Morphologies
Blood and Bone Marrow
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Neutrophils (Granulocyte Family)
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Neutrophil (PMN, Polymorphonuclear Neutrophil):
- Size: 10-15 μm
- Nucleus: Segmented (3-5 lobes), condensed chromatin, generally no nucleoli
- Cytoplasm: Pale pink or lilac color, fine, faint granules
- Function: Phagocytosis and killing of bacteria and fungi (primary defense against infection)
- Key Features: Segmented nucleus, small pinkish granules
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Band Neutrophil:
- Also known as “stab cell”
- Size: 10-15 μm
- Nucleus: Horseshoe-shaped (banded, not segmented)
- Cytoplasm: Same as neutrophil
- Significance: Immature neutrophil; increased numbers indicate a “left shift,” often seen in infection
- Key Features: Banded nucleus, similar to a neutrophil
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Metamyelocyte:
- Size: 10-18 μm
- Nucleus: Kidney bean-shaped (indented), coarser chromatin than band
- Cytoplasm: Pale blue to pink, many granules
- Significance: Less mature neutrophil precursor than a band
- Key Features: Indented nucleus, not segmented like a neutrophil
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Myelocyte:
- Size: 12-20 μm
- Nucleus: Round to oval, eccentric (off-center), coarser chromatin, may have visible nucleoli
- Cytoplasm: More abundant than in promyelocyte, distinct granules
- Significance: Immature neutrophil precursor
- Key Features: More cytoplasm and distinct granules compared to more immature precursors
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Promyelocyte:
- Size: 14-24 μm
- Nucleus: Round to oval, prominent nucleoli
- Cytoplasm: Basophilic, many large, azurophilic (purple) primary granules
- Significance: Immature neutrophil precursor
- Key Features: Large size, prominent nucleoli, many large granules
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Myeloblast:
- Size: 14-20 μm
- Nucleus: Round to oval, fine chromatin, prominent nucleoli
- Cytoplasm: Scant, basophilic, few or no granules
- Significance: The most immature granulocyte precursor; increased numbers suggest acute myeloid leukemia (AML)
- Key Features: Immature chromatin, prominent nucleoli, lack of abundant granules
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Neutrophil (PMN, Polymorphonuclear Neutrophil):
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Eosinophils (Granulocyte Family)
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Eosinophil:
- Size: 12-17 μm
- Nucleus: Usually bilobed (2 lobes)
- Cytoplasm: Packed with large, uniform, refractile granules that stain bright orange-red with eosin dye
- Function: Defense against parasites, allergic reactions
- Key Features: Bilobed nucleus, large orange-red granules
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Eosinophil:
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Basophils (Granulocyte Family)
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Basophil:
- Size: 10-14 μm
- Nucleus: Lobulated, but often obscured by granules
- Cytoplasm: Packed with large, irregular granules that stain dark blue or purple with basic dyes
- Function: Release of histamine and other mediators involved in allergic and inflammatory responses
- Key Features: Dark blue/purple granules obscuring the nucleus
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Basophil:
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Monocytes
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Monocyte:
- Size: 12-20 μm (largest of the normal WBCs)
- Nucleus: Kidney-shaped, horseshoe-shaped, or convoluted; lacy, less condensed chromatin; may have nucleoli
- Cytoplasm: Gray-blue, abundant, fine granules and vacuoles (“ground glass” appearance)
- Function: Phagocytosis, antigen presentation, cytokine production
- Key Features: Large size, kidney-shaped nucleus, “ground glass” cytoplasm
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Monocyte:
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Lymphocytes
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Small Lymphocyte:
- Size: 7-10 μm (similar to RBC size)
- Nucleus: Round or slightly indented, dense and darkly stained chromatin, usually no nucleoli
- Cytoplasm: Scant, light blue
- Function: Involved in adaptive immunity (T cells and B cells)
- Key Features: High N:C ratio, round nucleus, scant cytoplasm
