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Hematology 2 > Lecture 9 Chronic Lymphoproliferative Disorders > Flashcards

Lecture 9 Chronic Lymphoproliferative Disorders Flashcards

1
Q

What are the 4 main disorders of Chronic Lymphoproliferative Disorders?

A
  1. Chronic Lymphoproliferative Leukemia.
  2. Prolymphocytic Leukemia
  3. Hairy Cell Leukemia
  4. Sezary Syndrome
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2
Q

What cell is most affected by CLL, PLL and HCL?

A

The B cell is most affected (99% of the time) followed by the T cell <(<1% of the time).

99% of C.L.L, P.L.L. and HCL are malignant clonal B cells that infiltrate blood, bone marrow, lymph nodes and other organs.
Very small percentage <1% are T-Lymphocytes.

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3
Q

In Chronic Lymphoproliferative Disorders what is responsible for the increased number of cells?

A

Reduced death rate of cell death not increased cell production responsible for accumulation of cells.

Abnormal cells non-responsive to normal stimuli resulting in accumulation of long-lived dormant cells.

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4
Q

What is CLL, PLL, and HCL a malignant equivalent of?

A

CLL, PLL, and HCL are a malignant equivalent of different stages of normal lymphocyte development.

CLL-least mature
HCL-most mature
PCL- intermediate

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5
Q

Why is it important to differentiate whether the Lymphoproliferative disorder involves the B or T Cell?

A

The T Cell type is way more aggressive than the B Cell type.

When T-Cell epidermal (skin rash) and CNS more likely involved.

Note: Few cases of CLL and HCL show mixed lineage –> both B and T cell markers.

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6
Q

What factors may be a possible cause for CLL and what factors are not?

A

Viruses (e.g. Human T-Cell Leukemia Virus (HTLV-1) Type C Retrovirus) and genetics are thought to be possible causes.

Predisposing factors are age (5-6th decade), male gender, acquired immunological defects.

Radiation and leukomogenic agents not linked to CLL.

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7
Q

What is the clinical presentation of CLL?

A

Fatigue and reduced exercise tolerance are the most common first clinical symptoms.

Also:
- Bruising
- Pallor or jaundice associated w/ anemia
- Fever, infection
- Bone tenderness
- Weight loss
- Edema form lymph node obstruction
- Erythroderm (skin rash) with itching common.

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8
Q

What group in the population are more likely to get the disease of CLL?

A

Elderly
- 90% over age of 50 yrs,
- 65% over age of 60 years.
Men 2x’s more affected.

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9
Q

What other clinical symptom is unique to CLL compared to other leukemias?

A

Edema because of the lymphatic system involvement.

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10
Q

What may CLL transform to in terms of disease progression?

A

CLL is more unlikely to transform to other acute conditions than other leukemias.
May transform to PLL or to a more aggressive large cell lymphoma.

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11
Q

What are the early clinical presentation of CLL?

A

Enlarged lymph nodes and splenomegaly.

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12
Q

What organs are affected with CLL after the initial clinical presentation?

A
  1. Lymph nodes enlarge and new nodal areas develop.
  2. Splenomegaly increases and hepatomegaly develops..
  3. Lymphoid cells may spread to the gonads, skin, prostate, kidney and GI track.

Note: Tissue involvement.

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13
Q

What is the importance of CLL staging?

A

Staging (a categories system) is important to determine the areas of the body affected by the disease, progressiveness and severity. The Rai staging system goes from o, I, II, III, and IV as least severe to worst. The Binet staging system goes from A, B, to C as least severe to worst.

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14
Q

What is leukocytosis with peripheral blood lymphocytosis in an elderly patient highly suggestive of?

A

CLL

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15
Q

What may absolute lymphocyte counts look like in CLL?

A

Absolute lymphocyte counts between 10 and 150 x 10^9/L common in CLL but may be higher.

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16
Q

What are smudge cells and what are they associated with?

A

Lymphocytes may be more fragile than normal leading to formation of smudge cells during smear preparation, in vitro effect.

The appearance of smudge cells is highly associated with CLL.

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17
Q

What are the morphological appearance of lymphocytes in CLL?

A
  1. Some cases are normal looking (Mature and homogenous*) especially in early stages. May have soccer ball appearance.
  2. Lymphs may also be larger with clumped or condensed chromatin. Cytoplasm may be abundant or scanty.

Note: Although homogenous in any one patient may vary from case case.

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18
Q

How are the % of prolymphocytes in peripheral blood in CLL, CLL/PLL, and PLL used for diagnoses?

A

CLL < 10% Prolymphocytes
CLL/PLL 11-55% Prolymphocytes
PLL >55% Prolymphocytes

Important to measure prolymphocytes as PLL is a more aggressive disease.

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19
Q

What can help prevent the appearance of smudge cells during smear preparation?

A

Adding albumin (one drop to a few drops of blood) will provide a “cushion” and prevent smudge cell formation so accurate differential can be performed.

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20
Q

What are the laboratory findings in CLL?

A

Lab Findings in CLL:
1. Increased in absolute lymphocytes.
2. Neutrophils are variable with normal to slightly increased in early stages and decreased in advanced stages.
3. Anemia and thrombocytopenia in later stages.
4. Anemia is also a result of marrow infiltration, splenic pooling and also autoimmune hemolysis.
5. Plasma immunoglobulins can be increased but usually decreased in later stages.

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21
Q

What triggers autoimmune hemolysis in CLL patients?

A

In 15-35% of patients viral infection, disease progression, therapeutic agents, membrane damage by abnormal proteins.

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22
Q

What morphologies and lab findings in CLL suggest autoimmune hemolysis?

A
  1. DAT test positive
  2. Reticulocytosis, often spherocytes* (important clue), mild jaundice, shortened RBC survival, bone marrow erythroid hyperplasia.
  3. Autoimmune thrombocytopenia and neutropenia can also occur (although less frequent) due to antibodies to platelets and neutrophils.
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23
Q

Why is the patient more susceptable to infection in later stages of CLL?

A

Plasma immunoglobulins are decreased. (also neutropenia- me).

24
Q

When is a bone marrow and biopsy required in CLL diagnosis?

A

Not usually required except in aleukemic or subleukemic cases with no nodal or splenic involvement.

25
Q

What tests are required for a diagnosis of CLL?

A

CBC, immunophenotyping and clinical presentation is sufficient for a diagnosis.

Note: although do not need a bone marrow sample, >30% or more lymphocytes in marrow with persistent peripheral blood lymphocytosis is diagnostic of CLL.

26
Q

How are the assessment of chromosomal abnormalities used by the Dr. in CLL?

A
  1. Chromosomal abnormalities reviews can help assess severity and prognosis of CLL.
  2. Present in >50% of cases of CLL and indicative of worse prognosis.
  3. Most frequent is Trisomy 12, a marker for general lymphocyte proliferation. Predictive of progressive disease and need for treatment.
27
Q

How is immunophenotyping used in diagnosis of CLL?

A

Important diagnostic tool for classification of CLL. Looks at the antigen CD markers with flow cytometry.

CLL very complex in terms of analyzing antigens on cells.

28
Q

What are the three modes of therapy for CLL?

A
  1. Chemotherapy (reduce tumor burden and number of abnormal lymphocytes in peripheral blood)
  2. Radiation (to treat enlarged lymph nodes and splenomegaly resistant to treatment)
  3. Leukopheresis (to reduce large numbers of circulating lymphocytes where blood viscosity is a problem).
29
Q

What is the clinical presentation of Prolymphocytic Leukemia (PLL)?

A
  1. Extreme leukocytosis (>100)
  2. Marked splenomegaly (and to lesser extent liver enlargement)
  3. Immunological deficiencies frequently found.
  4. Generally Males in 60s
  5. Acute symptoms with fatigue, weakness, weight loss, sweats, and fever.
30
Q

How does the prognosis of PLL compare to CLL and HCL?

A

Prognosis considerably poorer than CLL and HCL.
More aggressive disease than CLL.

31
Q

What are the lab findings for PLL?

A
  1. WBC count high 25 to 1000 x 10^9/L.
  2. > 55% Prolymphocytes in PB.
  3. Prolymphs described as relatively large, mononuclear, oval to round nucleus with usually one and occ’l two distinctive nucleoli.
  4. Absolute neutrophil count usually low or high.
  5. Absolute monocytosis may also be present.
  6. Nucleated RBC’s and immature granulocytes may be present (leukoerythroblastic picture).
32
Q

What is the distinctive morphology of lymphocytes in the blood and bone marrow that distinguishes PLL from other lymphoid diseases?

A

The lymphocytes in PLL are a larger cell with light blue cytoplasm but the key feature is the distinctive nucleoli - often present in some cells, single, prominent and often more centrally located.

33
Q

What are the lab findings in the bone marrow for PLL?

A
  1. BM demonstrates almost total replacement by prolymphocyte infiltration.
  2. Most cases are B-Cell but T-Cell has been identified.
    Note: Immunophenotyping and chromosome studies are important to differentiate.
34
Q

What is the goal in PLL treatment?

A

Goal to reduce lymphocyte mass in blood, bone marrow and tissues.

PLL generally poor response to chemo drugs with occ’l success to combination of chemo agents.

35
Q

What are two key identifying features of Hairy Cell Leukemia (HCL)?

A

Two Key Features are:
1. Large spleen
2. Circulating mononuclear cells with cytoplasmic projections.

Note: Morphology can vary from case to case as cells may be smaller but will have the same “hairy” projections although they may be less obvious.

36
Q

What does the clinical presentation of HCL look like?

