Survival of a case of Bacillus cereus meningitis with brain abscess presenting as immune reconstitution syndrome after febrile neutropenia - a case report and literature review.

BACKGROUND: Bacillus cereus sometimes causes central nervous system infection, especially in compromised hosts. In cases of meningitis arising during neutropenia, CSF abnormalities tend to be subtle and can be easily overlooked, and mortality rate is high. We report a survived case of B. cereus meningitis/brain abscess in severe neutropenia, presenting as immune reconstitution syndrome. CASE PRESENTATION: A 54-year-old Japanese female with acute myelogenous leukemia developed B. cereus bacteremia and meningitis during consolidation chemotherapy. At the onset, she presented with mild meningism. She had marked leukocytopenia (WBC <100/µL, neutrophils 0/µL) and lumbar puncture yielded only mild pleocytosis. She was transferred to intensive care unit, and meropenem, linezolid and vancomycin was started. With intensive therapy, she recovered and once became afebrile. On day 19, however, her fever, meningism and consciousness level dramatically worsened despite recovery of bone marrow function. The antimicrobial chemotherapy was continued and finally she was cured with no complications. CONCLUSIONS: With early diagnosis and prompt initiation and of antibiotics, the case was successfully treated without any sequelae. It is important to remember that, even under optimal antimicrobial therapy, bone marrow recovery can cause transient reaggravation of the disease. In such cases, timely and appropriate evaluation should be done to make the clinical decision to change, continue, or intensify treatment.

Chylous ascites, anti-interferon-gamma autoantibody, and angioimmunoblastic T-cell lymphoma: a rare but intriguing connection over Mycobacterium avium.

We report a case of non-AIDS (acquired immunodeficiency syndrome), non-CAPD (Continuous Ambulatory Peritoneal Dialysis), non-cirrhotic, Mycobacterium avium peritonitis, which is a rare form of mycobacterial infection. A 66-year-old Japanese man who had been treated previously for angioimmunoblastic T-cell lymphoma (AITL), had developed disseminated M. avium infection. Antimycobacterial regimen improved his symptoms; however, following an interruption in treatment, he developed chylous ascites. The patient died of uncontrolled peritonitis despite intensive treatment. Anti-interferon-γ autoantibody was positive, and AITL was presumed to be involved in autoantibody production. A rare coexistence of chylous ascites, autoantibody, and AITL taught us an intriguing lesson on the pathogenesis of M. avium infection. Particularly, we conclude that treatment strategies for M. avium infection should aim to restore immunity.

Plasma presepsin level is an early diagnostic marker of severe febrile neutropenia in hematologic malignancy patients.

BACKGROUND: Febrile neutropenia (FN) is a common infectious complication in chemotherapy. The mortality of FN is higher in hematologic malignancy patients, and early diagnostic marker is needed. Presepsin is a prompt and specific marker for bacterial sepsis, but its efficacy in severe febrile neutropenia (FN) is not well confirmed. We tried to clarify whether it is a useful maker for early diagnosis of FN in patients during massive chemotherapy. METHODS: We measured plasma presepsin levels every 2-3 day in FN cases and evaluated its change during the course of massive chemotherapy. The patients had hematologic malignancy or bone marrow failure, and in all cases, neutropenia was severe during the episode. The baseline levels, onset levels, increase rate at FN onset, and onset / baseline ratio were evaluated for their efficacy of early FN diagnosis. RESULTS: Eleven episodes of bacteremia (six gram negatives and five gram positives) in severe neutropenia were analyzed in detail. While plasma presepsin level was strongly associated to the CRP level (r = 0.61, p < 0.01), it was not associated with the absolute WBC count (r = -0.19, p = 0.19), absolute neutrophil count (r = -0.11, p = 0.41) or absolute monocyte count (r = -0.12, p = 0.40). The average of onset presepsin level was 638 ± 437 pg/mL and the cutoff value (314 pg/mL) has detected FN onset in 9 of 11 cases. The two cases undetected by presepsin were both Bacillus species bacteremia. CONCLUSIONS: Plasma presepsin level is a reliable marker of FN even in massive chemotherapy with very low white blood cell counts. Closer monitoring of this molecule could be a help for early diagnosis in FN. But bacteremia caused by Bacillus species was an exception in our study.

Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) recognizes a novel ligand, Mac-2-binding protein, characteristically expressed on human colorectal carcinomas.

Dendritic cell (DC)-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a type II transmembrane C-type lectin expressed on DCs such as myeloid DCs and monocyte-derived DCs (MoDCs). Recently, we have reported that DC-SIGN interacts with carcinoembryonic antigen (CEA) expressed on colorectal carcinoma cells. CEA is one of the most widely used tumor markers for gastrointestinal cancers such as colorectal cancer. On the other hand, other groups have reported that the level of Mac-2-binding protein (Mac-2BP) increases in patients with pancreatic, breast, and lung cancers, virus infections such as human immunodeficiency virus and hepatitis C virus, and autoimmune diseases. Here, we first identified Mac-2BP expressed on several colorectal carcinoma cell lines as a novel DC-SIGN ligand through affinity chromatography and mass spectrometry. Interestingly, we found that DC-SIGN selectively recognizes Mac-2BP derived from some colorectal carcinomas but not from the other ones. Furthermore, we found that the α1-3,4-fucose moieties of Le glycans expressed on DC-SIGN-binding Mac-2BP were important for recognition. DC-SIGN-dependent cellular interactions between immature MoDCs and colorectal carcinoma cells significantly inhibited MoDC functional maturation, suggesting that Mac-2BP may provide a tolerogenic microenvironment for colorectal carcinoma cells through DC-SIGN-dependent recognition. Importantly, Mac-2BP was detected as a predominant DC-SIGN ligand expressed on some primary colorectal cancer tissues from certain parts of patients in comparison with CEA from other parts, suggesting that DC-SIGN-binding Mac-2BP bearing tumor-associated Le glycans may become a novel potential colorectal cancer biomarker for some patients instead of CEA.

Mediastinal seminoma occurring in Down syndrome.

The increased incidence of testicular tumor occurrence, especially seminoma, in Down syndrome has been well documented. However, primary mediastinal seminoma occurring in Down syndrome has not been reported. Incidental discovery of an anterior mediastinal tumor was made in a 28-year-old Japanese man with Down syndrome, who had been scheduled for bone marrow transplantation to treat aplastic anemia. Histopathological findings of the resected tumor were typical of seminoma. This case indicates that seminoma can occur in the mediastinum in addition to testis in Down syndrome.

Lipoid pneumonia with chronic myelomonocytic leukemia.

A case of lipoid pneumonia with chronic myelomonocytic leukemia is reported. A 61-year-old man was autopsied after suffering from myelodysplastic syndrome (chronic myelomonocytic leukemia) for 13 years. Interstitial lesions of the lungs were suspected as infiltration of leukemia cells before the autopsy. However, blastic leukemia cells were not observed in the lung, although they were seen in the bone marrow and spleen at autopsy. Instead, an unusual amount of cholesterol deposits was observed with mucormycosis and aspergillosis in the lungs. Cholesterol deposition was observed not only in perihilar but also in subpleural regions without apparent bronchial obstruction in both lungs. It is thought that malfunction of monocytes/macrophages resulted in repeated fungal infection and storage of cholesterol caused by tissue destruction and impaired tissue repairing.

Comparison of imatinib, dasatinib, nilotinib and INNO-406 in imatinib-resistant cell lines.

We compared the growth-inhibitory effects and inhibition profile of the SRC family kinases (SFKs) of imatinib, dasatinib, nilotinib and INNO-406. Dasatinib exhibited the strongest potency against BCR-ABL with little selectivity over SFKs. Nilotinib exhibited a weaker affinity than the other inhibitors, but was highly specific for ABL and may be useful for the treatment of P-glycoprotein overexpressing leukemic cells. INNO-406 had an intermediate affinity for BCR-ABL between that of dasatinib and nilotinib, and inhibited only SFKs LCK and LYN among SFKs. Both nilotinib and INNO-406 were potent inhibitors of the dasatinib-resistant T315A, F317L and F317V BCR-ABL mutations.

