[Primary leptomeningeal lymphoma with oculomotor paralysis as the initial presentation].

An 85-year-old man presented with right eye ptosis and visual abnormalities. Due to a lack of abnormal findings on plain magnetic resonance imaging (MRI) and laboratory examination, prednisolone therapy was initiated, and ocular myasthenia gravis and ocular symptoms subjectively improved. However, anorexia and conscious disorder appeared during the same period, and he was hospitalized for scrutiny. After admission, left eye adduction disorder and bilateral abduction nerve paralysis were also observed. Enhanced MRI revealed cranial nerve and leptomeninx enhancement. Subsequently, the patient developed seizures and died on the 10th day of hospitalization without being diagnosed. An autopsy revealed infiltration of B-cell lymphoma cells into the subarachnoid space, particularly in the parietal lobe. Similar infiltration was observed in the cerebellum, brainstem, spinal cord, and bilateral oculomotor nerve. Primary leptomeningeal lymphoma is a rare form of primary central nervous system lymphoma without simultaneous parenchymal brain lesions. Clinicians should be aware of this form of lymphoma and carefully monitor its possible occurrence, even when patients are already being treated for other neurological diseases.

The standardized uptake value calculated from 111In-ibritumomab tiuxetan single-photon emission computed tomography/computed tomography is a useful predictor of the clinical response in patients treated by 90Y- ibritumomab tiuxetan therapy.

90Y-Ibritumomab tiuxetan (IT) therapy is a radioimmunotherapy for indolent B-cell lymphoma. Several predictors of insufficient therapeutic effects have been reported. We performed a retrospective study at a single institute to investigate whether 111In SPECT/CT can predict the therapeutic effects and grade of cytopenia due to 90Y-IT therapy. We enrolled 16 consecutive patients who underwent 90Y-IT therapy, including 15 who underwent 111In-IT SPECT/CT. After 90Y-IT therapy, there were 4 patients in complete remission in whom the lesion SUVmax on 111In-IT SPECT/CT and soluble IL-2 receptor were significantly lower than those of the other patients (P<0.05 and P<0.05, respectively). Based on the log-rank test of factors associated with the progression-free survival (PFS), ≥2 previous treatment regimens was significantly associated with a poor prognosis (P<0.05). The SUV on 111In-IT SPECT/CT may be a good predictor of the clinical response to 90Y-IT therapy.

Monoclonal B-cell Lymphocytosis Exacerbated by Prednisolone Therapy for Dermatomyositis.

Lymphoproliferative diseases have been associated with various autoimmune diseases. We experienced a case of non-chronic lymphocytic leukemia type monoclonal B-cell lymphocytosis (MBL) that was exacerbated by increasing prednisolone for dermatomyositis and then improved by decreasing the dosage. Because MBL is difficult to diagnose, cases like ours may not be rare. These findings will facilitate our understanding of the mechanism underlying lymphoproliferative diseases and autoimmune diseases.

Immune Thrombocytopenic Purpura Complicated by Hepatitis C Virus-related Membranoproliferative Glomerulonephritis after Rituximab Therapy.

We herein report the case of a 54-year-old Japanese man with hepatitis C virus (HCV)-related membranoproliferative glomerulonephritis (MPGN), which developed at the time of relapse of immune thrombocytopenic purpura (ITP) after rituximab therapy. Antiviral therapy for HCV led to the improvement of both MPGN and ITP. Rituximab therapy may have contributed to the exacerbation of HCV infection and induced the development of HCV-related MPGN and the relapse of ITP. Our case suggested that HCV treatment should be prioritized over rituximab therapy for HCV-positive patients with ITP and that antiviral therapy for HCV may be effective for treating ITP itself.

Massive Hemoptysis Due to the Rupture of Thoracic Aortic Aneurysm Caused by Leukemic Cell Infiltration in a Patient With Chronic Myelomonocytic Leukemia.

