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https://www.readbyqxmd.com/read/29346478/differentiation-syndrome-associated-with-enasidenib-a-selective-inhibitor-of-mutant-isocitrate-dehydrogenase-2-analysis-of-a-phase-1-2-study
#1
Amir T Fathi, Courtney D DiNardo, Irina Kline, Laurie Kenvin, Ira Gupta, Eyal C Attar, Eytan M Stein, Stephane de Botton
Importance: Enasidenib mesylate, a mutant isocitrate dehydrogenase 2 (IDH2) protein inhibitor that promotes differentiation of leukemic myeloblasts, was recently approved by the US Food and Drug Administration for use in relapsed/refractory (R/R) mutant IDH2 acute myeloid leukemia (AML). During the first study of enasidenib in humans, a minority of patients with advanced myeloid neoplasms experienced unexpected signs/symptoms of a differentiation syndrome (DS), a potentially lethal entity...
January 18, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29344583/heterozygous-rtel1-variants-in-bone-marrow-failure-and-myeloid-neoplasms
#2
Judith C W Marsh, Fernanda Gutierrez-Rodrigues, James Cooper, Jie Jiang, Shreyans Gandhi, Sachiko Kajigaya, Xingmin Feng, Maria Del Pilar F Ibanez, Flávia S Donaires, João P Lopes da Silva, Zejuan Li, Soma Das, Maria Ibanez, Alexander E Smith, Nicholas Lea, Steven Best, Robin Ireland, Austin G Kulasekararaj, Donal P McLornan, Anthony Pagliuca, Isabelle Callebaut, Neal S Young, Rodrigo T Calado, Danielle M Townsley, Ghulam J Mufti
Biallelic germline mutations in RTEL1 (regulator of telomere elongation helicase 1) result in pathologic telomere erosion and cause dyskeratosis congenita. However, the role of RTEL1 mutations in other bone marrow failure (BMF) syndromes and myeloid neoplasms, and the contribution of monoallelic RTEL1 mutations to disease development are not well defined. We screened 516 patients for germline mutations in telomere-associated genes by next-generation sequencing in 2 independent cohorts; one constituting unselected patients with idiopathic BMF, unexplained cytopenia, or myeloid neoplasms (n = 457) and a second cohort comprising selected patients on the basis of the suspicion of constitutional/familial BMF (n = 59)...
January 9, 2018: Blood Advances
https://www.readbyqxmd.com/read/29344217/aleukemic-extramedullary-t-lymphoid-myeloid-bilineage-hematopoietic-and-lymphoid-malignancy-with-progression-to-bilineage-leukemia-at-relapse-a-case-report
#3
Mengyao Wu, Xiaoqiu Li, Feng Tang, Ping Zhu, Tianling Ding, Yan Yuan, Tong Chen
Bilineage T lymphoid and myeloid (T/My) neoplasms are rare entities among the hematopoietic and lymphoid malignancies. The majority of patients present with leukemic symptoms in which blasts are observed in the peripheral blood (PB) or bone marrow (BM) at a percentage of >20% of nucleated cells. Only a minimal number of cases of T/My bilineage hematopoietic and lymphoid malignancy have been reported with extramedullary infiltration as the initial symptom. The origin of the neoplastic cells in T/My bilineage malignancy has been documented as the hematopoietic stem cells...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29342995/-pediatric-myeloid-neoplasms-associated-with-eosinophilia-and-platelet-derived-growth-factor-receptor-beta-gene-rearrangement-a-case-report-and-literature-review
#4
X Y Zhang, T F Liu, C W Li, Q H Li, X F Zhu
Objective: To investigate the clinical features and therapeutic strategies of childhood myeloid neoplasms associated with eosinophilia and platelet-derived growth factor receptor beta (PDGFRB) gene rearrangement. Methods: Clinical data of myeloid neoplasms associated with eosinophilia and t (1;5) (q21;q33) chromosomal translocation of PDGFRB gene rearrangement in a child hospitalized in Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences on May 2015 was collected and analyzed...
January 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29337025/hepatosplenic-t-cell-lymphoma-a-review-of-clinicopathologic-features-pathogenesis-and-prognostic-factors
#5
Mariko Yabe, Roberto N Miranda, L Jeffrey Medeiros
Hepatosplenic T-cell lymphoma (HSTCL) is a rare and clinically aggressive type of T-cell lymphoma that arises most often in adolescents and young adults. Patients with HSTCL commonly present with B-symptoms and cytopenias which may suggest a diagnosis of acute leukemia initially. Patients present with extranodal disease involving the spleen, liver and bone marrow; lymphadenopathy is usually absent. The lymphoma cells can show a spectrum of cell sizes and are of T-cell lineage, often negative for CD4 and CD8 and positive for T-cell receptor γδ or, less often, αβ...
