Hematology Exam 4 Flashcards
List 3 types of hematologic neoplasms.
Leukemias, Lymphomas, Myelodysplastic syndromes (MDSs)
What do hematologic neoplasms result from?
Abnormal growth of the cells of the hematopoietic system
What is the difference between leukemias and lymphomas?
Leukemias primary site of disease is the blood or bone marrow, while lymphomas primary site of disease is in the lymph nodes and spleen.
What is the difference between chronic and acute leukemias?
Acute leukemias have an excess of precursor cells (blasts) and are more sudden and severe while chronic leukemias are excess mature cells and have a longer survival
What is the most common type of leukemia in children?
Acute lymphoblastic leukemia (ALL)
What is the most common type of leukemia in adults?
Chronic lymphocytic leukemia (CLL)
What is the difference between lymphoid and myeloid leukemia?
Lymphoid leukemias develop in lymphocytes, while myeloid leukemias develop in granulocytes or monocytes.
FAB classification system vs WHO classification system
FAB classification is only based on morphological characteristics.
WHO classification considers clinical features, morphology, immunophenotyping, cytogenetics, and molecular genetics.
Epigenetic mechanisms
Control how genes are expressed and silenced
Protooncogenes
Encode for proteins that are essential for NORMAL cellular function (GOOD genes)
Oncogenes
Mutation of protooncogene that alters the gene product and transforms the cell into a malignant phenotype (BAD gene)
Qualitative mutations
Structural change to the protooncogene and production of an abnormal protein product
Quantitative mutations
An overexpression of a normal protooncogene in a hematopoietic cell
Tumor suppressor genes
Code for proteins that protect cells from malignant transformation (GOOD)
List common treatments for leukemia and lymphomas
Chemotherapy, radiation, supportive therapy, targeted therapies, hematopoietic stem cell transplant
Describe hematologic remission
Normal bone marrow, recovery of peripheral blood counts, no microscopic evidence of leukemia cells
Describe cytogenetic remission
Absence of the cytogenetic defect determined by karyotyping methods
Describe molecular remission
Absence of leukemia cell nucleic acid sequences using highly sensitive molecular methods
What type of leukemia is Gleevec used for? What is Gleevec?
Chronic-phase CML - it is a tyrosine kinase inhibitor that reduces massive cell proliferation and induces apoptosis of CML cells
Targeted therapies
Act specifically on malignant cells while leaving normal cells untouched
When is ATRA used?
Used to treat patients with APL with PML-RARA gene
What is Rituximab?
a monoclonal antibody; anti-CD20 that binds the CD20 antigen on malignant lymphocytes
What is a syngeneic HSC donor?
Donated from an identical twin
What is an allogeneic HSC donor?
From an HLA-identical sibing or HLA-matched unrelated donor; most common!!
What is an autologous HSC donor?
From the patients’ own marrow or peripheral blood cells
What is the WHO classification for diagnosing a leukemia as acute?
Requires at least 20% blasts in bone marrow or peripheral blood
What is the FAB classification for diagnosing a leukemia as acute?
Requires at least 30% blasts in bone marrow or peripheral blood
What is the development of leukemia believed to be?
A progression of mutations that give cells a proliferative advantage while also hindering differentiation
What population is heavily affected with ALL (acute lymphoblastic leukemia)?
Children and adolescents
What are the two subtypes of ALL?
T-cell and B-cell
Signs/Symptoms of B cell ALL
Fatigue, fever, mucocutaneous bleeding, lymphadenopathy, splenomegaly, hepatomegaly, bone pain, infiltration into meninges/testes/ovaries
Signs/Symptoms T cell ALL
Large mass in the mediastinum, anemia, thrombocytopenia, organomegaly, bone pain, LESS SEVERE LEUKOPENIA than in B cell ALL
What does the prognosis of ALL depend on?
Age (children have better prognosis)
Lymphoblast load (More blasts = worse prognosis)
Immunophenotype
Genetic abnormalities (Hyperdiploidy = better prognosis)
What does B-ALL and T-ALL usually express?
CD34, TdT, HLA-DR
What does B-ALL express differently than T-ALL?
