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Shigeo Nakamura

Publications and source records attributed to Shigeo Nakamura.

At least 73 records · Page 4Linked to original sources

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↗

Idiopathic multicentric Castleman's disease. A clinicopathologic and immunohistochemical study of five cases.

Several lymphoproliferative disorders may be interpreted as multicentric Castleman's disease (MCD) clinicopathologically. These include HIV infection, autoimmune-disease-associated lymphadenopathy, idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia, "idiopathic MCD", POEMS syndrome (polyneuropathy, anasarca, organomegaly, endocrinopathy, M-proteins, and skin lesions), and non-Hodgkin's lymphomas. Among these, idiopathic MCD appears to be relatively rare. We report on the clinicopathologic and immunohistologic findings of five cases of idiopathic MCD and discuss the problems regarding their differential diagnosis. Some of the characteristic clinical findings of POEMS syndrome, including hepatosplenomegaly, skin change, endocrine abnormalities and anasarca, were present in all five cases. However, during the course of disease, minimal diagnostic criteria for POEMS syndrome, i.e., monoclonal plasma cell proliferation and sensory motor neuropathys, were absent in all five cases. The serum interleukin-6 level and the vascular endothelial growth factor level were found to be elevated in two of the cases examined. Various autoantibodies were detected in three cases. However, none of them fulfilled the diagnostic criteria for any of the definite autoimmune-disease. Histologically, three lesions exhibited a mixed type of Castleman's disease, and two exhibited the hyaline-vascular type. The majority of the germinal centers were of the hyaline-vascular or epithelioid germinal type, with a few hyperplastic germinal centers. The interfollicular area was characterized by prominent vascularity. Moderate to large sheets of plasma cells were observed in three mixed type cases. The polytypic nature of B-lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. Immunohistochemical study demonstrated that the majority of germinal centers exhibited a tight/concentric pattern of FDC network. Few CD57-positive T-cells were observed in the hyaline-vascular and epithelioid follicles. The lack of CD57-positive T-cells appears to be related to the formation of abnormal germinal centers in the MCD.

Aged↗

Atypical lymphoplasmacytic and immunoblastic proliferation from systemic lupus erythematosus. A case report.

A case of atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) in the lymph nodes associated with well-documented systemic lupus erythematosus (SLE) is presented. A 30-year-old Japanese female with an 18-year history of SLE presented with right neck lymphadenopathy of 3 months duration. A biopsy specimen showed a diffuse effaced lymph node architecture without follicles and minimal sinuses. At high power field, a polymorphous population of small- to medium-sized lymphocytes, plasma cells, plasmacytoid cells, as well as large, basophilic transformed lymphocytes and immunoblasts diffusely infiltrated the paracortical area. Interestingly, the immunohistochemical study demonstrated large, irregularly shaped accumulations of follicular dendritic cells (FDCs) surrounding the small vessels, which is an immunohistochemical finding characteristic of angioimmunoblastic T-cell lymphoma (AILT). However, the present lesion showed the following differences to AILT: (a) absence of CD3+, CD4+ and CD10+ clear cells, which are tumor cells of AILT; (b) absence of pronounced arborizing vascular proliferation; (c) on molecular analysis, the present case demonstrated a polyclonal pattern converse to the monoclonal T-cell receptor gamma chain gene rearrangement in most AILTs (d) absence of EBV infected lymphoid cells, which are frequently detected AILT. As previously suggested, the present case indicates that a clinical correlation as well as immunohistologic and genotypic studies may be necessary to discriminate between ALPIBPs and AILT.

Adult↗

p16/INK4a gene methylation is a frequent finding in pulmonary MALT lymphomas at diagnosis.

p16/INK4a gene alterations have been associated with tumor progression in lymphoid malignancies. However, their significance in mucosa-associated lymphoid tissue (MALT) lymphoma is unclear. We investigated p16 gene methylation and mutation in a large series of untreated cases of pulmonary MALT lymphoma and diffuse large B-cell lymphoma (DLBL), and correlated p16 gene alterations with a MALT lymphoma-specific API2-MALT1 fusion and the clinicopathologic features of MALT lymphoma. The API2-MALT1 fusion was detected by multiplex reverse transcription polymerase chain reaction in 25/60 (42%) cases of MALT lymphoma, but none of 11 DLBLs. Methylation-sensitive single-strand conformation analysis showed that p16 gene methylation was frequently detected in 36/60 (60%) cases of MALT lymphoma. The gene was similarly methylated in DLBL cases (6/11, 55%). A p16 gene mutation was found in one (p16 gene-methylation) of 44 MALT lymphomas and in none of six diffuse large B-cell lymphomas. Statistical analysis showed that the p16 gene methylation status did not correlate with API2-MALT1 fusion or any of the clinicopathologic factors including serum LDH, clinical stage, and increased large cells. These findings suggest that p16 methylation is not associated with tumor progression, but may be an early event in MALT lymphomagenesis that might be maintained through the progression of the tumor.

Adult↗

Sulpiride in combination with fluvoxamine increases in vivo dopamine release selectively in rat prefrontal cortex.

Coadministration of atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs) enhances the release of monoamines such as dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in the prefrontal cortex. To clarify the role of DA-D2/3 receptors in the combination effect, we examined the effects of coadministration of the selective DA-D2/3 antagonist sulpiride and the SSRI fluvoxamine on amine neurotransmitter release in rat prefrontal cortex. Sulpiride (10 mg/kg, i.p.) and fluvoxamine (10 mg/kg, i.p.) alone did not affect extracellular DA levels, while their coadministration caused a significant increase in DA levels. Sulpiride alone did not affect extracellular levels of 5-HT and NE in the prefrontal cortex, while fluvoxamine alone caused a marked increase in 5-HT levels and a slight increase in NE levels. Sulpiride did not affect the fluvoxamine-induced increases in extracellular levels of 5-HT and NE. The DA-D2/3 antagonist haloperidol (0.1 mg/kg) in combination with fluvoxamine also caused a selective increase in extracellular DA levels in the cortex. Coadministration of sulpiride and fluvoxamine did not affect extracellular DA levels in the striatum. Combination of systemic sulpiride and local fluvoxamine did not increase the DA levels, but that of systemic fluvoxamine with local sulpiride increased. The combination effect in increasing prefrontal DA levels was antagonized systemically, but not locally, by the 5-HT1A antagonist WAY100635 at a low dose. These findings suggest that the combination of prefrontal DA-D2/3 receptor blockade and 5-HT1A receptor activation in regions other than the cortex plays an important role in sulpiride and fluvoxamine-induced increase in prefrontal DA release.

Animals↗

NK-cell neoplasms in Japan.

Neoplasms putatively originating from precursor and mature natural killer (NK) cells are rare, and their clinical features are unclear. A nationwide survey was performed in Japan to clarify the clinical features of these neoplasms diagnosed between 1994 and 1998, and data for 237 patients who met the criteria for putative NK cell-lineage neoplasms were analyzed. Among them, 11 had myeloid/NK-cell precursor acute leukemia, 15 blastic NK-cell lymphoma, 21 precursor NK-cell acute lymphoblastic leukemia, 22 aggressive NK-cell leukemia/lymphoma, 149 nasal-type NK-cell lymphoma (123 nasal and 26 extranasal) and 19 chronic NK lymphocytosis. The median overall survival time of patients with aggressive NK-cell leukemia/lymphoma was 2 months, which for chronic NK lymphocytosis was more than 8 years, and that for the other types of NK-cell neoplasms was between 6 and 22 months. Nasal NK-cell lymphoma and extranasal NK-cell lymphoma share the same histology. The age of affliction was the same, but the sex was different with males predominantly having nasal NK-cell lymphoma and females extranasal NK-cell lymphoma. Patients with extranasal NK-cell lymphoma had the tendency to exhibit a more advanced state of disease, with significantly higher International Prognostic Index and LDH levels, and significantly lower hemoglobin and platelet levels. The overall survival, however, did not differ significantly. Precursor NK-cell acute lymphoblastic leukemia and blastic NK-cell lymphoma were arbitrarily defined by the presence or absence of 30% or more of blastic cells in the bone marrow or peripheral blood, but there were no significant differences for affected age, gender, involved sites or prognosis. Aggressive NK-cell leukemia/lymphoma and extranasal NK-cell lymphoma were arbitrarily defined by the presence or absence of 30% or more of large granular lymphocytes in the bone marrow or peripheral blood and it is possible that aggressive NK-cell leukemia/lymphoma is a leukemic phase of extranasal NK-cell lymphoma. The incidence of skin involvement, however, was significantly higher for extranasal NK-cell lymphoma, suggesting that the two diseases are different. In nasal NK-cell lymphoma, Epstein-Barr virus in tumor cells was detected in all patients tested, suggesting its causative role.

Disease-Free Survival↗

Clinicopathologic and prognostic significance of cytotoxic molecule expression in nodal peripheral T-cell lymphoma, unspecified.

Cytotoxic molecules (CMs) are apoptosis-inducing molecules that are present in azurophilic cytoplasmic granules of T lymphocytes. Expression of TIA-1 and granzyme B was examined for 100 cases of nodal peripheral T-cell lymphoma, unspecified (PTCL-U) to assess clinicopathologic significance of CM. Forty-one were positive for at least one CM. Patients with CM-positive PTCL-U showed younger onset (median, 55 years vs. 64 years, P = 0.01) and less male predominance (male:female ratio, 21:20 vs. 44:15, P = 0.02). CM-positive PTCL-U was significantly associated with several clinical factors to indicate poor prognosis, in comparison with CM-negative PTCL-U, such as poorer performance status (P = 0.006), more frequent B-symptoms (68% vs. 35%, P = 0.002), higher serum lactate dehydrogenase levels (P = 0.003), and more frequent extranodal involvement, particularly bone marrow involvement (33% vs. 9%, P = 0.004). Epstein-Barr virus was mostly found in CM-positive PTCL-U (51% vs. 2%, P < 0.0001). The CM-positive group showed higher distribution of the International Prognostic Index (P = 0.009) and the Prognostic Index for T-cell lymphoma (P = 0.004) scores than CM-negative group. Complete remission rate was 30% for the former but 63% for the latter. Overall survival of CM-positive PTCL-U was significantly lower than that of CM-negative patients (P = 0.004). Multivariate analyses confirmed that CM expression is a significant prognostic factor, independent from other clinical factors or prognostic index scores. These findings suggest that nodal CM-positive PTCL-U show distinct clinicopathologic characteristics among the current category of PTCL-U.

Adolescent↗

Characteristics of the promoters derived from the single-stranded DNA components of Milk vetch dwarf virus in transgenic tobacco.

Predicted promoter regions of Milk vetch dwarf virus (MDV) components (C1-C11) were isolated and fused with a beta-glucuronidase (GUS) reporter gene and the characteristics of the promoters were examined. In transgenic tobacco calli, promoters of MDV C4 (encoding a cell-cycle link protein), C5 and C7 (both encoding unknown proteins), C6 (encoding a nuclear-shuttle protein) and C8 (encoding a movement protein) generated a stronger level of GUS expression than the Cauliflower mosaic virus 35S RNA promoter (P35S). In leaves of transgenic tobacco plants, the promoters of C5 and C8 conferred a level of GUS activity comparable to that of P35S. Histochemical GUS analysis showed that the promoters of C4-C9, the latter encoding a capsid protein, were active in phloem and meristematic tissue. The promoter of C8 was also active in mesophyll and cortex cell types. A low level of activity was found for the promoters of C11, which encodes a master replication-initiator protein (Rep), and C1, C2, C3 and C10, which encode additional Reps, in both transgenic tobacco calli and plants.

Capsid Proteins↗

Japanese multicenter phase II study of CHOP followed by radiotherapy in stage I-II, diffuse large B-cell lymphoma of the stomach.

CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) followed by radiotherapy is regarded as standard care for localized aggressive lymphoma; however, prospective confirmation of its applicability to localized primary gastric lymphoma is inadequate, and most patients in Japan have been initially treated with gastrectomy. We conducted a multicenter phase II study to evaluate the feasibility and efficacy of the non-surgical treatment. Eligibility criteria required primary gastric diffuse large B-cell lymphoma, stage I-II(1), age 20-75, performance status 0-1 and adequate organ function. Treatment consisted of three cycles of CHOP followed by radiotherapy 40.5 Gy. Fifty-five patients were enrolled between December 1999 and February 2003, and 52 eligible patients were analyzed. Patient characteristics were as follows: median age, 61 years; 28 men, 24 women; 36 with stage I, 16 with stage II(1); 47 with a low International Prognostic Index (IPI) and five with a low-intermediate IPI. All but one patient completed planned treatment. No serious complications including massive hemorrhage or perforation were observed. A complete response was achieved in 48 of the 52 patients (92%, 95% confidence interval: 82-98%) and progressive disease in three. Two patients underwent salvage gastrectomy due to disease persistence or recurrence. With a median follow-up period of 28 months, 2-year progression-free and overall survivals were 88 and 94%, respectively. CHOP followed by radiotherapy is safe and highly effective in localized gastric diffuse large B-cell lymphoma. This organ-preserving treatment should be considered as a very reasonable therapeutic option.

Administration, Oral↗

CD109 expression in squamous cell carcinoma of the uterine cervix.

CD109 is a cell surface protein, a member of the alpha(2) macroglobulin/C3,C4,C5 family of thioester-containing proteins. The authors have recently reported that high expression of the CD109 gene was detected in approximately half of the examined lung and esophageal squamous cell carcinomas as well as in the testis, and that CD109 has the characteristics of a cancer-testis antigen. In the present study CD109 expression in cervical squamous cell carcinoma was compared with that in endometrial adenocarcinoma by reverse transcription polymerase chain reaction (RT-PCR). The result demonstrated that CD109 expression is significantly higher in cervical squamous cell carcinomas than in endometrial adenocarcinomas and normal cervix and endometrium. In contrast, when expression of RET finger protein (RFP) and bromodomain testis-specific (BRDT) genes, which are also known to be highly expressed in the testis, was examined, no significant difference in their expression levels was observed between squamous cell carcinomas and adenocarcinomas. These findings suggest that CD109 may become a molecular target for the development of new therapeutics for squamous cell carcinoma of various tissue origins.

Adenocarcinoma↗

Lymphoid variant of hyaline vascular Castleman's disease containing numerous mantle zone lymphocytes with clear cytoplasm.

We report two unusual cases of hyaline vascular type Castleman's disease showing a pale clear cuff of mantle zone lymphocytes presenting a marginal zone distribution pattern. These cells had medium-sized round or slightly indented nuclei and a moderate amount of clear cytoplasm. The histopathologic findings in our cases were similar to those of nodal marginal zone B-cell lymphoma. However, immunohistochemistry demonstrated that both the mantle zone lymphocytes and the pale cuff of the lymphoid cells were CD20+, CD79a+, sIgM+, sIgD+, CD5-, CD10-, CD43-, CD45RO-, Bcl-2+, Bcl-6- and cyclin D1-. The polytypic nature of these cells was demonstrated by immunohistochemistry and polymerase chain reaction. Reactive lymph node lesions only rarely show mantle cell hyperplasia with clear cytoplasm. This unusual mantle cell hyperplasia with clear cytoplasm associated with a hyaline vascular type of Castleman's disease should be differentiated from nodal marginal zone B-cell lymphoma, mantle cell lymphoma and follicular lymphoma. To avoid overdiagnosis and overtreatment, it is suggested that immunophenotypic and genotypic studies might be required, and furthermore careful attention should be paid to the morphologic examination.

Adult↗

Follicular lymphoid hyperplasia of the oral cavity representing progressive transformation of germinal center.

Follicular lymphoid hyperplasia (FLH) of the oral cavity is a rare and poorly understood lymphoproliferative disorder. We present a case of FLH of the oral cavity presenting with progressive transformation of germinal center (PTGC). The patient was a 49-year-old Japanese woman presenting with a hard mass in the right cheek. The resected specimen contained numerous lymphoid follicles with active germinal centers and a portion of the lymphoid follicles exhibited PTGC. The PTGCs contained a few large lymphoid cells resembling lymphocytic and histiocytic Reed-Sternberg cells of nodular lymphocyte-predominant Hodgkin lymphoma. The PTGC was surrounded by groups of epithelioid cells. In situ hybridization studies demonstrated strong expression of Epstein-Barr virus (EBV)-encoded small RNA in scattered large lymphoid cells in the PTGC. Although the etiology of FLH of the oral cavity remains unclear, the present case suggests that a subset of FLH of the oral cavity appears to be an EBV-associated lymphoproliferative disorder.

Cell Proliferation↗

Progressive transformation of germinal center presenting with histological features of hyaline-vascular type of Castleman's disease.

