Disorders of WBCs II Flashcards
What can lead to a neutropenia? What can be used to boost this cell count?
Drug toxicity (i.e. chemotherapy)
Severe Infection (most neutrophils are out of blood and into infected tissue)
–> Would be treated with GM-CSF or G-CSF
What can lead to a lymphopenia?
Immunodeficiency
High cortisol state (initiates apoptosis in lymphocytes)
Autoimmune destruction
Whole body radiation
What can lead to neutrophilic leukocytosis?
(high neutrophil count)
Bacterial infection
Tissue necrosis
High cortisol state
(band cells released into peripheral blood will have decreased CD16/Fc receptor)
What can lead to monocytosis?
(increased monocytes)
Chronic inflammatory states
Malignancy
What can lead to eosinophilia?
Allergic reactions
Parasitic infection
Hodgkin lymphoma
What can lead to basophilia?
Chronic Myelogenous Leukemia
What can lead to lymphocytic leukocytosis?
Viral infections
Bordetella pertusis
What is infectious Mononucleosis?
EBV infection results in lymphocytic leukocytosis compromised of reactive CD8+ Tcells
- CMV is a less common cause -
What are symptoms of infectious mononucleosis?
- Generalized lymphadenopathy
(hyperplasia of the paracortex - where CD8+ Tcells are)
- Splenomegaly (hyperplasia of periarterial lymphatic sheath - PALS)
- High white count with atypical lymphocytes
- *Complications:**
- Increased risk of splenic rupture (no contact sports for 1yr)
- Rash if exposed to penicillin
- Dormancy of virus in B cells (increases risk for recurrence or lymphoma)
What are characteristics of acute leukemia?
>20% blasts in bone marrow
Blasts also endter peripheral blood and result in increased WBC count
–> Blasts “crowd-out” normal hematopoieisis resulting in acute presentation of:
Anemia
Thrombocytopenia
Neutropenia
What differentiates an Acute Myeoloblastic Leukemia from an Acute Lymphoblastic Leukemia?
Increased blast count is due to either MPO+ Myeloblasts with (AML) or Tdt+ Lymphoblasts (ALL)
MPO = myeloperoxidase –> can be visualized as Auer Rods
What are the subclassifications of ALL?
T - ALL (Tdt+(CD2 to CD8)+)
or
B - ALL (Tdt+CD10+CD19+CD20+)
- better prognosis
- requires prophylaxis to scrotum and CSF
What translocations determine a good or poor prognosis for B - ALL?
t(12;21) has a good prognosis - more commonly seen in kids
t(9;22) has a poor prognosis - classic translocation of CML but can be seen in B-ALL; more commonly seen in adults
What is a distinct feature of T-ALL?
Mediastinal (thymic) mass (generally in a teenager)
Also known as: Acute Lymphobalstic Lymphoma; due to the mediastinal mass involvement
What is the characteristic translocation of AML?
t(15;17)
–> Leads to Retinoic Acid Receptor destruction
therefore, promyelocytes accumulate because they cannot mature
- Promyelocytes contain numerous Auer rods (risk for DIC)
ATRA (all trans retinoic acid) will cause blasts to mature into neutrophils, thus diminishing risk of DIC
What is acute monocytic leukemia?
Accumulation of monoblasts
- promyelocytes have developed to monoblasts; so they no longer have MPO/Auer Rods
–> Blasts characteristically infiltrate gums
What is acute megakaryoblastic leukemia?
Proliferation of megakaryoblasts (lack myeloperoxidase)
–> associated with Down Syndrome (beforer age of 5 – ALL is associated with DS after age of 5)
What patients have an increased risk of AML? What syndrome do tehy develop?
Patients exposed to a chelating agent or radiation therapy
- *–> develop a myelodysplastic syndrome**:
- Cytopenias with hypercellular bone marrow
- Abnormal maturation with increased blasts (<20%)
- Most patients die from infection or bleeding
- May progess to acute leukemia (>20%)
What is Chronic lymphocytic leukemia?
Neoplastic proliferation of naive CD5+CD20+ Bcells
Increased lymphocytes and smudge cells seen in blood smear
–> Can cause generalized lymphadenopath (then called small lymphocytic lymphoma)
What are complications of Chronic lymphocytic leukemia?
Hypogammaglobulinemia (lymphocytes are naive Bcells and won’t become plasma cells and secrete Ig)
Autoimmune hemolytic anemia (if cells do secrete Ig, they are autoimmune hemolytic Ig)
Transformation into diffuse Large Bcell Lymphoma
What is hairy cell leukemia?
Neoplastic proliferation of mature B cells
- Characterized by hairy cytoplasmic processes on cells-
- Cells are positive for TRAP (tartrate-resistant acid phosphatase)
What are clinical features of hairy cell leukemia?
