Biomedical subjects

Kazuhiko Shimizu

Publications and source records attributed to Kazuhiko Shimizu.

At least 19 recordsLinked to original sources

PubMed2007

Clinical implications of nodal marginal zone B-cell lymphoma among Japanese: study of 65 cases.

To clarify the clinical presentation and outcome of nodal marginal zone B-cell lymphoma (NMZBL), 65 Japanese patients with this disease were studied and compared with the published literature from western countries. The clinical findings of our 65 cases were similar to those of their cases in some aspects: (1) 58% of the patients were > 60 years old (median age, 64 years); (2) there was a slight female predominance; (3) 90% of the patients exhibited asymptomatic lymphadenopathy in the head and neck area; (4) only a minority of patients had B symptoms (6%) and poor performance status (8%); and (5) only 5% of patients were positive for M-protein. However, the 65 patients in this series exhibited relatively longer 5-year overall survival (85%) and failure-free survival (60%) than the NMZBL series published in western literature, suggesting that NMZBL should be classified as indolent lymphoma. Moreover, based on the histological findings, we further classified four histological subtypes as follows: (1) splenic type (n = 7); (2) floral type (n = 9); (3) mucosa-associated lymphoid tissue (MALT) type (n = 29); and (4) diffuse large B-cell lymphoma (DLBCL) + MALT type (n = 20). DLBCL + MALT type exhibited significantly poorer 5-year overall survival than the splenic variant. The recognition of DLBCL + MALT type appears important. No API2-MALT1 fusion transcript was detected in any of the 14 cases examined.

Adult↗

PubMed2006

Immunohistological findings of suppurative granulomas of Yersinia enterocolitica appendicitis: a report of two cases.

We report on the histopathologic and immunohistologic findings of two cases of suppurative granulomatous appendicitis of Yersinia enterocolitica (Y. ent.). Using formalin-fixed, paraffin-embedded materials, polymerase chain reaction revealed Y. ent. in both cases. Histologically, the epithelioid cell granulomas (EPGs) were transmural in both cases. The EPGs were predominantly nonsuppurative, and were surrounded by a lymphoid cuff composed of small lymphocytes. A portion of EPGs contained suppuration of the centers of the granulomas (central microabscesses). The EPGs were composed of numerous histiocytes with or without epithelioid cell features, along with scattered small T-lymphocytes and plasmacytoid monocytes. None of the EPGs contained monocytoid B-cells. Immunohistochemical study demonstrated that EPGs were usually surrounded by surface IgM/D+ small mantle zone lymphocytes. Moreover, CNA.42 immunostaining occasionally demonstrated residual follicular dendritic cells in the center of the EPGs. The overall histomorphologic and immunohistochemical findings demonstrated that the EPGs with Y. ent. are of the B-cell negative hypersensitivity type and occur in reactive germinal centers. In one case, regional lymph nodes contained EPGs showing the same histologic and immunohistologic findings as those of the appendix. The present study indicates that among abscesses forming epithelioid granulomatous lesions, EPGs with Y. ent. were B-cell negative granulomas, and it demonstrates histopathologic and immunohistochemical findings different from those of cat scratch disease and lymphogranuloma venerum, which contain numerous monocytoid B-cells.

Abdominal Abscess↗

PubMed2006

Histological varieties of Epstein-Barr virus-related lymph node lesion resembling autoimmune disease-like clinicopathological findings in middle-aged and elderly patients: a study of six cases.

Six cases were studied to further clarify clinicopathological findings of Epstein-Barr virus (EBV)-related lymph node lesions showing autoimmune disease-like clinicopathological findings (EBVAID) in middle-aged and elderly patients. The patients, four males and two females, ranged in age from 53 to 74 years, with a median age of 62 years. Clinically, they were characterized by systemic lymphadenopathy, "B"symptoms, polyclonal hypergammaglobulinemia, elevated serum lactate dehydrogenase and a transient presence of various autoantibodies, as well as an infrequent presence of atypical lymphocytosis in peripheral blood. Two cases were associated with idiopathic thrombocytopenic purpura. The clinical course was self-limiting. Histologically, three patterns could be delineated: pattern A, follicular hyperplasia with pronounced arborizing vasculature in the expanded paracortex (n=3); pattern B, follicular hyperplasia with pronounced interfollicular B-immunoblastic/plasma cell proliferation (n=2); and pattern C, paracortical hyperplasia containing numerous large transformed lymphocytes (n=1). In situ hybridization demonstrated a varying number of EBV-infected lymphocytes in the germinal center and in the interfollicular area. Polymerase chain reaction analysis demonstrated that neither clonal rearrangement of T-cell receptor gamma-chain nor immunoglobulin heavy-chain rearrangement was detected in the three cases examined. Although EBVAID appears to be rare in middle-aged and older adults, EBVAID exhibits histological variations and should be added to the differential diagnosis of various atypical or malignant lymphoproliferative disorders, in particular autoimmune-disease-associated lymphadenopathy and angioimmunoblastic T-cell lymphoma with a hyperplastic germinal center in middle-aged and elderly patients.

Aged↗

PubMed2006

Production of two novel monoclonal antibodies that distinguish mouse lymphatic and blood vascular endothelial cells.

We produced two novel rat monoclonal antibodies (LA102 and LA5) to identify mouse lymphatic vessels and blood vessels, respectively. We characterized the two antibodies as to the morphological and functional specificities of endothelial cells of both types of vessels. The antibodies were produced by a rapid differential immunization of DA rats with collagenase- and neuraminidase-treated mouse lymphangioma tissues. LA102 specifically reacted with mouse lymphatic vessels except the thoracic duct and the marginal sinus of lymph nodes, but not with any blood vessels. In contrast, LA5 reacted with most mouse blood vessels with a few exceptions, but not with lymphatics. LA102 recognized a protein of 25-27 kDa, whereas LA5 recognized a molecule of 12-13 kDa. Neither antibody recognized any currently identified lymphatic or vascular endothelial cell antigens. Immunoelectron microscopy revealed that the antigens recognized by LA102 and LA5 were localized on both luminal and abluminal endothelial cell membranes of each vessel type. Interestingly, LA102 immunoreactivity was strongly expressed on pinocytic or transport vesicle membrane in the cytoplasm of lymphatic endothelium. Besides endothelial cells, both antibodies also recognized some types of lymphoid cells. Since, the LA102 antigen molecule is expressed on some lymphoid cells, it may play important roles in the migration of lymphoid cells and in some transport mechanisms through lymphatic endothelial cells.

Animals↗

PubMed2006

Apoptosis related to steroid sulfatase at the cone-shaped projection in nephron morphogenesis.

Steroid sulfatase (STS) is a microsomal enzyme catalysing the hydrolysis of steroid 3beta-sulfates, including estrogen sulfate, at organ target sites. Steroid sulfatase activity, as well as the activity of various estrogens, has been reported to influence the development of organs. In the kidney, progenitor cells of nephrons develop from mesenchymal cells and finally attach to the ureteric duct at the region termed the cone-shaped projection. However, the mechanisms of this process have not been fully investigated. In the present study, STS-related apoptosis occurring between the renal vesicle and ureteric duct was examined using immunohistochemical techniques. Immunoreactivity to STS was demonstrated at the cortical metanephric mesenchyme surrounding new vessels and was pronounced at the junction between the renal vesicle and ureteric duct (cone-shaped junction). Steroid sulfatase-transfected LLC-RK1 cells (rat proximal cell line) were also examined in vitro. Apoptosis occurred when an estrogen precursor (ELS) was added at concentrations between 10(-4) and 10(-2) mol/L. These results indicate that STS is synthesized in the progenitor cells of proximal tubules. Moreover, STS may be related to apoptosis occurring at the junction between the renal vesicle and ureteric duct in a manner proportional to the availability of STS precursors.

Animals↗

PubMed2006

Incidental Langerhans cell histiocytosis of the parotid gland resembling marginal zone B-cell lymphoma: a case report.

Langerhans cell histiocytosis (LCH) manifesting as a parotid gland mass is an extremely rare clinical presentation. We report a case of LCH involving the bilateral parotid glands in an 81-year-old Japanese female. Pathologically, the lesion was characterized by numerous lymphoid follicles, dense lymphoplasmacytoid infiltrate and cystic dilatation of the parotid gland duct in addition to nodular and diffuse proliferation of LCs. Moreover, both LCs and small T-lymphocytes invaded the ductal epithelium forming a lymphoepithelial lesion-like morphology. The present case indicates that LCHs should be added to the different diagnosis for marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type involving the salivary glands.

Aged, 80 and over↗

PubMed2006

Malignant lymphoma in patients with systemic rheumatic disease (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and dermatomyositis): a clinicopathologic study of 24 Japanese cases.

We conducted clinicopathologic and immunohistochemical analyses of the prevalence of Epstein-Barr virus (EBV) among 24 patients with malignant lymphoma complicating systemic rheumatic diseases. (SRD) These 24 patients included 17 with rheumatoid arthritis (RA), 3 with systemic lupus erythematosus (SLE), 2 with systemic sclerosis (SS), and 2 with dermatomyositis (DM). There were 2 men and 22 women ranging in age from 30 to 86 years (mean: 64 years). The interval between the onset of rheumatic disease and that of malignant lymphomas ranged from 3 months to 35 years (mean: 142 months). The use of immunosuppressive drugs before the onset of malignant lymphoma was recorded in 15 patients. Among them, 5 patients received methotrexate (MTX) therapy. Malignant lymphomas were found at extranodal sites in 9 patients, and the disease was in the advanced stage in 17 patients. Histologic and immunohistochemical studies demonstrated that 18 cases (75%) were B-cell lymphoma (RA=12, SLE=2, SS=2, DM=2), 3 (12.5%) were peripheral T-cell lymphoma (RA=3), and 3 (12.5%) were classical Hodgkin lymphoma (RA=2, SLE=1). As in previous reports, there was an increased frequency of diffuse large B-cell lymphoma (50%) in the present series. Moreover, a majority of the diffuse large B-cell lymphomas exhibited activated B-cell phenotype. EBV-encoded small RNAs (Epstein-Barr early region [EBER]-) and/or LMP-1+tumor cells were identified in only 3 cases of classical Hodgkin lymphomas. Our findings suggested EBV-associated lymphoma comprised only a small fraction of all non-Hodgkin's lymphomas in the general SRD patient population.

Adult↗

PubMed2005

Plasmacytoid monocytes in cat scratch disease with special reference to the histological diversity of suppurative lesions.

It has been suggested that plasmacytoid monocytes (PMOs) play an essential role in T-cell-dependent immune response. Indeed, numerous PMOs are found in close topographical association with epithelioid cell granulomas in hypersensitivity-type granulomas, such as tuberculosis and sarcoidosis. The key pathologic process in cat scratch disease (CSD) usually involves a B-cell-associated granulomatous reaction. Histologically, CSD appears to exhibit a histopathologic diversity, including suppurative lesions without epithelioid cell granulomas (early lesion), in which the microabscesses were surrounded by monocytoid B-cells (MBCs), suppurative granulomas containing MBCs (intermediate lesion), and suppurative granulomas without MBCs (late lesion). However, the presence or absence of PMO in CSD has not been studied previously. We examined 14 cases of CSD. In early lesions, numerous clusters of PMO were detected in the MBCs. In intermediate lesions, both MBCs and PMOs were found to be decreased in number, while late lesions contained no or only a few MBCs and PMOs. Overall, these findings suggest that PMOs may play a role in MBC-associated granulomatous response and in hypersensitivity granulomatous response. Moreover, the association with MBCs and PMOs indicates a functional relationship of MBCs with PMOs in the formation of suppurative lesions in CSD.

Abscess↗

PubMed2005

Usefulness of immunohistochemistry for recognizing metastatic colorectal adenocarcinoma in infarcted lymph nodes.

Lymph node infarction is a spontaneous coagulative necrosis of the affected lymph node and is frequently associated with concurrent and subsequent malignant lymphoma. However, this phenomenon appears to be rarely associated with metastatic carcinomas. Here, we report on the histopathologic and immunohistologic findings of three cases showing lymph node infarction in the regional lymph node associated with metastatic colorectal adenocarcinoma. Histologically, coagulative necrosis of metastatic carcinoma was surrounded by a thick rim of granuloma consisting of histiocytes with or without epithelioid features, foamy cells, and a small number of lymphocytes. The immunohistochemical study of the coagulative necrosis demonstrated that cytokeratins (AEI/AE3 and CAM5.2) and carcinoembryonic antigen (CEA) were well preserved in all three cases. However, compared with viable tumor tissues, only a few tumor cells were positive for epithelial membrane antigen. Using formalin-fixed and paraffin-embedded tissues, immunostaining for cytokeratins and CEA of the lymph node containing necrotic carcinoma may provide clinically valuable information.

Adenocarcinoma↗

PubMed2005

Clinical implication of florid reactive follicular hyperplasia in Japanese patients 60 years or older: a study of 46 cases.

Florid reactive follicular hyperplasia (FRFH) of the enlarged lymph node in middle-aged or elderly patients requiring biopsy is a relatively uncommon phenomenon as compared with that in younger age groups. Between 1984 and January 2004, we encountered 46 patients, aged 60 years or older, in whom histology of biopsied lymph node specimens showed inappropriate FRFH for the patient's age. An apparent cause of lymphadenopathy was initially identified in 17 cases (37%): 11 with autoimmune disease and related disorders, 3 with cancer-reactive lymphadenopathy, 2 with Epstein-Barr virus-associated lymph node lesion exhibiting transient autoimmune-disease-like clinical findings, and 1 with atypical mycobacterial infection. Among 29 patients without specific etiology, 16 patients (55%) exhibited histologic findings of progressive transformed germinal center (PTGC). Only 1 of our patients developed malignant lymphoma during the follow-up period. The present study indicates that PTGC is included in the etiology of FRFH in elderly Japanese patients as well as imbalance of the immune system such as autoimmune-disease-associated lymphadenopathy and idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia. By in situ hybridization, Epstein-Barr virus genomes were demonstrated in only 6 (15%) of 39 cases examined.

Aged↗

PubMed2005

Reactive lymphoid hyperplasia of the lymph nodes with giant follicles: a clinicopathologic study of 14 Japanese cases, with special reference to Epstein-Barr virus infection.

To clarify the clinicopathologic and immunohistochemical features of reactive lymphoid hyperplasia with giant follicles (RHGF) among Japanese, 14 patients were studied. The subjects consisted of 9 males and 5 females, ranging in age from 9 to 61 years, with a mean age of 30 years and a median age of 24 years. None of the patients exhibited systemic symptoms. The affected lymph nodes were located in the head and neck area except in 1 case. At the time of lymph node biopsy, 1 patient was diagnosed as having acute infectious mononucleosis (IM) and 2 patients had a recent history of acute IM. One each with myelogenous leukemia or diffuse large B-cell lymphoma had a history of peripheral blood stem cell transplantation. There were no recurrences during follow-up periods ranging from 3 to 50 months. Histologically, 14 lesions were characterized by numerous enlarged, coalescing lymphoid follicles with distortion rather than effacement of the lymph node architecture. By in situ hybridization, Epstein-Barr virus (EBV) genomes were demonstrated in 5 (36%) of 14 cases. The present study indicates that a portion of RHGF appears to represent a histologic finding of acute IM. Moreover, as previously stated, RHGF should be differentiated from follicular lymphoma, particularly the floral variant.

Adolescent↗

PubMed2005

Distribution of Epstein-Barr virus in systemic rheumatic disease (rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis) with associated lymphadenopathy: a study of 49 cases.

Among systemic rheumatic diseases (SRDs), lymphadenopathy is frequently found in patients with rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs) may occur in patients following methotrexate therapy for RA and dermatomyositis (DM). However, little is known about the distribution of EBV in reactive LPDs in patients with SRDs who had no history of methotrexate therapy. We analyzed 49 such patients (SLE=25, RA=23, DM=1) for the presence and distribution of EBV+ cells using Epstein-Barr virus (EBV)-encoded small RNA (EBER) specific in situ hybridization. A positive signal for EBERs was identified in 9 (SLE=5, RA=4) (18%) of 49 cases, and 3 main distribution patterns of EBER+cells could be delineated: pattern A, more than 500 EBER-positive cells were located in the germinal centers as well as interfollicular area (SLE=2); pattern B, EBER + cells were located in a few germinal centers (RA=2); and pattern C, up to 100 EBER+ cells were located in the interfollicular area (SLE=3, RA=2). Recent EBV infection may be a cause of lymph node lesion in only 2 cases of patients with pattern A. However, the pathognomonic significance of pattern B and pattern C EBER + cell distribution patterns still remains unclear. Our study indicates that the underlying immune deficits of patients with SRDs may also play an important role in the development of EBV-associated LPDs in SRDs, as previously suggested by several authors.

Adult↗

PubMed2005

[A case of prostate cancer diagnosed pathologically by bone metastatic site biopsy].

A 61-year-old man consulted our hospital complaining of high prostate specific antigen (PSA) value and difficulty to urinate. Prostate biopsy had been performed at another hospital, but did not reveal cancer. PSA was 18.5 ng/ml. Transrectal ultrasound-guided prostate biopsy was performed, but cancer was not detected. Later, PSA rose rapidly, and findings suggesting bone metastasis at right pubic bone and left sacro-ilial joint were found on computed tomography (CT), bone scintigraphy and magnetic resonance imaging (MRI). A repeat prostate biopsy was performed, but cancer was not detected from the prostate. On right pubic bone biopsy, poorly to moderately differentiated adenocarcinoma was detected. PSA immunohistochemical staining was positive, and the diagnosis was bone metastasis from prostate cancer. After endocrine therapy was started, PSA declined and bone metastasis disappeared on bone scintigraphy.

Adenocarcinoma↗

PubMed2005

[Prognostic factors for PSA relapse of prostate cancer after endocrine therapy].

PURPOSE: Advanced prostate cancer responds well to endocrine therapy initially, but soon becomes refractory and has a poor prognosis. We analyzed the prognostic factors of prostate cancer responding well initially to endocrine therapy with lowering of serum prostate specific antigen (PSA) level but later showing PSA relapse. MATERIALS AND METHODS: In prostate cancer patients newly diagnosed from January 1992 to December 2004 at our institution, there were 93 patients in that the PSA level of 10 ng/ml or more before therapy initially dropped below 10 ng/ml by endocrine therapy, but showed PSA relapse thereafter. We investigated the relationship between clinical stage, pathological differentiation, initial PSA, duration between initiation of therapy and PSA nadir, the value of PSA nadir, duration between initiation of therapy and PSA relapse, PSA doubling time (PSA-DT) at relapse, PSA response three months after initiation of second line therapy and prognosis after PSA relapse. RESULTS: In Kaplan-Meier method, between all or some categories investigated showed significant difference in prognosis after PSA relapse. In multivariate analysis, the factors that significantly affected prognosis after PSA relapse were clinical stage, pathological differentiation, PSA nadir value, duration between initiation of therapy and PSA relapse and PSA response three months after initiation of second line therapy. CONCLUSION: We investigated the prognostic factors refractory to endocrine therapy. These results are useful in planning the therapy, and in explaining the status or future prospective of the disease to patients and families.

Aged↗

PubMed2005

[Prognostic factors of superficial bladder cancer recurring after initial transurethral resection].