We report three cases showing progressive transformation of the germinal center (PTGC) with histological features reminiscent of the hyaline-vascular (HV) variant of Castleman's disease (CD). Each case contained a few small HV germinal centers as well as PTGC and hyperplastic germinal centers with or without follicular lysis. Moreover, some of the PTGC were penetrated by hyalinized small vessels. Our three cases also showed some of the characteristic histological findings of HV type of CD: (i) reactive lymphoid follicles with small hyaline-vascular germinal centers surrounded by small lymphocytes in a concentrated fashion; (ii) a few small foci of plasmacytoid monocytes; (iii) perivascular fibrosis; (iv) interfollicular vascularity; (v) tight/concentric pattern of the follicular dendritic cell network; and (vi) absence of CD57+ T-cells in the HV follicles. The PTGC with coexistent HV type of CD may represent a certain form of reactive follicular hyperplasia. The possibility of PTGC should be considered and excluded before diagnosing CD.

Adult↗

Angioimmunoblastic T cell lymphoma with an unusual proliferation of Epstein-Barr virus-associated large B cells arising in a patient with progressive systemic sclerosis.

We report an unusual case of angioimmunoblastic T cell lymphoma arising in the setting of 5 years of immunosuppressive treatment for progressive systemic sclerosis. The lymph node lesion was accompanied by large blastic B cells with an association of Epstein-Barr virus. Southern blot study demonstrated the clonal rearrangement of T cell receptor beta-chain gene, but not of immunoglobulin heavy chain gene. Phenotypical examination of the lymph node also revealed the predominance of CD4+ T cells in addition to the proliferation of follicular dendritic cells, but no light chain restriction in large B cell components. In the clinical and laboratory aspects, neutrophilia (15.8 x 10(9)/l) and plasmacytosis (40%) in bone marrow were noted, which were considered to be closely related to elevated serum granulocyte colony-stimulating factor, interleukin (IL)-4 and IL-6. Based on the combined data described here, our preferred diagnosis was angioimmunoblastic T cell lymphoma with Epstein-Barr virus-associated B cell lymphoproliferative disorder, the pathogenesis of which was suggested to be closely associated with immunosuppressive treatment for progressive systemic sclerosis.

Aged↗

CD56-positive acute lymphoblastic leukemia.

We report a patient with lung cancer who developed CD56-positive acute lymphoblastic leukemia. He was referred to our hospital for thrombocytopenia. Atypical cells were found in the blood and the bone marrow. These cells were immunophenotypically positive for CD3epsilon, CD56, and terminal deoxynucleotidyl transferase, and negative for surface CD3, CD4, CD19, CD33, and myeloperoxidase. A small proportion of leukemic cells express CD13. There were no rearrangements of T-cell receptor (TCR)-beta, TCR-gamma, or immunoglobulin heavy chain. No Epstein-Barr virus was detected. Systemic examination did not detect any tumors other than pulmonary adenocarcinoma, and the patient was diagnosed as having acute natural killer (NK) cell leukemia. Chemotherapy was effective, and he achieved complete remission. The course of the disease was complicated by a lung abscess, and the patient died 3 months after the diagnosis. We considered that the diagnosis was blastic NK cell lymphoma/leukemia subtype. However, it actually was myeloid/NK cell precursor leukemia subtype that weakly expressed CD13.

Aged↗

Follicular colonization of nodal marginal-zone B-cell lymphoma resembling follicular lymphoma: report of 6 cases.

The formation of neoplastic B-cell follicles is accepted as a diagnostic criterion of follicular lymphoma. However, extranodal marginal-zone B-cell lymphomas (MZBLs) of mucosa-associated lymphoid tissue (MALT) type also sometimes contain numerous lymphoid follicles and may even have a predominantly follicular growth pattern. However, morphologic, immunohistochemical, and genotypic findings suggest that lymphoid follicles in extranodal MZBLs are neoplastic follicles formed as the result of colonization of previously reactive follicles by tumor cells (centrocyte-like cells). We present here 6 cases of nodal MZBL demonstrating a follicular growth pattern. Immunohistochemical study demonstrated that the tumor cells were CD10-, CD20+, CD79a+,CD138-, Bcl-2+, Bcl-6- and IRF4+. Residual nonneoplastic follicular center cells were CD10+, CD20+, CD79a+, Bcl-2-, and Bcl-6+. CD21/CD23 immunostain demonstrated a disrupted follicular dendritic cell pattern characteristic of follicular colonization in extranodal MZBL of MALT type. Taken in conjunction with the morphologic findings, nodal MZBL may also show a follicular growth pattern similar to extranodal MZBL of MALT type. The marginal-zone nature is most recognizable on immunohistochemistry, although the histologic appearance alone may cause some diagnostic problems. It is important for pathologists to consider this type of lesion in diagnostic practice.

Adult↗

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↗