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The 2016 WHO classification introduced the category of high-grade B-cell lymphoma (HGBL), which includes one poorly understood subset, blastoid-HGBL. Establishing the diagnosis and distinguishing blastoid-HGBL from B-acute lymphoblastic leukemia (B-ALL) in bone marrow can be challenging. We assessed 31 cases of blastoid-HGBL diagnosed initially in bone marrow and compared this group to 36 cases of B-ALL using immunophenotyping, fluorescence in situ hybridization, and targeted next generation sequencing analysis. The 31 blastoid-HGBL cases included 14 HGBL with MYC and BCL2 and/or BCL6 rearrangements (double hit lymphoma, DHL), 13 HGBL, not otherwise specified (NOS), and four cases with TdT expression that were difficult to classify. Compared with B-ALL, blastoid-HGBL cases more often showed increased intensity/bright expression of CD20, CD38, CD45, BCL-6, and MYC, and less frequent bright expression of CD10 and TdT. Cases of blastoid-HGBL also more frequently had MYC rearrangement, a complex karyotype and TP53 mutation (p

Mantle cell lymphoma (MCL) is a mature B-cell neoplasm characterized by t(11;14)(q13;q32) and cyclin D1 overexpression in >95% of cases. Classic MCL cases are composed of a monotonous population of small to medium-sized lymphocytes with irregular nuclear contours that are positive for cyclin D1 and SOX11, and negative for CD23 and CD200. By contrast, occasional MCL cases express CD23 and CD200 but lack of SOX11, and morphologically and immunophenotypically resemble chronic lymphocytic leukemia (CLL), termed as CLL-like MCL in this study. These neoplasms pose a diagnostic challenge and easy to be diagnosed as CLL in daily practice. We studied 14 cases of CLL-like MCL to define their clinicopathologic features and compared them with 33 traditional CLL cases. There were 8 men and 6 women with a median age of 62 years (range, 44-80). Compared with CLL, patients with CLL-like MCL have lower levels of peripheral blood and bone marrow involvement, and more frequently had mutated IGHV. Immunophenotypically, CLL-like MCL often showed moderate to bright expression of B-cell antigens and surface immunoglobulin light chain, dim and partial expression of CD23 and CD200, infrequent CD43 positivity, and lack of LEF1. The overall survival of patients with CLL-like MCL was similar to that of CLL patients. In conclusion, CD23+, CD200+, and SOX11-negative MCL closely resemble CLL, both clinically and pathologically, including a similar indolent clinical course. They may pose a diagnostic challenge. However, patients with CLL-like MCL also have distinctive immunophenotypic features that are useful to distinguish these neoplasms from CLL.

Strict registration is critical for imaging polarimetry; a highly accurate registration approach to the coronal image and imaging polarimetry of the Fe 6374 Å red coronal line have been researched in this paper. In order to improve the registration accuracy, this paper proposes the idea of image enhancement based on blind deconvolution combined with noise-adaptive fuzzy equalization algorithms. After image enhancement, the cross-correlation registration algorithm achieves better results. To diagnose a low-temperature corona, the polarization brightness of the red coronal line data and the Mauna Loa Solar Observatory (MLSO)/KCor data are compared to study the structural features and polarization information of the inner corona. We found that the polarization brightness radiation of the red coronal line has overall features similar to that of the MLSO/KCor data, but it has more detailed features, such as the cavity, polar plume, and interplume characteristics. Active regions, polar plumes, and interplumes show similar performance in red coronal line intensity, polarization brightness, degree of linear polarization, K-corona, and electron density along with the radial height. An interesting finding is that the polarization brightness of the red coronal line changes drastically along with the radial height across the cavity above the solar west limb, while neither the K-corona nor the electron density changes obviously. This seems to be a piece of possible evidence indicating that the red coronal line is not unpolarized in the cavity region.

Oil shale is an unconventional oil and gas resource, and because of its high utilization value, it has been listed as an important alternative energy source of the 21st century. In this study, through the analysis of raw ore, design and development of a composite dry sorting machine was proposed to sort the original ore, and the distribution rule of oil shale particles in separation tank was analyzed. The effects of trough height, amplitude, and frequency on layered separation of oil shale in trough were also systematically investigated. The results showed that under the best operating parameters (height = 55–60 mm, amplitude = 3.2–3.6 mm, and frequency = 36–39 Hz), the groove on the surface of the composite dry separation bed exhibited good sorting effect. The particles were clearly layered on the bed surface according to density. The oil content of the original ore was 4.39% and that of the obtained concentrate was 10.05%, and the yield was 40.57%. Moreover, the oil content of the tailings was 0.51%, and the yield was 59.43%. The composite dry separator shows a good separation effect on the recycling of oil shale.

Gains or amplification (amp) of chromosome 1q21/CKS1B are reported to be a high-risk factor in myeloma. In this retrospective study, we analyzed the impact of CKS1B gain/amp on overall survival in the context of other genetic aberrations, such as TP53 deletion, FGFR3-IGH, IGH-MAF, MYEOV/CCND1-IGH, and RB1, as well as karyotype. The cohort included 132 myeloma patients with CKS1B gain/amp detected by fluorescence in-situ hybridization. There were 72 men and 60 women with a median age of 65 years (range 39–88 years). A normal, simple, or complex karyotype was observed in 39.5%, 5.4%, and 55% of patients, respectively. “Double hit,” defined as CKS1B gain/amp coexisting with TP53 deletion, or “triple hit,” defined as double hit plus t(4;14)FGFR3-IGH or t(14;16)IGH-MAF, were identified in 25 patients (18.9%) and five patients (3.8%), respectively. Double and triple hit were highly associated with a complex karyotype (p = 0.02). Ninety-nine patients (99/128, 77.3%) received stem cell transplantation. The median follow-up time was 48.2 months (range 2–104 months); 68 patients (51.5%) died, with a median overall survival of 58.8 months. Multivariate analysis (Cox model) showed that double hit with TP53 deletion (p = 0.0031), triple hit (p = 0.01), and complex karyotype (p = 0.0009) were each independently associated with poorer overall survival. Stem cell transplantation was associated with better overall survival, mainly in patients with a double or triple hit and complex karyotype (p = 0.003). These findings indicate that the inferior outcome of myeloma patients with CKS1B gain/amp is attributable to the high number of high-risk patients in this group. The prognostic impact of CKS1B gain/amp depends on the background karyotype and TP53 status.

Summary The role of MYC dysregulation has been studied extensively in B-cell lymphomas, but little is known about its significance in T cell lymphomas. This study, for the first time in the literature, assessed the clinicopathologic and prognostic significance of MYC expression in ALK+ anaplastic large cell lymphoma (ALCL) cases. Using ≥50% as the cutoff value for positive MYC expression by immunohistochemistry, 17 of 46 (37%) cases were MYC+. Patients with MYC+ tumors were older (median age, 39 versus 29 years, p = 0.04) and more often showed a common morphologic pattern (100% versus 69%, p = 0.02), when compared with those with MYC-negative tumors. By fluorescence in situ hybridization analysis, 9 of 31 (29%) cases showed increased MYC copy number, and 1 of 31 (3%) case had an MYC rearrangement, and the remaining 21 (68%) cases showed no MYC aberrations. Among the cases with increased MYC copy number, 5 of 8 (62%) cases showed MYC copy gain and/or amplification and 3 of 8 (38%) had polysomy 8. MYC expression was associated with increased MYC copy number (p = 0.01). MYC expression, but not increased MYC copy number, correlated with shorter overall survival (OS) (p = 0.03). In conclusion, MYC expression identified a distinct group of ALK + ALCL patients with more aggressive behavior and shorter OS. Our data suggest that MYC expression is an adverse prognostic factor and may be useful in stratifying or predicting the prognosis of patients with ALK+ ALCL.

