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We developed a novel technology using the photoacoustic effect that improve needle tip visibility. We evaluated whether this technology improves needle tip visibility when performing a deep peripheral nerve block in a cadaver model. A photoacoustic needle was developed using a conventional echogenic needle with an intraluminal optical fiber. A pulsed laser sends light from a source through the fiber, which is converted to ultrasound at the needle tip using the photoacoustic effect. A nerve block expert performed deep nerve blocks using the photoacoustic needle and the ultrasound views recorded, with or without photoacoustic ultrasound at the needle tip. Needle tip visibility was evaluated by questionnaire (Likert scale 1: very poor, 5: very good) completed by anesthesiologists evaluating recorded images. The score was presented as median [first quartile, third quartile]. Statistical analysis was performed using the Wilcoxon matched-pairs signed rank test. The scores of needle tip visibility with photoacoustic ultrasound from the needle tip (4.3 [4.0, 4.5]) was significantly higher than that without photoacoustic ultrasound (3.5 [3.2, 3.8]) (p Clinical trial number University Hospital Medical Information Network Center Clinical Trials Registration System (UMIN000036974).

The 2017 revision of the World Health Organization classification of lymphoid neoplasms defined a new provisional entity, Burkitt-like lymphoma with 11q aberration (BLL-11q). BLL-11q lacks MYC rearrangement but has a chromosome 11q-gain/loss due to an inverted duplication event such as dup(11)(q23q13). Despite this classification, the association between 11q aberration and diffuse large B cell lymphoma (DLBCL) has not been fully characterized. Here, we describe an unusual case of DLBCL that presented as dup(11)(q11q24) without MYC rearrangement. A 68-year-old woman with left cervical lymphadenopathy was admitted to our hospital. Lymph node biopsy revealed diffuse proliferation of atypical large lymphoid cells positive for CD20, CD10, BCL6, MUM1, and BCL2, which led to a diagnosis of DLBCL. G-banding showed 46,X,-X,+7,dup(11)(q11q24),del(20)(q1?). Fluorescence in situ hybridization (FISH) detected duplicated CCND1 signals at 11q13.3 and duplicated KMT2A signals at 11q23.3 with similar intervals on dup(11)(q11q24). These results indicated that the chromosomal aberration was a simple duplication without inversion. FISH did not detect split MYC signals. Almost all cells were negative for MYC and CCND1. In contrast to BLL-11q, DLBCL seems to have a non-inverted simple duplication without terminal deletion. Thus, the distinction between an inverted duplication and a simple duplication by metaphase FISH is crucial, since the resultant genetic changes and disease phenotypes are different. Duplication of genes including KMT2A located on 11q may contribute to the pathogenesis of DLBCL.

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disease characterized by benign skin hamartomas, pulmonary cysts leading to spontaneous pneumothorax, and an increased risk of renal cancer. BHD syndrome is caused by germline mutations in the folliculin (FLCN) gene, a putative tumor suppressor, which result in loss of function of the folliculin protein and may cause cancer predisposition. In a 45-year-old woman with anemia, lymphadenopathy, and a history of recurrent spontaneous pneumothorax,F-18-FDG PET/CT detected diffuse and slight (18)F-FDG accumulation in the bone marrow, enlarged spleen, and systemic multiple enlarged lymph nodes. Genetic examination identified a germline nonsense mutation [c.998C > G (p.Ser333*)] on exon 9 of FLCN. Pathological examination of the lymph node revealed a diffuse neoplastic proliferation of plasmacytoid lymphocytes. The neoplastic lymphoid cells were positive for CD20, CD138, and light chain kappa as per immunohistochemistry and mRNA in situ hybridization, and a MYD88g ene mutation [c.755T > C (p.L252P)] was identified. Accordingly, she was diagnosed with lymphoplasmacytic lymphoma concomitant with BHD syndrome. To the best of our knowledge, this is the first report describing the development of hematological malignancy in a patient with BHD syndrome. The FLCN mutation might contribute lymphomagenesis as an additional mutation cooperating with the MYD88 mutation.

Disseminated cryptococcosis, usually involving the lungs and central nervous system, carries a high risk of morbidity and mortality in immunocompromised hosts. In this report, we describe a case of miliary pulmonary cryptococcosis in a patient with acute myeloid leukemia, initially resembling miliary tuberculosis. The diagnosis of disseminated cryptococcosis was made based on transbronchial lung biopsy with subsequent detection of Cryptococcus neoformans in blood and cerebrospinal fluid. The patient was treated with liposomal amphotericin B as induction therapy, followed by fluconazole as consolidation and maintenance therapies thereafter. The infection was improved immediately, and he successfully underwent hematopoietic stem cell transplantation. The present case serves as a timely reminder that a radiological miliary pattern necessitates a thorough search for a definitive microbiological and histopathological diagnosis.

Double-hit lymphoma is typically categorized as “high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements”, but in infrequent cases in which terminal deoxynucleotidyl transferase (TdT) expression is positive, it is categorized as B-lymphoblastic lymphoma (B-LBL). BCL2 rearrangements are usually caused by t(14;18)(q32;q21); variant translocations are very rare. Here, we describe an unusual case of double-hit pancreatic B-LBL with a variant translocation t(2;18)(p11;q21). A 69-year-old man was admitted because of an abdominal mass. Computed tomography scans demonstrated a diffusely enlarged pancreas and massive ascites. Cell block preparations of ascites cells revealed marked proliferation of blastic lymphoid cells positive for CD19, CD10, CD79a, PAX5, and TdT, indicating a diagnosis of B-LBL. G-banding and spectral karyotyping showed 45,XY,+X,t(2;18)(p11;q21),-4,der(5)t(1;5)(q12;p15),der(6)t(6;21)(q21;q?),t(8;14)(q24;q32),-15. Fluorescence in situ hybridization detected split BCL2 and IGH/MYC fusion signals. Almost all ascites cells were diffusely and strongly positive for MYC and BCL2. The patient died of progressive disease 20 days after admission. To our knowledge, this is the first reported case of MYC and BCL2 double-hit B-LBL with t(2;18)(p11;q21). High coexpression of MYC by t(8;14) and BCL2 by t(2;18) may be implicated in the development of B-LBL. Furthermore, double-hit B-LBL may be associated with a less favorable outcome compared with typical B-LBL.

