UNRAVELING RARE CASES IN ACUTE MYELOID LEUKEMIAS: THE SIGNIFICANCE OF SPECIALIZED REMOTE LABORATORIES IN HEMATOLOGICAL DIAGNOSIS

Abstract

Introduction: The diagnosis of onco-hematologic conditions in medical and hospital settings typically involves relying on centralized reference laboratories for investigative and clinical-laboratory diagnostic support. However, Flow Diagnostics is a specialized remote laboratory in oncology-hematology that has implemented a unique approach utilizing reflex testing methodology and real-time medical advisory services for all partnering facilities. Methods and results: Between January and May 2023, our remote oncology-hematology laboratory conducted immunophenotyping investigations using flow cytometry on 1862 cases. Among these, 1378 (75%) cases were aimed at investigating or diagnosing hematological diseases, while 474 (25%) cases were dedicated to measurable residual disease research. Among the 1378 cases subjected to immunophenotyping, we diagnosed 154 cases of acute myeloid leukemia (AML), including 18 (11.7%) cases identified as acute promyelocytic leukemia (APL) within the AML cohort. One particular APL case drew significant attention: a 31-year-old male patient presenting with a history of anemia and gum bleeding. The analysis of the complete blood count revealed severe pancytopenia (hemoglobin: 6 g/dL; WBC: 39,600 with 90% blast-like cells; platelets: 26,000/mm3), alongside a history of repeated blood transfusions. The patient experienced respiratory decompensation. Immunophenotyping analysis conducted via flow cytometry identified cells exhibiting moderate CD45 expression and moderate-to-high internal complexity. These cells accounted for 85.8% of the total analyzed cells, representing the blasts, and displayed the following positive phenotype for the markers: CD2 (weak), CD13 (heterogeneous), CD33 (strong, homogeneous), CD34 (moderate), CD45 (moderate), CD64 (moderate), CD117 (weak), and cMPO (strong). The cells were negative for CD4, CD11b, CD14, CD15, CD16, CD56, CD123, and HLA-DR. To further support the laboratory investigation, our reflex testing algorithm included qualitative detection of PML-RARA transcripts, prompting the medical advisory team to seek authorization from the clinical medical staff for performing the molecular biology test. Real-time PCR analysis confirmed the presence of the PML-RARA BCR3 transcript, indicating a positive result. The presence of the PML-RARA BCR3 transcript, in conjunction with weakly positive CD2 and moderately positive CD34 markers, is consistent with microgranular APL. Conclusions: This aforementioned case serves as a proof of concept for the value added by specialized remote laboratories, automated reflex testing methods, and real-time medical advisory services in the field of oncology-hematology. This approach enables the identification of rare and specific cases, such as CD34+ APL, reduces the turnaround time between investigative procedures and laboratory diagnosis, and ultimately decreases the overall cost of the diagnostic process.