Yasunori Fujioka

Kyorin University, Edo, Tokyo, Japan

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Publications (106)301.24 Total impact

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    ABSTRACT: We report a 48-year-old female who developed lymphoproliferative disorder (LPD) during treatment of rheumatoid arthritis (RA) with methotrexate (MTX). She presented with multiple tumors in the cervical lymph nodes (LNs), multiple lung shadows and round shadows in both kidneys with pancytopenia and a high CRP level. The LN showed CD8-positive T-cell LPD associated with Epstein-Barr (EB) virus-infected B-cells. Clonality assays for immunoglobulin (Ig) heavy chain and T-cell receptor gamma (TCRγ) were negative. The cessation of MTX without chemotherapy resulted in the complete disappearance of the tumors and abnormal clinical features. We compared this case with previously published ones and discuss the pathological findings, presuming that the proliferation of CD8 T-cells was a reactive manifestation to reactivated EB virus-infected B-cells.
    No preview · Article · Jan 2014 · Modern Rheumatology

  • No preview · Article · Mar 2013 · Journal of Clinical Oncology
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    Katsuya Chinen · Yasunori Fujioka
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    ABSTRACT: The POEMS syndrome (coined to refer to polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) is a rare variant of plasma cell disorders with multiple systemic manifestations. Recently, pulmonary hypertension (PH) has become established as a complication, but pathological studies of this condition are scarce and the detailed pathogenesis remains to be elucidated. We present herein a case of a 49-year-old woman who was diagnosed as having idiopathic PH and was treated in accordance. However, she eventually died of respiratory failure and an autopsy revealed the presence of smoldering plasma cell myeloma and multiple organomegaly in addition to severe PH. The latter was attributed to stenosis and occlusion of the arterioles of the lungs due to marked plasma cell proliferation, quite different from the histology of idiopathic PH. From these findings, together with the clinical details, we concluded that the patient's PH was a complication of the POEMS syndrome. This case showed a unique pulmonary vascular pathology featuring plasma cell proliferation and it provides clues towards understanding the pathogenesis with this background.
    Preview · Article · Nov 2012 · Case Reports in Medicine
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    ABSTRACT: Mycoplasma pneumoniae (Mp) may cause immune cell reactions as pivotal aspects of this clinically common respiratory pathogen. Our aim is to determine if Mp extract induces a cellular immune response associated with interleukin (IL)-17, leading to lung inflammation and lung injury. BALB/c mice were immunized with Mp extract intraperitoneally followed by its intratracheal administration, to mimic repeated Mp infection found in humans (repeated inoculation, RI group). Those with a single inoculation were compared as single inoculation group (SI group). Analysis of bronchoalveolar lavage fluid (BALF) demonstrated that keratinocyte-derived cytokine, tumor necrosis factor-α, and IL-6 were produced and peaked on days 0.5 or 1, followed by IL-17 on day 2. Levels of these mediators in BALF were higher in RI group than SI group (P < 0.05). Further, significantly more neutrophils were recruited to the lungs of the RI group (P < 0.05). These observations suggest that IL-17 is involved in the prolonged induction of neutrophils in mice treated with Mp extract.
    No preview · Article · Sep 2012 · Inflammation
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    Kohichi Yamauchi · Yasunori Fujioka · Naoyuki Kohno
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    ABSTRACT: The status of lymph nodes in the neck is the most important prognostic factor for the outcomes of patients with oral tongue cancer. However, surgical prophylaxis of the neck is controversial. We reviewed 22 patients with clinically T1/T2, N0 Union Internationale Contre le Cancer oral squamous cell carcinoma of the tongue. Patients were assigned to groups according to the management strategy selected for the neck. One group underwent a "watchful waiting" policy and the other underwent sentinel node navigation surgery (SNNS). Three of 11 patients (27%) in the watchful waiting group developed regional recurrence and underwent neck dissection. Only 1 of 11 patients (9.1%) in the SNNS group developed regional recurrence. Although the groups did not significantly differ, the SNNS group tended to have less regional recurrence. SNNS should be the third strategy formanaging early oral tongue carcinoma.
    Full-text · Article · Apr 2012 · Head & Neck
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    Full-text · Article · Jun 2011 · Clinical and Experimental Nephrology
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    Full-text · Article · Jun 2011 · Clinical and Experimental Nephrology
