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TAFRO syndrome, a rare systemic inflammatory disorder, commonly develops in an acute or subacute manner, with an aggressive clinical behavior. A substantial number of cases of TAFRO syndrome presenting with abdominal pain, and adrenal abnormalities on imaging have also been reported. A 54-year-old man developed severe acute abdominal pain. Bilateral adrenal swelling was detected on computed tomography. Although the abdominal pain resolved spontaneously, a fever and anasarca were observed. The patient was eventually diagnosed with TAFRO syndrome, and corticosteroid administration resulted in remission. TAFRO syndrome should be included in the differential diagnosis of acute abdomen and adrenal abnormalities.

An 84-year-old woman, who was diagnosed with rheumatoid arthritis (RA) and was treated with methotrexate and, subsequently, etanercept (ETN) for 6 years, presented with rapidly progressing painful ...

An unconscious 55-year-old man with a history of neurofibromatosis type 1 (NF1) was transported to the emergency department and was diagnosed with acute renal failure owing to a large bladder tumor. A submucosal tumor was also identified in the duodenum. The patient was diagnosed with a primary gastrointestinal stromal tumor (GIST) of the bladder and duodenum. After six cycles of regorafenib therapy, 18F-fluorodeoxyglucose accumulation in the duodenal GIST on positron emission tomography-computed tomography (PET-CT) showed a partial metabolic response. Currently, no standard drug therapy for unresectable or relapsed NF1-associated GIST has been established. Regorafenib may thus be considered as and appropriate initial therapy.

A 55-year-old man with several comorbidities including idiopathic interstitial pneumonia under long-term corticosteroid therapy, longstanding myocardial infarction, chronic heart failure, paroxysmal atrial fibrillation, gastro-esophageal reflux disease, constipation, and history of paralytic ileus, was diagnosed with chronic myelogenous leukemia (CML) in the chronic phase. He also tested positive for anti-topoisomerase I antibodies without clinical diagnosis of any connective tissue disease, including systemic sclerosis. Approximately 5 months after the initiation of nilotinib for CML, he developed upper abdominal distension with intermitting abdominal pain, and based on abdominal computed tomography findings, a diagnosis of pneumatosis intestinalis (PI) was made. Five courses of hyperbaric oxygen therapy quickly eliminated the PI and related symptoms without the cessation of nilotinib and, thereafter, additional oral prokinetic agents and non-absorbable antibiotics ensured the non-recurrence of PI. At 6 and 18 months after commencing nilotinib therapy, major and complete molecular response were achieved, respectively. It is suspected that both gastrointestinal hypokinesis related to the presence of anti-topoisomerase I antibodies and mucosal permeability due to corticosteroid therapy had existed. Thus, subsequent administration of nilotinib may have triggered PI by depressing gastrointestinal motility via the inhibition of c-kit.

Adult T cell leukemia/lymphoma(ATLL)is a highly aggressive peripheral T-cell neoplasm associated with infection by a specific retrovirus, human T-cell lymphotropic virus type-I(HTLV-I). This hematological malignancy is resistant to conventional chemotherapy, and has a poor prognosis. Two previous multicenter trials for ATLL(Japan Clinical Oncology Group 9303 and 9801)evaluated the efficacy of dose-intensified multi-agent chemotherapy with vincristine, cyclophosphamide, doxorubicin, and prednisolone(VCAP), doxorubicin, ranimustine, and prednisolone(AMP), and vindesine, etoposide, carboplatin, and prednisolone(VECP)with granulocyte-colony stimulating factor(G-CSF)and intrathecal prophylaxis. However, these trials showed a median survival of only 13 months, not yielding satisfactory outcomes. Thus, a novel therapeutic modality is needed. A defucosylated humanized monoclonal antibody targeting CC chemokine receptor 4(CCR4), designated mogamulizumab, recently became available for this purpose. CCR4 is a chemokine receptor expressed on helper T cells, regulatory T cells(Tregs), and certain types of T-cell neoplasms, such as ATLL. With an increased binding affinity to the Fc-gamma receptor on effector cells, this drug markedly enhances antibody-dependent cell-mediated cytotoxicity(ADCC)against ATLL cells expressing CCR4. In a phase II clinical trial for relapsed ATLL, objective responses were noted in 13 of 26 evaluable patients, including eight complete responses. Although mogamulizumab is a promising therapeutic alternative for patients with relapsed/refractory ATLL, there is some apprehension regarding treating patients with mogamulizumab before allogeneic hematopoietic stem cell transplantation(allo-HSCT). The fear is that it might affect regulatory T cell(Treg)reconstitution because these cells also express CCR4. Fewer circulating Tregs cause severe graft-versus-host disease(GVHD)after allo-HSCT because these cells have an Case Report

A 48-year-old man was diagnosed with multiple myeloma (IgG-k) and was treated with high-dose dexamethasone as an induction therapy followed by thalidomide-based regimens. Approximately 22 months after the initial diagnosis, the patient developed secondary plasma cell leukemia (PCL) with a white blood cell (WBC) count of 20.2 × 109/L including 79.5% plasma cells. A G-banding chromosomal analysis in the bone marrow showed an t(11;14) abnormality of up to 5%, which was not detected at initial diagnosis. We immediately started bortezomib and dexamethasone therapy, but in just 7 days, the WBC count elevated to 48.5 × 109/L, and approximately 95% of them were medium-sized atypical lymphoid cells with multilobated nuclei. Although we subsequently initiated alternative regimens, the patient’s condition deteriorated, and he died 4 months after developing PCL. Approximately 2 months before his death, the diameter of myeloma cells in the bone marrow enlarged by approximately twofold, and pleomorphic nuclei were present, indicating an anaplastic myeloma transformation. Concurrently, a 100% increase of the t(11;14) clone frequency was observed in the G-banding-analyzed bone marrow cells. Morphological transformation of myeloma cells into multilobated plasma cell nuclei can be considered as the starting point of the sequential process leading to anaplastic myeloma.

