Leukocyte Count and Disorders Quiz

Leukemia and Lymphoma

Leukemia and lymphoma are cancers of blood cells.
The objective of this presentation is to understand the clinical and pathological features, and laboratory diagnosis of various types of blood disorders.
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Normal lab values for leukocytes include a count of 4500-11,000/mm³, segmented neutrophils 54-62%, bands 3-5%, eosinophils 1-3%, basophils 0-0.75%, lymphocytes 25-33%, and monocytes 3-7%.
Leukopenia is a white blood cell count below 4.5 thousand and leukocytosis is a count above 11 thousand.
Usually, only one cell line is affected.
Blood cell differentiation, or hematopoiesis, begins with a hematopoietic stem cell, which differentiates into a multipotent progenitor cell and further into myeloid or lymphoid progenitors.
Images depict various blood cell types such as bands, platelets, eosinophils, neutrophils, lymphocytes, and basophils.
Erythroid cells mature from pronormoblast to reticulocyte.
Normal bone marrow contains fat and megakaryocytes.
Bone marrow smears show maturation of neutrophils (blasts, promyelocyte, myelocyte, metamyelocyte, band, mature).
Normal peripheral blood smear (PBS) shows erythrocytes, neutrophils, platelets, and monocytes.
White cell disorders include decreased white blood cell count (leukopenia) due to decreased production or increased destruction, and increased white blood cell count (leukocytosis), which can be reactive or neoplastic.
Lymphadenopathies are divided into benign and malignant.
Abnormal bone marrow findings include low cellularity and high cellularity.
Bone marrow suppression may be caused by toxicity by drugs.
A decreased white blood cell count (leukopenia) can be caused by decreased production or increased destruction of cells. Decreased production will include lymphopenia and neutropenia.
Neutropenia, also known as agranulocytosis, is a decreased count of neutrophils/granulocytes, often resulting in severe infections (<500 cells/µl) and can be caused by increased destruction (e.g., immune response, infections like splenomegaly) or decreased production (e.g., bone marrow hypoplasia, drug induced effects).
Specific types of infections such as DiGeorge Syndrome and HIV, along with high doses of steroids, radiation, and use of specific drugs, can result in lymphopenia.
Different types of leukocytosis and their possible causes are detailed.
Transient leukocytosis can occur from release of marginating pool of leukocytes, and results in increased white blood cell count.
Döhle bodies, toxic granules, and cytoplasmic vacuoles are abnormal structures found in blood cells.
Leukemoid reactions cause unusually high white blood cell counts (> 50,000).
Infections Mononucleosis (IM) is a benign, self-limited lymphoproliferative disorder affecting teens and caused by Epstein-Barr virus (EBV). This virus infects oropharynx, liver, and B cells, and is transmitted by saliva.
Atypical lymphocytes are often seen in IM.
Complications of IM includes risk of splenic rupture and risk of B-cell lymphoma.
Laboratory findings will often include lymphocytosis, atypical lymphocytes, and a positive heterophile antibody reaction.
The Monospot test is used to detect IgM antibodies that cross-react with horse or sheep red blood cells. It is usually positive within 1-6 weeks of infection.
A confirmatory test that shows the levels of EBV antigens, such as viral capsid antigens, early antigens, and Epstein-Barr nuclear antigen, with increasing antibody titles over time will confirm IM.

Neoplasms of White Cells

Myeloid neoplasms include acute myeloid leukemia (AML), chronic myeloproliferative disorders/neoplasia (MPD/MPN), and myelodysplastic syndromes (MDS).
Lymphoid neoplasms include acute lymphoblastic leukemia (ALL), chronic lymphoid leukemia (CLL), lymphoma (Hodgkin and non-Hodgkin), and plasma cell neoplasm.
AML includes an accumulation of immature myeloid forms (blasts) in the bone marrow.
MDS involves ineffective hematopoiesis due to defective maturation of myeloid progenitors, often leading to cytopenia.
Myeloproliferative disorders (MPN or MPD) feature increased production of one or more blood cell types.
Acute leukemia presentations often include abrupt onset and marrow function depression (symptoms such as anemia, fever, infection, bleeding due to thrombocytopenia), and mass effects (bone pain, lymphadenopathy, hepatosplenomegaly). Central nervous system involvement can also occur (headache, vomiting, nerve palsies).
WHO classification of ALL includes precursor B and precursor T acute lymphoblastic leukemia/lymphoma, Burkitt's leukemia/lymphoma, and biphenotypic acute leukemia, based on both immunophenotypic and genotypic attributes. These classifications utilize TdT assay and a monoclonal antibody panel for T-cell and B-cell associated antigens.

Acute Lymphoblastic Leukemia (ALL)

ALL is the most common cancer in children.
ALL consists of lymphoblasts, which are B-cells (pre-B) or T-cells (pre-T).
85% of ALL cases are B-ALL and T-ALL is seen in adolescent males.
20% or greater lymphoblasts in the bone marrow, hypercellular marrow will be seen with lymphoblasts.
Both blasts stain positive for TdT nuclear staining.
High WBC, circulating blasts, low platelets count, and neutropenia are common features on a peripheral blood smear.
Genetic assays, such as testing for ABL1, ABL2, AICDA, BCL2, BCL6, et cetera, determine the genetic mutations present.
Flow cytometry distinguishes different ALL subtypes (AML 1,2,3; B-ALL, T-ALL) based on distinctive antigens and their expression.

Acute Myeloid Leukemia (AML)

AML is a disease of adults.
Clinical features are similar to ALL.
20% myeloblasts are found in the bone marrow.
Myeloblasts stain + for myeloperoxidase (MPO).
Crystal aggregates of MPO (Auer rods) may be seen.
Common genetic aberration is t(8;21)
AML can occur after chemotherapy (t-AML).
It is characterized by an aggressive nature requiring aggressive therapies like chemotherapy or stem-cell transplantation.
WHO has defined classifications for AML based on differentiation (MO, M1, M2, M3, M4, M5, M6, and M7)
Other abnormal findings relating to AML include involvement of the skin (granulocytic sarcoma) along with specific types of AML (e.g., acute promyelocytic leukemia [M3], acute monoblastic leukemia [M5]).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

CLL/SLL is the most common adult leukemia.
Patients often present asymptomatically, presenting with fatigue, weight loss, and anorexia.
Lymphocytosis (> 5000 cells/mm³) often feature in PBS.
Smudge cells are characteristic.
Often involves lymph nodes (SLL) and spleen and liver.
Specific markers are expressed in CLL/SLL cells (CD19, CD20, CD23, and CD5) and often show trisomy 12 or deletion of 11q, which can be used as a staging and prognostic factor.
BCL2 overexpression can also be present.
Infections are the most frequent cause of death in patients with CLL/SLL, due to the disruption of immunity.

Hairy Cell Leukemia

It is an indolent disease affecting primarily middle-aged men.
Mature B cells display characteristic hairy cytoplasmic processes.
The disease is TRAP (Tartrate-resistant acid phosphatase) positive.
Markers CD19 and CD20, along with the immunoglobulin class (IgG), are frequently found.
Patients usually present with symptoms of pancytopenia and infections.
Splenomegaly is a prominent feature.

Adult T-Cell Leukemia/Lymphoma (ATLL)

ATLL is caused by the human T cell leukemia virus type 1 (HTLV-1)
Mature CD4+ T cells are involved.
The disease is transmitted sexually or through blood products or breast feeding.
It is common in Japan, the Caribbean, and South America.
Skin rash, adenopathy, and frequently hepatosplenomegaly are common presenting symptoms, often with lytic bone lesions and hypercalcemia.
Peripheral blood tests often show lymphocytosis with cloverleaf or flower-like cells.
The disease follows an aggressive course with a poor prognosis.

Mycosis Fungoides/Sezary Syndrome

Mycosis fungoides involves CD4+ T cells that target skin tissue.
The disease frequently progresses from rash to plaques to tumors.
Sezary cells are T cells with cerebriform nuclei.
Sezary cells are found in the epidermis, which can accumulate, forming Pautrier microabcesses.
Symptoms of Sezary syndrome includes erythroderma and leukemia of Sezary Cells, which are often visible in the peripheral blood smear.

Lymphoma Classification

Lymphomas are classified based on location (nodal or extranodal), B or T cell origin, cell size, cell growth pattern, surface markers, and cytogenetic translocations (e.g., t(14:18)).
Types of lymphomas, including Hodgkin's lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), are broadly divided based on size, presence or absence of reed-sternberg cells, growth patterns, and spread (contiguous vs. non-contiguous). Further classifications for specific lymphomas are categorized.
Precursor lymphoblastic leukemia/lymphoma, and specific classifications are present for various specific lymphomas such as the various types of follicular lymphoma vs. other types, mantle cell lymphoma, and marginal zone lymphomas.
Working formulations for classifying lymphomas by grades according to their cell structures are described.
Specific types of lymphomas are described from the WHO classification to aid in the diagnosis and classification of specific types.
Clinical presentations and pathology descriptions for specific lymphomas including Burkitt's lymphoma and diffuse large B cell lymphoma with various types and locations (e.g. spleen) are presented.

Additional Information

This summary provides a broad overview of leukemia and lymphoma. For detailed information on specific conditions or treatments, please consult a medical professional.