B-ALL expresses CD34, CD19, CD22, and TdT
T-ALL expresses CD2, CD3, CD4, CD5, CD7, CD8
What is the worst prognosis among all ALLs? What is a good B-ALL prognosis?
B-ALL with the t(9;22) mutation –> Philadelphia chromosome
Good = hyperdiploidy with B-ALL
CBC findings associated with AML
variable WBC count, myeloblasts present, anemia, and thrombocytopenia
Bone marrow findings associated with AML
hypercellular, >20% blasts
Signs/Symptoms of AML
pallor, fatigue, fever, bruising, bleeding, splenomegaly (different from ALL because lymphadenopathy is rare and CSF involvement is rare)
Chromosomal translocation
A chromosome breaks and a portion of it reattaches to a different chromosome
Chromosomal inversion
A chromosome rearrangement where segment of a chromosome is reversed end to end
Describe tumor lysis syndrome and its typical findings
A group of metabolic complications that can occur in patients with malignancy; characterized by hyperkalemia, hyperphosphatemia, hyperuricemia, hyperuricosuria, hypocalcemia
Understand the genetic nomenclature (ex. What does t(16;16)(p13.1;q22);CBFB-MYH11 mean?)
There is a translocation on chromosome 16 occurring at band 13.1 on the short arm of chromosome 16 and band 22 on the long arm of chromosome 16 with CBFB and MYH11 genes fusing.
AML with T(8;21)
Translocation b/t chromosome 8 and 21 - presents as FAB M2; myeloblasts have granular cytoplasm with Auer rods present
AML with T/INV(16;16)
Translocation/Inversion on chromosome 16; presents as FAB M4 - myeloblasts, monoblasts, and promyelocytes seen
AML with T(15;17)
Translocation between chromosome 15 and 17; AML with PML-RARA - presents as FAB M3 - hypergranular promyelocytes some with Auer rods
AML with T(9;11)
Translocation between chromosome 9 and 11; Presents as FAB M5 - increased monoblasts and immature monocytes, pseudopodia often seen; granules and vacuoles can be seen - associated with gingival and skin involvement
What does many Auer rods indicate?
Myeloid lineage
Describe M0 classification of AML.
Acute myeloid leukemia, minimally differentiated; NO evidence of cellular maturation - no auer rods, no granules, and negative for all cytochemical staining
Describe M1 classification of AML.
Acute myeloid leukemia without maturation; <10% of WBCs show maturation to promyelocyte stage or beyond. Blasts may compromise >90% nonerythroid cells in the bone marrow. Staining: At least 3% of blasts stain positive with MPO or SBB stains.
Describe M2 classification of AML.
Acute myeloid leukemia with maturation; Clear evidence of maturation to and beyond the promyelocyte stage; >10% promyelocytes, myelocytes, metamyelocytes. Auer rods often present. Hypercellular BM. Stains positive for SBB, MPO, and CAE.
Describe M3 classification of AML.
Acute promyelocytic leukemia (APL). Blasts and promyelocytes with heavy granulation predominate. Abnormal promyelocytes with heavy granulation, Auer rods in bundles can be seen. Associated with T(15;17) and DIC
Describe M4 classification of AML.
Acute myelomonocytic leukemia; significantly elevated WBC count with presence of myeloid AND monocytic cells which constitute at least 20% of all BM cells. Stains positive with MPO, SBB and NSE
Describe M5 classification of AML.
Acute monoblastic and monocytic leukemias; >80% of BM cells are of monocytic origin, contains promonocytes and extramedullary involvement is common. Stains positive with NSE and MPO, negative for SBB
Describe M6 classification of AML.
Pure erythroid leukemia; >80% of BM cells are erythroid AND 30% erythroblasts. MANY nRBCS can be seen with megaloblastoid asynchrony (nucleus is not maturing as quickly as the cytoplasm) and multinucleated
Describe M7 classification of AML
Acute megakaryoblastic leukemia; dysplastic features in all cell lines; presence of at least 20% blasts and 50% of them must be of megakaryocytic origin. “Dry tap” is common, blasts may appear lymphoid.
