Kunimoto Ichikawa

Autoimmune hemolytic anemia in a patient with TAFRO syndrome

TAFRO syndrome is a systemic inflammatory disorder characterized by low platelet counts, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. Patients with TAFRO syndrome occasionally have courses complicated by immunological diseases. Herein, we describe a case of TAFRO syndrome associated with autoimmune hemolytic anemia (AIHA). The patient was admitted because of menorrhagia. She had thrombocytopenia, pleural effusion and ascites, hepatomegaly, and multiple lymphadenopathies. Her symptoms worsened, especially fever, pleural effusion and ascites, and she developed AIHA. Steroid pulse therapy followed by 45 mg of prednisolone (PSL) improved not only the symptoms of TAFRO syndrome but also those of AIHA. There have been no reports, to our knowledge, of AIHA associated with TAFRO syndrome, and detailed studies on this syndrome are needed.

A case of T cell prolymphocytic leukemia involving blast transformation

We report a case of T cell prolymphocytic leukemia (T-PLL) involving blast transformation. At the initial diagnosis, most peripheral blood cells demonstrated proliferation of indolent T cell small cell variants, i.e., small to medium prolymphocytes with inconspicuous nucleoli and a normal karyotype. These cells were positive for surface CD4, CD5, and CD7, and cytoplasmic CD3, but negative for surface CD3 and CD8 and cytoplasmic terminal deoxynucleotidyl transferase (TdT). The T cell receptor (TCR) Cβ1 gene was rearranged in the cells. Large prolymphocytes with prominent nucleoli, irregular nuclei, and cytoplasmic vacuoles that exhibited chromosome 8 trisomy were observed about 1.5 years later. The CD4+CD8− single positive effector memory T cells transformed into surface CD4+CD8+ double positive precursor T cells. The clonal TCR gene rearrangement patterns of these cells were identical throughout the clinical course, suggesting clonal blast transformation. The CD4+CD8+ cells demonstrated increased chromosome 8 trisomy combined with complex chromosome abnormalities with t(14;14)(q11.2;q32) containing a 14q32 chromosome after transformation. T cell leukemia 1a (TCL1a) (14q32.1) may be implicated in this case. The TCL1a oncoprotein is expressed in approximately 70% of T-PLL cases. The disease gradually developed resistance to chemotherapy, and the patient died of the disease. It is known that indolent T-PLL can become aggressive. Therefore, similar transformations may occur in other aggressive T-PLL cases, particularly those involving trisomy 8 and TCL1a.

Usefulness of Systemic Computed Tomography (ct) Scanning in the Detection of Malignant Lymphadenopathy [retracted]

We developed a prediction model to distinguish between malignant and nonmalignant lymphadenopathies. We first analyzed clinical features of 222 patients with lymphadenopathy (161 malignant and 61 nonmalignant) in the derivation group. Through logistic regression analysis we identified 6 covariates that independently predict malignancy: age (X1), abdominal lymphadenopathy (X2), lymphadenopathy of the other sites (X3), number of enlarged lymph node regions (X4), absence of fever (X5), and largest lymph node size (X6). We determined the formula as follows: predictive score=-2.3+x1+2.8x2+1.3x3+1.6x4-2.2x5+1.8x6.A higher score correlated with increased likelihood of malignancy. With the cutoff value of 0.4, the sensitivity and specificity of the model were 91.9% and 77.0%, respectively. The validation study using 117 cases (82 malignant and 35 nonmalignant) yielded 90.2% sensitivity and 68.6% specificity. A maximum lymph node size of less than 2.0 cm on systemic computed tomography (CT) scanning indicated a low probability of malignant lymphadenopathy. In this model, 4 of the 6 covariates were obtained by CT scanning, which strongly indicates the usefulness of initial evaluation with systemic CT scanning in the detection of malignant lymphadenopathy.