[New crossmatch procedure: computer crossmatch experience in a blood service division].

We established a computer crossmatch system in our hospital to commence 24-hour-a-day blood services. About 97% of red blood products were shipped using this system. Among them, only one patient developed a mild delayed hemolysis. ABO-mismatched transfusion or release of incompatible blood components was not reported at all. Since the turnaround time is shortened, cost reductions were achieved by reductions in blood units tied up in the crossmatched blood inventory, leading to reduced blood ordering.

Primary malignant lymphoma of the right atrium resulting in superior vena caval syndrome in an HIV-positive patient: depiction at multislice computed tomography and magnetic resonance imaging.

An HIV-positive 32-year-old male presenting with superior vena cava syndrome underwent multislice computed tomography (MSCT) and magnetic resonance imaging (MRI), which showed a large tumor in the right atrium, which extended to the superior vena cava. Pathologic examination revealed that the mass was consistent with B cell-type malignant lymphoma. The tumor size markedly decreased after the initiation of chemotherapy and patient recovery has been uneventful for 1 year.

Mycobacterium shigaense Causes Lymph Node and Cutaneous Lesions as Immune Reconstitution Syndrome in an AIDS Patient: The Third Case Report of a Novel Strain Non-tuberculous Mycobacterium.

A 40-year-old man complaining of progressive body weight loss was diagnosed to have acquired immunodeficiency syndrome. Within 2 weeks after the initiation of combination antiretroviral therapy, he developed fever, massive cervical lymphadenopathy and a protruding subcutaneous abscess. A lymph node biopsy and abscess drainage revealed non-caseous granuloma and mycobacterium. The mycobacterium belonged to Runyon II group, but it showed no matches to any previously reported species. According to sequence analyses, the strain was identified as Mycobacterium shigaense. After six months of antimycobacterial treatment, the lesions were all successfully cured. This is the third case report of the novel mycobacterium, M. shigaense, presenting in associatioin with immune reconstitution syndrome.

Clinical and pathological aspects of human immunodeficiency virus-associated plasmablastic lymphoma: analysis of 24 cases.

Plasmablastic lymphoma (PBL) is a rare AIDS-related malignancy with a poor prognosis. Little is known about this entity, and no standard treatment regimen has been defined. To establish an adequate treatment strategy, we investigated 24 cases of PBL arising in human immunodeficiency virus-positive individuals. Most of the patients were in the AIDS stage, with a median CD4 count of 67.5/µL. Lymph nodes (58 %), gastrointestinal tract (42 %), bone marrow (39 %), oral cavity (38 %), and CNS (18 %) were the most commonly involved sites. Histology findings for the following were positive at varying rates, as follows: CD10 (56 %); CD30 (39 %); CD38 (87 %); MUM-1 (91 %); CD138 (79 %); EBER (91 %); and LMP-1 (18 %). There was a marked increase in patients in 2011-12, and the cases found in that period appeared to be more aggressive, showing a higher rate of advanced-stage PBL. Fourteen cases were treated with CHOP, while the others were treated with more intensive regimens, including bortezomib and hematopoietic stem cell transplantation. The overall median survival time was 15 months. A CD4 count of >100/µL at diagnosis and attaining complete remission in the first-line chemotherapy were associated with better outcomes (P = 0.027 and 0.0016, respectively). Host immune status and chemosensitivity are associated with improved prognosis in PBL.

The anti-leukemic efficacy of the third generation bisphosphonate ONO5920/YM529.

