Acute promyelocytic leukemia presented as a relapse of acute myeloid leukemia

Abstract

myelocytes to segmented neutrophils, 9% eosinophils, 5% monocytes, 42% erythroid precursors, 21% lymphocytes, and 6% plasma cells. Interestingly, many mature and immature eosinophils were present with large coarse basophilic granules, abnormal nuclear segmentation, and occasional cytoplasmic vacuoles ( Fig. 1D-F). In addition, mild dysgranulopoiesis was noted. A CD34 immunohistochemical stain demonstrated the absence of blasts in the BM biopsy (inlet in Fig. 1C). PDGFRA and PDGFRB translocations were negative by fluorescent in situ hybridization (FISH). BCR/ABL1 fusion transcripts and KIT (exons 8 and 17) mutations were negative by polymerase chain reaction (PCR). Cytogenetic testing showed a 46 XY, inv(16)(p13.1q22),add(18)(p11.3) [5]/46,XY [15] karyotype (Fig. 1A). FISH analysis using break-apart probes in the BM cells confirmed the presence of CBFB/MYH11 translocation in 53 of 200 (27%) interphase nuclei (Fig. 1B). A comprehensive screening of the mutational profile of this patient was conducted on the PB mononuclear cells using a multiplexed targeted gene panel including 53 commonly mutated genes in myeloid neoplasms. Mutational analysis demonstrated mutations in KRAS (c.38G>A, p.Gly13Asp; 34.9%) and PRPF40B (c.2347C>T, p.Arg783Trp; 48.8%) genes. The patient fulfilled the criteria for a diagnosis of AML with inv (16) KIT, FLT3 and RAS [4,5]. The presence of a KRAS mutation in our patient is in agreement with other studies where secondary genetic lesions specifically in the RAS family of genes have been described in patients with AML with inv(16) and led to the hypothesis that these alterations represent cooperative secondary events with the CBFB/MYH11 translocation [5,6]. Several components of the RNA splicing machinery including PRPF40B have been found mutated in AML [7]. Eosinophilia can be related to other myeloid or lymphoid neoplasms. Eosinophils in abnormal PDGFRA, PDGRFB or FGFR1-related neoplasms or chronic myelomonocytic leukemia resemble normal eosinophils. Eosinophils in chronic eosinophilic leukemia can show a wide range of normal to abnormal eosinophils including vacuoles, atypical segmentation, sparse granules, or sometimes Charcot-Leyden crystals.Low blast counts (less than 20%) in AML patients with inv(16), t(8;21)(q22;q22) and t(15;17)(q22;q12) have been described in the literature. In a recent study of 208 cases of AML with inv(16)/t(16;16), Schwind et al. [1] found that BM blast percentages ranged from 2 to 89%.From a practical standpoint, it is not uncommon to detect blast percentages below 20% in AML with inv(16) or t(16;16) patients. However, to our knowledge this is the first described case of inv(16) associated AML with absent blasts in both PB and BM. In this case, the main morphologic clue which helped the clinical and morphologic classification of the patient was the presence of abnormal granules in eosinophilic precursors. In accordance with the WHO criteria, this case is classified as an AML despite the absence of myeloid blasts. Our report demonstrates that careful morphol...

Acute Myeloid Leukemia Acquiring Promyelocytic Leukemia-Retinoic Acid Receptor Alpha at Relapse

“…Acquisition of PML-RARA as relapsed AML is rarely reported in literature. To the best of our knowledge, we found only one similar case reported by Vitale et al In their case, it was hypothesized that there was a subclonal PML-RARA under detectable threshold and the subclone could have undergone selection during initial chemotherapy [5, 6]. Our patient also had acquisition PML-RARA as relapse of AML, after receiving 1 year of chemotherapy.…”