WBC Disorders Flashcards
Leukopenia and leukocytosis basic principles
A. Hematopoiesis occurs via a stepwise maturation of CD34+ hematopoietic stem cells
(Fig. 6.1). B. Cells mature and are released from the bone marrow into the blood. C. A normal white blood cell (WBC) count is approximately 5-10 K/µL.
1. A low WBC count(< 5 K) is called leukopenia. 2. A high WBC count (> 10 K) is called leukocytosis. 3. A low or high WBC count is usually due to a decrease or increase in one
particular cell lineage.
Leukopenia: neutropenia and causes
Neutropenia refers to a decreased number of circulating neutrophils. Causes include
1. Drug toxicity (e.g., chemotherapy with alkylating agents) - Damage to stem cells
results in decreased production of WBCs, especially neutrophils. 2. Severe infection (e.g., gram-negative sepsis) - Increased movement of
neutrophils into tissues results in decreased circulating neutrophils. 3. As a treatment, GM-CSF or G-CSF may be used to boost granulocyte production,
thereby decreasing risk of infection in neutropenic patients.
Leukopenia: lymphopenia and causes
Lymphopenia refers to a decreased number of circulating lymphocytes. Causes
include
1. Immunodeficiency (e.g., DiGeorge syndrome or HIV) 2. High cortisol state (e.g., exogenous corticosteroids or Cushing syndrome)-
induces apoptosis of lymphocytes 3. Autoimmune destruction (e.g., systemic lupus erythematosus) 4. Whole body radiation - Lymphocytes are highly sensitive to radiation;
lymphopenia is the earliest change to emerge after whole body radiation.
Leukocytosis: Neutrophilic
A. Neutrophilic leukocytosis refers to increased circulating neutrophils. Causes include
1. Bacterial infection or tissue necrosis - induces release of marginated pool and
bone marrow neutrophils, including immature forms (left shift); immature cells
are characterized by decreased Fe receptors (CD16).
2. High cortisol state - impairs leukocyte adhesion, leading to release of
marginated pool of neutrophils
Monocytosis
Monocytosis refers to increased circulating monocytes. Causes include chronic
inflammatory states (e.g., autoimmune and infectious) and malignancy.
Eosinophilia
Eosinophilia refers to increased circulating eosinophils. Causes include allergic
reactions (type I hypersensitivity), parasitic infections, and Hodgkin lymphoma.
Eosinophilia is driven by increased eosinophil chemotactic factor.
Basophilia
Basophilia refers to increased circulating basophils; classically seen in chronic
myeloid leukemia
Lymphocytic leukocytosis
E. Lymphocytic leukocytosis refers to increased circulating lymphocytes. Causes
include
1. Viral infections - T lymphocytes undergo hyperplasia in response to virally
infected cells. 2. Bordete lla pertussis infection - Bacteria produce lymphocytosis-promoting
factor, which blocks circulating lymphocytes from leaving the blood to enter the
lymph node.
INFECTIOUS MONONUCLEOSIS (IM)
EBV infection that results in a lymphocytic leukocytosis comprised of reactive CD8+
T cells; CMV is a less common cause.
1. EBV is transmitted by saliva (“kissing disease”); classically affects teenagers
B. EBV primarily infects
1. Oropharynx, resulting in pharyngitis
2. Liver, resulting in hepatitis with hepatomegaly and elevated liver enzymes
3. B cells C. CD8+ T-cell response leads to
1. Generalized lymphadenopathy (LAD) due to T-cell hyperplasia in the lymph node
paracortex 2. Splenomegaly due to T-cell hyperplasia in the periarterial lymphatic sheath
(PALS) 3. High WBC count with atypical lymphocytes (reactive CD8+ T cells) in the blood
(Fig. 6.2)
Testing for Mono
D. The monospot test is used for screening.
1. Detects IgM antibodies that cross-react with horse or sheep red blood cells
(heterophile antibodies) 2. Usually turns positive within 1 week after infection 3. A negative monospot test suggests CMV as a possible cause of IM. 4. Definitive diagnosis is made by serologic testing for the EBV viral capsid antigen.
Complications of mono
E. Complications
1. Increased risk for splenic rupture (Fig. 6.3); patients are generally advised to
avoid contact sports for one month. 2. Rash if exposed to ampicillin 3. Dormancy of virus in B cells leads to increased risk for both recurrence and
B-cell lymphoma, especially if immunodeficiency (e.g., HIV) develops.
Acute Leukemia basics
A. Neoplastic proliferation of blasts; defined as the accumulation of > 20% blasts in the bone marrow.
B. Increased blasts “crowd-out” normal hematopoiesis, resulting in an “acute”
presentation with anemia (fatigue), thrombocytopenia (bleeding), or neutropenia
(infection).
C. Blasts usually enter the blood stream, resulting in a high WBC count.
1. Blasts are large, immature cells, often with punched out nucleoli
D. Acute leukemia is subdivided into acute lymphoblastic leukemia (ALL) or acute
myelogenous leukemia (AML) based on the phenotype of the blasts.
