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N Funata

Publications and source records attributed to N Funata.

At least 37 records · Page 2Linked to original sources

Granulocytic sarcoma of the thymus in a nonleukaemic patient.

We report a case of granulocytic sarcoma arising from the thymus in a 17-year-old nonleukaemic patient. The patient presented with an anterior mediastinal tumour and underwent surgical resection. Histological examination showed a diffuse infiltrate of immature round cells in the thymus. Tumour cells were diffusely peroxidase positive, but naphthol AS-D chloroacetate esterase negative. Immunohistochemical staining revealed expression of CD34 and terminal deoxynucleotidyl transferase (TdT), but not of CD13 and CD33. Ultrastructurally, electron-dense or medium-density granules were present in the cytoplasm. Four months after successful autogenic bone marrow transplantation, pleural and pericardial fluid contained tumour cells with azurophilic granules, which expressed CD13 and CD33, but not CD34 and TdT. The patient died of the disease 18 months after clinical manifestation, but still without developing leukaemia. The granulocytic sarcoma in the present case may have originated from myeloid precursors in the thymus and remained within the extramedullary site despite the differentiation into a more committed myeloid lineage at the relapse.

Adolescent↗

Polymerase chain reaction screening of immunoglobulin heavy chain and T cell receptor gamma gene rearrangements: a practical approach to molecular DNA analysis of non-Hodgkin's lymphoma in a surgical pathology laboratory.

Characterization of the clonality of non-Hodgkin's lymphoma (NHL) by the rearranged segments of immunoglobulin heavy chain (Ig(H)) or T cell receptor (TCR) genes is not only useful in the confirmation of the diagnosis but also for the future assessment of how a secondary lymphoma, such as a recurrence or another primary lymphoma, occurs. As a practical approach to obtaining and registering this information in a surgical pathology laboratory, FR3 and FR1 regions of Ig(H) gene and TCRgamma gene were concurrently amplified by polymerase chain reaction (PCR) using each pair of consensus primers and the same PCR protocol. Examined samples consisted of 134 primary NHL (phenotypically, 108 B cell and 26 T cell NHL), 19 reactive lymphadenopathies, as well as five secondary lymphomas whose primary lesions were included in this study. Among the primary NHL, the combined PCR analysis disclosed the clonality in 103 of 134 NHL (77%), by FR3 PCR in 77 B cell and two T cell NHL, by FR1 PCR in 59 B cell and one T cell NHL, and by TCRgamma PCR in 11 B cell and 17 of 26 T cell NHL, but in none of the reactive lymphadenopathies. Among the secondary lymphomas, the same pattern of PCR analysis was obtained in two cases (the durations between first and second lymphomas; 6 and 10 months), which suggested recurrence. In contrast, different results were obtained in three cases (17-37 months), which indicated another primary or emergence of the subclones. The results of Southern blot analysis were concordant with the PCR results of the first and the secondary lymphomas. Although the combined PCR analysis cannot replace Southern blot hybridization because of its lower detection rate, it can select those cases suitable for further Southern blot analysis thus reducing the number of unnecessary examinations by nearly 75%. This approach may also be useful in the comparative evaluation of primary and secondary lymphomas.

Biomarkers, Tumor↗

Significance of thymidine phosphorylase as a marker of protumor monocytes in breast cancer.

Tumor-associated monocytic cells (TAMs) are a major component of the stroma responsible for tumor formation. TAMs generate various kinds of mediators for their function, one of which is thymidine phosphorylase (TP). TP is an angiogenic enzyme that is known to be up-regulated in tumor tissues. Here, we focused on the clinical implication of TP expression in TAMs by studying 229 primary breast carcinoma tissues. Immunohistochemical analysis demonstrated that monocytic TP+ tumors had a significantly worse prognosis than did monocytic TP- tumors (P < 0.01, log-rank test). A multivariate analysis confirmed that monocytic TP status provided an independent prognostic value (P < 0.0001). Furthermore, of interest was that monocytic TP status could categorize the CD68+ patients, who had an extensive accumulation of CD68+ TAMs, into two subgroups with strikingly contrasting prognoses: a good prognostic monocytic TP- group and a poor prognostic monocytic TP+ group. This indicates that there are both antitumor and protumor types of TAM. Subanalysis showed that microvessel density was significantly increased in CD68+/monocytic TP+ tumors compared with CD68+/monocytic TP- tumors. Experimentally, TAMs are known to function in diverse manners, antitumor and protumor; however, little is known about clinically recognizable markers to characterize the TAMs in histological sections. TP might be such a marker, which would be useful for identifying the character of TAMs, particularly the protumor phenotype.