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Large Lymphocyte:
- Size: 12-16 μm (larger than RBCs)
- Nucleus: Round or slightly indented, may have more open chromatin
- Cytoplasm: More abundant than in small lymphocytes, may contain a few granules
- Function: Can include activated T cells, B cells, or NK cells
- Key Features: More cytoplasm than small lymphocytes, but still a high N:C ratio
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Reactive (Atypical) Lymphocyte:
- Size: Variable, often larger than normal lymphocytes
- Nucleus: Variable shape (may be indented, folded, or irregular), less condensed chromatin, may have prominent nucleoli
- Cytoplasm: Abundant, may be basophilic (dark blue) or vacuolated, may indent around RBCs
- Function: Lymphocytes responding to an antigen (e.g., viral infection)
- Key Features: Abundant, often dark-staining cytoplasm, irregular nucleus
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Plasma Cell:
- Size: 10-20 μm
- Nucleus: Eccentric (off-center), round, “clock-face” or “cartwheel” chromatin pattern
- Cytoplasm: Deeply basophilic, often with a perinuclear halo (area near the nucleus that is less stained)
- Function: Antibody production
- Key Features: Eccentric nucleus, “clock-face” chromatin, deeply basophilic cytoplasm
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Small Lymphocyte:
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Additional Cells (Less Common)
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Blasts:
- General Features:
- Large size
- High N:C ratio
- Fine, dispersed chromatin
- Prominent nucleoli
- May have scant cytoplasm
- Myeloblast:
- Granules may be present
- May have Auer rods (rod-shaped inclusions) - Pathognomonic for AML (but not always present)
- Positive for myeloperoxidase (MPO) stain
- Lymphoblast:
- Usually lack granules and Auer rods
- Negative for MPO stain
- General Features:
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Nucleated Red Blood Cells (nRBCs):
- Also known as erythroblasts
- Immature RBCs with a nucleus
- Normally found in the bone marrow, but can appear in the peripheral blood in certain conditions
- Stages of nRBCs:
- Pronormoblast (Proerythroblast)
- Basophilic Normoblast
- Polychromatic Normoblast
- Orthochromic Normoblast
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Blasts:
Blood
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Normal Red Blood Cells
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Normocytes:
- Description: Normal-sized RBCs
- Size: Approximately 6-8 μm in diameter (roughly the size of a lymphocyte nucleus)
- Shape: Biconcave disc (round with central pallor)
- Color: Pink to orange-red with a central pallor that occupies about 1/3 of the cell diameter
- Clinical Significance: The predominant cell type in healthy individuals
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Normocytes:
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Abnormal Red Blood Cells (Poikilocytes)
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Anisocytosis = General term for variation in RBC size
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Microcytes:
- Description: Small RBCs
- Size: <6 μm in diameter (MCV <80 fL)
- Associated Conditions: Iron deficiency anemia, thalassemia, sideroblastic anemia, anemia of chronic disease
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Macrocytes:
- Description: Large RBCs
- Size: >9 μm in diameter (MCV >100 fL)
- Shape: Round (not oval, unless megaloblastic)
- Associated Conditions: Vitamin B12 deficiency, folate deficiency, alcoholism, liver disease, hypothyroidism, myelodysplastic syndromes (MDS), reticulocytosis
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Microcytes:
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Hypochromia:
- Description: RBCs with decreased hemoglobin content
- Appearance: Pale with an increased central pallor (>1/3 of the cell diameter)
- Associated Conditions: Iron deficiency anemia, thalassemia, sideroblastic anemia
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Polychromasia:
- Description: RBCs with a bluish tint due to residual RNA
- Appearance: Larger than mature RBCs, lack central pallor, stain blue-gray with Wright stain
- Significance: Indicates increased erythropoiesis (reticulocytes)
- Associated Conditions: Hemolytic anemia, acute blood loss, response to therapy
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Spherocytes:
- Description: Small, spherical RBCs with no central pallor
- Appearance: Small, round, intensely stained (lack central pallor)
- Associated Conditions: Hereditary spherocytosis, autoimmune hemolytic anemia
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Elliptocytes (Ovalocytes):
- Description: Elongated or oval-shaped RBCs
- Appearance: Elliptical or oval shape
- Associated Conditions: Hereditary elliptocytosis, iron deficiency anemia, thalassemia
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Target Cells (Codocytes):
- Description: RBCs with a bullseye appearance
- Appearance: Central area of hemoglobin surrounded by a clear ring and then an outer ring of hemoglobin
- Associated Conditions: Liver disease, thalassemia, hemoglobinopathies (e.g., HbC disease), iron deficiency anemia, post-splenectomy
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Sickle Cells (Drepanocytes):
- Description: Crescent-shaped or sickle-shaped RBCs
- Appearance: Elongated, crescent or sickle shape
- Associated Conditions: Sickle cell anemia (HbSS), sickle cell trait (HbAS)
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Schistocytes (Fragmented Cells):
- Description: Fragments of RBCs with irregular shapes and pointed ends
- Appearance: Small, irregularly shaped fragments
- Associated Conditions: Microangiopathic hemolytic anemia (MAHA) - thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), disseminated intravascular coagulation (DIC), mechanical heart valves
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Acanthocytes (Spur Cells):
- Description: RBCs with irregularly spaced, thorny projections
- Appearance: Irregular, spiky projections of varying length
- Associated Conditions: Liver disease, abetalipoproteinemia
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Echinocytes (Burr Cells):
- Description: RBCs with evenly spaced, blunt projections
- Appearance: Small, uniform, spiky projections
- Associated Conditions: Uremia (kidney failure), pyruvate kinase deficiency, artifact (crenation)
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Teardrop Cells (Dacrocytes):
- Description: RBCs shaped like teardrops or pears
- Appearance: One end is rounded, and the other end is elongated or pointed
- Associated Conditions: Primary myelofibrosis, thalassemia, myelodysplastic syndromes, extramedullary hematopoiesis
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Stomatocytes:
- Description: RBCs with a slit-like area of central pallor (mouth-like appearance)
- Appearance: Slit-like central pallor
- Associated Conditions: Hereditary stomatocytosis, alcoholism, liver disease
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Agglutination
- Definition: The clumping or aggregation of red blood cells due to antibody- or complement-mediated interactions
- Appearance:
- Irregular Clumps: RBCs form irregular, three-dimensional clumps or clusters
- Grape-like Clusters: Agglutinates often appear as grape-like clusters of RBCs
- Random Distribution: The clumps are randomly distributed throughout the smear
- Macroscopic Agglutination: In some cases, the agglutination may be visible to the naked eye as clumping in the EDTA tube
- Associated Conditions:
- Cold Agglutinin Disease (Cold AIHA): IgM autoantibodies bind to RBCs at low temperatures
- Autoimmune Hemolytic Anemia (AIHA): IgG or IgM autoantibodies against RBCs
- Transfusion Reactions: Antibodies against donor RBC antigens
- Paroxysmal Cold Hemoglobinuria (PCH): Donath-Landsteiner antibody (IgG) binds to RBCs at low temperatures
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Rouleaux Formation
- Definition: The stacking of red blood cells in a linear arrangement, resembling stacks of coins or poker chips
- Appearance:*
- Stacks of Coins: RBCs are arranged in linear stacks, resembling stacks of coins or poker chips
- Even Distribution: The stacks are relatively uniform and evenly distributed
- Reversible: Rouleaux formation is reversible; the RBCs can be easily dispersed by adding saline
- Associated Conditions:
- Multiple Myeloma: Increased levels of monoclonal immunoglobulins (paraproteins)
- Waldenström Macroglobulinemia: Increased levels of IgM
- Chronic Inflammatory Conditions: Increased fibrinogen and acute phase reactants
- Hypergammaglobulinemia: Increased levels of immunoglobulins
- Artifact: Can be an artifact if the counting area of the smear is too thick
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Basophilic Stippling:
- Description: Presence of small, dark-blue granules scattered throughout the RBC cytoplasm
- Composition: Ribosomal RNA precipitates
- Associated Conditions: Thalassemia, lead poisoning, myelodysplastic syndromes (MDS)
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Howell-Jolly Bodies:
- Description: Round, dark-purple nuclear remnants in RBCs
- Composition: DNA fragments
- Associated Conditions: Splenectomy or splenic dysfunction, hemolytic anemia, megaloblastic anemia
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Pappenheimer Bodies:
- Description: Small, irregular, iron-containing granules in RBCs
- Composition: Iron (non-heme iron)
- Require Prussian blue stain to visualize
- Associated Conditions: Sideroblastic anemia, post-splenectomy, myelodysplastic syndromes
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Heinz Bodies:
- Description: Inclusions composed of denatured hemoglobin
- Require supravital stain (e.g., crystal violet or brilliant cresyl blue) to visualize
- Associated Conditions: G6PD deficiency, unstable hemoglobin variants
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Bone Marrow
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Hematopoietic Stem Cells and Progenitor Cells (Blasts)
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Hematopoietic Stem Cells (HSCs):
- Description: Rare, self-renewing cells that give rise to all blood cell lineages
- Morphology: Difficult to identify morphologically
- Identification: Best identified by immunophenotyping using flow cytometry (e.g., CD34+, CD38-)
- Significance: The source of all blood cells; mutations in HSCs can lead to hematologic malignancies
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Multipotent Progenitors (MPPs):
- Description: Cells derived from HSCs that have lost some self-renewal capacity but can still differentiate into multiple lineages
- Morphology: Difficult to distinguish morphologically from HSCs
- Identification: Identified by immunophenotyping
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Common Myeloid Progenitor (CMP):
- Description: A progenitor cell that gives rise to granulocytes, monocytes, macrophages, and megakaryocytes
- Morphology: Difficult to distinguish morphologically from other progenitor cells
- Identification: Identified by immunophenotyping
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Common Lymphoid Progenitor (CLP):
- Description: A progenitor cell that gives rise to lymphocytes (T cells, B cells, and NK cells)
- Morphology: Difficult to distinguish morphologically from other progenitor cells
- Identification: Identified by immunophenotyping
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Hematopoietic Stem Cells (HSCs):
Myeloid Lineage
These cells are part of the granulocytic and monocytic series * Myeloblast: * Description: Immature granulocyte precursor * Size: 14-20 μm * Nucleus: Large, round to oval, fine chromatin, 1-5 distinct nucleoli * Cytoplasm: Scant to moderate amount, deeply basophilic, lacks granules * Distinguishing Features: * High nucleus-to-cytoplasm (N:C) ratio * Prominent nucleoli * Lack of granules * Clinical Significance: Increased in acute myeloid leukemia (AML)
* **Promyelocyte:**
* Description: More mature than myeloblast
* Size: 15-25 μm
* Nucleus: Round to oval, slightly coarser chromatin than myeloblast, 1-3 nucleoli
* Cytoplasm: More abundant than myeloblast, basophilic, contains primary (azurophilic) granules
* Distinguishing Features:
* Presence of primary (azurophilic) granules
* Nucleoli may still be visible
* Clinical Significance: Increased in AML, especially acute promyelocytic leukemia (APL)
* **Myelocyte:**
* Description: Intermediate stage in granulocyte maturation
* Size: 12-18 μm
* Nucleus: Round and eccentric (off-center), condensed chromatin, nucleoli usually absent
* Cytoplasm: Less basophilic than promyelocyte, contains both primary and secondary (specific) granules
* Distinguishing Features:
* Smaller size than promyelocyte
* Eccentric nucleus
* "Dawn of neutrophilia": The cytoplasm appears pinkish due to the development of secondary granules (in neutrophilic myelocytes)
* Types:
* Neutrophilic myelocyte: Produces neutrophilic granules (stain pink or lavender)
* Eosinophilic myelocyte: Produces eosinophilic granules (stain orange-red)
* Basophilic myelocyte: Produces basophilic granules (stain dark blue or purple)
* **Metamyelocyte:**
