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92 Cards in this Set
- Front
- Back
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t(X;18)(p11.2;q11.2)
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Synovial sarcoma
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t(9;22)(q34;q11)
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Philadelphia chromosome, CML, ALL
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t(9;12)(p24;p13)
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CML, ALL
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t(8;21)(q22;q22)
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Acute myeloblastic leukemia with maturation
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t(8;14)(q24;q32)
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Burkitt's lymphoma
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t(2;5)(p23;q35)
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Anaplastic large cell lymphoma
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t(2;3)(q13;p25)
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Follicular thyroid cancer
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t(17;22)
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DFSP
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t(15;17)
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Acute promyelocytic leukemia
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t(14;18)(q32;q21)
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Follicular lymphoma
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t(12;21)(p12;q22)
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ALL
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t(12;15)(p13;q25)
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Acute myeloid leukemia, congenital fibrosarcoma, secretory breast carcinoma
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t(11;22)(q24;q11.2-12)
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Ewing's sarcoma
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t(11;14)(q13;q32)
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Mantle cell lymphoma
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t(1;12)(q21;p13)
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Acute myelogenous leukemia
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Name this disorder. What is a clinical course?
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Hereditary elliptocytosis. Clinically insignificant with no or mild hemolytic anemia. However an overlap with a severe disorder called hereditary poikilocytosis (deformed cells) exists
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G6PD deficiency causes defects in what biochemical pathway that explains mostly episodic nature of hemolyis. What is the inheritance pattern
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Pentose shunt used by erythrocytes to regenetrate glutathione with NADPH as a hydrogen donor. Hemolysis is due to oxidative stress (Favism, dapsone etc). Smear during acute episodes will show evidence of hemolyis and bite cells. X-linked, though notably females can be symptomatic due to random X chromosome incativation (subset of cells will be G6PD deficient)
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what is the molecular origin of Hemoglobin Lepore and what phenotype would you expect in a beta-/Lepore heterozygote
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Hb Lepore is beta-delta fusion protein that is inefficiently produced and migrates with S on cellulose acetate, but is typically 15% of total. beta-/Lepore have b thal major or close to it.
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Usefulness of FLT3 studies?
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Internal tandem duplications and/or insertions and, rarely, deletions in the FLT3-gene are implicated in 20-25% of all acute myeloid leukemias (AML) and are a negative prognostic factor.
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What is Chediak-Higashi disease
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AR syndrome of oculocutaneous albisnism, neutropenia, and thrombocytopenia. Platelets and neutrophils have huge granules that cannot degranulate properly
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Diagnostic utility of CD117
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Is a pan-myeloid marker, among WHO diagnostic criteria for various AML subtypes (often co-expressed with CD13, CD33, CD34, MPO). It is the c-kit proto-oncogene.
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Cell lineage associated with CD13?
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Myeloid. Associated with most AML subtypes.
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Lineage associated with CD33 expression?
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Myeloid. Associated with most AML subtypes.
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Relationship between this condition and hereditary elliptocytosis?
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The image shown is typical of hereditary pyropoikilocytosis, in which the patient is a double heterozygote for genes causing hereditary elliptocytosis (Mutations in protein 4.1, alpha spectrin, beta spectrin, band 3, and glycophorin C have been described in HE).
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CD5 and CD20 co-expression by flow occurs in which neoplasms?
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CD5+/CD20+ in CLL and MCL; can differentiate using CD23, which is (+) in CLL, negative in MCL (also CD20 is dim in CLL).
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Name two markers that are useful for distinguishing follicular lymphoma from CLL, mantle cell and marginal zone lymphomas.
