Immunoproliferative

Diseases
IMSE 311

Rochelle Darlucio-Yabut, RMT, MPH

Our Lady of Fatima University
College of Medical Laboratory Science
Malignant Transformation of Hematologic Cells
✓ Cell Properties
✓ Genetic Changes

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Classification of Hematologic Malignancies
✓ French-American British (FAB) Cooperative Group
✓ Revised European American Lymphoma (REAL)

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Leukemias

✓ Myelogenous leukemia
✓ Lymphocytic Leukemia

• Further divided into:

✓ Chronic Leukemia
✓ Acute Leukemia

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Leukemias

• Acute Lymphocytic Leukemia (ALL)

✓ characterized by the presence of very poorly differentiated precursor
cells (blast cells) in the bone marrow and peripheral blood

✓ Four types:
✓ CALLA (CD10)-expressing precursor B-cell ALL
✓ pre–B-cell ALL without CALLA (CD10)
✓ T-cell ALL
✓ mature B-cell ALL

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Leukemias
• Chronic Lymphocytic Leukemia or Lymphoma
✓ Chronic lymphocytic leukemia (CLL)
✓ involves the expansion of a clone of B cells that have the appearance of small mature
lymphocytes.

✓ Small lymphocytic lymphoma (SLL)

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 Leukemias
• Hairy Cell Leukemia
✓ characterized by infiltration of the bone marrow and spleen by leukemic cells
without the involvement of lymph nodes
✓ bone marrow disease and pancytopenia
✓ malignant lymphocytes are round and often have irregular “hairy” cytoplasmic
projections from their surface
✓ CD19, CD20, and CD22—and the IL-2 receptor, CD25
✓ CD 103
✓ acid phosphatase isoenzyme 5
✓ Polymerase Chain Reaction (PCR)- mutated gene BRAF-V600E

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Lymphomas
• Hodgkin lymphoma (HL)
• Non-Hodgkin, or lymphocytic lymphomas (NHLs)

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Lymphomas
• Hodgkin Lymphoma (HL)
✓one of the most common lymphomas
✓divided into nodular lymphocytic-predominant HL (NLPHL) and classic HL

✓Classic Hodgkin Lymphoma

✓ characterized by the presence of Hodgkin and Reed-Sternberg (RS) cells in affected
lymph nodes and lymphoid organ

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Lymphomas
• Non-Hodgkin Lymphoma (NHL)
• staged, I through IV - Ann Arbor classification system
• Immunosuppression: greatest risk factor
• autoimmune diseases, congenital immunodeficiency disorders, organ
transplantation, and exposure to certain infectious agents
• Diffuse Large B-cell Lymphoma (DLBCL) - most common NHL
• Follicular lymphoma

• 3 characteristics usually identify lymphomas as having a B-cell origin

• (1) surface immunoglobulin,
• (2) other cell surface proteins
• (3) rearranged immunoglobulin genes

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Plasma Cell Dyscrasias
• characterized by the overproduction of a single immunoglobulin
component called a myeloma protein (M protein), or paraprotein, by
a clone of identical plasma cell

• Multiple myeloma
• Waldenström macroglobulinemia
• Premalignant conditions MGUS
• Smoldering multiple myeloma (SMM).

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Plasma Cell Dyscrasias
• Monoclonal Gammopathy of Undetermined Significance (MGUS)
• produce a monoclonal immunoglobulin but do not have symptoms of organ
damage or other laboratory findings that are associated with multiple
myeloma or the other plasma cell dyscrasias

• three criteria that define the presence of MGUS:

• (1) a serum monoclonal protein concentration of less than 3 g/dL
• (2) a plasma cell count of lower than 10% of the total cells in the bone marrow
• (3) the absence of signs or symptoms associated with multiple myeloma, known as the
CRAB features (increased serum calcium, renal failure, anemia, lytic bone lesions)

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Plasma Cell Dyscrasias
• Multiple Myeloma
• a malignancy of mature plasma cells that accounts for about 10% of all
hematologic cancers.
• have excess plasma cells in the bone marrow, a monoclonal immunoglobulin
component in the plasma or urine, and lytic bone lesions
• express CD38, CD56, and CD138
• Bence Jones proteins
• Clinical Manifestations: skeletal, hematologic, and immunologic