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    ABSTRACT: Sentinel node navigation surgery (SNNS) is currently considered to provide better staging of regional metastasis. For rapid and accurate sentinel lymph node analysis, one-step nucleic acid amplification using cytokeratin 19 (CK19) has been applied, particularly in breast cancer. On the other hand, additional quantitative reverse transcription PCR targets containing cytokeratins have been reported recently in head and neck cancer. In this report, CK19 and p63 were immunohistochemically examined in primary tumours for use as molecular markers and were compared with cytokeratin 903 (CK903), cytokeratin 8/18 (CK8/18) and cytokeratin (AE1/AE3), which are used in diagnostic immunohistochemistry for head and neck squamous cell carcinoma. The study reviewed 17 patients with T1/T2, N0 (UICC) oral squamous cell carcinoma of the tongue who were treated surgically at Kyorin University Hospital between 2002 and 2009. The intensity and proportion of tumour cells stained for CK19, CK903, p63, CK8/18 and AE1/AE3 were evaluated. CK19 and CK8/18 staining in cytoplasm was patchy among carcinoma cells, indicating weak expression. Staining proportion for p63, CK903 and AE1/AE3 was greater than for CK19 and CK8/18, although staining intensity for CK903 was weaker than for p63 and AE1/AE3. The difference in total score between CK19 and CK8/18 staining and p63, CK903 and AE1/AE3 staining was statistically significant (p<0.001). p63 and AE1/AE3 may be better markers than CK903, CK19 and CK8/18. This suggests that p63 is of clinical utility in SNNS and that CK19 is unsuitable for early tongue carcinoma. Further studies are needed before clinical application of these markers.
    Full-text · Article · Jun 2011 · Journal of clinical pathology
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    ABSTRACT: Human Mycoplasma pneumoniae (MP) pneumonia is characterized by alveolar infiltration with neutrophils and lymphocytes and lymphocyte/plasma cell infiltrates in the peri-bronchovascular area (PBVA). No mouse model has been able to mimic the pathological features seen in human MP pneumonia, such as plasma cell-rich lymphocytic infiltration in PBVA. To figure out the mechanism for inflammation by MP infection using a novel mouse model that mimics human MP pneumonia, mice were pre-immunized intraperitoneally with Th2 stimulating adjuvant, alum, alone or MP extracts with an alum, followed by intratracheal challenge with MP extracts. The toll-like receptor-2, which is the major receptor for mycoplasma cell wall lipoproteins, was strongly up-regulated in alveolar macrophages in a latter group after the pre-immunization but prior to the intratracheal challenge. Those findings demonstrated that acceleration of innate immunity by antecedent antigenic stimulation can be an important positive-feedback mechanism in lung inflammation during MP pneumonia.
    No preview · Article · May 2011 · Results in Immunology
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    ABSTRACT: Anti-glomerular basement membrane (anti-GBM) disease is thought to be distinct from vasculitis. In contrast, there have been several papers suggesting the presence of angiitis in cases that were positive for anti-GBM antibody (Ab), as well as for either myeloperoxidase (MPO)- or proteinase 3 (PR3)-anti-neutrophil cytoplasmic antibody (ANCA) (Group I). We experienced four patients who had anti-GBM Abs, but not MPO- and PR3-ANCA (Group II), and two of these patients were found to have vasculitis. Therefore, we performed an in-depth study on these two patients. The patients with anti-GBM disease were isolated from 578 cases whose renal tissues were examined, and they were categorized into two groups. We have already published the data about Group I. We then proceeded to study two vasculitic patients in Group II clinically, pathologically, and serologically. The anti-GBM Ab and ANCA levels were detected by enzyme-linked immunosorbent assays. Renal specimens were studied by routine staining as well as immunohistochemical investigations of CD31 and type IV collagen. The total number of patients with anti-GBM disease was 7 (7/578 = 1.2%), with 3 patients belonging to Group I and 4 patients belonging to Group II. Two patients in Group II were diagnosed to have vasculitis, but the remaining 2 patients did not. One vasculitic patient was complicated by pulmonary hemorrhage, while the other vasculitic patient displayed peripheral neuropathy as well as a small cavity lesion in the lung. The latter patient was found to be positive for perinuclear (p)-ANCA, but not for any other ANCA subsets. The renal pathology in the two vasculitic patients showed crescentic glomerulonephritis (CSGN) and immunoglobulin (Ig) G linear deposits along the glomerular capillary loops. The former patient showed fibrinoid angiitis in an afferent arteriole as well as peritubular capillaritis. The latter patient demonstrated peritubular capillaritis. These peritubular capillaritides were diagnosed by the loss of CD31 and type IV collagen staining, the blurred appearance of peritubular capillary walls by periodic acid-Schiff staining, and the pericapillary infiltration of inflammatory cells. The incidence of anti-GBM disease was very low, and our patients were categorized into two groups (Groups I and II) based on whether or not they were positive for MPO- or PR3-ANCA. Two patients in Group II were found to have vasculitis. According to our results, we concluded that the anti-GBM disease of Group II could also be associated with vasculitis.
    No preview · Article · Apr 2011 · Clinical and Experimental Nephrology
