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Biomedical subjects

K Aozasa

Publications and source records attributed to K Aozasa.

At least 163 records · Page 9Linked to original sources

Nodular sclerosing Hodgkin's disease showing positive reaction for anti-IL 6/BSF2 antibody.

A 53-year-old man presented with bilateral cervical lymph node swelling and low fever. Swollen lymph node was biopsied, and diagnosed as nodular sclerosing Hodgkin's disease (HD). By combined radio- and chemotherapy, he went into complete remission. After 3 years, fever of 38-39.2 degrees C and lymph node swelling appeared in the para-aortic region and later became systemic. A biopsy was diagnosed as syncytial variant of HD with aid of immunohistochemistry on frozen sections. Large atypical mono- or binucleated cells reacted with anti-interleukin 6 (IL-6) antibody. The patient's disease progressed with fever, and he died 66 months after the onset of disease. A previous biochemical study showed that IL-6 displayed a real relation to the generation of fever. Therefore it is suggested that fever in this patient is related to IL-6.

Combined Modality Therapy↗

[Adult T-cell leukemia/lymphoma, histologically presenting Ki-1 positive anaplastic large cell lymphoma].

A 48-year-old woman was admitted with neck tumors and cutaneous nodules. On the histological basis of the skin nodule biopsy, a metastatic anaplastic carcinoma was suspected. Immunohistochemical studies showed the presence of Ki-1 antigen, IL-2 receptor antigen, leukocyte common antigen (LCA), CD3 and CD4 on the tumor cells compatible with Ki-1 positive anaplastic large-cell lymphoma. This case was, however, finally diagnosed as adult T cell lymphoma (ATL) of a helper/inducer phenotype. She was born in Kagoshima. The serum anti-ATL associated antigen (ATLA) was positive. Southern blot analysis on the DNA extracted from the skin tumor cells showed a monoclonal integration of HTLV-1 proviral DNA. The results suggested that Ki-1 positive lymphomas may include a subset of ATL with a large-cell histology.

Antigens, CD↗

High endothelial venules in extranodal lymphomas with emphasis on their prognostic significance.

In the present study, the frequency of occurrence of high endothelial venules (HEVs) in extranodal lymphomas at various sites was examined, and its prognostic implication subsequently estimated. The presence of HEVs was tested for by an immunohistochemical method using the monoclonal antibody, HECA-452, known to be specific for HEVs. The number of cases at each extranodal site were 13 in the thyroid, three in the salivary gland, 15 in the gastrointestinal(GI) tract, 20 in the brain, six in the lung, 12 in the pleura, nine in the testis, 10 in the bone, 19 in the skin and seven in the breast. Histologically, 26 of the 114 cases (23%) were of high grade malignancy according to the Working Formulation. Immunohistochemistry revealed 89 cases (78%) to be of B-cell type, eight (7%) T-cell type and 17 (15%) others. HEVs were observed frequently among the cases of lymphoma of the salivary gland (100%), thyroid (77%), GI tract (53%), lung (50%) and breast (43%). Evident were a preponderance of female patients (P less than 0.02) and those with histologically favorable lymphoma types (P less than 0.001), and a more favorable prognosis (P less than 0.001) for cases with HEVs over those without. There were no significant differences in age and immunologic type distributions between cases with and without HEVs. The findings suggest that the presence of HEVs could be used as an indicator for a favorable prognosis in cases of extranodal lymphoma.

Adolescent↗

Soft tissue sarcoma of the pleural cavity.

Seventeen cases of soft tissue sarcoma (STS) developing in the pleural cavity were collected from Japanese hospitals, and their clinical and pathologic findings summarized. Eight of the 17 patients had a 15-year to 50-year (mean, 28.8) history of chronic pleural inflammatory disease (pleuritis, pyothorax, and pulmonary tuberculosis) before the onset of the pleural sarcoma. Histologically, malignant fibrous histiocytoma was the most common tumor type (11 cases), followed by angiosarcoma (four). The age at diagnosis of the sarcoma ranged from 15 to 74 years (mean, 58); the male-to-female ratio was 3.3:1. In the eight cases of sarcoma associated with chronic pleural inflammatory disease, male preponderance was more marked (7:1). The commonest presenting symptom was chest pain. A mass could be detected by chest roentgenograms in 13 patients and computed tomographic scans in 15 patients. No patient had distant metastases at first admission. Thirteen patients were treated by surgery, chemotherapy, and/or radiation therapy. Thirteen of the 17 patients died 1 to 87 months (mean, 14.2) after therapy for STS. The actuarial 1-year survival rate was 38.5%. These findings suggest that long-standing pleural inflammation might be an etiologic factor for development of pleural STS.

Adolescent↗

Prognostic significance of argyrophilic nucleolar organizer staining in soft-tissue sarcomas.

The utility of argyrophilic stain for nucleolar organizer region (AgNOR) for estimating proliferative activity and prognosis of soft-tissue sarcomas (STS) was examined. Formalin-fixed and paraffin-embedded sections of 38 cases with STS were used; the reaction product of AgNOR stain was observed as dots mainly in the nucleoli. The mean number of AgNOR dots per nucleus of tumor cells was calculated in 200 cells (AgNOR count). The AgNOR count, ranging from 1.4 to 16.1 (mean, 7.5), showed a good correlation with cellularity (r = 0.483, p less than 0.003) and histologic grade (r = 0.626, p less than 0.00005), but less shown with mitotic counts (r = 0.350, p less than 0.04). The prognosis of cases with AgNOR low-count group (5-year survival rate was 74.6%) was much better than those in high count group (33.3%) (p less than 0.0005). The AgNOR count correlated well with reactivity of tumor cells for Ki-67 staining, which was available only in freshly prepared sections. These findings suggested that the AgNOR staining is a simple and useful method for estimating tumor-cell proliferation and prognosis of patients with STS.