Adult↗

Microsatellite instability and loss of heterozygosity in primary and secondary proliferative lesions of the parathyroid gland.

Clonality and genetic abnormalities were evaluated to characterize proliferative lesions of the parathyroid gland. Fourteen lesions from patients with single-gland proliferation (adenomas [PA]), 6 lesions from patients with multiple-gland proliferation (primary hyperparathyroidism [PHPT]), and 47 lesions from 16 patients with secondary hyperparathyroidism (SHPT) were examined. Based on the X chromatin inactivation pattern, which was revealed by a HUMARA assay of lesions from female patients (n = 34; 24 informative cases), monoclonality was demonstrated in 6 of 10 PA (60%), 2 of 5 PHPT (40%), and 6 of 9 SHPT lesions (14 of 27 lesions, 52%). By PCR analysis using 17 microsatellite markers on eight chromosomes (chromosomes 1, 2, 3, 5, 6, 11, 13, and 17), loss of heterozygosity was sporadically observed in 4 of 14 PA, 3 of 6 PHPT, and 7 of 47 SHPT lesions, in most cases on a single locus of chromosome 11. On the other hand, microsatellite instability was observed more frequently: ie, in six PA, five PHPT, and nine SHPT lesions. The profile of microsatellite instability depended on the type of proliferation: microsatellite instability (MI) seemed to cluster in the region of chromosome 11 in PA. Microsatellite instability on TP53 was observed in 3 of 6 PHPT lesions and in 2 of 47 SHPT lesions but in no PA lesions. Microsatellite instability on Mfd47 was observed in only some cases of SHPT. Although no significant correlation was identified among histologic features, clonality, and genetic abnormalities in cases of primary proliferation, genetic abnormalities were more frequently observed in SHPT lesions that lacked fat tissues. Thus, genetic instability might be important in proliferative disorders of the parathyroid gland, either with or without uremia. However, genetic instability seems to be induced by different mechanisms in the three types of proliferation studied. In SHPT, the absence of fat tissues may indicate that the proliferation is accompanied by genetic changes.

Adenoma↗

Study on the etiopathogenesis of multiple spongy necrosis of the pontine base in three autopsy cases.

The etiopathogenesis of multiple spongy necrosis (MSN) of the pontine base was analyzed by examining the spatial relationship with intra- and extrafascicular vascular structures by reconstruction of serial sections of nine lesions from three autopsy cases. All nine lesions in the fascicles were distributed without any spatial relationship to the intrafascicular vessels. Instead, these lesions were distributed in parallel with arterial and venous transverse main branches between the anteromedial and anterolateral groups of the pontine vessels. On the other hand, all lesions in the middle cerebellar peduncle were arranged obliquely along the arterial and venous main trunks of the lateral group vessels with sparing of the perivascular narrow zone of the white matter. Moreover, narrow fascicles, even though located in the dorsomedial region of the pontine base, which is consistently involved in MSN, were spared, and thick transverse and longitudinal fascicles were selectively involved. The marginal zone of fascicles was spared, and focal coagulation necrosis was sometimes found in MSN lesions. Additionally, normal fascicles did not have their own nutritional arteries, and were nourished by arterioles and capillaries from the surrounding pontine gray matter. Neither severe organic stenosis nor occlusion of pontine vessels was found. On the basis of the close topographical relationship of MSN lesions with the pontine vascular architecture in addition to preferential involvement of thick fascicles with sparing of the marginal zone and inclusion of focal coagulation necrosis, it is proposed that the etiopathogenesis of MSN is pontine ischemia on a background of the characteristic parenchymal and vascular architecture of the pontine base. As to the cause of the ischemia, it is proposed that some functional disorder such as arterial vasoconstriction in the pontine base or the vertebrobasilar artery is responsible, rather than organic changes in the vessels.

Adenocarcinoma↗

Neuroendocrine differentiation in thymic epithelial tumors with special reference to thymic carcinoma and atypical thymoma.