A 45-year-old woman was diagnosed with hepatosplenic T-cell lymphoma (HSTCL), a rare subtype of peripheral T-cell lymphoma. She received different types of chemotherapy, but disease progression was observed. To reduce the tumor burden before an unrelated bone marrow transplantation, combination chemotherapy consisting of the gemcitabine, carboplatin, and dexamethasone (GCD) was administered as bridging therapy, resulting in a reduction in the number of lymphoma cells. We were then able to perform bone marrow transplantation. Although she experienced some adverse events, she successfully achieved long-term remission. We herein report a successful case of HSTCL treated with unrelated stem cell transplantation following the GCD regimen as bridging chemotherapy.

Background: We developed a novel technology using the photoacoustic effect that improve needle tip visibility. We evaluated whether this technology improves needle tip visibility when performing a deep peripheral nerve block in a cadaver model.Methods: A photoacoustic needle was developed using a conventional echogenic needle with an intraluminal optical fiber. A pulsed laser sends light from a source through the fiber, which is converted to ultrasound at the needle tip using the photoacoustic effect. A nerve block expert performed deep nerve blocks using the photoacoustic needle and the ultrasound views recorded, with or without photoacoustic ultrasound at the needle tip. Needle tip visibility was evaluated by questionnaire (Likert scale 1 : very poor, 5 : very good) completed by anesthesiologists evaluating recorded images. The score was presented as median [first quartile, third quartile]. Statistical analysis was performed using the Wilcoxon matched-pairs signed rank test. Results: The scores of needle tip visibility with photoacoustic ultrasound from the needle tip (4.3 [ 4.0, 4.5 ]) was significantly higher than that without photoacoustic ultrasound (3.5 [ 3.2, 3.8 ]) (pConclusions: Ultrasound emitted at the needle tip using the photoacoustic effect improves needle tip visibility during deep peripheral nerve blocks.

Chromosomal rearrangements involving the MECOM locus, which consists of two genes MDS1 and EVI1 located at 3q26.2, are found in different types of myeloid malignancies [1,2]. Among these, the t(3;1...

Scopulariopsis alboflavescens is a soil saprophyte that is widely distributed in nature. Recently, there have been increasing number of reports of invasive infections with Scopulariopsis species in immunocompromised patients. In this report, we described an adult woman with acute myeloid leukemia and who developed S. alboflavescens pneumonia. Liposomal amphotericin B and voriconazole combination therapy was unsuccessful and the patient died because of pneumonia. Scopulariopsis is highly resistant to available antifungal agents and almost invariably fatal. This case report should alert clinicians to the importance of listing Scopulariopsis as a pathogenic fungus in immunocompromised patients.

Immune reconstitution affects clinical outcomes after allogeneic hematopoietic stem cell transplantation (HSCT), and it has been suggested that lymphocyte recovery affects survival after HSCT. However, few studies have examined lymphocyte recovery in Asian patients who received mycophenolate mofetil (MMF) prophylaxis for graft-versus-host disease. We retrospectively evaluated early lymphocyte recovery after HSCT among Japanese adults who received MMF prophylaxis. Patients were divided into two groups according to their median absolute lymphocyte count (ALC) on day 28 after HSCT as follows: the “low ALC group” (≤ 0.22 × 109 cells/L) and the “high ALC group” (> 0.22 × 109 cells/L). With a median follow-up of 317 days, the high ALC group showed significantly better overall survival than the low ALC group (at 1 year: 62 vs. 46%, P = 0.02). The high ALC group also tended to have better non-relapse mortality than the low ALC group (at 1 year: 13 vs. 23%, P = 0.08). There was no significant difference in relapse rate between the high and low ALC groups (at 1 year: 29 vs. 35%, P = 0.2). We conclude that among Japanese patients who received MMF prophylaxis, ALC on day 28 after HSCT was effective in predicting overall survival and non-relapse mortality.

Constitutional translocations that coincide with t(9;22)(q34;q11.2) may lead to unnecessary treatments in chronic myeloid leukemia (CML) patients, as, under the standard criteria, a diagnosis of CML with additional chromosomal abnormalities indicates an accelerated phase (AP). In the present report, a 47-year-old male had pain in the right foot due to gout. Peripheral blood examination showed leukocytosis with left shift. Bone marrow aspiration revealed myeloid hyperplasia with megakaryocytosis. RT-PCR revealed the major BCR-ABL fusion transcript, and CML in the chronic phase was diagnosed, followed by nilotinib treatment. Although WBC counts decreased immediately, G-banding analysis showed 46,XY,t(8;22)(q24;q11.2),t(9;22)(q34;q11.2) [20]. The t(8;22)(q24;q11.2) translocation is known to be recurrent in Burkitt's lymphoma. The diagnosis was changed to CML in AP, leading to B-lymphoid crisis. Unexpectedly, the karyotype was 46,XY,t(8;22)(q24;q11.2) [20] in hematological complete remission, even after 3 months. Fluorescence in situ hybridization on metaphase spreads revealed the MYC signal on the der(22)t(8;22), indicating that the 8q24 breakpoint was centromeric to MYC at 8q24.21. G-banding analysis of phytohemagglutinin-stimulated peripheral blood T-lymphocytes also indicated 46,XY,t(8;22)(q24.1;q11.2). We conclude that the t(8;22) is constitutional in this patient. As the tumor suppressor gene TRC8/RNF139 is disrupted by constitutional t(8;22)(q24.13;q11.21) in dysgerminoma, it may be associated with the onset of CML.

Oncogene amplification is uncommon in acute myeloid leukemia (AML). Cytogenetically, it is primarily found as double minute chromosomes (dmin) or homogeneously staining regions (hsr). A 62-year-old woman was admitted to our hospital because of anemia and thrombocytopenia. Her bone marrow was hypercellular with 78.6% myeloperoxidase- positive blasts. Some had micronuclei. The patient was diagnosed with AML M2 and remains in complete remission (CR) after induction therapy. G-banding at diagnosis showed 51,XX,t(11;16)(q13;p11.2),+r1,+mar1×4. Spectral karyotyping confirmed t(11;16) and revealed that the ring and the marker chromosomes were derived from multiple copies of ring chromosome 8. Fluorescence in situ hybridization (FISH) with a MYC probe at 8q24 detected amplified MYC signals on 1 large and 4 small ring chromosomes 8. One MYC signal was deleted from one of the 2 chromosomes 8. FISH with a FUS probe at 16p11.2 showed monoallelic deletion of FUS. Immunohistochemistry demonstrated MYC protein overexpression at diagnosis and almost negative expression in CR. These results indicate that MYC amplification could occur in ring chromosomes without dmin. A cryptic MYC deletion suggests that an episome model could be applicable to MYC amplification in ring chromosomes as observed for dmin and hsr. Furthermore, considering 2 further reported cases, t(11;16)(q13;p11) may be a very rare but recurrent translocation in AML.

