7. Imaging as a diagnostic tool

around 20% of MS cases [1, 12]. NPM1 cytoplasmic and nuclear staining indicates NPM1 gene mutations. To exclude the possibility of lymphoma the tumors should be interrogated for different T and B lineage markers such as, CD3, CD20, and CD79a. Aberrant expression of B/T-cell markers is possible, however, if criteria for a mixed-lineage leukemia are fulfilled the case is not classified as MS according to WHO 2016. Particular antigenic constellations may

Myeloid Myeloperoxidase (MPO), CD33, CD68 (detected by KP1 monoclonal antibody but not by

Myelomonocytic Homogeneous expression of CD68 (KP1), while CD68 (PG-M1) and MPO in distinct

MS is also associated with several cytogenetic and chromosomal abnormalities (please see next section for detailed report). Consequently, fluorescence in situ hybridization (FISH) should be

Cytogenetic analysis conducted with bone marrow and peripheral blood blasts in MS patients has demonstrated cytogenetic abnormalities in more than 50% of instances [21]. Nonetheless, the rates of specific cytogenetic abnormalities associated with MS are rather diverse. Studies have elicited the frequent association of between MS and core binding factor (CBF) leukemia and AML with MLL rearrangements [22]. The most common chromosomal abnormality, t(8;21), is associated with pediatric MS or in patients with ocular involvement [21, 23, 24]. The second predominant chromosomal aberration associated with pediatric MS is inv16 [3, 25]. However, studies by Pileri et al. showed the relative rarity of t(8,21) in adult MS patients [21]. Instead, trisomy 8, monosomy 7 and MLL rearrangements constitute the majority of the cases [21]. The prevalence of inv16 was also not well documented in adult patients. In addition, other chromosomal aberrations including monosomy 5, 7 or 8 were reported in isolated cases. Nucleophosmin (NPM)-1 mutations have been reported to be in 15% of MS patients. This particular variant of MS elicits clinical attributes similar to NPM-1 positive AML and manifest primarily in M4 and M5 French American British (FAB) subclasses of AML [26]. NPM-1

more precisely define subtypes shown in Table 1.

Immunophenotypic

profiles

employed as a part diagnostic work up for patient stratification [20].

Most common markers

PG-M1), CD34, CD117

subpopulations Monoblastic CD68 (PG-M1), CD14, lacking MPO, CD163, CD11c

Megakaryoblastic CD61, von Willebrand factor Erythroid CD71, glycophorin A, glycophorin C

Table 1. Common immunophenotypes.

118 Hematology - Latest Research and Clinical Advances

Promyelocytic Myeloperoxidase (MPO), CD15, CD117, lacking CD34 and TdT

6. Cytogenetics and molecular genetics of myeloid sarcoma

Timely identification of MS has a significant impact on the treatment outcomes and achieving remission in case of AML. As often, these extramedullary tumors serve as sanctuary sites for future relapse. However, detection and simultaneous identification of MS is challenging. The standard AML diagnosis does not include MS, nor there are any specific diagnostic regimens for MS. Consequently, in majority of cases diagnosis of MS is either significantly delayed or remain undetected. In this context, multimodal imaging procedure can be beneficial for early detection of tumors [30]. This generally involves employment of traditional imaging techniques such as, positron emission tomography (PET), CT and MRI [25]. Particularly, in the last decades, PET/CT is becoming an essential tool for disease detection [25]. In this context, 18Ffluorodeoxygenase (18F-FDG)PET/CT has been recognized as a very potent instrument for the identification of not only leukemia but also extramedullary invasion of blast cells [8, 31, 32]. In a prospective study, Stölzel et al. have successfully employed whole-body 18F-FDG PET/CT in 94 AML patients, consisting of both newly diagnosed and relapsed cases of AML for detection of MS [33]. In a different study, Aschoff et al. have demonstrated the sensitivity of 18F-FDG PET/CT by reducing the number of false-positive associated with traditional PET imaging [34]. In addition, 18F-FDG PET/CT has also been able identify new sites of MS, which is not identified by traditional imaging techniques [8].

Although, encouraging, 18F-FDG PET/CT does have some restrictions. Several reports have shown that 18F-FDG PET/CT is not sensitive enough to pick up extramedullary infiltration in the soft tissues such as skin meninges and mucus membranes. In addition, 18F-FDG is not a tumor specific marker but rather depends on the glucose uptake by the cells [8]. As such, there is an increase chance of false-positive signals associated with 18F-FDG PET/CT specifically, in brain and kidney that have high basal glucose metabolism [9]. As an alternative, various groups have used 18F-fluorodeoxythymidine (FLT), a thymidine analogue and proliferating marker, as a tracer for PET/CT in place of 18F-FDG [8]. Unlike 18F-FDG, 18F-FLT has generally low uptake in different organs, such as brain and kidney and therefore elicits comparatively less background [35]. Although, as of now there has been no prospective/retrospective study with 18F-FLT PET/CT for MS detection, but the sensitivity and accuracy of 18F-FLT PET/CT has been demonstrated in different cancers including, non-small cell lung cancer (NSCLC) and NPM-ALK-Positive lymphoma [8, 36].