We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated MYC rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (D...

Rare patients with chronic myeloid leukemia (CML) can present initially in lymphoblastic crisis (LBC) mimicking Ph + B-lymphoblastic leukemia (B-ALL). We retrospectively reviewed 275 adults who diagnosed initially as Ph + B-ALL and identified 28 patients with at least one of three features supporting the diagnosis of CML-LBC: 1) a large discrepancy between the blast count and Ph + clone; 2) Ph + clone persistent when B-ALL in remission; 3)

Acute myeloid leukemia (AML) with intrachromosomal amplification of chromosome 21 (iAMP21) is rare and has not been well characterized. We report 13 patients, 7 men and 6 women, with a median age of 65 years. Eleven patients presented with AML with myelodysplasia-related changes, and two patients had therapy-related AML. Cytopenias were detected in all patients (11 pancytopenia and two bi-lineage cytopenia). Myelodysplastic changes were observed in all 11 patients with adequate cells to evaluate. Myelofibrosis was present in ten patients. All patients had a complex karyotype, including abnormalities of chromosomes 5, 7, 17, and hsr(21)(q22), and ten patients showed TP53 deletion and/or mutation. Eleven patients received AML-based chemotherapy, one of whom also received hematopoietic stem cell transplant. By the end of the last follow-up, eight patients died with median survival of 3.2 months, four patients were alive with persistent AML, and one was in complete remission. The median overall survival was 6 months for all patients. We conclude that AML with iAMP21 is often associated with cytopenias, myelodysplasia, a complex karyotype, TP53 mutation/deletion, and a poor prognosis despite current therapies.

Dermatopathic lymphadenopathy is a distinctive form of paracortical lymph node hyperplasia that usually occurs in the setting of chronic dermatologic disorders. The aim of this study is to update our understanding of the clinicopathologic and immunophenotypic features of dermatopathic lymphadenopathy. The study cohort was 50 lymph node samples from 42 patients diagnosed with dermatopathic lymphadenopathy. The patients included 29 women and 13 men with a median age of 49 years (range, 12–79). Twenty-two (52%) patients had a dermatologic disorder, including mycosis fungoides (n = 6), chronic inflammatory dermatoses (n = 13), melanoma (n = 1), squamous cell carcinoma (n = 1), and Kaposi sarcoma in the context of human immunodeficiency virus infection (n = 1). Twenty (48%) patients did not have dermatologic manifestations. Lymph node biopsy specimens were axillary (n = 22), inguinal (n = 21), cervical (n = 4), and intramammary (n = 3). All lymph nodes showed paracortical areas expanded by lymphocytes; dendritic cells, including interdigitating dendritic cells and Langerhans cells; and macrophages. Melanophages were detected in 48 (98%) lymph nodes. Immunohistochemical analysis provided results that are somewhat different from those previously reported in the literature. In the paracortical areas of lymph node, S100 protein was expressed in virtually all dendritic cells, and CD1a was expressed in a significantly greater percentage of cells than langerin (80 vs. 35%, p

Programmed cell death protein-1 (PD-1) is currently the most extensively studied inhibitory checkpoint molecule. Many malignant neoplasms express the PD-1 ligands, PD-L1, and/or PD-L2, which bind to PD-1 on T cells and induce T cell “exhaustion.” By doing so, the malignant cells escape from an antitumor immune response (immune evasion). Blockade of the PD-1/PD-L1 pathway releases T cells from the inhibitory effects exerted by tumor cells and restores a T cell-mediated antitumor immune response. Here, we focus on understanding the immune biology of the PD-1/PD-L1 pathway in large-cell lymphomas, including classic Hodgkin lymphoma (CHL), diffuse large B cell lymphoma (DLBCL), and anaplastic large-cell lymphoma (ALCL), and the current status of PD-1 blockade immunotherapy in treating patients with these lymphomas. PD-1/PD-L1 pathway and PD-1 inhibitors have been widely tested in patients with a variety of lymphomas. Nivolumab and pembrolizumab have been approved by the U.S. Food and Drug Administration for treating patients with some types of relapsed or refractory (R/R) lymphomas. The highest response rate has been achieved in patients with CHL, due to a high frequency of genetic alterations of 9p24.1 and high expression of PD-1 ligands. The frequency of alterations of chromosome 9p24.1 and expression of PD-L1/PD-L1 in DLBCL (except some specific subtypes) is low; therefore, it is not recommended to treat unselected DLBCL patients with PD-1 inhibitors. Studies have shown a high frequency of PD-L1 expression in ALCL, especially in anaplastic lymphoma kinase (ALK)+ type. Several cases reports have described a dramatic and durable response to PD-1 blockade in patients with R/R ALCL, suggesting that patients with R/R ALCL may be potential candidates for PD-1 blockade immunotherapy. Understanding the immune biology of lymphoid neoplasms has helped us identify the specific lymphoma types that are vulnerable to PD-1 inhibitors, such as CHL, and specific subtypes of DLBCL. However, our knowledge of many other lymphomas, including ALCL, in this area is still very limited and the future of PD-1 inhibitors in treating those lymphomas remains unclear.

Mantle cell lymphoma (MCL) with MYC rearrangement (MYC-R) is rare and little is known about the importance of MYC extra copies (EC) in the absence of MYC-R in MCL patients. This study includes 88 MCL patients with MYC tested by fluorescence in situ hybridization and/or conventional cytogenetics, including 27 with MYC-R, 21 with MYC-EC, and 40 with normal (NL) MYC. MCL patients with MYC-R more often had blastoid/pleomorphic morphology; a higher frequency of CD10, MYC, and simultaneous MYC and BCL2 expression; a higher level of MYC; and a higher Ki67 proliferation rate (p

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematopoietic neoplasm whose immunophenotype remains incompletely characterized, particularly in terms of distinction from reactive plasmacytoid dendritic cells (PDCs). This limitation complicates detection of low-level involvement by BPDCN as well as minimal residual disease (MRD) assessment following therapy. We conducted the current study to characterize the immunophenotype of BPDCN in a cohort of 39 patients, and compared it to reactive PDCs. We found that, in addition to CD56 expression (97%), BPDCN showed a number of aberrancies, including decreased/negative CD38 (82%), positive CD7 (64%), negative CD2 (81%), negative CD303 (56%), increased HLA-DR (69%) and decreased CD123 (78%). Although BPDCN cells were characterized by CD56 expression, reactive PDCs consistently included a CD56-positive subset, ranging 1.3%-20% (median 4.5%) of total PDCs, challenging MRD detection. These CD56+ reactive PDCs, however, were consistently positive for CD2 and CD303, brightly positive for CD38, and negative for CD7, distinctively different from BPDCN. Based on these findings, we set up a 10-color flow cytometry assay for BPDCN and validated it to a sensitivity of 0.01%. This panel was prospectively tested in 19 bone marrow samples from 7 BPDCN patients, and it effectively distinguished BPDCN cells from background reactive PDCs in all cases. In summary, by understanding the immunophenotype of reactive and neoplastic PDCs, BPDCN can be effectively detected by flow cytometry to a very low level using a panel of markers in addition to CD56, and such assay can be used for initial bone marrow workup as well as MRD detection after therapy.