A 61-year-old woman with rheumatoid arthritis who was undergoing hemodialysis for end-stage renal failure was transferred to our hospital due to severe thrombocytopenia and anemia. A bone marrow biopsy showed the complete absence of megakaryocytes and erythroblasts. Cyclosporine treatment resulted in the improvement of her megakaryocyte and erythroblast levels, and a decrease in her serum level of anti-c-Mpl (thrombopoietin receptor) antibodies. After this initial improvement, her anemia progressively worsened, despite the continuous administration of immunosuppressive therapy with cyclosporine. Her platelet and leukocyte counts remained stable. This is the first report of a probable case of anti-c-Mpl antibody-associated pure red cell aplasia and acquired amegakaryocytic thrombocytopenic purpura.

An 86-year-old man presented with enlarged left submandibular, left inguinal, and superficial femoral lymph nodes. He was diagnosed with Langerhans cell sarcoma (LCS) on the basis of the histopathological findings of the left inguinal lymph node biopsy. In addition, laboratory examinations revealed normocytic normochromic anemia, and bone marrow aspiration and biopsy led to a diagnosis of idiopathic cytopenia of undetermined significance (ICUS). Because of the patient's age, he was administered a regimen of cyclophosphamide, pirarubicin, vincristine, and prednisolone (THP-COP), and achieved a partial response after six courses. However, he developed acute myeloid leukemia (AML) 11 months after completion of the THP-COP therapy, and received only supportive care until his death. LCS is an extremely rare and aggressive dendritic cell neoplasm. To the best of our knowledge, only 67 cases have been reported in the literature. There are case reports describing the concurrence of hematological malignancies. Herein, we report the first documented development of LCS in a patient with ICUS who progressed to AML, and summarize the published data on the epidemiology of and therapeutic options for LCS.

脂肪性肝疾患（FLD）の発生に及ぼすアルコール摂取の影響には不明な点が残されている．今回我々は2008年1月から12月までに腹部超音波検査を含む健康診断を受診した3185名を対象に脂肪肝の頻度に対するアルコール摂取の影響を多重ロジスティック回帰分析により解析した．内臓脂肪性肥満，空腹時高血糖，脂質異常症はいずれも脂肪肝頻度の増加と関連していた．1日アルコール摂取量20 g未満（少量飲酒群），20 g以上から40 g未満（軽度飲酒群）および40 g以上から60 g未満（中等度飲酒群）では脂肪肝のオッズ比は有意に低下した．男女別に飲酒の影響を検討したところ，男性では軽度飲酒群から中等度飲酒群におけるFLDの調整オッズ比は非飲酒群および1日アルコール摂取量60 g以上の多量飲酒群より低かった．一方，女性ではアルコール摂取の影響は明らかでなかった．以上の結果からFLDに及ぼす飲酒の影響には性差があり，男性では軽度ないし中等度までのアルコール摂取は過栄養性FLDの発生を抑制する可能性が示唆された．

Double- and triple-hit lymphomas (DHL/THL), high-grade B-cell lymphomas with an extremely poor prognosis, are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint. The successful use of dose-adjusted (DA) EPOCH-R in patients with MYC-positive lymphoma and Burkitt lymphoma (BL) was recently reported. A 74-year-old man with acute renal dysfunction and hyperkalemia was transferred to our emergency center by ambulance. PET-CT revealed a left renal hilar mass enveloping the abdominal para-aortic domain and bladder and hydronephrosis. High (18)F-FDG uptake revealed lymph node, peritoneum, and multiple bone metastases. Analysis of the bone marrow aspirate revealed abnormal lymphoid cells with deeply basophilic cytoplasm and numerous vacuoles resembling Burkitt cells. Chromosomal analysis revealed a complex chromosomal karyotype, including t(14;18)(q32;q21), and FISH analysis confirmed split BCL2, BCL6, and MYC signals. Bone marrow biopsy revealed diffusely infiltrating large abnormal lymphoid cells with a CD10⁺, CD20⁺, BCL2⁺, BCL6⁺, c-MYC⁺ and MUM1(-) immunophenotype. B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and BL, was diagnosed. The patient achieved a partial response after eight courses of DA-EPOCH-R chemotherapy. Our experience suggests that DA-EPOCH-R may be an effective treatment for DHL/THL.

症例は74歳，男性．2002年7月に肝細胞癌と診断され，2003年9月までに合計3回のTAEを施行されいる．2004年2月ごろより背部痛を自覚，エコー，CTにて肝S4に腫瘤を認めたため精査目的で入院となった．腹部エコーでは肝S4に直径6cmほどの不整型で境界不明瞭な低エコー腫瘤を認めた．腹部CTでは動脈相で腫瘍辺縁のみ濃染するhypovascularな腫瘤で，中心部にはlipiodolの沈着を認めた．その他，肺および胸椎に多発性転移を認めた．臨床経過並びに画像所見よりTAE後の肉腫様変化と診断した．入院中に突然死したため死因を検索する目的からも病理解剖が行われた．腫瘍は肝左葉から肝被膜を超えて横隔膜へ浸潤していた．他臓器では両側副腎，肺，胸椎への転移が確認された．また心筋内には最大径5mm以下の微小な転移巣が多発していた．組織所見では肝腫瘍および各転移巣で錯綜する短紡錘形の腫瘍細胞の増殖を認めた．免疫染色ではcytokeratin, vimentinともに陽性を示し，肝癌の肉腫様変化に矛盾しなかった．肉腫様肝癌が心臓に転移した稀な症例と考えられたので報告する．