January 11, 2018: Human Pathology
https://www.readbyqxmd.com/read/29332607/the-role-of-t2-weighted-gradient-echo-in-the-diagnosis-of-tumefactive-intrahepatic-extramedullary-hematopoiesis-in-myelodysplastic-syndrome-and-diffuse-hepatic-iron-overload-a-case-report-and-review-of-the-literature
#6
Abel A Belay, Andrew M Bellizzi, Alan H Stolpen
BACKGROUND: Extramedullary hematopoiesis is the proliferation of hematopoietic cells outside bone marrow secondary to marrow hematopoiesis failure. Extramedullary hematopoiesis rarely presents as a mass-forming hepatic lesion; in this case, imaging-based differentiation from primary and metastatic hepatic neoplasms is difficult, often leading to biopsy for definitive diagnosis. We report a case of tumefactive hepatic extramedullary hematopoiesis in the setting of myelodysplastic syndrome with concurrent hepatic iron overload, and the role of T2*-weighted gradient-echo magnetic resonance imaging in differentiating extramedullary hematopoiesis from primary and metastatic hepatic lesions...
January 15, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29327708/myeloproliferative-neoplasms-with-concurrent-bcr-abl1-translocation-and-jak2-v617f-mutation-a-multi-institutional-study-from-the-bone-marrow-pathology-group
#7
Craig R Soderquist, Mark D Ewalt, David R Czuchlewski, Julia T Geyer, Heesun J Rogers, Eric D Hsi, Sa A Wang, Carlos E Bueso-Ramos, Attilio Orazi, Daniel A Arber, Elizabeth O Hexner, Daria V Babushok, Adam Bagg
Myeloproliferative neoplasms arise from hematopoietic stem cells with somatically altered tyrosine kinase signaling. Classification of myeloproliferative neoplasms is based on hematologic, histopathologic and molecular characteristics including the presence of the BCR-ABL1 and JAK2 V617F. Although thought to be mutually exclusive, a number of cases with co-occurring BCR-ABL1 and JAK2 V617F have been identified. To characterize the clinicopathologic features of myeloproliferative neoplasms with concomitant BCR-ABL1 and JAK2 V617F, and define the frequency of co-occurrence, we conducted a retrospective multi-institutional study...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29323085/cd19-negative-b-lineage-acute-lymphoblastic-leukemia-a-diagnostic-and-therapeutic-challenge
#8
Shashi Bansal, Upendra Sharma, Akansha Jain, Richa Sharma, Bhargav Yagnik
B-lineage acute lymphoblastic leukemia (B-ALL) is an aggressive neoplasm of B-lymphocyte precursors that express the pan B-cell marker CD19 in all the cases. Rarely, a case may be assigned as B-lineage even if CD19 is negative. Here, a 16-year-old male presented with complaints of pain abdomen, on and off fever, joint pain, and hepatosplenomegaly for 2 months. Bone marrow examination was suggestive of acute leukemia with numerous leukoblasts on aspiration. On flow cytometry, gated blast population was negative for CD19, cytoCD3, and myeloperoxidase MPO and positive for CD34, TdT, HLA-DR, CD22, CD79a, and CD10...
October 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/29323084/fibroblast-growth-factor-receptor-1-associated-myeloproliferative-neoplasm-and-t-lymphoblastic-lymphoma
#9
Gayathri Gopan, T M Anoop, N P Prakash, Rakul Nambiar, R Krishnachandran
Myeloid and lymphoid hematological malignancies with eosinophilia and abnormalities of fibroblast growth factor receptor-1 (FGFR1) result from the formation of abnormal fusion genes that encode constitutively activated tyrosine kinases. The WHO classification (2008) of hematolymphoid neoplasms recognizes a category of myeloid and lymphoid neoplasms with eosinophilia and abnormalities of FGFR1. Here, we present the case of a 30-year-old-woman who was diagnosed with T-lymphoblastic lymphoma from lymph node biopsy and myeloproliferative neoplasm with eosinophilia from bone marrow studies...
October 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/29314691/mastocytosis-pathogenesis-clinical-manifestation-and-treatment
#10
Nicola Wagner, Petra Staubach
The term mastocytosis designates a group of rare disorders characterized by typical skin lesions, frequently associated episodes of anaphylaxis, and clinical symptoms related to the release of various mediators. Dermatologists/allergists are frequently the first to establish the diagnosis. The condition is based on clonal mast cell proliferation, usually in the skin or bone marrow and only rarely in the gastrointestinal tract or other tissues. In general, mastocytosis has a good prognosis in terms of life expectancy...
