cell
(granulocyte-monocyte colony forming unit)
Unipotent
stem cell
Proerythroblast Lymphoblast
Myeloblast Monoblast
Megakaryocyte
Basophilic
erythroblast
Neutrophil
promyelocyte
Eosinophil
promyelocyte
Basophil
promyelocyte
Promonocyte
Polychromatophilic
erythroblast
Prolymphocyte
Neutrophil
myelocyte
Eosinophil
myelocyte
Basophil
myelocyte
Megakaryoblast
Orthochromatic
eryhtroblast
Neutrophil
metamyelocyte
Eosinophil
metamyelocyte
Basophil
metamyelocyte
Reticulocyte
Neutrophil
stab cell
Eosinophil
stab cell
Basophil
stab cell
Erythrocyte
Lymphocyte
Neutrophil Eosinophil Basophil Monocyte Platelet
Erythropoiesis
blast cell
proerythroblast
basophilic
erythroblast
polychromatic
erythroblast
orthochromatic
erythroblast
reticulocyte
How do we
distinguish
erythropeitic
cells?

No granules, round nucleus

Determine stage based on


cell size, nucleus, cytoplasm color
Erythropoiesis
How do we
distinguish
erythropeitic
cells?
Erythropoiesis
Nucleus becomes smaller
and eventually disappears
Basophilic to eosinophilic
Cells become smaller
Young Mature
Erythropoiesis
Originate from blast cell
No granules
Determine stage based on
cell size, nucleus, cytoplasm color
blast cell
Erythropoiesis

Cells are large

(+) nucleoli

Basophilic cytoplasm
proerythroblast
proerythroblast
Erythropoiesis

Smaller than erythroblast

(-) nucleolus

Intensely basophilic because of


ribosomes
basophilic
erythroblast
basophilic
erythroblast
Erythropoiesis

Smaller

Condensed checkerboard nucleus*

Gray-green cytoplasm because of


hemoglobin accumulation
polychromatic
erythroblast
polychromatic
erythroblast
*Writes stain
Erythropoiesis
polychromatic
erythroblast
polychromatic
erythroblast
Erythropoiesis

Normoblast

Smaller pyknotic nucleus

Pink cytoplasm due to


accumulation of hemoglobin
orthochromatic
erythroblast
orthochromatic
erythroblast
Erythropoiesis

No nucleus

Pink/orange with bluish hue (due


to remaining ribosome)

Reticular network seen on cresyl


blue
reticulocyte
reticulocyte

Decrease in basophilia

Increase in hemoglobin
concentration

Decrease in cell volume

Increase in chromatin
condensation, followed by
extrusion of a pyknotic
nucleus
Summary of
erythropoiesis
Identify
CLUE
Checkerboard
nuclues
Polychromatophilic
erythroblast
Identify
CLUE
Small condensed
nuclues
Normoblast
Orthochromatic
erythroblast
Identify
CLUE
Absent nuclues
Reticulocyte
Identify
CLUE
Intensely
basophilic
(-)Nucleolus
Basophilic
erythroblast
Identify
CLUE
Basophilic
(+)Nucleoli
Proerythroblast
Granulopoiesis
Pluripotent
stem cell
Unipotent
stem cells
Unipotent
stem cells
Unipotent stem cell
(granulocyte-monocyte colony forming unit)
Unipotent
stem cell
Proerythroblast Lymphoblast
Myeloblast Monoblast
Megakaryocyte
Basophilic
erythroblast
Neutrophil
promyelocyte
Eosinophil
promyelocyte
Basophil
promyelocyte
Promonocyte
Polychromatophilic
erythroblast
Prolymphocyte
Neutrophil
myelocyte
Eosinophil
myelocyte
Basophil
myelocyte
Megakaryoblast
Orthochromatic
eryhtroblast
Neutrophil
metamyelocyte
Eosinophil
metamyelocyte
Basophil
metamyelocyte
Reticulocyte
Neutrophil
stab cell
Eosinophil
stab cell
Basophil
stab cell
Erythrocyte
Lymphocyte
Neutrophil Eosinophil Basophil Monocyte Platelet
Pluripotent
stem cell
Unipotent
stem cells
Unipotent
stem cells
Unipotent stem cell
(granulocyte-monocyte colony forming unit)
Unipotent
stem cell
Proerythroblast Lymphoblast
Myeloblast Monoblast
Megakaryocyte
Basophilic
erythroblast
Neutrophil
promyelocyte
Eosinophil
promyelocyte
Basophil
promyelocyte
Promonocyte
Polychromatophilic
erythroblast
Prolymphocyte
Neutrophil
myelocyte
Eosinophil
myelocyte
Basophil
myelocyte
Megakaryoblast
Orthochromatic
eryhtroblast
Neutrophil
metamyelocyte
Eosinophil
metamyelocyte
Basophil
metamyelocyte
Reticulocyte
Neutrophil
stab cell
Eosinophil
stab cell
Basophil
stab cell
Erythrocyte
Lymphocyte
Neutrophil Eosinophil Basophil Monocyte Platelet
Pluripotent
stem cell
Unipotent
stem cells
Unipotent
stem cells
Unipotent stem cell
(granulocyte-monocyte colony forming unit)
Unipotent
stem cell
Proerythroblast Lymphoblast
Myeloblast Monoblast
Megakaryocyte
Basophilic
erythroblast
Neutrophil
promyelocyte
Eosinophil
promyelocyte
Basophil
promyelocyte
Promonocyte
Polychromatophilic
erythroblast
Prolymphocyte
Neutrophil
myelocyte
Eosinophil
myelocyte
Basophil
myelocyte
Megakaryoblast
Orthochromatic
eryhtroblast
Neutrophil
metamyelocyte
Eosinophil
metamyelocyte
Basophil
metamyelocyte
Reticulocyte
Neutrophil
stab cell
Eosinophil
stab cell
Basophil
stab cell
Erythrocyte
Lymphocyte
Neutrophil Eosinophil Basophil Monocyte Platelet
Granulopoiesis
blast cell promyelocyte myelocyte metamyelocyte
band
granulocytes
How do we
distinguish
granulopeitic
cells?

Presence of granules

Identify type of granules

If non-specic, promyelocyte
Young Mature
Granulopoiesis
promyelocyte

Cells are large

Large nucleus

(+) nucleoli

(+) purple-staining azurophilic nonspecic


granules
promyelocyte
Granulopoiesis

Wide range in cell size

Frequently indented nucleus round nucleus

(+) purple-staining azurophilic nonspecic


and (+)lilac-staining specic granules
myelocyte
myelocyte
Granulopoiesis
metamyelocyte

Nucleus becomes
attened
metamyelocyte
Granulopoiesis

Nucleus becomes
horse-shoe shaped
band
band
Granulopoiesis

Nucleus becomes
segmented into lobes
granulocytes
granulocytes
Granulopoiesis
x400
Platelet formation
Pluripotent
stem cell
Unipotent
stem cells
Unipotent
stem cells
Unipotent stem cell
(granulocyte-monocyte colony forming unit)
Unipotent
stem cell
Proerythroblast Lymphoblast
Myeloblast Monoblast
Megakaryocyte
Basophilic
erythroblast
Neutrophil
promyelocyte
Eosinophil
promyelocyte
Basophil
promyelocyte
Promonocyte
Polychromatophilic
erythroblast
Prolymphocyte
Neutrophil
myelocyte
Eosinophil
myelocyte
Basophil
myelocyte
Megakaryoblast
Orthochromatic
eryhtroblast
Neutrophil
metamyelocyte
Eosinophil
metamyelocyte
Basophil
metamyelocyte
Reticulocyte
Neutrophil
stab cell
Eosinophil
stab cell
Basophil
stab cell
Erythrocyte
Lymphocyte
Neutrophil Eosinophil Basophil Monocyte Platelet
Pluripotent
stem cell
Unipotent
stem cells
Unipotent
stem cells
Unipotent stem cell
(granulocyte-monocyte colony forming unit)
Unipotent
stem cell
Proerythroblast Lymphoblast
Myeloblast Monoblast
Megakaryocyte
Basophilic
erythroblast
Neutrophil
promyelocyte
Eosinophil
promyelocyte
Basophil
promyelocyte
Promonocyte
Polychromatophilic
erythroblast
Prolymphocyte
Neutrophil
myelocyte
Eosinophil
myelocyte
Basophil
myelocyte
Megakaryoblast
Orthochromatic
eryhtroblast
Neutrophil
metamyelocyte
Eosinophil
metamyelocyte
Basophil
metamyelocyte
Reticulocyte
Neutrophil
stab cell
Eosinophil
stab cell
Basophil
stab cell
Erythrocyte
Lymphocyte
Neutrophil Eosinophil Basophil Monocyte Platelet
Platelet development

Begins with formation of unipotential


progenitor cell

Precursor is megakaryoblast

Blast matures to become megakaryocyte

Megakaryocyte sheds platelets


Megakaryoblast

Large cell with single large nucleus

Basophilic nongranular cytoplasm

Divide mitotically to megakaryocyte


Megakaryocyte

Extremely large cell with single, large


polyploid nucleus

Lie just outside the sinusoids

Fragments to platelets
Megakaroblast Megakarocyte Megakarocyte

Rare

Large lobed
nucleus

Extremely large

Polyploid

Near sinusoids
Normal marrow
Fat
Megakaryocyte
Section of Active Marrow
Megakaryocyte
Megakaryocyte
Megakaryocyte
Megakaryocyte
Clinical correlation
Marrow from patient with acute myeloblastic
leukemia; same mag. as preceding.
Acute myelogenous
leukemia
Comparison of normal and AML leukemic bone marrows
Acute myelogenous
leukemia
Low magni!cation of
marrow of patient with
AML. Note obliteration of
marrow space with tumor
cells.
Acute myelogenous
leukemia
Higher magni!cation of
previous slide.
Acute myelogenous
leukemia
What symptoms might a
patient with these blood
ndings have?
Base your answer solely on
examination of the marrow and
blood smears.
The end

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