Erythropoiesis progresses from stem cell expansion on stromal cells through the formation of an erythroblastic island. Our aim was to assess the feasibility of using human stromal cells for erythroid production and differentiation. When cord blood CD34+ cells were cocultured with telomerized human stromal cells (hTERT-stromal cells) for 2 weeks, the CD34+ cells and burst-forming units-erythroid (BFU-E) significantly expanded, and a few hematopoietic cells transmigrated below the stromal layer. When nonadherent hematopoietic progenitor cells that had expanded above the hTERT-stromal cells (group B) were collected and subjected to our erythroid-differentiation protocol, they differentiated into erythroblasts with a slight hemoglobin synthesis. When the few hematopoietic cells that had transmigrated below the stromal layer were expanded for an additional 2 to 6 weeks, they exhibited a cobblestone-like appearance, and a large amount of BFU-E clambered weekly from the underside of the stromal layer to above the stromal layer (group C). When the hematopoietic progenitor cells in group C were subjected to the erythroid-differentiation protocol, large numbers of mature erythroblasts (more than 300,000 times the initial CD34+ cell number) were produced. Our hTERT-stromal expansion protocol may contribute to the construction of a system for large-scale, long-term production of erythroid cells.

A 55-year-old female with stage IVA follicular lymphoma in third complete remission underwent allogeneic peripheral blood stem cell transplantation. Neutrophil engraftment was achieved on day +18; however, platelet counts remained below 10 × 10(3)/µL, necessitating transfusions twice a week for more than 3 months. Bone marrow showed a decreased number of megakaryocytes with hypolobulated nuclei. No graft versus host disease, viral infection, or disease relapse was observed. Furthermore, severe thrombocytopenia below 5.0 × 10(3)/µL refractory to transfusion appeared on day +240 after influenza virus infection. Treatments with intravenous immunoglobulin, romiplostim, and rituximab were administered without any recovery. Subsequently, eltrombopag was initiated on day +443, after which platelet counts rose gradually and continued to rise above 20 × 10(3)/µL after 10 weeks of administration. The serum thrombopoietin (TPO) level was markedly elevated, and anti-TPO receptor (TPOR) antibody was detected in the patient's serum. Anti-TPOR antibody may play an important role in some cases of prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation with unknown etiology, and eltrombopag could be a novel therapeutic option for such cases.

Chemotherapy-induced peripheral neuropathy (CIPN) is difficult to manage. A phase III trial conducted in the United States demonstrated that duloxetine was effective for CIPN caused by taxane and platinum-based chemotherapy. No randomized trial of duloxetine for CIPN has been conducted in Japan. In this open-label, randomized, crossover study, eligible patients were randomized to Group A or Group B. Group A received duloxetine 20 mg/day orally for the first week and 40 mg/day for the next 3 weeks. Group B received vitamin B12 (VB12) 1.5 mg/day orally for 4 weeks. After a 2- to 4-week washout period, treatment was crossed over for another 4 weeks. The severity of numbness and pain was assessed using a visual analog scale (VAS). Thirty-four patients were enrolled. Obvious decreases in the mean VAS scores for numbness and pain were observed for the periods of duloxetine administration. Significant differences were observed between the duloxetine-first (Group A) and the VB12-first (Group B) groups with respect to numbness (p = 0.03) and pain (p = 0.04) at 4 weeks after administration. Fatigue was observed in six of the 34 participants (17.6 %). Our data suggests that duloxetine has a beneficial effect on CIPN caused by oxaliplatin, paclitaxel, vincristine, or bortezomib in Japanese patients.

A 79-year-old female diagnosed with T cell/histiocyte-rich large B cell lymphoma in complete remission after six cycles of rituximab-combined chemotherapy developed severe anemia, reticulocytopenia, and bone marrow erythroid hypoplasia. She was diagnosed with pure red cell aplasia (PRCA) accompanied by Coombs-negative autoimmune hemolytic anemia evidenced by a lack of glycophorin-A-positive cells in the bone marrow, haptoglobin under the detection level, and a high titer of RBC-bound IgG. Anti-erythropoietin receptor (EPOR) antibody was detected in the serum, and oligoclonal α/β and γ/δ T cells were also detected in her peripheral blood by Southern blotting analysis. Parvovirus B19 DNA was not detected by PCR. Although the treatment with rituximab had limited efficacy (specifically, only for hemolysis), subsequent cyclosporine therapy led to prompt recovery of erythropoiesis with the disappearance of anti-EPOR antibody and oligoclonal T cells. This is the first case report of anti-EPOR antibody-associated PRCA in a patient with malignant lymphoma treated successfully with cyclosporine.

