White Blood Cell Inclusions and Abnormalities:
Neutrophilia: Increased Amount of Neutrophils and Usually Lymphopenia (Decreased Amount of Lymphocytes)
Associated with:
- Bacterial infection
- Inflammation
- Heart attack
- Burns
- Prednisone
- Adrenaline/Epinephrine
- Stress/Anxiety/Nervousness
- Malignancy like CML
- Appendicitis
- Splenectomy
- Left Shift: Increase of bands in the bloodstream
- Severe Left Shift: Leukemoid reaction (resembles Pelger-Huet anomaly)
Neutrophilia
Polymorphonuclear (segmented) neutrophils
Neutropenia: Lower Levels of Neutrophils
- Acute or chronic
- Often have an infection
- May be experiencing symptoms, including fever, abscess, otitis, difficulty swallowing, gingival pain and sensitivity
- Associated with the following conditions:
- Aplastic anemia
- Vit. B12 deficiency
- Glycogen storage disease
- Barth, Cohen, Pearson or Pudlak syndromes
- Congenital immunological disorder
- Certain viruses
- Some drug usage
- Some bacterial infections, such as TB or typhoid
- Cancer patients on chemotherapy may present with neutropenia as seen in the image below
Eosinophilia: Increased Amounts of Eosinophils
May indicate:
- Bacterial infection
- Parasite infection
- Allergic reaction
- Asthma
- Hay Fever
- Rhinitis
- Sinus Infection
- Drug Allergy
- Skin Allergy
- Addison's Disease
- Stress Reaction
- Autoimmune reaction such as Lupus
- Leukemia (Chronic Myelogenous Leukemia/CML, Acute Lymphocytic Leukemia/ALL, Eosinophilic Leukemia, Hodgkin Lymphoma, Non-Hodgkin Lymphoma)
- HIV
- Coccidioidomycosis (Valley Fever)
- Interstitial Nephropathy
Eosinopenia: Decreased Amounts of Eosinophils
Acute infections, burns, stress reactions, Cushing's syndrome, use of steroids, and leukocytosis can all result in eosinopenia.
Basophilia: Increased Amounts of Basophils
May indicate:
- Allergic reaction
- Itching, due to release of histamine (pruritis)
- CML
- Drug sensitivity
- Ulcerative colitis
- Juvenile RA
- Iron deficiency
- Viral infection
- Certain cancers
- Exposure to ionizing radiation
- Endocrinopathy
Basopenia: Decreased Amounts of Basophils
Basopenia can be caused by
- urticaria (hives),
- ovulation,
- hyperthyroidism or
- medication to treat that condition, hypersensitivity reactions, or
- leukocytosis.
Vacuoles/Vacuolization: Sign of Activation, Active Phagocytosis, Bacterial Infection, Viral Infection, Sepsis or Some Types of Cancers
Vacuoles appear as unstained areas within the cytoplasm like bubbles. Associated with:
- Bacterial infection (Granulocytes)
- Sepsis
- Fungal infection
- Viral Infection (Agranulocytes)
- Poisoning
- Burns
- Chemotherapy
- Drugs, like sulfa or chloroquine
- Artifact
- Increased storage time in EDTA anticoagulant
- Autoantibodies
- Acute alcoholism
- Exposure to high doses of radiation
- A blood film made >2 hours post-venipuncture
Vacuolization in activated monocyte
Vacuolization in active monocyte
Neutrophilic vacuolization is typically seen with toxic granulation, which may indicate serious bacterial infection, sepsis or toxicity
Dohle Bodies
Dohle Bodies are rough endoplasmic reticulum remnants of RNA and appear as gray-blue areas with various shapes within the cytoplasm. They are found in neutrophils and seen in conditions such as bacterial infections, burns, poisoning, and cytotoxic drugs such chemotherapy, May-Hegglin Anomaly, or pregnancy.