Lymph node infarction is very rare, and is frequently associated with neoplasms, such as malignant lymphoma and non-neoplastic disease, or interventions such as fine-needle aspiration (FNA). A 76-year-old-man presented with cervical lymph node swelling. Although FNA was performed, the findings were insufficient for a definitive diagnosis. Consequently, surgical biopsy of the cervical lymph node was performed, which revealed total infarction; a diagnosis of classical Hodgkin lymphoma was made later. Both lymphoma itself and FNA may cause total lymph node infarction, which makes diagnosis confusing. Therefore, it is important to repeat the biopsy rather than repeat FNA to correctly diagnose malignant lymphoma, including Hodgkin lymphoma.

In multiple myeloma (MM), MYC rearrangements that result in increased MYC expression are associated with an aggressive form of MM and adverse outcome. However, the consequences of MYC amplification in MM remain unclear. Here, we describe an unusual case of plasma cell leukemia (PCL) harboring MYC amplification on double minute chromosomes (dmin). A 79-year-old woman was initially diagnosed as having BJP-κ type MM with bone lesions. After seven months, the disease progressed to secondary PCL: leukocytes 49.1 × 109/L with 77% plasma cells showing lymphoplasmacytic appearance. The bone marrow was infiltrated with 76% plasma cells immunophenotypically positive for CD38 and negative for CD45, CD19, CD20, and CD56. The karyotype by G-banding and spectral karyotyping was 48,XX,der(14)t(11;14)(q13;q32),+der(14)t(14;19)(q32;q13.1),+18,6~95dmin[15]/46,XX[5]. Fluorescence in situ hybridization detected multiple MYC signals on dmin and double IGH/CCND1 fusion signals on der(14)t(11;14) and der(14)t(14;19). Most plasma cells were diffusely and strongly positive for MYC and CCND1 by immunohistochemistry. The patient died of progressive disease after one week. MYC amplification led to high expression of MYC and rapid disease progression, indicating its clinical significance in the pathogenesis of MM/PCL. MYC amplification on dmin may be a very rare genetic event closely associated with the progression to PCL and coexistence of IGH/CCND1 fusions.

Kanazawa Sutra (KanS) is a medicinal thread that is used for the treatment of anal fistula. It is used as a substitute for Kshara Sutra (KS) which is used in Ayurvedic medicine. KanS is composed of Ficus carica latex (FCL), Capsicum annuum tincture (CAT), Achyranthes fauriei Kshara (which is processed ash from the whole plant) and powdered Curcuma longa rhizome (CLR). In this study, we evaluated the ingredients of KanS by measuring nitric oxide (NO) production in murine macrophage-like cell line J774.1 as well as examining cytotoxicity to rat skeletal muscle myoblasts (L6) and L6 differentiation, with a view to improving its pharmacological effect. We focused on Mallotus japonicus bark (MJB), which is described in the Japanese Pharmacopeia and belongs to the Euphorbiaceae family. Its biological activities were evaluated in a similar manner to the evaluation of KanS ingredients. We found that MJB extracts showed similar biological activity to Euphorbia neriifolia latex (ENL), an ingredient of KS. We conclude that the NO inhibitory activity of KanS is mainly due to CLR, and its cytotoxicity to L6 and inhibitory activity on L6 differentiation are mainly due to CLR and FCL. As CAT has no characteristic activity, the biological activity and the anal fistula treatment ability of KanS would be improved by substituting MJB for CAT.

To identify strategies for reducing emesis induced by the CHOP regimen, which includes high-dose steroids, we prospectively evaluated the efficacy of palonosetron in Japanese patients. Palonosetron was administered at a dose of 0.75 mg via intravenous injection over 30 min before chemotherapy on day 1. Patients kept diaries of chemotherapy-induced nausea and vomiting (CINV) incidence from the start of chemotherapy until 168 h afterwards, in which they documented the occurrence and severity of nausea, vomiting, anorexia, and the use of rescue medication. The primary endpoint was the overall occurrence rate of nausea, vomiting, and anorexia; these rates were 56, 12, and 62 %, respectively, including all grades. The rates and severity of symptoms tended to worsen 120-168 h after completing oral prednisolone. We defined complete response (CR) as no vomiting and no use of rescue therapy. The CR rates of post palonosetron 0.75 mg treatment in the acute (0-24 h), delayed (24-168 h), and overall phases (0-168 h) were 86, 66, and 62 %, respectively. Antiemetic strategies of CHOP regimen for day 6 and, thereafter, should be investigated.

The t(11;20)(p15;q11∼12) translocation is a very rare but recurrent cytogenetic aberration that occurs in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). This translocation was shown to form a fusion gene between NUP98 at 11p15 and TOP1 at 20q12. Here, we describe a new case of de novo AML M2 with t(11;20) which was associated with another balanced translocation. An 81-year-old man was admitted to undergo salvage therapy for relapsed AML. G-banding and spectral karyotyping showed 46,XY,t(2;5)(q33;q31),t(11;20)(p15;q12)[20]. Expression of the NUP98/TOP1 fusion transcript was confirmed: NUP98 exon 13 was in-frame fused with TOP1 exon 8. The reciprocal TOP1/NUP98 fusion transcript was also detected: TOP1 exon 7 was fused with NUP98 exon 14. After achieving hematological complete remission, the karyotype converted to 46,XY,t(2;5)(q33;q31)[19]/46,sl,t(11;20)(p15;q12)[1]. FISH analysis demonstrated that the 5q31 breakpoint of t(2;5) was centromeric to EGR1. In all 10 cases described in the literature, the NUP98 exon 13/TOP1 exon 8 fusion transcript was expressed, indicating that it may be responsible for the pathogenesis of MDS/AML with t(11;20). On the other hand, the TOP1/NUP98 transcript was coexpressed in 4 cases of de novo AML, but not in 3 cases of therapy-related MDS. Thus, this reciprocal fusion may be associated with progression to AML.

