Lymphoproliferative Disorders

Lymphoproliferative Disorders

• B and T lymphocyte malignant proliferation

• Chronic, slow progression

• Mainly affects elderly

• related to compromised immune systems

• Diagnosed w/ flowcytometry and chromosomal analysis

Chronic Lymphocytic Leukemia (CLL)

• B lymph proliferation

• May be due to chromosomal abnormalities

• Small lymphs accumulate in spleen, lymph nodes, BM→ spills out into peripheral circulation

CLL Lab/ peripheral findings

• Key: mature lymphs but are nonfunctional

• High WBC counts

• 90% lymphs

• Infection-prone due to immunocompromised

• 10% develop into AIHA (autoimmune hemolytic anemia)

• Spherocytes, nRBCs

• Smudge cells

  • fragile remnants lacking identifiable membrane or nuclear structure

• WBC: >100,000/ cu mm

• M:E ratio 10-20:1

• Peripheral blood is almost exclusively small lymphocytes with a few lymphoblasts

CLL symptoms

• Fatigue

• pallor

• weight loss

CLL disease progression/ genes

• BCL2: Anti-apoptosis gene in 80% of cases

  • Dysfunctional B cells live longer

• RAI staging system

• Common hypogammaglobinemia

CLL may lead to

• splenomegaly

• lymphadenopathy

• anemia

• thromboneutropenia

• altered immune funtion

• AIHA

CLL treatments

• Irradiation

• drugs

• aklylating agents

• Monoclonal Abs

• Allogenic stem cell transplant

Hair Cell Leukemia (HCL) + marker

• Rare B cell malignancy (2%)

• “Hairy” mononuclear cells

  • Fragile

  • hair-like projections off cytoplasm

  • Spongy, looks like chromatin

• Diagnose with cytochemical stain: tartrate resistant acid phosphatase (TRAP)

• CD103: hairy cell marker

TRAP (tartrate acid phosphatase)

• Diagnoses HCL

• Hair cells STRONGLY positive, other cells may be somewhat positive

  • Hairy cells remain stained when tartrate acid is added but other cells become negative

HCL symptoms

• Pancytopenia

• splenomegaly

• bleeding

• infection

• anemia

• Dry tap: BM too fibrous and BM cannot be aspirated

HCL treatment

• Therapeutic splenectomy

  • Improves cytopenias, hypersplenism, physical symptoms

• Interferon alpha

• 2-chlorodeoxyadenosine (2-CdA)→ had remissions

Sezary Syndrome

• T-cell lymphoma associated w/ mycosis fungoides

  • Cutaneous manifestation

• Infiltration of abnormal lymphs

• May affect spleen, BM, lymph nodes

• Deletions on chromosomes 10 and 17, or duplications on 8 and 17

Sezary peripheral blood

• Large cells (8-20 um)

• Nucleus: ovoid, clefted, or folded

• Chromatin: smooth, homogenous

• may look like monocytes

Prolymphocytic Leukemia

• Variant of CLL

• Majority of circulating prolymphocytes

  • has more cytoplasm than mature lymphocytes

• Symptoms:

  • Splenomegaly

  • Liver involvement

  • Elevated WBC count

Hodgkin’s Lymphoma

• Cervical lymph nodes are firm to the touch and does not disappear

• Hypermetabolism:

  • Low grade fever

  • weight loss

• Lymph node biopsy determines diagnosis

Hodgkin’s Lymphoma peripheral smear

• Presence of Reed-Sternberg cell

  • Large, multinucleated

  • looks like “owl’s eye”

• May involve liver, spleen, BM

Non- Hodgkin’s Lymphomas

• 3x more common than Hodgkin’s

• May present as painless cervical lymph node involvement

• Treatment: radiation, chemotherapy

• Disease may spready to:

  • GI system

  • Respiratory system

  • skin

  • liver

  • spleen

Non- Hodgkin’s Lymphoma peripheral smear

• Lymphoma cells may be present

  • Diagnosis based on histological types of lymphocytic cells

Normal Plasma Cell

• Evolves from B lymphocyte

• Medium sized

• off center nucleus

• well-defined golgi

• cytoplasm: blue/cornflower color

• Chromatin: organized in a pinwheel structure

• Makes IGs

  • 4 polypeptide chains

  • 2 heavy chains

    • Gamma (γ), alpha (α), mu (µ), epsilon (ε), and

      delta (δ)

  • 2 light chains

    • Kappa (κ) and lambda (λ)

• IEP (immunoelectrophoresis) separates IGs via ABs directed against each fraction and ran against electric field

Multiple Myeloma (MM)

• Abnormal proliferation of plasma cells

  • Accumulates in BM and other locations

• Mono clonal

  • Purposeless production of one specific Ab

• Excess of IgG

• Usually in older ages

• Translocations on

  • t11:14

  • t4:14

MM BM findings + other factors

• Plasma cell accumulation in BM

• Contributing factors:

  • Atomic radiation exposure

  • Organic solvents exposure

  • Textile toxins exposure

  • basically other exposure to chemicals, pesticides, herbicides

• May also be caused by chromosome abnormalities

MM pathophysiology

1. Acceleration of plasma cells in BM

• Caused by cytokine IL-6

• Colorless inclusions: Russell bodies, or other crystal inclusions'

• in IgA myeloma: Flame cells (pictured) may be seen

• Deep pink cytoplasm

2. Activation of bone resorption factors or osteoclasts

• Increased osteoclast activity→ bone loss

• Increased serum calcium→ kidney failure/ kidney stones

3. Production of abnormal monoclonal protein

MM diagnosis

• Increased plasma cells in BM and may be in peripheral blood

• Rouleaux formation

  • Nonspecific binding of RBCs

  • Reduced zeta potential from abnormal proteins

  • Falsely decreased RBC count

  • False increased MCV and MCHC

  • Increased ESR

• Bence-Jones protein in urine

  • Precipitates out when heated, different from other proteins

MM symptoms

• Anemia→ fatigue

• Excess calcium→ excess thirst/ urination, nausea

• Plasma cell acceleration→ pain bone, back, ribs

• Calcium from bones into circulation→ bone fractures

• Vertebrae compression→ weakness and numbness in legs

MM screening and treatment

• CVC

• BM procedures

• urinalysis

• protein panel

• Serum protein electrophoresis

• Serum beta microglobulin

• chemotherapy/ radiation

• Some may show punched out lesions on skull on initial radiography

Plasma cell leukemia

Complication of MM

Increased plasma cells in circulating blood

Waldenstrom’s Macroglobulinemia

• Overproduction of IgMs from abnormal lymphocytes

  • Interferes with coag factors by coating platelets→ less functional

• Peripheral blood: rouleaux, plasmacytoid lymphocytes

• Cryoglobulins found in some patients

• May head to Raynaud’s phenomenon

• Causes bleeding

Waldenstrom’s Macroglobulinemia Treatment

• Chemotherapy

• Stem cell transplantation

• Plasmapheresis