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Plasma Cell Dyscrasias
• Waldenström Macroglobulinemia
• a malignant proliferation of IgM-producing lymphocytes which is also known
as a lymphoplasmacytic lymphoma.
• Malignant cells: B cells or plasma cells
• Have elevated macroprotein or IgM paraprotein

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 Plasma Cell Dyscrasias
• Heavy-Chain Diseases
• rare B-cell lymphomas that are characterized by the production of a monoclonal
immunoglobulin (Ig) heavy chain
• Production of abnormal heavy chains that have lost part of their CH1 or variable
domain
• Alpha heavy-chain disease: most common
• lymphoma that involves the MALT and can occur as one of three forms: gastrointestinal,
respiratory, or lymphomatous
• Gamma chain disease: very rare disorder
• three forms:
• disseminated lymphoma with lymphadenopathy and generalized symptoms
• localized disease with lymphoma limited to the bone marrow
• localized disease involving areas outside of the lymph nodes
• Mu heavy-chain disease: extremely rare disorder
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Role of the Laboratory in Evaluating
Immunoproliferative Diseases
• three types of specialized tests
• Immunophenotyping by flow cytometry
• Evaluation of immunoglobulins
• Genetic testing

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IMMUNODEFICIENCY
DISEASES
IMSE 311

Rochelle Darlucio-Yabut, RMT, MPH

Our Lady of Fatima University
College of Medical Laboratory Science 18
Immunodeficiencies
• disorders in which a part of the body’s immune system is missing or
dysfunctional

• Primary immunodeficiencies (PIDs)

• inherited dysfunctions of the immune system.

• Secondary immunodeficiency

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Nine Categories of Primary Immunodeficiencies
• Category 1: Combined Immunodeficiencies
• Category 2: Combined Immunodeficiencies With Associated or Syndromic Features
• Category 3: Predominantly Antibody Deficiencies
• Category 4: Diseases of Immune Dysregulation
• Category 5: Congenital Defects of Phagocyte Number, Function, or Both
• Category 6: Defects in Innate Immunity
• Category 7: Autoinflammatory Disorders
• Category 8: Complement Deficiencies
• Category 9: Phenocopies of Primary Immunodeficiencies

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PRESENTATION TITLE 21
Category 1: Combined Immunodeficiencies

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Category 2: Combined Immunodeficiencies
With Associated or Syndromic Features

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Category 3: Predominantly Antibody
Deficiencies

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 Category 4: Diseases of Immune Dysregulation
• Autoimmune lymphoproliferative syndrome (ALPS)
• involve mutations in genes coding for caspase enzymes involved in apoptosis

• CD25 deficiency
• lack of T regulatory (Treg) cells

• Chediak-Higashi syndrome
• immunodeficiency with hypopigmentation (loss of skin color) caused by a
mutation in the LYST gene
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Category 5: Congenital Defects of Phagocyte
Number, Function, or Both
• Chronic granulomatous disease (CGD)
• inheritance of either an X-linked or autosomal recessive gene that affects neutrophil
microbiocidal function

• Other Microbiocidal Defects

• Neutrophil glucose-6-phosphate dehydrogenase deficiency
• leads to an inability to generate enough NADPH to supply reducing equivalents to the NADPH
oxidase system
• Myeloperoxidase deficiency
• may have recurrent candidal infections

• Leukocyte Adhesion Deficiency (LAD)

• deficiency in a protein called CD18
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Category 6: Defects in Innate Immunity
• Chronic mucocutaneous candidiasis
• mutations in genes coding for IL-17

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Category 7: Autoinflammatory Disorders
• 2 classifications:
• Inflammasome
• Hyper IgD syndrome (periodic fever syndrome)
• Muckle-Wells syndrome

• Noninflammasome
• Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS)
• Early-onset inflammatory bowel disease (IBD)

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Category 8: Complement Deficiencies
• C1q, C4, and C2- lupuslike syndrome

• C5–C9- recurrent Neisseria meningitidis infections.

• C1 esterase inhibitor- hereditary neuroangioedema

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Category 9: Phenocopies of Primary
Immunodeficiencies
• Chronic mucocutaneous candidiasis
• genetic mutation in the AIRE gene, but also involves an antibody to either (or
both) IL-17 and IL-22

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References:
• Stevens, C and Miller, L. (2017). “Clinical Immunology and Serology, A
Laboratory Perspective”. 4th edition

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