Yasuharu Sato

Okayama University, Okayama, Okayama, Japan

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Publications (98)270.98 Total impact

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    ABSTRACT: IgG4-related disease is a recently established systemic condition. Tubulointerstitial nephritis is the most common renal manifestation. Glomerular lesions, particularly membranous glomerulonephritis, can develop simultaneously. Some patients present with serological renal dysfunction associated with elevated IgG or IgE levels and hypocomplementemia, while others are incidentally found to have abnormalities in kidneys on imaging. A majority of patients with IgG4-related kidney disease have similar lesions at other anatomical sites, which help us to suspect this condition. Serum IgG4 elevation (>135 mg/dL) is the most, although not entirely, specific marker for the diagnosis. Imaging findings varies from small nodules to bilateral diffuse abnormalities. In addition to the renal parenchyma, the renal pelvis and perirenal adipose tissue can be affected. Histological features include dense lymphoplasmacytic infiltration, storiform or "bird's eye" fibrosis (highlighted by PAM stain), and IgG4-positive plasma cell infiltration (>10 cells/high-power field and IgG4/IgG-positive cell ratio >40%). Immune complex deposition is detectable in the tubular basement membrane by immunofluorescence and/or electron microscopy. Patients usually respond well to corticosteroids, but highly active diseases may require other immunosuppressive therapies. Further investigations will be required to fully understand pathophysiology underlying this emerging condition.
    No preview · Article · Oct 2014 · International journal of clinical and experimental pathology
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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.
    No preview · Article · Oct 2014 · Pathology International
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    ABSTRACT: A 28-year-old male was referred to our hospital for fever of unknown origin (FUO). He had histories of FUOs at the age of 23 and 25. After the admission he experienced tarry stools, then endoscopic examination was performed and found multiple ulcerations in the small intestine. Because anemia was refractory, partial resection of intestine was performed. Histological examination of the resected specimen showed angiocentric proliferation of atypical cells with irregular nuclear contour. They were CD3 +, CD56-, TIA1 +, TCR[beta]+, TCR[gamma]- by immunohistochemistry and EBER-ISH +. There was no other lesion except duodenum, jejunum, and regional mesenteric lymph node and then the diagnosis of primary intestinal NK/T cell lymphoma of T-cell lineage was rendered. Five courses of cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone were performed. Although the lesions became scar endoscopically, scattered CD3 +, EBER + cells persisted to be detected microscopically. Additional cord blood transplantation was performed twice, but the patient died because of pneumonitis and encephalitis 17 months after the initial diagnosis. Primary intestinal NK/T cell lymphoma is a rare and highly aggressive disease in spite of intensive chemotherapy. We report this case with a review of the literature.
    No preview · Article · Oct 2014 · Pathology
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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.
    No preview · Article · Jul 2014 · Human pathology
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    ABSTRACT: Follicular lymphoma (FL) is a heterogeneous disease, and there are many different subgroups, such as in terms of age of onset, involved organ (especially extranodal sites such as gastrointestinal tract) and genetic abnormality. Grade 3B is currently regarded as a distinct entity by molecular genetic analyses, but the independence of Grade 3A remains unclear. Variations of clinical course are known in FL. Some cases are very indolent, but others are not. The latter cases show histological transformation to diffuse large B-cell lymphoma (DLBCL) (high-grade transformation) and an aggressive course. Histological transformation to DLBCL is reported to occur in about 30-40% of patients, at a rate of about 3% each year. However, it reaches a plateau at about 16 years, so the stratification of patients in whom transformation would or would not occur is very important for the therapeutic strategy. From genome-wide analysis by next-generation sequencing, EZH2, CREBBP and MLL2, which are histone-modifying genes, have been shown to be frequently mutated in FL and to have an important role in lymphomagenesis. IGH-BCL2 translocation and CREBBP mutations are early events, whereas MLL2 and TNFSFR14 mutations represent late events during disease evolution. In the 2008 WHO classification, three new variants: (1) pediatric follicular lymphoma, (2) primary intestinal follicular lymphoma and (3) in situ follicular lymphoma, are included. Pathologists and clinicians should consider these new developments when deciding on the diagnostic and therapeutic strategy. [J Clin Exp Hematop 54(1): 3-9, 2014].
    No preview · Article · Jun 2014 · Journal of Clinical and Experimental Hematopathology
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    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.
    No preview · Article · Jun 2014 · Acta Oto-Laryngologica
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    ABSTRACT: We describe a 74-year-old Japanese man with systemic fibroinflammatory conditions closely resembling those of immunoglobulin G4-related disease (IgG4-RD). Radiology and histology showed characteristics of IgG4-related tubulointerstitial nephritis, despite normal serum IgG4 value and scanty IgG4-positive plasma cell infiltration in each organ. This case suggests that a condition closely mimicking IgG4-RD may develop without IgG4-positive plasma cells and those exceptional cases should also be taken into account in the differential diagnosis of IgG4-RD.
    Full-text · Article · Jun 2014 · Modern Rheumatology
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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.
    Full-text · Article · May 2014 · Cancer Science
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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.
    No preview · Article · Apr 2014 · The American journal of surgical pathology
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    ABSTRACT: Background: Few studies have investigated the prognostic factors for nasal natural killer (NK)/T-cell lymphoma. Methods: This was a retrospective multicenter clinical study. The clinical records of 36 patients with nasal NK/T-cell lymphoma who had been first treated between 1996 and 2011 were collected from 12 hospitals. Results: High serum levels of C-reactive protein (≥1.0 mg/dL), lactate dehydrogenase (≥350 IU/L), and soluble interleukin-2 receptor (sIL-2R; ≥600 U/mL) were associated with worse prognosis. A prognostic score was devised by totaling the number of these 3 predictors: 0 or 1 = score 0; and 2 or 3 = score 1. As for tumor invasion, local invasion beyond the nasal cavity was associated with poor prognosis, and a prognostic score was devised as: tumor restricted to nasal cavity, yes = score 0; no = score 1. A novel prognostic index (NPI) was established based on these scores from 0 to 2. Disease-specific survival rates at 5 years were: 90.0% for NPI = 0; 29.3% for NPI = 1; and 0.0% for NPI = 2. Conclusion: Our NPI is valid for anticipating prognosis of nasal NK/T-cell lymphoma.
    No preview · Article · Apr 2014 · Head & Neck
  • 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).
    No preview · Article · Mar 2014 · Nippon rinsho. Japanese journal of clinical medicine
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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.
    Preview · Article · Mar 2014 · Cancer Science
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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 The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9995992971155224.
    Preview · Article · Feb 2014 · Diagnostic Pathology

