ANCA-associated vasculitis with scleritis, corneal melt, and perforation rescued by rituximab: Case report and literature review

Key Clinical Message: Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, specifically with myeloperoxidase (MPO)-ANCA, would have a risk for developing corneal melt and perforation abruptly in a short period. It is desirable to have a team of collaboration of rheumatologists and other specialties. Abstract: An 80-year old man who had been diagnosed 5.5 years previously as ANCA-associated vasculitis by temporal artery biopsy developed corneal melt and perforation with scleritis in both eyes. He underwent successful cataract surgery and retained ambulatory vision with the aid of intravenous rituximab. Two additional patients with similar manifestations were found in the literature

A case of an atypical variant of type A thymoma presenting with a gradually enlarging tumor over a 10-year period

Case Reportjournal articl

Unusual progression of herpes simplex encephalitis with basal ganglia and extensive white matter involvement

We report a 51-year old male with herpes simplex encephalitis (HSE) showing unusual progression and magnetic resonance (MR) findings. The initial neurological manifestation of intractable focal seizure with low-grade fever persisted for three days, and rapidly coma, myoclonic status, and respiratory failure with high-grade fever emerged thereafter. The polymerase chain reaction (PCR) result of cerebrospinal fluid (CSF) was positive for HSV-1 DNA. In the early stage, MR images (MRI) were normal. On subsequent MR diffusion-weighted (DW) and fluid-attenuated inversion recovery (FLAIR) images, high-intensity areas first appeared in the left frontal cortex, which was purely extra-temporal involvement, and extended into the basal ganglia, then the white matter, which are relatively spared in HSE. Antiviral therapy and immunosuppressive therapy did not suppress the progression of HSE, and finally severe cerebral edema developed into cerebral herniation, which required emergency decompressive craniectomy. Histological examination of a biopsy specimen of the white matter detected perivascular infiltration and destruction of basic structure, which confirmed non specific inflammatory change without obvious edema or demyelination. The present case shows both MR and pathological findings in the white matter in the acute stage of HSE

Severe thrombocytopenia and maculopapular erythema-induced by regorafenib in a patient with advanced gastrointestinal stromal tumor

　A 28-year-old Japanese male was diagnosed with a gastrointestinal stromal tumor and multiple liver metastases at 23 years of age underwent gastrectomy and partial hepatectomy. At 27 year of age, multiple liver metastases and peritoneal dissemination were observed and the patient was switched to sunitinib. Approximately, one year later, the liver metastases worsened, and the patient was switched to regorafenib. Fatigue and palmar-plantar erythrodysesthesia syndrome occurred seven days after starting regorafenib, and thrombocytopenia occurred nine days later. Eleven days later, small erythema with fever and erythematous papules appeared throughout the body; therefore regorafenib was discontinued, and oral administration of steroids was initiated accordingly. After 17 days, platelets count decreased to 14,000/μL, prompting platelet transfusion. Maculopapular erythema was diagnosed based on the skin findings and histopathological examination. Oral and topical steroids were initiated and the maculopapular eruption gradually improved. A drug hypersensitivity reaction to regorafenib was diagnosed and treatment was discontinued, after which the patient entered a clinical trial for a new drug. We encountered a case of marked thrombocytopenia and maculopapular erythema during the early stages of regorafenib treatment. Regorafenib occasionally causes serious adverse events; therefore, careful observation and prompt treatment are necessary

Development of primary central nervous system post-transplant lymphoproliferative disorder immediately after cytomegalovirus viremia in an MDS patient who received cord blood transplantation

　Epstein–Barr virus (EBV) plays a central role in the pathogenesis of posttransplant lymphoproliferative disorder (PTLD), and EBV reactivation after allogenic hematopoietic stem cell transplantation (allo-HSCT) is highly correlated with cytomegalovirus (CMV) reactivation, which might be a risk factor for PTLD. We encountered a myelodysplastic syndrome patient with PTLD in the central nervous system who experienced sequential CMV and EBV reactivation immediately after allo-HSCT. Previous studies have suggested relationships between CMV and EBV reactivation and between CMV reactivation and PTLD. Our case suggests the importance of CMV monitoring in patients after allo-HSCT to preventPTLD

Role of the expression of collagen prolyl-4-hydroxylase α subunits 1 and 2 in the development and prognosis of breast cancer

　Background: The expression of prolyl-4-hydroxylase (P4H), an enzyme involved in collagen biosynthesis, is significantly upregulated during breast cancer development and progression. However, the molecular mechanisms by which P4H expression in cancer cells induces progression have not been elucidated. Thus, we aimed to determine the significance of the expression of isoforms 1 and 2 of P4H in breast cancer.　Methods: We performed immunohistochemical analysis for P4HA1 and P4HA2 on the tumor samples obtained from 182 patients with breast cancer and examined the correlation between clinicopathological factors and markers related to epithelial-mesenchymal transition and ischemia. Protein expression levels were investigated using western blotting. In addition, breast cancer cell cultures were used to characterize the expression.　Results: Expression of both P4HA1 and P4HA2 was upregulated in cancer cells compared with that in normal mammary glands; the high-P4H expression group tended to have a poorer prognosis than the low-P4H expression group. In particular, P4HA2 was strongly associated with tumor grade; P4HA2 expression showed a weak negative correlation with HIF-2α expression. In cultured breast cancer cells, the immunohistological expression of P4H and HIF increased tovarious degrees under hypoxia, while P4H protein levels increased in a time-dependent manner. 　Conclusion: P4HA2 can be used as a marker of breast cancer grade and a prognostic factor. Differential expression of P4HA1 and P4HA2 was observed in an ischemic environment,suggesting that each may be affected by the type of collagen involved

