36 - Pathology of WBCs I Flashcards

1
Q

What are the three types of WBC disorders?

A

Leukopenia

  • Neutropenia
  • Agranulocytosis

Reactive proliferations of WBCs

  • Leukocytosis
  • Lymphadenitis

Neoplastic proliferation of WBCs

  • Lymphoid neoplasm ***
  • Myeloid neoplasm (leukemia)
  • Langerhans cell histocytosis
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2
Q

What is the focus of these lectures?

A

Lymphoid neoplasm

This is LYMPHOMA + LEUKEMIA ***

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3
Q

Define lymphoma

A

Lymphoid neoplasms arising as discrete masses

THERE IS A MASS

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4
Q

Define leukemia

A

Lymphoid or myeloid neoplasms with involvement of blood and bone marrow

THERE IS NO MASS

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5
Q

Why is this only a general rule?

A

Lymphoma can progress to a late stage where there is involvement of the blood and bone marrow, so then lymphoma would include leukemia

Leukemia is a blood and bone marrow cancer, but lymphoid can also be involved in later stages

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6
Q

When lymphoma is suspected, what are the different tools for diagnosis?

A
  • Hematoxylin and eosin staining (H&E)
  • Immunophenotyping***
  • Cytogenetics/FISH (to identify chromosomal aberration)
  • Molecular diagnostics (PCR to detect monoclonal population and neoplastic lymphoid population)
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7
Q

Describe immunophenotyping

A

This is the main method for diagnosis

  • Consists of identifying the cell type
  • This is done by looking at protein expression
  • Done by immunohistochemistry and flow cytometry
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8
Q

What are the important things to look at in the clinical presentation of a lymphoma patient?

A
  • Age
  • Location
  • Multiple or single sites of involvement (one lymph node or many)
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9
Q

What is the clinical presentation of a lymphoma patient?

A
  • PAINLESS, non-tender lymphadenopathy (big lymph nodes***)
  • Fatigue
  • Malaise
  • Night sweats
  • Fever***
  • Weight loss
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10
Q

What is the first step in diagnosis?

A

Get a biopsy if you are suspecting lymphoma

Start with an H&E stain

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11
Q

What are you looking for on the LOW POWER H&E stain?

A

Low power evaluation
- Is the lymph node architecture preserved?
Or is it effaced? (loss of B and T cell area)
- If it is effaced, what is the pattern of the atypical proliferation? Nodular, diffuse, both?

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12
Q

What are you looking for on the HIGH POWER H&E stain?

A

Do all the cells look similar?
MONOMORPHIC ***

Are there multiple cell types?
POLYMORPHIC***

KNOW THIS TERMINOLOGY

Also look at: (just know the stuff above, this is extra)

  • Size (small, medium, large)
  • Nucleus (irregular, regular, round)
  • Chromatin (clumped, vesicular, open)
  • Cytoplasm (abundant/scant, color)
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13
Q

How do you determine if a lymphoid neoplasm consists of mature or immature neoplasms?

A

Look at the morphology and immunophenotype

Immature lymphoid cell = lymphoblasts

Mature lymphoid cell = mature (peripheral) lymphoma

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14
Q

Describe the general trend in immunopheonotypes

A

B cell marker
- CD20

T cell marker
- CD3

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15
Q

What are the B cell markers that you need to know?

A
  • CD19
  • CD20
  • Lamda light chain positive
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16
Q

What is the purpose of cytogenetic/molecular analysis

A
  • You can determine whether or not a population is monoclonal
  • It can extrapolate patients into prognostic categories
  • Allows you to determine therapeutic targets

This is not highly tested, focus on immunophenotypes

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17
Q

Why do the classifications of tumors change a lot?

A
  • It is very complex and complicated

- WHO put out a classification of tumors of hematopoietic and lymphoid tissues in 2001, edited in 2008

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18
Q

How does the WHO classify lymphomas?

A

Identify specific entities using a multiparametric approach

  • Clinical features
  • Morphology
  • Immunophenotype
  • Cytogenetics
  • Molecular analysis
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19
Q

What are all the different types of lymphoma covered in these two lectures?

A

Mature (peripheral) lymphoid neoplasms

  • B cell lymphomas (follicular, Mantle cell, Burkitt’s)
  • T cell lymphomas (adult T-cell leukemia/lymphoma, mycosis fungoides/Sezary syndrome)

Immature (precursor) T cell neoplasms

  • T lymphoblastic leukemia/lymphoma
  • Anaplastic large T cell lymphoma
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20
Q

Why is lymphoma relevant to study?

A
  • Lymphoma is the most common tumor type found in 10-14 year olds and 15-19 year olds
21
Q

How do we determine the staging of lymphoma?

** NEED TO KNOW ***

A

Stage I
- Single lymph node region or extralymphatic site

Stage II
- Two or more lymph node regions or extralymphatic sites on the SAME side of the diaphragm

Stage III
- Lymph node regions or extralymphatic sites are found on BOTH sides of the diphragm

Stage IV
- Disseminated or diffuse involvement of one or more extralymphatic sites

22
Q

If you see an A or B next to the stage. what does it mean?

A

Whether or not it is symptomatic

A = Asymptomatic
B = Fever, night sweats or >10% weight loss
23
Q

Describe the occurrence of B cell lymphomas

A
  • Comprise over 90% of lymphoid neoplasms worldwide.
  • This is why this is important
  • Incidence rate per 100,000 is 26.13 and is increasing.
24
Q

What types of B cell lymphoma originate from the germinal center of the lymph node?