- Single
- Multiple
- Blue-gray inclusion
- Vary in size/shape
- Denatured aggregates of free ribosomes
- Stacks of endoplasmic reticulum
- Usually seen with toxic granulation and/or vacuolization
- Associated with May-Hegglin Anomaly and giant platelets
- Associated with Alder's Anomaly
- Associated with Chediak-Higashi Syndrome
- Seen with infections
- Seen with physical trauma
- Seen in burns
- Common in sepsis
- Sometimes seen in pregnancy (normal)
- Some drugs will cause this
- Seen in neoplastic conditions
- Seen in leukemoid reactions
May Hegglin Anomaly
May-Hegglin Anomaly is associated with thrombocytopenia and giant platelets. It also has large inclusions that resemble Dohle bodies in all the leukocytes. There is no toxic granulation.
- Associated with Dohle Bodies in granulocytes
- Rare autosomal dominant disorder
- Associated with giant platelets
- Associated with thrombocytopenia and purpura
May Hegglin Anomaly results in cytoplasmic inclusions resembling Dohle bodies, and it is seen in leukocytes, typically neutrophils. May Hegglin Anomaly is seen frequently with giant platelets as well, as seen here in this peripheral blood smear.
Toxic Granulation (Hypergranulation)
Often seen with vacuoles and Dohle bodies. Toxic granulation is characterized by the presence of few to many prominent primary blue-black granules in the cytoplasm of neutrophils, and they're unevenly distributed. This is associated with:
- bacterial infection
- sepsis
- burns
- poisoning/toxins
- chemotherapy
- pregnancy
- inflammation
- Chemistry correlation: increased c-reactive protein
Toxic granulation is seen here in a neutrophil in response to either an infection, allergen, or as a side effect of medication, chemotherapy, or burns.
Toxic granulation is common in inflammatory processes and in bacterial sepsis
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Toxic granules are released during the degranulation process and are of several types.
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Hypogranulation or Degranulation:
Hypogranulation, or degranulation, is characterized by a decrease in number or complete absence of specific (primary) granules. This means either an infection is present, or the possibility of myelodysplastic syndrome.
Neutrophilic hypogranulation (no granules) seen here with a Pelger Huet Cell (hyposegmentation). Pelger Huet Cells are seen in Pelger Huet Anomaly, some types of cancers, and are also referred to as Pelgroid Cells.
Primary (Specific) Azurophilic Granules:
Azurophilic granules are specific, primary granules found in phagocytic cells of the immune system. They are filled with lysing antimicrobial defensins, or enzymes that fuse with the phagocytic vacuoles. They play a key role in destroying microbes, degrading parts of the cells (membranes/walls/proteins), breaking things down, clearing debris, and a role in the inflammatory or anti-inflammatory and pain responses. Types of enzymes include:
- Myeloperoxidase
- Acidic
- Antimicrobial
- Contains a heme pigment, which is responsible for the yellow-greenish color of pus
- Cytotoxic
- Acidic
- Phospholipase A2
- Cell lysis
- Digestion
- Inflammation
- Cell lysis
- Acid hydrolases
- Degradation
- Degradation
- Elastase
- Serine protease
- Breaks down collagen, elastic connective tissue, and bacterial membranes
- Serine protease
- Serine protease
- Clips protein bonds like molecular scissors
- Digestion
- Immunity
- Coagulation of blood
- Helps wall off bacterial invasions
- Clips protein bonds like molecular scissors
- Lysozyme
- Acidic
- Antimicrobial
- Found in secretions, mucous, tears, saliva, conjunctiva
- Breaks down peptidoglycan found in bacterial cell walls
- Acidic
- Cathepsin G
- Decreases intracellular pathogens
- Breaks down tissues
- Anti-inflammatory response
- Pain
- Decreases intracellular pathogens
- Proteinase 3
- Antimicrobial
- Antimicrobial
- Proteoglycan
- Extracellular matrix
- Extracellular matrix
- Bacteriacidal/Permeability Increasing Protein
- Pokes holes in the cell membranes of microbes
- Pokes holes in the cell membranes of microbes
- Defensin
- Pokes holes in the cell membranes of microbes and cancer cells
- Pokes holes in the cell membranes of microbes and cancer cells
Pelger Huet Anomaly (Pelgeroid Cells)/Hyposegmentation: <3 lobed neutrophil or Dysplastic Nucleus:
Pelger-Huet cells have a bilobed or peanut-shaped nucleus, or even a non-segmented nucleus in neutrophils. This is referred to as "hyposegmentation". The chromatin is still coarse, as seen in a mature cell. Associated with:
- Pelger-Huet Anomaly
- Inherited (autosomal dominant)
- Most common genetic disorder of the leukocytes, due to mutation of the lamin B receptor
- Affects the majority of the PMN's seen on the slide and majority of the granulocytes
- May be linked to a type of Muscular Dystrophy or premature aging
- Inherited (autosomal dominant)
- Pseudo Pelger-Huet Anomaly
- Acquired
- Affects <50% of the granulocytes
- May accompany malignancy or a myelodysplastic disorder
- AML
- CML
- Filovirus
- Enterovirus
- Malaria
- Vitamin B12 or folate deficiency
- Muscular Dystrophy
- Leukemoid reaction
- Drug toxicity or reaction
- May be seen with impaired cognitive skeletal abnormality or a heart defect
- Acquired
- Myeloproliferative or myelodysplastic disorders
- Associated with agranular cytoplasm
- Abnormal nuclear segmentation (bilobed appearance or monoloblated)
- Homozygous state (very rare)
- A pathologist review may be required if these are seen on the slide
Pelger-Huet cell with bilobed appearance
Bilobed Pelger-Huet Cell
Dysplastic neutrophil
Hypersegmentation: >5 lobed neutrophil
These are neutrophils with 6+ nuclear lobes. This is referred to as "hypersegmentation". A typical blood CBC with differential will reveal a normal MCHC, decreased RBC count, increased MCV and MCH, decreased reticulocyte count or %, decreased platelets, anisocytosis, poikilocytosis, macrocytes, ovalocytes, and neutrophils with >5 lobes. These are associated with:
- Megaloblastic anemias (Vitamin B12 or folate deficiency or both)
- Vitamin B12 Deficiency: decreased intrinsic factor, celiac disease, malabsorption, pancreatitis)
- Folate Deficiency: diet, alcoholism, cirrhosis, pregnancy, malabsorption, surgery, enzyme deficiency, methotrexate, nitrous oxide
- Copper Deficiency
- Zinc Overload
- Vitamin B12 Deficiency: decreased intrinsic factor, celiac disease, malabsorption, pancreatitis)
- Chronic infections
- Rarely inherited (asymptomatic)
- Myelokathexis
- Neutropenia
- Bone marrow hyperplasia of myeloid cells
- Increased cellular apoptosis
- Impaired DNA synthesis during RBC production
- Neutropenia
- Myelokathexis
- Chemotherapy
- Antimicrobials such as azathioprine, trimethoprim
- Chemistry correlations include increased LDH, increased homocysteine and methylmalonic acid, decreased vitamin B 12 level
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Sezary Cells
Sezary cells are neoplastic CD4+ T-lymphocytes. They are abnormal and have a convoluted, twisted nucleus sometimes resembling a clover. Sezary disease or syndrome consists of abnormal T-cells that result in cutaneous lymphomas of the skin and microabscesses, erythroderma and hepatosplenomegaly, along with Sezary cells seen in the peripheral blood smear. These T-cells have an overabundance of mucopolysaccharides. Mycosis fungoides with lymphadenopathy may result in Sezary disease at the end stages. Sezary disease is very rare.
Auer Rods
Auer Rods are elongated clumps of granular material (fused lysosomes and neutrophilic granules) azuric in color that are seen in the cytoplasm of leukemic blasts in Acute Myelogenous Leukemia (AML) and Acute Promyelocytic Leukemia, or AML M2 and M3. They are also seen in the myelodysplastic syndromes and myeloproliferative disorders. Auer rods are shaped like needles and may or may not be pointed at the ends.