* Description: A stage in granulocyte maturation intermediate between myelocyte and band neutrophil
* Size: 10-15 μm
* Nucleus: Indented (kidney bean-shaped), condensed chromatin, no nucleoli
* Cytoplasm: Abundant, contains secondary granules
* Distinguishing Features:
* Indented nucleus
* No nucleoli
* Types:
* Neutrophilic metamyelocyte
* Eosinophilic metamyelocyte
* Basophilic metamyelocyte
* **Band Neutrophil:**
* Description: An immature neutrophil with a horseshoe-shaped (band-shaped) nucleus
* Size: 10-12 μm
* Nucleus: Band-shaped, condensed chromatin, no nucleoli
* Cytoplasm: Pinkish-lilac, fine granules
* Distinguishing Features:
* Band-shaped nucleus with parallel sides and no segmentation
* Absence of a thin filament connecting the nuclear lobes
* **Monoblast:**
* Description: Earliest recognizable monocyte precursor
* Size: 12-20 μm
* Nucleus: Large, round to oval, fine chromatin, prominent nucleoli
* Cytoplasm: Abundant, basophilic, lacks granules
* Distinguishing Features:
* High N:C ratio
* Prominent nucleoli
* Lack of granules
* **Promonocyte:**
* Description: More mature than monoblast
* Size: 14-18 μm
* Nucleus: Large, indented or folded, lacy chromatin, may have nucleoli
* Cytoplasm: Gray-blue, abundant, fine granules
* Distinguishing Features:
* Indented or folded nucleus
* Cytoplasmic granules
* **Megakaryoblast:**
* Description: Immature megakaryocyte precursor
* Size: 20-50 μm
* Nucleus: Large, single nucleus with multiple lobes, prominent nucleoli
* Cytoplasm: Deeply basophilic, lacks granules
* Distinguishing Features:
* Large size
* Multi-lobated nucleus
* Lacks granules
* **Promegakaryocyte:**
* Description: More mature than megakaryoblast
* Size: 25-80 μm
* Nucleus: Large, multi-lobated, less distinct nucleoli
* Cytoplasm: More abundant than megakaryoblast, less basophilic, contains some granules
* Distinguishing Features:
* Large size
* Granular cytoplasm
* **Megakaryocyte:**
* Description: Mature platelet-producing cell
* Size: 30-100 μm (largest cell in the bone marrow)
* Nucleus: Large, multi-lobated, condensed chromatin
* Cytoplasm: Abundant, pinkish-blue, contains numerous granules
* Distinguishing Features:
* Extremely large size
* Multi-lobated nucleus
* Abundant granular cytoplasm
* Function: Produces platelets by shedding portions of its cytoplasm
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Erythroid Lineage
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Pronormoblast (Proerythroblast):
- Description: The earliest recognizable erythroid precursor
- Size: 14-20 μm
- Nucleus: Large, round, fine chromatin, 1-2 distinct nucleoli
- Cytoplasm: Deeply basophilic (due to high RNA content)
- Distinguishing Features:
- High N:C ratio
- Intense basophilia of the cytoplasm
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Basophilic Normoblast:
- Description: More mature than pronormoblast
- Size: 12-17 μm
- Nucleus: Round, slightly condensed chromatin, no nucleoli
- Cytoplasm: Intensely basophilic
- Distinguishing Features:
- Smaller size than pronormoblast
- More condensed chromatin
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Polychromatic Normoblast:
- Description: As hemoglobin synthesis increases, the cytoplasm becomes less basophilic
- Size: 10-15 μm
- Nucleus: Round, more condensed chromatin
- Cytoplasm: Gray-blue (polychromatic) due to the presence of both hemoglobin and ribosomes
- Distinguishing Features:
- Gray-blue cytoplasm
- More condensed chromatin
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Orthochromic Normoblast:
- Description: The final nucleated stage of erythroid maturation
- Size: 8-10 μm
- Nucleus: Small, dense, pyknotic (about to be extruded)
- Cytoplasm: Pink (due to predominant hemoglobin)
- Distinguishing Features:
- Small, dense nucleus
- Mostly pink cytoplasm
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Reticulocyte:
- Anucleated red blood cell with residual RNA, not found in the bone marrow
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Pronormoblast (Proerythroblast):
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Key Considerations
- Mast Cells: Although present in the bone marrow, mast cells are technically tissue cells and not part of the hematopoietic lineages. They are granulated cells important in allergic responses.
- Plasma Cells: Although derived from lymphocytes, plasma cells can also reside in the bone marrow. They have distinct eccentric nuclei and deeply basophilic cytoplasm.