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CD10 and Bcl-6 are positive in FL, negative in the others. Also note that Bcl-2 staining within the follicular centers is virtually pathognemonic for FL. Must look within the germinal centers because both B and T cells outside the GC can express bcl-2 normally
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Hyperglycemia can ... MCV and what can you do about it
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Spuriously increase due to swelling of the RBCs in the counting medium in the machine. Spun HCT in combination with RBC on the machine can provide a more accurate estimate
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Translocation and (corresponding loci) in Burkitt lymphoma
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Most often t(8;14), translocation between c-myc and the IgH locus. Less commonly to light chain loci on 2q11 [t(2;8)] or 22q11 [t(8;22)]
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Numerous tingible-body macrophages and a high mitotic rate with a "starry sky appearance" should make you think of...
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Burkitt lymphoma
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Burkitt lymphoma immunophenotype.
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Is of B-cell origin, so CD19+, CD20+, CD22+; CD10+ and bcl6+, so most likely of follicular origin (note similarity to FL in these markers); very high proliferative fraction, so nearly 100% of tumor cells are positive for Ki-67; also CD5- (would be pos in CLL, MCL), CD23- (pos in CLL). Cells express IgM with ligh chain restriction.
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Gender predilection of mature B-cell lymphomas.
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Overall M > F with the exceptions of follicular lymphoma (F=58%), and mediastinal LBCL (F=66%)
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what neoplasm is associated with t(11;14)?
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(IgH-cyclin-D1) mantle cell lymphoma note: translocation studies are positive only about 40% of the time, so a negative result does not exclude mantle cell lymphoma
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Define AML-M3, most frequent translocation, and basic immunophenotyoe
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Acute promyelocytic leukemia; AML with t(15;17)(q22;q21);(PML/RARa); CD33, CD13 (heterogeneous) positive/ CD34(low to negative), CD15(dim), HLADR(negative or dim)
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Variant translocations associated with FAB AML-M3
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t(11;17)(q23;q21), PLZF on 11 No Auer rods, regular nuclei, pseudo Pelger-Huet cells Resistant to ATRA AND t(5;17)(q23;q12), NPM on 5 rare, atypical APL, no Auer rods, responds to ATRA AND t(11;17)(q13;q21), NuMA on 11
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alpha naphthyl acetate esterase and alpha naphthyl butyrate esterase (nonspecific esterases) are specific for which cell lineages?
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Monocytic, megakaryocytic. For example, expected to stain AML M4 (myelomonocytic) and M5 (monocytic/monoblastic)
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most common molecular genetic abnormality in childhood acute lymphoblastic leukemia (ALL)
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TEL/AML-1 fusion gene resulting from a cryptic t(12;21)(p13;q22). All are B-cell and CD10 positive. Associated with improved prognosis.
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CD25 associations
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Diagnostic in ATLL, associated with but not necessary for hairy cell leukemia
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Name the abnormality: Dense azurophilic granules, resembling toxic granulation in neutrophils, are seen in all leukocytes. Most characteristic of these disorders are the metachromatic granules surrounded by a clear zone seen in lymphocytes.
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The Alder-Reilly anomaly is associated with the genetic mucopoly- saccharidoses. Patients with mucopolysaccharidoses lack the lysozymal enzymes necessary to break down mucopolysaccharides. Dense azurophilic granules, resembling toxic granulation in neutrophils, are seen in all leukocytes. Most characteristic of these disorders are the metachromatic granules surrounded by a clear zone seen in lymphocytes.
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Disease? Common translocation? Blasts are deeply basophilic with prominent vacuoles.
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Burkitt leukemia; t(8;14). Blasts are deeply basophilic with prominent vacuoles.
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Name the abnormality: Neutrophils with more rounded nuclear contours with mature chromatin and normal cytoplasmic granularity.
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The three Pelger-Huet cells in this view show more rounded nuclear contours with mature chromatin and normal cytoplasmic granularity.