Monocytosis:
Monocytosis is an increase in the number of monocytes. It is associated with the following conditions:
- Inflammation (chronic)
- Infection (acute or chronic): bacterial or viral
- Autoimmune diseases like rheumatoid arthritis, lupus or irritable bowel syndrome
- Malignancy
- Obesity
- Lipid storage diseases
- Sarcoidosis
Reactive Monocytes
Reactive monocytes tend to "push away" the other cells around them.
Reactive monocytes are sometimes seen in certain viral infections, including viral meningitis, cytomegalovirus (CMV), and Epstein-Barr Virus (EBV). Other causes include trauma, malignancy such as carcinoma, lymphoma or plasma cell myeloma, leukemia, chronic infection, an autoimmune disorder, or a splenectomy. Flow cytometry can aid in absolute diagnosis, as well as immunophenotyping and cytogenetic studies.
The vacuolated larger cell on the left is an activated monocyte.
Reactive Lymphocytes
Reactive lymphocytes are enlarged lymphocytes seen in the peripheral smear as a result of antigen stimulation associated with viral illnesses, drugs, radiation exposure, immunizations, hormones, and autoimmune disorders such as Rheumatoid arthritis. They are commonly observed in association with Epstein-Barr Virus (EBV), Cytomegalovirus, Toxoplasma gondii, Hepatitis C, Hantavirus, Group B streptococcal infection and Treponema pallidum, causative agent of syphilis.
The cytoplasm of reactive lymphocytes moves and the reactive cells tend to "hug" the other cells around them.
The cytoplasm of reactive lymphocytes moves and the reactive cells tend to "hug" the other cells around them.
Epstein-Barr Virus (EBV)
- Causative agent of "mono" (infectious mononucleosis) or "kissing disease"
- Human Herpesvirus 4 (HHV-4) (One of 8 Human Herpesviruses) and one of the most common in humans
- Spread via saliva or mucous membranes, blood, body fluids or semen
- Individuals can catch it by sharing toothbrushes, drinking glasses, kissing, sharing personal items, etc...
- Infects immune B cells and epithelial cells
- Symptoms include sore throat, fatigue, fever, swollen lymph nodes, enlarged spleen, swollen liver, possible rash
Complications:
- Gullain-Barre' syndrome
- Chronic Fatigue syndrome and malaise and body aches lasting for months (28% of the time)
- Certain cancers, including Hodgkin Lymphoma, Burkitt's Lymphoma, Gastric Cancer, Stomach Cancer, Nasopharyngeal Carcinoma, Hairy Leukopenia, Central Nervous System Lymphomas
- Associated with a higher risk of autoimmune diseases, including dermatomyositis, systemic lupus erythematous, rheumatoid arthritis, lymphomatoid granulomatosis, and multiple sclerosis
- May take 2-3 months to completely heal after infection
The Virus Particle:
- 120-180 nanometers (nm) in size
- Double-stranded DNA surrounded by a protein nucleocapsid
- Surrounded by a lipid envelope
- Surrounded by glycoprotein projections to infect the host cells
https://upload.wikimedia.org/wikipedia/commons/thumb/b/bb/Viral_Tegument.svg/680px-Viral_Tegument.svg.png
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Epstein-Barr Virus Particle; By Liza Gross - (2005) Virus Proteins Prevent Cell Suicide Long Enough to Establish Latent Infection. PLoS Biol 3(12): e430 DOI: 10.1371/journal.pbio.0030430 http://biology.plosjournals.org/perlserv?request=get-document&doi=10.1371/journal.pbio.0030430, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=861856
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https://upload.wikimedia.org/wikipedia/commons/thumb/3/34/EBV_infection_cycle_in_healthy_humans.png/2560px-EBV_infection_cycle_in_healthy_humans.png
SYMPTOMS:
Exudative pharyngitis (https://upload.wikimedia.org/wikipedia/commons/d/db/Mononucleosis.JPG)
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By Mikael Häggström.When using this image in external works, it may be cited as:Häggström, Mikael (2014). "Medical gallery of Mikael Häggström 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 2002-4436. Public Domain.orBy Mikael Häggström, used with permission. - See above. All used images are in public domain., Public Domain, https://commons.wikimedia.org/w/index.php?curid=6198887
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WHAT YOU NEED TO LOOK FOR UNDER THE MICROSCOPE:
A reactive lymphocyte "pushing away" red blood cells
Reactive lymphocytes are a sign to look for when EBV or infectious mononucleosis is suspected. These are B lymphocytes that have been infected and have lost their typical shape, creating movement of cytoplasm that causes them to "push" other cells out of the way or "envelop" (wrap) them in a specific manner. Note how the nucleus has also lost its regular shape and become distorted.