January 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/29314186/aggressive-nk-cell-leukaemia-and-extranodal-nk-t-cell-lymphoma-are-two-distinct-diseases-that-differ-in-their-clinical-presentation-and-cytogenetic-findings
#11
Ching-Fen Yang, Chih-Yi Hsu, Donald Ming-Tak Ho
AIMS: Distinguishing between aggressive NK-cell leukaemia (ANKCL) and extranodal NK/T-cell lymphoma (ENKTCL) with secondary bone marrow involvement is challenging, as they are rare bone marrow NK/T-cell neoplasms and share similar features. METHODS AND RESULTS: We studied bone marrow NK/T-cell neoplasms by classifying them into those with no extramedullary mass (group 1, 8 cases) and those with extramedullary mass (group 2, 13 cases). Both groups showed similar clinical presentations and pathological features...
January 4, 2018: Histopathology
https://www.readbyqxmd.com/read/29311096/early-detection-and-evolution-of-pre-leukemic-clones-in-therapy-related-myeloid-neoplasms-following-autologous-sct
#12
Gerbrig Berger, Leonie I Kroeze, Theresia N Koorenhof-Scheele, Aniek O de Graaf, Kenichi Yoshida, Hiroo Ueno, Yuichi Shiraishi, Satoru Miyano, Eva van den Berg, Hein Schepers, Bert A van der Reijden, Seishi Ogawa, Edo Vellenga, Joop H Jansen
Therapy-related myeloid neoplasms (tMNs) are severe adverse events that can occur following treatment with autologous hematopoietic stem cell transplantation (ASCT). This study aimed to investigate the development of tMN following ASCT at the molecular level by whole exome sequencing (WES) and targeted deep sequencing (TDS) in sequential (pre-) tMN samples. WES identified a significantly higher number of mutations in tMN as compared to de novo MDS (median 27 vs 12, p=0.001). The mutations found in tMN did not carry a clear ageing-signature, unlike the mutations found in de novo MDS, indicating a different mutational mechanism...
January 8, 2018: Blood
https://www.readbyqxmd.com/read/29310833/myeloid-neoplasm-with-eosinophilia-associated-with-isolated-extramedullary-fip1l1-pdgfra-rearrangement
#13
Talal Hilal, Veena Fauble, Rhett P Ketterling, Katalin Kelemen
Myeloid neoplasms with eosinophilia associated with PDGFRA rearrangement are very responsive to tyrosine kinase inhibitors (TKIs). Herein, we report a case of a 53-year-old man with eosinophilia and a well-differentiated extramedullary myeloid tumor with evidence of FIP1L1/PDGFRA rearrangement by fluorescent in situ hybridization in the extramedullary tissue. His bone marrow evaluation revealed a hypercellular marrow with eosinophilia but without evidence of a FIP1L1/PDGFRA rearrangement. The patient was treated with imatinib at a dose of 100 mg daily and responded with normalization of his peripheral eosinophil count...
January 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29296745/copy-number-alterations-detected-as-clonal-hematopoiesis-of-indeterminate-potential
#14
Koichi Takahashi, Feng Wang, Hagop Kantarjian, Xingzhi Song, Keyur Patel, Sattva Neelapu, Curtis Gumbs, Latasha Little, Samantha Tippen, Rebecca Thornton, Courtney D DiNardo, Farhad Ravandi, Carlos Bueso-Ramos, Jianhua Zhang, Xifeng Wu, Guillermo Garcia-Manero, P Andrew Futreal
Recent studies have revealed that clonal hematopoiesis of indeterminate potential (CHIP) is an important risk factor for therapy-related myeloid neoplasms (t-MNs). CHIP is currently defined as a clonal hematopoietic population carrying somatic point mutations in 1 of the leukemia-associated genes. Patients with t-MNs often present with chromosomal abnormalities in addition to somatic point mutations. It remains unclear whether chromosomal abnormalities can cooccur with point mutations as part of CHIP. Here we report that 3 of 14 patients with t-MNs had low amplitude but detectable chromosome arm-level copy number alterations (CNAs) in the peripheral blood samples that were taken at the time of their primary cancer diagnosis and before exposure to therapy...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296743/hmga2-collaborates-with-jak2v617f-in-the-development-of-myeloproliferative-neoplasms
#15
Koki Ueda, Kazuhiko Ikeda, Takayuki Ikezoe, Kayo Harada-Shirado, Kazuei Ogawa, Yuko Hashimoto, Takahiro Sano, Hiroshi Ohkawara, Satoshi Kimura, Akiko Shichishima-Nakamura, Yuichi Nakamura, Yayoi Shikama, Tsutomu Mori, Philip J Mason, Monica Bessler, Soji Morishita, Norio Komatsu, Kotaro Shide, Kazuya Shimoda, Shuhei Koide, Kazumasa Aoyama, Motohiko Oshima, Atsushi Iwama, Yasuchika Takeishi
High-mobility group AT-hook 2 (HMGA2) is crucial for the self-renewal of fetal hematopoietic stem cells (HSCs) but is downregulated in adult HSCs via repression by MIRlet-7 and the polycomb-recessive complex 2 (PRC2) including EZH2. The HMGA2 messenger RNA (mRNA) level is often elevated in patients with myelofibrosis that exhibits an advanced myeloproliferative neoplasm (MPN) subtype, and deletion of Ezh2 promotes the progression of severe myelofibrosis in JAK2V617F mice with upregulation of several oncogenes such as Hmga2...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290596/management-of-older-adults-with-myelodysplastic-syndromes-mds
#16
REVIEW
Marlise R Luskin, Gregory A Abel
The myelodysplastic syndromes (MDS) are a varied group of hematologic neoplasms that lead to bone marrow failure, and also carry a risk of progression to acute myeloid leukemia. Patients with MDS suffer significant impairments to both their quality of life and survival. Age is the dominant risk factor for the development of MDS, with a median age at diagnosis over 70years. Consequently, patients with MDS frequently have concurrent comorbidities and/or frailty which may be coincident or related to the disease itself...
