WBC & LN Part, 3: Chronic Leukemias Flashcards
what are the chronic Leukemias?
Chronic Lymphocytic Leukemia (CLL)
Hairy Cell Leukemia
HTLV-1
Mycosis Fungoides / Sézary syndrome
what is the most common type of leukemia in the Western world?
What increases the risk of this leukemia progressively?
what sex is more susceptible to this leukemia?
this leukemia is characterized by what?
what is the pathogenesis of this leukemia?
CLL (chronic lymphocytic leukemia)
age (older than 60 yrs), more in males, and insidious onset
accumulation of B cells that don’t function
clonal B cells get arrested in the B-cell differentiation pathway, intermediate between pre-B cells and mature B cells
what can we expect in the lab report for CLL?
Hb?
White cell count?
peripheral blood smear?
bone marrow?
immunoglobin?
markers?
Hb = anemia in late stage disease
White cell count = very elevated
peripheral blood smear = lymphocytosis (smudge cells)
bone marrow = involved due to neoplastic B cells
immunoglobin = low level of surface Ig expressed
markers = CLL expressed pan B cell markers (CD19, CD 20)
- CD 5 and CD 23 will be positive
what is this? how do you know?
CLL, look at the smudge cells
what is this?
how do you know?
CLL
smudge cells
what is this?
how do you know?
Chronic Lymphocytic Leukemia: peripheral blood smear showing numerous small lymphocytes with condensed nuclei and scant cytoplasm.
‘smudge’ cells (red arrow). This is due to the cell fragility. These cells smudge while preparing the smear.
what are the clinical features of CLL?
- Asymptomatic (incidental)
- AIHA (autoimmune hemolytic anemia
- Hepatosplenomegaly
- Hypogammaglobulinemia (which predisposes to infections)
- Thrombocytopenia
- Generalized lymphadenopathy
CLL may transform to what?
What is Richter syndrome?
what is the its prognosis?
what causes it?
if there is transformation, what is the prognosis?
aggressive lymphoma
- rapidly enlarging mass within lymph node/spleen which is a “diffuse large B cell lymphoma”
- transformation is because of additional mutation
- transformation is associated with poor prognosis (survival less than a year following transformation)
what is Hairy Cell Leukemia?
how do you spot hairy cell leukemia in a microscope?
On who does it happen the most?
what is the pathogenesis?
- chronic lympho-proliferative disorder of B lymphocytes
- cells have prominent cytoplasmic hair-like projections
- Middle age, Male, age of 55 years
- mutation in BRAF causing overexpression of cyclin D1 (cell cycle regulator)
what can be expected in a lab report in hairy cell leukemia?
Hb
total WBC count
platelet count
peipheral blood smear
Bone Marrow
Hb = decreased (anemia)
total WBC = decreased
platelet count = decreased (pancytopenia)
peripheral blood smear = neutropenia, presence of hairy cells
bone marrow = (dry tap)
- leukemic cells have hair-like structure on surface of cytoplasm
- involved, where they are enmeshed in extra cellular matrix
what is this?
hairy cell leukemia (hairy cells)
what is this?
hairy cell leukemia
what is this?
what is it for?
TRAP (tartrate-resistant acid phosphatase) stain
hairy cell leukemia
what are the Clinical features & Treatment: Hairy cell leukemia?
What type of infection are patients with Hairy cell leukemia more prone to?
what is the survival rate?
what is the treatment for hairy cell leukemia?
- massive splenomegaly, consistent feature
- lymphadenopathy is rare
- pancytopenia from marrow involvement, and splenic sequestration
prone for infection: Mycobacterium avium intracellular
- this may be due to unexplained monocytopenia
indolent course, survival rate is high
- Cladribine (2-CDA), which inhibits adenosine deaminase (ADA) and increases the level of toxic deoxyadenosine
what is Adult T cell Leukemia / Lymphoma?
what is the latency for this disease?
what countries have the highest incidence of this disease?
how is it transmitted?
lympho-proliferative disorder seen in adults, associated with HTLV 1 infection
long latency
Japan, West Africa, Caribbean
blood, sexual, transplacental, breast milk (low risk)
What cell is affected in HTLV-1?
what is Adult T cell Leukemia’s pathogenesis?
What does TAX activate?
what does that do?
what will TAX inhibit?
- it selects (tropism) CD4+ T cells
- HTLV-1 has a region referred to as TAX (essential for viral replication) which can activate transcription of several host cell genes and at the same time inactivates cell cycle inhibitor (p16/INK4a) as well as activating cyclin D1
- TAX activates NF-kB (transcription factor that helps by making cell anti-apoptotic)
- Inhibits p53
what can be expected in a lab report of Adult T cell Leukemia / Lymphoma?
CBC?
Peripheral blood smear?
biochemical test?
skin biopsy?
serum?
radiology?
CBC = leukocytosis
Peripheral blood smear = lymphocytosis, abnormal lymphoid cells described as‘flower cells’
biochemical test = hypercalcemia
skin biopsy = T-cell markers positive (CD4)
serum = HTLV-1
radiology = lytic bone lesions
what is this?
how do you know?
adult T-cell leukemia/lypmhoma
because of ‘flower cells’ seen
what are the clinical features of adult T-cell leukemia/lymphoma (HTLV-1)?
- lymphadenopathy
- hepato-splenomegaly
- skin lesions
- hypercalcemia
- lytic bone lesions
what is this?
adult HTLV-1
Note: Nodular skin tumors
what is Mycosis Fungoides / Sézary syndrome?
Mycosis Fungoides and Sézary syndrome are different manifestations of tumor arising from CD4+ T helper cells
* they are a common type of cutaneous T-cell lymphoma
what are the clinical features of Mycosis Fungoides / Sézary syndrome?
What will a immunophenotype reveal about Mycosis Fungoides / Sézary syndrome?
- Mycosis fungoides progresses from patch to plaque to tumor phase
- but patients may simultaneously have more than one type of lesion
- indolent disease
mature T cell markers: CD2, CD3, CD4, on skin biopsies
what is this?
what disease?
patches
Mycosis Fungoides
what disease?
what is this?
Mycosis Fungoides
patches and plaque
what disease?
what is this?
Mycosis Fungoides
tumors
what disease is this?
what is this?
Mycosis fungoides
Leonine Facies
what will histology reveal in Mycosis Fungoides / Sézary syndrome?
where may it spread?
histology shows infiltration of epidermis and dermis by neoplastic T cells, typically a “band-like and patchy infiltrate” in upper dermis of atypical lymphocytes
may spread to lymph nodes
what disease is this?
what should be noted?
Mycosis Fungoides / Sézary syndrome
Note: ‘band-like’ infiltrate along dermo-epidermal junction
what is this?
what should be noted?
Mycosis Fungoides
Note: disruption of the epidermal-dermal junnction. Abnormal lymphocytes are seen within the epidermis, and on surface.
what disease is this?
what should be noted about this?
mycosis fungoides
Pautrier abscesses (collections of neoplastic lymphocytes) arrow
what is Sézary syndrome characterized by?
how are sézary cells characterized?
- is characterized by tumor dissemination to other organs and spill over into peripheral blood (Mycosis fungoides with a leukemic phase)
- “Sézary cells” are characterized by cerebriform nuclei
what are these?
Sézary cells
what are Sézary cells?
They are medium to large lymphocytes with characteristic cerebriform nuclei and scant cytoplasm.
