Neoplasia: therapy-related malignancy: practice question

A Pathology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pathology · Neoplasia: therapy-related malignancy

Sample item

A 24-year-old man treated for a testicular germ cell tumour with an etoposide-containing regimen develops acute myeloid leukaemia two years later. Cytogenetics shows an 11q23 (KMT2A) rearrangement, and there was no preceding myelodysplasia. Which statement best explains this leukaemia?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

A. Topoisomerase II inhibitor exposure, with short latency and no myelodysplastic phase

Therapy-related myeloid neoplasms follow two patterns. Topoisomerase II inhibitors such as etoposide and anthracyclines cause leukaemia after 1 to 3 years with balanced translocations involving 11q23 or 21q22 and no myelodysplastic phase. Alkylators cause leukaemia after 5 to 10 years, usually preceded by myelodysplasia with deletion of 5q or loss of chromosome 7.

Option by option

  • A. Topoisomerase II inhibitor exposure, with short latency and no myelodysplastic phase (correct)

    Short latency, KMT2A rearrangement and no myelodysplasia fit topoisomerase II inhibitor exposure.

  • B. Radiation exposure, with the BCR-ABL fusion at diagnosis

    BCR-ABL defines chronic myeloid leukaemia and is not the hallmark of therapy-related AML after etoposide.

  • C. Alkylating agent exposure, with long latency and preceding myelodysplasia with monosomy 7

    Alkylator-related disease has a long latency, myelodysplasia and monosomy 7 or deletion 5q, which does not match this case.

  • D. Antimetabolite exposure, with deletion of 5q and trilineage dysplasia

    Antimetabolites such as methotrexate are not the typical cause of therapy-related AML with 11q23 rearrangements.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Pathology question

What is the answer to this Pathology question?

The best answer is A, Topoisomerase II inhibitor exposure, with short latency and no myelodysplastic phase. Therapy-related myeloid neoplasms follow two patterns.

Why is "Radiation exposure, with the BCR-ABL fusion at diagnosis" not the answer?

BCR-ABL defines chronic myeloid leukaemia and is not the hallmark of therapy-related AML after etoposide.

Why is "Alkylating agent exposure, with long latency and preceding myelodyspl…" not the answer?

Alkylator-related disease has a long latency, myelodysplasia and monosomy 7 or deletion 5q, which does not match this case.

Why is "Antimetabolite exposure, with deletion of 5q and trilineage dysplasia" not the answer?

Antimetabolites such as methotrexate are not the typical cause of therapy-related AML with 11q23 rearrangements.

What concept does this question test?

It tests Neoplasia: therapy-related malignancy in Pathology. Topoisomerase II inhibitors such as etoposide and anthracyclines cause leukaemia after 1 to 3 years with balanced translocations involving 11q23 or 21q22 and no myelodysplastic phase. Alkylators cause leukaemia after 5 to 10 years, usually preceded by myelodysplasia with deletion of 5q or loss of chromosome 7.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Neoplasia: therapy-related malignancy?

Learn each disease as a bundle: cause, key histology, markers, and the clinical hallmark. Then use the flashcards and the other Pathology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.