Describe the association between AMLs and trisomy 21
Patients with Down Syndrome are 50% more likely to experience AML within the first 5 years than patients without Down Syndrome
What does MPO stain? Which cells stain positive and negative for MPO?
Stains primary granules
Positive: blasts of AML (AML, AMML)
Negative: lymphocytes bc agranular (ALL, AMoL, megakaryocytic leukemia)
What does SBB stain? Which cells stain positive and negative for SBB?
SBB stains cellular lipids
Positive: granulocytes from myeloblast through maturation series (AML, AMML, AMoL)
Negative: Monocytic cells can be weakly pos or neg, and lymphoid is neg (ALL, megakaryocytic)
What are esterases used to differentiate between?
Granulocytes and myeloblasts from monocytic cells
What cells stain positive for NSE? Negative?
Positive: Monocytes (AMoL, AMML)
Negative: Granulocytes and Lymphocytes
What cells stain positive for CAE? Negative?
Positive: Granulocytes (AMML)
Negative: All other cells (AMoL)
What testing is often employed to identify leukemia and lymphoma subtypes?
Flow cytometry, immunohistochemistry, bone marrow or lymph node biopsy, CBC
What are B symptoms? Why are they important?
Fever, drenching night sweats, and loss of >10% body weight over 6 months. They are important in the prognosis and staging of lymphomas.
What is the Ann Arbor staging system?
First applied to Hodgkin lymphoma, further qualified by absence or presence of B symptoms –> defines limited vs extensive disease
What is the lugano classification system?
A simplification of the original Ann Arbor staging, currently used in non-Hodgkin lymphoma. Groups patients into limited and advanced
Describe stage I of the Ann Arbor/Lugano classification system
1 node involved
Describe stage II of the Ann Arbor/Lugano classification system
2 or more nodes located on the same side of the diaphragm
Describe stage III of the Ann Arbor/Lugano classification system
Nodes on both sides of the diaphragm
Describe stage IV of the Ann Arbor/Lugano classification system
Multiple nodule groups on both sides of the diaphragm with involvement with extralymphatic organs
What is the IPI?
The IPI is the internal prognostic index for Non Hodgkin Lymphoma and has largely replaced anatomic staging as the primary prognostic tool.
What are the 5 parameters of the IPI?
Age (>60 or <60)
Serum LDH (>normal or <normal)
Performance status (0/1 versus 2-4)
Stage (limited or advanced)
Extranodal involvement (less than or equal to 1 site or greater than 1 site)
What is the population most affected by CLL?
most common leukemia in OLDER ADULTS
Is CLL a disorder of B cells or T cells?
B cells
How is CLL detected?
Usually asymptomatic so detected by an abnormality in routine CBC
What is the diagnosis of CLL?
Presence of at least 5 x 10^9 cells/L circulating B lymphs for more than 3 months
Is CLL more common in women or men?
Men
What lab findings are associated with CLL?
> 85% lymphs; Small and mature lymphs with condensed chromatin that looks like a soccer ball –> “soccer ball lymphs” and smudge cells are common due to fragility of lymphs present
How does the Rai classification system differ from the Binet classification system for CLL?
Rai system uses lymphocytes and HGB
Binet system uses HGB and PLTS and number of enlarged nodal areas
Describe the low risk stage of Rai system for CLL
Lymphocytosis >5 x 10^9/L
Describe the intermediate risk stage of Rai system for CLL
Lymphocytes >5 x 10^9/L and lymphadenopathy and splenomegaly or hepatomegaly or both
Describe the high risk stage of Rai system for CLL
Lymphocytes >5 x 10^9/L and HGB <11 g/dL
Describe stage A of the Binet system for CLL
HGB >10 g/dL and PLTS >100 x 10^9/L and <3 enlarged nodal areas
Describe stage B of the Binet system for CLL
HGB >10 g/dL and PLTS >100 x 10^9/L and >3 enlarged nodal areas
Describe stage C of the Binet system for CLL
HGB <10 g/dL and PLTS <100 x 10^9/L and any number of enlarged nodal areas
Treatments for CLL
Rutuximab or targeted agents
PLL (prolymphocytic leukemia) population most affected
Disease of the elderly but very rare
Clinical presentation of PLL
Massive splenomegaly (protruding stomach)
Marked absolute lymphocytosis
High incidence of tissue involvement
Is PLL B cell or T cell? indolent or aggressive?