To determine the neuroendocrine (NE) features of thymic epithelial tumor, immunohistochemistry and electron microscopy studies were performed on eight NE tumors (thymic carcinoids) and 26 non-NE tumors (nine thymic carcinomas, five atypical thymomas, and 12 thymomas other than lymphocytic thymoma). Immunohistochemical studies were performed with antibodies against general markers for NE cells (synaptophysin, alpha subunit of a guanine nucleotide-binding protein, Go, and small-cell lung carcinoma cluster 1 antigen), and a broad panel of antibodies for hormonal substances. Thymic carcinoid showed synchronous diffuse immunoreactivity for the three NE markers and contained cells that were positive for a variety of hormonal products: human chorionic gonadotropin (hCG) alpha-subunit (eight of eight), hCG beta-subunit (three of eight), adrenocorticotropic hormone (ACTH) (three of eight), calcitonin (two of eight), calcitonin gene-related peptide (two of eight), and serotonin (one of eight). Conversely, although positivity for NE markers was neither synchronous nor diffuse in non-NE tumors, seven of nine thymic carcinomas, three of five atypical thymomas (focal or dispersed distribution), and none of the five thymomas were positive for at least two of these NE markers. A small number of neoplastic cells were positive for hCGalpha-subunit or ACTH in three thymic carcinomas and one atypical thymoma. Ultrastructurally, dense core granules (DCG) were much more frequent in thymic carcinoid, but several DCG-like granules were identified in 12 of 13 non-NE tumors with or without immunoexpression of NE markers. The presence of focal or dispersed NE cells in thymic carcinoma and atypical thymoma may reflect multidirectional differentiation within the tumor, which, like cytological atypia, epithelial CD5 expression, and lack of immature T cell infiltration, may be another feature of this group at thymic tumors.

Adenocarcinoma↗

Significance of circulating hepatocyte growth factor level as a prognostic indicator in primary breast cancer.

The circulating hepatocyte growth factor (HGF)/scatter factor level is frequently increased in advanced cancer patients. In this study, we have assessed the prognostic value of the circulating HGF level determined by enzymatic immunoassay in primary breast cancer patients. Of 200 primary breast cancer patients, 54 (27.0%) showed the increase of serum HGF level according to the age-matched cutoff values. The prognosis of the patients with the increased HGF level was statistically worse than that of the patients with normal HGF level (P = 0.0001, log-rank test). Multivariate analysis confirmed that the increase in HGF level was an independent prognostic indicator in primary breast cancer patients. In the background analysis, the increase in serum HGF level was significantly associated with tumor size, nodal status, and histological evidence of venous invasion. The data indicate that up-regulation of the circulating HGF level may predict systemic tumor spread and early relapse in primary breast cancer patients.

Adult↗

Expression of CD44 variants in gastric carcinoma with or without Epstein-Barr virus.

The significance of CD44 variants in gastric carcinoma has not been fully investigated in terms of the pathological features of the carcinoma, including its association with Epstein-Barr virus (EBV). In this study, a total of 104 primary gastric carcinoma tissues (EBV-associated gastric carcinomas, EBVaGC, and EBV-negative carcinomas) were evaluated by immunohistochemistry. When the immunoreactivity of formalin-fixed, paraffin-embedded sections was graded on a scale of 0-3, the frequencies of grades 0-1, 2 and 3 were, respectively, 77%, 16% and 7% using monoclonal antibody (MAb) 3G5, which recognizes V3-5, and 70%, 14% and 15% with MAb 2F10, which recognizes V6. The expression of CD44 variants is independently correlated with lymph node metastasis and EBV-association in gastric carcinoma. Significant correlations were observed between V3-5 expression and lymph vessel invasion or lymph node metastasis, and between V6 expression and lymph node metastasis. The expression of both variants was significantly correlated with EBV-association. EBV-association and lymph node metastasis contributed independently to CD44 variant expression by multivariate analysis. Thus, the mechanism and significance of CD44 variant-expression are different in gastric carcinomas with or without EBV. EBVaGC is a distinct type of gastric carcinoma which should be considered separately from EBV-negative carcinoma.

Adolescent↗

Primary gastric T-cell lymphoma with and without human T-lymphotropic virus type 1.