Body Fluids
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Neutrophils:
- Morphology: Similar to neutrophils in peripheral blood (segmented nucleus, pink-lilac granules)
- Significance: Increased numbers often indicate bacterial infection or inflammation
- Degenerated Neutrophils: In older fluids, neutrophils may appear pyknotic (shrunken, dark nucleus) or may be lysed
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Lymphocytes:
- Morphology: Similar to lymphocytes in peripheral blood (round nucleus, scant cytoplasm)
- Significance: Increased numbers may suggest viral infection, tuberculosis, fungal infection, or chronic inflammation
- Reactive Lymphocytes: (Atypical lymphocytes)
- More abundant cytoplasm
- Basophilic cytoplasm
- May have nucleoli
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Monocytes/Macrophages:
- Morphology: Large cells with a kidney bean-shaped or horseshoe-shaped nucleus, abundant gray-blue cytoplasm, and vacuoles
- Significance: Found in various inflammatory conditions and infections; can also indicate hemorrhage (erythrophagocytosis)
- Distinguishing Features: Cytoplasmic vacuoles and/or phagocytized material can be diagnostic of specific processes
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Eosinophils:
- Morphology: Similar to eosinophils in peripheral blood (bilobed nucleus, large, orange-red granules)
- Significance: Often associated with parasitic infections, allergic reactions, or hypersensitivity reactions
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Basophils:
- Morphology: Similar to basophils in peripheral blood (irregular, lobulated nucleus obscured by dark blue/purple granules)
- Significance: Less common than other cell types; may be seen in allergic reactions or certain malignancies
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Mesothelial Cells (Serous Fluids - Pleural, Peritoneal, Pericardial):
- Morphology:
- Round to oval cells
- Eccentric nucleus (off-center)
- Abundant cytoplasm (often blue-gray or pink)
- May have a “skirt” or “ruffled border”
- May be multinucleated
- Significance: Normal lining cells of the serous membranes
- Increased numbers can indicate inflammation or irritation of the serous membranes
- Reactive Mesothelial Cells: May have more prominent nucleoli, increased cytoplasm, and mitotic figures
- Morphology:
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Synovial Lining Cells (Synovial Fluid):
- Morphology:
- Round to oval cells
- Eccentric nucleus
- Moderate amount of cytoplasm
- Significance: Normal cells found in synovial fluid
- Increased numbers may indicate inflammation or joint damage
- Morphology:
Additional Cells (Less Common)
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Blast Cells:
- Morphology:
- Large cells with a high nuclear-to-cytoplasmic (N:C) ratio
- Fine chromatin
- Prominent nucleoli
- May have scant cytoplasm
- Significance: Suggestive of leukemia or lymphoma with involvement of the body fluid
- Classification: Requires flow cytometry and other specialized tests to determine lineage (myeloid vs. lymphoid)
- Morphology:
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Malignant Cells (Non-Hematologic):
- Morphology:
- Highly variable, depending on the type of cancer
- May have abnormal nuclear features (e.g., irregular shape, coarse chromatin, prominent nucleoli)
- May have abundant cytoplasm with vacuoles or other inclusions
- Significance: Indicates metastatic cancer in the body fluid
- Origin: Usually represent metastatic carcinoma from a solid tumor
- Identification: Requires careful cytological evaluation and correlation with clinical history and imaging studies
- Morphology:
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Ependymal Cells (Cerebrospinal Fluid - CSF):
- Morphology:
- Columnar or cuboidal cells
- Round to oval nucleus
- Finely granular cytoplasm
- Significance: Normal cells lining the ventricles of the brain and the central canal of the spinal cord
- Increased numbers may indicate disruption of the ventricular system
- Morphology:
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Hemosiderin-Laden Macrophages (All Fluid Types):
- Morphology:
- Phagocytes that contain pigment granules of broken-down red blood cells with hemosiderin (iron storage complex).
- Significance: Indicate prior hemorrhage (bleeding) into the body fluid
- Morphology:
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Lipophages (Fat-Laden Macrophages, Gitter Cells):
- Morphology:
- Macrophages with numerous vacuoles containing lipids
- Significance: Indicate tissue destruction and fat necrosis
- Commonly seen in CSF after stroke or traumatic brain injury
- Morphology:
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Crystals (Synovial Fluid):
- Urate Crystals: Needle-shaped, negatively birefringent crystals seen in gout
- Calcium Pyrophosphate Dihydrate (CPPD) Crystals: Rhomboid or rod-shaped, weakly positively birefringent crystals seen in pseudogout
- Cholesterol Crystals: Flat, notched, rhomboid-shaped crystals seen in chronic effusions
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Organisms:
- Bacteria: Small, round, or rod-shaped organisms that may be seen within or outside of cells
- Fungi: May appear as yeast or hyphae
- Parasites: Rare, but may be seen in certain infections
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Other Artifacts and Contaminants:
- Air Bubbles
- Starch Granules (from gloves)
- Contaminating Cells from Adjacent Tissues