Minimal Diagnostic Value of Karyotyping for Suspected Myelodysplastic Syndrome in the Absence of Bone Marrow Dysplasia

BACKGROUND: Myelodysplastic syndrome (MDS) is a group of hematopoietic stem cell disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and cytopenias. Marrow morphology, cytogenetics, and sequencing panels are important for the diagnosis and prognosis of MDS and are often obtained in parallel for clinical workup. The diagnostic utility of time-consuming cytogenetic analyses in cases without any significant dysplasia is uncertain.

OBJECTIVE: We sought to determine the diagnostic utility of cytogenetic analysis of bone marrow aspirate/biopsies obtained for the indication of suspected MDS in the absence of morphological dysplasia.

METHODS: We identified bone marrow aspirate/biopsy cases obtained for the indication of suspected MDS between 2021-01-01 and 2022-06-22 from the Greater Vancouver Area, Canada that underwent cytogenetic analysis at clinical request. Anemia, neutropenia, and thrombocytopenia were defined as peripheral blood counts of hemoglobin <120 g/L for women or <130 g/L for men, neutrophils <2 x10⁹/L, and platelets <150 x10⁹/L, respectively.

RESULTS: Fifty-four cases met criteria for review (55.5% male sex; mean age = 62.6 years [SD = 16.6 years]). The mean (SD) peripheral blood count parameters for the cohort were: hemoglobin 108 g/L (22 g/L), mean corpuscular volume 94 fL (8 fL), neutrophil count 2.84 x10⁹/L (2.08 x10⁹/L), and platelet count 175 x10⁹/L (132 x10⁹/L). Anemia, neutropenia, thrombocytopenia, pancytopenia, and any cytopenia were present in 41 (75.9%), 23 (42.6%), 26 (48.1%), 13 (24.1%), and 48 cases (88.9%), respectively. For cases with anemia, neutropenia, or thrombocytopenia, the corresponding mean (SD) peripheral blood counts were: 99 g/L (18 g/L), 1.25 x10⁹/L (0.56 x10⁹/L), and 77 x10⁹/L (44 x10⁹/L), respectively. Marrow was hypocellular and hypercellular for age in 11 (20.4%) and 9 (16.7%) of the cases, respectively. The only abnormal karyotypes were 2 cases of loss of chromosome Y (3.7%; 70-year-old with 18/20 metaphases and 84-year-old with 14/20 metaphases). Both cases had no evidence of hematologic neoplasia, which is in keeping with an age-related finding. Additionally, targeted myeloid panel next-generation sequencing was performed for 8/54 cases for suspected myeloid neoplasm. There were: 3 cases with no reportable variants, 3 cases with variants of uncertain significance, and 2 cases with pathogenic TET2 variants. None of the cases with reportable variants identified were found in cases showing loss of chromosome Y.

CONCLUSION: This study suggests that in the absence of myeloid dysplasia of the bone marrow, there is minimal diagnostic value of cytogenetic analysis for the workup of suspected MDS.

No relevant conflicts of interest to declare.