The t(12;17)(p13;q11∼21) translocation is a very rare but recurrent cytogenetic aberration observed predominantly in early pre-B acute lymphoblastic leukemia (ALL) with CD19+CD10-CD33+ phenotype. This translocation was shown to form a fusion gene between TAF15 at 17q12 and ZNF384 at 12p13. On the other hand, der(1;18)(q10;q10) has been detected as a rare unbalanced whole-arm translocation leading to trisomy 1q in myeloid malignancies. We describe here the first case of mixed phenotype acute leukemia (MPAL) with a t(12;17)(p13;q21)/TAF15-ZNF384, which also had der(1;18)(q10;q10) as an additional abnormality. A 74-year-old woman was diagnosed with MPAL, B/myeloid, because bone marrow blasts were positive for myeloperoxidase, CD19, and CD22. Chromosome analysis showed 46,XX, +1,der(1;18)(q10;q10),t(2;16)(q13;q13),t(12;17)(p13;q21). Expression of the TAF15-ZNF384 fusion transcript was confirmed: TAF15 exon 6 was fused in-frame to ZNF384 exon 3. This type of fusion gene has been reported in 1 acute myeloid leukemia case and 3 ALL cases. Thus, at present, it is difficult to find a specific association between the structure of the TAF15-ZNF384 fusion gene and the leukemia phenotype. The TAF15-ZNF384 fusion may occur in early common progenitor cells that could differentiate into both the myeloid and lymphoid lineages. Furthermore, der(1;18)(q10;q10) might play some role in the appearance of an additional myeloid phenotype.

Kleine-Levin syndrome is a rare sleep disorder of unknown etiology characterized by repetitive episodes of hypersomnia between asymptomatic periods. We report the case of a 13-year-old girl who presented with drowsiness triggered by influenza A as the first episode. Magnetic resonance imaging (MRI) on day 6 showed transient reduction of diffusion in the corpus callosum splenium. The patient was diagnosed with encephalopathy with a reversible splenial lesion. The symptoms resolved after 10 days, but additional episodes of hypersomnia lasting 5-10 days occurred 1, 5, 6, 11, 13, and 25 months after the first episode. MRI during hypersomnia indicated no lesions, and sleep duration and cognition were normal between episodes. The patient was diagnosed with Kleine-Levin syndrome. Electroencephalographic and clinical findings during the first episode were similar to those during the other episodes. Encephalopathy with a splenial lesion and Kleine-Levin syndrome may have similar pathological mechanisms causing a disturbance in consciousness.

Waste disposal site is one of the important sinks of chemicals. A significant amount of perfluoroalkyl and polyfluoroalkyl substances (PFASs) such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexanoic acid (PFHxA) have been brought into it. Because of their aqueous solubility, PFASs are released to landfill effluent waters, from which PFASs are efficiently collected by adsorption technique using granular activated carbon (GAC). The exhausted GAC is reactivated by heating processes. The mineralization of PFASs during the reactivation process was studied. Being thermally treated in N2 atmosphere, the recovery rate of mineralized fluorine and PFC homologues including short-chained perfluorocarboxylic acids was determined. If the reagent form of PFOA, PFHxA, and PFOS were treated at 700 °C, the recovery of mineralized fluorine was less than 30, 46, and 72 %, respectively. The rate increased to 51, 74, and 70 %, if PFASs were adsorbed onto GAC in advance; moreover, addition of excess sodium hydroxide (NaOH) improved the recovery to 74, 91, and 90 %. Residual PFAS homologue was less than 1 % of the original amount. Steamed condition did not affect destruction. The significant role of GAC was to suppress volatile release of PFASs from thermal ambient, whereas NaOH enhanced destruction and retained mineralized fluorine on the GAC surface. Comparing the recovery of mineralized fluorine, the degradability of PFOS was considered to be higher than PFOA and PFHxA. Whole mass balance missing 9~26 % of initial amount suggested formation of some volatile organofluoro compounds beyond analytical coverage.

No optimum treatment of iatrogenic immunodeficiency-associated lymphoproliferative disorders due to methotrexate in patients with rheumatoid arthritis (MTX-LPD) has yet been established, although MTX withdrawal is known to have a substantial effect on tumor regression. Here, we retrospectively analyzed 20 cases of MTX-LPD. Tumor shrinkage occurred in 18 of 20 cases, but only following MTX withdrawal. This tumor regression ratio was considerably better than in previous reports, and appeared due to longer "watchful waiting." Lymphocyte recovery at 2 weeks after MTX withdrawal was significantly higher in cases with tumor regression in 1 month than in those without tumor regression (p = 0.001). Median time to maximal efficacy after MTX cessation in cases without chemotherapy was 12 weeks (range 2-76). In conclusion, watchful waiting for a longer period after MTX cessation with observation of early lymphocyte recovery and uninterrupted continuation of other anti-rheumatoid drugs may be an acceptable management plan for MTX-LPD.

We examined serum levels of various cytokines, chemokines, growth factors, and adhesion molecules in patients with uncomplicated influenza (n = 20) and influenza virus-associated encephalopathy (IE) (n = 18) to understand the underlying mechanism of IE. We found that IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, G-CSF, GM-CSF, TNF-α, TIMP-1, MMP-9, sE-selectin, and neutrophil elastase were elevated significantly in sera from patients with uncomplicated influenza and those with IE, compared with normal controls (n = 20). Of note, neutrophil elastase, sE-selectin, IL-8, and IL-13 were elevated significantly in IE as compared with uncomplicated influenza. In the present study, for the first time, we found that serum levels of neutrophil elastase were increased in patients with IE compared with uncomplicated influenza, which suggested that cerebral endothelial damage in the development of IE was mediated by neutrophil elastase. The present study implied that anti-elastase agents are possibly an effective therapeutic protocol for IE, but this needs further elucidation.

