Karyotyping, widely used in various clinical settings, is a fundamental tool for identifying genetic aberrations of either germline or somatic origin. In the diagnosis of hematologic neoplasms, it serves as a solid foundation for investigations in suspected cases of acute and chronic leukemias, myelodysplastic syndromes, among others. However, when analyzing the complete genomic content of an individual, incidental findings may arise. Even when the sample analyzed has high diagnostic value — such as bone marrow — it is possible, albeit rarely, for the identified alterations to be of germline origin, not necessarily associated with a neoplastic process. These findings become particularly relevant given the lack of systematic genomic screening in the general population, which may lead to the unexpected identification of previously unknown constitutional variants.

To identify and describe constitutional cytogenetic abnormalities unrelated to hematologic neoplasms in patients referred for oncohematological karyotyping.

Over a nine-month period, a total of 3,822 oncohematological karyotype tests were performed at Flow Diagnósticos. For this study, individuals were selected based on complementary tests — such as immunophenotyping and bone marrow morphology — that did not show significant abnormalities. Bone marrow samples were processed for oncohematological karyotyping as part of the routine diagnostic workup for suspected neoplasms. To clarify the origin of certain findings, a second karyotype was performed using phytohemagglutinin stimulation, aimed at constitutional genetic analysis. Comparison of the two tests enabled a better understanding of the nature of the identified genetic aberration.

In five patients, cytogenetic abnormalities were found involving the sex chromosomes (X and Y). One patient presented a structural alteration consistent with a Robertsonian translocation. Additionally, 14 individuals were referred to the laboratory with previously identified constitutional abnormalities, with trisomy 21 being the most frequent and well-documented finding in the literature. In total, 0.4% of the individuals referred for oncohematological karyotyping exhibited genetic aberrations unrelated to hematologic malignancies.

Clinical investigation of suspected hematologic disorders requires an integrated analysis of bone marrow samples, including cell morphology, immunophenotyping, and karyotyping. It is the combination of these tests that allows for a more accurate and reliable diagnostic approach in identifying hematologic neoplasms. In the cases analyzed, all genetic alterations were confirmed to be germline, exhibiting a non-clonal profile, often representing incidental findings. Proper interpretation of these variants — supported by consultation of public databases describing known aneuploidies and classical chromosomal abnormalities — is essential for correct clinical classification. The trained assessment by a qualified professional is equally important. Accurate characterization of these findings was crucial for guiding clinical decision-making and avoiding unnecessary treatments aimed at non-neoplastic genetic alterations.