Tadashi Yoshino

Tottori University, TTJ, Tottori, Japan

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Publications (343)1038.19 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer, often associated with Merkel cell polyomavirus (MCPyV). Recently, immunoglobulin (Ig) expression was reported in MCC, thereby suggesting that B cells might be their cellular ancestors. We tested 30 MCCs (20 MCPyV-positive and 10 MCPyV-negative) using immunohistochemistry for the expressions of IgG, IgA, IgM, Igκ, Igλ, terminal desoxynucleotidyl transferase, paired box gene 5 (PAX5), octamer transcription factor-2 (Oct-2), and sex-determining region Y-box 11 (SOX11). We performed in situ hybridization for Igκ-mRNA or Igλ-mRNA and Ig heavy chain (IgH) gene rearrangement (IgH-R) analyses. The expressions of PAX5, TdT, Oct-2, and SOX11 were not significantly different between MCPyV-positive and MCPyV-negative MCCs. At least 1 of IgG, IgA, IgM, or Igκ was expressed in MCPyV-positive (14/20, 70%) and none in MCPyV-negative MCCs (P=0.0003). There was a higher tendency for Igκ-mRNA expression (7/19, using in situ hybridization) and IgH-R (10/20, using polymerase chain reaction) in MCPyV-positive than in MCPyV-negative MCCs (0/10 and 2/10, respectively), thus suggesting a different Ig production pattern and pathogenesis between the 2 types of MCC. Ig expression or IgH-R in MCPyV-positive MCCs might be associated with MCPyV gene integration or expression in cancer cells but do not necessarily suggest a B-cell origin for MCCs. IgH expression or IgH-R nonsignificantly correlated with improved prognosis. However, these might be important factors that influence the survival of neoplastic cells and might allow the development of novel therapies for patients with MCPyV-positive MCCs.
    The American journal of surgical pathology. 12/2014; 38(12):1627-35.
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    ABSTRACT: A cell line named PRU-1, derived from a Langerhans cell (LC) histiocytosis (LCH) skull lesion of a 7-year-old boy, was established and characterized. PRU-1 is an adherent spindle-shaped cell line that shows no Birbeck granules on electron microscopy. Flow cytometric analysis of cells collected from the early seventh passage showed no LC phenotypes of CD1a and S100 protein. Immunostaining of PRU-1 cells also revealed no expression of LC markers but showed expression of CD11c, CD54 (ICAM-1) and CD68, which was also observed in some peripherally located cells of the original LCH lesion. The PRU-1 cells stained positive for factor XIIIa and negative for CD34, suggesting a dermal dendritic cell phenotype. Cytogenetic analyses revealed abnormalities such as 39,XY,-2,-4,-8,-12,-12,-14,add(18)(q21),20,+mar and 44,XY,-11,-14,add(18)(q21). TCRγ rearrangement in the PRU-1 cells was not amplified by PCR. Tumorigenicity was not proven by xenografting into SCID mice. A conditioned medium from PRU-1 culture induced the proliferation of peripheral blood lymphocytes as well as the activation of monocytes from a healthy donor into CD1a-positive LC-like cells. Because the phenotypic characteristics of PRU-1 differed from those of CD1a-positive abnormal LC-like cells (LCH cells), it was likely that the PRU-1 cells were derived from peripherally located cells of the LCH lesion rather than LCH cells. LCH has been regarded as a type of granulomatous neoplasm with several intermingled inflammatory cells and influenced by stimuli such as Merkel cell polyomavirus (MCPyV) infection or cigarette smoking. However, in the PRU-1 cells, MCPyV-DNA was not detected by PCR. Stromal cell-like PRU-1 cells are likely to produce some growth or differentiation factors, which may play important roles in LCH lesion formation, cell maintenance and LC-like cell induction.
