I. Introduction
Myeloproliferative neoplasms (MPNs) are neoplastic disorders of bone marrow hematopoietic stem cells, in which the hematopoietic cells proliferate abnormally. Philadelphia-chromosome-negative (Ph-negative) MPNs, one of pathological subgroups of MPNs, mainly comprise polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). For PV, ET and PMF, the annual incidence rates ranges from 0.01 to 2.61, 0.21 to 2.27, and 0.22 to 0.99 per 100,000 population, respectively [1]. These Ph-negative MPN diseases exhibit a varied but partially overlapping set of clinical and cytomorphological features. This inevitably makes the task of objectively classifying a bone marrow trephine biopsy sample into one of the above Ph-negative MPN diseases quite challenging in some cases [2]– [7]. In order to create a standard set of pathologic measurements that aid in distinguishing the three diseases of Ph-negative MPNs in routine clinical diagnosis, the World Health Organization (WHO) has established a set of diagnostic guidelines to associate clinical diagnostic data with observed histological and cytological features and molecular-genetic findings [4]– [7]. The present guidelines clearly show that morphological features play a key role in diagnosis and classification. This, however, may cause low reproducibility of diagnostic results and inter-observer variability among hematopathologists [5], [6]. In an attempt to resolve these challenges, computer-assisted diagnosis (CAD) techniques can be introduced to assist pathologists in classifying the different subtypes of Ph-negative MPNs efficiently and objectively by using digital pathology images [8], [9]. Here, trephine histology is used to help in the identification of these bone marrow diseases with CAD techniques. Trephine histology examination is one of the bone marrow examinations and suitable for representing core bone marrow biopsy specimens. Trephine histology allows a complete assessment of bone marrow structure and of the pattern of distribution of any abnormal infiltrate [2] , [3], [5]. The staining protocol used in trephine histology, namely Hematoxylin and Eosin (H&E) staining, is a fairly standard protocol used worldwide.