The programmed cell death 1 (PD-1) pathway is a recently recognized mechanism of tumor immune evasion. In this study, programmed cell death ligand 1 (PD-L1) expression was evaluated in 95 patients with systemic anaplastic large cell lymphoma: 45 ALK+ and 50 ALK-. ALK+ anaplastic large cell lymphoma was more often positive for PD-L1 than ALK- anaplastic large cell lymphoma (76% vs 42%, p = 0.002). ALK- anaplastic large cell lymphoma showed a strong correlation between PD-L1 expression and STAT3 activation (measured by pSTAT3Tyr705) (r = 0.8, p 0.05). Negative ALK status and high IPI score (≥3) were associated with shorter overall survival (p = 0.009 and p = 0.0005, respectively). Overall survival was not different between patients with PD-L1+ vs PD-L1- anaplastic large cell lymphoma (p = 0.44), regardless of ALK status and International Prognostic Index (IPI) score. We conclude that PD-L1 expression is more common in ALK+ anaplastic large cell lymphoma than ALK- anaplastic large cell lymphoma. In ALK- anaplastic large cell lymphoma, PD-L1 is strongly correlated with STAT3 activation and is associated with more frequent EMA and less frequent CD2 expression. PD-L1 has no prognostic significance in predicting the outcome of patients with systemic anaplastic large cell lymphoma, regardless of ALK status. PD-L1 expression on the anaplastic large cell lymphoma cells suggests these patients as potential candidates for PD-1 blockade immunotherapy.

While patients with double-hit lymphoma (DHL) are now frequently treated with intensive front-line immunochemotherapy, outcomes for those who fail these regimens and subsequently receive curative-intent second-line immunochemotherapy are unknown. We identified 55 such patients who achieved an overall/complete response rate of 29%/11%, median progression-free/overall survival (PFS/OS) of 2/5·1 months and one-year PFS/OS of 10/19% following the start of second-line therapy. These outcomes may serve as a standard against which future second-line treatment strategies for relapsed/refractory DHL can be measured and justify investigation of non-cytotoxic therapies in the second-line setting for these patients.

Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for patients with myelofibrosis (MF). Bone marrow (BM) morphologic evaluation of myelofibrosis following allo-HSCT is known to be challenging in this context because resolution of morphologic changes is a gradual process. Patients and methods We compared BM samples of patients with myelofibrosis who underwent first allo-HSCT and achieved molecular remission by day 100 with BM samples of patients who continued to have persistent molecular evidence of disease following allo-HSCT. Results The study group included 29 patients: 17 primary MF, 7 post-polycythemia vera (PV) MF, and 5 post-essential thrombocythemia (ET) MF. In this cohort there were18 JAK2 p.V617F, 8 CALR; 1 MPL, and 2 patients had concurrent JAK2 p.V617F and MPL mutations. The control group included 5 patients with primary MF, one with post-PV MF, one with post-ET MF (5 JAK2 p.V617F; 2 CALR). Following allo-HSCT, both groups showed reduction in BM cellularity and number of megakaryocytes. The study cohort also less commonly had dense megakaryocyte clusters and endosteal located megakaryocytes and showed less fibrosis. There was no statistical difference in BM cellularity, presence of erythroid islands, degree of osteosclerosis, or megakaryocyte number, size, nuclear lobation, presence of clusters or intrasinusoidal location. Conclusions Following allo-HSCT at 100 days, morphologic evaluation of BM in patients with MF cannot reliably predict persistence versus clearance of molecular evidence of MF. Decreased BM MF, dense megakaryocyte clusters, and endosteal localization of megakaryocytes are suggestive of disease response.

The application of a femtosecond laser direct inscribed 45° tilted fiber grating (TFG) in a net-normal-dispersion mode-locked Er-doped fiber laser, as an in-fiber polarizer, has been systematically studied. The 45° TFG with a grating length of ~ 12.6 mm and a grating period of ~ 2.2 μm has a polarization dependent loss of ~ 9.8 dB and supports various types of dissipative soliton (DS) outputs. The achieved single DS mode-locked pulse centered at 1570.55 nm has a 3 dB bandwidth of 15.64 nm and a pulse duration of ~ 4.68 ps. By simply employing a section of single-mode fiber, the output pulse duration can be dechirped to ~ 250 fs. The fundamental repetition rate is 25.47 MHz and the maximum pulse output power is 24.04 mW. By appropriately adjusting the intra-cavity polarization states and increasing the pump power, the bound-state DS, as well as a harmonic mode-locked DS, can be generated. The bound-state pulse is composed of two identical DS pulses with a temporal interval of ~ 26.27 ps. The second- and third-order harmonic mode-locked DS pulses with repetition rates of 50.93 MHz and 76.40 MHz are obtained for pump powers of 298 mW and 528 mW, respectively. Our results indicate that the feasibility and versatility of the femtosecond laser inscribed 45° TFG to realize nonlinear polarization evolution mode-locking in various operation regimes. Combined with the flexibility of the femtosecond laser direct inscription technique, such a 45° TFG paves a promising route for the development of robust, compact and high-energy ultrafast all-fiber lasers.

Several morphologic variants of ALK+ anaplastic large cell lymphoma (ALCL) are recognized. The small cell (SC) and lymphohistiocytic (LH) variants are reported to be associated with poorer outcome in children with ALK + ALCL. In this study of 102 adults with ALK + ALCL, there were 18 (18%) cases of SC and/or LH variants. Patients with SC/LH ALK + ALCL more often had peripheral blood involvement than patients with non-SC/LH neoplasms (60% vs 0%, p = 0.02). There were no other significant differences in clinical features between patients with SC/LH versus non-SC/LH ALK + ALCL. Compared with non-SC/LH cases of ALK + ALCL, neoplasms with SC/LH features were more often positive for CD2 (92% vs. 36%, p = 0.0007), CD3 (81% vs. 15%, p = 0.0001), CD7 (80% vs. 37%, p = 0.03), and CD8 (54% vs. 7%, p = 0.0006). There were no other significant differences in the immunophenotype between SC/LH and non-SC/LH ALK + ALCL cases. The initial chemotherapy regimens and the response rates were similar between patients with ALK + ALCL with SC/LH patterns versus those with non-SC/LH patterns. After a median follow-up of 30.8 months (range, 0.3-208 months), patients with high (>3) International Prognostic Index (IPI) scores had significantly shorter overall survival than patients with low (