BACKGROUND: Gastric T-cell lymphomas are rare, and their incidence and viral status have not yet been fully clarified. METHODS: Sixty-seven cases of surgically resected gastric lymphomas from city hospitals in Tokyo were evaluated. The surface phenotype was determined by immunohistochemistry, gene rearrangement by Southern blot hybridization, association with Epstein-Barr virus (EBV) by EBV-encoded small RNAs in situ hybridization, and the presence of human T-cell lymphotropic virus type 1 (HTLV-1) by serology, Southern blot hybridization, and polymerase chain reaction analysis. RESULTS: Five of the 67 cases were T-cell lymphoma (7%): 3 cases were HTLV-1 negative (-) and 2 were HTLV-1 positive (+). Systemic eosinophilia was observed in the three HTLV-1(-) gastric lymphomas. Neoplastic cells were morphologically similar in both groups, but a granulomatous reaction with marked eosinophilia was observed only in the two cases of HTLV-1(-) lymphoma. They also had characteristics of natural killer (NK) cell-like T-cell lymphoma, expressing NK markers and TCRgamma gene rearrangement. Positivity with HML-1 (specific for intestinal epithelial T-cells lymphoma was observed in one HTLV-1(+) lymphoma. The EBV gene was detected in only one case of B-cell lymphoma but not in any case of T-cell lymphoma. CONCLUSIONS: Gastric T-cell lymphoma occurs in 7% of gastric lymphomas in Japan and is comprised of HTLV-1-related lymphomas and lymphomas unrelated to HTLV-1, including NK cell-like lymphomas with eosinophilia.

Adult↗

Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases.

The authors analyzed 153 cases of histologically verified intracranial germ cell tumors. The histological diagnosis was germinoma in 63 patients (41.2%), teratoma in 30 (19.6%), and other types of tumors in 60 patients (39.2%). The patients were treated by a consistent policy of surgical removal with histological verification followed by radiation therapy with or without chemotherapy. The 10- and 20-year survival rates of patients with pure germinoma were 92.7% and 80.6%, respectively. The 10-year survival rates of patients with mature teratoma and malignant teratoma were 92.9% and 70.7%, respectively. Patients with pure malignant germ cell tumors (embryonal carcinoma, yolk sac tumor, or choriocarcinoma) had a 3-year survival rate of 27.3%. The mixed tumors were divided into three subgroups: 1) mixed germinoma and teratoma; 2) mixed tumors whose predominant characteristics were germinoma or teratoma combined with some elements of pure malignant tumors; and 3) mixed tumors with predominantly pure malignant elements. The 3-year survival rates were 94.1% for the first group, 70% for the second group, and 9.3% for the third group, and the differences were statistically significant. Twenty-six patients with malignant tumors received chemotherapy that consisted of cisplatin and carboplatin combinations with or without radiation therapy. However, chemotherapy was not significantly more effective than radiation therapy alone. From these treatment results, the authors classified tumors into three groups with different prognoses and proposed a treatment guideline appropriate for the subgroups.

Adolescent↗

Microsatellite instability and loss of heterozygosity in gastric lymphoma.

To evaluate the significance of microsatellite instability (MI) and loss of heterozygosity (LOH) in the development of gastric lymphoma, we examined 33 tissue-samples of 20 primary gastric B-cell lymphomas (6 low-grade lymphomas of mucosa-associated lymphoid tissue [MALT; 10 samples] and 14 diffuse large B-cell lymphomas [23 samples]). MI and LOH were evaluated at 13 microsatellite loci. In MALT lymphoma, four of six cases showed MI at one to two microsatellite loci (average 1.0 per case, 0.8 per sample), whereas in diffuse B-cell lymphoma, all samples showed MI at one to five microsatellite loci (average 2.4 per case, 2.7 per sample) (p < 0.05 and p = 0.0001). MI at the c-myc gene locus was most frequent in both types of gastric lymphomas (3 of 6 and 11 of 14 cases, respectively). Regional heterogeneity of the MI pattern was observed in two of four cases of MALT lymphoma and in four of five cases of diffuse B-cell lymphoma. On the other hand, LOH was observed only in one MALT lymphoma and in three diffuse B-cell lymphomas. Genetic instability may be an important mechanism for the development and progression of gastric lymphoma. Frequent MI at the c-myc locus might reflect an activated state and the importance of this gene in mucosal lymphocytes of chronic gastritis.

