MLAB 1415- Hematology

Keri Brophy-MartinezLymphoid Malignancies

Introduction

Two broad categories Leukemia

A malignant disease of hematopoietic tissue characterized by replacement of normal bone marrow elements with abnormal (neoplastic) blood cells.

Abnormal cells are also seen in peripheral blood Lymphoma

Abnormal proliferation of lymphoid cells within the lymphatic tissue or lymph nodes, results in a solid tumor

Pathogenesis

Acquired genetic factors Proto-oncogenes Tumor suppressor genes

Inherited genetic factors Wiskott Aldrich Ataxia telangiectasia

Environmental factors EBV infection Helicobacter pylori

Classification

Factors to consider Morphological appearance of cells

Clonality Flow cytometry Chromosome analysis

Translocations present? Molecular analysis Clinical information & history

MATURE B CELL NEOPLASMS

Chronic Lymphocytic Leukemia(CLL) General requirements for diagnosis

Peripheral blood and bone marrow lymphocytosis (>5 x 109/L)

Lymphocytes are small with mature appearance Nucleus is round, with block-type chromatin Cytoplasm scarce

Smudge cells common Occur due to the cell’s fragility in making a smear

Prolymphocyte < 10%

CLL Blood Picture

Chronic Lymphocytic Leukemia Clinical features

Occurs in persons >50 years old Chronic fatigue, infection

Result of bone marrow replacement of normal cells with lymphocytes.

Skin and organ infiltration and enlargement Median survival is 10 years

Chronic Lymphocytic Leukemia Treatment

Usually treatment is not required until lymphocytosis causes other cells to be crowded out resulting in infections.

Treatment depends on the stage at which the disease is diagnosed and is usually for the symptoms, not the disease. Chemotherapy

Prolymphocytic Leukemia

Aggressive Non-responsive to treatment

Poor prognosis Low incidence rate Origin can be B or T cell

Prolymphocytic Blood Picture

Punched out nucleolus

Hairy cell leukemia (HCL)

Presents in middle age

Affects males7:1 over females Spleenomegaly

Pancytopenia common Increases opportunity for infections

Bone marrow aspirate can result in a “dry tap” due to marrow fibrosis.

Hairy cell leukemia can be treated with a one-time chemotherapy regimen with a good prognosis of long-term survival.

Hairy cell

TRAP stain

Mature T cell Neoplasms

Less common than B cell Lymphoma ~10% of all lymphomas

Occur in extranodal sites

Sezary’s syndrome

Leukemic phase of the most common cutaneous T-cell lymphoma, mycosis fungoides.

Lymphadenopathy Red skin due to disesemination

Sezary Cell

Hodgkin’s Lymphoma

Cause is unknown, but has been linked to Epstein-Barr virus.

Bimodal distribution Diagnosed between 15 and 35 years of age Over 50 population

Males have higher incidence rates Lymph node are involved

Regional, contiguous sites

Hodgkin’s Lymphoma

Characteristic cell is the Reed-Sternberg Found in tissue biopsy Giant size (up to 45µm in diameter) Abundant acidophilic cytoplasm Multinucleated or polylobated nucleus Gigantic nucleoli

Hodgkin’s lymphoma

Treatment and prognosis Radiation of localized involvement Chemotherapy Combination of above With early diagnosis, long-term disease-free

survival is seen in about 80-90% of cases.

Nodular Lymphocyte Predominant Hodgkin’s Lymphoma Cause is unknown at this time. Predisposing

factors seem to be chemicals, ionizing radiation and certain viruses.

Reed-Sternberg cells are NOT present. B cell origin Widely disseminated, extranodal

Burkitt Lymphoma Three variants

Endemic Common in Africa Children aged 4-7 Jawbone mass

Sporadic Children & adults Abdominal mass

Immunodeficiency-associated

Rapid growth and tumor cell death results in “starry sky” appearance of the biopsy caused by macrophages cleaning up the dead cells.

Plasma Cell Disorders

• Disorders that do not involve lymph nodes

• Secrete monoclonal immunoglobulin into the serum and /or urine

• Disorders• Plasma Cell Myeloma• Plasmacytoma• Monoclonal gammopathy of undetermined

significance (MGUS)

Plasma Cell Myeloma

Overproduction of abnormal plasma cells which are the final stage in the development of B lymphocytes.

These cells secrete immunoglobulin, resulting in lytic bone lesions

Risk increases with age- rare under 40 Median age 70 years old

Suspected cause is chronic stimulation of the immune system from environmental sources. Ionizing radiation Viruses

Etiology

50% greater risk for men than women Risk increases with age; rare under 40

Median age 65 years old

Suspected cause is chronic stimulation of the immune system from environmental sources. Ionizing radiation Viruses

Features Increased production of immunoglobulin heavy and light chains

(monoclonal gammopathy) Heavy chains: IgG, IgA, IgD, IgE, IgM Light chains: kappa, lambda Most common type of plasma cell myeloma is increased production

of IgG. Bence-Jones protein

Light chains spill into the urine and can be detected by lab test Causes kidney damage

Hyperviscosity syndrome Excess immunoglobulin causes viscous blood which sludges and

causes fluid congestion.

Normal Immunoglobulin production decreased Results in infections

Lab Findings

CBC and peripheral smear Red cells form characteristic rouleaux formation (resemble stacked

coins) Plasma cells may be seen in peripheral blood

Bone marrow Increased number of plasma cells which form “sheets”

ESR Increased - serum protein causes red cells to stick together and fall faster

Chemistry studies Increased BUN and creatinine (kidney tests) Increased calcium Increased LDH

Plasma Cell Myeloma

C: hyperCalcemiaR: Renal insufficiencyA: AnemiaB: lytic Bone lesions

Plasma Cell Myeloma

Treatment Chemotherapy Radiation for localized areas Bone marrow/stem cell transplant for

younger patients Poor prognosis for individuals that are

symptomatic

References

http://www.itriagehealth.com/wl/disease/burkitt-lymphoma-%28lymph-node-tumor%29#wrapperTop

http://www.med-ed.virginia.edu/courses/path/innes/wcd/lympleuk.cfm

McKenzie, S. B., & Williams, J. L. (2010). Clinical Laboratory Hematology . Upper Saddle River: Pearson Education, Inc.