    Oncology reports. 10/2014;
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    ABSTRACT: Primary intestinal follicular lymphoma (FL) is a variant of FL characterized by frequent duodenal involvement and a very indolent clinical behavior without therapy. Unlike nodal FL, there have been no reports of histologic transformation (HT) or death attributable to primary intestinal FL. Here, we report the first case of primary duodenal FL showing HT. A Grade 1 FL in the duodenum was incidentally detected in a 73-year-old man. A watch-and-wait strategy was adopted because the disease was stage IE. Six months later, bone marrow involvement was suspected. The intestinal lesions had not changed during the first year since the initial diagnosis. Sixty-two months after the initial diagnosis, a biopsy specimen showed diffuse large B-cell lymphoma (DLBCL). A perforation of the intestine occurred before chemotherapy was started. Partial resection was performed and subsequent chemotherapy was administered. The clone of the initial FL and DLBCL were identical according to PCR analysis, indicating that the primary intestinal FL had transformed into DLBCL. Although HT is rare, it could occur in some patients with primary intestinal FL. Based on this case, it may be necessary to re-evaluate the clinical watch-and-wait strategy for primary intestinal FL in some patients.
    Pathology International 10/2014; · 1.72 Impact Factor
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    ABSTRACT: Objective: This study examined whether the occurrence of late neck metastasis in early tongue squamous cell carcinoma can be predicted by evaluating HMGB1 (high mobility group box 1) expression in the primary lesion. Methods: A case-control study was conducted. The cases comprised 10 patients with late neck metastasis. The controls consisted of 16 patients without recurrence. All were examined immunohistochemically for HMGB1 protein expression. The odds ratio for late neck metastasis in relation to HMGB1 was estimated. Results: Results for HMGB1 were dichotomised into positive staining scores (score, 5-7) and negative scores (0-4). Six cases (60 per cent) and four controls (25 per cent) were HMGB1-positive. Although no significant result was seen, compared with HMGB1-negative patients the odds ratio for late neck metastasis in HMGB1-positive patients was 3.8 (95 per cent confidence interval, 0.6-26.5) after adjusting for other factors. Conclusion: In the present study, immunohistochemical study of HMGB1 in early tongue squamous cell carcinoma did not appear to be very useful for predicting occult neck metastasis. Further study is necessary to clarify the relationship between HMGB1 expression and late neck metastasis in early tongue squamous cell carcinoma.
    The Journal of laryngology and otology. 09/2014;
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    ABSTRACT: Primary cutaneous, extranodal natural killer/T-cell lymphoma, nasal type (PC-ENKTL), is a rare Epstein-Barr virus (EBV)-associated neoplasm with poorly defined clinicopathologic features. We performed a multinational retrospective study of PC-ENKTL and CD56-positive EBV-negative peripheral T-cell lymphoma (PC-CD56+PTCL) in Asia in an attempt to elucidate their clinicopathologic features. Using immunohistochemistry for T-cell receptors (TCRs), in situ hybridization for EBV, and TCR gene rearrangement, we classified 60 tumors into 51 with PC-ENKTL (20 of NK-cell, 17 T-cell, and 14 indeterminate lineages) and 9 with PC-CD56+PTCL. Tumors of T-cell origin accounted for 46% of PC-ENKTLs with half of these cases being TCR-silent. As compared with T-lineage tumors, PC-ENKTLs of NK-cell lineage had more frequent involvement of regional lymph nodes and more frequently CD8-negative and CD56-positive. Cases of PC-ENKTL showed more frequent tumor necrosis, younger age, and a higher frequency of CD16 and CD30 expression than cases of PC-CD56+PTCL. CD56-positive T-lineage PC-ENKTL tumors (n=8) had more localized disease in the TNM (tumor-node-metastasis) staging and were more often of γδ T-cell origin compared with cases of PC-CD56+PTCL (n=9). PC-ENKTLs and PC-CD56+PTCLs were equally aggressive, with a 5-year overall survival rate of 25%. Tumor necrosis and CD16 expression may serve as useful surrogates for differentiating PC-ENKTL from PC-CD56+PTCL. A single lesion, an elevated lactate dehydrogenase level, and the presence of B symptoms were independent poor prognostic factors for PC-ENKTL in multivariate analysis. Further studies with more cases are warranted to delineate the clinicopathologic features and significance of EBV in these rare lymphomas.
