Epstein-Barr Virus-Positive Cutaneous and Systemic Plasmacytosis with TAFRO Syndrome-like Symptoms Successfully Treated with Rituximab.

Histopathologic findings in the lymph nodes of patients with thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome are similar to those of idiopathic multicentric Castleman's disease (iMCD), but TAFRO syndrome is different from iMCD in how it can progress rapidly and be fatal. These patients present scarce lymphadenopathy and low immunoglobulin levels. We present a case of cutaneous and systemic plasmacytosis (C/SP) that caused TAFRO syndrome-like symptoms which were successfully treated with rituximab. A 67-year-old woman presented with fever and a pruritic skin rash. Numerous plasma cells were observed in the peripheral blood and imaging revealed organomegaly, anasarca, and generalized lymphadenopathy. Subsequently, she rapidly developed thrombocytopenia as well as renal and heart failure. She tested positive for the Epstein-Barr virus (EBV), elevated immunoglobulins, and C/SP, which are also atypical for TAFRO syndrome, thereby complicating the diagnosis. However, after using the Japanese TAFRO Syndrome Research Group diagnostic criteria, we promptly administered rituximab to treat the C/SP with TAFRO-like symptoms and saved her life. Finally, histopathological observations of the lymph node biopsy helped confirm EBV-positive hypervascular-type iMCD. Therefore, diagnosing TAFRO-like syndromes based on the Japanese diagnostic criteria and following the associated treatment even without a confirmed diagnosis is crucial to improving the patient outcomes.

Cytomegalovirus Oophoritis Mimicking Burkitt's Lymphoma Recurrence: A Case Report and Literature Review.

Cytomegalovirus (CMV) oophoritis is an extremely rare and fatal condition. We encountered a 63-year-old woman with CMV oophoritis who had been treated for Burkitt's lymphoma. Positron emission tomography/computed tomography performed after chemotherapy showed a high 18F-fluoro-2deoxy-D-glucose uptake in both ovaries, which required distinguishing relapse. CMV oophoritis was diagnosed on histology following bilateral salpingo-oophorectomy. Although the patient later developed recurrent episodes of CMV antigenemia, after which complications of CMV retinitis appeared, and she ultimately died of CMV meningitis, surgical resection with antiviral medication resolved her abdominal symptoms and cleared CMV antigenemia for several weeks. It is therefore worth considering surgical resection in combination with antiviral drugs as a treatment option.

Immune thrombocytopenia associated with Pfizer-BioNTech's BNT162b2 mRNA COVID-19 vaccine.

The recent global pandemic of coronavirus disease 2019 (COVID-19) has led to vaccination in many parts of the world for herd immunity, and as vaccination has progressed, several rare adverse events have been reported. Immune thrombocytopenia (ITP) has been reported to be one of the rare adverse events caused by vaccination with MMR (measles-mumps-rubella) vaccine and influenza vaccine. In addition, ITP has been reported to occur in a small number of cases associated with the COVID-19 messenger ribonucleic acid (mRNA) vaccine. However, there are few reports on the details of the treatment and clinical course; optimal treatment has not yet been established. We report the case of a 20-year-old woman who developed ITP after receiving Pfizer-BioNTech's BNT162b2 vaccine. She had generalized subcutaneous hemorrhage, 14 days after vaccination. At the time of our visit, she had marked thrombocytopenia and intraoral bleeding; she was diagnosed with ITP. Treatment with oral steroids was started and the platelet count promptly improved after 4 days of treatment. Since the response to treatment was very good, we tapered off the steroids. As these vaccines will be increasingly used in the future, it is important to recognize ITP as a possible adverse event.

[Successful treatment with ponatinib in combination with hyper-CVAD for chronic myeloid leukemia in the lymphoid blastic phase].