Human bone marrow VCAM-1+ macrophages provide a niche for reactive and neoplastic erythropoiesis

Resident bone marrow macrophages provide a microenvironment for erythropoiesis, forming erythroblastic islands (EBIs) via adhesion molecules. In this study, we examined vascular cell adhesion molecule-1 (VCAM-1) expression in human bone marrow specimens using immunohistochemistry. VCAM-1 was strongly expressed in CD169+ macrophages in EBIs and weakly in sinusoidal vascular endothelial cells. In reactive erythropoiesis, including hemolytic and megaloblastic anemia, the extended cytoplasm of VCAM-1+ CD169+ macrophages circumscribed the erythroid cells. The strong affinity between VCAM-1+ macrophages and erythroid cells was also observed in polycythemia vera (PV), essential thrombocythemia (ET), and chronic myelogenous leukemia (CML). VCAM-1 density was significantly higher in PV than in ET and CML (p < 0.001), and correlated with blood erythrocyte count in all three neoplasms (p < 0.001). In ET, the VCAM-1 density was higher in cases with the JAK2 mutation than with the CALR mutation. In myelodysplastic syndrome with erythroid predominance but unclear EBI formation, punctate VCAM-1+ cytoplasmic processes of macrophages were seen between erythroblasts, similar to those seen between granulocytic precursors in CML, suggesting incomplete contact of VCAM-1+ macrophages with dysplastic erythroid cells. These results suggest that VCAM-1+ macrophages create a niche for reactive and neoplastic erythropoiesis and may be a therapeutic target in PV

腹腔鏡検査にて確定診断に至った結核性腹膜炎の一例

　症例は63歳女性．元医療従事者であった．１ヵ月続く腹痛と38度の発熱で近医を受診し，腹水貯留を認め，腹水検査でヒアルロン酸とCA125が高値であったことから癌性腹膜炎を疑われ当院内科に紹介された．画像検査より癌性腹膜炎を疑われたが，原発は同定できなかった．細胞診はclassII であったが，卵巣癌，腹膜癌，悪性中脾腫を疑われたことから，腹腔鏡検査目的に当科紹介となった．腹腔鏡検査で黄白色粒状の病変を認め，病理組織検査にて類上皮細胞性肉芽腫を認め，結核等の感染症が疑われた．病歴聴取にて３年前の職務中に結核排菌患者に濃厚接触歴あり，腹腔鏡再検査にて，塗抹，培養，PCR 陰性であったが，腹水中ADA 高値より結核と診断し結核専門病院に転院した．抗結核薬開始され速やかに症状は軽快した．結核性腹膜炎は非常に稀な疾患であるが，腹腔鏡検査で診断に至った症例を経験した．原因不明腹水を認めた場合，癌性腹膜炎のみならず感染性腹膜炎の可能性も念頭に置き早期から同時に精査する必要がある．　A 63-year-old woman, who was a former healthcare professional, visited a nearby clinic for headache and a fever of 38℃ that had lasted for a month. Ascites was observed, and ascitic fluid examination showed high hyaluronan and CA125 levels, suggesting cancerous peritonitis. She was referred to the internal medicine department at our institution. Although the primary site was not identified, imaging findings suggested cancerous peritonitis. Cytology showed class II features, with the possibility of ovarian cancer, peritoneal cancer, or malignant mesothelioma. She was referred to our department for laparoscopic examination, which showed epithelioid cell granulomas, suggesting an infectious disease, which could include tuberculosis. History taking revealed close contact with a tuberculosis-shedding patient at work 3 year ago. Although the smear, culture, and polymerase chain reaction tests were negative, on laparoscopic reexamination, tuberculosis was diagnosed because of elevated adenosine deaminase in the ascitic fluid. She was transferred to a tuberculosis specialty hospital;antituberculosis therapy was started, and the symptoms quickly resolved. We experienced a very rare case of tuberculous peritonitis, diagnosed laparoscopically. Ascites from an unknown cause requires close examination for not only cancerous peritonitis but also infectious peritonitis

Sphingosine-1-phosphate receptor 1 expression in angiosarcoma : Possible role in metastasis and a potential therapeutic target

Sphingosine-1-phosphate (S1P) is a potent lipid mediator that has been implicated in the migration of lymphocytes and endothelial cells through S1P receptors. S1PR1 is strongly expressed in angiosarcoma, a malignant tumor of endothelial cell origin that has a high propensity for metastasis and poor prognosis; however, the pathological significance of S1PR1 expression is not clear. In this study, we investigated the effect of S1PR1 modulation on cell migration, and examined its potential role as a therapeutic target against metastatic dissemination of angiosarcoma. S1PR1 expression in the human angiosarcoma cell line MO-LAS was assessed by immunocytochemical examination and Western blotting. Effects of S1PR1- specific small interfering RNA (siRNA) and that of FTY720-P (a functional S1PR1-antagonist) on MO-LAS cell chemotactic migration towards sphingosine-1-phosphate (S1P) or 10% fetal bovine serum (FBS) were assessed by Transwell migration assay; wound healing assays for random cell migration were performed using a live cell analyzer. Immunostaining revealed high expression of S1PR1 on the MO-LAS cell membrane. Transwell and wound-healing assays showed that S1P enhanced chemotactic and random migration of MO-LAS cells, respectively. Inhibition of S1PR1 expression with siRNA significantly attenuated chemotaxis of cells towards S1P and 10% FBS. Further, FTY720-P strongly induced the internalization and degradation of S1PR1 even in the presence of serum containing S1P. It attenuated chemotactic cell migration of MO-LAS towards both S1P and serum, as well as the random motility of cells at nanomolar concentrations. These results suggest that the S1P/S1PR1 axis may be a potential therapeutic target for inhibition of angiosarcoma metastasis by controlling its cell motility