Hemoptysis is occasionally experienced in patients with hematological malignancies who have respiratory tract infection and severe thrombocytopenia. Thrombocytopenia due to hematological disease is one cause of hemoptysis. Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy characterized by both a myeloproliferative neoplasm and a myelodysplastic syndrome. This malignancy often infiltrates various extramedullary organs and has a poor prognosis. An 84-year-old Japanese man with CMML was suffered from hemoptysis and dyspnea. When he arrived at the emergency room, hemoptysis stopped. His white blood cell count was 866 × 109/L with 3.5% blast cells and 36.5% monocytes; hemoglobin was 6.7 g/dL; platelets count was 19 × 109/L; and C-reactive protein was 16.23 mg/dL. Chest X-ray examination revealed an invasion shadow near the mediastinum in the left upper lung field. Chest computed tomography revealed a tumorous lesion in the left upper lobe, which had progressed to the mediastinum and formed an infiltration shadow around it. He was administered the antibiotics and the hemostatic agents under hospitalization. He also received blood transfusion for anemia and thrombocytopenia. Rapid improvement in oxygenation was observed along with a rapid decrease in blood levels in the sputum. On the eighth days of hospitalization, however, the patient newly developed massive hemoptysis and died. Autopsy revealed rupture of a thoracic pseudoaneurysm due to infiltration of leukemia cells in the tunica media and lung. Clinicians should consider thoracic aortic aneurysms as a possible cause of hemoptysis even in cases with small hemoptysis. It should be noted that in CMML patients, direct infiltration of leukemia cells in the vascular wall can cause aneurysm formation.

Characteristics and prognosis of patients with non-immunoglobulin-M monoclonal gammopathy of undetermined significance: a retrospective study.

Non-immunoglobulin (Ig)-M monoclonal gammopathy of undetermined significance (MGUS) is a precursor lesion with the potential to evolve into a malignant plasma cell neoplasm. The prevalence of MGUS differs by ethnicity and is lower in the Japanese population than in the Western population. However, there is limited evidence about the clinical course of MGUS in Asian races. The present study aims at elucidating the clinical course and prognosis of Japanese patients with non-IgM MGUS in the clinical setting. We retrospectively examined 1009 patients with non-IgM MGUS identified by screening procedures. The median overall survival of these patients was > 20 years, and only one-fifth patients died of plasma cell neoplasms. The cumulative incidence of plasma cell neoplasms requiring treatment was 19%. Multivariate analysis revealed that immunoparesis and female gender were independent factors affecting treatment requirement. Although the characteristics and clinical course of patients with non-IgM MGUS obtained in this study were found to be essentially similar to those of previous studies, we report here for the first time that female gender is a significant independent factor for requiring treatment.

Vanadate inhibits endoplasmic reticulum stress responses.

The disruption of endoplasmic reticulum function leads to an accumulation of unfolded proteins, which results in endoplasmic reticulum stress. In the present study, we investigated the effect of vanadate on such stress. Endoplasmic reticulum stress increased glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) expressions in glial cell cultures. We found that vanadate inhibited the endoplasmic reticulum stress-induced increase in GRP78 and CHOP expressions at both mRNA and protein levels. Thus, these results suggest that vanadate modulates endoplasmic reticulum stress responses and that novel vanadate-responsive protein(s) might be involved in these processes.

A unique modulator of endoplasmic reticulum stress-signalling pathways: the novel pharmacological properties of amiloride in glial cells.

BACKGROUND AND PURPOSE: Stress on the endoplasmic reticulum (ER) can trigger rescuer responses such as the unfolded protein response (UPR). However, pharmacological modulators of these ER-regulated stress responses are not well understood. In the present study, we found that amiloride, a potassium-sparing diuretic, has unique properties relating to such stress. EXPERIMENTAL APPROACH: We treated mouse primary cultured glial cells with amiloride, in the absence and presence of the ER stress-inducing reagents tunicamycin (Tm) or dithiothreitol, and measured UPR and ER stress-induced cell death. IRE1alpha phosphorylation, eIF2alpha phosphorylation, X-box binding protein 1 (XBP1) splicing, glucose regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) expression by reverse transcription-polymerase chain reaction and Western blotting were used to assess UPR and lactate dehydrogenase activity was determined to measure ER stress-induced cell death. KEY RESULTS: Amiloride completely inhibited ER stress-induced activation of IRE1alpha, an ER-localized stress sensor protein, splicing of XBP1, and subsequent expression of GRP78 at the mRNA and protein levels. ER stress induces the phosphorylation of eIF2alpha, leading to the expression of CHOP or an attenuation of translation in cells. Surprisingly, treatment with amiloride alone markedly promoted the phosphorylation but actually inhibited ER stress-induced CHOP expression. Finally, we found that amiloride (200 microM) synergistically enhanced ER stress-induced cell death, which was mediated through caspases. On the other hand, a low dose of amiloride (20 microM) significantly prevented Tm-induced cell death. CONCLUSIONS AND IMPLICATIONS: These results suggest that amiloride can modulate UPR. They also suggest amiloride to be an important pharmacological agent and provide basic information for understanding and preventing ER stress-related diseases.