The prognosis of chronic myeloid leukemia (CML) has improved dramatically with the introduction of tyrosine kinase inhibitors. Although the use of second-generation tyrosine kinase inhibitors is now available for initial cases, a small number of patients with CML unfortunately still experience progression to the accelerated or blastic phase of the disease. We recently managed a patient with chronic-phase CML, who developed a T315 mutation early in the course of treatment with dasatinib and progressed to the lymphoid blastic phase. The patient responded quickly to ponatinib therapy in combination with hyper CVAD, leading to cord blood transplantation. We report here the first case of a patient with CML in the lymphoid blastic phase treated with ponatinib in combination with hyper CVAD, which was tolerable despite adverse events such as infection, bilirubin elevation, and hypertension, and who was able to proceed to transplantation after achieving a complete molecular response.

Autoimmune Myelofibrosis in Sjögren's Syndrome: Report of a Case.

BACKGROUND Autoimmune myelofibrosis (AMF) is a rare clinicopathologic entity of bone marrow fibrosis that occurs in association with autoimmune disorders. Steroids are very effective for treatment of AMF and the disease has a good prognosis and should be distinguished from primary myelofibrosis. CASE REPORT A 49-year-old man with bleeding and petechial hemorrhage of the extremities presented to our institution. His platelet count was 1×109/L. Bone marrow aspiration revealed a dry tap, and bone marrow biopsy confirmed small lymphocyte infiltration and increased reticular fibers, consistent with immune thrombocytopenia. Testing for mutations in JAK2, MPL, and CALR was negative. Because the patient had a history of Raynaud's phenomenon, he was suspected to have collagen disease. Anti-Sjögren's-syndrome-related antigen-A antibody testing, Schirmer's test, and fluorescein staining all came back positive, which led to a diagnosis of Sjögren's syndrome. Given the bone marrow findings, the patient also was diagnosed with AMF. Treatment with steroids resulted in an immediate improvement in his platelet count. CONCLUSIONS In the present case, treatment with steroids resulted in prompt improvement in platelet counts and subsequent marrow biopsy showed MF-0 reticulin fibrosis. Bone marrow fibrosis rarely is seen in association with autoimmune disease, and its significance and mechanism are still to be determined.

Case Report: Composite Angioimmunoblastic T-Cell Lymphoma and Epstein-Barr Virus-Positive B-Cell Lymphoproliferative Disorder as Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders.

Immunosuppressants are widely used to treat patients with rheumatoid arthritis (RA), and their adverse effects have been known to cause other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs). We report a patient with RA who had been treated with methotrexate (MTX) and tacrolimus (TAC) and who developed whole body lymphadenopathy. We simultaneously confirmed angioimmunoblastic T-cell lymphoma (AITL) through a right cervical lymph node biopsy and Epstein-Barr virus-positive B-cell lymphoproliferative disorder (EBV-positive B-LPD) through a bone marrow examination. After cessation of immunosuppressant therapy, both LPDs completely disappeared. Patients with AITL are occasionally reported to develop B-cell lymphoma through reactivation of the EBV, which leads to clonal expansion in the microenvironment. Immunohistochemistry results revealed that both LPD components were positive for EBV-encoded RNA. Moreover, in this patient, the plasma EBV DNA level was found to be high; therefore, EBV infection was a probable etiology. Synchronous coexistence of AITL and B-LPD as an OIIA-LPD has rarely been reported. This case report is the first to discuss the disappearance of both LPDs on withdrawal of immunosuppressants only. AITL occasionally accompany B-LPD; however, this composite lymphoma comprised AITL and B-LPD, and OIIA-LPDs should not be overlooked.

NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of esophageal cancer regulates the survival and migration of tumor-associated macrophages and cancer cells.

