A 64-year-old man has neck and abdominal lymph nodes that have grown rapidly over 6 weeks, with night sweats and an LD 4 times the upper reference limit. A node biopsy shows sheets of medium-to-large B cells: CD20+, CD10+, BCL6+, strong BCL2, Ki-67 about 90%, with CD5 and cyclin D1 negative. FISH with break-apart probes shows MYC rearranged, BCL2 rearranged and BCL6 not rearranged. Under the WHO 5th edition, how is this lymphoma classified?

DLBCL/HGBL with MYC and BCL2 rearrangements

Diffuse large B-cell lymphoma, NOS

In AML with inv(16)(p13.1q22) and the CBFB::MYH11 fusion, the marrow film typically shows:

Abnormal eosinophils with large purple granules

Blasts with single, long, slender Auer rods

Promyelocytes with bundles of Auer rods

Blasts with cup-shaped nuclear indentations

A patient with chronic-phase CML has taken imatinib for 12 months. Quantitative RT-PCR reports BCR::ABL1 at 0.08% on the International Scale (IS). This result indicates:

Treatment failure; check for ABL1 mutations

Loss of complete hematologic response

Deep molecular response (MR4.5)

Molecular and cytogenetic testing (WHO abnormalities, BCR::ABL1, JAK2)

6 ASCP MLS practice questions on Molecular and cytogenetic testing (WHO abnormalities, BCR::ABL1, JAK2), part of Hematology. The first 6 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 64-year-old man has neck and abdominal lymph nodes that have grown rapidly over 6 weeks, with night sweats and an LD 4 times the upper reference limit. A node biopsy shows sheets of medium-to-large B cells: CD20+, CD10+, BCL6+, strong BCL2, Ki-67 about 90%, with CD5 and cyclin D1 negative. FISH with break-apart probes shows MYC rearranged, BCL2 rearranged and BCL6 not rearranged. Under the WHO 5th edition, how is this lymphoma classified?
1. ADiffuse large B-cell lymphoma, NOS
2. BBurkitt lymphoma
3. CBlastoid mantle cell lymphoma
4. DDLBCL/HGBL with MYC and BCL2 rearrangements
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Answer: D · DLBCL/HGBL with MYC and BCL2 rearrangements
The tumor is a germinal-center B-cell lymphoma (CD10+, BCL6+) with rearrangements of both MYC and BCL2. The WHO 5th edition gives this its own category, diffuse large B-cell lymphoma/high-grade B-cell lymphoma with MYC and BCL2 rearrangements, often called double-hit; cases with MYC and BCL6 rearrangements no longer qualify. Burkitt lymphoma also has a MYC rearrangement and a very high Ki-67, but it lacks a BCL2 rearrangement and BCL2 protein is weak or absent. DLBCL, NOS is used only when the double rearrangement is absent, and mantle cell lymphoma is CD5+ and cyclin D1+ with t(11;14). Because double-hit lymphomas behave aggressively, FISH for MYC and BCL2 is part of the workup of large B-cell lymphomas.
- A: DLBCL, NOS is used only when the MYC and BCL2 double rearrangement is absent.
- B: Burkitt lymphoma has a MYC rearrangement but no BCL2 rearrangement, and BCL2 protein is weak or absent.
- C: Mantle cell lymphoma is CD5+ and cyclin D1+, with t(11;14).
Question 2 · Medium
Which B-cell neoplasm is defined by t(11;14)(q13;q32) with strong cyclin D1 expression?
1. AFollicular lymphoma
2. BMantle cell lymphoma
3. CChronic lymphocytic leukemia
4. DMarginal zone lymphoma
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Answer: B · Mantle cell lymphoma
The t(11;14) moves CCND1, the cyclin D1 gene, next to IGH, and the excess cyclin D1 pushes cells through the G1 phase of the cell cycle. It is the defining lesion of mantle cell lymphoma, which often spills into the blood. Like CLL, mantle cell lymphoma is CD5 positive, but it is usually CD23 negative and cyclin D1 or SOX11 positive. The same translocation occurs in some plasma cell myelomas.
- A: Follicular lymphoma carries t(14;18) with BCL2 overexpression.
- C: CLL does not carry t(11;14) and is usually CD23 positive.
- D: Marginal zone (MALT) lymphoma is linked to t(11;18), not t(11;14).
Question 3 · Easy
