Hematopoiesis and WBC Disorders - SRS Flashcards
What is the definition of leukemia?
Term coined by Virchow to indicate a malignancy which greatly increases the “Leuko” fraction of the blood, but now also includes aleukemic leukemias
What is a lymphoma?
Solid tumors derived from lymphoid tissue that primarily involve lymph nodes and peripheral organs
What does the category “granulocyte” include? 3
- Neutrophils
- Eosinophils
- basophils
Myeloid disorders (leukemias) involve the precursors of what cell types? 4
- Erythroid
- granulocytic
- monocytic
- megakaryocytes
What are the “so called” myeloid cells?
Granulocytes and monocytes only
As far as Lymph node involvement is concerned, how are low grade and high grade non-hodgkin lymphomas different?
- Low grade: Tend to involve multiple nodes (“matted” nodes)
- High grade: Tend to involve a single node, localized group of nodes or extranodal site
What is the appearance and feel of lymphoma nodes?
Fleshy tan and rubbery firm
What are the two most common stain types for peripheral WBCs?
Wright and Giemsa
In adults, where does myelopoiesis nearly exclusively take place?
Bone marrow
In what portions of the developing fetus does prenatal hematopoiesis occur?
- Yolk sac
- Liver
- spleen
- Bone marrow
Identify the seven cells shown here.
- Band neutrophil
- Platelet
- Eosinophil
- Lymphocyte
- Segmented Neutrophil
- Monocyte
- Basophil
What is a monocyte?
Circulating macrophage or histiocyte precursor
Guess what?
Chicken butt.
Also, some small lymphocytes, small RBCs (spherocytes) and a smudge cell. Smudge cell is probably from an incompetent lab tech, or is just some schmutz.
A bone marrow aspirate is best for?
Illustrating cytology and enumeration of cells
What is a needle core biopsy best for?
Assess cellularity and architecture
What stain should be used on air dried thin smears of blood?
Romanovsky
How is the “manual WBC differential” performed?
Light microscopic examination of a “wright stained” peripheral blood smear and counting 100 white cells.
What is hyper-segmentation?
PMNs with 5 or more lobes
If you see a PMN with 5 or more lobes, what are three situations which can give rise to this type of hyper-segmentation?
- megaloblastic anemias
- myeloproliferative disorders
- chemotherapy
What would you call the increased and prominent azurophilic (primary) granules and cytoplastic vacuoles seen with infections?
Toxic granulation and vacuolization
What is a left shift?
Absolute increase in neutrophils with an increase in bands +/- metamyelocytes or myelocytes- seen in infections and leukemias
What are these cells?
What is the arrow pointing to?
What else is visible in these cells?
Neutrophils, arrow is pointing to Döhle bodies, blue cytoplasmic patches of dilated endoplasmic reticulum
Also see toxic granulations, coarse purple cytoplasmic granules
The relative change in one type of WBC expressed as a % of overall # of WBCs usually doesn’t mean much. What does matter?
What matters for each WBC type is the “absolute’ count or % of total multiplied by the total WBC count; e.g.,
Absolute Neutrophil Count = % Neutrophils X total WBC count
Absolute neutrophils = 46% X 10,000 cell/microliter
= 4,600 neutrophils/uL
What are the normal white cell ranges in adults?
4.8-10.8
What are the normal granulocytes (%) in adults?
40-70
Nl neutrophils in adults? ((×103/μL)
1.4-6.5
nl lymphocytes in adults? (×103/μL)
1.2-3.4
nl monocytes in adults? (×103/μL)
0.1 - 0.6
nl eosinophils in adults? (×103/μL)
0 - 0.5
nl basophils in adults? (×103/μL)
0 - 0.2
nl red cells in adult males and female respectively?
Men: 4.3 - 5.0 (×106/μL)
Women: 3.5-5.0 (×106/μL)
nl platelets in adults? (×103/μL)
150 - 450
What is the lifespan of a neutrophil (granulocyte) in peripheral blood?
1 - 48 hours
What percent of mature PMN’s circulate in the intravascular pool?
less than 5%
What is the lifespan of an eosinophil in peripheral blood?
1 - 48 hours (average 8 hrs)
What is the typical lifespan of a B-cell in peripheral blood?
Hours to days
What is the lifespan of T-cells in peripheral blood?
Days to years
What are two causes of neutrophilic leukocytosis?
- acute bacterial infections, particularly those by pyogenic organisms
- sterile inflammation, example = tissue necrosis d/t MI or burns
What are four causes (broad) or eosinophilic leukocytosis? 4 bold, 6 total
- Allergic disorders (asthma, hay fever)
- helminthic parasitic infestations
- drug reactions
- autoimmune disorders
- vasculitides
- Hodgkin and some NHL’s
Basophilic leukocytosis (basophilia) is rare, and often indicates what disease is occuring?
A myeloproliferative disease (e.g. chronic myeloid leukemia)
Monocytosis can be caused by what 6 things?
- Chronic infections
- bacterial endocarditis
- rickettiosis
- malaria
- autoimmune disorders
- inflammatory bowel disease
Lymphocytosis accompanies monocytosis in many disorders associated with what three things?