Tumor-associated macrophages (TAMs) have important roles in the angiogenesis and tumor immunosuppression of various cancers, including esophageal squamous cell carcinomas (ESCCs). To elucidate the roles of TAMs in ESCCs, we compared the gene expression profiles between human peripheral blood monocyte-derived macrophage-like cells (Macrophage_Ls) and Macrophage_Ls stimulated with conditioned medium of the TE series human ESCC cell line (TECM) (TAM_Ls) using cDNA microarray analysis. Among the highly expressed genes in TAM_Ls, we focused on neural cell adhesion molecule (NCAM). NCAM knockdown in TAM_Ls revealed a significant decrease of migration and survival via a suppression of PI3K-Akt and fibroblast growth factor receptor 1 (FGFR1) signaling. Stimulation by TECM up-regulated the level of FGFR1 in Macrophage_Ls. Recombinant human fibroblast growth factor-2 (rhFGF-2) promoted the migration and survival of TAM_Ls and TE-cells through FGFR1 signaling. Our immunohistochemical analysis of 70 surgically resected ESCC samples revealed that the up-regulated FGF-2 in stromal cells, including macrophages, was associated with more aggressive phenotypes and a high number of infiltrating M2 macrophages. These findings may indicate a novel role of NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of ESCCs.

Cyr61 promotes CD204 expression and the migration of macrophages via MEK/ERK pathway in esophageal squamous cell carcinoma.

Tumor-associated macrophages (TAMs) are known to be involved in the progression of various human malignancies. We previously demonstrated that CD204 was a useful marker for TAMs contributing to the angiogenesis, progression, and prognosis of human esophageal squamous cell carcinoma (ESCC). We also showed that conditioned media of ESCC cell lines induced CD204 expression in THP-1 human monocytic leukemia cells. Here, we performed a cDNA microarray analysis between THP-1 cells stimulated with TPA (macrophage [MΦ]-like THP-1 cells) treated with and without conditioned medium of ESCC cell line to clarify the molecular characteristics of TAMs in ESCC. From the microarray data, we discovered that Cyr61 was induced in CD204-positive-differentiated THP-1 cells (TAM-like THP-1 cells). In the ESCC microenvironment, not only cancer cells but also TAMs expressed Cyr61. Interestingly, the expression levels of Cyr61 showed a significant positive correlation with the number of CD204-positive macrophages in ESCCs by immunohistochemistry. Recombinant human Cyr61 (rhCyr61) promoted cell migration and induced the expression of CD204 along with the activation of the MEK/ERK pathway in MΦ-like THP-1 cells. Pretreatment with a MEK1/2 inhibitor significantly inhibited not only the Cyr61-mediated migration but also the CD204 expression in the MΦ-like THP-1 cells. These results suggest that Cyr61 may contribute to the expression of CD204 and the promotion of cell migration via the MEK/ERK pathway in TAMs in the ESCC microenvironment.

The global distribution of pure anorthosite on the Moon.

It has been thought that the lunar highland crust was formed by the crystallization and floatation of plagioclase from a global magma ocean, although the actual generation mechanisms are still debated. The composition of the lunar highland crust is therefore important for understanding the formation of such a magma ocean and the subsequent evolution of the Moon. The Multiband Imager on the Selenological and Engineering Explorer (SELENE) has a high spatial resolution of optimized spectral coverage, which should allow a clear view of the composition of the lunar crust. Here we report the global distribution of rocks of high plagioclase abundance (approaching 100 vol.%), using an unambiguous plagioclase absorption band recorded by the SELENE Multiband Imager. If the upper crust indeed consists of nearly 100 vol.% plagioclase, this is significantly higher than previous estimates of 82-92 vol.% (refs 2, 6, 7), providing a valuable constraint on models of lunar magma ocean evolution.

A Novel C-C Single-Bond Formation Accompanying C-O Bond Cleavage by Use of a Ketone, an Alkylating Reagent, and a Low-Valent Vanadium Complex in the Presence of a Catalytic Amount of Molecular Oxygen.

A C-C single-bond-forming reaction from ketones with accompanying C-O bond cleavage mediated by a RMgBr or RLi-vanadium(II)-O(2) system has been accomplished. Different from conventional reductive coupling reactions of ketones such as the McMurry coupling, the present method forms a C-C single (instead of a double) bond and yields a product that contains components derived from the ketone and the alkylating reagent in a one-pot reaction. Collaboration of both a low-valent vanadium(II) species and a higher-valent vanadium species produced from vanadium(II) and a catalytic amount of O(2) effects the abstraction of the oxygen atom from a C-O bond.