Pathology of WBC, LN, Spleen, and Thymus Flashcards
When does an ANC become serious?
below 500
What can cause severe neutropenia
- Drug toxicity
- Aplastic anemia
- Megaloblastic anemia
- Immune destruction
- Hypersplenism
What happens as a result of severe neutropenia?
- Overwhelming bacterial and fungal infections
What causes leukocytosis?
- Increased marrow priduction
- Increased release from marrow
- Decreased margination
- Decreased extravasation into tissues
What is acute suppurative lymphadenitis?
painful “fluctuant” LAD
suppurative material due to infections with pyogenic organisms
Neutrophils are in the upper half of the image
List the 7 types of B cell non hodgkin leukemia/lymphoma
- Chronic lymphocytic leukemia/Small lymphocytic lymphoma
- Follicular lymphoma
- Diffuse large B cell lymphoma
- Burkitt lymphoma
- Mantle cell lymphoma
- Marginal zone lymphoma
- Hairy cell leukemia
What falls under category of lymphoid neoplasia?
- B cell and T cell
- Plasma cell
- Hodgkin
- NK cell
what falls under myeloid neoplasia?
- AML
- Myelodysplasia
- Myeloproliferative neoplasia
Differentiate leukemia vs lymphoma?
Leukemia is in the blood or bone marrow and lymphoma is in lymph nodes
Most common cancer of kids? How does it present?
- Acute Lymphoblastic Leukemia/Lymphoma
- Sudden onset of:
- Fatigue
- Fever
- Bleeding bruising
- Pain
- Headache
- N/V
What is ALL?
- Occurs when there are mutations to lymphoid stem cells resutling in a “leukemic stem cell”
- this means it can self renew and it also causes arrest of maturation resulting in blasts
How could a bone marrow aspirate of a patient with ALL look?
- It may not aspirate at all if the bone marrow is densely packed with the leukemic cells, it is too “sludge-y”
what cancer is this and how do you know?
- ALL
- Cells are large with dark nuclear chromatin and scant agranular cytoplasm
In patients with ALL what will flow cytometry markers be?
- TdT (seen in prolymphocytess)
- B cell markers:
- CD19, CD20, CD10, and Pax-5
- T cell markers:
- CD1-CD5, CD7, CD8
With ALL what factors play into a good prognosis vs bad?
Good:
- 2-10 yo
- Low peripheral WBC count
- Hyperdiploidy
- t(12:21)
Bad:
- Age <2 or adolescent/adult
- High WBC count greater than 100K
What is this?
CLL/SLL
- Peripheral smear demonstrates lymphocytosis with small matrue lymphocytes and smudge cells
- Non Hodgkins B cell
When staining for CLL/SLL what can indicate that it is CLL?
Using a CD5 stain
What is richter transformation?
- Transformation from CLL/SLL to an aggressive tumor
- Mutations usually involve P53 or MYC
Describe the translocation seen in follicular lymphoma?
- t(14:18)
- This moves the IgH gene next to BCL-2 and anti-apoptotic factor
Left: follicular hyperpasia
Righ: Follicular lymphoma
Diffuse large B cell lymphoma?
- Large tumors in the LN or the spleen, this is an aggressive fast growing cancer
- Two special types:
- Immunodeficiency relatetd LCL linked to EBV activation
- Primary effusion lymphoma linked to HHV-8
In DLBCL, what is the frequent somatic mutation seen?
BCL-6
Burkitt lymphoma a B cell non Hodgkin lymphoma
“starry sky”
In burkitt lymphoma, what are the “stars”?
Tingible body macrophages
Describe the translocation in Burkitts lymphoma?
- Extremely fast growing tumors
- t(8:14), moves IgH next to MYC
3 major types of Burkitt lymphoma?
- Endemimc african burkitt lymphoma, EBV universal and mandibular growth occurs
- Sporadic
- HIV related
They respond well to treatment especially younger patients
What is this
Mantle cell lymphoma
- Small mature appearing cells, very aggressive tumor
Describe mantle cell lymphoma
- B cell malignancy resembling the mantle cell layer
- Small mature looking cells, but very aggressive
- t(11:14) moves IgH next to cyclinD1
Describe Marginal Zone Lymphoma
- Can occur in LN or at extranodal sites
- Picture was of a MALT-oma, this is an extranodal example
- They are assoc. with chronic inflammation caused by H pylori
- Hashimoto thyroiditiws can result in MZL of thyroid
- Chronic sialadenitis can be assoc with MZL of salivary glands
Describe Hairy Cell lymphoma
- Non Hodgkins B cell
- Neoplastic B cells have hair like projections on them to keep distance betwen cells
- Bone marrow is packed with cells
- Induction of reticulin fibrosis leads to dry tap
- MASSIVE splenomegaly
- CD25 and CD11c
How does Myeloma presesnt?