BACKGROUND Salvage immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation is the standard-of-care second-line treatment for patients with relapsed/refractory diffuse large B-cell lymphoma after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Outcomes after receipt of second-line immunochemotherapy in patients with aggressive B-cell lymphomas who relapse or are refractory to intensive first-line immunochemotherapy regimens (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab [R-EPOCH], rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine [R-HyperCVAD], rituximab, cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate alternating with ifosfamide, etoposide, and cytarabine [R-CODOX-M/IVAC]) remain unknown. METHODS Outcomes of patients with non-Burkitt, aggressive B-cell lymphomas and relapsed/refractory disease after first-line treatment with intensive immunochemotherapy regimens who received platinum-based second-line immunochemotherapy were reviewed retrospectively. Analyses were performed to determine progression-free survival (PFS) and overall survival (OS) from the time of receipt of second-line immunochemotherapy. RESULTS In total, 195 patients from 19 academic centers were included in the study. The overall response rate to second-line immunochemotherapy was 44%, with a median PFS of 3 months and a median OS of 8 months. Patients with early treatment failure (primary refractory or relapse

Hyperdiploidy (chromosomal number 51‐65) is a common cytogenetic abnormality in pediatric patients with B‐lymphoblastic leukemia (B‐ALL) and belongs to the favorable cytogenetic subgroup. Hyperdiploidy in adult B‐ALL is much less common and its clinical significance has not been well studied. Among the 1205 patients with B‐ALL (1018 adults and 187 children) from our institution, 78 had a hyperdiploid karyotype, including 45 (4.4%) adults and 33 (17.6%) children (P

Summary Mantle cell lymphoma (MCL) is usually CD23 negative, a feature helpful in distinguishing MCL from chronic lymphocytic leukemia/small lymphocytic lymphoma. However, a subset of MCL cases can be CD23+. Limited data are available regarding the clinicopathological features and prognosis of patients with CD23+ MCL. In this study, we reviewed 798 cases of MCL and identified 103 (13%) that were CD23+ by flow cytometry, all of which were positive for cyclin D1 and/or associated with CCND1/IGH. In all cases of CD23+ MCL, CD23 expression was dim partial or dim, unlike moderate to bright CD23 expression observed in chronic lymphocytic leukemia/small lymphocytic lymphoma. The clinicopathological features and outcome of patients with CD23+ MCL were compared with 240 patients with typical MCL negative for CD23. Patients with CD23+ MCL more often had an elevated leukocyte count (33% versus 18%, P = .009), bone marrow involvement (89% versus 78%, P = .02), stage 4 disease (87% versus 77%, P = .03), and a leukemic presentation (42% versus 11%, P = .0001). CD23+ MCL was also more often positive for CD200 (17% versus. 4.6%, P = .0005) and less commonly positive for SOX11 (55% versus. 74%, P = .027). All other clinicopathological features were similar. With similar treatment regimens and observation times, patients with CD23+ MCL had a significant better overall survival (P = .02) and progression-free survival (P = .029). In conclusion, CD23 expression was observed in 13% of MCL cases and is associated with a better prognosis in patients with MCL. CD23 is associated with leukocytosis, a leukemic presentation, bone marrow involvement, CD200 expression, and a lower frequency of SOX11 positivity.

KIT mutations are observed in about 20-40% of acute myeloid leukemia with t(8;21)(q22;q22.1)/RUNX1-RUNX1T1 [abbreviated AML t(8;21) here] with mutations involving exon 17 being the most common. Despite high frequencies of KIT mutations in both AML t(8;21) and systemic mastocytosis (SM), AML t(8;21) associated with SM is uncommon, and restricted to KIT exon 17 mutated cases. In this study, we report two cases of AML t(8;21) associated SM that KIT mutation occurred in exon 8 (T417_D419delinsY). In both patients, the bone marrow displayed increased round/ovoid mast cells with bilobated nuclei and absence of CD2 and CD25 expression. RUNX1/RUNX1T1 fusion was shown in both myeloblasts and mast cells by FISH. Patient #1 was refractory to induction chemotherapy and died at day 50; patient #2 had residual AML, marked SM, and persistent RUNX1/RUNX1T1 fusion after induction therapy.

Studies have suggested that SOX11 expression has prognostic implications in patients with mantle cell lymphoma (MCL), but the data are controversial. In this study, we describe the clinicopathologic and prognostic features of 75 patients with SOX11-negative MCL. Compared with patients with SOX11-positive MCL, SOX11-negative MCL patients more frequently had leukemic non-nodal disease (21% vs. 4%, P=0.0001). SOX11-negative MCLs more often showed classic morphology (83% vs. 65%, P=0.005), were more often positive for CD23 (39% vs. 22%, P=0.02) and CD200 (60% vs. 9%, P=0.0001), and had a lower proliferation index (Ki67 23% vs. 33%, P=0.04). Overall survival (OS) was not significantly different between patients with SOX11-negative versus SOX11-positive MCL (P=0.63). High Ki67 index and blastoid/pleomorphic morphology were associated with shorter OS in both SOX11-negative (P

Lymphoblastic leukemia (ALL) following myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN) is very rare. We report five cases: four had ALL diagnosed after MDS or MDS/MPN and one had ALL and MDS diagnosed simultaneously. At the onset of ALL, all patients showed co-existing MDS or MDS/MPN. Map-back FISH was performed in four patients, showing that ALL and MDS were cytogenetically related in two patients and unrelated in the other two patients. All five patients were treated with ALL-based chemotherapies, two patients with ALL clonally related to MDS were refractory to the therapies, whereas the other three patients achieved remission. We conclude that ALL developed after MDS is extremely rare. In some patients, ALL is clonally related to MDS and these patients may be refractory to ALL-based chemotherapies. In other patients who have no evidence of clonal relation between ALL and MDS, these patients more likely respond to ALL-based treatment regimens.

The concurrent presence of JAK2 V617F, monocytosis, and bone marrow fibrosis can be observed in both chronic myelomonocytic leukemia (CMML) and primary myelofibrosis (PMF). It can be challenging to distinguish CMML with JAK2 mutation and fibrosis from other myeloid neoplasms, particularly PMF. To identify key features that may help distinguish these 2 entities, we retrospectively studied 21 cases diagnosed as "CMML" with JAK2 V617F and bone marrow fibrosis that were identified from a cohort of 610 cases of CMML diagnosed in 2006 to 2016. Upon further review, we confirmed the diagnosis of CMML in 7 cases, 11 cases were reclassified as PMF, and 3 cases had features intermediate between CMML and PMF (gray zone). These 11 cases of PMF with monocytosis featured a higher JAK2 V617F allelic burden (median, 43%; range, 20%-62%) and atypical pleomorphic megakaryocytes with hyperchromatic nuclei. Complete blood count showed more pronounced myeloid left shift. In contrast, 7 CMML cases had significantly lower JAK2 V617F allelic burden (median, 17%; range, 5%-36%; P < .0001) and dysplastic megakaryocytes along with variable degree of dysplasia in other lineages. The median survival of PMF and CMML patients was 32 and 40 months, respectively. We conclude that besides morphology of megakaryocytes and other features, JAK2 V617F allelic burden can help differentiate CMML from PMF with monocytosis. SRSF2 and RAS mutations are observed in both disease categories. Rare gray-zone cases exist with hybrid features.