Lymphomatoid Granulomatosis with Central Nervous System Involvement Successfully Treated with Cyclophosphamide, High-dose Cytarabine, Dexamethasone, Etoposide, and Rituximab (CHASER therapy) Followed by Brain Irradiation: A Case Study

Lymphomatoid granulomatosis (LYG) is a rare subtype of diffuse large B-cell lymphoma. It is an extranodal angiocentric and angiodestructive lymphoproliferative disease involving the lungs, skin, and central nervous system (CNS), including abundant reactive T cells with varying numbers of atypical clonal Epstein–Barr virus (EBV)-infected B cells [1]. Clinical diagnosis of LYG is difficult because of a lack of characteristic manifestations, suitable laboratory tests, and imaging findings. No optimal treatment for LYG has yet been established, especially in cases involving the CNS. Several previous reports of rituximab monotherapy, rituximab-containing chemotherapy, interferon alpha-2b, or hematopoietic stem cell transplantation have been published [2], as well as a report of cyclophosphamide (CPM), high-dose cytarabine, dexamethasone, etoposide, and rituximab (CHASER therapy) for lung lesions of LYG [3]. Spontaneous remission has also been reported in patients with LYG involving the CNS and lungs [4]. Here, we describe a case of LYG with lung onset responsive to corticosteroid treatment, but with subsequent CNS involvement resistant to corticosteroid and rituximab monotherapy, which was successfully treated with CHASER therapy followed by brain irradiation. We also propose the value of repetitive evaluation of specimens and gradient-echo T2*-weighted magnetic resonance imaging (T2*-MRI) for diagnosis of CNS involvement in LYG (CNS–LYG). A healthy 40-year-old woman presented with persistent fever, cough, and dyspnea 2 years before admission to our hospital. Thoracic computed tomography (CT) performed at a local hospital revealed diffuse ground-glass opacity with nodular lesions in both lungs (Figure 1A). Blood examination showed highly elevated soluble interleukin-2 receptor (11,726 U/ml), and slightly elevated aspartate aminotransferase (86 IU/L) and alanine transaminase (131 IU/L). EBV antiviral capsid antigen (VCA) IgG and Epstein–Barr nuclear antigen (EBNA) were positive, and EBV anti-VCA IgM was negative, indicating past EBV infection. Pathological diagnosis was performed using videoassisted thoracic surgery (VATS), revealing atypical large lymphoid cells infiltrating the regions around the blood vessels (Figure 2A). These infiltrating lymphocytes comprised a large number of CD3-positive T cells and a few large CD20-positive B cells (Figure 2B). However, the lymphocytes were negative for EBV-encoded small RNA (EBER) according to in situ hybridization. Although LYG was suspected from the results, a definitive diagnosis was not made at the time. Prednisolone (50 mg/day; 1 mg/kg/day) was administered orally. The patient’s fever and respiratory symptoms disappeared and thoracic CT revealed disappearance of the bilateral nodular lesions (Figure 1B). However, 1 month after initiation of steroid therapy, prednisolone was tapered to 30 mg/day and she developed neurological deficits, including left facial dysesthesia, dysarthria, and gait disturbance due to left dominant spastic paraplegia, limb ataxia, and sensory disturbance. CPM (100 mg/day) was added and prednisolone was repeatedly increased or decreased from 50 to 2.5 mg/day, with no improvement. The patient was therefore

Successful perioperative management of factor XI deficiency with administration of fresh-frozen plasma in a subdural hematoma patient