The antitumor effect of high-dose chemotherapy (HDC) followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) is considered superior to that of conventional chemotherapy. However, the long-term benefits of this strategy in Japan remain unclear.Therefore, in this study, 109 cancer patients enrolled between 1989 and 1999 were treated with HDC and auto-PBSCT. Patients were evaluated for long-term survival and late-onset complications, including secondary malignancy. The mean number of CD34+ cells harvested per apheresis was larger in the group receiving high-dose cytosine arabinoside or high-dose etoposide plus granulocyte colony-stimulating factor (G-CSF) than in the group receiving conventional chemotherapy plus G-CSF. The 5-year overall survival rates for non-Hodgkin’s lymphoma patients in first complete remission (CR) (83.2%), second or subsequent CR (74.1%), or first partial remission (PR) (66.7%) at the time of transplantation were significantly higher than those with no remission (35.7%) at the time of transplantation (first CR,P < .05; second or subsequent CR,P < .05; first PR,P < .05). The 5-year overall survival (OS) rates for breast cancer was 40.8%, and the disease-free survival rate was extremely low (8.8%). The 5-year OS rates for chemotherapy-sensitive and chemotherapy-resistant diseases at the time of transplantation were 32.7% and 35.7%, respectively, a difference that was not considered significant. The 5-year OS for germ cell tumor was 80.0%, and the disease-free survival rate was 77.9%. The rate of therapy-related death was 8.2%. The occurrence rate of secondary malignancy was 0.9%. Late-onset complications were observed in 4 cases (glomerulonephritis, interstitial pneumonitis, ulcerative colitis, and acute myelogenous leukemia). At 3.7%, the occurrence rate was not very high, but most complications of auto-PBSCT were life threatening and interfered with patients’ quality of life. A careful follow-up is required for at least 2 years after transplantation, because the mean occurrence time of late-onset complications is 16.7 months posttransplantation.

Primary malignant lymphoma of the uterine cervix is a rare disease, and the therapeutic strategy has not been clearly established. A 45-year old woman presented with vaginal bleeding and hypermenorrhea in January 2012. Physical examination revealed a mass in the pelvic cavity approximately the size of a neonate's head. Pelvic magnetic resonance imaging(MRI) showed a solid mass 11 cm in size in the uterine cervix with homogeneous low intensity on T1-weighted images, iso-high intensity on T2-weighted images, and heterogeneous iso-high intensity on gadolinium-diethylenetriaminepentaacetate(Gd- DTPA)-enhanced images. Multiple lymphadenopathy were also detected in the pelvis. The Papanicolaou smear indicated class 5 cervical cytology, and a subsequent histological examination by a punch biopsy of the cervix showed diffuse infiltration of medium- to large-sized mononuclear cells that stained positive for CD20 and CD79a and negative for CD3, CD5, and EBER. Bone marrow biopsy revealed no abnormality. Positron emission tomography-computed tomography(PET-CT)showed strong fluorodeoxyglucose(FDG)accumulation in the uterine cervix mass, and in the pelvic and right inguinal lymphadenopathy. The patient was diagnosed with diffuse large B-cell lymphoma of the uterine cervix, Ann Arbor stage II AE. She was successfully treated with 8 courses of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone(R-CHOP) chemotherapy, and maintains a complete remission.

A 58-year-old female diagnosed with early stage esophageal carcinoma in our hospital underwent endoscopic resection by endoscopic submucosal dissection (ESD) in April 2013. F-FDG PET/CT performed immediately prior to the ESD showed focal F-FDG accumulations in the vertebral body of Th8, and vertebral body and arch of L4 with SUV max of 3.98–4.42 (Fig. 1a–c). No masses or osteoclastic lesions were observed. MRI findings of the lesions showed low intensity on T1WI and high intensity on STIR image (Fig. 2a–d). To clarify the cause of the FFDG accumulation in the bone, we performed bone biopsy from the vertebral arch of L4. Histopathological findings revealed hypercellular marrow (80 % cellularity) and increases in number and size of megakaryocytes, most of which were in maturated form with hyperlobulated nuclei, which are usually found in cases with myeloproliferative neoplasm (MPN) (Fig. 3a, b). Reticulin fibrosis of marrow was observed minimally by Gitter staining (Fig. 3c), and collagen fibrosis was not observed. In contrast, laboratory workup for peripheral blood showed no abnormality: WBC 6,920/lL (stab 0.0 %, seg 61.0 %, lymph 30.0 %, mono 6.0 %, eosino 1.5 %, and baso 1.5 %), RBC 452 9 10/ lL, Hb 14.1 g/dL, Ht 40.6 %, PLT 33.3 9 10/lL, reticulocytes 1.2 %, LDH 229 U/L, VB12 351 mg/dL, and NAP score 223. Bone marrow biopsy subsequently performed from the left iliac bone showed normocellular marrow, but the number of megakaryocytes was also increased (Fig. 3d). Furthermore, JAK2 V617F mutation was detected in the bone marrow sample by real-time qualitative PCR with a sensitivity of more than 2 % of all alleles. G-banding showed normal diploid karyotype, and BCR–ABL translocation was not detected by FISH analysis. 5 months after the first visit, her laboratory data of peripheral blood was within the normal range, and FFDG PET/CT also showed similar F-FDG accumulation in the bone, without new lesions. We will continue to follow her progress carefully. The JAK2 V617F mutation is present in patients with Philadelphia-negative MPN, including over 90 % of polycythemia vera cases and about half of essential thrombocythemia and primary myelofibrosis cases [1]. The JAK2 V617F mutation may also be detected in healthy individuals without overt MPN [2]. Nielsen et al. [2] reported that the JAK2 V617F mutation was detected in 18 of 10,507 participants (0.2 %) in the general population, and three of these 18 individuals with the JAK2 V617F mutation developed overt myeloproliferative disorder during up to 17.6 years of follow-up. In the present case, focal F-FDG accumulation in bone marrow and histopathological findings, other than the finding of the left iliac bone marrow as positive for JAK2 V617F mutation, suggest that the patient is more likely to develop some form of overt MPN in the A. Fujimi (&) Y. Kanisawa Department of Hematology and Oncology, Oji General Hospital, 3-4-8 Wakakusa-cho, Tomakomai 053-8506, Japan e-mail: Akihito.fujimi@ojihosp.or.jp