ACUTE LYMPHOBLASTIC LEUKEMIA
A. Neoplastic accumulation of lymphoblasts ( > 20%) in the bone marrow
1. Lymphoblasts are characterized by positive nuclear staining for TdT, a DNA
polymerase. 2. TdT is absent in myeloid blasts and mature lymphocytes.
B. Most commonly arises in children; associated with Down syndrome (usually arises
after the age of 5 years)
C. Subclassified into B-ALL and T-ALL based on surface markers
B-ALL
B-ALL is the most common type of ALL.
1. Usually characterized by lymphoblasts (TdT+) that express CD10, CD19, and
CD20. 2. Excellent response to chemotherapy; requires prophylaxis to scrotum and CSF
(Fig. 6.5) 3. Prognosis is based on cytogenetic abnormalities.
i. t(12;21) has a good prognosis; more commonly seen in children
ii. t(9;22) has a poor prognosis; more commonly seen in adults (Philadelphia+
ALL)
T-ALL
T-ALL is characterized by lymphoblasts (TdT+) that express markers ranging from
CD2 to CD8 (e.g., CD3, CD4, CD7). The blasts do not express CD10.
Usually presents in teenagers as a mediastinal (thymic) mass (called acute
lymphoblastic lymphoma because the malignant cells form a mass)
ACUTE MYELOID LEUKEMIA
A. Neoplastic accumulation of immature myeloid cells (> 20%) in the bone marrow
B. Myeloblasts are usually characterized by positive cytoplasmic staining for
myeloperoxidase (MPO). 1. Crystal aggregates of MPO may be seen as Auer rods (Fig. 6.6).
C. Most commonly arises in older adults (average age is 50-60 years)
D. Subclassification based on cytogenetic abnormalities, lineage of immature myeloid
cells, and surface markers.
AML may also arise from pre-existing dysplasia (myelodysplastic syndromes),
especially with prior exposure to alkylating agents or radiotherapy.
1. Myelodysplastic syndromes usually present with cytopenias, hypercellular bone
marrow, abnormal maturation of cells, and increased blasts(< 20%). 2. Most patients die from infection or bleeding, though some progress to acute
leukemia.
Acute promyelocytic leukemia (APL)
Acute myeloid leukemia
Characterized by t(15;17), which involves translocation of the retinoic acid
receptor (RAR) on chromosome 17 to chromosome 15; RAR disruption blocks maturation and promyelocytes (blasts) accumulate.
ii. Abnormal promyelocytes contain numerous primary granules that increase
the risk for DIC. iii. Treatment is with all-trans-retinoic acid (ATRA, a vitamin A derivative),
which binds the altered receptor and causes the blasts to mature (and
eventually die).
Acute monocytic leukemia
Acute myeloid leukemia
i. Proliferation of monoblasts; usually lack MPO
ii. Blasts characteristically infiltrate gums (Fig. 6.7).
Acute megakaryoblastic leukemia
Acute Myeloid leukemia
i. Proliferation of megakaryoblasts; lack MPO
ii. Associated with Down syndrome (usually arises before the age of 5)
Chronic Leukemia- basics
A. Neoplastic proliferation of mature circulating lymphocytes; characterized by a high
WBC count
B. Usually insidious in onset and seen in older adults
CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
A. Neoplastic proliferation of naïve B cells that co-express CD5 and CD20; most common leukemia overall
B. Increased lymphocytes and smudge cells are seen on blood smear (Fig. 6.8).
C. Involvement of lymph nodes leads to generalized lymphadenopathy and is called small lymphocytic lymphoma.
D. Complications include
1. Hypogammaglobulinemia - Infection is the most common cause of death in CLL.
2. Autoimmune hemolytic anemia
3. Transformation to diffuse large B-cell lymphoma (Richter transformation) - marked clinically by an enlarging lymph node or spleen
HAIRY CELL LEUKEMIA
Neoplastic proliferation of mature B cells characterized by hairy cytoplasmic
processes (Fig. 6.9)
B. Cells are positive for tartrate-resistant acid phosphatase (TRAP).
C. Clinical features include splenomegaly (due to accumulation of hairy cells in red pulp) and “dry tap” on bone marrow aspiration (due to marrow fibrosis). Lymphadenopathy is usually absent.
D. Excellent response to 2-CDA (cladribine), an adenosine deaminase inhibitor;
adenosine accumulates to toxic levels in neoplastic B cells.
ADULT T-CELL LEUKEMIA/LYMPHOMA (ATLL)
A. Neoplastic proliferation of mature CD4 + T cells
B. Associated with HTLV-1; most commonly seen in Japan and the Caribbean
C. Clinical features include rash (skin infiltration), generalized lymphadenopathy
with hepatosplenomegaly, and lytic (punched-out) bone lesions with hypercalcemia.
MYCOSIS FUNGOIDES
Neoplastic proliferation of mature CD4+ T cells that infiltrate the skin, producing
localized skin rash, plaques, and nodules. Aggregates of neoplastic cells in the
epidermis are called Pautrier microabscesses. B. Cells can spread to involve the blood, producing Sezary syndrome.
1. Characteristic lymphocytes with cerebriform nuclei (Sezary cells) are seen on
blood smear (Fig. 6.10).