The number of patients with subdural hematoma (SDH) is increasing as a result of an aging society. Emergency surgery is necessary when neurological status deteriorates in patients with SDH, but the presence of coagulation abnormalities can become a problem in such situations. We report an elderly patient presenting with a prolonged activated partial thromboplastin time (APTT) successfully treated with fresh-frozen plasma (FFP) during emergency surgery for SDH. An 83-year-old woman came to Juntendo Shizuoka Hospital (Shizuoka, Japan) with right hemiplegia. Brain computed tomography showed a left SDH. Preceding events of head injury were absent. She was scheduled to have surgery, but routine screening tests showed a prolonged APTT of 122.5 s (reference range 25–40 s). Prothrombin time (PT)/international normalized ratio and platelet counts were normal at 0.98 and 267 × 10/L, respectively. She had no history of bleeding tendency, including menorrhagia. Because her consciousness was clear with a Glasgow Coma Scale of E4V4M6, her operation was postponed in order to investigate and treat the prolonged APTT. Application of the mixing test accompanied by a 2-h incubation at 37°C showed a normalized APTT, which suggested the presence of a coagulation factor deficiency, and we initiated treatment by administering 4 U of FFP, which was equivalent to approximately 10 mL/kg of FFP, because her bodyweight was 45 kg. A total of 9 h after admission and soon after FFP transfusion was completed, her level of consciousness deteriorated to a Glasgow Coma Scale of E2V3M5, and computed tomography scans showed a midline shift of the brain (Fig. 1a). The patient was given an emergency burr hole craniostomy (Fig. 1b). Postoperative bleeding was not observed, coagulation tests showed a corrected APTT of 38.9 s, and thus no additional FFP infusions were given. Further analysis showed a prominent factor XI deficiency with activity level below 1.0%. One week after the operation, APTT prolongation was again seen at 55.8 s, which is in concordance with a diagnosis of factor XI deficiency, because the half-life of factor XI is approximately 2–3 days. Abnormal prolongation of APTT can occur as a result of intrinsic coagulation factor deficiencies or the presence of coagulation factor inhibitors, and the etiology can be distinguished by carrying out a mixing test. The mixing test is easily applicable, simply done by mixing the patient’s plasma with normal plasma, and assessing the APTT before and after mixing. Prolongation of APTT will not be corrected when there is a coagulation factor inhibitor, but vice versa when coagulation factor deficiency is the etiology. It must be stressed that a 2-h incubation at 37°C is essential when applying the mixing test, because demonstration of an uncorrected APTT might require time as a result of slow-acting inhibitors in some cases. The most well-recognized disorders that show prolonged APTT along with a normal PT are hemophilia A and hemophilia B, which occur as a result of deficiencies of factor VIII and IX, respectively. Patients with factor XI and XII deficiencies also present with prolonged APTT and normal PT, but patients with factor XII deficiency are usually not prone to bleeding. In contrast, patients with factor XI deficiency are frequently diagnosed when abnormal bleeding occurs after surgery or trauma. Perioperative treatment of factor XI deficiency with FFP is typically carried out at around 15–20 mL/kg/day for approximately a week, but we only administered a single 4-U infusion of FFP, because we were not aware of the diagnosis at the time. Except for patients with factor XI deficiency, who are sometimes treated with FFP because factor XI concentrate is available in only a few countries, the common treatment for coagulation factor deficiencies in patients with prolonged APTT and normal PT is replacement therapy with the specifically lacking coagulation factor concentrate. However, when lifethreatening bleeding occurs, there is no time to explore which coagulation factor is deficient. Therefore, we recommend application of the mixing test accompanied by a 2-h incubation at 37°C to patients with severe bleeding, prolonged APTT and normal PT, Geriatr Gerontol Int 2016; 16: 143–149 bs_bs_banner

Strongly suspicious hemolysis caused by azacitidine in a myelodysplastic syndrome patient

result of CAS might decrease BP variability. In selected high-risk patients, it is possible that dayto-day BP variability is not simply caused by daily life. For high-risk patients, day-to-day BP variability is an important phenotype and a signal to call attention to the risk. In high-risk patients, endovascular treatment might cure not only the localized vascular disease, but also systematic atherothrombotic vascular disease through the improvement of BP variability.

