Lymphoblastic lymphoma expressing CD56 and TdT.
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Adult↗
Biomedical subjects
T Koshikawa
Publications and source records attributed to T Koshikawa.
Mutations of the P53 tumor suppressor gene as clonal marker for multiple primary lung cancers.
OBJECTIVES: Second primary lung cancers are prevalent after treatment for initial lung cancer, and the lung is also one of the most frequent sites for recurrence after removal of early-stage lung cancer. The objective of the present study is to clarify the clonal origin of the second tumor with the p53 gene mutation used as a clonal marker. METHODS: Of 794 consecutive patients who underwent pulmonary resection for primary lung cancer from 1980 to 1993, 22 required second pulmonary resection during the follow-up period, with a median interval of 38 months. We examined 16 of these patients for mutations of the p53 gene occurring in exons 5 through 8 by the polymerase chain reaction/single strand conformation polymorphism method. Differential diagnosis was also made on a morphologic basis, considering the degree of cellular differentiation and cytologic subtypes. RESULTS: Nine of the 16 patients analyzed had at least one p53 mutation in their tumors. We were thus able to make molecular diagnoses for these patients. The mutational status of the p53 gene was discordant in all nine patients, suggesting a different clonal origin despite the fact that six of them had almost identical histologic features. CONCLUSIONS: Analysis of p53 gene mutations was thus useful in distinguishing second primary lung cancers from recurrent tumors. The observed heterogeneity of p53 status was also in line with the "field cancerization" concept.
Adenocarcinoma↗
Epithelial hyperplasia of usual type expresses both S100-alpha and S100-beta in a heterogeneous pattern but ductal carcinoma in situ can express only S100-alpha in a monotonous pattern.
Immunohistochemical identification of myoepithelial cells using alpha-smooth muscle actin provides little information about the nature of solid or quasi-solid portions of epithelial hyperplasia and ductal carcinoma in situ (DCIS) because actin-rich myoepithelial cells are usually demonstrated only in the stromal-epithelial junction of both lesions. We studied the differential distribution of alpha-subunit (S100-alpha) and beta-subunit (S100-beta) of S100 protein in actin-negative areas of usual epithelial hyperplasia and DCIS by employing the streptavidin method with monospecific rabbit antibodies against each subunit. All usual epithelial hyperplasias (n = 17) were composed of heterogeneous epithelial cell types; cells expressing S100-alpha and/or S100-beta were intermingled with non-expressing cells, resulting in a mosaic-like pattern. On the contrary, DCIS (n = 32) uniformly lacked immunoreactive S100-beta; S100-alpha was diffusely expressed in 24 (68.8%) DCIS (three solid/comedo, 13 cribriform, four endocrine, one micropapillary, three papillary variants) and negative in the remaining eight (31.2%) DCIS (one cribriform, two micropapillary, four papillary and one apocrine variants). In conclusion, in contrast to usual epithelial hyperplasia that expresses both S100-alpha and S100-beta in a heterogeneous pattern, DCIS can express only S100-alpha in a monotonous pattern, possibly signifying unidirectional differentiation toward secretory glandular epithelium.
Adult↗
Anaplastic large cell lymphoma: a distinct molecular pathologic entity: a reappraisal with special reference to p80(NPM/ALK) expression.
