Answer
The cytogenetic abnormalities that are myelodysplastic syndrome (MDS) related and are sufficient to categorize acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MRC) (even without morphologic evidence of dysplasia) are as follows:
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Complex karyotype: Three or more unrelated abnormalities, none of which include the recurrent cytogenetic abnormalities encountered in AML [7]
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Unbalanced abnormalities: -7/del(7q), -5/del(5q), i(17q)/t(17p), -13/del(13q), del(11q), del(12p)/t(12p), and idic(X)(q13) [1]
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Balanced abnormalities: t(11;16)(q23;p13.3), t(3;21)(q26.2;q21.2), t(1;3)(p36.3;q21.1), t(2;11)(p21;q23), t(5;12)(q33p13.2t(5;7)(q33q11.2), t(5;17)(q33p13.2 t(5;10)(q33q21), and t(3;5)(q25;q34) [1]
Cases of AML with NPM1 or biallelic CEBPA mutations as the only genetic alterations are classified separately, even if morphologic evidence of dysplasia is present. [1, 8, 9]
A variety of MDS-associated mutations, including those involving U2AF1, ASXL1, and TP53, have been reported to be more common in AML-MRC than in AML not otherwise specified (AML-NOS). [2] TP53 mutations are frequently associated with a complex karyotype. [16] PIGN gene expression aberration appears to be associated with genomic instability and leukemic progression in AML-MRC. [17] This gene may play an essential role in regulating mitotic integrity to maintain chromosomal stability and preventing leukemic transformation/progression.
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). This image depicts dysgranulopoiesis: hypogranulosis.
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). This image displays dysgranulopoiesis: vacuolization. Image courtesy of Rector and Visitors of the University of Virginia.
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). Dysgranulopoiesis demonstrating Chediak-Higashi-like granules (arrow) is shown.
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). Dyserythropoiesis is seen.
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). The bone marrow core biopsy evaluation reveals dysmegakaryopoiesis with numerous small hypolobated megakaryocytes.
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). Dysmegakaryopoiesis in the multinucleated form is noted.
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). This image reveals a dysplastic promyelocyte with a cytoplasmic vacuole (left), blast (center), and dysplastic neutrophil with pseudo-Pelger-Huet anomaly and hypogranularity (right).
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). Note the dysplastic neutrophil with large pseudo-Chediak-Higashi granules.
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). A dysplastic red blood cell with budding nuclei (left) is seen with a monocyte (center), and a blast (right).
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). Numerous dysplastic erythroid cells are seen, demonstrating nuclear budding, irregular nuclear contours, and multinucleation.
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). A cluster of dysplastic megakaryocytes with small hypolobated nuclei is seen on a bone marrow aspirate smear preparation.
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). Note the dysplastic neutrophil with large pseudo-Chediak-Higashi granules.
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). A posttreatment bone marrow evaluation (left) shows a hypercellullar marrow (hematoxylin and eosin) with small dysplastic megakaryocytes containing hypolobated nuclei (arrows), as well as clusters of medium to large blasts (circles) with dispersed chromatin, and prominent nucleoli located away from the bony trabeculae (ie, atypical localization of immature precursors [ALIP]). Immunohistochemistry shows CD34+ blasts (upper right) and strong nuclear staining of scattered marrow elements for p53 (lower right), each comprising about 10% of overall cellularity. These findings are consistent with persistent [posttherapy AML-MRC with high p53 expression by immunohistochemistry. A TP53 mutation was confirmed on molecular genetic analysis performed concurrently.
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). Dysgranulopoiesis demonstrating Chediak-Higashi-like granules (arrow) is shown.
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Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). The bone marrow aspirate shows a binucleate erythroid precursor.