A
  1. Growth and accumulation of hairy cells in marrow, blood, and spleen leads to cytopenias and splenomegaly causing anemia, bleeding and infection.
  2. Males affect 5x’s more than females, median age is 55 yrs.
  3. Weakness, fatigue, and abdominal discomfort.
  4. Splenomegaly most consistent finding (enormous) 90% of cases.
  5. Lymphadenopathy and hepatomegaly less common.
37
Q

What is the most pronounced clinical feature in HCL?

A

Splenomegaly is very pronounced (enormous) similar to Myelofibrosis in the Chronic Myeloproliferative Disorders.

38
Q

What are the lab findings on hairy cells in HCL, in terms of % and morphological description?

A
  1. Hairy cells in peripheral blood in more than 90% of cases.
  2. Hairy cells account for less than 50% of WBC differential (usually).
  3. Hairy cells possess abundant, agranular, light grayish-blue cytoplasm with irregular hair like projections.
  4. Nucleus usually round to oval, sometimes folded or bilobed.
  5. Chromatin, loose and lacy. Nucleoli in some cases.
39
Q

Besides the observations of hairy cells, what are the other lab findings with HCL?

A
  1. Pancytopenia (most consistent lab obs.)
  2. Granulocytopenia and monocytopenia also present.
  3. Increased reticulin fibers are noted in marrow biopsy in almost all patients.
40
Q

What is an issue that can occur when taking a bone marrow sample for HCL?

A

The bone marrow is often “dry tap” because of marrow fibrosis. If successful shows lymphoid cells with relatively abundant cytoplasm.

41
Q

Why does cytopenia result in HCL?

A

Infiltration of marrow by malignant hairy cells and fibrous tissue and also by pooling of blood cells in enlarged spleen.

42
Q

What cytochemical stain is positive for Hairy Cells but negative in almost all other lymphoid cells?

A

Tartrate resistant acid phosphotase (TRAP).

Very helpful for differentiation.

43
Q

Are analyzing chromosomal abnormalities helpful in diagnosing HCL?

A

No, although they have been described but not consistent anomalies identified.

44
Q

Is immunophenotyping helpful with HCL?

A

Yes, helpful with most common surface markers.

45
Q

What are the treatments for HCL?

A
  1. Asymptomatic - no treatment
  2. Symptomatic -
    a) May require splenectomy (partially improves cell counts because cells no longer pooled in enlarged spleen).
    b) Chemo drugs not very effective & may worsen cytopenia because of their toxicity.
    c) Patients not responding to splenectomy especially problematic.
    d) New drugs (i.e. cladribine) show promise to induce partial or complete remission.
46
Q

What is Sezary Syndrome?

A

Sezary Syndrome is a T cell cutaneous lymphoma produced in the lymphatic tissue, migrates to the skin, which is early site of involvement.

47
Q

What is the skin presentation of Sezary Syndrome called and how does it present?

A

Early lesions are itchy, then reddened plague forms around face and body folds which can progress to larger areas of the body and tumor nodules.

Lesions on the skin are infiltrated with malignant T-cells (as determined by biopsy) - at this stage disease is known as mycosis fungoides.

48
Q

What body parts are affected by Sezary Syndrome?

A
  1. Extensive skin involvement w/ progression to lymphadenopathy, splenomegaly, and a leukemic blood picture.
  2. Bone marrow and peripheral blood.
49
Q

When is the disease known as Sezary Syndrome?

A

When sezary cells are seen in the peripheral blood.

50
Q

Describe sezary cell morphology?

A
  1. Lymphoid cell nuclei are folded, convoluted often with a cerebriform nuclei (brainlike).
  2. Chromatin is hyperchromatic (very dense), cytoplasm scant, may be slightly larger to twice the size of normal lymphocyte.
51
Q

What are the two types of sezary cells?

A

Sezary cells come in two separate morphologies.
1. Lutzner cell - similar in size to lymphocyte, grooved nuclear pattern, scant cytoplasm.
2. Larger type - similar in size to neutrophils and monocytes. Nucleus oval, round or reniform with grooved nuclear pattern , dense chromatin, lower N/C ratio.

52
Q

What problem can their be in identifying sezary cells?

A

The large type can really look like monocytes. Need to look at the pattern in the nucleus.

53
Q

How is early detection of Sezary Syndrome important to prognosis?

A
  1. Survival with early stage mycosis fungoides is excellent as pression is very slow w/ 10 yr survival rate at 97-98%.
  2. Later stage is an aggressive lymphoma with low (10-20%) 5 year survival rate.
54
Q

What is the typical patient with Sezary Syndrome?

A

Male, average age 55-60 years.

55
Q

How is death caused in Sezary Syndrome?

A

Death related to invasion by abnormal cells lymph nodes, organs such as liver & spleen and bone marrow.

Hematology 2 (25 decks)

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