Lymphoproliferative Disorders (Exam III) Flashcards
Normal adult peripheral blood
- 60-80% T lymphocytes
- up to 20% B lymphocytes (have surgace Ig)
- Up to 22.3% NK cells
chronic lymphoproliferative disorders
clonal proliferations of morphogically and immunophenotypically mature B or T cell
Classification
- morphology
- immunophenotype
- molecular genetics
- cytogenetics
- clinical features
B cell leukemia
Chronic lymphocytic leukemia
Hairy Cell Leukemia
T cell leukemia
Sezary syndrome
Lymphomas
Hodgkin’s Lymphoma
Non Hodgkins lymphoma
Plasma cell disorders
Multiple Myeloma
- Leukemia Variant Plasma Cell leukemia
Waldenstroms Macroglobulinemia
CLL (B cell) show
failed apoptosis - high levels of antipoptotic protein BCL2
- long lived and immunologically dysfunctional lymphocytes in PB and BM
- Gradual accumulation of small mature B lymphocytes
CLL replace normal BM elements
Anemia, thrombocytopenia, neutropenia
Extramedullary hematopoiesis CLL
Splenomegaly
hypersplenism - Anemia, Thrombocytopenia, neutropenia
CLL impaited immunologic activity
Hypogammaglobulinemia
- increased infection
Autoimmunity
- Autoantibodies against RBCs, PLT, or both
CLL is more prevalent in
2x in males
90% of CLL cases
> 50%
Rare in young adults
Signs and symptoms CLL
symptoms develop gradually.
accidently discovered during doctor visit
- Unexplained lymphocytosis
- Lamphadenopathy
- Splenomegaly
CLL chronic fatige
anemia
infections CLL
neutropenia / hypogammaglobulinemia
easy bruising CLL
thrombocytopenia
Dermatologic manifestations
clinical feature of CLL
CLL - Early phase
tumor cells are predominately small in size
low proliferation rate
cells are living longer
- prolonged survival
CLL - Transformation phase
increase in immature cells
Frequent occurence of extramedullar proliferation
Lab findings CLL
Decreased Hgb and Hct
- anemia
- normocytic, normochromic RBCs
Decreased PLT count
- thrombocytopenoa
Variable WBC
- Neutropenia
- lymphocytosis
CLL lymphocytes
Hypercondensed “soccer ball” nuclear chromatin pattern
smudge cells CLL
Fragile lymphocytes “smudged” in smear process
- remedy: add albumin
do NOT count in differential
Bare nuclei are common
CLL additional morphology
Increased Prolymphocytes
Activated Lymphocytes
Increased Lymphoplasmacytoid cells
- Lymphocytes that look similar to plasma cells
BM infiltration
Non diffuse
- nodular pattern
- interstitial pattern
diffuse pattern
Nodular pattern
distinct randomly distributed aggregates of small lymphocytes
focal nodular
Interstital pattern
Lymphocytes infiltrate the interstitum without displacing fat cells
Diffuse pattern
entire BM space between bone trabeculae is replaced by small lymphocytes
Immunophenotype CLL
Positive: CD19, CD20, CD21, CD23
Negative: CD10
Positive: CD5 (usually T cell marker)
PB lymphocytosis (diagnosis)
PB lymphocytosis
- absolute lymphocyte count >5x10^9/L - normal is 1.3-3.4x10^9/L)
- monoclonal (identical)
- sustained for 3 months or longer
BM Lymphocytosis (diagnosis)
- 30% lymphocytic cells appearing morphologically mature
- previously required, still often performed
Prognosis/Treatment CLL
many live 10 years post diagnosis
Nodular or Interstitial BM patterns have longer life expectancy than diffuse paterns
- still able to preserve normal hematopoiesis
Most patients die with resiual leukemia and usually succmb to infection or CLL unrelated cause
CD23 indicates
mature state
common treatments CLL
- Fludarabine
- Radiation
Fludarabine
chemotherapy that induces apoptosis
radiation
enlarged spleen and lymph node masses
Morphology ALL vs CLL
ALL - smoother nuclear chromatin pattern pf lymphoblasts
CLL - heavy condensation of nuclear chromatin
Cytochemistry ALL vs CLL
ALL - Lymphoblasts are TdT+
CLL - CLL lymphocytes are TdT-
Hairy cell leukemia (HCL)
- Rare B lymphocyte derived chronic leukemia
- Fine hairlike irregular cytoplasmic projections
- BM - “fried egg” appearance where lymphocytic infiltrates have clear cytoplasm seperating one from another
- increase B lymphocytes in 90% of cases
Cytochemistry HCL
strong acid phosphatase and TRAP reaction
Cell markers HCL
CD19, CD20, CD22, CD11c, CD25, CD103
TRAP
Acid phosphatase stain repeated with addition of tartrate
- abolishes all acid phosphatase activity, except isoenzyme 5
- hairy cells contain isoenzyme 5
Positive staining = orange-red precipitate
TRAP is used to differentiate
Hairy cell luekemia (+) from other acid phosphatase (+) staining
Sezary Syndrome
Leukemia phase of T cell lymphoma
Cutaneous manifestation
Abnormal circulation lymphocytes (Sezary Cells)
1. small lymph nuclear folding and groovin (cerebriform)
- whorl like
- looks monocyte-like but
- NSE dot pattern
- CD2,CD3, CD4, CD5
cutaneous manifestation
mycosis fungoides
lymphoma definition
heterogenous group of diseases that arise from cells of the lymphoid tissue
lymphomas 2 categories
- hodgkin disease (hodgkin’s lymphoma)
- Lymphocytic lymphoma (aka non-hodgkins lymphoma)
symptoms of lymphoma
- enlarged lymph nodes, usually painless
- weight loss
- night sweats
- chills
- fatigue
- frequent infections
Hodgkin’s lymphoma
group of neoplasms characterized by the presence of a Reed-Sternberg cell
2 groups:
- Nodular Lymphocyte Predominant Hodgkin’s Lymphoma (NLPHL)
- Classical Hodgkin’s Lymphoma (CHL)
Hodgkin’s lymphoma - Etiology
Viral Cofactor
- Epstein Barr Virus on exam
- Cytomegalovirus
- Herpesvirus 6
Reed Sternberg cell (Hodgkins)
Malignant (clonal) prolferation of Reed-Sternberh cells and its variants
- giant cell (up to 45 um)
- abundant acidophilic cytoplasm j
- Multinucleated or polyoblated nucleaus
- “owl eyes”
L & H, or popcorn cell
(RS cell variants)
- variable amount og pale staining cytoplasm
- convoluted nucleaus - popcorn
- indistinct nucleolus
- Found in Nodular Lymphocytic Predominant Hodgkin’s Lymphoma (NLPHL)
Lacunar Cell
(RS cell variant)
RS cell where cytoplasm retracts during formalin fixation step
Empty space surroinds it
Hodgkins lymphoma Epidemiology
- 15% of lymphoma cases
Bimodial Distribution
- 15-35%
- over 50 years old
Lymphocytic lymphomas
(Non Hodgkins lymphoma)
malignant (clonal) proliferation of lymphocytic cells that are not Reed Sternberg cells
- makes up the majority of lymphoma cases
- Poorer prognosis than Hodgkin Lymphoma
- Several classsification schemes have been identified using
1. grown pattern (nodular vs. diffuse)
2. Cytologic features
3. Immunophenotype
4. Genotype