A
  • Follicular lymphoma

- Burkitt lymphoma

25
Q

What types of B cell lymphoma originate from the mantle zone of the lymph node?

A

Mantle cell lymphoma

26
Q

Describe follicular lymphoma

A
  • A B cell lymphoma
  • Common in middle age patients
  • You will find a widespread disease at diagnosis
  • This includes both peripheral and central lymphadenopathy
  • Splenomegaly
  • 40-70% will have progressed to having bone marrow involvement
  • 10% will have progressed to having peripheral blood involvement
27
Q

What cells does follicular lymphoma affect?

A

Follicular lymphomas are composed of follicle germinal center cells

  • Centroblasts
  • Centrocytes
28
Q

What cell involvement differences will we see in low grade follicular lymphoma vs high grade follicular lymphoma?

A

Low grade

  • Mostly centrocytes
  • This is a good sign
  • Centrocytes are small dark cells with condensed chromatin

High grade

  • More than 15 centroblasts
  • This is a bad sign
  • Centroblasts are immature cells
29
Q

What are the immunophenotype markers that will be present in follicular lymphoma? Which will be negative?

A

NEED TO KNOW

Positive: CD19, CD20, CD10, Bcl-2

Negative: CD5, CD3

30
Q

What is Bcl-2?

A

An anti-apoptotic protein

It prevents the tumor cells from undergoing cell suicide

31
Q

Describe a case study of a follicular lymphoma

A
  • 43yo female presents with palpable lymph nodes.
  • Abdominal CT scan shows retroperitoneal mass and extensive lymphadenopathy and splenomegaly
  • CBC is unremarkable
  • Laparoscopic removal of an enlarged lymph node was performed
32
Q

Describe the typical presentation of Mantle cell lymphoma

A
  • Presents in the 5th to 6th decade ***
  • MALE predominance ***
  • Presents with generalized lymphadenopathy, bone marrow involvement and liver involvement
  • Lymphocytosis (high lymphocyte count) is seen in 30% of patients
  • Splenomegaly is seen in 50% of patinets (liver also commonly affected)
33
Q

What do we call Mantle cell lymphoma when there is small bowel involvement?

A

Lymphomatoid polyposis

34
Q

What immunophenotype markers will we see in Mantle cell lymphoma? Which will be negative?

A

KNOW THIS

Positive

  • CD19. CD20
  • CD5
  • Cyclin D1

Negative

  • CD23
  • CD3
35
Q

Give a case study of a patient with Mantle cell lymphoma

A
  • 56yo male presents with fever, night sweats, and unexplained weight loss. Palpable lymph nodes are identified in his axilla and groin.
  • Abdominal CT scan shows hepatosplenomegaly and generalized lymphadenopathy.
  • CBC shows low hemoglobin and hematocrit- anemic and elevated lymphocyte count.
  • Laparoscopic removal of an enlarged lymph node and bone marrow biopsy was performed
36
Q

What are the three different types of Burkitt lymphoma?

A

1 - Endemic Burkitt Lymphoma (African)
2 - Sporadic Burkitt Lymphoma (non-African, non-endemic)
3 - Immunodeficiency Burkitt Lymphoma (HIV/AIDS)

37
Q

Describe endemic Burkitt Lymphoma

A
  • Found in equitorial Africa
  • It is the most common childhood malignancy in Africa
  • Common in 4-7 year olds
  • Usually occurs with the Epstein Barr virus (EBV)
38
Q

Describe sporadic Burkitt Lymphoma

A
  • Seen throughout the world in children and young adults
  • Accounts for 30-50% of all childhood lymphomas
  • The median age of adult is 30 years old
39
Q

Describe immunodeficiency Burkitt Lymphoma

A
  • Seen in HIV infected patients

- Often times the initial manifestation of AIDS

40
Q

What are ALL Burkitt Lymphoma patients at risk for?

A

CNS involvement

41
Q

What is the clinical presentation of endemic BL?

A

50%: Jaws, facial bones

Involvement of ovaries, kidneys and breast: frequent

42
Q

What is the clinical presentation of sporadic BL?

A

Majority: Abdominal masses, ileo-cecal region.

Involvement of ovaries, kidneys and breast: frequent

Rarely Jaw – very rare

43
Q

What is the clinical presentation of immunodeficiency BL?

A

Nodal localization and involvement of BM is frequent

44
Q

Describe the morphology of Burkitt Lymphoma

A

Diffuse monomorphic infiltrates ***

Tingible body macrophages are present (starry-sky pattern) ***

45
Q

Describe the diffuse monomorphic infiltrates of BL

A

KNOW THIS EXACT WORDING
- Diffuse monomorphic infiltrate of intermediate sized round to slightly irregular lymphoid cells with multiple peripherally placed nucleoli

You will also see a high mitotic rate

46
Q

Describe the tingible body macrophages in BL

A

KNOW THIS EXACT WORDING

  • Tingible body macrophages present (“starry-sky pattern”)***
  • tingible=stainable
  • A tingible body macrophage is predominantly found in germinal centers, containing many phagocytized, apoptotic cells in various states of degradation, referred to as tingible bodies
47
Q

What are the immunophenotypes that will be present in Burkitt Lymphoma? Which will be negative?

A

KNOW THIS

Positive

  • CD10
  • CD19
  • CD20

Negative
- Bcl-2

48
Q

Describe the prognosis of Burkitt Lymphoma

A

Prognosis:

  • Aggressive disease – Medical emergency!
  • Responds very well to therapy.
  • 90% cure – low stage
  • 70% cure - high stage