The t(8;21)(q22;q22) translocation is specifically observed in acute myeloid leukemia (AML) M2 subtype, whereas del(5q) is one of the most common cytogenetic aberrations in myelodysplastic syndromes (MDS). Thus, t(8;21)(q22;q22) and del(5q) appear to be mutually exclusive, and the association between them has not been characterized yet. Here, we report an 81-year-old woman with coexistent t(8;21)(q22;q22) and del(5q) at initial diagnosis. The bone marrow was infiltrated with 18.4% myeloblasts, and showed marked myeloid and erythroid dysplasia. Myeloblasts were positive for CD19 and CD56 as well as CD13, CD33, CD34 and HLA-DR. G-banding and spectral karyotyping showed 46,XX,del(5)(q?),t(8;21)(q22;q22)[18]/46,XX[2]. Both del(5)(q?) and t(8;21)(q22;q22) were present in a single clone. Fluorescence in situ hybridization (FISH) on metaphase spreads detected a RUNX1/RUNX1T1 fusion signal on the der(8)t(8;21)(q22;q22), and confirmed deletion of CSF1R signaling at 5q33-q34 on the del(5)(q?). Furthermore, FISH on interphase nuclei revealed that the RUNX1/RUNX1T1 fusion signal and deletion of CSF1R signaling were found in 66.0% and 58.0% of interphase cells, respectively, suggesting that del(5)(q?) occurred in cells with RUNX1/RUNX1T1. These results indicated a diagnosis of AML with t(8;21)(q22;q22)/RUNX1/RUNX1T1 rather than MDS, even though the percentage of bone marrow myeloblasts was less than 20%. Based on these findings, together with those of other reported cases, del(5q) seems to be an extremely rare but recurrent secondary aberration in AML with t(8;21)(q22;q22).

Rhabdomyolysis is characterized by a marked elevation of the creatine kinase (CK) levels and myoglobinuria, thus leading to renal dysfunction. Various viruses or bacteria can be etiologic agents, but mycosis has only rarely been reported to be a cause of rhabdomyolysis. In this report, we describe an adolescent male with acute myeloid leukemia who underwent allogeneic bone marrow transplantation and thereafter developed rhabdomyolysis and Candida parapsilosis fungemia almost at the same time. Following treatment for C. parapsilosis, the transaminase and CK levels both satisfactorily decreased. This case illustrates that C. parapsilosis infection may be a causative agent of rhabdomyolysis in immunocompromised patients.

The t(8;21)(q22;q22) translocation involving RUNX1 at 21q22 and RUNX1T1 at 8q22 is found in 10% of cases of acute myeloid leukemia (AML) M2 subtype. This translocation results in the formation of a RUNX1/RUNX1T1 fusion gene, which contributes to leukemic transformation by transcriptional repression of normal RUNX1 target genes, on der (8)t(8;21)(q22;q22). AML with t(8;21) is usually associated with a good response to chemotherapy and long-term diseasefree survival. It has been reported that variant translocations, the majority of which are complex three-way translocations, occur in approximately 3 to 4% of cases of AML with t(8; 21). However, clinical and hematological features of AML with variant t(8;21) remain to be completely characterized. Here, we describe a new complex translocation t(8;11;21) (q22;q24;q22) in a case of AML with RUNX1/RUNX1T1. A 62-year-old man was admitted because of anemia and thrombocytopenia. He had no history of chemotherapy or radiotherapy. Peripheral blood analysis showed hemoglobin 7.8 g/dL, platelets 33 × 10/L, and leukocytes 4.6 × 10/L with 14% myeloblasts. Bone marrow was hypercellular with 18.2% myeloblasts, 60.0% mature myeloid cells, 5.6% eosinophils, 4.4% monocytes, 6.6% lymphocytes, and 2.6% erythroblasts. Myeloblasts had Auer rods and a few azurophilic granules in the basophilic cytoplasm. Myeloid dysplasia including the pseudo-Pelger-Huet anomaly was also found (Fig. 1A). Myeloblasts were positive for myeloperoxidase staining and immunophenotypically positive for CD13, CD19, CD33, CD34, CD56, and HLA-DR. In light of the cytogenetic and genetic abnormalities described below, we made a diagnosis of AML with RUNX1/RUNX1T1 according to the World Health Organization classification. Initial induction therapy with cytarabine and idarubicin failed, but the patient achieved hematological and cytogenetic complete remission (CR) after re-induction therapy with cytarabine and daunorubicin. The residual myeloblasts were negative for CD19 and CD56 after the attainment of CR. He received a further three courses of consolidation therapy with high-dose cytarabine, and remained in molecular CR for more than 10 months. G-banding analysis of bone marrow cells at diagnosis showed 46, XY, t (8;11;21) (q22; q24; q22) [20] (Fig. 1B). Spectral karyotyping confirmed three derivative chromosomes: der(8)t(8;21)(q22;q22), der(11)t(8;11)(q22;q24), and der(21)t(11;21)(q24;q22) (Fig. 1C). Fluorescence in situ hybridization (FISH) on metaphase spreads detected the RUNX1/RUNX1T1 fusion signal on the der (8) t (8;21) (q22; q22) (Fig. 1D). Reverse-transcription polymerase chain reaction also confirmed the RUNX1/RUNX1T1 fusion transcript. We have presented a complex three-way translocation t(8; 11;21)(q22;q24;q22) and detected the RUNX1/RUNX1T1 fusion gene in a patient with AML. In the Mitelman database, four AML M2 cases with t (8;11; 21) involving 8q22 and 21q22 have been described (Table 1). Their breakpoints in chromosome 11 were clustered to 11p15 (two cases) and 11q13 (two cases). Thus, to our knowledge, this is the first case with a complex t(8;21) translocation involving the breakpoint 11q24. With regard to breakpoints in other chromosomes, Kim et al. summarized 24 adult cases of AML with variant t(8;21), and demonstrated that there was no overlap of breakpoints in the involved chromosomes, except for 20p13 (two cases). Thus, there seem to be few recurrent breakpoints involved in variant t(8;21). The t(8;11;21)(q22;q24;q22) translocation generated only the RUNX1/RUNX1T1 fusion gene on the der(8)t(8;21)(q22

Background Human herpesvirus 6 (HHV-6) encephalitis is a known life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, few studies have focused on the occurrence of HHV-6 encephalitis in patients receiving mycophenolate mofetil (MMF) combined with a calcineurin inhibitor as prophylaxis for graft-versus-host disease (GVHD). This study aimed to investigate the impact of MMF administered for GVHD prophylaxis in the occurrence of HHV-6 encephalitis after allo-HSCT and the characteristics of this condition. Methods and results We retrospectively analyzed 73 patients who underwent allo-HSCT (83 transplants) at our hospital between April 2010 and December 2015. MMF (2-3 g/d) was administered along with a calcineurin inhibitor. Seven patients (8.0%) developed encephalitis due to HHV-6. The median period from allo-HSCT to the onset of HHV-6 encephalitis was 23 days (range, 17-98 days). The cumulative incidence of HHV-6 encephalitis on day 100 after treatment was 12% and 6% in patients who underwent cord blood transplantation (CBT) and non-CBT (ie, bone marrow transplantation and peripheral blood stem cell transplantation), respectively (P = 0.344). Neurological symptoms of encephalitis were more severe in non-CBT cases than those in CBT cases. All patients diagnosed with HHV-6 encephalitis were treated with ganciclovir or foscarnet. None of the enrolled patients died from HHV-6 encephalitis. Conclusions Mycophenolate mofetil may have the potential to increase the frequency of severe HHV-6 encephalitis in patients undergoing CBT and non-CBT. Thus, MMF should be administered with caution, and patients should be monitored closely for HHV-6 encephalitis even those who did not undergo CBT.

chromosomes, and revised the karyotype as follows (Fig. 2ab): 44,XY,-2,inv(3)(p25q21),der(5)del(5)(p?) del(5)(q?),der(7)(11?::7p13→7q22::7?::1?),add(9) (p13),-11,der(17)t(2;17)(q11.2;p11.2),der(20)t(2;20) (? ;q11 .2 ) ,2dmin[2] /42 , s l ,de l (1 ) (q? ) , r (6 ) ,de r (7 ) (7? : :p13→qter ) , -12 , -16 , -der (17) t (2 ;17) ,der (17) (2?::?::2?::17p11.2→17q23::12?),-2dmin[1]. Furthermore, dmin were shown to be derived from chromosomes 8. We next performed fluorescence in situ hybridization (FISH) with a probe for MYC located at 8q24 (Vysis LSI IGH/ MYC/CEP 8 Tri-Color Dual Fusion Probes), and detected multiple MYC signals on dmin (Fig. 1c). The patient underwent non-myeloablative cord blood transplantation (CBT) after conditioning with total body irradiation (TBI), fludarabine, and melphalan. However, the disease relapsed due to graft failure. G-banding at relapse after CBT showed 41~42,XY,2,inv(3)(p25q21),-4,der(5)del(5)(p?)del(5)(q?),der(7) (11?::7p13→7q22::7?::1?),add(9)(p13),-11,-12,-16,der(17) (2?::?::2?::17p11.2→17q23::12?),der(20)t(2;20)(?;q11.2) [cp5]/46,XY[15]. Thus, dmin disappeared, although other structural abnormalities remained. The patient next received an unrelated bone marrow transplant (u-BMT) after conditioning with TBI, fludarabine, and busulfan, but the disease progressed again. Unexpectedly, some of the myeloblasts had micronuclei (Fig. 1d). The similar karyotype did not include dmin (Fig. 1e): 40~43,XY,2,inv(3)(p25q21),-4,der(5)del(5)(p?)del(5)(q?),der(7) (11?::7p13→7q22::7?::1?),add(9)(p13),-11,-12,-16,der(17) (2?::?::2?::17p11.2→17q23::12?),der(20)t(2;20)(?;q11.2) [cp14]/41,sl,add(2)(q11.2),add(8)(q24),-add(9),+add(9) (p13)[5]/46,XY[1]. FISH also showed only three or four MYC signals (Fig. 1f). The patient succumbed to pneumonia 19 months after initial diagnosis. Double minute chromosomes (dmin) are small, acentric, extrachromosomal fragments that frequently mediate oncogene amplification and reflect rapid disease progression in human tumors. It has been shown that elimination of dmin can be induced by treating cancer cells with low concentrations of hydroxyurea or gemcitabine in vitro, resulting in reduced tumorigenicity and reversion of phenotype [1, 2]. Morphologically, the loss of dmin is facilitated by incorporation of dmin into micronuclei. However, this phenomenon has been reported only infrequently in primary tumor cells from patients [3]. A 58-year-old man was initially diagnosed with myelodysplastic syndrome, refractory cytopenia with multilineage dysplasia (MDS-RCMD). G-banding showed 44~45,XY,der(2;17)(q10;q10),inv(3)(p25q21),-5,-7,add(9) (p13),-11,-20,+mar1,+mar2,+mar3[cp8]/45,sl,+8[3]/46 ,XY[9]. After 11 months, the disease progressed to acute myeloid leukemia (AML). Peripheral blood values were as follows: hemoglobin 105 g/L, platelets 80 × 10/L and leukocytes 3.9 × 10/L with 22 % myeloblasts. Bone marrow was hypercellular with 46.6 % myeloblasts, which had many granules with vacuoles but no micronuclei (Fig. 1a). G-banding revealed the appearance of dmin (Fig. 1b): 42~45,XY,der(2;17)(q10;q10),inv(3)(p25q21),-5,-7,add(9) (p13),-11,-20,+mar1,+mar2,+mar3,0~85dmin[cp13]/42,sl ,add(1)(q21),add(1)(q32),+der(2)add(2)(p21)add(2)(q21),der(2;17),-inv(3),add(7)(p22),-12,-16,+mar4[2]/46,XY[5]. Spectral karyotyping (SKY) clarified the origin of marker

myeloperoxidase and α -naphthyl butyrate esterase staining. Surface marker analyses with three-color fl ow cytometry by CD45/side scatter gating revealed that immature cells (76.9% of all bone marrow cells) were positive ( 20%) for CD4 (25.3%), CD13 (86.7%), CD33 (100.0%) and CD34 (99.2%). Considering cytogenetic abnormalities and MLL rearrangements described below, we made a diagnosis of AML with a variant MLL translocation in the World Health Organization classification, or AML M4 in the French – American – British classification. Induction therapy with idarubicin and cytosine arabinoside was started, and the patient achieved a hematological complete remission (CR). However, she suffered from severe pneumonia and heart failure, and died of multiple organ failure 2 months after the initial diagnosis. Chromosome analysis of the bone marrow cells at the initial diagnosis showed 50,XX, 4, 6, 8,?t(10;11)(p12;q14)