The p80(NPM/ALK) expression activated by the t(2;5) (p23;q35) translocation recently has been shown to play an important role in the pathogenesis of anaplastic large cell lymphoma (ALCL). However, the clinicopathologic significance of identification of p80 among ALCL cases has not been completely resolved. Difficulties also exist in the histologic and immunophenotypic identification of ALCL and Hodgkin's disease (HD) as separate processes, often complicating the clinicopathologic evaluation of and therapeutic approach to these entities. In order to clarify these issues, 67 specimens of ALCL and 63 specimens of HD (31 of the nodular-sclerosing type [NS-HD] and 32 of the mixed-cellularity type [MC-HD]) were immunostained using anti-p80 antibody and other relevant markers on paraffin sections. The clinicopathologic and immunophenotypic features were reviewed on the basis of p80 reactivity. The expression of p80 was detected in 43 of 67 cases of ALCL (64%), but none of HD. The p80+ ALCL cases constituted a very homogeneous group of tumors, characterized by the occurrence in a much younger group and relatively more favorable clinical course than the p80- ALCL, which were in keeping with the data previously reported. They showed virtually the identical immunophenotypic findings of p80+, CD30+, EMA+, CD15-, bcl-2-, and Epstein-Barr virus (EBV) with T- and null-cell phenotype, and showed the distinct morphologic features, including three cases of lymphohistiocytic/small-cell variant, as follows: the indented nuclei, often termed as reniform, embryolike, and horseshoelike; multiple, irregular, but indistinct nucleoli; and few reactive cells of eosinophils and epithelioid cells. Conversely, the 24 p80- ALCL cases, in which epithelial membrane antigen (EMA) and bcl-2 positivities were 33% and 55%, respectively, were heterogeneous and could be subdivided into five different categories, namely (a) 11 cases of HD-like ALCLs, (b) six cases of p80 common ALCL, (c) three cases of secondary ALCL, (d) two cases of primary cutaneous ALCL, and (e) two cases of primary classical ALCL that lacked p80 expression. This study clearly demonstrated that the immunohistochemical detection of p80 is of a crucial importance in delineating the biologically distinct entity of "primary classical ALCL" from various diseases that show morphologic and immunohistologic overlap, including HD and HD-like ALCL.
Adolescent↗
Clinicopathologic study of nasal T/NK-cell lymphoma among the Japanese.
A high prevalence of nasal lymphoma expressing a T- or natural killer (NK)-cell phenotype (NTCL) with frequent association of Epstein-Barr virus (EBV) has been indicated in Asians. To characterize NTCL among the Japanese, the clinicopathologic features of 32 cases were evaluated and the cases were also analyzed for EBV-RNA using an ISH method. Morphologically, 31 cases were identified by atypical pleomorphic lymphoid infiltrates with polymorphous, angicentric, and necrotic features. Their lymphoma cells ranged in size from small to large and were mixed in varying proportion from case to case. The other one case showed a monomorphic 'blastic' appearance. EBV-encoded small RNA (EBER) was detected in the neoplastic cells of 27 of the 32 cases examined. In the five EBV-negative cases, one was the 'blastic' type. Clonal T-cell receptor gene rearrangement was detected in none of seven cases examined. The patients had a median follow-up of 9 months (range, 1 month to 14 years and 11 months). The Kaplan-Meier estimate of overall survival was 49% at 5 years, correlating with clinical stage. These data support the concept that most cases of NTCL are identified as tumors with T/NK-cell characteristics and EBV association, distinctly different from other peripheral T-cell lymphomas. Furthermore, the one case of an EBV-negative 'blastic' variant appears not to fit well into the pleomorphic category but more closely resembles the pathologic features of extranasal angiocentric lymphoma with lymphoblastoid appearance. This study also showed no clear difference in clinical aspects other than the original site or in prognosis, between NTCL and extranasal angiocentric lymphomas despite the higher incidence of EBV association and the tendency for that peculiar anatomical site to be restricted to the former group.
Adolescent↗
Structure and function of the hemolymph node in rats.
Hemolymph nodes (HLs) are unique lymph nodes, in that their lymphatic sinuses contain numerous erythrocytes. In this study, we compared the internal structure and immunologic function of HLs with those of ordinary lymph nodes (OLs) and the spleen. Electron microscopy revealed erythrocytes passing through the walls of blood vessels in the intermediate sinus area (IMSA) of a HL between expanded endothelial cell junctions. However, no direct communication was found between lymphatic sinuses and blood vessels. Numerous carbon particles appeared in the IMSA of HLs on 5 days after intravenous carbon particle injection, while OLs lacked particle deposition. Immunohistochemical studies showed that lipopolysaccharide (LPS) reached the IMSA of HLs and extravasated into medullary cords 4 hours after intravenous LPS injection, resulting in the appearance of more IgM-stained lymphocytes in the IMSA of HLs than in that of OLs on day 5. The ability of organs to produce antibodies was determined by counting the number of plaque forming colonies after intravenous injection of sheep red blood cells (SRBC). The HLs antibody-producing ability was between that of OLs and the spleen. These results suggest that HLs possess functionally open blood vessels in the IMSA and their immunologic capability is between that of OLs and the spleen. These findings suggests that HLs are lymphoid organs that have characteristics between those of the OLs and the spleen, both ultrastructurally and functionally.
Animals↗
Prognostic significance of cyclin D1 and retinoblastoma expression in combination with p53 abnormalities in primary, resected non-small cell lung cancers.
This study was conducted to evaluate the prognostic significance of cyclin D1 and retinoblastoma (Rb) expression in combination with abnormal p53 accumulation in primary, resected non-small cell lung cancers (NSCLCs). We evaluated immunohistochemically the expression of cyclin D1 and Rb in 208 NSCLC patients whose resections were consecutively performed between January 1984 and December 1988 and determined their prognostic significance by comparison with follow-up data. Expression of cyclin D1 and Rb was detected immunohistochemically in 39 and 80% of the 208 NSCLCs, respectively. The Kaplan-Meier survival curve demonstrated that absence of cyclin D1 expression was significantly associated with shortened survival (P = 0.01 by the log-rank test), particularly in adenocarcinomas (n = 100; P = 0.004). Expression status of the Rb protein was not significantly associated with clinical outcome in any of the cohorts. The predictive power of these prognosticators was also assessed in combination with findings for abnormal p53 accumulation by multivariate analysis using the Cox proportional hazards modeling. Patients with cyclin D1-negative tumors had a significantly greater risk of earlier death than those with cyclin D1-positive tumors (risk ratio, 1.61; P = 0.03), particularly in adenocarcinomas (risk ratio, 2.49; P = 0.002). Cases showing abnormal p53 accumulation tended to have a shortened survival only when the tumors were adenocarcinomas (risk ratio, 1.75; P = 0.06). Absence of cyclin D1 expression may be a useful prognosticator for shortened survival in primary, resected NSCLCs with particular significance for adenocarcinomas. In contrast, Rb expression status is not a useful prognostic factor for any type of NSCLC.
Adenocarcinoma↗
Allelic-expression imbalance of the insulin-like growth factor 2 gene in hepatocellular carcinoma and underlying disease.
It has been well documented that the liver is an exceptional organ in which the monoallelic expression of insulin-like growth factor 2 (IGF2) due to genomic imprinting is relaxed during the postnatal period, resulting in biallelic expression thereafter. In the present study, changes in the status of genomic imprinting were examined in 15 hepatocellular carcinomas (HCCs) as well as in 29 liver biopsies of chronic hepatitis or liver cirrhosis without clinical evidence of HCC, following screening for heterozygotes with an ApaI polymorphism in IGF2 in 34 HCCs and 80 such non-HCC cases. Extreme allelic-expression imbalance, leading to restoration of monoallelic IGF2 expression, was observed in 15 (100%) of 15 informative HCCs for the polymorphism with this monoallelic IGF2 expression appearing to be non-random from the paternal allele. Interestingly, the same allelic-expression imbalance was also present in a significant fraction of noncancerous liver specimens of patients with underlying disease known to be associated with HCC development. In contrast, the status of genomic imprinting of H19, another gene closely mapped at 11p15 under opposite imprinting, was strictly maintained in seven (100%) of seven cases informative for an RsaI polymorphism of H19. Together with the previous reports on altered genomic imprinting of IGF2 and H19 in embryonal lesions such as Wilms tumors as well as in lung cancers, the results suggest that perturbations of imprinting status occur as locus and tumor-type specific events in the development of human cancers.
Alleles↗
Centroblastic and centroblastic-centrocytic lymphomas associated with prominent epithelioid granulomatous response without plasma cell differentiation: a clinicopathologic study of 12 cases.
To clarify the clinicopathologic features of B-cell lymphoma associated with prominent epithelioid granulomatous responses other than immunocytomas, 12 patients were studied. There were six men and six women. The lymphoma generally affected elderly patients (median age, 58.5 years) and was mostly nodal in origin. Seven of the 12 patients had a localized lesion (stage I or II), and five had an advanced lesion (stage III or IV). Histologically, four patients showed a follicular growth pattern and eight a diffuse growth pattern. Based on the updated Kiel classification, nine patients showed centroblastic lymphomas, and three showed centroblastic-centrocytic lymphomas. The epithelioid cells were accumulated in large, poorly demarcated masses. Trabecular fibrosis compartmentalized in the lymph nodes, producing a vague nodular pattern in low-power fields. Immunohistochemical studies of the tumor cells revealed positive membrane staining with L26 in all 12 patients and with LN-1 antibody in 9 of 10 patients. Expression of the bcl-2 protein was present in all seven patients tested. Genotypic investigation exhibited germline configuration of the immunoglobulin heavy chain gene, the T-cell receptor beta-chain gene and the bcl-2 gene in all three patients investigated. By in situ hybridization, Epstein-Barr virus genomes were detected in only a few tumor cells in three of the patients tested. This study indicated that most, if not all, of the B-cell lymphomas with prominent epithelioid granulomatous responses other than immunocytoma were of follicular center cell origin.
Adult↗
Inconsistent association of Epstein-Barr virus with CD56 (NCAM)-positive angiocentric lymphoma occuring in sites other than the upper and lower respiratory tract.
We previously described nine cases of angiocentric lymphoma of a possible natural killer (NK)-cell lineage with a surface CD3-CD56+ phenotype occurring in sites other than the upper and lower respiratory tract. This study was performed to investigate the association of Epstein-Barr virus (EBV) with these lymphomas, using the polymerase chain reaction (PCR) for the presence of EBV-DNA, in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs) and immunohistology for EBV-determined nuclear antigen-2 (EBNA-2) and latent membrane protein-1 (LMP-1) in paraffin sections. PCR and ISH produced almost identical results, and EBERs were identified in the nuclei of the lymphoma cells of three cases, two of which exhibited LMP-1 in the cytoplasm of tumour cells without EBNA-2 expression. Molecular genetic analysis revealed EBV to be incorporated into these three EBER-positive cases either clonally or biclonally. It was revealed by re-evaluation of their morphology with the established EBV status on each case that, in contrast to the rather variable and irregular cellular composition of the EBV-positive tumours, the EBV-negative tumours stood out because of their remarkably uniform 'blastoid' appearance, and could be grouped as blastic NK-cell lymphoma. The relationship of the EBV-positive cases with nasal NK-cell tumours has yet to be clarified.
Adult↗
Clinicopathologic study of PRAD1/cyclin D1 overexpressing lymphoma with special reference to mantle cell lymphoma. A distinct molecular pathologic entity.
Mantle cell lymphomas (MCLs) are frequently associated with the overexpression of PRAD1/cyclin D1, activated by 11q13 translocation and its molecular counterpart BCL-1 gene rearrangement. We recently described the correlation of positive nuclear staining using monoclonal antibody against a PRAD1/cyclin D1 product with mRNA overexpression in MCLs. In the present study, we immunohistochemically investigated the PRAD1/cyclin D1 protein in a large series of 334 lymphoproliferative disorders, including 39 cases of MCLs on paraffin sections. Based on the cyclin D1 positivity, CD5 expression, and the morphologic features of the tumor tissue, four groups of MCL-related lesions were identified among the B-cell lymphomas examined: 36 cases with cyclin D1 overexpression, 35 (95%) of which exhibited CD5-positivity and MCL-morphology (Group 1); four cases of lymphomas with MCL morphology and CD5 expression but lacking cyclin D1 overexpression (Group II); four cases of lymphomas without cyclin D1 overexpression and surface CD5 but that fall within the morphologic boundaries of MCLs (Group III); and 11 cases of CD5-positive diffuse large cell lymphomas without cyclin D1 overexpression (Group IV). The Group I cases demonstrated quite homogeneous clinicopathologic features identical to those of MCLs. This group showed a poor prognosis (11% had 5-year survival), which is highly contrasted with that of Group II (100%). Although the four groups of MCL-related lesions sometimes overlapped in their histologic or phenotypic spectrums, each appeared to show distinct clinicopathologic and prognostic profiles. Our study provides a basis for further clarification of the nature of the neoplasms of Groups II, III, and IV. Moreover, this comprehensive study may indicate that the overexpression of PRAD1/cyclin D1 is biologically essential to defining MCLs.
Aged↗
Tobacco, alcohol and dietary factors associated with the risk of oral cancer among Japanese.
The mortality rate among Japanese men due to oral cancer is increasing, but risk factors among Japanese other than smoking and drinking have not been examined. To investigate the dietary factors involved in oral cancer, we conducted a hospital-based case-referent study in Aichi, Japan. Cases comprised 189 men and 77 women aged 20-79 years with one of the following cancers: tongue, mouth, oropharynx and hypopharynx. The reference group comprised 9,858 male and 26,669 female out-patients without cancer. Smoking and drinking were highly associated with an increased risk of oral cancer. Japanese sake showed a lower odds ratio (OR) than beer or hard liquor (OR= 3.6, 4.5 and 4.8, respectively). In the cross analysis between smoking and drinking, smoking combined with drinking increased the risk of oral cancer to three times that of smoking only (OR=6.2 vs. 2.2). Frequent intake of raw vegetables (OR = 0.5) and fruit (OR = 0.5) were inversely associated with the risk of oral cancer after adjustment for age, sex, smoking, drinking and year of visit. Western-style breakfast and salty food preference decreased the risk of oral cancer, and salty food preference was still statistically significant by multivariate analysis (OR= 0.7). In conclusion, smoking cessation, drinking control and frequent intake of raw vegetables and fruit among Japanese are likely to be effective preventive measures against oral cancer.
Adult↗
Imprint cytology of cat scratch disease. A report of eight cases.
The cytologic features of cat scratch disease (CSD) from eight cases in imprint smears are presented. All patients were clinicopathologically diagnosed with CSD as follows: 1) a history of animal exposure was recorded 2 to 4 weeks before lymphadenopathy; 2) the disease occurred in the autumn and winter months; 3) a characteristic histopathology in the biopsied lymph node specimens was observed; and 4) Warthin-Starry silver stain-positive bacteria were detected in four of the seven cases examined. The characteristic cytologic finding was the presence of confluent epithelioid cells with nearby and central scattering of neutrophils against a background of polymorphic inflammatory cells. Furthermore, a varying number of medium-sized to large lymphoid cells with an appearance suggestive of monocytoid B lymphocytes (MBLs) were noted to be associated with the epithelioid cells. These cytologic findings closely paralleled the histologic patterns of epithelioid cell granulomas, with and without MBLs, which we have previously reported are probably associated with the disease.
Adult↗
Prognostic significance of abnormal p53 accumulation in primary, resected non-small-cell lung cancers.
PURPOSE: This study was conducted to evaluate the prognostic significance of p53 abnormalities in primary, resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Methodologic validation of immunohistologic detection of p53 abnormalities in routine pathology sections was assessed using 31 lung cancer specimens for which p53 gene status was known from our previous molecular biologic studies. Applying the optimized cutoff value, we evaluated the prognostic significance of p53 abnormalities in an independent cohort of 208 NSCLC patients with complete follow-up data, whose resections were consecutively performed between January 1984 and December 1988. RESULTS: Immunohistologic detection of p53 abnormalities appeared to be reliable and showed approximately 90% concordance with the p53 gene status. Using the selected cutoff value of 10%, 46% of 208 NSCLCs showed p53 abnormalities. There was no relationship between p53 abnormalities and clinical outcome in the entire cohort, which represented all histologic subtypes of NSCLC (P = .58). Based on the reasoning that the influence of p53 abnormalities may have been obscured by distinct biologic roles depending on histologic subtypes, we also separately analyzed subsets of patients with adenocarcinomas (n = 100) and with squamous cell carcinomas (n = 88) and found that it may be a useful prognosticator only in adenocarcinoma patients (P = .04). CONCLUSION: p53 abnormalities are not a significant prognostic factor in primary, resected NSCLC when all histologic subtypes are combined, but may be a useful prognosticator for adenocarcinomas. Additional studies are warranted for further evaluation, specifically of adenocarcinomas.
Adenocarcinoma↗
Risk factors of thyroid cancer among women in Tokai, Japan.
To analyze the risk factors of thyroid cancer among Japanese women who generally consume much more iodine than Europeans, we conducted a hospital-based case-referent study at Aichi Cancer Center Hospital (ACCH) in Nagoya, Japan. Ninety-four female patients aged between 20-79 years with papillary or follicular carcinoma of the thyroid, and 22,666 female outpatients without cancer were used. Past history of benign thyroid mass or goiter (odds ratio: OR = 13.9) and hyperthyroidism (OR = 5.0) showed increased ORs of thyroid cancer. Thyroid cancer cases consumed coffee less frequently (OR = 0.5) and had had more experience of delivery than referents (> or = 3 times; OR = 2.5). Western style breakfast (OR = 0.5) also decreased the OR. For the multivariate analysis, past history of thyroid diseases (OR = 4.3) was positively associated with the risk of thyroid cancer and everyday coffee consumption (OR = 0.6) tended to decrease the risk. These results suggest that thyroid hormone-related factors may be involved in the risk of thyroid cancer in Japan, too. To clarify the risk involved in Japanese food, another comparative study including detailed information on iodine intake between countries and individuals is required.
Adenocarcinoma, Follicular↗
[Association of Epstein-Barr virus with primary malignant lymphomas of the digestive tract].
The association of Epstein-Barr virus (EBV) with 85 non-Hodgkin lymphomas of the digestive tract in nonimmunocompromised cases was investigated, using in situ hybridization technique to detect EBV encoded small RNAs in paraffin sections. 85 cases (83 B-cell type and 2 T-cell type) included 3 gingivas, 1 tongue, 3 palates, 10 tonsils, 43 stomachs, 2 jejunums, 12 ileums, 3 ileo-cecal regions, 5 colons and 3 rectums. Out of 85 cases, 4 (4.7%) were EBV-positive, comprising 1 B-cell lymphoma of the tonsil, 2 B-cell lymphomas of the stomach, and 1 T-cell lymphoma of the rectum. On the other hand, EBV-positive rate in nasal/nasopharyngeal lymphomas examined for comparison was very high, 81.8% (9 out of 11). These results show that EBV is associated with only a small proportion of lymphomas of the digestive tract in nonimmunocompromised case, suggesting the existence of the other oncogenetic factors in the pathogenesis of this group of lymphomas.
Adult↗
In vivo occurrence of p16 (MTS1) and p15 (MTS2) alterations preferentially in non-small cell lung cancers.
Frequent homozygous deletions of the p16 (MTS1) gene encoding a cyclin-dependent kinase inhibitor were recently reported in various tumor cell lines including examples derived from lung cancers, but direct evidence for their occurrence in lung cancer patients has not been reported thus far. In the present study, alterations of p16 and/or p15, a p16-related cyclin-dependent kinase, were observed not only in lung cancer cell lines but also in the corresponding tumor specimens in vivo, excluding the possibility of in vitro artifacts. Interestingly, a clear specificity was also noted in terms of the affected histological subtype; i.e., only non-small cell lung cancers carried alterations (6 of 20 as compared to 0 of 20 small cell lung cancer cell lines).
Base Sequence↗
Ki-1 (CD30) positive anaplastic large cell lymphoma of T-cell phenotype developing in association with long-standing tuberculous pyothorax: report of a case with detection of Epstein-Barr virus genome in the tumor cells.
We report a case of CD30 positive anaplastic large cell lymphoma of T-cell phenotype developing in association with long-standing tuberculous pyothorax. Phenotypic analysis showed CD1a-, CD2+, CD3+, CD4+, CD5-, CD8-, CD10-, CD19-, CD20 +/-, CD21-, CD25-, CD56-, T-cell receptor (TCR) alpha/beta antigens-, and HLA-DR+ phenotype. Neither rearrangement of TCR beta and gamma chain genes or of immunoglobulin heavy chain gene was detected in DNA extract from fresh material. The lymphoma cells were also shown to express the latent membrane protein-1 and the Epstein-Barr virus (EBV)-encoded nuclear antigen-2 by immunohistochemistry and EBV-encoded small RNAs by in situ hybridization.
Aged↗