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    ABSTRACT: Both myeloperoxidase-associated antineutrophil cytoplasmic antibody (MPO-ANCA) and antiglomerular basement membrane antibody (anti-GBM Ab) positivity have been demonstrated in patients with rapidly progressive glomerulonephritis (RPGN), either with or without pulmonary hemorrhage; however, the implications of these antibodies in such patients have not yet been elucidated. The cases with dual positive antibodies were studied clinically, serologically, and pathologically, and the implications of antibodies are discussed here. Four patients with prior pulmonary fibrosis, who subsequently developed RPGN and pulmonary hemorrhage, were studied clinically, serologically, and pathologically. The clinical data were reviewed extensively and the dual positive antibodies were detected by enzyme-linked immunosorbent assays. Pathological studies were performed with a renal biopsy in one patient, a gastric biopsy in another patient, and autopsy materials in the remaining 2 patients. All 4 patients had prior pulmonary fibrosis before the symptoms of RPGN when the dual positivity of MPO-ANCA and anti-GBM Ab was detected. Three cases were accompanied by pulmonary hemorrhage around the time of RPGN whereas the remaining case demonstrated pulmonary hemorrhage a few years later. Renal tissue specimens in 3 cases showed circumferential crescents and linear immunoglobulin G deposits along the glomerular capillary loops in glomeruli. Two autopsy specimens revealed vasculitis of the small arteries and arterioles of the kidney, and one of them showed similar vasculitic findings in both the gastrointestinal tract walls and the adipose tissues of the adrenal glands. Additionally, a case with pulmonary hemorrhage occurring after remission was associated with re-elevated MPO-ANCA levels but without anti-GBM Ab positivity. A gastric biopsy was unremarkable and non-contributory for the diagnosis, but this case showed vasculitic symptoms of peripheral neuritis and retinal hemorrhage. Taken together, all 4 cases demonstrated prior pulmonary fibrosis and dual positivity of MPO-ANCA as well as anti-GBM Abs at the time of RPGN, and were associated with either pulmonary hemorrhage or its occurrence thereafter. Four cases that showed prior pulmonary fibrosis as well as subsequent RPGN and pulmonary hemorrhage were both MPO-ANCA- and anti-GBM Ab-positive at the time of RPGN. The glomeruli disclosed features compatible with anti-GBM Ab disease, but the clinical and pathological vasculitic manifestations, including prior pulmonary fibrosis that might be an early manifestation of ANCA disease, suggested the occurrence of MPO-ANCA-associated vasculitis. Furthermore, 1 case subsequently showed repetitive pulmonary hemorrhage with re-elevated MPO-ANCA positivity but without anti-GBM Ab positivity, and this event was possibly due to MPO-ANCA-associated alveolar capillaritis. As anti-GBM Ab disease is generally thought not to manifest the clinical and pathological features of vasculitis excluding the kidney, MPO-ANCA might be a key factor regarding the occurrence of this dual positive disease.
    Full-text · Article · Apr 2011 · Clinical and Experimental Nephrology
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    ABSTRACT: Most tumors in the central nervous system are drug resistant partly because of the presence of the blood-brain barrier (BBB) between circulating blood and tumor tissues. Primary central nervous system lymphoma (PCNSL) is one of the exceptions, as it is highly sensitive to high-dose methotrexate (MTX)-based chemotherapy. The aim of this study was to evaluate the BBB function of tumor capillary endothelial cells in PCNSL. Expression of three major drug efflux transporters that belong to the ATP-binding cassette (ABC) superfamily, P-glycoprotein encoded by the human multidrug resistance gene (MDR1 Pgp; ABCB1), breast cancer resistance protein (BCRP; ABCG2), and multidrug resistance-associated protein 1 (MRP1; ABCC1), was evaluated. Immunohistochemistry was performed in capillary endothelial cells of 30 tumor areas from 22 PCNSL cases and compared with that of 30 gliomas. The microenvironment around tumor capillaries was assessed by examining the distribution of astrocytes and by counting the number of macrophages and T-cells, the principal cytokine producers. In PCNSL, expression of MDR1 Pgp and BCRP in tumor capillary endothelial cells was decreased in 63 and 93% of tumor areas examined, respectively, and these reduction levels differed significantly from those of gliomas (P<0.05). When the PCNSLs were further segregated by way of infiltration of tumor cells into three patterns (dense, perivascular and sparse), decreased MDR1 Pgp and BCRP in tumor capillary endothelial cells were much more prominent in dense and perivascular patterns. In all tumors and non-tumor areas of the brain, MRP1 was undetected on capillary endothelial cells. Assessment of the microenvironment around the tumor capillaries suggested that dissociation from astrocytes and infiltration of macrophages and T-cells was involved in the down-regulation of MDR1 Pgp and BCRP in capillary endothelial cells. In conclusion, we report that expression of the major ABC transporters of the BBB, MDR1 Pgp and BCRP, decreases in tumor capillary endothelial cells of PCNSL. Thus, decreased expression may permit delivery of chemotherapeutic agents to the tumor tissues.
    No preview · Article · Feb 2011 · Oncology Reports
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    ABSTRACT: Malignant pigmented villonodular synovitis (PVNS) (or malignant giant cell tumor of tendon sheath (GCTTS) is an extremely rare condition defined as a malignant lesion occurring with concomitant or previously documented PVNS at the same site. To date, only less than 20 cases have been reported in English literatures. We report a case of malignant PVNS in the knee in a 56-year-old woman with unpredictable rapid progression. This case raised a caution that when atypical components in specimens of recurrent benign PVNS are detected, even if low-grade or tiny, both pathologists and surgeons should consider the risk of malignant PVNS, which could display aggressive clinical progression.
    Full-text · Article · Jan 2011 · The Open Orthopaedics Journal
  • Katsuya Chinen · Kazuhiko Hirano · Yasunori Fujioka