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare disorder characterized by severe thrombocytopenia associated with total absence or a selective decrease in bone marrow megakaryocytes. A 67-year-old male presented with a 2-month bleeding tendency. He was referred to our hospital because of severe thrombocytopenia. Bone marrow biopsy showed complete absence of megakaryocytes without dysplasia in cells of the myeloid and erythroid lineages. AATP was diagnosed. In addition, mild normocytic normochromic anemia and reticulocytosis were also observed and haptoglobin was below the detectable level. Coombs-negative autoimmune hemolytic anemia (AIHA) was diagnosed based on the high titer of RBC-bound IgG and negative direct and indirect coombs test results. He was first treated with cyclosporine 200 mg per day and subsequently with prednisolone but only slight temporary improvement was achieved. Administration of eight doses of rituximab 375 mg/m(2) per week ameliorated both thrombocytopenia and anemia. AATP should be considered in the differential diagnosis of thrombocytopenia, and immunosuppressive therapy is a potential first-line treatment. This is the first case report of AATP accompanied by AIHA successfully treated with rituximab.

A 69-year-old male was referred to our hospital because of anemia, renal insufficiency, and a positive urine test for Bence-Jones protein. A bone marrow examination showed 73.7% of myeloma cells with lymphoplasmacytic morphology, the strong expressions of CD20 and CD23 by flow cytometry, and the chromosomal aberration of CCND1/IGH by FISH analysis. He was diagnosed with multiple myeloma, IgG-λ type. The initial treatment with bortezomib plus dexamethasone (BD) provided a rapid decrease in the level of IgG; however, he developed bortezomib-induced recurrent paralytic ileus accompanied by aspiration pneumonia during the second course. Interestingly, CD23 expression on myeloma cells decreased from 87.7% to 2.2% after 2 courses of BD. Negative CD23 expression was maintained following lenalidomide plus dexamethasone therapy. There are extremely few reports on CD23 expression on myeloma cells, and this is the first case report of multiple myeloma in which CD23 expression was lost after BD therapy.

We report a case of anal variceal bleeding successfully treated with endoscopic injection sclerotherapy (EIS). A 64-year-old man with alcoholic liver cirrhosis was hospitalized because of repeated anal bleeding. Colonoscopy revealed external anal varices connecting with rectal varices. Three days after admission, external anal variceal bleeding was observed. Angiography revealed that the anorectal varices formed by hepatofugal inferior mesenteric vein drained into the internal iliac vein. On angiography, the variceal blood flow rate was extremely low, therefore we performed EIS. Seven days after therapy, thrombosis of anorectal varices was observed.

A 54-year-old man was referred to our hospital with an esophageal lesion. On esophagogastroduodenoscopy a pedunculated elevated lesion about 15mm in diameter was identified in the abdominal esophagus. The surface of the lesion had irregular nodules with white coating. We found no Barrett's mucosa around the lesion. A biopsy specimen of this tumor showed well-differentiated adenocarcinoma. A lower esophagus-proximal gastrectomy was performed because this tumor was suspected to invade the submucosal layer. Eventually, the histological diagnosis after resection was esophageal adenocarcinoma arising from cardiac glands, limited to the mucosal layer (M2). This origin of the esophageal adenocarcinoma is rare. Furthermore, this form of the tumor is especially unusual, and there have been few reports of similar cases.

A case of adenocarcinoma arising in Meckel’s diverticulum in a 58-year-old man is reported. Abdominal computed tomography and ultrasonography showed a solid tumor in the middle of abdomen. Capsule endoscopy (CE) showed tumorous lesion in the distal ileum. Single-balloon enteroscopy (SBE) subsequently showed the tumor in Meckel’s diverticulum. Furthermore, biopsy specimen obtained from the lesion revealed it as adenocarcinoma. At laparotomy, we found the tumor at the blind end of the diverticulum and enlarged lymph node about 7 cm in diameter in the small intestinal mesentery. Segmental resection of the ileum, including the tumor-bearing diverticulum, was performed along with regional lymph node dissection. Histologically, origin of the tumor was assumed to be ectopic gastric mucosa. Although neoplasm in Meckel’s diverticulum is difficult to diagnose preoperatively, the combination of CE and SBE was useful. Based on our search, this is thought to be the first case of neoplasm in Meckel’s diverticulum diagnosed endoscopically.

We generated red blood cells (RBC) from cord blood (CB) CD34+ cells using a four-phase culture system. We first cultured CB CD34+ cells on telomerase gene-transduced human stromal cells in serum-free medium containing stem cell factor (SCF), Flt-3/Flk-2 ligand, and thrombopoietin to expand CD34+ cells (980-fold) and the total cells (10,400-fold) (first phase). Expanded cells from the first phase were liquid-cultured with SCF, interleukin-3 (IL-3), and erythropoietin (EPO) to expand (113-fold) and differentiate them into erythroblasts (second phase). To obtain macrophages for the next phase, we expanded CD34+ cells from a different donor using the same coculture system. Expanded cells from the first phase were liquid-cultured with granulocyte-macrophage colony stimulating factor, macrophage-colony stimulating factor (M-CSF), IL-3, and SCF to generate monocytes/macrophages (75-fold), which were incubated with type AB serum and M-CSF to fully differentiate them into macrophages. Erythroblasts were then co-cultured with macrophages in the presence of EPO to expand (threefold) and fully differentiate them (61% orthochromatic erythroblasts plus 39% RBC) (third phase). RBC were purified from erythroblasts and debris through a deleukocyting filter to generate 6.0 x 10(12) RBC from 1.0 unit of CB (3.0 transfusable units). Qualitatively, these RBC showed a hemoglobin content, oxygenation of hemoglobin, and in vivo clearance similar to those of adult peripheral RBC. Finally, an almost complete enucleation of orthochromatic erythroblasts (99.4%) was achieved by the cultivation method recently described by Miharada et al. in the absence of macrophages and cytokines (fourth phase). RBC were purified from remnant erythroblasts and debris by passage through a deleukocyting filter to generate 1.76 x 10(13) RBC from 1.0 unit of CB (8.8 transfusable units), the highest yield ever reported. Thus, this method may be useful for generating an alternative RBC supply for transfusions, investigating infectious agents that target erythroid cells, and as a general in vitro hematopoietic model system.