t(3;8)(q26.2;q24) is a rare recurrent cytogenetic abnormality that is associated with myeloid neoplasms. Of 20 patients with t(3;8)(q26.2,q24), 8 had therapy-related acute myeloid leukemia (AML), 3 therapy-related myelodysplastic syndrome, 4 blast phase of chronic myeloid leukemia, 1 relapsed AML, 1 AML transformed from chronic myelomonocytic leukemia, 1 blast phase of an unclassifiable myeloproliferative neoplasm, 1 de novo myelodysplastic syndrome, and 1 de novo AML. Nineteen patients presented with cytopenia. Multilineage dysplasia was observed in 16/18 patients, and megakaryocytes were markedly decreased in 11/20 patients. Blasts showed a primitive myeloid immunophenotype in 17 patients, negative for myeloperoxidasein in 14/17, and aberrant CD7 expression in 5/17 patients. Fluorescence in situ hybridization showed MECOM rearrangement in 18/19 and MYC in 16/18 patients. Myc was shown to be expressed in all 14 cases assessed. Gene mutation testing was performed in 14 patients, and 7 showed at least one mutation including ASXL1 (2/6), TET2 (2/6), SRSF2 (2/6), and NRAS (2/13). At last clinical follow-up, 18 patients died and 2 were alive with persistent disease, with a median survival of 6 months. The authors conclude that t(3;8)(q26.2;q24) often leads to MECOM and MYC rearrangement, occurs predominantly in therapy-related myeloid neoplasms or at disease progression, and shares some similarities with myeloid neoplasms associated with inv(3)/GATA2-MECOM. Patients with myeloid neoplasms associated with t(3;8)(q26.2;q24) have a dismal outcome.

PURPOSE Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score–weighted (PSW) analysis were performed. RESULTS Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.

IgM plasma cell myeloma (PCM) is a rare subtype of myeloma, and its response to novel therapies has not been fully characterized. We describe clinicopathological features and outcome of 17 patients with IgM PCM (11 men and 6 women) with a median age of 63 years. Patients presented with serum hyperviscosity (77%), bone lesions (71%), anemia (65%), renal dysfunction (53%), and hypercalcemia (35%). Median serum IgM level was 6.4 g/dL (0.7-12.1 g/dL). Bone marrow plasma cells (median, 80%; range, 20%-90%) were frequently of lymphoplasmacytic type (8/17; 47%). Immunophenotypically, the myeloma cells were positive for CD38, CD138, CD20 (5/16; 31%), CD56 (4/16; 25%), and CD117 (2/12; 17%); negative for CD19; and decreased or absent CD27 and CD81 in all cases. Seven (41%) patients had a complex karyotype, and fluorescence in situ hybridization showed CCND1-IGH (13/16; 81%), and deletions of 17p13/TP53 (29%) and 13q14/RB1 (38%). No MYD88 L265P mutation was detected. Most patients (94%) received proteasome inhibitor with or without immunomodulatory drug, 62% of patients required multiple regimens because of refractory disease, and 11 (65%) of 17 patients underwent autologous stem cell transplant (ASCT). The median OS was 67 months. After a median follow-up of 38 months (range, 3-106 months), only 5 patients achieved complete remission, 5 had persistent disease, and 7 died (2 progressed to plasma cell leukemia and 1 to blastic variant). In summary, IgM PCM is highly associated with t(11;14) and lymphoplasmacytic morphology. Patients are refractory to novel therapy and progression to high-risk myeloma is common, suggesting a need for alternative novel therapies.

The short article reviews the state-of-the-art of multi-axis toolpath planning, especially for polymer extrusion. The existing approaches for geometry-based and performance-based toolpath planning are emphasized and highlighted. The future perspectives of continuous fiber-reinforced composites are addressed to overcome the research gaps as well as improve the performance of products induced by polymer extrusion.

Carbon included in coke and coal was used as a reduction agent and fuel in blast furnace (BF) ironmaking processes, which released large quantities of carbon dioxide (CO2). Minimizing the carbon consumption and CO2 output has always the goal of ironmaking research. In this paper, the reduction reactions of iron oxides by carbon, the gasification reaction of carbon by CO2, and the coupling reactions were studied by thermodynamic functions, which were derived from isobaric specific heat capacity. The reaction enthalpy at 298 K could not represent the heat value at the other reaction temperature, so the certain temperature should be confirmed by Gibbs frees energy and gas partial pressure. Based on Hess’ law, the energy consumption of the ironmaking process by carbon was calculated in detail. The decrease in the reduction temperature of solid metal iron has been beneficial in reducing the sensible heat required. When the volume ratio of CO to CO2 in the top gas of the furnace was given as 1.1–1.5, the coupling parameters of carbon gasification were 1.06–1.28 for Fe2O3, 0.71–0.85 for Fe3O4, 0.35–0.43 for FeO, respectively. With the increase in the coupling parameters, the volume fraction of CO2 decreased, and energy consumption and CO2 output increased. The minimum energy consumption and CO2 output of liquid iron production were in the reduction reactions with only CO2 generated, which were 9.952 GJ/t and 1265.854 kg/t from Fe2O3, 9.761 GJ/t and 1226.799 kg/t from Fe3O4, 9.007 GJ/t and 1107.368 kg/t from FeO, respectively. Compared with the current energy consumption of 11.65 GJ/t hot metal (HM) and CO2 output of 1650 kg/tHM of BF, the energy consumption and CO2 of ironmaking by carbon could reach lower levels by decreasing the coupled gasification reactions, lowering the temperature needed to generate solid Fe and adjusting the iron oxides to improve the iron content in the raw material. This article provides a simplified calculation method to understand the limit of energy consumption and CO2 output of ironmaking by carbon reduction iron oxides.

Cutaneous T-cell lymphomas may present with a clinical course that is incongruent with the associated histologic findings. Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma classically presents as an abrupt eruption of disseminated ulcerated annular plaques with aggressive behavior and a poor prognosis. Herein we describe a vulvar primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma with a locally aggressive clinical course that was strikingly responsive to radiation therapy. As aggressive therapy involving systemic chemotherapy is indicated for primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, appropriate clinico-pathologic correlation is crucial for preventing potentially excessive or insufficient therapeutic intervention. Our case also highlights the pivotal role of both radiation therapy and infection control in the management of aggressive cutaneous vulvar lymphomas.

The urinary bladder is rarely involved by hematopoietic neoplasms (lymphoma and leukemia). Lymphomas represent approximately 0.2% of all neoplasms of the bladder. Bladder lymphomas can be either primary or secondary to systemic lymphomas. Primary bladder lymphomas are extremely rare and most commonly seen in middle-aged women. Marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is the most common primary bladder lymphoma. Some studies suggest that primary bladder lymphomas may be associated with chronic cystitis, but this relationship is controversial. Primary bladder lymphomas are generally thought to be indolent with a favorable prognosis. Secondary bladder lymphomas are much more common, usually occurring in patients with systemic lymphomas at an advanced stage. Chronic lymphocytic leukemia/small lymphocytic lymphoma and diffuse large B-cell lymphoma are the most common secondary bladder lymphomas. The prognosis of patients with secondary bladder lymphomas is poor. In contrast to lymphomas, acute leukemia involving the bladder is less frequent. The acute leukemia in the bladder includes acute myeloid leukemia, B-lymphoblastic leukemia/lymphoma, or T-lymphoblastic leukemia/lymphoma, with the acute myeloid leukemia being more often than the lymphoblastic leukemia.