    No preview · Article · Jan 2011 · Internal Medicine
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    ABSTRACT: We present a case of aortic intramural hematoma, a variant of aortic dissection, with metastatic carcinoma invasion within the aortic wall and pseudolumen. An elderly male patient with a history of controlled hypertension initially experienced chest pain. A computed tomographic scan revealed aortic intramural hematoma; thus, conservative therapy was performed. One and a half months later, tumors in both adrenal glands and the lumbar vertebra were discovered. The primary site was not identified, and the patient died following septic shock 1 month later. An autopsy revealed intramural hematoma throughout the aorta, as well as systemic metastases of adrenocortical carcinoma with invasion into the aortic wall and formation of a pseudolumen accompanied by disruption of the vasa vasorum. As far as we know, this is the second case of aortic dissection associated with metastatic carcinoma. The highly aggressive nature of the tumor cells was demonstrated by high mitotic ratio and Ki-67 labeling index. The tumor was also positive for matrix metalloproteinase-12, thus suggesting disruption of the aortic media.
    No preview · Article · Dec 2010 · Pathology - Research and Practice
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    ABSTRACT: We recently encountered 2 patients with mobile cardiac calcified amorphous tumors who were successfully treated by surgery. Both patients had mitral annular calcification and were on hemodialysis. These tumors showed swinging motion on echocardiography and they grew rapidly. Intraoperatively, the tumors were found to be fragile and they easily detached from their origin. The histologic findings were thrombus with angiogenesis, fibrin, and calcium deposition. This rapid-growing mobile tumor in end-stage renal failure patients is speculated to increase the risk of embolic events and should be included as a special entity of cardiac amorphous tumors.
    No preview · Article · Nov 2010 · The Annals of thoracic surgery
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    ABSTRACT: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare clinicopathological entity causing severe pulmonary hypertension (PH). Its histological features include widespread tumor emboli of the small arteries and arterioles of the lung, associated with thrombus formation and fibrocellular and fibromuscular intimal proliferation. Although PTTM has drawn increased attention as a fatal complication of gastric carcinoma (GC), comprehensive studies are still lacking. In order to clarify clinical and pathological features of GC-induced PTTM, recent autopsy cases were analyzed with a review of the literature. Of 36 autopsy cases with GC, 6 (16.7%) were affected by PTTM. Four were male and 2 female, with a mean age of 72.7 years. Three patients presented with PTTM-related clinical manifestations and died of PTTM. They showed clear morphological evidence of PH. The other 3 patients had PTTM as an incidental finding irrespective of clinical manifestations or PH. No patient was diagnosed antemortem as PTTM. All PTTM cases were associated with advanced GC, with a histology of adenocarcinoma of poorly differentiated type (n=4) or signet-ring cell type (n=2). Expression of tissue factor and vascular endothelial growth factor was confirmed immunohistochemically in tumor cells in all cases. The results were all in line with previous studies. In addition, the current study revealed vascular lesions characteristic of PTTM morphology to be present exclusively in the lung. In conclusion, our study shows a 16.7% incidence of PTTM in GC patients, with half of them developing PH and dying of PTTM, confirming a clinical significance as a non-negligible lethal complication of GC. In addition to many known clinicopathological characteristics of PTTM, the current study pointed to some PTTM issues requiring clarification, including the pathogenesis of the exclusive pulmonary distribution of vascular lesions of PTTM. Since details remain to be elucidated, interdisciplinary research is a high priority with a close collaboration between pathologists and clinicians in order to overcome this lethal condition.