It can be both; B cell more common. It is an aggressive disease.
What is noted on CBC of PLL
prolymphocytes
Treatment for PLL
Alemtuzumab (for T-PLL) but is suboptimal
Indolent vs Aggressive diseases
Indolent = slow moving
Aggressive = fast moving and harder to treat
HCL (Hairy cell leukemia) B cell or T cell disease? Indolent or aggressive?
B cell lineage - indolent disease
HCL population most commonly affected
Middle aged people (median age of 50 years) more common in men
Clinical presentation of HCL
splenomegaly and cytopenias
Lab findings in those with HCL
hairy cells –> lymphs with kidney bean nucleus and ragged projections around the cell; may have a dry tap
What monoclonal antibody will help identify clusters of hairy cells for HCL?
Anti-CD20
What cells are TRAP positive that were discussed in this unit??
HCL
Treatment for HCL
Splenectomy, nucleoside analogues cladribine and pentostatin
LGL (large granular lymphocytic leukemia) population most affected
Older adults (median age 60 years)
Clinical presentation of LGL
Most patients asymptomatic; present with neutropenia, anemia, or both
Treatment for LGL
Myeloid growth factors and immunosuppressive agents
Is LGL T cell or B cell?
T cell
Notable findings/Key phrases for ATLL (Adult T cell Lymphoma): Is it T cell or B cell?
T cell disorder - associated with HTLV-1 and “flower cells” are seen in morphology
Notable findings/Key phrases for BL (Burkitt Lymphoma): Is it T cell or B cell?
B cell lymphoma - deeply basophilic cytoplasm with distinct vacuoles called starry sky cells are seen in morphology
orbits and mandible are common extranodal sites of involvement
Notable findings/key phrases for FL (Follicular lymphoma): Is it T cell or B cell?
B cell lymphoma - condensed chromatin pattern with distinct nuclear clefts seen in morphology
Notable findings/key phrases for MCL (mantle cell lymphoma): Is it T cell or B cell?
B cell lymphoma with extensive lymphadenopathy requires overexpression of cyclin D1 or t(11,14)
Notable findings/key phrases for DLBCL (diffuse large B cell lymphoma)
B cell lymphoma; the most common form of NHL. Large lymphs seen with diffuse pattern in the lymph node. Treated with Rituximab
What monoclonal antibody is Rituximab?
Anti-CD20
Notable findings/key phrases for MZL
B cell lymphoma that can be MALT, splenic, or nodal. MALT is most common. Splenic lymphs have polar distribution on cytoplasmic projections.
Notable findings/key phrases for MF/SS
T cell lymphoma that is cutaneous disease of the elderly. Morphology include cells that are brain-like/cerebriform
PTCL-NOS: T cell or B cell?
T cell antigen mismatch
What is a plasma cell neoplasm? Give examples
Malignant disorder of terminally differentiated B cells that secrete monoclonal immunoglobulin such as MM and WM
Functional hypogammaglobulinemia
Normal immunoglobulin production is decreased
M-spike
a spike seen on electrophoresis graph in the gamma region (monoclonal spike)
Order of incidence of heavy chain involvement in PCNs from most common to least common
IgG > IgA > IgM > IgD > IgE
Multiple myeloma: what is it, clinical findings, morphology, etc.
BM based PCN with an increase in IgG being made; associated with osteolytic lesions and presence of rouleaux with lots of plasma cells in BM
What is used to treat MM?
Daratumumab - anti-CD38
Waldenstrom’s Macroglobulinemia: what is it, associated with which gene mutation
PCN associated with aberrant secretion of IgM - associated with MYD88 gene found in >90% of cases
How do we differentiate HL and NHL?
Presence/absence of Reed-Sternberg Cells that have an owl-eye appearance
Classic HL vs LPHL: cells seen and clinical findings
Classic HL: presence of RS cells with nodes that spread in a contiguous matter (in order)
LPHL: presence of L&H cells (popcorn cells) with nodes that spread in a non-contigous matter (random)