    The American journal of surgical pathology. 09/2014;
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    ABSTRACT: Concurrent chemoradiotherapy has become one of the standard management approaches for newly diagnosed, localized, nasal NK/T-cell lymphoma (NKTCL). Few data are available on the prognostic biomarkers of NKTCL among patients treated with concurrent chemoradiotherapy. To evaluate the prognostic significance of immunophenotypic biomarkers for patients treated with concurrent chemoradiotherapy, latent membrane protein 1 (LMP1), cutaneous lymphocyte antigen (CLA), and cell origin were examined with samples from 32 patients who were enrolled in the Japan Clinical Oncology Group 0211 trial and treated with concurrent chemoradiotherapy. LMP1 and CLA were positive in 66% (19/29) and 29% (9/31) of the cases examined, respectively. The median follow-up duration was 68 months (range, 61-94). The patients with LMP1-positive tumors showed a better overall survival (OS) than the patients with LMP1-negative tumors [hazard ratio, 0.240; 95% confidence interval (CI), 0.057-1.013; 80% CI, 0.093-0.615; P=0.035]. All five patients with LMP1-negative tumors who experienced disease progression died of lymphoma, and both patients with local failure had LMP1-negative tumors. There was no significant difference in OS according to CLA expression. Twenty-seven (84%) cases were of NK-cell origin, two were of αβ T-cell origin, and three were of γδ T-cell origin. In contrast to those with tumors of NK-cell origin, all five patients with NKTCL of T-cell origin were alive without relapse at the last follow-up. Our results indicate that LMP1 expression is a favorable prognostic marker and suggest that a T-cell origin of the tumor may be a favorable prognostic marker for patients with localized NKTCL treated with concurrent chemoradiotherapy.This article is protected by copyright. All rights reserved.
    Cancer Science 09/2014; · 3.48 Impact Factor
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    ABSTRACT: Abstract Conclusion: In tongue squamous cell carcinoma (SCC), high levels of regulatory T-cell (Treg) infiltration in tumor nests are observed in the cases with poor prognosis. Objectives: The role of Tregs in head and neck cancers remains unclear. The aim of this study was to observe the distribution of Tregs in different stages of tongue SCC and estimate the effects on prognosis. Methods: Thirty-four cases with tongue SCC were examined immunohistochemically for CD4, CD8, and Forkhead box P3 (Foxp3). Immunoreactive cells were counted in cancer stroma and nest regions, and relationships between cell numbers and disease-free survival rates were analyzed. Results: In the 34 cases, univariate analysis for disease-free survival indicated high-level infiltration of Tregs (CD4(+)Foxp3+) into both cancer nests and stroma and presence of helper T (CD4(+)Foxp3-) cells in cancer stroma as potential predictors of significantly worse prognosis. In early-stage cases (stage I/II), high-level infiltration of Tregs in cancer nests correlated significantly with poor disease-free survival rate. Multivariate analysis for disease-free survival found no independent variables.
    Acta oto-laryngologica. 06/2014;
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    ABSTRACT: Type AB thymoma is generally regarded to be a mixture of type A and type B thymomas, but has not been studied extensively. In this study, we precisely investigated the characteristics of type AB thymoma immunohistochemically and compared it with other types of thymoma, including type A, metaplastic, and type B1 thymoma. In type A thymoma, the tumor cells were composed solely of pan-cytokeratin (CK-AE1/AE3)(+) claudin-1(+) vimentin(-) epithelial membrane antigen (EMA)(-) short spindle cells. Metaplastic thymoma exhibited biphasic architecture of epithelial islands of short spindle cells, which were phenotypically almost identical to the tumor cells in type A thymoma, and anastomosing bundles of CK-AE1/AE3(-) claudin-1(-) vimentin(+) EMA(+) fibroblast-like long spindle-shaped epithelial cells. Interestingly, we found that there were two distinctive subtypes of cell in type AB thymoma: the conventional subtype and the metaplastic subtype. The conventional subtype is characterized by type A-like components resembling type A thymoma. The metaplastic subtype is characterized by type A-like components extensively resembling the anastomosing bundles of fibroblast-like long spindle epithelial cells. Interestingly, the metaplastic subtype was a major subtype (14/19 cases), while the conventional subtype was a minor one (5/19 cases). In contrast to the rarity of metaplastic thymoma, the metaplastic subtype of type AB thymoma appears to be a major subtype of type AB thymoma.