A 57-year-old woman with a pancreatic body tumor was admitted to our hospital. She was diagnosed with unresectable advanced pancreatic cancer (stage IVb) due to portal vein invasion, arterial invasion, retro peritoneal invasion and lymphnode metastases, so radiation therapy (50 Gy/25 Fr) with concurrent arterial infusion of gemcitabine (GEM) was carried out. After the chemo-radiation therapy, her arterial infusion treatment of GEM was continued in our outpatient clinic for 3 months until she was complicated with ascites due to peritoneal dissemination. Peritonitis carcinomatosa was controlled by S-1 oral administration with intraperitoneal infusion of MMC and CDDP. For 18 months after discharge, she has maintained good quality of life without any adverse effects by a continuous dose of S-1 at our outpatient clinic.

A 67-years old woman was referred to our hospital in October 1992 with thrombocytopenia and splenomegaly. A bone marrow biopsy revealed decreased cellularity, with moderately increased reticulin fibrosis and discrete dysmorphic megakaryocytes but no signs of dysplasia in the erythroid or the myeloid lineages. The karyotype of the bone marrow cells was t(12;17) (q24;q11). She was diagnosed as having agnogenic myeloid metaplasia. The patient received only blood transfusions until November 1998 when leukocytosis with immature cells started to appear. The bone marrow aspiration analysis showed increased cellularity and chromosomal analysis demonstrated the presence of t(9;22) (q34;q11) without any t(12;17) (q24;q11) abnormality. Because IFN therapy and oral administration of hydroxyurea did not show any cytological effect, administration of imatinib mesylate was started from December 2001. The Ph-positive cells as demonstrated by the FISH method had decreased to 7% by April 2003. But the t(12;17)(q24;q11) positive clones, which were observed on the first admission, again appeared in the peripheral blood, whereas Ph clones were detected in only one out of 24 cells examined. During the course of treatment with imatinib mesylate for chronic myelogenous leukemia which developed from agnogenic myeloid metaplasia accompanied with t(12;17)(q24;q11) translocation, the co-existence of two clones derived from, possibly, stem cells was identified.

A 31-year-old man referred to our hospital for treatment of his chronic myeloid leukemia (CML) in the first chronic phase by bone marrow transplantation. We pretreated him with cyclophosphamide and total body irradiation and bone marrow transplantation (BMT) was carried out. On day 31, the engraftment was confirmed and on day 52, acute graft versus host disease (GVHD) was observed. On day 189, he lost consciousness due to cyclosporine A-induced leukoencephalopathy and 375 mg cyclosporine A was changed to 100 mg prednisolone. On day 199, liver dysfunction (AST 410 IU/L, ALT 557 IU/L, gammaGTP 385 IU/L, ALP 363 IU/L, D-Bil 0.3 mg/dl) developed and a liver biopsy was performed. PCR analysis of DNA from the liver biopsy specimen was positive for HHV-6 and immunostaining using anti-HHV-6 and anti-HHV-6b antibodies showed positive staining in the cytosol of hepatocytes. No other viruses were found to induce hepatitis. From these results, he was diagnosed as having HHV-6 hepatitis and it was successfully treated with gancyclovir (GCV) administration.

A 51-year-old woman with severe aplastic anemia underwent allogeneic peripheral blood stem cell transplantation using blood stem cells from an HLA-identical sibling. Adenovirus type 11 hemorrhagic cystitis developed and progressed to nephritis and hemophagocytic syndrome. Oral ribavirin was effective not only for the hemorrhagic cystitis and nephritis but also for the hemophagocytic syndrome. Since therapeutic strategies for adenovirus infection after hematopoietic stem cell transplantation have not been established, we present our case and discuss the therapeutic approach.

Administration of imatinib exacerbated psoriasis vulgaris in a case of chronic myelogenous leukemia (CML). After the cessation of imatinib therapy, the psoriasis was alleviated. Upon readministration of imatinib, the psoriasis worsened despite the improvement of hematological and cytogenetic findings in the CML. Psoriasis is known to be an autoimmune skin disease characterized by Th1 cell-mediated hyperproliferation of keratinocytes, and the type 1 helper T (Th1) cell subset increased with imatinib therapy. Thus, the exacerbation of psoriasis was likely due to the increase in Th1 cells associated with imatinib therapy.

A 77-year-old man was diagnosed as having essential thrombocythemia in 1992. Treatment with hydroxyurea was started in 1997, which stabilized the platelet count. The patient then suffered from pharyngalgia and rhinitis with a high fever, immediately after which he developed tarry stools and anemia and was admitted to our hospital. The physical examination revealed splenomegaly, oral aphthous ulcers, genital ulcers and skin lesions on the lower limbs. His hematological and biochemical tests revealed anemia and increased level of C-reactive protein. He also had an HLA-B51 phenotype. The findings of gastro-intestinal and colon fiberoscopy showed a duodenal ulcer and multiple ulcers on ascending colon. He was thus diagnosed as having intestinal tract-type Behçet disease. After withdrawal of the hydroxyurea administration, the intestinal ulcers, oral aphthous ulcers and genital ulcers improved.