Ras proteins are frequently over-expressed in leukemia and contribute to leukemogenesis. We evaluated the anti-leukemic efficacy of a new third-generation bisphosphonate, ONO5920/YM529 (YM529). YM529 prevents the prenylation of Ras proteins and inhibited the growth of leukemic cells including a P-glycoprotein (P-gp) over-expressing cell line in a concentration- and time-dependent manner by inducing apoptosis in vitro. Moreover, YM529 synergistically augmented the anti-leukemic activities of paclitaxel and daunorubicin in vitro. Importantly, YM529 prolonged the survival of NOD/SCID mice engrafted with human primary leukemic cells. These findings indicate that the YM529 may become a novel molecular therapeutic class for treatment of leukemias.

Fluctuation in therapeutic control associated with interchange of prednisolone tablet formulations: assessment of bioequivalence by dissolution test.

A 47-year-old woman received combination therapy with prednisolone (PSL), danazol, cepharanthin, ascorbic acid, and cimetidine for the treatment of idiopathic thrombocytopenic purpura. The platelet count was well controlled for over 1 year. Then the PSL tablet formulation was altered from Tablet A to Tablet B with the same treatment regimen, but the platelet counts fell drastically thereafter. However, the platelet counts recovered by changing the PSL tablet formulation back from Tablet B to Tablet A. In vitro dissolution testing was undertaken to assess bioequivalence between Tablet A and Tablet B. PSL in Tablet B was released more slowly compared with that in Tablet A regardless of the medium pH conditions, and the difference in the release rate between the two tablet formulations increased with increasing medium pH value. The difference exceeded the allowance limit (15%) for judgment of bioequivalence under conditions above pH 4, indicating that Tablet A and Tablet B might be nonbioequivalent. The intragastric pH of the patient was probably raised due to coadministration of cimetidine. Therefore the present results suggest that the disparity in the immunosuppressive effects between the two PSL tablet formulations was attributable to the difference in their dissolution behavior in the gastrointestinal tract. We consider that it is better to avoid interchanging PSL tablet formulations in clinical practice.

Sarcoidal granulomas in the mediastinal lymph nodes after treatment for marginal zone lymphoma of the esophagus: report of a case with review of the concept of the sarcoidosis-lymphoma syndrome.

Patients with sarcoidosis have a high risk of development of malignant lymphoma, and this association was coined the term "sarcoidosis-lymphoma syndrome". Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a distinct clinicopathological entity, and the stomach is the most common site. The occurrence of this type of lymphoma in the esophagus is extremely rare. In this report, we describe the first documented case of sarcoidal granulomas in the mediastinal lymph nodes after treatment for MALT lymphoma of the esophagus. A 60-year-old Japanese female was found to have a submucosal tumor in the esophagus. Histopathological study revealed proliferation of small- to medium-sized lymphoid cells with convoluted nuclei, and immunohistochemically, these lymphoid cells were diffusely positive for CD20, bcl-2, and MUM1. R-CHOP therapy was performed, which led to tumor remission. Two years later, swelling of the mediastinal lymph nodes was detected. Histopathological study of the lymph nodes revealed presence of variably-sized epithelioid granulomas without caseating necrosis but no malignant lymphoma was noted. Sarcoidal granulomas can be observed in patients with malignant tumors including malignant lymphoma and carcinoma without history of systemic sarcoidosis. It is important to recognize that systemic sarcoidosis and sarcoidal reaction without evidence of systemic disease can occur after development of malignant lymphoma, therefore, sarcoidal reaction must be included in the differential diagnostic consideration of recurrent malignant lymphoma.

Primary cutaneous anaplastic large cell lymphoma occurring in an atopic dermatitis patient: a case report with review of the literature with emphasis on their association.