Background Several morphologic patterns of ALK+ anaplastic large cell lymphoma (ALCL) are recognized: common, small cell, lymphohistiocytic, Hodgkin-like, and composite patterns.1 Small cell (SC) and lymphohistiocytic (LH) patterns are thought to be closely associated with poorer outcome in children with ALK+ ALCL.2 However, the clinicopathologic and prognostic features of SC/LH patterns of ALK+ ALCL are not yet reported in adults. Recently, we found PD-L1 expression in a large subset of ALK+ ALCL cases, however, PD-L1 expression in SC/LH versus non-SC/LH ALCL has not been reported. Methods Among 102 adult patients with ALK+ ALCL seen at our institution from January 1, 2007 through August 30, 2018, 18 (18%) cases had a SC and/or LH pattern. The clinical, pathologic, and outcome data were compared between SC/LH and non-SC/LH ALK+ ALCL cases using Fisher’s exact test. Overall survival (OS) was analyzed using the Kaplan-Meier method and compared using the log-rank test. Results There were no significant differences in clinical features including age, gender, nodal versus extranodal involvement, B symptoms, stage, leukocytosis/lymphocytosis, and serum LDH levels between patients with SC/LH versus non-SC/LH ALK+ ALCL. Compared to non-SC/LH cases, SC/LH ALCL was more often positive for CD2 (92% vs. 36%, p = 0.0007), CD3 (81% vs. 15%, p = 0.0001), CD7 (80% vs. 37%, p = 0.03), and CD8 (54% vs. 7%, p = 0.0006). SC/LH ALCL showed a trend of decreased PD-L1 expression than non-SC/LH cases (24% vs. 46%, p = 0.11). There were no significant differences in the expression of CD4, CD5, CD25, CD43, CD45, CD56, TCR A/B, TCR G/D, cytotoxic markers, EMA, Ki-67 proliferation index. The induction chemotherapy and response rate in patients with SC/LH ALK+ ALCL were similar to patients with non-SC/LH ALK+ ALCL. After a median follow-up of 30.5 months (range, 0.3–224 months), there was no significant difference in OS between patients with SC/LH versus non-SC/LH ALK+ ALCL (p = 0.88). Conclusions In adults with ALK+ALCL, the SC/LH morphologic pattern is associated with a CD8+ T cell immunophenotype and retention of expression of T cell markers (CD2, CD3, and CD7). The trend of decreased PD-L1 expression in SC/LH ALCL suggests that these patients may not be ideal candidates for PD-L1 immunotherapy. The SC/LH patterns of ALK+ ALCL have no impact on the prognosis of adult patients which is in contrast to the reported association of the SC/LH patterns with poorer outcome in children with ALK+ ALCL. Ethics Approval The study was approved by the Institutional Review Board at MD Anderson Cancer Center, Approval number: PA16-0897 References Swerdlow SH, Campo E, The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375–2390. Brugieres L, Deley MC, CD30 (+) anaplastic large-cell lymphoma in children: Analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology. Blood 1998;92:3591–3598.

Background Few data on recurrent bacterial meningitis (RBM) in children are available. Here, we estimated the frequency of RBM in children and investigated the predisposing conditions, etiology, and clinical characteristics of RBM in children. Methods Cases of RBM in the Beijing Children’s Hospital medical record database between January 2006 and December 2019 were collected. Results In total, 1905 children with bacterial meningitis (BM) were documented in the Beijing Children’s Hospital medical record database. A total of 43 patients had RBM. The rate of RBM in children was 2.3% (43/1905). Forty (93.0%) patients had predisposing conditions, including 15 (34.9%) cases of inner ear malformations, 5 (11.6%) cases of dermal sinus tracts, 9 (20.9%) cases of head injury, 5 (11.6%) cases of congenital cranial meningocele, 3 (7.0%) cases of congenital skull base defects, 3 (7.0%) cases of immunodeficiency, and other 3 (7.0%) cases of unknown reason. Among all the 121 BM episodes, a total of 64 episodes were etiologically confirmed BM and the other 57 episodes were probable BM. Streptococcus pneumoniae (n = 52) was accounted for 81.3% of confirmed BM episodes. Thirty-four of the 37 patients with congenital or acquired anatomical defects were available to follow up after surgeries, and all of them had no BM after surgeries. Three patients with antibody deficiencies got intravenous immunoglobulin therapy and they did not suffer BM anymore. Conclusions RBM is rare in children. The majority of children with RBM had predisposing conditions including congenital/acquired anatomical defects and immunodeficiency. Interventions should be implemented to solve the underlying conditions to avoid RBM.

Objectives It has been believed that immunoglobulins can only be produced by B lymphocytes and plasma cells. We have previously reported that IgG can be expressed in myeloblasts from patients with acute myeloid leukemia (AML) and plays a role in the proliferation and apoptosis of leukemic cells. However, its clinical impact has not been assessed. Methods We assessed the expression of different classes of immunoglobulin in peripheral blood and bone marrow samples from 132 AML patients and correlated the levels of expression with clinicopathologic and molecular genetic features, as well as clinical outcome. Results We found that, in addition to IgG, all classes of immunoglobulin are expressed in myeloblasts, including IgG, IgM, IgA, IgD, IgE, Igκ, and Igλ. The levels of IgG expression (coupled with Igκ or Igλ) are higher than those of IgM, IgA, IgD, and IgE. Using receiver operating characteristic (ROC) curve analysis, we identified two distinct groups of AML patients with differential expression of immunoglobulin and different clinical outcomes. Conclusions High levels of immunoglobulin expression are associated with monocytic differentiation, multilineage dysplasia, TET2 and KRAS mutations, and poor overall survival. Assessment of immunoglobulin may serve as a useful marker for prognostic stratification and target therapy.

Sporadic reports of t(3;12)(q26.2;p13) indicate that this abnormality is associated with myeloid neoplasms, myelodysplasia, and a poor prognosis. To better characterize neoplasms with this abnormality, we assessed 20 patients utilizing clinicopathological data, cytogenetic, and targeted next-generation sequencing analysis. We also performed literature review of 58 prior reported cases. Patients included ten men and ten women with median age 55.8 years (range, 27.8–78.8). Diagnoses included 11 acute myeloid leukemia (AML, 5 de novo and 6 secondary), 5 myelodysplastic syndromes (MDS, 3 de novo excess blasts-2 and 2 therapy-related), 2 chronic myeloid leukemia BCR-ABL1-positive blast phase (1 de novo and 1 secondary), 1 primary myelofibrosis (secondary), and 1 mixed-phenotype acute leukemia T/myeloid (MPAL, secondary). Morphologic dysplasia was identified in all AML cases (5/5), MDS cases (4/4), therapy-related cases (3/3), half of myeloproliferative neoplasm cases (1/2), and one MPAL case assessed. The t(3;12) was detected de novo and in subsequent workups in 9 and 11 patients, respectively. Seven patients had t(3;12) only and eight patients had additional chromosome 7 abnormalities. Fluorescence in-situ hybridization detected MECOM (n = 11) and ETV6 (n = 7) rearrangements in all cases assessed. FLT3 internal tandem duplication was identified in five (25%) patients. We identified 13 genetic abnormalities in the de novo group (n = 9), and 25 in the secondary disease group (n = 11). All patients received chemotherapy, with seven allogeneic and two autologous stem cell transplantations. At last follow-up, 14 (70%) patients died with median survival of 6.3 months (range, 0.1–17.3) after detection of t(3;12). In summary, t(3;12)(q26.2;p13) is a rare cytogenetic abnormality in myeloid neoplasms. Myelodysplasia, chromosome 7 abnormalities, and high blast counts are common, and the prognosis is poor. Given the close relationship between the presence of this cytogenetic abnormality and the MDS-related changes, we recommend adding t(3;12)(q26.2;p13) to the list of AML with myelodysplasia-related changes defining abnormalities of the World Health Organization 2017 classification of myeloid neoplasms.