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 05/2014; · 2.68 Impact Factor
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    ABSTRACT: Primary cutaneous γδ T-cell lymphoma (PCGD-TCL) is an aggressive lymphoma consisting of clonal proliferation of mature activated γδ T-cells of a cytotoxic phenotype. Because PCGD-TCL is a rare disease, there are few clinicopathological study reports. In addition, T-cell receptor (TCR) γδ cells are typically immunostained in frozen sections or determined by TCRβ negativity. We retrospectively analyzed 17 primary cutaneous T-cell lymphomas of the γδ phenotype (CTCL-γδ) in a clinicopathological and molecular study using paraffin-embedded sections. Eleven of 17 patients had CTCL-γδ without subcutaneous panniculitis-like T-cell lymphoma (SPTCL) features and 6 had CTCL-γδ with SPTCL features. Immunophenotypically, some significant differences were found in CD8 and CD56 positivity between our patient series of CTCL-γδ patients with SPTCL features and SPTCL-γδ patients described in the previous literature. The univariate analysis of 17 CTCL-γδ patients showed that more than 60 years old age, presence of visceral organ involvement, and small-to-medium cell size were poor prognostic factors. In addition, the 5-year overall survival rate was 42.4% for the CTCL-γδ patients without SPTCL features and 80.0% for those with SPTCL features. Consequently, there was a strikingly significant difference in overall survival among SPTCL, CTCL-γδ with SPTCL features and CTCL-γδ without SPTCL features (P = 0.0005). Our data suggests that indolent subgroup may exist in CTCL-γδ. Studies on more cases including multinational areas are warranted to delineate the clinicopathological features and the significance in these rare lymphomas.This article is protected by copyright. All rights reserved.
    Cancer Science 05/2014; · 3.48 Impact Factor
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    ABSTRACT: IgG4-related lymphadenopathy with increased numbers of Epstein-Barr virus (EBV)-infected cells has been reported but not fully described. We analyzed 31 cases of IgG4-related lymphadenopathy and 24 cases of extranodal IgG4-related diseases for their possible relationship with EBV. Other types of reactive lymph nodes (22) and angioimmunoblastic T-cell lymphoma (AITL) (10) were also studied for comparison. EBV-encoded RNA (EBER) in situ hybridization revealed EBER cells in 18 of 31 cases (58%) of IgG4-related lymphadenopathy. Increased EBER cells were found in only 4 of 22 (18.1%) non-IgG4-related reactive lymphoid hyperplasia in patients of a similar age (P=0.002) and in only 5 of 24 (21%) extranodal IgG4-related biopsies (P=0.006). Interestingly, all patients with EBER progressively transformed germinal center-type IgG4-related lymphadenopathy had systemic lymphadenopathy and/or extranodal involvement. AITL also is associated with EBV, and IgG4-related lymphadenopathy sometimes mimics the morphology of AITL; however, the number of IgG4 cells in AITL was significantly less than that in IgG4-related lymphadenopathy (P<0.001). Increased numbers of regulatory T cells are seen in IgG4-related disease; however, there was not a significant difference between the EBER and EBER cases. In conclusion, the presence of increased numbers of EBV-infected cells in IgG4-related lymphadenopathy, compared with other reactive lymphadenopathy or extranodal IgG4-related disease, suggests that there may be a relationship at least between nodal IgG4-related disease and EBV. It is important to avoid overdiagnosing these cases as malignant lymphomas or EBV-related lymphoproliferative disorders.