  • No preview · Article · Jan 2014 · Acta oto-laryngologica
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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.
    Preview · Article · Jan 2014 · Modern Pathology
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    ABSTRACT: The objective of this study was to delineate the frequency of delayed diagnosis in cases of subacute thyroiditis (SAT) and intervals between onset of clinical symptoms and appearance of abnormal laboratory findings. We reviewed the medical records of 27 patients (7 men and 20 women) with SAT who visited our hospital between 2007 and 2013. On presentation to the hospital, 5 of 27 SAT cases (18.5%) showed normal laboratory findings. Among these 5 cases, the mean interval between symptom onset and thyrotropin (TSH) suppression was 6.3 weeks, and the mean interval to elevation of fT4 was 6.7 weeks. The longest interval from symptom onset to appearance of an abnormal laboratory finding was 11 weeks. Sometimes time-lag exists between onset of clinical symptoms and the appearance of abnormal laboratory findings in patients with SAT. The possibility of this disease should not be excluded from the differential diagnoses for patients with clinical symptoms consistent with SAT but showing normal laboratory findings.
    No preview · Article · Dec 2013 · Auris, nasus, larynx
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    ABSTRACT: ABSTRACT While the use of PCR-based clonality analysis of formalin-fixed paraffin embedded (FFPE) tissue has recently become widespread, the detection sensitivity for lymphoma subtypes using FFPE samples is not well known. Here, we analyzed T-cell receptor γ chain (TCRG) gene rearrangement clonality in 100 cases of T or NK/T cell lymphoma and examined detection sensitivity according to lymphoma subtypes. Clonality was detected in approximately 80% of the major T-cell lymphoma subtypes: peripheral T-cell lymphoma, not otherwise specified, 84% (21/25 cases); angioimmunoblastic T-cell lymphoma, 71% (15/21 cases); and adult T-cell leukemia/lymphoma, 80% (8/10 cases). The number of clonal peaks differed according to subtype. TCRG gene rearrangement was not detected in 63 cases of B-cell lymphoma or reactive lesions. Thus, clonality analysis can effectively and reliably detect TCRG gene rearrangement in T-cell lymphoma cases and could, therefore, be a useful diagnostic tool in routine practice.
    No preview · Article · Dec 2013 · Leukemia & lymphoma
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    ABSTRACT: Conclusion: Cutting needle biopsy (CNB) combined with immunohistochemical study of myeloperoxidase (MPO) is a useful minimally invasive diagnostic procedure for histiocytic necrotizing lymphadenitis (HNL). Objectives: HNL is mainly diagnosed by pathological findings of open surgical biopsy (OSB) specimens. Recently the appearance of anti-MPO positive histiocytes has been reported as a highly specific pathological diagnosis for HNL. Considering the cosmetic impact and burden on the patients, we performed CNB combined with immunohistochemical study of MPO for the diagnosis of HNL. Few studies have reported the utility of this method in the diagnosis of HNL. Methods: A retrospective study was conducted using clinical data from 20 HNL patients. Results: CNB was performed in 8 patients and OSB in 13 (OSB after CNB in 1). MPO-positive histiocytes were observed in all of the 20 cases. The accuracy of the diagnoses was finally confirmed by the clinical courses in all cases.
    No preview · Article · Dec 2013 · Acta oto-laryngologica
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    ABSTRACT: Conclusion: The characteristic ultrasound appearance of mucosa-associated lymphoid tissue (MALT) lymphoma of the head and neck provides diagnostic information regarding masses or swellings in the head and neck region. Objectives: There are only a few reports about ultrasound features of malignant lymphoma (ML) of the head and neck. We have noticed that the ultrasound appearances of cases with MALT lymphoma resembled each other even when the appearances of other images like computed tomography were absolutely different. The objective of this study was to delineate the reliability of this characteristic ultrasound appearance of MALT lymphoma of the head and neck. Methods: The ultrasound examinations of 30 patients with histopathologically proven primary ML of the head and neck (15 cases of MALT) were reviewed. The ultrasound results of each case were independently compared to the results of the histopathological examination. Results: Two ultrasound patterns were observed for MALT lymphoma. The first was characterized by a marked hypoechoic area with interspersed linear echogenic strands (linear echogenic strands pattern), and the second was characterized by multiple, relatively large, hypoechoic segments (segmental pattern). Histopathologically, these patterns could be explained on the basis of the expansion of lymphoma cells demarcated by narrow or wide fibrous bands.
    No preview · Article · Nov 2013 · Acta oto-laryngologica
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    ABSTRACT: Mantle cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin's lymphoma characterized by chromosomal translocation t(11;14)(q13;q32), positive CD5, and nuclear cyclin D1 overexpression with unfavorable prognosis. We report herein a case of MCL in a 73-year-old male diagnosed with diffuse large B-cell lymphoma (ileal tumor) at another hospital, who subsequently relapsed with CD5-negative MCL. At the 1st relapse, he developed neck lymph node swelling, of which biopsy showed proliferation of atypical large pleomorphic cells with CD5-negativity by both immunohistochemistry and flow cytometry. At the 2nd relapse, he again developed an ileal tumor, of which biopsy showed positivity for CD5, CD20, and cyclin D1. In MCL, CD5-negative expression has sometimes been reported as having pleomorphic and blastoid variants. The present case was also histologically the pleomorphic type, but the CD5 expression changed from negative at the onset and the 1st relapse to positive at the 2nd relapse. This is a rare and interesting case because of the different expression of CD5 at all stage. This phenomenon made the diagnosis of MCL difficult.
    No preview · Article · Oct 2013 · Medical Molecular Morphology

Publication Stats

2k Citations
270.98 Total Impact Points


  • 2008-2015
    • Okayama University
      • Department of Pathology and Oncology
      Okayama, Okayama, Japan
  • 2014
    • Tokyo Medical University
      Edo, Tokyo, Japan
    • Osaka City University
      Ōsaka, Ōsaka, Japan
  • 2012
    • Nagoya University
      • Clinical Laboratory
      Nagoya, Aichi, Japan