- chronic immunological stimulation
- viral infections
- bordatella pertussis infection
What are three broad causes of increased leukocyte production in the marrow?
- Chronic infection or inflammation
- paraneoplastic
- myeloproliferative disorders
What are three things that cuase increased release of leukocytes from marrow stores?
- Endotoxemia
- infection
- hypoxia
What are two things that cause decreased margination of leukocytes?
- exercise
- catecholamines
What is one thing that causes decreased extravasation of leukocytes into tissues?
Glucocorticoids
Neutrophils and their precursors are distributed in five pools… Sampling of the peripheral blood assesses only the circulating pool!!! What are the five pools?
- Precursor pool
- storage pool
- marginating pool
- circulating pool
- tissue pool
What is a leukamoid reaction? What is it not?
A marked elevation in white cell count - usually greater than 20k/uL
Though it simulates chronic myelogenous leukemia, it is not.
How do you tell the difference between the leukamoid reaction and chronic myelogenous leukemia?
- Leukamoid reaction: Leukocyte alkaline phosphatase score elevated
- Chronic Myelogenous leukemia: Low alkaline phosphatase score
A leukoerythroblastic reaction will have the presence of immature granulocytes and erythroid precursors in the blood. What are some examples of conditions this is commonly seen in?
- severe hemolytic anemia
- bone marrow infiltration by:
- metastatic tumor
- granulomas
- infiltrative process (fibrosis)
- chronic myeloproliferative neoplasms
- particularly myelofibrosis
What is the critical value for neutropenia (granulocytopenia)?
absolute count < 500/µL or < 0.5 x 109/L (<1000/uL clinically worrisome)
The lower a patients neutrophil count, the higher the risk of infection. What is the most common cause of acquired neutropenia?
What is the most common cause of clinically significant neutropenias?
- Infections
- Drugs - agranulocytosis, severe neutropenia
Neutropenia pathogenisis typically includes what two general causes?
Decreased or ineffective production
Accelerated removal or destruction
Neutropenia d/t decreased or ineffective production may be d/t inherited or acquired causes. Give examples of each.
Inherited - severe congenital neutropenia - Kostmann syndrome
Acquired - aplastic anemia, myelodysplastic syndrome, nutritional deficiencies
What are some examples of neurtopenia that involve accelerated removal or destruction?
- Immunologic disorders
- Splenomegaly
- Severe infections, such as overwhelming bacterial infection
Peripheral blood eosinophilia may be relative or absolute. What are the criteria for each?
Relative Eosinophilia: >3% total wbc differential count
Absolute Eosinophilia: Total Eosinophils >0.5 x 109/L
Absolute eosinophilia is further divided into what three categories?
What are the criteria for each category?
Mild Eosinophilia 0.35-0.90 x 109/L
Moderate Eosinophilia 1.00-5.00 x 109/L
Marked Eosinophilia >5.00 x 109/L
What are the majority of circulating Lymphocytes?
> 80% are T cells
What causes acute infectious mononucleosis?
Epstein Barr virus (EBV)
What are four characteristic findings in acute infectious mononucleosis?
- Severe fatigue
- Sore throat
- Lymphadenopathy
- Lymphocytosis due to variant forms (Downey cells)
What cells does EBV infect?
B cells
EBV infects B cells via glycoprotein binding of CD21/CR2 (C3d complement receptor). May present asymptomatically in kids or with sore throat, fever, febrile rash and lymphadenopathy.
Hepatitis, anemia, thrombocytopenia, splenomegaly.
There is a subsequent B and T cell response. What cells soon predominate in tissues and blood?
- Cytotoxic/supressor CD8+ T cells and CD 16+ NK cells soon predominate in tissues and blood destroying infected B cells
What does this describe?
- sensitive fairly specific heterophile antibody test positive in 1-2 weeks in 85% (Serum absorbed with guinea pig kidney still binds horse erythrocytes)
Monospot test
What will be identified in heterophile negative EBV cases?
Epstein Barr virus antibodies to capsid antigen
Identify the two cells shown here.
Left: normal small lymphocyte with a compact nucleus filling the entire cytoplasm
Right: atypical T lymphocyte on the right has abundant cytoplasm and a large nucleus with fine chromatin. EBV infected patient
Identify these cells
Atypical lymphocytes - larger with more cytoplasm, nucleoli in nuclei. Cytoplasm indented by surrounding RBC’s
Atypical lymphocytes often associated with infectious mononucleosis
Absolute lymphocytopenia is detected by automated hematology. How do we examine morphology?
Microscopic examination
What would you do to test an absolute lymphocytopenia with hemogram abnormality?
bone marrow aspirate and biopsy
If you have a patient with absolute lymphocytopenia and a suspected immune deficiency what four testing options are best?
- Flow cytometry immunophenotyping
- Serum protein concentration
- Serum protein electrophoresis
- Quantitative serum immunoglobulins
What are some common causes of lymphocytopenia?