Chromosomal abnormalities of intravascular large B-cell lymphoma (IVLBCL), a rare form of extranodal diffuse large B-cell lymphoma, have been described in only a small number of cases. A 59-year-old female presented with pancytopenia and splenomegaly. Bone marrow was normocellular with 30.4% abnormal large lymphoid cells that were positive for CD5, CD19, CD20, HLA-DR and λ chain. Bone marrow biopsy showed intrasinusoidal infiltration of large lymphoid cells. G-banding and spectral karyotyping of the bone marrow cells demonstrated a complex karyotype as follows : 48,XX,-8,+r(11),+12,del(12)(p?) ×2,+18,der(19)(19?::p13 → qter),der(21)t(8;21)(q11.2;p11.2). Fluorescence in situ hybridization on interphase nuclei revealed three signals of CCND1 at 11q13, but two signals of BIRC3 at 11q22 and MLL at 11q23, indicating that r(11) contained CCND1. Together with other reported cases, our results indicate that the gain of 11q as well as trisomy 18 may be among the recurrent chromosomal aberrations in IVLBCL. Furthermore, an additional ring chromosome 11 could be a novel mechanism leading to the gain of 11q.

Background In T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), activating mutations of NOTCH1 are observed in more than 50% of cases, whereas the t(7;9)(q34;q34) involving NOTCH1 at 9q34 and TRB@ at 7q34 is an extremely rare but recurrent translocation. Patient A 41-year-old male with a large mediastinal mass, pleural effusion, and lymphadenopathy was diagnosed as having T-LBL. Lymphoma cells were positive for CD4, CD8, CD2, CD3, CD5, CD7, CD10, and TdT. Results G-banding and spectral karyotyping of pleural effusion cells showed 47,XY,dup(1)(q21q32),t(7;9)(q34;q34),+20. Genomic polymerase chain reaction (PCR) revealed that the 5' end of TRB@ J1-5 was connected with the middle of NOTCH1 exon 25 (434 bp downstream from its 5' end) in a 'head-to-head' configuration on the der(9)t(7;9), although nine extra bases were inserted between the two genes. Reverse transcription-PCR confirmed expression of the TRB@/NOTCH1 fusion transcripts. Similarly, the 5' end of J1-5 was fused to the shortened exon 25 with nine extra bases. The NOTCH1 breakpoint in exon 25 was very close to transcription start sites of deleted Notch1 in murine T-ALL. Conclusions The TRB@/NOTCH1 fusion gene with a NOTCH1 breakpoint in exon 25, which has not previously been detected in four other reported cases with t(7;9), could lead to aberrant expression of the truncated NOTCH1 by TRB@ enhancer elements. The resultant NOTCH1 receptor deleting most of the extracellular domain may be implicated in the pathogenesis of T-LBL by ligand-independent, constitutive activation of the NOTCH1 pathway, suggesting avenues for future therapy with γ-secretase inhibitors.

Objectives: The t(9;11)(p22;p15) is a very rare but recurrent translocation in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) blast crisis. The translocation results in a fusion gene between NUP98 at 11p15 and PSIP1 encoding two transcriptional coactivators, p52 and p75, at 9p22. Here, we describe the first case of myelodysplastic syndrome (MDS) with t(9;11)(p22;p15). Patient: A 64-yr-old woman presented pancytopenia, trilineage dysplasia, and 9.2% blasts in the bone marrow, indicating the diagnosis of MDS. Results: G-banding and spectral karyotyping showed 46,XX,t(9;11)(p22;p15)[20]. Reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing detected four types of NUP98/PSIP1-p52 and two types of NUP98/PSIP1-p75 fusion transcripts. Essentially, the NUP98 exon 12 or exon 11 by alternative splicing was fused in-frame with the PSIP1 exon 8. Real-time quantitative (RQ) PCR for NUP98/PSIP1/GAPDH demonstrated a 4-log decrease after cord blood transplantation and a 2-log increase at relapse. Conclusions: The fusion genes combining NUP98 exon 11/12 with PSIP1 exon 8, which have never been detected in other AML/CML cases, may be implicated in the pathogenesis of MDS. Furthermore, RQ-PCR for NUP98/PSIP1 could be useful to monitor minimal residual disease.

Myelodysplastic syndromes (MDS) with pure red cell aplasia (PRCA) have been shown to be a rare form of MDS. A 35-year-old man presented with pancytopenia: hemoglobin 59 g/L, reticulocytes 2 × 10(9)/L, platelets 33 × 10(9)/L, and leukocytes 1.8 × 10(9)/L with 1% blasts. Bone marrow was hypercellular with 50.4% myeloid cells, 0.0% erythroblasts, 25.4% basophils, and 5.6% myeloblasts. Dysplastic changes including pseudo-Pelger-Huët anomaly of neutrophils and mononuclear micromegakaryocytes were found. Immunohistochemistry with glycophorin C confirmed erythroid aplasia. Cytogenetic analysis showed 46,XY,i(17)(q10)[18]/47,XY,+8[2]. Considering two reported cases, these findings indicate that isolated i(17q) may be implicated in the pathogenesis of MDS with PRCA as a recurrent cytogenetic aberration.

Pure erythroid leukemia (PEL) is an extremely rare disorder characterized by neoplastic proliferation of immature erythroblasts. A 66-year-old man, who had received chemoradiotherapy for hypopharyngeal cancer, was admitted because of pancytopenia. Bone marrow was infiltrated with 81% proerythroblasts positive for CD71 and CD235a. An increased number of macrophages with active hemophagocytosis was also present. Chromosome analysis showed hypodiploid complex abnormalities. The patient died of progressive disease despite induction chemotherapy. Erythroblastic infiltration into the liver and hemophagocytosis in the spleen were found at autopsy. Therapy-related PEL with hemophagocytic syndrome and hepatic infiltration of PEL has never been reported.

