36 - Pathology of WBCs I Flashcards
What are the three types of WBC disorders?
Leukopenia
- Neutropenia
- Agranulocytosis
Reactive proliferations of WBCs
- Leukocytosis
- Lymphadenitis
Neoplastic proliferation of WBCs
- Lymphoid neoplasm ***
- Myeloid neoplasm (leukemia)
- Langerhans cell histocytosis
What is the focus of these lectures?
Lymphoid neoplasm
This is LYMPHOMA + LEUKEMIA ***
Define lymphoma
Lymphoid neoplasms arising as discrete masses
THERE IS A MASS
Define leukemia
Lymphoid or myeloid neoplasms with involvement of blood and bone marrow
THERE IS NO MASS
Why is this only a general rule?
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
When lymphoma is suspected, what are the different tools for diagnosis?
- Hematoxylin and eosin staining (H&E)
- Immunophenotyping***
- Cytogenetics/FISH (to identify chromosomal aberration)
- Molecular diagnostics (PCR to detect monoclonal population and neoplastic lymphoid population)
Describe immunophenotyping
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
What are the important things to look at in the clinical presentation of a lymphoma patient?
- Age
- Location
- Multiple or single sites of involvement (one lymph node or many)
What is the clinical presentation of a lymphoma patient?
- PAINLESS, non-tender lymphadenopathy (big lymph nodes***)
- Fatigue
- Malaise
- Night sweats
- Fever***
- Weight loss
What is the first step in diagnosis?
Get a biopsy if you are suspecting lymphoma
Start with an H&E stain
What are you looking for on the LOW POWER H&E stain?
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?
What are you looking for on the HIGH POWER H&E stain?
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)
How do you determine if a lymphoid neoplasm consists of mature or immature neoplasms?
Look at the morphology and immunophenotype
Immature lymphoid cell = lymphoblasts
Mature lymphoid cell = mature (peripheral) lymphoma
Describe the general trend in immunopheonotypes
B cell marker
- CD20
T cell marker
- CD3
What are the B cell markers that you need to know?
- CD19
- CD20
- Lamda light chain positive
What is the purpose of cytogenetic/molecular analysis
- 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
Why do the classifications of tumors change a lot?
- It is very complex and complicated
- WHO put out a classification of tumors of hematopoietic and lymphoid tissues in 2001, edited in 2008
How does the WHO classify lymphomas?
Identify specific entities using a multiparametric approach
- Clinical features
- Morphology
- Immunophenotype
- Cytogenetics
- Molecular analysis
What are all the different types of lymphoma covered in these two lectures?
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
Why is lymphoma relevant to study?
- Lymphoma is the most common tumor type found in 10-14 year olds and 15-19 year olds
How do we determine the staging of lymphoma?
** NEED TO KNOW ***
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
If you see an A or B next to the stage. what does it mean?
Whether or not it is symptomatic
A = Asymptomatic B = Fever, night sweats or >10% weight loss
Describe the occurrence of B cell lymphomas
- Comprise over 90% of lymphoid neoplasms worldwide.
- This is why this is important
- Incidence rate per 100,000 is 26.13 and is increasing.
What types of B cell lymphoma originate from the germinal center of the lymph node?
- Follicular lymphoma
- Burkitt lymphoma
What types of B cell lymphoma originate from the mantle zone of the lymph node?
Mantle cell lymphoma
Describe follicular lymphoma
- 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
What cells does follicular lymphoma affect?
Follicular lymphomas are composed of follicle germinal center cells
- Centroblasts
- Centrocytes
What cell involvement differences will we see in low grade follicular lymphoma vs high grade follicular lymphoma?
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
What are the immunophenotype markers that will be present in follicular lymphoma? Which will be negative?
NEED TO KNOW
Positive: CD19, CD20, CD10, Bcl-2
Negative: CD5, CD3
What is Bcl-2?
An anti-apoptotic protein
It prevents the tumor cells from undergoing cell suicide
Describe a case study of a follicular lymphoma
- 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
Describe the typical presentation of Mantle cell lymphoma
- 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)
What do we call Mantle cell lymphoma when there is small bowel involvement?
Lymphomatoid polyposis
What immunophenotype markers will we see in Mantle cell lymphoma? Which will be negative?
KNOW THIS
Positive
- CD19. CD20
- CD5
- Cyclin D1
Negative
- CD23
- CD3
Give a case study of a patient with Mantle cell lymphoma
- 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
What are the three different types of Burkitt lymphoma?
1 - Endemic Burkitt Lymphoma (African)
2 - Sporadic Burkitt Lymphoma (non-African, non-endemic)
3 - Immunodeficiency Burkitt Lymphoma (HIV/AIDS)
Describe endemic Burkitt Lymphoma
- 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)
Describe sporadic Burkitt Lymphoma
- 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
Describe immunodeficiency Burkitt Lymphoma
- Seen in HIV infected patients
- Often times the initial manifestation of AIDS
What are ALL Burkitt Lymphoma patients at risk for?
CNS involvement
What is the clinical presentation of endemic BL?
50%: Jaws, facial bones
Involvement of ovaries, kidneys and breast: frequent
What is the clinical presentation of sporadic BL?
Majority: Abdominal masses, ileo-cecal region.
Involvement of ovaries, kidneys and breast: frequent
Rarely Jaw – very rare
What is the clinical presentation of immunodeficiency BL?
Nodal localization and involvement of BM is frequent
Describe the morphology of Burkitt Lymphoma
Diffuse monomorphic infiltrates ***
Tingible body macrophages are present (starry-sky pattern) ***
Describe the diffuse monomorphic infiltrates of BL
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
Describe the tingible body macrophages in BL
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
What are the immunophenotypes that will be present in Burkitt Lymphoma? Which will be negative?
KNOW THIS
Positive
- CD10
- CD19
- CD20
Negative
- Bcl-2
Describe the prognosis of Burkitt Lymphoma
Prognosis:
- Aggressive disease – Medical emergency!
- Responds very well to therapy.
- 90% cure – low stage
- 70% cure - high stage