Objective To explore the clinical utility of detecting chromosome copy number variants (CNVs) in the fetus by noninvasive prenatal testing (NIPT) using the low-pass whole-genome sequencing. Methods Eight hundred and seventy-three singleton pregnancies with chromosomal microarray analysis (CMA) available between January 2017 to December 2019 and stored enough plasma sample for NIPT testing were included in this study. The CMA results show that forty-eight pregnancies with CNVs and eight hundred and twenty-five pregnancies are normal. Each pregnancy's plasma sample was blindly tested with NIPT at a depth of 0.51-1.19x for CNVs detection. The performance of the NIPT method for CNVs detection compared with the CMA method is evaluated. Results A total of fifty-two CNVs ranging from 0.1–47.3 Mb identified in forty-eight samples were identified by NIPT, of which thirty-four CNVs were consistent with CMA results. Additionally, eighteen CNVs were missed by NIPT. The overall sensitivity and specificity for the detection of CNVs were 65.38% (95% CI: 51.76%-76.89%) and 97.45% (95% CI: 96.12%-98.35%), respectively. However, for the detection of CNVs larger than 2 Mb and CNVs less than 2Mb, the sensitivities were 81.58% (95% CI: 66.27%-91.09%) and 21.43% (95% CI: 6.84%-48.32%), respectively. Conclusion Our study demonstrated that the NIPT might be an alternative method for screening CNVs comparable with other studies. However, CNVs less than 2Mb in length shows poor sensitivity by NIPT. Noninvasive CNVs detection based on the NIPT method still needs more clinical validation studies and technical improvement to achieve clinically acceptable accuracy.

Blastoid and pleomorphic mantle cell lymphomas (MCLs) are variants of aggressive histology MCL (AH-MCL). AH-MCL can arise de novo (AH-DN) or transform from prior classic variant MCL (AH-t). This study is the first integrated analysis of clinical and genomic characteristics of AH-MCL. Patient characteristics were collected from diagnosis (AH-DN) and at transformation (AH-t). Survival after initial diagnosis (AH-DN) and after transformation (AH-t) was calculated. Regression tree analysis was performed to evaluate prognostic variables and in univariate and multivariate analyses for survival. Whole-exome sequencing was performed in evaluable biopsy specimens. We identified 183 patients with AH-MCL (108 were AH-DN, and 75 were AH-t; 152 were blastoid, and 31 were pleomorphic). Median survival was 33 months (48 and 14 months for AH-DN and AH-t, respectively; P = .001). Factors associated with inferior survival were age (≥72 years), AH-t category, Ki-67 ≥50% and poor performance status. AH-t had a significantly higher degree of aneuploidy compared with AH-DN. Transformed MCL patients exhibited KMT2B mutations. AH-MCL patients with Ki-67 ≥50% had exclusive mutations in CCND1, NOTCH1, TP53, SPEN, SMARCA4, RANBP2, KMT2C, NOTCH2, NOTCH3, and NSD2 compared with low Ki-67 (

Objective To investigate the predisposing conditions, etiology and clinical characteristics of recurrent bacterial meningitis (RBM) in children.Methods Seventy patients of RBM treated in Beijing Children's Hospital from January 2006 through December 2018 were retrospectively analyzed.Results Predisposing conditions of RBM include: inner ear malformations 24(34.3%), dermal sinus tracts 15(21.4%), head trauma 15(21.4%), meningoencephalocele 12(17.1%), and immune deficiency 4(5.7%). Sixty-seven occasions of meningitis had positive bacterial cultures. Thirty-one occasions of Streptococcus pneumoniae ( S. pneumonia ) meningitis and 3 occasions of Haemophilus influenzae type b (Hib) meningitis occurred in the 24 patients with inner ear malformations; Seventeen occasions of S. pneumonia meningitis occurred in the 15 patients with head trauma, while 8 occasions of S. pneumonia meningitis in 12 patients with Meningoencephalocele; There were 2 Enterococcus faecalis meningitis, 1 Escherichia coli meningitis and 1 Staphylococcus aureus meningitis in 15 patients with dermal sinus tracts; Two of 4 patients with immune deficiency suffered S. pneumoniae meningitis.Conclusions Predisposing conditions of RBM in children include inner ear malformations, head trauma, meningoencephalocele, dermal sinus tracts, and immune deficiency. The most common etiology of RBM with inner ear malformation, head trauma, meningoencephalocele, and immune deficiency is S. pneumoniae . Empiric antibiotic treatment of RBM in children should cover S. pneumoniae.

Platelet hyperactivity is the hallmark of diabetes, and platelet activation plays a crucial role in diabetic vascular complications. Recent studies have shown that upon activation, platelet-derived miRNAs are incorporated into vascular smooth muscle cells (VSMCs), regulating the phenotypic switch of VSMC. Under diabetes, miRNA deficiency in platelets fails to regulate the VSMC phenotypic switch. Therefore, manipulation of platelet-derived miRNAs expression may provide therapeutic option for diabetic vascular complications. We seek to investigate the effect of calpeptin (calpain inhibitor) on the expression of miRNAs in diabetic platelets, and elucidate the downstream signaling pathway involved in protecting from neointimal formation in diabetic mice with femoral wire injury model. Using human cell and platelet coculture, we demonstrate that diabetic platelet deficient of miR-223 fails to suppress VSMC proliferation, while overexpression of miR-223 in diabetic platelets suppressed the proliferation of VSMC to protect intimal hyperplasia. Mechanistically, miR-223 directly targets the insulin-like growth factor-1 receptor (IGF-1R), which inhibits the phosphorylation of GSK3β and activates the phosphorylation of AMPK, resulting in reduced VSMC dedifferentiation and proliferation. Using a murine model of vascular injury, we show that calpeptin restores the platelet expression of miR-223 in diabetes, and the horizontal transfer of platelet miR-223 into VSMCs inhibits VSMC proliferation in the injured artery by targeting the expression of IGF-1R. Our data present that the platelet-derived miR-223 suppressed VSMC proliferation via the regulation miR-223/IGF-1R/AMPK signaling pathways, and inhibition of calpain alleviates neointimal formation by restoring the expression of miR-223 in diabetic platelet.

Background: Data on pyogenic liver abscess (PLA) of children in China have been limited. Method: We retrospectively reviewed PLA cases from January 2017 to June 2019 at Beijing Children’s Hospital. Clinical features and pathogens were analyzed. Results: We diagnosed 15 PLA patients in our center. Median age of onset was 3.2 years and the median diagnostic time was 9 days. Four patients (26.7%) had underlying diseases and seven patients (46.7%) had multiple organ involvement. The sensitivity achieved 100% when ultrasound and contrast-enhanced CT scan were combined use to diagnose PLA. Two patients were defined pathogen through metagenomic next-generation sequencing (mNGS). Finally, eleven patients (73.3%) were cured during follow-up time and four patients (26.7%) dead. Compared to the survival group and the death group, the patients in death group were more likely to have multiple organ involved (100 vs. 27%, P < 0.05) and bilateral lobe occupied ( P < 0.05) . Conclusions: PLA often occurs in patients with underlying disease. Multiple organs involved may lead to poor prognosis. mNGS can be a new method to detect pathogen.