    The American journal of surgical pathology 04/2014; · 4.06 Impact Factor
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    ABSTRACT: Follicular lymphoma (FL) of the gastrointestinal tract, particularly duodenal follicular lymphoma (DFL), is a rare variant of FL with indolent clinical behavior, and this disease is included in 2008 WHO classifications. In contrast to nodal follicular lymphoma (NFL), DFL occurs most frequently in the second part of the duodenum, lacks follicular dendritic cell meshworks, and has memory B-cell characteristics. However, its molecular pathogenesis is still unclear. In the present study, we examined 10 DFL, 18 NFL, 10 gastric MALT lymphoma samples by gene expression analysis. Quantitative RT-PCR experiments and immunohistochemical analysis for 72 formalin-fixed, paraffin-embedded tissues from an independent series, including 32 DFL, 19 gastric MALT lymphoma, and 27 NFL samples were performed for validation of microarray data. Gene expression profiles of the 3 lymphoma types were compared using 2,918 differentially expressed genes (DEGs) and results suggested that DFL shares characteristics of MALT lymphoma. Among these DEGs, CCL20, and MAdCAM-1 were up-regulated in DFL and MALT but down-regulated in NFL. In contrast, protocadherin gamma subfamily genes were up-regulated in DFL and NFL. Quantitative RT-PCR and immunohistochemical studies demonstrated concordant results. Double immunofluorescence studies revealed that CCL20 and CCR6 were co-expressed in both DFL and MALT. We hypothesize that increased expression of CCL20 and MAdCAM-1 and co-expression of CCL20 and CCR6 may play an important role in tumorigenesis. This article is protected by copyright. All rights reserved.
    Cancer Science 03/2014; · 3.48 Impact Factor
  • Mai Takeuchi, Yasuharu Sato, Tadashi Yoshino
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    ABSTRACT: Diagnosis of malignant lymphoma is based on the 4th edition of World Health Organization (WHO) Classification of Tumours of Haematopoietic and Lymphoid Tissues. The frequency of malignant lymphoma subtypes depends on age, race and geography. In Asian countries, Hodgkin lymphoma and follicular lymphoma are less frequent compared to Western countries. However, the number of patients with follicular lymphoma is now increasing in Japan. In contrast, in Japan, adult T-cell leukemia/lymphoma is more frequent than in Western and other Asian countries, because it relates to distribution of human T-cell leukemia virus type 1(HTLV-1).
    Nippon rinsho. Japanese journal of clinical medicine 03/2014; 72(3):436-40.
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    ABSTRACT: A 77-year-old man, with a lengthy medical history of chronic dysuria, constipation, hypertension, myocardial infarction, and a submandibular lymphadenopathy that was excised 3 years ago, was hospitalized due to elevated liver enzyme levels. He demonstrated hypergammaglobulinemia, hyperproteinemia, high levels of IgG and IgG4, eosinophilia, sclerosing cholangitis, and retroperitoneal fibrosis. He was diagnosed with IgG4-related disease (IgG4-RD). While hospitalized, he had several episodes of syncope while standing and was diagnosed with autonomic nerve dysfunction. Thirty days after hospitalization, he died of nonocclusive mesenteric ischemia (NOMI). Post-mortem, his submandibular lymphadenopathy lesion was diagnosed with progressively transformed germinal center (PTGC)-type IgG4-related lymphadenopathy. At autopsy, small and large intestines showed mucosal necrosis and the wall muscles of the transverse to sigmoid colon were necrotic. The sigmoid colon was fibrotic and infiltrated with numerous IgG4+ plasma cells and eosinophils; infiltration into Auerbach's plexus was also observed. The IgG4-RD lesions were also detected in the mesentery of the sigmoid colon, retroperitoneal soft tissue, abdominal aorta, liver, extrahepatic bile duct, bilateral lungs, bilateral kidneys, urinary bladder, prostate, epicardium, bilateral coronary arteries, and lymph nodes. Interestingly, infiltration into the lesions was most notable around the peripheral nerves in every organ. Thus, this case describes an IgG4-RD that progressed from PTGC-type IgG4-related lymphadenopathy to systemic IgG4-RD, suggesting that IgG4-RD may affect many organs through peripheral nerve involvement.Virtual slide: http://www.diagnosticpathology.diagnomx.eu/vs/9995992971155224.