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Three most common cytogenetic abnormalities in myelodysplastic syndromes
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cytogenetic abnormalities in 80% of MDS: ~25% have complex abnormalities (poor prognosis); ~15% isolated monosomy 7 or 7q-; ~10% isolated 5q- (good prognosis)
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General approach to immunophenotypic difference between B and T-cell ALL
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Both are typically CD34+, CD99+ (B-cell: CD19+, HLA-DR+) (T-cell: CD19-, HLA-DR-; CD7+ (not specific to T-ALL), CD3+ (cytoplasmic), CD4/CD8+/- (maybe other T-cell markers positive like CD2, CD5))
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Define FAB AML-M5
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Acute monocytic/monoblastic leukemia. >20% blasts, >80% of nonerythroid cells monocytic lineage. Expect monocytic markers (CD14, CD64, CD11c, lysozyme), myeloid markers (CD13, C33, CD117), HLA-DR+, usually negative CD34. Associated with soft tissue invasion, notably gingival hyperplasia. Previously M4 and M5 may have included AML with anomalies of 11q23 (topo II inhibitors, children). May have t(9;11)
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Significance of ALK1
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ALK1 staining is relatively specific for Anaplastic Large Cell Lymphoma. ALK1 expression is the most important prognostic factor in ALCL, and these tumors have an average 80% 5-year survival rate, as compared to 40% for ALK1-negative ALCL. ALK1 is also positive in a DLBCL subset expressing cytoplasmic IgA (will be positive for B-cell markers)
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Cell specificity of CD68?
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histiocytes
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Hypercalcemia in the setting of a lymphoid malignancy?
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Adult T-cell leukemia/lymphoma. Is HTLV-associated. Cells are CD25+ (IL-2 receptor).
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Immunophenotype of hairy cell leukemia
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Positive: sIg (usually G), CD19, CD20/FMC7, CD22, CD79a, CD11c, CD25, CD103, TRAP, DBA-44 Negative: CD5, CD10, CD23, CD79b Note TRAP (tartrate-resistant acid phosphatase) positivity
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Define FAB AML-M4
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Acute myelomonocytic leukemia. >20% blasts in marrow and 20-80% of nonerythroid cells are monocyte lineage (monoblasts, promonocytes, monocytes) (contrast this with M5=monocytic/monoblastic in which >80% of nonerythroid cells are monocyte lineage). Variable staining with MPO, SBB, CAE, and NSE. Frequently responsive to therapy. Previously M4 and M5 may have included AML with anomalies of 11q23 (topo II inhibitors, children)
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Epidemiology of B-ALL
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B-ALL: 75% of cases in children under 6 years old
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Epidemiology of B-LBL
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B-LBL: 10% of lymphoblastic lymphoma, 75% of cases in patients under 18 years old
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Epidemiology of T-ALL
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T-ALL: 15% of childhood ALL, 25% of adult ALL
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Epidemiology of T-LBL
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T-LBL: 85-90% of lymphoblastic lymphoma, more common in adolescents and males
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B-ALL/B-LBL cytochemistry
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MPO, SBB: negative AND PAS : nuclear is partially encircled by a rim of PAS reactivity
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B-ALL/B-LBL immunohistochemistry
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TdT and HLA-DR + AND CD19, CD79a, CD10, CD24 (Note that t(4;11)(q21;q23) cases are typically negative for CD10 and CD24) AND Variably positive for CD20 and CD22 AND CD 45 may be negative. Cytoplasmic Mu chain (cyt-mu) in pre-B ALL
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T-ALL cytochemistry, immunophenotype
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Acid phosphatase positive (90% of cases); TdT+, CD3 is the only consistent linage specific marker
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Key characteristics of Angioimmunoblastic T-Cell Lymphoma
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systemic disease with polyclonal gammopathy. lymph nodes with effaced architecture, CD21+ follicular dendritic cells, polymorphous infiltrate, and prominent high endothelial venules. EBV+ B cells may be numerous. CD4 > CD8. loss of one or several pan-T-cell markers such as CD2, CD3, CD5, or CD7. CD10 is present on T cells (this is important)
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Define FAB AML-M4
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Acute myelomonocytic leukemia. >20% blasts in marrow and 20-80% of nonerythroid cells are monocyte lineage (monoblasts, promonocytes, monocytes). Variable staining with MPO, SBB, CAE, and NSE. Frequently responsive to therapy (this may only go for the inv16 which is in a separate category and confers relatively better prognosis). Previously may have included AML with anomalies of 11q23 (topo II inhibitors, children)
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Immunophenotypic distinction between AML with t(8;21) and AML with t(15;17)
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Both are CD13+, CD33+, t(8;21) CD34+, HLA-DR+ (also often CD19+), t(15;17) CD34 neg, HLA-DR neg
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What is leukocyte adhesion deficiency
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AR defect in membrane integrins that contain beta-2, CD11b, or CD18. Causes periodontitis and delayed cord separation. Integrins are necessary for neutrophil adhesion (selections are needed for rolling).