We report a patient with adult T-cell lymphoma who developed acute myeloid leukemia (AML) after allogeneic cord blood transplantation (CBT). Fluorescence in situ hybridization (FISH) studies and molecular analysis using short tandem repeat (STR) sequences proved the AML to be of donor origin. Although 25 cases of donor cell leukemia (DCL) occurring after allogeneic bone marrow transplantation have previously been reported, there have been no reports of DCL after CBT. This case is the first-reported DCL patient after CBT.

Here we report a case of myelodysplastic syndrome (MDS) with myelofibrosis associated with Bowen's disease. A female patient had undergone an operation and chemotherapy for ovarian cancer when she was 65 years old, and she developed MDS at the age of 70 years old. PCR-single strand conformation polymorphism (SSCP) analysis of peripheral blood mononuclear cells, a Bowen's disease lesion, and normal skin showed an abnormal peak in TP53 exon5. Direct sequencing revealed that they all had missense mutation in codon 175 (G to A) of arginine switched to histidine, suggesting a germline mutation of TP53. It was speculated that p53 function was lost by TP53 germline mutation with the loss of a wild type allele induced by the chemotherapy against ovarian cancer, leading to the development of MDS. No therapeutic effects of low dose melphalan or cyclosporine A on MDS were observed, however one month of 30 mg/day prednisolone administration induced a hematological response.

A 65-year-old male diagnosed with hypertension and hypertrophic cardiomyopathy in April 2010 at a different hospital was administered angiotensin II receptor blocker and low-dose aspirin. Although laboratory data at that time showed eosinophilia (2,860/lL), further examination was not performed. He had a history of smoking 1.5 packs of cigarettes a day for 45 years, but no history of diabetes mellitus. He developed cerebral infarction in January 2012, but recovered uneventfully with conservative treatment, including statins for dyslipidemia. He was subsequently referred to our hospital to investigate the eosinophilia. On physical examination, he had several swollen lymph nodes in bilateral inguinal regions, but no cutaneous lesion was observed. Laboratory data were as follows: WBC 10,600/ lL, eosinophil 840/lL, Hb 11.2 g/dL, Plt 8.8 9 10/lL, FDP 12.0 lg/mL, LDH 352 U/L, BUN 17.5 mg/dL, Cr 1.00 mg/dL, IgE 8,600 IU/mL, ACTH 15.3 pg/mL and cortisol 9.4 lg/dL, as well as negative test results for ANA and MPO-ANCA. The urinalysis showed proteinuria and microhematuria. Parasite eggs were not detected in the feces. Bone marrow examination showed 9.1 % eosinophils among all nucleated cells without dysplasia, and FIP1L1-PDGFRa and BCR-ABL chromosomal aberrations were not detected by FISH analysis. Chest and abdominal CT showed several enlarged inguinal lymph nodes up to 18 mm in the minor axis. Although he stated that he had recognized these inguinal masses about 10 years previously and that they had not changed markedly in size, we performed biopsy from the right inguinal lymph node. Histopathological findings revealed needle-shaped clefts in the lumen of arterioles with multinucleated giant cell infiltration surrounded by normal lymphoid follicles (Fig. 1a–c). Perivascular inflammatory cell infiltration, mainly of eosinophils, was also observed. Flow cytometric analysis of lymph node showed no abnormality. The diagnosis of cholesterol crystal embolism (CCE) to lymph node was made. As he presented no other clinical manifestations of CCE, no further therapeutic intervention was performed. CCE is a rare systemic disease caused by occlusion of small arteries by cholesterol crystals released from atheromatous plaques of the aorta or major branches. Chest CT in this patient also showed calcification and wall thickness of the thoracic aorta, which can be a source of cholesterol crystals (Fig. 2). The common manifestations of CCE are characteristic skin lesions, such as livedo reticularis, cyanosis or ulceration, renal impairment, and gastrointestinal disorder. CCE involvement of lymph node is extremely rare. Only a few preand postmortem cases of CCE to lymph node have been reported to date [1, 2]. CCE usually occurs following an invasive vascular procedure, or anticoagulant or thrombolytic therapy, but it can also occur spontaneously. We surmised that the CCE in this patient was spontaneous, as he had not undergone any such intervention during this clinical course. The exact time at which the CCE developed was unclear, but pathological findings of lymph nodes showing CCE with giant cell infiltration and no signs of fibrosis suggested that it had been a relatively recent event. Hence, we suspect that the A. Fujimi (&) A. Hashimoto Y. Kanisawa Department of Hematology and Oncology, Oji General Hospital, 3-4-8 Wakakusa-cho, Tomakomai 053-8506, Japan e-mail: Akihito.fujimi@ojihosp.or.jp

A seventy-six year old female patient with chronic myelogenous leukemia (CML), (chronic phase), was treated with imatinib and obtained a major cytogenetic response after 6 months of treatment. However, resistance to imatinib appeared 9 months later due to an ABL gene point mutation, and the patient's platelet count and BCR/ABL positive rate had remarkably increased. We discontinued imatinib and used IFNalpha or hydroxyurea, resulting in the disappearance of the ABL gene mutation clone. After that, we obtained a secondary hematologic response with the administration of imatinib.

A 31-year-old pregnant woman was referred to our hospital due to anemia and thrombocytopenia, and was diagnosed as having myelodysplastic syndrome (refractory anemia) with autoimmune thrombocytopenia. Administration of high dose methylprednisolone and gamma-globulin did not raise her platelet count, and she subsequently delivered a healthy baby after the transfusion of a large amount of platelets. Although the anemia spontaneously improved after delivery, the platelet count remained unchanged. Prednisolone was thus administered a second time, which did finally increase the platelet count. This is the first reported case of a pregnant woman with myelodysplastic syndrome in whom corticosteroid administration was effective for thrombocytopenia.