Splenomegaly (due to red pulp expansion - most leukemias are white pulp)
Dry tap with bone marrow aspiration
No Lymphadenopathy
What is main treatment for hairy cell leukemia?
2-CDA
–> Adenosine Deaminase Inhibitor causes adenosine to accumulate in toxic levels in neoplastic Bcells
What is Adult Tcell Leukemia Lymphoma (ATLL)?
Neplastic proliferation of mature CD4+ Tcells
- Associated with HTLV-1 (Human Tcell Leukemia Virus-1 from Japan and Caribbean)
Symptoms:
Rash
Generalized LAD with HSM
Lytic bone lesions with hypercalcemia
What is myelodysplastic syndrome?
Neoplastic proliferation of mature cells of myeloid lineage
- disease of late adulthood
- Results in high WBC count with hypercellular bone marrow
- Cells of all myeloid lineages are increased
- -> classified based on dominant myeloid cell produced
What are complications of myelodysplastic syndrome?
- Increased risk for hyperuricemia and gout (increased turn over of cells and nuclei –> increased purine degredation)
- progression to marrow fibrosis (“burnout” phase)
- transformation to acute leukemia
What is chronic myeloid leukemia?
- Neoplastic proliferation of mature myeloid cells, especially granulocytes
- Basophils are characteristically increased
- Caused by t(9;22) which is a BCR-ABL fusion with increased tyrosine kinase activity
- First line of treatment is imatinib (blocks tyrosine kinase activity)
- Splenomegaly is common (enlarging spleen suggests acclerated phase of disease, leading to acute leukemia - AML or ALL)
How do you distinguish CML from a leukemoid reaction?
CML granulocytes are LAP (leukocyte alkaline phosphatase) negative (cells for leukomoid rxn would have LAP to fight infection)
CML is associated with increased Basophils
CML granulocytes exhibit t(9;22)
What is polycythemia vera?
Neoplastic proliferation of mature myeloid cells, especially RBCs
Granulocytes and platelets are also increased
Associated with JAK2 kinase mutation
Symptoms:
**Hyperviscosity ** (blood is loaded with RBCs)
Blurry vision and headache
Increased risk of venous thrombosis(Budd Chiari)
Flushed face due to congestion
Itching after bathing (due to mast cell increase and release of histamine from the bathing)
What is the treatment of polycythemia vera?
Phlebotomy (Leach ‘em!)
Second line treatment is hydroxyurea
How is polycythemia vera distinguished from reactive polycythemia?
In PV, SaO2 is normal and EPO is decreased
In reactive due to lung disease that causes hypoxemia, SaO2 is low and EPO is increased
In reactive due to ectopic EPO production (renal cell carcinoma), SaO2 is normal and EPO is increased
What is Essential Thrombocythemia?
Neoplastic proliferation of mature myeloid cells, especially platelets
RBC and granulocytes are also increased
Associated with JAK2 kinase mutation
Symptoms:
Increased risk of bleeeding and/or thrombosis
Rarely progresses to marrow fibrosis or leukemia
No significant risk of hyperuricemia or gout (overproduction of platelets does not result in increased production of nuclei)
What is myelofibrosis?
Neoplastic proliferation of mature myeloid cells, particularly Megakaryocytes
- Driven by JAK2 mutation
- Megakaryocytes produce excess PDGF resulting in marrow fibrosis
Symptoms:
Splenomegaly due to extramedullary hematopoiesis (no room in BM to make blood)
Leukoerythroblastic smear
Increased risk of infection, thrombosis, and bleeding(due to improper production of bone marrow derived cells)
Tear drop cells (cells stretched as they attempt to leave fibrosed bone marrow)
What types of lymphomas derive from small Bcell lymphomas?
Follicular lymphoma
Mantle cell lymphoma
Marginal zone lymphoma
What are characteristics of follicular lymphoma?
Neoplastic small CD20+ Bcells that make follicle-like nodules
Presents in late adulthood with painless, generalized lymphadenopathy
Driven by t(14;18) - Ig Heavy chain translocates to Bcl2
Lots of Bcl2 is produced and stabilizes mitochondrial membrane, preventing apoptosis
Follicles are where developing Bcells should die if they are unable to progress into beneficial plasma cells - t(14;18) prevents this
How is follicular lymphoma treated?
With low dose CTX or rituximab (anti-CD20 antibody)
–> given to patients experiencing symptoms as most are asymptomatic
What are complications of follicular lymphoma?
Progression to diffuse large Bcell lymphoma
–> presents with enlarging lymph nodes
How is follicular lymphoma distinguished from follicular hyperplasia of infection?