Adult↗

Fibrillary inclusions in neoplastic and fetal acinar cells of the pancreas.

We report a case of pancreatic acinar cell carcinoma which contained a large number of pleomorphic inclusions with fibrillary internal structures and mature zymogen granules. To clarify the significance of fibrillary inclusions in the differentiation of acinar cells of the pancreas, we further investigated fetal pancreases (gestational weeks 16, 17, 19, 20 and 28). We found two types of inclusions: type A, corresponding to fibrillary inclusion of neoplastic acinar cells, was observed only in a 19-week fetus; type B showed a homogeneous density similar to that of zymogen granules. Type B was observed in all the fetuses after the 17th gestational week. Although the type A inclusion might be generated through a different mechanism than the type B inclusion, the appearance of a large number of fibrillary inclusions in neoplastic acinar cells may represent a transient form of zymogen granule.

Carcinoma, Acinar Cell↗

Relapsing oral and colonic ulcers with monoclonal T-cell infiltration. A low grade mucosal T-lymphoproliferative disease of the digestive tract.

BACKGROUND: Some cutaneous T-cell lymphoproliferative diseases (LPD), such as lymphomatoid papulosis and pityriasis lichenoides et varioliformis acuta, are characterized by an indolent or waning and waxing clinical course. However, such T-cell LPD are rarely documented in other organs. METHODS: A patient with T-cell LPD of the digestive tract characterized by repetitive episodes of self-healing ulcers in the oral and intestinal mucosa over the course of 17 years is reported. Biopsy specimens from oral and intestinal mucosa were studied by conventional pathology, immunocytochemistry, and Southern blot analysis of T-cell receptor (TCR)-beta and -gamma gene rearrangement. RESULTS: Immunocytochemically, the infiltrating lymphocytes were lamina propria T cells with a dominant phenotype CD3+, CD4+/-, CD8-, and HML-1-. DNA study revealed the same rearranged configuration of TCR-beta and -gamma genes in specimens from both oral and colonic lesions. CONCLUSIONS: The present case may represent a novel T-cell lymphoproliferative disease (i.e., a digestive-tract mucosal counterpart of cutaneous dysplastic LPD).

Colonic Diseases↗

Vascular changes in acute Wernicke's encephalopathy.

The nature and distribution of vascular changes in acute Wernicke's encephalopathy (WE) were analyzed in three autopsy cases. Lesions of the lateral vestibular nucleus of the medulla oblongata (three cases) and lateral ventricular wall (one case) were examined by reconstruction of 200 serial sections, and the capillary diameter in the tegmentum of the medulla oblongata was measured morphometrically in all cases. The vascular changes commonly found in and around the parenchymal lesions in all cases were: (1) dilatation and endothelial swelling of almost all vessels ranging from small arteries to veins, being especially severe with undulation in small arteries and arterioles, and (2) fibrinoid degeneration and hemorrhage involving selectively the arterioles and capillaries on the arterial side. These vascular changes in the medulla oblongata were essentially the same as those in the third ventricular wall, but differed in their severity. Capillary diameter in these cases was significantly larger than that in seven control cases. Such vascular changes, especially a dysoric change on the arterial side, could not be ascribed to secondary change following changes in the parenchyma, and were, therefore, considered to be a lesion essential to WE, as in the case of the parenchymal lesion.

Adolescent↗

Pyothorax-associated lymphoma: development of Epstein-Barr virus-associated lymphoma within the inflammatory cavity.

Pyothorax-associated lymphoma (PAL) is a B cell lymphoma that develops in Japanese patients with tuberculosis-associated chronic pyothorax (TaCP). Epstein-Barr virus (EBV) has been shown to be causally related to PAL. To clarify the developmental process of PAL, the systemic and local presence of EBV, and serum profile of anti-EBV antibodies was investigated in TaCP. EBV genome was found in peripheral blood mononuclear cells by PCR in a 10(-4)-10(-5) amount of Raji cell-DNA in three of four patients with TaCP, but was also identified in patients with pyothorax caused by other diseases (2/2) or without pulmonary diseases (2/6). EBER1 in situ hybridization and EBNA2 immunocytochemistry revealed clusters of EBV-carrying cells in the cavity content (3/18) but not at the pyothorax wall; EBV(+) histological lymphoma cells were found in two cases and EBV(+) mononuclear cells were found in one case. A simultaneous increase in serum titers of anti-EBV viral capsid antigen IgG and IgA antibodies was observed in TaCP (4/16). These results suggest that a local factor, an inflammatory cavity, has a pivotal role in the development of PAL, which might be reflected in the serum titers of anti-EBV antibodies in patients with TaCP.

