Correlation of cytomorphology and histopathology in the diagnostic process of myeloid malignancies

Bone marrow cytomorphology and histopathology are the cornerstones for the initial diagnosis of myelodysplastic syndromes (MDS) and other related myeloid disorders. They provide a rapid first insight into diagnostic categories and thus help in clinical decision making. However, difficulties in the morphologic assessment of MDS exist due to inter- and intra-observer variability. In this study, we directly compared the results of cytomorphology and histopathology obtained in a real-world diagnostic scenario in 90 patients with myeloid malignancies aiming to evaluate their validity for diagnosing and classifying various myeloid malignancies. While both techniques placed 80% of our bone marrow samples into the same diagnostic category and thus showed a good correlation, our study also demonstrates the limitations in correlating marrow cytomorphology and histopathology, even following stringent and repetitive diagnostic assessments. This was particularly true for CMML, where not only additional diagnostic tools such as molecular genetics or clinical evaluation but also the analysis of the peripheral blood smears aided in finding the correct diagnosis. Overall, our data emphasize the need for a comprehensive diagnostic review in a patient-for-patient setting when a myeloid malignancy is suspected or confirmed. We propose that the combination of cytomorphologic and histopathologic assessment with clinical, laboratory, and genetic parameters is essential in achieving high diagnostic accuracy in an interdisciplinary setting

CDKN1B, encoding the cyclin-dependent kinase inhibitor 1B (p27), is located in the minimally deleted region of 12p abnormalities in myeloid malignancies and its low expression is a favorable prognostic marker in acute myeloid leukemia

The online version of this article has a Supplementary Appendix. Background Alterations of the short arm of chromosome 12 (12p) occur in various hematologic malignancies and ETV6 and CDKN1B, which are located on 12p, have been implicated as leukemogenic genes of interest. Design and Methods We selected seven patients with myeloid malignancies and small 12p deletions detected by fluorescence in situ hybridization encompassing only the region centromeric of ETV6 and further evaluated them by single nucleotide polymorphism microarrays. Results The minimally deleted region contained only nine genes. These genes were subsequently analyzed by microarray expression profiling in an independent cohort of 781 patients, most, but not all, of whom had different hematologic malignancies CREBL2, MANSC1, and CDKN1B were expressed in more than 25% of cases, while the other six genes were expressed in only a minority of cases. As CDKN1B is a cell cycle regulator and functions as a tumor suppressor gene, this gene was selected for further expression studies in 286 patients with acute myeloid leukemia. When comparing patients with low CDKN1B expression (expression level <1,160; 1 st quartile) with those with intermediate or high expression (2 nd -4 th quartiles), certain mutations were observed more frequently in the former: RUNX1-RUNX1T1 (11/83, 13.3% versus 5/203; 2.5%; P=0.001), PML-RARA rearrangements (11/83, 13.3% versus 4/203, 2.0%; P<0.001), 11q23/MLL rearrangements (6/83, 7.2% versus 4/203, 2.0%; P=0.038), and FLT3-TKD mutations (7/63, 11.1% versus 6/167, 3.6%; P=0.047). The median overall survival of patients with low CDKN1B expression was longer than that of patients with intermediate/high expression (not reached versus 14.9 months; P=0.005). Likewise, patients with low CDKN1B expression had a longer event-free survival than those with intermediate/high expression (31.0 versus 9.7 months; P=0.013). Conclusions CDKN1B is an interesting candidate gene as a potential biomarker for prognostication in acute myeloid leukemia. Key words: 12p deletion, ETV6, CDKN1B, acute myeloid leukemia (AML), prognosis. leukemia. Haematologica 2011;96(6):829-836. doi:10.3324/haematol.2010 CDKN1B, encoding the cyclin-dependent kinase inhibitor 1B (p27), is located in the minimally deleted region of 12p abnormalities in myeloid malignancies and its low expression is a favorable prognostic marker in acute myeloid leukemia Citation: Haferlach C, Bacher U, Kohlmann A, Schindela S, Alpermann T, Kern W, Schnittger S, and Haferlach T. CDKN1B, encoding the cyclin-dependent kinase inhibitor 1B (p27), is located in the minimally deleted region of 12p abnormalities in myeloid malignancies and its low expression is a favorable prognostic marker in acute myeloi