Notice of Retraction: Usefulness of Systemic CT Scanning in the Detection of Malignant Lymphadenopathy

To the Editor We published the article “Usefulness of Systemic CT Scanning in the Detection of Malignant Lymphadenopathy” in the November 2011 issue of Medicine.1 It has come to our attention that we made an error, and 143 cases of the 339 cases analyzed did not fit the criteria for patient selection described in the Patients and Methods section. In addition to the 143 cases without complete data, 5 cases originally categorized in the benign group because of benign pathologic results turned out to have active malignancies. When we re-evaluated the corrected data in logistic regression analysis, we found that only 2 of the 6 covariates identified in the paper as independently predicting malignancy were significant. As a result, we wish to retract this article. We regret any problems our article and actions may have caused and we retract this article from the literature.

CD4+CD8− T cell large granular lymphocytic leukaemia with central nervous system involvement

pipeline and an increasing number of new targets, clinical evaluation is likely to become rate-limiting. Approaches to overcome these challenges may be to enrich phase I ⁄ II trials with the molecular profile of tumours and to conduct integrated genomic profiling for specimens from patients enrolled in clinical trials. In addition, the development of robust predictive markers for response that are applicable in a routine clinical setting will be critical for this evaluation (Figure 1). The present findings further emphasize the importance of developing tools to relate findings from comprehensive biomarker studies to a standard clinical setting, which is still heavily dependent on evaluating FFPE specimens. In conclusion, we find that stratification based on high tumour cell content in fresh frozen tissue promotes selection of aggressive endometrial carcinomas. Thus, potential biomarkers identified need to be validated in population-based settings to determine their clinical relevance. Also, biomarkers that are only prevalent in subgroups with low tumour cell content may go unrecognized. The relevance of this phenomenon for other cancer types remains to be further investigated.

C-kit-positive acute myelogenous leukemia effectively treated with imatinib: A case report and review of the literature

than ADR in elderly inpatients, and so, these are possibly the major types in the present study. Also, ROC analysis did not fit well for the present cohort. In summary, the present study provided the cut-off number of drugs for screening of elderly patients at high risk of ADR. Prospective studies and intervention studies examining the effect of drug reduction on ADR and comorbid conditions are required to confirm this finding.

18F-Fluorodeoxyglucose positron emission tomography/computed tomography revealed the presence of simultaneous colon cancer in mucosa-associated lymphoid tissue lymphoma.

A 76-year-old Japanese woman was refered to our hospital because of right buccal mucosa swelling. The pathological specimen showed infiltration of small to medium-sized mature lymphocytes with a MIB-1 labering index of 5.0%. The cells were positive for CD20, CD79a and Bcl-2, and negative for CD5, CD10, CD21 and CD23. Southern blot analysis showed immunoglobulin (Ig)H gene rearrangement. Chromosomal analysis was unsuccessful because of the low growing activity. Although fluorescence in situ hybridization (FISH) analyses failed to detect API2-MALT1 and IGH-BCL2 gene fusions, increased copy numbers of both MALT1 and BCL2 signals (three instead of two) suggested the triplicate of 18q21 locus, for example trisomy 18. The patient was diagnosed as extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Staging investigation with Ffluorodeoxyglucose positron emission tomography/ computed tomography (FDG-PET/CT) showed uptake signals in the right buccal mucosa and ascending colon with standardized uptake value (SUV) max values of 8.2 and 16.6, respectively (Fig. 1). F-Fluorodeoxyglucose positron emission tomography/computed tomography is widely used in the management of patients with malignant lymphoma. The SUV max of MALT lymphoma is generally low (~2.0–8.0). Therefore, relatively high SUV max of the colon uptake suggested the presence of another disease rather than a distant MALT lesion. Indeed, the following colonoscopy showed an infiltrative ulcerating lesion of well-differentiated Figure 1 F-Fluorodeoxyglucose positron emission tomography/computed tomography image at diagnosis shows F-fluorodeoxyglucose uptake in the right buccal mucosa and ascending colon. Standardized uptake value max of ascending colon is much higher than that of right buccal mucosa. Geriatr Gerontol Int 2011; 11: 537–538