Antibodies, Viral↗

Intracranial meningioma masquerading as a primary pleuropulmonary tumor.

Extracranial metastasis was found in an intracranial meningioma with low proliferative potential before the detection of the primary tumor. Pleuropulmonary tumors were incidentally detected on chest X-ray in an asymptomatic 25 year old female. Excised tumors of the right pleura and lung showed histological features similar to meningotheliomatous meningioma, which led to the discovery and excision of the intracranial tumor. Both tumors showed the same histologic pattern: meningotheliomatous meningioma with low mitotic activity. The proliferative component, determined by the monoclonal antibody Ki-67, was further evaluated in the primary tumor and the metastases of the present case, as well as in 12 other intracranial meningiomas. Ki-67 positive ratios at the primary and metastatic sites of the present cases were 1.2 and 1.1%, respectively, which is as low as other benign meningiomas, and this suggests that factors other than the proliferative potential is responsible for extracranial metastasis of meningioma.

Adult↗

[The significance of invasion and vessel permeation in squamous cell carcinoma of the uterine cervix with invasion to a depth of 3 mm or less].

Nine-five patients with squamous cell carcinoma of the cervix invading to a depth of 3 mm or less (microinvasive carcinoma) were retrospectively viewed in regard to the depth of stromal invasion, the width of horizontal spread, confluent invasion, vessel permeation and lymph node metastasis. The type of treatment and outcome were also evaluated. Confluent invasion was found in 6 patient (6%), and vessel permeation in 9 patients (9%). Lymph node dissections were performed on 85 patients, but no lymph node metastasis was found, irrespective of the presence of confluent invasion or vessel permeation. Fifty-five patients with no vessel permeation were treated by conization or total or modified racial hysterectomy, and none had a recurrence of the disease. Our results suggest that the presence of confluent invasion or vessel permeation does not influence the incidence of lymph node metastasis, but data in the literature indicate that confluent invasion and vessel permeation are risk factors for lymph node metastasis and invasive recurrence of the disease. We conclude that patients with invasion of depth 3m or less, with no confluent invasion and no vessel permeation, can be treated by conservative operation.

Adult↗

Pyothorax-associated pleural lymphoma. A case evolving from T-cell-rich lymphoid infiltration to overt B-cell lymphoma in association with Epstein-Barr virus.

BACKGROUND: Pyothorax-associated pleural lymphomas (PAPL) occur in patients with long-standing pyothorax. Epstein-Barr virus (EBV) plays an important role in its development. METHODS: An atypical case of PAPL is reported and its clinical features are compared with those of five cases of ordinary PAPL. RESULTS: The histology of the lymphoma changed from prominent T-cell infiltration to an overt B-cell lymphoma of diffuse, large cell-type. DNA studies of the lymphoma at the first presentation demonstrated dual rearrangement in the T-cell receptor beta (TCR beta) and immunoglobulin heavy chain J region (IgJH) genes. EBV genome analysis demonstrated monoclonal expansion of EBV-infected cells. EBV gene products were present only in large lymphocytes with B-cell phenotype. The same rearranged band of the IgJH gene, but not clonal rearrangement of the TCR beta gene, was observed in the overt B-cell lymphoma at the relapse. The same EBV-infected clone was observed throughout the course of the disease. The tumor was localized at the pyothorax wall, and cell-mediated immunity, reflected by a positive tuberculin reaction, was preserved only in the current case. CONCLUSIONS: T-cell-rich lymphoid infiltration in the current case is a variant of EBV-associated PAPL, which is infiltrated by reactive T-cells with clonal accentuation. This is the first documented case of EBV-associated PAPL evolving from T-cell-rich lymphoid infiltration.

Aged↗