Dear Editor, Prominent nuclear indentations or invaginations of blasts are also called “cuplike” nuclei. Acute myeloid leukemia with cuplike nuclei (AML-CN) has distinct clinicopathologic and molecular features including lack of CD34 and HLA-DR expression, normal karyotype, NPM1 mutations, and FLT3internal tandem duplication (ITD) and often looks like acute promyelocytic leukemia (APL), microgranular variant [1–3]. Here, we present an interesting nuclear morphology of blasts, that is, nuclear bilobation at diagnosis and nuclear indentation at relapse, in BCR/ABL1-positive, CD34and HLA-DRnegative AML. A 67-year-old man was admitted to hospital because of marked leukocytosis. He had been diagnosed with pharyngeal squamous cell carcinoma 5 years earlier and had received concurrent radiotherapy and chemotherapy with cisplatin. He had no hepatosplenomegaly or lymphadenopathy on admission. Peripheral blood values were hemoglobin 92 g/L, platelets 32×10/L, and leukocytes 282.8×10/L with 84 % blasts. More than half of the blasts had bilobed nuclei with fine chromatin, agranular basophilic cytoplasm, and no Auer rods (Fig. 1a). Bone marrow was hypercellular with 70.0 % blasts stained positive for myeloperoxidase. Immunophenotyping determined that they were also positive for CD13 and CD33, but negative for CD34 and HLA-DR (Fig. 1b). Chromosome analysis of bone marrow cells showed 46,XY,t(1;9;22)(q32;q34;q11.2)[20]. Fluorescence in situ hybridization (FISH) revealed the BCR/ABL1 fusion signal on der(22)t(9;22)(q34;q11.2) (Fig. 1c). Reverse-transcription polymerase chain reaction confirmed the p210-type BCR/ABL1 fusion transcript, whereas PML/RARA fusion and FLT3-ITD were negative. Considering the normal peripheral blood count 12 months before admission and no hepatosplenomegaly, we made a diagnosis of BCR/ABL1-positive AML rather than chronic myeloid leukemia in blast crisis. According to the World Health Organization classification, a diagnosis of therapy-related myeloid neoplasms was also made. The patient received standard induction therapy followed by treatment with dasatinib and achieved complete remission. However, after 3 months, bone marrow examination revealed 23.4 % blasts. The karyotype was 46,XY, t ( 1 ; 9 ; 2 2 ) ( q 3 2 ; q 3 4 ; q 1 1 . 2 ) [ 1 ] / 4 6 , s l , a d d ( 1 ) (q32),add(18)(q21)[15]/46,XY[4]. Spectral karyotyping (SKY) confirmed the complex translocation (Fig. 1d). The leukocyte count increased to 70.8×10/L with 93 % blasts. Unexpectedly, approximately 30 % of the blasts showed nuclear indentation (Fig. 1e), while nuclear bilobation was rare. Because of the appearance of cuplike nuclei, we examined NPM1 mutations and detected the type A mutation in the bone marrow cells at diagnosis and at relapse, although NPM1 mutations are observed at low frequency in therapy-related myeloid neoplasms [4, 5]. FLT3-ITD was also negative at relapse. The patient died of progressive disease 11 months after the initial diagnosis. K. Yamamoto (*) :K. Yakushijin :Y. Sanada : S. Kawamoto : H. Matsuoka :H. Minami Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan e-mail: kyamamo@med.kobe-u.ac.jp

We describe here a new case of therapy-related acute leukemia with t(1;21)(p36;q22). A 25-year-old man was admitted because of anemia and thrombocytopenia. Four years before, he had received combination chemotherapy including etoposide for seminoma. Bone marrow was hypercellular, with 49% myeloperoxidase (MPO) staining-negative blasts. Chromosome analysis showed 46,XY,t(1;21)(p36.3;q22)[11]/49,sl,+8,+16,+20[9]. Fluorescence in situ hybridization demonstrated that RUNX1 signals at 21q22 were split onto the der(1)t(1;21) and der(21)t(1;21). Immunophenotypic analyses revealed that blasts were positive for CD19, CD79a, and cytCD22, as well as MPO, CD13, and CD33, fulfilling the diagnostic criteria of mixed phenotype acute leukemia, B/myeloid. The patient died of disease progression after 10 months. Thus, acute leukemia with t(1;21) and RUNX1 rearrangement could be associated with B/myeloid mixed phenotype as well as previous topoisomerase II inhibitor therapy and poor prognoses.

We describe here a novel unbalanced whole-arm translocation der(3;10)(q10;q10) in a 58-year-old man with acute monocytic leukemia. Bone marrow was massively infiltrated with 22.2% monoblasts, 55.4% promonocytes, and 5.6% monocytes. These monocytic cells were positive for myeloperoxidase and alpha-naphthyl butyrate esterase staining. Surface marker analysis revealed that they were positive for CD4, CD13, CD33, CD56, and HLA-DR but negative for CD14 and CD34. Chromosome analysis of the bone marrow cells showed 46,XY,+3,der(3;10)(q10;q10)[18]/46,XY[2]. Spectral karyotyping confirmed der(3;10)(q10;q10) as a sole structural abnormality. By acquisition of a normal chromosome 3 but not a chromosome 10, the der(3;10)(q10;q10) resulted in trisomy 3q and monosomy 10p. The +3,der(3;10)(q10;q10) is thought to play a crucial role in the pathogenesis of acute monocytic leukemia because of the gain of 3q or the loss of 10p.

A 69-year-old man was admitted because of macrocytic anemia and peripheral monocytosis: hemoglobin 75 g/L and white blood cells 16.0x10(9) /L with 22% monocytes. Five years prior, he had received CHOP regimen and radiotherapy for diffuse large B-cell lymphoma. Bone marrow was hypercellular with trilineage dysplasia and 2.4% blasts. Chromosome analysis showed 46,XY,t(1;11)(p32;q23),del(5)(q13q35),+8,inv(9)(p11q13),-15,-21,+mar1. These findings indicated a diagnosis of therapy-related myelodysplastic/myeloproliferative neoplasms (t-MDS/MPN). Fluorescence in situ hybridization revealed that the breakpoint at 11q23 was centromeric to the MLL gene. Taken together with the previously reported cases, trilineage dysplasia and del(5q) without MLL rearrangement suggests that alkylating agents may have a crucial role in the pathogenesis of t-MDS/MPN, which is a rare but recognizable entity.