Although the risk of malignant lymphoma in patients with atopic dermatitis (AD) remains controversial, an increased risk of malignant T-cell lymphoma in patients with AD has been reported. Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a relatively common distinct clinicopathological entity. However, occurrence of C-ALCL in patients with AD has been rarely reported. Herein, we describe the 5(th) reported case of C-ALCL occurring in a patient with AD and review the clinicopathological features. A 30-year-old Japanese male with a long-standing history of AD presented with a gradually enlarged nodular lesion in the right abdominal wall, which had spontaneously regressed without therapy. Two years later, multiple nodular lesions appeared in his trunk, and swelling of multiple lymph nodes was also detected. Histopathological studies demonstrated diffuse proliferation of large-sized lymphocytes with large convoluted nuclei containing conspicuous nucleoli and relatively rich cytoplasm in the skin and lymph node. Immunohistochemically, these lymphocytes were positive for CD30, CD8, and MUM1, and negative for CD3, CD4, and ALK1. Accordingly, a diagnosis of primary C-ALCL was made. The patient died of disease after various courses of chemotherapy. Our clinicopathological review revealed that the prognosis of C-ALCL occurring in patients with AD is poor because two of 5 patients died of disease. Therefore, albeit extremely rare, AD patients with C-ALCL should be monitored closely, and additional clinicopathological studies are needed to clarify the pathogenesis of C-ALCL occurring in patients with AD.

Primary bone marrow diffuse large B-cell lymphoma accompanying cold agglutinin disease: A case report with review of the literature.

Cold agglutinin disease (CAD) is a well-recognized complication of lymphoproliferative disorders. It has been previously recognized that cases of primary CAD frequently exhibit underlying malignant lymphoma in the bone marrow. Lymphoplasmacytic lymphoma is the most common subtype of malignant lymphoma; however, diffuse large B-cell lymphoma (DLBCL) has also been documented, albeit extremely rare. The current report presents a case of primary bone marrow DLBCL accompanying CAD. A 76-year-old male presented with fever and fatigue. Laboratory tests revealed anemia and elevated bilirubin and cold agglutinins with a titer of 8,192 at 4°C. Bone marrow biopsy demonstrated DLBCL and systemic surveillance failed to detect tumorous lesions or lymphadenopathy. Following R-THP-COP therapy, cold agglutinins titer was markedly decreased (by <4); however, malignant lymphoma relapsed and cold agglutinin levels increased again (4,096). This is the second documented case of primary bone marrow DLBCL accompanying CAD. Previously, malignant lymphoma exclusively involving the bone marrow, namely primary bone marrow lymphoma (PBML), has been recognized as a rare and aggressive subtype. The analyses of the present study revealed that the incidence of hemolytic anemia in primary bone marrow DLBCL may be high compared with conventional DLBCL. Therefore, additional analyses are required to clarify the clinicopathological features of PBML.

Concomitant occurrence of IgG4-related pleuritis and periaortitis: a case report with review of the literature.

IgG4-related sclerosing disease is an established disease entity with characteristic clinicopathological features. Some recent reports have demonstrated that this disease can occur in the respiratory system including the pleura. Herein, we describe the first documented case of concomitant occurrence of IgG4-related pleuritis and periaortitis. A 71-year-old Japanese female with a history of essential thrombocythemia presented with persistent cough and difficulty in breathing. Computed tomography demonstrated thickening of the right parietal pleura, pericardium, and periaortic tissue and pleural and cardiac effusions. Histopathological study of the surgical biopsy specimen of the parietal pleura revealed marked fibrous thickening with lymphoplasmacytic infiltration. Phlebitis was noted, however, only a few eosinophils had infiltrated. Immunohistochemical study revealed abundant IgG4-positive plasma cell infiltration and high ratio of IgG4-/IgG-positive plasma cells (84%). Therefore, a diagnosis of IgG4-related pleuritis was made with consideration of the elevated serum IgG4 level (684 mg/dL). Recently, the spectrum of IgG4-related sclerosing disease has expanded, and this disease can occur in the pleura, pericardium, and periaortic tissue. Although histopathological analysis of the pericardium and periaortic tissue was not performed in the present case, it was suspected that thickening of the pericardium and periaortic tissue was clinically due to IgG4-related sclerosing disease. Our clinicopathological analyses of IgG4-related pleuritis and pericarditis reveal that this disease can present as dyspnea and pleural and pericardial effusion as seen in the present case, therefore, it is important to recognize that IgG4-related sclerosing disease can occur in these organs for accurate diagnosis and treatment.