Which lymphoma is characterized by t(8;14)(q24;q32), which places MYC next to the immunoglobulin heavy chain gene?
1. AFollicular lymphoma
2. BBurkitt lymphoma
3. CMarginal zone lymphoma
4. DMantle cell lymphoma
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Answer: B · Burkitt lymphoma
In Burkitt lymphoma, MYC on chromosome 8 is moved next to IGH on chromosome 14, so MYC is driven by the active immunoglobulin enhancer and the cells divide very fast. Less common variants move MYC next to the kappa (t(2;8)) or lambda (t(8;22)) light chain genes. Cells in the blood or marrow are medium-sized with deep blue, vacuolated cytoplasm. The tumor grows quickly and needs urgent treatment.
- A: Follicular lymphoma carries t(14;18), which activates BCL2.
- C: Marginal zone (MALT) lymphoma is linked to t(11;18), not t(8;14).
- D: Mantle cell lymphoma carries t(11;14), which activates cyclin D1.
Question 4 · Medium
In AML with inv(16)(p13.1q22) and the CBFB::MYH11 fusion, the marrow film typically shows:
1. ABlasts with single, long, slender Auer rods
2. BPromyelocytes with bundles of Auer rods
3. CBlasts with cup-shaped nuclear indentations
4. DAbnormal eosinophils with large purple granules
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Answer: D · Abnormal eosinophils with large purple granules
inv(16) or t(16;16) joins CBFB with MYH11, one of the two core-binding factor leukemias. The marrow usually has a myelomonocytic picture with increased abnormal eosinophils whose immature granules are large and purple-violet. Like t(8;21), it carries a relatively favorable prognosis. The fusion can be hard to see on a karyotype, so FISH or RT-PCR is used to confirm it.
- A: Single, long, slender Auer rods are typical of AML with RUNX1::RUNX1T1.
- B: Bundles of Auer rods (faggot cells) are typical of APL with PML::RARA.
- C: Cup-shaped blast nuclei are associated with NPM1-mutated AML.
Question 5 · Hard
A patient with chronic-phase CML has taken imatinib for 12 months. Quantitative RT-PCR reports BCR::ABL1 at 0.08% on the International Scale (IS). This result indicates:
1. ATreatment failure; check for ABL1 mutations
2. BLoss of complete hematologic response
3. CMajor molecular response
4. DDeep molecular response (MR4.5)
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Answer: C · Major molecular response
The International Scale sets a standardized baseline at 100%, and a major molecular response (MR3) is a BCR::ABL1 level of 0.1% or less, a 3-log reduction. At 12 months of therapy, this is the optimal milestone in European LeukemiaNet guidance. Deeper responses are lower still: MR4 is 0.01% or less and MR4.5 is 0.0032% or less. A rising level on repeat testing prompts ABL1 kinase domain mutation testing.
- A: Failure at 12 months is a level above 1%.
- B: A level this low reflects a response far deeper than hematologic remission.
- D: MR4.5 requires a level of 0.0032% or less.
Question 6 · Hard
Under the WHO 5th edition, a 50-year-old's marrow shows 12% myeloblasts, some with long, slender Auer rods. The karyotype is 46,XY,t(8;21)(q22;q22.1)[20]. The correct classification is:
1. AAML with RUNX1::RUNX1T1 fusion
2. BCML in myeloid blast phase
3. CMDS with increased blasts (MDS-IB2)
4. DAML with CBFB::MYH11 fusion
Answer and explanation in LearnFree account

Molecular and cytogenetic testing (WHO abnormalities, BCR::ABL1, JAK2)

Which B-cell neoplasm is defined by t(11;14)(q13;q32) with strong cyclin D1 expression?

Which lymphoma is characterized by t(8;14)(q24;q32), which places MYC next to the immunoglobulin heavy chain gene?

In AML with inv(16)(p13.1q22) and the CBFB::MYH11 fusion, the marrow film typically shows:

A patient with chronic-phase CML has taken imatinib for 12 months. Quantitative RT-PCR reports BCR::ABL1 at 0.08% on the International Scale (IS). This result indicates:

Under the WHO 5th edition, a 50-year-old's marrow shows 12% myeloblasts, some with long, slender Auer rods. The karyotype is 46,XY,t(8;21)(q22;q22.1)[20]. The correct classification is: