MLT GlobeHematology: WBC disorders & leukemias – page 4
145 Hematology MCQs on WBC disorders & leukemias with answers and explanations.
In polycythemia vera, serum erythropoietin is typically:
The JAK2-mutant clone proliferates independently of erythropoietin, and feedback suppresses EPO. A high EPO points to secondary erythrocytosis such as hypoxia or renal tumors.
A 32-year-old with acute leukemia develops prolonged PT and aPTT, low fibrinogen and raised D-dimer at diagnosis. Blasts contain many granules and bundles of Auer rods. Which genetic change is most likely?
Heavily granular promyelocytes with bundles of Auer rods ('faggot cells') plus DIC is classic acute promyelocytic leukemia, defined by t(15;17) PML::RARA. Granule procoagulants trigger DIC, which is why APL is a medical emergency.
A patient has a WBC of 60 × 10^9/L with a left shift. Which result best supports a leukemoid reaction rather than chronic myeloid leukemia?
Neutrophils in a leukemoid reaction (infection, inflammation) are activated and have a high LAP score. In CML the LAP score is characteristically low. Basophilia, splenomegaly and BCR::ABL1 all favour CML.
Mononuclear cells with fine cytoplasmic projections are found in a patient with pancytopenia and splenomegaly. Which cytochemical stain is classically positive in these cells?
The 'hairy' projections plus pancytopenia and splenomegaly point to hairy cell leukemia, whose cells are TRAP positive. Today flow cytometry (CD11c, CD25, CD103) and BRAF V600E testing are also used.
Blasts are positive for non-specific esterase (alpha-naphthyl acetate), and the staining disappears when sodium fluoride is added. The blasts are most likely:
Monocytic cells stain strongly with non-specific esterase, and this activity is inhibited by sodium fluoride. Granulocytes are positive for specific esterase (naphthol AS-D chloroacetate) instead.
Gum hypertrophy and skin infiltration at diagnosis of acute leukemia are most typical of which type?
Leukemic monocytes readily leave the blood and infiltrate tissues such as gums, skin and the CNS. Gingival hyperplasia is a classic clinical clue to acute monocytic or myelomonocytic leukemia.
According to the WHO classification, the usual minimum blast percentage in blood or bone marrow for a diagnosis of acute myeloid leukemia is:
WHO sets the threshold at 20% blasts (the older FAB system used 30%). AML with certain defining genetic changes, such as t(15;17) or t(8;21), can be diagnosed below 20%.
A mutation found in about 95% of patients with polycythemia vera is:
JAK2 V617F (or, less often, a JAK2 exon 12 mutation) is present in nearly all cases of PV. CALR and MPL mutations are seen in essential thrombocythemia and primary myelofibrosis; FLT3-ITD is an AML mutation.
Teardrop cells, nucleated RBCs with immature granulocytes (a leukoerythroblastic picture) and a 'dry tap' on marrow aspiration suggest:
In primary myelofibrosis, marrow fibrosis blocks aspiration (dry tap) and forces haematopoiesis to the spleen and liver, releasing teardrop cells and immature cells into the blood.
Atypical lymphocytes with folded, 'cerebriform' nuclei in the blood of a patient with a generalized red skin rash suggest:
Sézary cells are malignant CD4+ T cells with convoluted cerebriform nuclei. Sézary syndrome is the leukemic form of cutaneous T-cell lymphoma, with erythroderma and lymphadenopathy.
A sustained platelet count above 450 × 10^9/L with large platelets, no reactive cause and a CALR mutation is most consistent with:
Essential thrombocythemia is an MPN with persistent thrombocytosis (at least 450 × 10^9/L) and a JAK2, CALR or MPL mutation in most patients. Reactive causes such as iron deficiency, infection or surgery must be excluded first.
In CML monitoring by RQ-PCR, a major molecular response (MMR) is defined as a BCR::ABL1 level on the International Scale of:
MMR (MR3) is a 3-log reduction, i.e. BCR::ABL1 ≤0.1% IS. ≤1% corresponds roughly to complete cytogenetic response, and ≤0.0032% is the deeper MR4.5.
A patient has erythrocytosis, low serum erythropoietin and a negative JAK2 V617F test. Which additional test is most useful to support polycythemia vera?
About 3% of PV cases lack V617F but carry JAK2 exon 12 mutations. CALR and MPL mutations are found in ET and PMF, not PV.
Multifocal dense aggregates of spindle-shaped mast cells in marrow, aberrant CD25 expression and serum tryptase above 20 ng/mL point to systemic mastocytosis. Which mutation is typical?
KIT D816V is found in most adults with systemic mastocytosis and is a diagnostic criterion. JAK2 and MPL mutations drive classic MPNs.
An elderly woman has macrocytic anemia, normal-to-high platelets, <5% marrow blasts and hypolobated megakaryocytes. Karyotype shows a single deletion of 5q. This subtype of MDS is known for:
MDS with isolated del(5q) has a relatively good prognosis and responds well to lenalidomide. ATRA is used for APL, not MDS.
In the WHO 5th edition, a low-blast myelodysplastic neoplasm with ring sideroblasts is defined mainly by a mutation in which gene?
SF3B1 mutations are strongly linked to ring sideroblasts; WHO 5th names this entity MDS with low blasts and SF3B1 mutation. NPM1 mutation defines an AML type.
AML showing monocytic and granulocytic blasts plus abnormal eosinophils with large purple-violet granules is associated with:
inv(16)/t(16;16) gives myelomonocytic AML with abnormal eosinophils and carries a favorable prognosis. t(15;17) is APL with hypergranular promyelocytes.
A 25-year-old has AML with maturation. Blasts contain single long, slender Auer rods and there is a salmon-pink perinuclear hof. Which genetic finding is most likely?
t(8;21) RUNX1::RUNX1T1 typically shows AML with maturation, long thin Auer rods and good prognosis. KMT2A::AFF1 is mainly seen in infant B-ALL.
In AML with a normal karyotype, which mutation is linked to a higher relapse risk and is a target for specific kinase inhibitors?
FLT3-ITD is associated with a higher relapse risk and is targeted by FLT3 inhibitors such as midostaurin, gilteritinib and quizartinib; under ELN 2022 it is classed as intermediate risk regardless of allelic ratio. NPM1 mutation without FLT3-ITD and in-frame bZIP CEBPA mutations are favorable, and IDH2 is targeted by an IDH inhibitor, not a kinase inhibitor.
A 2-year-old with Down syndrome has blasts with cytoplasmic blebs, MPO negative, and marrow fibrosis. Flow cytometry is likely to show positivity for:
This is acute megakaryoblastic leukemia, common in young children with Down syndrome; blasts express platelet glycoproteins CD41 (GPIIb) and CD61 (GPIIIa). CD14/CD64 indicate monocytic lineage.