    No preview · Article · Oct 2010 · Pathology - Research and Practice
  • Atsushi Kurata · Kazuhiko Hirano · Motoo Nagane · Yasunori Fujioka
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    ABSTRACT: We present a case of a young woman with an immature teratoma of the right ovary that showed systemic metastases. The patient initially experienced abdominal distention at the age of 15 years. Radiographic assessment revealed a right ovarian tumor; thus, right salpingo-oophorectomy was performed, and the resected ovarian tumor showed a multilocular cystic lesion with partially solid areas. Pathologic diagnosis was an immature teratoma, grade 2. As brain, lung, and liver metastases were discovered within 2 years after the operation, sequential resections of the metastatic foci were performed before chemotherapy as well as during the early and late stages of chemotherapy. The resected specimens of each metastatic focus contained histologically more mature elements of the primary immature teratoma and exhibited a decrease in the Ki-67 labeling index, the later the resection was performed. As far as we know, this is the first case of brain metastasis stemming from an immature teratoma of the ovary. In addition, it was highly suggestive that chemotherapy itself was the main etiological factor for the promotion of maturation. The favorable prognosis of this malignant tumor even after brain metastasis was verified by the 10-year-survival of the patient.
    No preview · Article · Sep 2010 · International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists
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    ABSTRACT: We present a case of a middle-aged woman with myeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis that demonstrated immunohistochemically positive MPO capillaries of the pleura. The patient initially presented with proteinuria and microscopic hematuria at the age of 38. Acute progressive glomerulonephritis and pulmonary hemorrhage occurred 4 years later, and a high serum titer of MPO-ANCA was detected therefore a diagnosis of microscopic polyangiitis was made. Steroid-pulse therapy was performed and the pulmonary shadow improved, but the renal failure did not improve, thus, hemodialysis was initiated. Thereafter, an 18-year asymptomatic phase followed, but high serum levels of MPO-ANCA persisted during this period. Chronic pulmonary hemorrhage was discovered at the age of 60, and video-assisted thoracoscopic surgery was performed. Resected tissue revealed diffuse aloveolar hemorrhage accompanied by marked hemosiderin deposition, whereas MPO-immunopositive capillaries were identified only in the pleura. To our knowledge, this is the first report demonstrating MPO-positive capillaries in a disease other than glomerulonephritis. Judging from this unique case, MPO-positive endothelial cells may appear only during the hyperacute stage before hemorrhage, and may diminish thereafter, thus, may be associated with the trigger of microscopic polyangiitis.
    No preview · Article · Sep 2010 · Pathology International

  • No preview · Article · Jul 2010 · Journal of Orthopaedic Science

Publication Stats

1k Citations
301.24 Total Impact Points


  • 1999-2014
    • Kyorin University
      • • Department of Pathology
      • • School of Medicine
      Edo, Tokyo, Japan
  • 1992-2008
    • Hokkaido University Hospital
      Sapporo, Hokkaidō, Japan
  • 1989-2007
    • Hokkaido University
      • Department of Pathology
      Sapporo, Hokkaido, Japan
  • 2000-2002
    • Hyogo College of Medicine
      • Department of Internal Medicine
      Nishinomiya, Hyōgo, Japan