ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in three infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALKrearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (seven and twelve from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated-ERK, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, while CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, ten with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis, and provides guidance for the clinical management of this emerging histiocytic entity.Molecular tumour pathology - and tumour genetic

Cell-free DNA from nail clippings as source of normal control for genomic studies in hematologic malignancies

Comprehensive genomic sequencing is becoming a critical component in the assessment of hematologic malignancies, with broad implications for patient management. In this context, unequivocally discriminating somatic from germline events is challenging but greatly facilitated by matched analysis of tumor:normal pairs. In contrast to solid tumors, conventional sources of normal control (peripheral blood, buccal swabs, saliva) could be highly involved by the neoplastic process, rendering them unsuitable. In this work we describe our real-world experience using cell free DNA (cfDNA) isolated from nail clippings as an alternate source of normal control, through the dedicated review of 2,610 tumor:nail pairs comprehensively sequenced by MSK-IMPACT-heme. Overall, we find nail cfDNA is a robust source of germline control for paired genomic studies. In a subset of patients, nail DNA may have tumor DNA contamination, reflecting unique attributes of the hematologic disease and transplant history. Contamination is generally low level, but significantly more common among patients with myeloid neoplasms (20.5%; 304/1482) compared to lymphoid diseases (5.4%; 61/1128) and particularly enriched in myeloproliferative neoplasms with marked myelofibrosis. When identified in patients with lymphoid and plasma-cell neoplasms, mutations commonly reflected a myeloid profile and correlated with a concurrent/evolving clonal myeloid neoplasm. For nails collected after allogeneic stem-cell transplantation, donor DNA was identified in 22% (11/50). In this cohort, an association with recent history of graft-vs-host disease was identified. These findings should be considered as a potential limitation for the use of nail as normal control but could also provide important diagnostic information regarding the disease process

Enterprise architecture adoption issues and challenges: a systematic literature review

This article on Systematic Literature Review (SLR) provides the issues and challenges faced by organizations when adopting EA. Firstly, a review of literature that discusses the problems and challenges was undertaken. Methods and theories adopted were reviewed to identify the existing approach and perspective on resulting factors that influenced EA adoption. Based on the inclusion and exclusion criteria defined in the review process, 16 articles were selected. A total of 19 challenges and problems were identified such as EA misconceptions, overlapping organizational rules, unclear leadership as well as lack of business and IT alignment. A sum of 15 factors from multidimensional contexts that influenced the EA adoption in the organization were also discussed, such as top management support, governance, communication as well as EA knowledge and skill. This SLR also reflected that there were relatively little empirical studies conducted on EA adoption studies. The existing studies tend to apply single and multiple theories from the organization and management domains in one study. By understanding such issues and challenges, risks can be reduced and avoided when introducing EA to organizations, and subsequently ease the deployment process. Thus, this article may shed light on understanding the organizational-related factors and the underlying relationships of EA adoption. As a result, an effective adoption of EA can be facilitated in the organizations

Proposed conceptual Iot-based patient monitoring sensor for predicting and controlling dengue

Dengue is an epidemic-disease by mosquito-borne virus that spreads easily in geographically affected areas. Dengue outbreak management system has increasingly being developed in identifying and controlling the spread of dengue but with some limitation. The growing development of wearable Internet of Things (IoT), cloud computing, analytical approaches provide better alternative for dengue prediction and control. Previous literature collecting various parameters for analyzing dengue pattern. However, with the increasing number of analytical solution there is a need to investigate the high related parameters that should be use in analyzing and monitoring dengue outbreak before designing an IoT devices. Besides, there is a need for an alternative to ensure that early warning can be detected by monitoring the patient infected by the dengue, this paper aims to propose a conceptual IoT-based patient monitoring sensor for predicting and controlling dengue outbreak. Therefore, this paper provides a recent review of the latest methods and algorithms used to design wearable sensor for patient monitoring in dengue outbreak. Based on the review, this paper outlines the parameters that will be used in dengue for analyzing purposes. Finally, a conceptual IoT-based patient monitoring sensor were proposed comprising three different sensors to further work with analytical tools for dengue prediction pattern. The proposed conceptual design may help researcher to use the parameter identified for development of IoT sensor for dengue outbreak

Transport phenomena of carbazole biodegradation by immobilized thalasosspira profundimaris cell and mechanical properties

Carbazole is a heterocyclic aromatic compound that imposes threat to the environment when contaminates water source. A marine-isolated bacterium, Thalassospira profundimaris shows ability to degrade carbazole. The use of free-cell for bioremediation is inefficient as the cells are exposed to harsh environmental condition. In this study, immobilizations of T. profundimaris in gellan gum were investigated to develop robust systems for bioremediation. The mechanical strength and its relationship with transport of carbazole was investigated. The findings proved that concentration of immobilization media affects diffusivity and mechanical strength. Higher media concentration formed a stronger bead with lower diffusivity where lower concentration formed soft bead with higher diffusivity. The optimum concentration of gellan gum was 0.7% (w/v) with 61% carbazole degradation recorded and an optimum diffusivity of 36.8 × 10-7 cm2/s. It has the highest Young's modulus (0.041810 N/mm2) among other concentrations. The findings of the optimum carbazole degradation, strength and diffusivity were profound to increase the performance of the bacteria entrapped inside the immobilization media for bioremediation and withstand harsh environment

ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.NEUROPatholog

ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity