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Biomedical subjects

T Koshikawa

Publications and source records attributed to T Koshikawa.

At least 55 records · Page 3Linked to original sources

Clinicopathologic study of CD56 (NCAM)-positive angiocentric lymphoma occurring in sites other than the upper and lower respiratory tract.

The expression of the neural cell adhesion molecule (NCAM) (CD56, NKH-1) is a rare phenomenon in malignant lymphoma. Recently, several authors, including our group, described the clinicopathologic, phenotypic, and genotypic features of NCAM-positive tumors as a unique subgroup within a larger category of hematolymphoid malignancies. Ten cases of CD56+ angiocentric lymphoma occurring in sites other than the upper aerodigestive tract were studied for evaluating their characteristics. The disease occurred in six men and four women varying from 24 to 85 years (mean age, 53 years) who often exhibited a striking predilection for extranodal sites of involvement, such as the skin, gastrointestinal tract, and muscle, usually in the absence of peripheral lymphadenopathy. Although the cytologic appearances and immunophenotypic profile varied from case to case, these tumors often exhibited azurophilic granules, an angiocentric growth pattern, and surface CD3-, T-cell receptor (TCR) antigens-, and CD56+ phenotype without B-cell phenotype, except for a single case of CD3+, TCR alpha/beta+, and CD56+ phenotype. Genotype investigation exhibited germline configuration of the TCR beta and gamma chain genes and the immunoglobulin heavy chain gene in all five cases of surface CD3- phenotype examined, whereas the case of CD3+ phenotype showed rearrangement of TCR beta. They seem to constitute a distinct entity of the lineage spectrum spanning from natural killer (NK) cell to NK-like T cell.

Adult↗

Clinicopathologic study of primary gastric lymphoma of B cell phenotype with special reference to low-grade B cell lymphoma of mucosa-associated lymphoid tissue among the Japanese.

Resection specimens from 83 patients with primary gastric lymphoma (PGL) of B cell phenotype at stage IE and at stage IIE according to the Ann Arbor classification were investigated. Histologically, these lymphomas could be divided into four types: Type I lesions (n = 24) were entirely made up of MALT lymphoma; Type II lesions (n = 13) were predominantly MALT lymphoma containing one to a few foci of high-grade B cell lymphoma; Type III lesions (n = 22) consisted largely of high-grade lymphoma with small areas of low-grade MALT lymphoma; and Type IV lesions (n = 24) were pure high-grade B cell lymphoma, mostly of the large cell type. All patients had undergone primary gastric resection, and 14 received additional chemotherapy (n = 12), or both chemotherapy and radiotherapy (n = 2). The survival probability was significantly higher for Types I and II lymphomas than for Types III and IV tumors (P < 0.05 by the generalized Wilcoxon test). According to The General Rules for the Gastric Cancer Study by the Japanese Research Society for Gastric Cancer, the stage of disease showed a clear distinction between each of them (P < 0.01 by the generalized Wilcoxon test). This staging method seemed to serve well as a prognostic indicator. The histological typing of the PGL of the present series also seemed to correlate with the gross appearance, pathologic stage and prognosis. Furthermore, the expression of cyclin D1, bcl-2 and p53 protein, and PCNA was immunohistochemically investigated in 42 cases of the present series. Most of the low-grade PGL (Types I and II) had less than 60% PCNA-positive cells, whereas the high-grade PGL (Types III and IV) had more than 60% positive cells. In a study for cyclin D1 protein, no cases showed the nuclear staining pattern characteristic for mantle cell lymphoma, and the cytoplasmic staining frequently observed in the node-based large B cell lymphoma was seldom identified in the PGL. This discrepancy might suggest a lineage difference among the morphologically similar, but site-different, lymphomas. On the other hand, bcl-2 protein overexpression was almost equal in frequency between the gastric and node-based high-grade B cell lymphomas. This is in contrast to the reports from Western countries, in which the majority of high-grade gastric tumors were bcl-2 negative.

Adult↗

Angioimmunoblastic T-cell lymphoma (angioimmunoblastic lymphadenopathy with dysproteinemia [AILD]-type T-cell lymphoma) followed by Hodgkin's disease associated with Epstein-Barr virus.

A patient is described with angioimmunoblastic T-cell lymphoma (AIL) (angioimmunoblastic lymphadenopathy with dysproteinemia [AILD]-type T-cell lymphoma), which was later followed by Hodgkin's disease. At the time of the initial diagnosis, histological examination of a cervical lymph node showed a typical picture of AIL with abundant clear cells which were CD45RO+, CD43+, and CD20-, and there was no evidence of a monoclonal B-cell proliferation by immunohistochemical analysis. In situ hybridization for Epstein-Barr virus (EBV) was negative. Interposed by a bout of recurrence, the patient developed, 16 years later, a left subparotid mass which showed histologic features of Hodgkin's disease, mixed cellularity type. Diagnostic Reed-Sternberg cells and their variants were CD30+, CD15- and CD20+. Neither rearrangement of TCR beta and gamma chain genes nor of immunoglobulin heavy chain and kappa light chain genes was detected in DNA extract from fresh material. In situ hybridization showed the presence of EBV within the Reed-Sternberg cells. The data show that EBV was not etiologically related to AIL in this case. Further, the deficit in cellular immunity that accompanied AIL conceivably permit primary EBV infection or reactivation of latent infection, which eventuated in development of Hodgkin's disease, but the exact pathogenesis remains uncertain.

Blotting, Southern↗

A case of neural cell adhesion molecule-positive peripheral T-cell lymphoma associated with human T-cell lymphotrophic virus type 1 showing an unusual involvement of the gastrointestinal tract during the course of the disease.

We report a case of neural cell adhesion molecule (NCAM)-positive peripheral T-cell lymphoma (PTCL), pleomorphic, medium and large cell type according to the updated Kiel classification, which was associated with human T-cell lymphotrophic virus type 1 (HTLV-1). The patient showed an unusual involvement of the gastrointestinal tract forming a bulky mass during the course of his disease, and a relatively indolent clinical course for 53 months until death. Phenotypic analysis showed CD2+, CD3-, CD4+, CD5+, CD7+, CD8-, CD16-, CD56+, and CD57- phenotype. Human T-cell lymphotrophic virus type 1 antibody was detected by the enzyme-linked immunosorbent assay. The proviral integration of HTLV-1 and the monoclonal rearrangements of T-cell receptor beta and gamma genes also were confirmed in DNA extract from fresh material. This fact calls attention to NCAM as one of the potential factors playing a role in the localization and behavior of lymphomas even within the category of PTCL associated with HTLV-1, ie, adult T-cell leukemia/lymphoma (ATLL).

Antigens, Surface↗

Immunohistochemical analysis of cyclin D1 protein in hematopoietic neoplasms with special reference to mantle cell lymphoma.

Immunohistochemical expression of PRAD1/cyclin D1 protein has been investigated in 106 tissue specimens of 104 cases of lymphoma, non-neoplastic lymphoid disorders and other hematologic malignancies by employing the monoclonal antibody 5D4 with formalin-fixed paraffin-embedded sections, using the microwave oven heating method. Positive neoplastic cells were found in 60 (74%) of 81 cases of non-Hodgkin's lymphoma. The positivity pattern was nuclear in 17 (85%) of 20 cases of mantle cell lymphoma in which cytoplasmic staining was also seen. This pattern of cyclin D1 positivity was in contrast to the negative staining of normal reactive mantle zones. In the other cases, positivity appeared to lie within the cell cytoplasm without nuclear staining, and most of the nodal follicular and diffuse B-cell lymphomas variously expressed PRAD1/cyclin D1. In contrast, the reaction was absent in a significant number of T-cell and extranodal B-cell lymphomas. Immunolocalization of PRAD1/cyclin D1 expression appears to be a useful diagnostic adjunct to discriminate mantle cell lymphoma from other non-Hodgkin's lymphomas.

Antigens, CD↗

Interdigitating cell sarcoma: a morphologic and immunologic study of lymph node lesions in four cases.

Interdigitating cell sarcoma is an extremely rare tumor. Its presentation and histologic appearance has varied among the reported cases. In this study, the authors investigated four cases of the hematolymphoid malignancy arising within lymph nodes, which were considered to be of interdigitating cell origin. All patients presented in the 6th to 8th decade of life with peripheral lymphadenopathy, and had a relatively indolent clinical course, without bone marrow or skin involvement. Carcinomas were observed as a second neoplasm in two of four patients. Distinctive morphologic features are proliferation of histiocyte-like cells with nuclear pleomorphism and occasionally multinucleated, paracortical distribution sparing of B-cell regions, fibrosis, sinus infiltration, and a prominent eosinophil/plasma cell infiltrates. The combination of light microscopic, fine structural, and immunohistochemical features suggested that these tumors derive from interdigitating cells; these tumor cells expressed CD68 (KP1), S-100 protein and HLA-DR, but lack CD21 (1F8), desmosomes and Birbeck granules. The diagnosis of interdigitating cell sarcoma should be considered on any pleomorphic tumor with the features described in this report.

Aged↗

Immunocytochemically demonstrated expression of epithelial membrane antigen and carcinoembryonic antigen by exfoliated urinary cells in patients with bladder cancer.

The localization of epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA) in exfoliated cells from voided urine was examined to clarify whether immunostaining for these markers is more useful than conventional cytology for diagnosis of patients with transitional cell carcinoma of the bladder. Both EMA and CEA were present more frequently in specimens from higher-grade and higher-stage tumors than lower-grade and lower-stage tumors. Cells positive for one or both of these markers were also found in specimens from cancer patients with only suspicious results by conventional cytology. In grade 1 tumors, the positive rates were 50% for EMA staining and 40% for CEA staining compared with 10% for conventional cytology. In 12 patients with cystitis, results for EMA staining and conventional cytology were all negative, whereas CEA staining proved positive in 6 patients (50%). None of 10 normal subjects with conventional cytology had positive results for EMA or CEA staining. These findings indicate that immunocytochemistry for EMA is a more useful adjunctive method than CEA staining or conventional cytology for detection of tumor cells, especially in cases of low-grade bladder cancer.

Aged↗

Predominantly tumor-limited expression of a mutant allele in a Japanese family carrying a germline p53 mutation.

Germline mutations of p53 have been implicated as a cause of cancer susceptibility in the Li-Fraumeni syndrome. Since inactivation of p53 has been suggested to play an important causative role in lung cancer, the present study of the prevalence of germline mutations in 148 patients with this neoplasm was performed. None of 138 randomly chosen patients were found to carry such mutations, while a single patient had a nonsense mutation at codon 213 among 10 patients selected for early onset and/or occurrence of multiple primary cancers. In contrast to the previous report of biallelic expression of p53 in a case with a germline missense mutation, preferential expression of the wild-type allele was observed in the heterozygous state in both normal lung and peripheral blood lymphocytes of our case, whereas expression of mutant mRNA was readily detectable in her lung cancer in the absence of the remaining wild-type allele. Interestingly, the family history of the proband showed a mild aggregation of adulthood cancers and a high prevalence of stomach cancer, a rare component in American families affected by the syndrome. These observations suggest the presence of heterogeneity with regard to molecular and clinical features of germline p53 mutations.

Adult↗

Clinicopathologic study of 212 cases of peripheral T-cell lymphoma among the Japanese.

BACKGROUND: Postthymic/peripheral T-cell malignancy shows significant histopathologic and clinical diversity, even in its prognosis, and the correlations remain to be debated. METHODS: The clinicopathologic features of 212 Japanese patients with these neoplasms were investigated. RESULTS: There were 131 male and 81 female patients, whose ages ranged from 2 to 90 years (mean, 51.7 years). Lymphadenopathy was the most frequent clinical presentation, and the patients also had frequent skin lesions, hyperimmunoglobulinemia, hypercalcemia, and a rapid clinical course. Furthermore, the differences in the histologic features of each subcategory reflected the clinical pictures. The immunophenotypic analysis was indispensable in establishing a correct diagnosis, and the high-grade tumors often showed loss of pan-T antigens. CONCLUSIONS: The histopathologic classification proposed by Suchi et al., which has been incorporated into the updated Kiel classification, showed a good prognostic correlation.

Adolescent↗

Aggressive rectal lymphoma of large granular lymphocytes with the histologic feature of an angiocentric growth pattern.

The authors report an unusual large cell lymphoma of the rectum composed of large granular lymphocytes (LGL) with histologic characteristics of an angiocentric growth pattern. Immunophenotyping showed that most of the tumor cells were CD3-, CD4-, CD8+, CD16+, CD56+, and CD57-. Fine structural analysis of the tumor cells found substantial numbers of electron-dense granules. Genotypic investigation showed a germline configuration of the T-cell receptor beta and gamma chain genes and the immunoglobulin heavy chain gene. The clinical course was aggressive, with rapid dissemination to the lungs, liver, and subcutis. The lesion was resistant to chemotherapy. There was, however, no evidence for peripheral blood or bone marrow involvement. This case report demonstrates the need for continued inquiry into the possible association of LGL with angiocentric lymphoproliferative lesions and gut-associated T-lymphocyte lesions.

Adult↗

Imprint cytology of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue arising in the thymus: a case report.

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising in the thymus is a very rare tumor with characteristic morphologic features. We describe a case of thymic low-grade B-cell MALT lymphoma occurring in a 59-yr-old woman with Sjögren's syndrome, in whom the definite diagnosis was difficult at the time of surgery. An immunohistologic and genotypic study, however, was diagnostic of lymphoma. A review of cytologic material was undertaken, and it was felt that the cytologic features in Giemsa-stained preparations in imprint smears were present that initially should have enabled the correct cytodiagnosis and distinction from the other thymic lesions. The findings presented in this study were considered to contribute to the cytodiagnosis of a thymic lesion, which might, in the past, have been erroneously interpreted as another lymphoproliferative disorder.

Cytodiagnosis↗

Changes in histopathological features of gastric carcinoma over a 26-year period (1965-1990).

Epidemiological study has shown that the incidence rate of gastric carcinoma in Japan has declined recently. To explore the factors that have influenced this decrease, the changing pattern in clinico-pathological features of gastric carcinoma was studied from the epidemiological point of view. The 5,015 cases of gastric carcinoma treated with gastrectomy at Aichi Cancer Center Hospital from 1965-1990 were divided into two histopathological types: the well-differentiated and other types. Proportional distribution was compared over the three different periods (1965-1973, 1974-1982, 1983-1990) according to the clinico-pathological features of the gastric carcinoma, i.e., sex, age, lesional location, etc. The recent relative decline of gastric carcinoma is due mainly to the decline of carcinoma of the well-differentiated type. This decline has been highly correlated to the decline in carcinoma of the antrum, which has been the most common in Japan. This changing pattern of clinicopathological features of Japanese gastric carcinoma might be affected by the change of exposure patterns to epidemiological factors, i.e., a Westernizing diet.

Age Factors↗

Diabetes mellitus induces accelerated growth of aortic smooth muscle cells: association with overexpression of PDGF beta-receptors.

The mechanism of diabetic macroangiopathy was studied from the view point of phenotypic change of aortic smooth muscle cells (SMC). The growth rates of cultured SMC of diabetic rats or rabbits were higher than those of non-diabetic animals (controls). This difference of the growth responses was observed specifically with platelet-derived growth factor (PDGF). Of the three PDGF dimers, PDGF-AB heterodimer (PDGF-AB) and PDGF-BB homodimer (PDGF-BB) stimulated growth of diabetic SMC more than that of control SMC but PDGF-AA homodimer (PDGF-AA) did not. The binding of 125I-PDGF to the diabetic SMC was greater than that to control SMC. This was due to increase in the number of cell surface receptors for PDGF. On in vitro culture, SMC from diabetic rats expressed more PDGF beta-receptor mRNA than SMC from non-diabetic rats. Moreover, in vivo, the aortic media of diabetic rabbits expressed PDGF beta-receptor mRNA, but that from non-diabetic rabbits did not. Thus diabetic SMC over-react on PDGF stimulation through over-expression of the PDGF beta-receptor gene. The significance of this fact in development of diabetic macroangiopathy is discussed.

Animals↗

Tumour necrosis factor-alpha can modulate the phenotype of aortic smooth muscle cells.

In culture, rabbit aortic smooth muscle cells (SMC) from an atheroma differed phenotypically from SMC from normal media (M-SMC) in their growth rate, secretion of SMC-derived growth factor (SDGF), and metabolism of acetylated low density lipoproteins (a-LDL). The factor responsible for this in vivo phenotypic change of SMC was investigated in vitro. After preincubation of M-SMC with 0.1-10 U ml-1 of tumour necrosis factor-alpha (TNF) for 1-3 days, the cells grew faster than control cells and secreted a substantial amount of SDGF. The population doubling time and secretion of SDGF were inversely correlated. Moreover, after preincubation with TNF, the SMC metabolized [125I]a-LDL, unlike control M-SMC. These findings show that TNF can modulate the phenotype of SMC and suggest that it is important in the pathogenesis of atherosclerosis.

Animals↗

[A clinicopathologic study of primary gastric lymphoma of B-cell type among the Japanese with special reference to low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT)].

The most common primary site of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is the gastrointestinal tract, particularly the stomach. The relationship of MALT lymphomas, however, with the more commonly occurring large B-cell gastric lymphoma has not been directly discussed except in the report of Chan et al. (1990), which lacked clinical information regarding the behavior of these tumors. To elucidate the relationship between high-grade large-cell lymphoma and MALT lymphoma, we studied in detail the histopathological and clinicopathologic features with the survival date of 77 Japanese cases of primary gastric lymphoma (PGL) of B-cell type. Based on degree of morphologically recognizable low- or high-grade components of the tumor, PGL was divided into four types: 18 cases of pure MALT lymphoma (type I); 13 cases of MALT lymphoma with small area of high-grade lymphoma (type II); 22 cases of high-grade lymphoma with small areas of MALT lymphoma (type III); and 24 cases pure high-grade lymphoma (type IV). Corresponding to the differences in the histologic pictures of each type, there were differences in the gross appearance, pathologic stage (including depth of invasion) and prognosis. These data suggests that both MALT and high-grade lymphomas of the stomach belong to the same cell lineage and constitute a pathological spectrum and that the histological grouping of PGL is clinico-pathologically useful.

Adult↗

Lewis blood group-related antigen expression in normal gastric epithelium, intestinal metaplasia, gastric adenoma, and gastric carcinoma.

The expression of blood group-related antigens of the Lewis system in normal gastric mucosa, intestinal metaplasia, gastric adenoma, and gastric carcinoma was examined. Ninety-five percent of normal foveolar epithelial samples stained positive for Lewis(b) antigen, whereas only 10.0% expressed Lewis(a) antigen. In contrast, intestinal metaplasia specimens had increased Lewis(a) antigen expression and slightly decreased Lewis(b) antigen expression. A similar pattern of Lewis(a) and Lewis(b) expression was observed in gastric adenomas and intestinal type adenocarcinomas. Lewis(x) and Lewis(y) were detected in all normal deep glands, but were not expressed in the majority of intestinal metaplasia specimens. In addition, only 20-40% of gastric adenomas and gastric carcinomas expressed Lewis(x) and Lewis(y) antigens. These changes in Lewis antigen expression in intestinal metaplasia, adenomas, and intestinal type adenocarcinomas suggest that altered expression of Lewis blood group-related antigens may correlate with cell transformation processes.

Adenocarcinoma↗