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September 2023 – Cytogenetics & Hematopathology

By MCL Education • September 8, 2023

A 55-year-old man was referred for pancytopenia with several months of increasing fatigue and increased frequency in infections. FISH studies, chromosomal analysis, and flow cytometry are shown in Figure 1, Figure 2, and Figure 3, respectively. Histopathologic findings on peripheral blood demonstrated atypical promyelocytes with kidney shaped nuclei, purple cytoplasm, and Auer rods. On banded analysis, of 20 metaphases, 12 demonstrated the abnormality highlighted by arrows in Figure 2. T-cell gene rearrangement and eosinophil panel were both negative.

Based on histopathologic evaluation and supplementary studies, what is the most likely diagnosis?

Acute lymphoblastic leukemia
Acute myeloid leukemia with monocytic differentiation
Acute promyelocytic leukemia
Acute basophilic leukemia

The correct answer is ...

Acute promyelocytic leukemia.

Flow cytometry (images above) identified blasts that express CD34 (dim), CD45 (dim), CD13, CD15 (dim), CD33, CD117, signifying a myeloid differentiation. The FISH studies and chromosomal analysis (images above) both demonstrate a translocation between chromosomes 15 and 17, more specifically t(15;17)(q24.1;q21.2). These in combination with the histomorphology features are diagnostic of acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) that has abnormal maturation of promyelocytes. It is defined by its fusion of the PML gene and the RARA gene mostly by t(15;17)(q24.1;q21.2). APL typically occurs in the age range of 20-59 and represent about 5%-8% of AML in younger patients.^(2,4) Histologic features show bilobed or kidney-shaped nuclei and Auer rods. Cytoplasm can be bright pink, red, or purple. Patients with this diagnosis have a 10%-20% risk of relapse.

APL can have a variety of clinical manifestations including weakness, fatigue, infection, or pancytopenia. It is important for APL to be diagnosed and treated quickly, as one of the most important complications to be aware of is the risk of coagulopathy and disseminated intravascular coagulation, which can lead to death if untreated.

References

Acute promyelocytic leukaemia (APL) side effects. Blood Cancer UK. Accessed May 23, 2023. https://bloodcancer.org.uk/understanding-blood-cancer/leukaemia/acute-promyelocytic-leukaemia/apl-treatment-side-effects/apl-side-effects/.
Amoth H, Perry AM. APL with PML::RARA. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/leukemiaapl.html. Accessed May 19, 2023.
Jimenez JJ, Chale RS, Abad AC, Schally AV. Acute promyelocytic leukemia (APL): a review of the literature. Oncotarget. 2020;11(11):992-1003. Published 2020 Mar 17. doi:10.18632/oncotarget.27513.
Platzbecker U, Khoury J, Akkari Y, et al. Myeloid proliferation and neoplasms. In: WHO Classification of Tumours Editorial Board. Haematolymphoid tumours [Internet; beta version ahead of print]. Lyon (France): International Agency for Research on Cancer; 2022 [cited 2023 05 16]. (WHO classification of tumours series, 5th ed.; vol. 11). Available from: https://tumourclassification.iarc.who.int/chapters/63.