About 70% of bladder cancers are superficial at the initial state. If diagnosed at an early stage, the tumor may be resected completely and easily. However, recurrence is seen in many cases. Prognostic factors of recurrence were investigated in 55 cases of bladder cancer newly diagnosed (excluding carcinoma in situ) between 1995 and 2003, and in which complete resection by transurethral resection (TUR) was possible at first recurrence after initial TUR. One- and three-year postoperative non-recurrence rates were 51.9% and 36.3%, respectively. None of the factors studied, i.e., stage, grade, tumor multiplicity (at initial and at first recurrence), change of stage and grade at first recurrence compared with that of initial TUR, duration to recurrence and adjuvant therapy after TUR, were found to influence the prognosis after recurrence. Similar results were obtained for third TUR. Recurred pTa, grade 1 or solitary cancer at initial or at recurrence had the same prognosis as pT1, grade 2-3 or multiple cancers, and careful follow-up is needed.

Adult↗

PubMed2004

Low-grade central osteosarcoma of the rib.

We report a case of low-grade central osteosarcoma of the rib, mimicking fibrous dysplasia protuberans or parosteal osteosarcoma. A 13-year-old boy presented with a densely ossified exophytic tumor in the left sixth rib. The surgically resected rib revealed an ossified tumor that had developed within bone and had formed an exophytic mass. Microscopic examination revealed parosteal osteosarcoma-like low-grade central osteosarcoma. Low-grade central osteosarcomas rarely affect the rib, and exophytic tumor formation is also rare. This tumor required differentiation from fibrous dysplasia protuberans and parosteal osteosarcoma because of its clinical presentation.

Adolescent↗

PubMed2004

Clinical implication of idiopathic plasmacytic lymphadenopathy with polyclonal hypergammaglobulinemia: a report of 16 cases.

Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia is considered identical to multicentric Castleman's disease (MCD) reported in western countries. Clinically, both IPL and MCD are characterized by multicentric lymphadenopathy, prominent polyclonal hypergammaglobulinemia, elevated erythrocyte sedimentation rate, elevated serum interleukin-6 concentration, bone marrow plasmacytosis, and various abnormal laboratory data such as anemia and positive autoantibodies. However, IPL has a significantly better 5-year survival rate than that of MCD. Moreover, none of the present 16 cases developed Kaposi's sarcoma or B-cell lymphoma. Histologically, the interfollicular area contains a sheet of polytypic mature plasma cells in both IPL and MCD. In MCD, the majority of lymphoid follicles had hyaline-vascular germinal centers. However, lymphoid follicles of IPL usually exhibit a hyperplastic germinal center. Immunostaining also demonstrated a normal/reactive follicular dendritic cell network pattern in the germinal center of IPL. Moreover, there were no human herpes virus-8-positive cells detected by immunohistochemistry. The overall clinicopathologic and immunohistochemical findings of our 16 cases suggest that IPL is distinct from MCD reported in Western countries.

Adult↗

PubMed2004

Clinical implication of dermatopathic lymphadenopathy among Japanese: a report of 19 cases.

To clarify the clinicopathologic and immunohistochemical features of dermatopathic lymphadenopathy not associated with mycosis fungoides among Japanese, 19 patients were studied. Seventy-four percent of the patients were more than 50 years old (median; 63 years, mean 61 years). Systemic symptoms such as fever were recorded in 68% and multicentric lymphadenopathy was noted in 83% of patients. An association of autoimmune disease or positivity of autoantibodies was recorded in 6 patients. Five patients showed cutaneous hypersensitivity reactions to a drug. Histologically, in addition to the dermatopathic lymphadenopathy, numerous immunoblasts were observed in 2 cases and sheet-like proliferation of mature plasma cells in 3 cases. Various atypical or malignant lymphoproliferative disorders exhibiting immunologic abnormalities such as angioimmunoblastic T-cell lymphoma or autoimmune disease-associated lymphadenopathy frequently occur in middle-aged and elderly patients. At least some of the patients with dermatopathic lymphadenopathy should be clinicopathologically differentiated from these lymphoproliferative disorders.

Adult↗