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Sequence of myelocyte maturation
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Myeloblast > promyelocyte > myelocyte > metamyelocyte > band > segmented form
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Significance of hyperlobulated neutrophils (ie, > 6 lobes).
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Suggests B12 or folate deficiency.
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translocation, fusion protein in acute myeloid leukemia (AML-M2)
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t(8;21), AML1(RUNX1)/ETO fusion gene
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malignancy associated with t(15;17)?
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promyelocytic leukemia (AML-M3)
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translocation and abnormal gene product associated with acute promyelocytic leukemia (AML-M3)
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t(15;17), PML/RAR-alpha protein
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what can CLL transform into?
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if you see prolymphocytes in the blood (larger cell with blasty chromatin and nucleoli) numbering >10% but <55%, it is CLL with increased prolymphocytes (CLL/PL) or transformation into diffuse large B cell lymphoma (Richter's)or Hodkin's lymphoma
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Most important defining feature of AML M0
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< 3% myeloperoxidase positive myeloblasts
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Define AML M6a and M6b
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Acute erythroid leukemia with a) >= 50% erythroid precursors and >= 20% myeloblasts, and b) >80% of the marrow cells representing immature erythroid cells without evidence of a significant myeloblastic component.
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Minimal percentage of blasts (in BM or blood) required to meet definition of acute leukemia?
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20%
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General significance of CD34
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Marker for immaturity.
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Four correlated prognostic factors in CLL.
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1. Mutational status of IgVH genes: unmutated = worse prognosis. 2. ZAP-70 positive = worse prognosis 3. CD38+ = worse 4. Trisomy 12 (associated with unmutated IgVH)= worse
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What genes are involved in the translocation associated with mantle cell lymphoma?
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t(11;14) - translocation of the cyclin D1 (bcl-1) located on 11q13 with the heavy chain immunoglobulin gene located on 14q32.
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Most common cytogenetic abnormalities involving chromosomal loss in plasma cell myeloma
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13q14 or monosomy 13
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Immunophenotype of follicular lymphoma
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Surface Ig+, B-cell antigens (CD19, 20, 22, 79a), CD10+, BCL2+ (grade 3 and cutaneous may be negative), BCL6+
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Eponym describing morphological abnormality in these cells?
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Pelger-Huet cells (left) and pseudo Pelger-Huet (right) - look the same, don't they? Note that P-H is a harmless, autosomal recessive trait. If homozygous, neutrophils are mononuclear rather than bilobed.
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What is the May-Hegglin Anomaly?
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Autosomal dominant defect of MYH9 (nonmuscle myosin heavy chain). Giant platelets and neutrophils containing Dohle bodies are observed; the syndrome is associated with asymptomatic to mild (and never fatal) bleeding/bruising syndromes.
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Three cell surface marker that distinguish CLL from mantle cell, follicular, and marginal zone lymphomas by flow?
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CD23 is positive in CLL, negative in the others. Also, CLL is CD20 dim and sIg dim (others are more strongly CD20+ and sIg+). FMC7 is positive in mantle cell and not CLL (which may be a reflection of CD20 brightness in mantle cell)
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What is FMC7?
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Antibody recognizing a conformational epitope on CD20; typically negative in CD20 dim cell populations (such as CLL)
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Useful marker to distinguish reactive lymph node from follicular lymphoma?