Venetoclax is effective in relapsed patients with mantle cell lymphoma (MCL). Mechanisms of resistance to venetoclax in MCL are poorly understood. We describe the clinical outcomes and genomic characteristics of 24 multiply relapsed patients (median of five prior lines of therapy) who received venetoclax-based therapies; 67% had progressed on BTK inhibitors (BTKi) and 54% had blastoid or pleomorphic histology. Median follow up after venetoclax treatment was 17 months. The overall response rate was 50% and complete response (CR) rate was 21%, 16 patients had progressed and 15 died. The median progression free, overall and post venetoclax survival were 8, 13.5 and 7.3 months respectively. Whole-exome sequencing (WES) was performed on samples collected from seven patients (including five pairs; before starting venetoclax and after progression on venetoclax). The SMARCA4 and BCL2 alterations were noted only after progression, while TP53, CDKN2A, KMT2D, CELSR3, CCND1, NOTCH2 and ATM were altered 2-4-fold more frequently after progression. In two patients with serial samples, we demonstrated clonal evolution of novel SMARCA4 and KMT2C/D mutations at progression. Mutation dynamics in venetoclax resistant MCL is demonstrated. Our data indicates that venetoclax resistance in MCL is predominantly associated with non-BCL2 gene mutations. Further studies are ongoing in MCL patients to evaluate the efficacy of venetoclax in combination with other agents and understand the biology of venetoclax resistance in MCL.

There is a paucity of data regarding outcomes and response to standard therapy in patients with limited-stage (LS) agressive B-cell lymphoma (LS-ABCL) who harbor MYC rearrangement (MYC-R) with or without BCL2 and/or BCL6 rearrangements. We conducted a multicenter retrospective study of MYC-R LS-ABCL patients who received either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), or more intensive immunochemotherapy (IIC) plus or minus consolidative involved-field radiation therapy (IFRT). One hundred four patients from 15 academic centers were included. Forty four patients (42%) received R-CHOP, of whom 52% had IFRT. Sixty patients (58%) received IIC, of whom 40% had IFRT. Overall response rate was 91% (84% complete response [CR]; 7% partial response). Patients with double-hit lymphoma (DHL; n = 40) had a lower CR rate compared with patients with MYC-R only (75% vs 98%; P = .003). CR rate was higher in the IFRT vs no-IFRT group (98% vs 72%; P < .001). Median follow-up was 3.2 years; 2-year progression-free survival (PFS) and overal survival (OS) were 78% and 86% for the entire cohort, and 74% and 81% for the DHL patients, respectively. PFS and OS were similar across treatment groups (IFRT vs no IFRT, R-CHOP vs IIC) in the entire cohort and in DHL patients. Our data provide a historical benchmark for MYC-R LS-ABCL and LS-DHL patients and show that outcomes for this population may be better than previously recognized. There was no benefit of using IIC over R-CHOP in patients with MYC-R LS-ABCL and LS-DHL.

Low-grade myofibroblastic sarcoma (LGMS) is a rare, low-grade, malignant tumor and is mainly composed of myofibroblasts with varying degrees of differentiation. LGMS results in considerable diagnostic difficulty. We report a case of LGMS that occurred in multiple organs, including the diaphragmatic pleura, and head and neck region. A 34-year-old man was hospitalized in 2014 after coughing and shortness of breath for 10 days, and abdominal distension, abdominal pain, and bilateral lower extremity edema for 4 days. Before this admission, he had an abdominal tumor diagnosed in 1994 and 2003, a nasopharynx tumor in 2010, and a temporal lobe tumor in 2013. All tumors were resected surgically and the diagnosis was atypical fibrous histiocytoma and atypical fibrous xanthoma. Before surgeries for these tumors, no positron emission tomography-computed tomography (PET-CT) or whole-body scans were performed, and after surgery, there was no follow-up. After thoracoscopy and PET-CT after the most recent admission, the patient was diagnosed with LGMS with metastasis to the bone, nodes, and thoracic and abdominal cavities. The patient was discharged with albumin infusion treatment. Although LGMS is rare, it is potentially serious. Therefore, clinicians should be aware of such disease and make an early diagnosis and perform close follow-up.

High-grade B-cell lymphomas with MYC, BCL2, and BCL6 rearrangements (triple hit lymphoma) are uncommon. We studied the clinicopathologic features of 40 patients with triple hit lymphoma and compared them to 157 patients with MYC/BCL2 double hit lymphoma and 13 patients with MYC/BCL6 double hit lymphoma. The triple hit lymphoma group included 25 men and 15 women with a median age of 61 years (range, 34−85). Nine patients had a history of B-cell lymphoma. Histologically, 23 (58%) cases were diffuse large B-cell lymphoma and 17 cases had features of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Most cases of triple hit lymphoma were positive for CD10 (100%), BCL2 (95%), BCL6 (82%), MYC (74%), and 71% with MYC and BCL2 coexpression. P53 was overexpressed in 29% of triple hit lymphoma cases. The clinicopathological features of triple hit lymphoma patients were similar to patients with MYC/BCL2 and MYC/BCL6 double hit lymphoma, except that triple hit lymphoma cases were more often CD10 positive compared with MYC/BCL6 double hit lymphoma (p

Objective Diffuse large B-cell lymphoma (DLBCL) can be classified as germinal center B cell-like (GCB) or activated B cell-like (ABC)/non-GCB based on cell-of-origin (COO) classification. This study evaluated the prognostic significance of COO classification in 250 patients diagnosed with de novo DLBCL who received R-CHOP therapy. We also assessed whether the genomic status of MYC, BCL2, or MYC/BCL2 double expression (DE) could provide additional prognostic information for DLBCL patients. Methods The clinicopathologic features and outcome of patients with GCB DLBCL were compared to patients with non-GCB DLBCL using Fisher's exact test. The prognostic significance of COO, MYC-R, and MYC/BCL2 DE were studied using multivariate Cox proportional hazard analysis. Results There were 162 men and 88 women with a median age of 62 years (range, 18-86). Forty-five of 250 (18%) cases harbored MYC rearrangement (R). The frequency of MYC-R was much higher in GCB than in non-GCB tumors (40/165, 24% vs 5/85, 6%) (P = .0001). MYC/BCL2 DE was observed in 53 of 125 (42%) cases. COO classification failed to predict overall survival (OS) in DLBCL patients, either those patients with MYC-R were included (P = .10) or not (P = .27). In contrast, MYC-R and MYC/BCL2 DE significantly correlated with inferior OS (P = .0001 and P = .001, respectively). In multivariate analysis, MYC-R and MYC/BCL2 DE were still independent prognostic factors in DLBCL patients. Conclusions MYC-R and MYC/BCL2 DE are independent prognostic factors for DLBCL patients treated with R-CHOP. In this cohort, COO classification failed to stratify patient outcome.