In EBV, >10% of the lymphocytes will be "atypical".
In EBV, >10% of the lymphocytes will be "atypical".
Two reactive lymphocytes "pushing away" red blood cells
Two reactive lymphocytes
7 reactive lymphocytes
OTHER TESTS:
TREATMENT:
- Monospot rapid agglutination test
- Immunoserology testing
- Antibody testing for specific antibodies
TREATMENT:
- Drinking lots of fluid
- Plenty of rest
- Ibuprofen or Tylenol for pain
Lymphocytosis: Increased Amount of Lymphocytes
Lymphocytosis is a result of infection, leukemia, lymphoma, or lymphadenopathy.
Lymphocytosis with reactive monocytes and lymphocytes is seen in the image above.
B-Cell Chronic Lymphocytic Leukemia (B-CLL)
.The image above shows pancytopenia with B-lymphocyte blasts, smudge cells, bite cells, teardrop RBCs, helmet RBCs, acanthocyte RBCs
Chronic Lymphocytic Leukemia (CLL). This type of lymphocytosis is a CLL with built-up abnormal lymphocytes.
Chronic Lymphocytic Leukemia (CLL)
Infectious mononucleosis with marked lymphocytosis and reactive lymphocytes
Ehrlichia:
Ehrlichia chaffeensis is a tickborne disease resulting in inclusions in monocytes and red blood cells.
Intracellular (Inside) and Extracellular Bacteria
Microbial organisms may be found inside white blood cells resulting from bacterial or fungal infections. Sometimes multiple organisms may be seen if there has been contamination of an intravenous (IV) line. Macrophages engulf bacteria in intracellular bacterial infections. Vacuoles may also be present. Extracellular bacteria from the same or other species may be seen in between cells, which may indicate contamination rather than infection. Presence of intracellular bacteria in addition to extracellular bacteria, as seen in the image below, rules out contamination.
Intracellular and extracellular yeast in a peripheral blood smear may either indicate an intravenous line contamination or an immunocompromised patient.
Other intracellular microbial organisms that may be seen in neutrophils include Cryptococcus neoformans, an encapsulated yeast, Histoplasma capsulatum, a type of mold, and others.
Intracellular and extracellular yeast in a peripheral blood smear may either indicate an intravenous line contamination or an immunocompromised patient.
Other intracellular microbial organisms that may be seen in neutrophils include Cryptococcus neoformans, an encapsulated yeast, Histoplasma capsulatum, a type of mold, and others.
Anaplasma/Anaplasmosis
Anaplasma phagocytophilum is a tickborne disease resulting in large inclusions in neutrophils.
Gaucher Disease:
Gaucher disease is diagnosed by the presence of Gaucher cells, which are large macrophages, 20-80 micrometers in diameter, containing one or more small, round, oval eccentric (off-centered) nuclei. The cytoplasm appears like crumpled tissue or "chicken scratch". These are found in the bone marrow, spleen, liver or other affected tissues.
Niemann-Pick Disease:
Niemann-Pick disease is characterized by the presence of Niemann-Pick cells, large macrophages 20-90 micrometers in diameter. The nucleus is small and eccentric. The cytoplasm is foamy due to the presence of many vacuoles (empty spaces). This cell is found in the bone marrow and lymphoid tissue of those affected. Those with the disease may also have a few of these in their peripheral blood as well.
