In recent years, computerized image analysis has been widely used in histology and cytology in order to examine tissue differentiation, for tumor classification [11, 12, 15–17] and for the search of new prognostic variables in neoplasias [18–20]. This approach has also been used in basic research for analyzing nuclear texture changes that reflect chromatin remodeling of cells after incubation with carcinogens , hormones  and therapeutic agents [23, 24].
Chromatin remodeling, which is primarily due to epigenetic events, can be found during cell differentiation or malignant transformation [20, 21, 23, 24, 26]. In normal hemopoiesis, gene expression during normal cell maturation is controlled by genetic and epigenetic changes . Blast cells in acute myeloid leukemia and MDS always present epigenetic abnormalities and their DNA methylation signature is different to that of any stage of normal myeloid maturation, an observation which permits to distinguish normal and leukemic blasts [30–33].
In the present study we examined the utility of computerized chromatin texture analysis for the diagnosis of normal and atypical immature myeloid precursors in routine BM smears. In normal BM, all except three of the quantitative features examined, presented significant differences between blasts and promyelocytes. Thus, chromatin texture analysis in routine BM cytology is able to define cells in early stages of myeloid maturation.
In MDS, genetic and epigenetic alterations provoke abnormalities of proliferation, maturation, and apoptosis [5, 6, 32–34], which, of course, are reflected in subtle alterations of the chromatin structure. The expression of various lineage and maturation-related membrane proteins may be discordant in granulopoietic precursors [32–34] provoking also morphological atypias. All these alterations hamper the cell classification. The difficulties in classify several cases with MDS are well known. The European LeukemiaNet created a consensus-based cell library elaborated by experienced morphologists and downloaded it in the Internet . Its purpose is to be a guide for daily work and training. Furthermore, it is still recommended that the morphologic diagnosis of MDS should be achieved by a consensus of two experienced morphologists [3, 6]. Our study underlines these problems of classification. The cells diagnosed as atypical immature myeloid precursors in the present study did not - on light microscopic examination - reveal a Golgi apparatus, and would be therefore morphologically classified as blasts. However, the nucleus showed features more close to that of promyelocytes or nuclei of an "intermediate" state between blasts and promyelocytes.
Computerized texture analysis confirmed this subjective impression, since 4 features presented intermediate values between blasts and promyelocytes and 6 variables pointed out a similarity with nuclei of promyelocytes. Although the cytoplasm in these atypical cells still reveals characteristics of a blast, the nuclear structure is more similar to a promyelocyte, thus indicating an asynchronous maturation in MDS patients.
The existence of this intermediate maturation stage is of clinical importance. Cytologists basing their diagnosis mainly on cytoplasmic criteria will count these atypical immature cells together with blasts and thus increase the blast count. Other observers, emphasizing the similarity of the nuclear features, might count them together with promyelocytes, or count them separately, thus diminishing the blast count. This may imply in a different classification for the patient.
The BM blast count is considered very important for the classification of MDS in the revised WHO classification  as well as for the determination of the IPSS and WPSS scores [2, 31, 32]. Furthermore, the blast count is considered to be an independent prognostic feature of utmost importance in MDS [2, 6, 7, 33, 35–37]. Therefore, additional pathophysiological and molecular studies should be performed in order to investigate whether these atypical precursor cells should not be counted as blasts, as suggested by our investigation.