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bcl-2 will be positive in germinal center of follicular lymphoma; germinal center will be negative in a reactive node (mantle zone is positive). Note that bcl-2 is not specific to FL; its main usefulness is in distinguishing FL from a reactive node.
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Name the four subtypes comprising AML with recurrent cytogenetic abnormalities.
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1. t(8;21)(q22;q22) - FAB M1-M2 2. inv(16)(p13q22) or t(16;16)(p13;q22) - FAB M4Eo 3. t(15;17)(q22;q12) - FAB M3/APL 4. AML with abnormalities of 11q23 (children, topo II inhibitor exposure)
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Approximate relative incidence of Hodgkin Lymphoma subtypes
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Hodgkin's Lymphomas make up about 30% of all lymphomas. NLPHL (5%), CHL (95% of HL), NSHL (70% of CHL), Mixed cellularity, Lymphocyte rich, Lymphocyte depleted (rarest CHL type).
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Avascular necrosis of a head of femur and proliferative retinopathy are suggestive of what hemoglobinopathy?
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SC disease
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HHV-8 is associated with what three diseases
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Kaposi's sarcoma, primary effusion lymphoma, and the systemic/plasmacytic variant of Castleman's.
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What is a hemoglobin Constant-Spring and how can it cause HBH disease
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HbCS is a termination codon mutant of alpha 2 chain producing an unstable alpha chain. In combination with two chain deletion in cis (SEA or Phil) in produces HBH disease due to low level of alpha 1 gene expression.
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Defects of MYH9 (chromosome 22q12-13) gene are associated with which syndromes?
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May-Hegglin anomaly, Epstein, Fechter and Sebastian syndromes all charactrerized by macrothrombocytopenias, and in case of MHA-Dohle body like inclusions (RNA) in granulocytes
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Where is the IgH locus?
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14q32
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retinoic acid is of use in which malignancy (and what is the translocation)?
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promyelocytic leukemia (PML): t(15;17) results in PML-RARA fusion protein, causing aberrant repression of retinoic acid receptor-mediated gene transcription
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Neoplasm assoc with t(9;22).
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most characteristic of CML; ABL at 9q34, BCR at 22q11. Also associated with some cases of ALL, especially in children, and imparts a worse prognosis.
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what neoplasm is associated with t(14;18)?
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follicular lymphoma (IgH-BCL2)
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Immunophenotypic distinction between characteristic neoplastic cells of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and classical HL (CHL).
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NLPHL (L&H cell = lymphocytic and histiocytic, AKA "popcorn cell") = CD20+, CD45+, EMA+, bcl-6+, CD15-, CD30-, background predominantly CD20+ B-cells, wreath-like CD3+ CD57+ cells surrounding L&H cells AND CHL (Reed-Sternberg cell) = CD15+, CD30+, fascin+, CD20-, CD45-, EMA-, background lymphs mostly T-cells
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Name the abnormality or syndrome: Neutrophils contain markedly abnormal "giant" cytoplasmic granules which are formed by the inappropriate fusion of lysosomes and endosomes.
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Chediak-Higashi syndrome, characterized by recurrent pyogenic infections of the respiratory tract and skin, partial albinism, and multiple neurologic abnormalities. Neutrophils contain markedly abnormal "giant" cytoplasmic granules which are formed by the inappropriate fusion of lysosomes and endosomes. Autosomal recessive defect of the LYST gene.
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Two Core binding factor related genes?
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RUNX1 and CBFB Rearrangements of these genes involved in AML. Secondary cooperating mutations include KRAS, NRAS, and KIT.
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most common cause of congenital hemolytic anemia Inheritance pattern?
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Congenital Spherocytosis. Autosomal dominant for most common variants Autosomal recessive for uncommon severe forms Mutations in proteins that stabilize membrane including spectrin, ankyrin, band3, protein 4.1 amd 4.2. Most common is ankyrin deficiency 60%, seconnd most common is spectrin beta chain 20%. Flow cytometry of eosin-malemide binding to band3 is a new test for HS (osmotic fragility is a classic test)
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