Histiocytes:
Sea blue histiocytes are large macrophages with a diameter of 20-60 micrometers. The nucleus is small and eccentric. The cytoplasm contains prominent blue-green granules and vacuoles. The cells are located in the spleen, liver, and bone marrow. These are associated with:
- Familial sea blue histiocytosis
- Myeloproliferative diseases
Chediak-Higashi Anomaly:
Chediak-Higashi Anomaly is represented by leukocytes containing large gray-blue granules in the cytoplasm. Cells affected include neutrophils, lymphocytes, monocytes, and the other granulocytes. This is associated with things like:
- leukemias
- albinism
Author: John Lazarchick
Category: Myeloid Disorders > Congenital Neutropenia syndromes
Published Date: 10/15/2002
"Neutrophil from a patient with Chediak-Higashi Syndrome. Note the large irregular cytoplasmic granules."http://imagebank.hematology.org/getimagebyid/1781?size=3
Alder-Reilly Anomaly:
Alder-Reilly Anomaly is characterized by neutrophils containing deep purple-lilac-reddish granules all throughout the cytoplasm, indistinguishable from toxic granulation. Occasionally, this characteristic may be seen in eosinophils and basophils as well.
Azurophilic Granules:
Azurophilic granules occasionally surrounded by halos may be seen in peripheral blood lymphocytes associated with mucopolysaccharide storage disorders such as Sanfilippo Syndrome, a rare, autosomal recessive lysosomal storage disease. The cause is a deficiency in an enzyme required to break down the glycosaminoglycan heparin sulfate, a component of the extracellular matrix and cell surface glycoprotein receptors.
Symptoms include severe deterioration of the central nervous system beginning at an early age ranging from 2-6 years of age. Aggression, speech difficulties, hyperactivity, sleep problems, developmental delays, excessive hairiness, and seizures may exhibit themselves at this point. By age 10, symptoms become more severe and may progress to loss of motor and cognitive skills, somatic diseases, and even vegetation. The disease is fatal usually by age 30. Treatments are under research and include supportive treatments until enzymatic treatment can be developed to replace the deficient enzyme.
Symptoms include severe deterioration of the central nervous system beginning at an early age ranging from 2-6 years of age. Aggression, speech difficulties, hyperactivity, sleep problems, developmental delays, excessive hairiness, and seizures may exhibit themselves at this point. By age 10, symptoms become more severe and may progress to loss of motor and cognitive skills, somatic diseases, and even vegetation. The disease is fatal usually by age 30. Treatments are under research and include supportive treatments until enzymatic treatment can be developed to replace the deficient enzyme.
Intracellular Organisms:
FUNGI:
Sometimes, engulfed intracellular yeast, and even extracellular yeast in peripheral blood may be seen, particularly if the patient is immunocompromised. Histoplasma capsulatum and Cryptococcus neoformans is also occasionally seen in neutrophils of infected individuals.
BACTERIA:
Intracellular bacteria engulfed by leukocytes, including monocytes and neutrophils is occasionally seen in the peripheral blood of patients with infections or sepsis. Anaplasma phagocytophilum and Ehrlichia chaffeensis are rare infections caused by bacteria carried by ticks.
Sometimes, engulfed intracellular yeast, and even extracellular yeast in peripheral blood may be seen, particularly if the patient is immunocompromised. Histoplasma capsulatum and Cryptococcus neoformans is also occasionally seen in neutrophils of infected individuals.
BACTERIA:
Intracellular bacteria engulfed by leukocytes, including monocytes and neutrophils is occasionally seen in the peripheral blood of patients with infections or sepsis. Anaplasma phagocytophilum and Ehrlichia chaffeensis are rare infections caused by bacteria carried by ticks.
Gram positive bacilli Propianibacterium is seen on this blood slide
Candida albicans budding yeast
Histoplasma capsulatum yeast
Cryptococcus neoformans yeast
Gram negative rods
Basket Cell or Smudge Cell:
Basket cells, or smudge cells, are formed due to fragile cells, typically lymphocytes, that are easily damaged during the slide preparation. In EBV, or infectious mononucleosis, or chronic lymphocytic leukemia (CLL), these cells are more common.