Bone-marrow minimal residual disease (MRD) causes relapse after chemotherapy in patients with acute myelogenous leukemia (AML). We postulate that the drug resistance is induced by the attachment of very late antigen (VLA)-4 on leukemic cells to fibronectin on bone-marrow stromal cells. We found that VLA-4-positive cells acquired resistance to anoikis (loss of anchorage) or drug-induced apoptosis through the phosphatidylinositol-3-kinase (PI-3K)/AKT/Bcl-2 signaling pathway, which is activated by the interaction of VLA-4 and fibronectin. This resistance was negated by VLA-4-specific antibodies. In a mouse model of MRD, we achieved a 100% survival rate by combining VLA-4-specific antibodies and cytosine arabinoside (AraC), whereas AraC alone prolonged survival only slightly. In addition, overall survival at 5 years was 100% for 10 VLA-4-negative patients and 44.4% for 15 VLA-4-positive patients. Thus, the interaction between VLA-4 on leukemic cells and fibronectin on stromal cells may be crucial in bone marrow MRD and AML prognosis.

A 63-year-old woman had previously been admitted to another hospital due to fever, abdominal pain and diarrhea. She was treated with fasting, antibiotics and G-CSF administration because of the coexistence of neutropenia, and the symptoms improved. However, discontinuation of G-CSF administration resulted in a recurrence of the neutropenia accompanied with enterocolitis. After admission to our hospital, a diagnosis for idiopathic AIN was performed as she tested positive in both granulocyte immunofluorescence and granulocyte agglutination tests. Administration of corticosteroid following G-CSF resulted in a continuous increase in the neutrophil count and the disappearance of anti-neutrophil autoantibodies.

We report an elderly patient with paroxysmal nocturnal hemoglobinuria (PNH), having recurrent gastrointestinal infections and hemolytic episodes caused by cellular immunodeficiency due to a decreased number of T cells. On admission to our hospital, the patient had normal neutrophil count and function, but had decreased T cell count, decreased mitogenic reaction to PHA and ConA, and negative reaction to the tuberculin test. Thus, a cellular immunodeficiency state was suggested and postulated to be due to decreased T cell count caused by the loss of PNH clone of T cells. We previously reported that the administration of G-CSF to normal donors of allogeneic peripheral stem cell transplantation increases the lymphocyte count. Based on this experience, we administered G-CSF to this patient. This resulted in an increase in the T cell count, normalization of the mitogenic response to PHA and ConA, positive reaction to the tuberculin test and increases in the blood levels of Thl cytokines and Th2 cytokines, with an improvement in the gastrointestinal infections and hemolytic episodes. This suggested that G-CSF administration resulted in the recovery of cell-mediated immunity in the gastrointestinal mucosa. At 9 months after the start of G-CSF administration, these complications have not recurred. This is the first report of a patient of this type and suggests that G-CSF administration may be useful in the treatment of elderly PNH patients with cellular immunodeficiency.

A 53-year-old woman with rapidly progressive consciousness disturbance and high fever for three days was brought to our emergency room by ambulance. Her temperature was 41.5 C, with systolic blood pressure of 60 mmHg and heart rate of 100 bpm. She had oral dyskinesia and muscle rigidity and tremor of the limbs. Laboratory data showed leukocytosis (18,200/lL), thrombocytopenia (1.8 9 10/lL), renal insufficiency (Cr 1.05 mg/dL), and SIADH (Na 117 mEq/L). Brain MRI revealed no abnormalities. Cerebral spinal fluid was clear, and HSV, EBV, and CMV DNA were not detected by PCR. Plasma exchange and methylprednisolone pulse were performed on the diagnosis of suspected thrombocytic thrombocytopenic purpura (TTP), which immediately reduced the high fever; however, unconsciousness was not improved. The diagnosis of TTP was eliminated three days afterward based on normal ADAMTS13 activity. Interestingly, peripheral blood smears on admission showed a large number of neutrophils with radially hypersegmented nuclei (Fig. 1a), a phenomenon first reported by Hernandez [1] and termed botryoid nuclei (BN). BN were observed in 92 % of neutrophils, and also in 25 % of monocytes (Fig. 1b). Furthermore, on the next day, no BN of neutrophils or monocytes was detected. She was transferred to Sapporo Medical University and diagnosed with autoimmune limbic encephalitis with voltage-gated potassium channel antibody. BN has been reported in patients with heat stroke and in children with acute encephalopathy. To our knowledge, this is the first case report of BN of neutrophils and Fig. 1 Botryoid nuclei of neutrophils (Fig. 1a) and monocytes (Fig. 1b) (May Grunwald Giemsa staining, 91000)

We treated two chronic phase chronic myelogenous leukemia patients with imatinib mesylate. Hematological complete remission and significant regression of bone marrow fibrosis were observed in both patients. The large amount of TGF-beta produced by increased bone marrow megakaryocytes might have caused the myelofibrosis, and it was revealed that imatinib mesylate brought about regression of the myelofibrosis by reducing the number of megakaryocytes in both patients.

Summary. We report an elderly patient with paroxysmal nocturnal haemoglobinuria (PNH), having recurrent enterocolitis and haemolytic attacks associated with cellular immunodeficiency. On admission, the patient had normal neutrophil count and function but a decreased T-cell count, decreased mitogenic reactions, and a negative tuberculin test. Granulocyte colony-stimulating factor (G-CSF) was administered, resulting in an increased T-cell count, normalization of T-cell function, increased blood levels of helper T cell (Th)1 and Th2 cytokines and improvement in the enterocolitis and haemolytic attacks. This suggests that G-CSF may be useful in the treatment of elderly PNH patients with cellular immunodeficiency.