- Chemotherapy or irradiation therapy
- Cortisone “Steroid” therapy
- Administration of erythropoietin
- Pregnancy
- Various diseases
What are some “various diseases” associated with lymphocytopenia?
- AIDS
- Hodgkin’s disease
- Idiopathic or acquired aplastic anemia
- Acute bacterial infection
- Cancer stomach, ovary and breast
- Systemic lupus erythematosus
- Occasionally viral infections
Lymph node architecture includes a mantle zone and a germinal center. What are the three zones of the germinal center?
- Dark Zone
- Basal Light zone
- apical light zone
In what zone does the following happen?
“Proliferation of B cells and somatic hypermutation”
Dark Zone
In what zone of the germinal center does the following take place?
“Generation of memory cells and plasma cell precursors and class switching”
Apical light zone
In what zone of the germinal center does the following take place?
“Positive selection for binding to antigen on follicular dendritic cells”
Basal Light zone
In what zone will you find follicular dendritic cells?
Basal light zone
Identify the areas indicated by the boxes.
What cells are found inside the area demarcated by the black circle?
Upper right = cortex
lower left = medulla, with cords and sinus
“circle” = paracortex T-cells
Identify as many of the indicated structures as possible!
Capsule
- Subcapsular sinus
- Monocytoid B cells
- IgG or IgM+. IgD-, BCL2-
Secondary Follicle
- Germinal Center (BCL2-)
- B-blast (small noncleaved)
- sIgM+, transient
- Centroblast (large noncleaved)
- sIg-, persistent
- Centrocyte (small/large cleaved)
- sIgG+, persistent
Mantle Zone (mostly naïve)
Marginal Zone
- IgM+, IgD- (memory cell)
Interfolliclar region/sinuses
Primary Follicle (naïve B-cells)
- IgM+,IgD+,CD5-/+,BCL2+
Painless enlargement of a lymph node or group of nodes is known as?
Lymphadenopathy
What is the most likely cause of lymphadenopathy?
Infection, particularly viral and in children
Although most lymphadenopathy is d/t infection, some areas of nodal enlargement are of greater concern. What are these special case nodes?
Supraclavicular and axillary lymph node enlargement is of greater concern
If you see a lymph node that is greater than 4cm (in diameter I assume) it is most likely what?
Malignant
What do you see here?
Hilar adenopathy
What is the major cause of adenopathy in patients older than 60?
Metastatic carcinoma
What does this describe?
“Swollen Edematous Tender (painful) lymph node with distended capsule”
Lymphadenitis
The most common nodal groups associated with lymphadenitis are the cervical and mesenteric. What is lymphadenitis typically associated with?
Acute bacterial infection of a localized body site, affecting the local nodes draining the site.
What does this describe?
Enlarged but painless; capsule is proportionally enlarged. Nodes are palpable (> 2cm).
Chronic nonspecific lymphadenitis
What are the three patterns of chronic nonspecific lymphadenitis?
Stimulates B-cell populations = Follicular hyperplasia
Stimulates T-cell populations = paracortical hyperplasia
Prominence of Lymphatic sinusoids = Sinus histiocytosis
Chronic nonspecific lymphadenitis may have a pattern of follicular hyperplasia with expansion of the germinal centers with an increase in what cell types?
What are three specific causes?
- Tingible (huh?) body macrophages
- Causes…
- HIV
- Toxoplasmosis
- Rheumatoid arthritis
When a chronic nonspecific lymphadenitis occurs with paracortical hyperplasia there is expansion of T-cell rich paracortical regions. What are four examples of causes for this?
- Infectious mono
- Acute viral infections
- following vaccinations
- reactions to Dilantin
Chronic nonspecific lymphadenitis may present with sinus histiocytosis, describe this as best you can.
Hyperplasia of macrophages lining sinuses, for instance in axillary nodes draining a region of breast cancer
What happens at each of the three indicated sites?
- Follicles - B cell transformation/proliferation
- Paracortex - T cell transformation/proliferation
- Sinuses - Histiocyte recruitment
What happens in the indicated portion of this lymph node?
Follice: B cell transformation and proliferation
What does this immunohistochemistry stain for B CD20 reveal?
Follicular hyperplasia (reactive hyperplasia)
What happens in the area indicated?
Paracortex: T cell transformation and proliferation
What does this stain for CD3 reveal?
Diffuse paracortical hyperplasia (reactive hyperplasia subtype)
This high power view of the dark zone shows several mitotic figures and numerous macrophages containing phagocytosed apoptotic cells. What are these phagocytosed apoptotic cells called?
Tingible bodies
A patient comes to you with the lesions shown in the picture. History reveals that they had been scratched by a cat, splinter or thorn or any combination of the three prior to their appearance.
What organism caused this?
Bartonella henslae - causes cat scratch disease
Cat scratch disease is typically a self limited lymphadenitis of the neck and head and occurs commonly in kids. It rarely presents with encephalitis, osteomyelitis or thrombocytopenia.
What leasions do you initially see on microscopy?
Later?
Initially sarcoid-like granulomas
Later stellate necrotizing granulomas