- Lytic bone lesions, spontaneous fractures
- Hypercalcemia
- Renal failure
- Immune abnormalities
Describe what is seen.
- Plasma cells left
- Plasmablasts below left
- Mott cells below
- Dutcher nbodies bottom right
What are the CRAB criteria for multiple myeloma?
- C: hypercalcemia due to osteolysis, may present as altered mental status, Short QT, siezures, N/V, constipation
- R: renal insufficiency due to immunoglobins that are being filtered and combining with renal glycoproteins forming casts called Bence Jones proteins, proteinuria, systemic amyloidosis AL
- A: anemia as result of marrow infiltration of myeloma, IL-6 and other suppressive cytokinds, renal disease, MOST COMMON OF ALL CRAB
- B: bone lesions
What is seen?
multiple myeloma
Lymphoplasmacytic lymphoma?
- B cell clonal neoplasm of small mature B cells with plasmacytic differentiation
- Waldenstrom’s macroglobulinemia
- Monoclonal gammopathy
- Hyperviscosity
What is seen
Classic HL wit hreed sternberg cells, which are positive for CD15, CD30 and Pax-5
Describe Nodular LP hodgkin lymphoma
- Lymphohistiocytic variants (LH) cells aka popcorn cells are present
- Positive for CD20 and negative for CD15 and CD30
- Can transform into DLBCL
What is used to diagnose ALL, B cell NHL, Myeloma, and HL?
- ALL: morphology, staining, flow cytometry
- B cell NHL: Morphology staining flow cytometry
- Myeloma: Morphology staining, SPEP/Immuno fix
- HL: Morphology and staining
anaplastic large cell lymphoma (ALCL)
- May be ALK +, seen in younger patients and has better prognosis
- ALK -, seen in older with worse prognosis
Adult T cell leukemia/lymphoma?
- Assoc. with HTLV-1 infection
- Leukemia has poor prognosis and you can see a cloverleaf cell
- Skin involvement is common and you can see exfoliation to necrotizing nodules
Describe Myucosis fungoides and Sezary syndrome.
- MF: t cell lymphoma that presents with cutanoeous lesions, starting as a plaque and progressing to tumors
- SS: T cell lymphoma presenting with erythroderma and leukemia
- “Red Man”
- NOT assoc. with HTLV-1
What is seen
AMLm you can see the blasts and there are granules so that tells you they are of myeloid descent
How does AML present?
- Fever fatigue bleeding bruising
- May have blasts in the peripheral smear and >20% blasts in the marrow
- May also be an Aleukemic Leukemia, nothing in peripheral blood
Describe AML with t(8:21)
- AML with neutrophilic maturation, seen in younger patients and has a good prognosis and response to tx
- RUNX-1 and RUNX1T1 fusion disrupts the core binding factor mediated hematopoetic differentiation and maturation
Describe AML with t(15:17), what are these patients at risk for, how is it treated?
- Referred to Acute Promyelocytic Leukemia (APL)
- Auer rods are seen in the smear
- RARa/PML translocation, this blocks RA from binding RAR and this stalls differentiation resultig in leukemic blasts
-
RISK FOR DIC
- these cells express tissue factor which activates facctor X triggering clotting
- Can treat with all transRA
What is myelodysplastic syndrome?
- Clonal DO with morphologic manifestations that go through many cell lineages
- This is a precursos to AML
- transformation to AML is more likely if MDS is due to priro cytotoxic therapy/radiation
How does myelodysplastic syndrome manifest?
- Cytopenias present, tap BM to see
- Classification is based on:
- Dysmorphic features of 1+ lineages
- Chromosomal analysis
- If the blast count is increased but not yet criteria for AML
what is this
CML
Proliferation of mature myeloid cells
Describe CML.
- Philadelphia chromosome, the BCR-ABL tyrosine kinase, this can be treated with a tyrosine kinase inhibitor
- You see marked leukocytosis with WBC > than 100K, splenomegaly and extramedullary hematopoiesis
What is Langerhans cell histiocytosis?
- Clonal proliferations of immature dendritic cells
- Grooved nuclei of langherhans cells are seen as well as tennis racket shaped Birbek granules in electron microspy
What causes congestive splenomegaly?
Liver dysfunction
Differentiate hyperslenism and splenomegaly.
Hyeprsplenism has cytopenias with it and splenomegaly does not