Disruption of normal node architecture
Lack of tingible body macrophages in growth centers of follicles
Expression of Bcl2 in follicles (preventing apoptosis)
Monoclonality
What are characteristics of mantle cell lymphoma?
Neoplastic small CD20+ Bcells that expand the mantle zone of a lymph node
Presents in late adulthood with painless lymphadenopathy
Driven by t(11,14) translocation. Cyclin D1 translocates to Ig heavy chain locus causing overexpression and promoting phosphoryation of enzymes driving G1/S transition in cell cycle
What are characteristics of a marginal zone lymphoma?
Neoplastic small CD20+ Bcells proliferating in the marginal zone of the lymph node
- Associated with chronic inflammatory states (i.e. Sjogren, H. pylori gastritis, Hashimoto’s thyroiditis, etc)
What are characteristics of Burkitt lymphoma?
Neoplastic intermediate sized CD20+ Bcells
Associated with EBV
Presents with extranodal mass in child or young adult
African form usually involves jaw (sporadic involves abdomen)
Driven by translocations of c-myc
Most common is t(8;14)
c-myc promotes cell growth
What histological signs suggest Burkitt’s lymphoma?
Starry sky appearance
High rate of mitotic figures
Whare characteristic of Diffuse Bcell lymphoma?
Neoplastic large CD20+ Bcells that grow diffusely in sheets
Most common form of Non-hodgkin lymphoma
Clinically aggressive (b/c it’s poorly differentiated)
What cells are characteristic of Hodgkin’s Lymphoma?
Proliferation of Reed-Sternberg cells
Large CD15+CD30+ Bcell with multilobed nuclei with prominent nucleoli
They give the appearance of “owl eyes”
What do Reed Sternberg cells do that cause Hodgkin lymphoma symptoms/issues?
They secrete cytokines
- Occasionally result in “B” symptoms (fever, chills, night sweats)
- Cytokines attract reactive lymphocytes, plasma cells, macrophages, and eosinophils (cause the bulk of the lymphnodal mass)
- May lead to fibrosis
What are the subtypes of hodgkin lymphomas?
Nodular sclerosis (70%): enlarging cervical neck or mediastinal lymph node; usually young female; lymph node has broad bands of fibrosis with lacunar cells (reed-sternberg cells specifically for this subtype)
**Lymphocyte-rich: ** best prognosis
Mixed cellularity: associate with abundant eosinophils (eosinophils brought in by IL-5)
Lymphocyte-depleted: worst prognosis (seen in HIV+ and elderly)
What is multiple myeloma?
Malignant proliferation of plasma cells in bone marrow
- Most common primary malignancy of bone
- High serum IL-6 is sometimes present
What causes the bone pain associated with multiple myeloma?
MM has bone pain with hypercalcemia
- caused by neoplastic plasma cells secreting osteoclast activating factor (binding to RANK receptor) leading osteoclasts to eating bone
–> leads to lytic “punched-out” lesions seen on x-ray especially in vertebrae and skyll
- increased risk of fracture
What causes the elevated serum protein of multiple myeloma?
Neoplastic plasma cells overproducing immunoglobulin
Results in “M spike” in electrophoresis (indicates monoclonal immunoglobulin - usually IgG or IgA)
Patients lose antigenic diversity and are at risk for infection (most common cause of death)
What is the risk of increased serum protein with multiple myeloma?
Increased protein decreases charge between RBCs resulting in Rouleaux formation on blood smear
- RBCs clump and pile up on smear
What are symptoms of multiple myeloma?
Bone pain and hypercalcemia
Lytic “punched-out” lesions in bone
Increased serum protein
Primary AL amyloidosis (free light chain circulates in blood and deposits in tissues)
Proteinuria of free light chain (Bence-Jones proteins)
Deposition in kidney tubules leads to risk for renal failure (myeloma kidney)
What is monoclonal gammopathy of undetermined significance?
Increased serum protein with M spike on SPEP
- Other features of multiple myeloma are absent (no lytic lesions, hypercalcemia, AL amyloid, or Bence-Jones proteinuria)
- Present in 5% of patients over 70
1% of those develop MM each year
(it’s like a pre-myeloma state)
What is Waldenstrom Macroglobulinemia?
Bcell lymphoma with monoclonal IgM production
Symptoms:
Generalized LAD; lytic lesions absent
Increased serum protein with M spike
Visual and neurological deficits (ie. retinal hemorrhage or stroke due to increased blood viscosity)
Increased risk of bleeding (increased viscosity leads to platelets reduced ability to aggregate)
How is Waldenstrom macroglobulinemia treated?
Plasmapheresis (pull out IgM and reduce blood viscosity)