    Diagnostic Pathology 02/2014; 9(1):41. · 2.41 Impact Factor
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    ABSTRACT: IgG4-related disease is a systemic disorder with unique clinicopathological features and uncertain etiological features and is frequently related to allergic disease. T helper 2 and regulatory T-cell cytokines have been reported to be upregulated in the affected tissues; thus, the production of these cytokines by T helper 2 and regulatory T cells has been suggested as an important factor in the pathogenesis of IgG4-related disease. However, it is not yet clear which cells produce these cytokines in IgG4-related disease, and some aspects of the disorder cannot be completely explained by T-cell-related processes. To address this, we analyzed paraffin-embedded sections of tissues from nine cases of IgG4-related submandibular gland disease, five cases of submandibular sialolithiasis, and six cases of normal submandibular gland in order to identify potential key players in the pathogenesis of IgG4-related disease. Real-time polymerase chain reaction analysis confirmed the significant upregulation of interleukin (IL)4, IL10, and transforming growth factor beta 1 (TGFβ1) in IgG4-related disease. Interestingly, immunohistochemical studies indicated the presence of mast cells expressing these cytokines in diseased tissues. In addition, dual immunofluorescence assays identified cells that were double-positive for each cytokine and for KIT, which is expressed by mast cells. In contrast, the distribution of T cells did not correlate with cytokine distribution in affected tissues. We also found that the mast cells were strongly positive for IgE. This observation supports the hypothesis that mast cells are involved in IgG4-related disease, as mast cells are known to be closely related to allergic reactions and are activated in the presence of elevated non-specific IgE levels. In conclusion, our results indicate that mast cells produce T helper 2 and regulatory T-cell cytokines in tissues affected by IgG4-related disease and possibly have an important role in disease pathogenesis.Modern Pathology advance online publication, 3 January 2014; doi:10.1038/modpathol.2013.236.
    Modern Pathology 01/2014; · 5.25 Impact Factor
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    ABSTRACT: From a clinicopathological conference on nine elderly patients with Epstein-Barr virus (EBV)-associated T/natural killer (NK)-cell lymphoma, we have addressed the patients' backgrounds, clinical manifestations, histopathological findings, cytogenesis, complications and prognoses. Among these elderly patients (>65 years old), seven patients had extranodal NK/T-cell lymphoma, nasal type (ENKL) with an NK-cell phenotype, and two patients had EBV(+) T-cell lymphomas or lymphoproliferative disorders (LPD) with cutaneous lesions mimicking pityriasis lichenoides et varioliformis acuta (PLEVA) or hydroa vacciniforme (HV). No patients had a previous episode of EBV-related symptoms such as infectious mononucleosis, chronic active EBV infection, HV or hypersensitivity to mosquito bites. Elderly patients with ENKL may show the centroblastoid variant. EBV(+) CD8(+) CD56(+/-) lymphocytes may be responsible for the development of PLEVA or HV-like cutaneous lesions in the elderly.
    The Journal of Dermatology 01/2014; 41(1):40-2. · 2.35 Impact Factor
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    ABSTRACT: The purpose of this study was to reveal the diagnostic accuracy of initial pathologic assessment of biopsied samples in patients with gastrointestinal follicular lymphoma lesions. A total of 48 follicular lymphoma patients (Lugano system stage I: n=30; II1: n=4; II2: n=4; IV: n=10) with gastrointestinal involvement who underwent endoscopic biopsy were enrolled and retrospectively reviewed. Nine of the 48 patients (18.8%) were not appropriately diagnosed as having follicular lymphoma at the initial biopsy. The initial pathological diagnosis included extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) (n=4), necrotic tissue (n=2), duodenitis (n=1), or suspected lymphoma of unspecified subtype (n=2). The reasons for these inappropriate diagnoses were insufficient histopathological analysis lacking CD10 and BCL2 staining (n=7) and unsuitable biopsy samples taken from erosions or ulcers that contained scanty lymphoma cells or no lymphoid follicles (n=2). In conclusion, incomplete histopathological analysis and unsuitable biopsy samples are pitfalls in the diagnosis of gastrointestinal follicular lymphoma.
    Annals of diagnostic pathology 01/2014;
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    ABSTRACT: Langerhans cell (LC) sarcoma (LCS) is a high-grade neoplasm with overtly malignant cytologic features and an LC phenotype. We very recently suggested that LC behaves as a reservoir for common dermotropic Merkel cell polyomavirus (MCPyV) and determined the relationship between LC histiocytosis (LCH), which has an underlining oncogenic capacity, and MCPyV as a trigger for a reactive process rather than a neoplastic process. We propose LC to be a reservoir for MCPyV and hypothesize that some LCS subtypes may be related to the MCPyV agent. We examined seven LCS tissues using multiplex quantitative PCR (Q-PCR) and immunohistochemistry with anti MCPyV large-T (LT) antigen antibody. High viral loads of MCPyV DNA sequences (viral load = relative levels of MCPyV) were detected (0.328-0.772 copies/cell (Merkel cell carcinoma (MCC) = 1.0)) using Q-PCR in 43% (3/7) tissues, but LT antigen expression was not observed (0/7). Frequent MCPyV-DNA amplification suggests that LCS in some patients may be related to MCPyV infection. Moreover, the higher viral load of LCS (median, 0.453 copies/cell) than low load of LCH (0.003, median of 12 cases) (P < 0.01) may suggest a virally induced tumorigenic process in some LCS. Although the absence of LT antigen expression may indicate a different role for MCPyV in this pathology, some subtypes of LCS may develop in the background of MCPyV-infected LC. To the best of our knowledge, this is the first report on the relationship between MCPyV and LCS. The recent discovery of MCPyV opened new therapeutic avenues for MCC. These data open novel possibilities for therapeutic interventions against LCS.
    Infectious Agents and Cancer 01/2014; 9:15.
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    ABSTRACT: A 62-year-old Japanese male was diagnosed with primary intestinal follicular lymphoma involving the duodenum, jejunum, and rectum without lymph node involvement. The patient was classified as low risk by the follicular lymphoma international prognostic index (FLIPI) system. Treatment was deferred because he had no symptoms. Eleven months after the diagnosis, his soluble interleukin-2 receptor (sIL-2R) levels had risen from 383 to 617 U/mL. Lymphoma progression involving an enlarged perigastric lymph node was also documented. This report illustrates a case of rapidly progressed intestinal follicular lymphoma, suggesting the possible usefulness of sIL-2R levels as an indicator of lymphoma progression.
    Case reports in oncological medicine. 01/2014; 2014:549248.
  • Internal Medicine 01/2014; 53(12):1397. · 0.97 Impact Factor
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    ABSTRACT: Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42–89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus IgH/BCL-2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) (MYD88) L265P mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; immunoglobulin M and G paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and MYD88 L265P mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma.
    Human pathology 01/2014; · 3.03 Impact Factor

Publication Stats

4k Citations
1,038.19 Total Impact Points


  • 2011–2014
    • Tottori University
      • Faculty of Medicine
      TTJ, Tottori, Japan
  • 1994–2014
    • Okayama University
      • • Department of Medical Technology
      • • Department of Pathology and Oncology
      • • Department of Ophthalmology
      • • Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
      • • Medical School
      Okayama, Okayama, Japan
  • 2013
    • The Australian Society of Otolaryngology Head & Neck Surgery
      Evans Head, New South Wales, Australia
  • 2012–2013
    • Kinki University
      Ōsaka, Ōsaka, Japan
    • Kagawa Prefectural Central Hospital
      Takamatu, Kagawa, Japan
  • 2009–2011
    • Kurume University
      • Department of Pathology
      Куруме, Fukuoka, Japan
  • 2008–2011
    • Nagoya University
      • • Clinical Laboratory
      • • Division of Dermatology
      Nagoya-shi, Aichi-ken, Japan
    • Aichi Medical University
      • Department of Pathology
    • Mie University
      • Department of Hematology and Oncology
      Tsu-shi, Mie-ken, Japan
    • Shinshu University
      • Division of Hematology
      Shonai, Nagano, Japan
  • 2003–2010
    • Aichi Cancer Center
      Ōsaka, Ōsaka, Japan
  • 2007
    • San Raffaele Scientific Institute
      Milano, Lombardy, Italy
  • 2006
    • Novartis Institutes for BioMedical Research
      Cambridge, Massachusetts, United States
  • 2002–2006
    • Hiroshima City Hospital
      Hirosima, Hiroshima, Japan
  • 2005
    • Akita University Hospital
      Akita, Akita, Japan
  • 2002–2003
    • Nagoya City University
      • Department of Pathology
      Nagoya, Aichi, Japan
  • 2000
    • Aichi Prefectural Institute of Public Health
      Nagoya, Aichi, Japan