December 28, 2017: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/29288421/first-line-treatment-with-bendamustine-and-rituximab-in-patients-with-intermediate-high-risk-splenic-marginal-zone-lymphomas
#17
Roberto Castelli, Luigi Bergamaschini, Giorgio Lambertenghi Deliliers
Splenic marginal zone lymphomas (SMZLs) are rare indolent B cell neoplasms that affect the spleen, bone marrow, and blood. Although they have an indolent course in the majority of patients, who have a median survival of 8-10 years, ∼ 30% may experience a worse outcome. The prognostic criteria of progression are lymph node and extra-nodal involvement, high lymphocyte counts, anaemia, and thrombocytopenia. The treatment of SMZLs include a "wait and watch strategy", splenectomy, and alkylating agents ± rituximab...
December 29, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29283939/rabdomyosarcoma-of-the-mandible-an-uncommon-clinical-presentation
#18
Cleverton Roberto de Andrade, Guilherme Dos Santos Trento, Fabiano Jeremias, Elisa Maria Aparecida Giro, Marisa Aparecida Cabrini Gabrielli, Mario Francisco Real Gabrielli, Oslei Paes de Almeida, Valfrido Antonio Pereira-Filho
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. Most patients present with a mass in the head and neck region, urogenital region, or with distal extremity involvement. The authors describe a challenging case of a 6-year-old male patient presenting with mandibular RMS. The clinical/radiographic/tomographic evaluations classified the tumor as an advanced stage (stage IV), with a mass of 6.0 cm involving the left side of the mandible and parotid region. The biopsy revealed round, spindled, and pleomorphic cells with hyperchromatic nuclei and rare larger rhabdomyoblasts with eosinophilic cytoplasm...
December 27, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/29278963/a-plasma-cell-myeloma-with-post-therapy-anaplastic-morphology-osteomyelosclerosis-and-strong-pan-cytokeratin-ae1-ae3-expression-a-potential-diagnostic-pitfall
#19
Vani Bharani, Prashant Sharma, Amanjit Bal, Gaurav Prakash
Reactive and neoplastic plasma cells can display considerable morphological anaplasia as well as variable immunoreactivity for epithelial markers including epithelial membrane antigen, pan-cytokeratin (panCK) and high-molecular-weight cytokeratin, potentially creating diagnostic dilemmas. We describe the case of a 51-year-old male, previously treated for IgGλ plasma cell myeloma, whose bone marrow biopsy showed focal replacement by sheets of pleomorphic malignant cells and grade 3 myelofibrosis, raising the morphological possibility of a carcinomatous infiltration...
December 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29277359/soho-state-of-the-art-update-and-next-questions-mpn
#20
REVIEW
Prithviraj Bose, Jason Gotlib, Claire N Harrison, Srdan Verstovsek
The discovery of the activating Janus kinase (JAK)2V617F mutation in 2005 in most patients with the classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) spurred intense interest in research into these disorders, culminating in the identification of activating mutations in MPL in 2006 and indels in the gene encoding calreticulin (CALR) in 2013, thus providing additional mechanistic explanations for the universal activation of JAK-signal transducer and activator of transcription (JAK-STAT) observed in these conditions, and the success of the JAK1/2 inhibitor ruxolitinib, which first received regulatory approval in 2011...
January 2018: Clinical Lymphoma, Myeloma & Leukemia
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