Adolescent↗

Monocytoid B-cell lymphoma arising in extranodal organs.

Six cases of monocytoid B-cell lymphoma (MBCL) developing in extranodal sites (thyroid, three; stomach, two; rectum, one) are described. Patients were all women aged 46 to 65 years (median, 53 years). Three patients with thyroid lymphoma presented with an increasing goiter, two with positive serum antithyroid antibodies, and one patient had chronic lymphocytic thyroiditis (CLTH). The histologic type of surgically resected specimens was a diffuse proliferation of atypical lymphoid cells with monocytoid appearance, i.e., abundant pale cytoplasm with distinct cell border and small reniform nucleus. These cells were CD20+, 22+, 24-, 9- showing their B-cell origin. The monoclonal nature of the proliferating cells was confirmed by restricted expression of immunoglobulin (Ig) light chain and/or gene rearrangement study in three cases. Two cases of thyroid lymphoma in which the monoclonality could not be confirmed had histologic appearances characteristic of malignant lymphoma. All three patients with gastric or rectal lymphoma had reactive lymphoid hyperplasia (RLH) near the tumors. These findings showed presence of MBCL in the extranodal sites with invariable coexistence with lymphoid follicles formed by CLTH in thyroid or RLH in stomach and rectum.

Aged↗

Histologic and immunohistologic diversity of non-Hodgkin's lymphoma of lymph node origin.

To examine whether nodal non-Hodgkin's lymphomas (NHL) share common features in every nodal site, histologic and immunohistologic findings were analyzed site by site. Cases selected were nodal NHL of neck (17 cases), submandibular (10 cases), inguinal (9 cases), and abdominal cavity (22 cases). No significant differences in age distribution were found. A slight female preponderance was present in cases with inguinal NHL. Histologic and immunohistologic findings showed that nodal NHL were heterogeneous; (1) T-cell type was frequent in the neck but exceptional in other sites, (2) frequency of high-grade tumors was much higher in the intra-abdominal cavity but low in other sites, and (3) follicular lymphoma was common in the submandibular and inguinal regions. Previous studies indicated that histologic and/or immunologic types of NHL correlated with pathogenesis of lymphoma; EB virus and HTLV-1 for B and T lymphomagenesis, respectively, and acquired immunodeficiency syndrome (AIDS) for development of high-grade tumors. The present results may provide an insight to consider as a possible pathogenesis of NHL.

Abdomen↗

Histiocytic neoplasias: immunohistochemical evaluation of their frequencies among malignant lymphoma and related conditions in Japan.

Through histologic review of 1,766 cases with malignant lymphoma and related conditions, 35 cases (2%) were selected as probable histiocytic neoplasias. Proliferating cells in these cases had voluminous, granulated cytoplasm, and round to irregularly shaped nuclei often with bi- or multinucleated forms showing monomorphous or polymorphous proliferation accompanying small lymphocytes, plasma cells, and, less frequently, eosinophils. Cases showing proliferation of convoluted cells with numerous benign-appearing histiocytes or large cells with clear cytoplasm were excluded under a diagnosis of T-cell lymphoma. To evaluate the immunologic character of proliferating cells, immunohistochemistry using antibodies Mx-Pan B, MB-1, MT-1, UCHL-1, lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, S-100 alpha, S-100 beta, Leu M1, epithelial membrane antigen, and Ki-1 were carried out in 23 cases. Naphthol-ASD-chloracetate reaction and toluidine blue stain were also performed. These procedures revealed that 12 cases (52%) were B-cell type, three cases (13%) T-cell type, six cases (26%) true histiocytic type, and two cases null type. Therefore, the frequency of cases with true histiocytic neoplasias among cases with malignant lymphoma and related conditions in Japan may be 0.5%.

Antibodies, Monoclonal↗

Intermediate lymphocytic lymphoma: its frequency and characteristics in Japan.

The nature of intermediate lymphocytic lymphoma (ILL) in Japan was investigated. For this purpose, we have reviewed 1,766 cases of malignant lymphoma and related diseases, and 38 cases were selected as ILL. In two cases, small lymphoid cells proliferated as a wide mantle of atrophic secondary follicles. The frequency of ILL in nodal and extranodal non-Hodgkin's lymphoma was 3.4% and 3.9%, respectively. The frequency was high in orbit and salivary gland lymphomas; two out of three cases and one out of six cases, respectively. Age range (median) and sex ratio (M:F) in nodal and extranodal cases were 34-65 (52) years and 2.1:1 and 22-82 (61) years and 1.1:1, respectively. The majority of nodal ILL presented as systemic disease, but extranodal ILL usually presented as localized disease. ILL when treated with chemotherapy and/or radiotherapy had a favorable prognosis, the 5-year survival rate was 82%.

Adult↗

Histological factors contributing to favorable prognoses of soft tissue sarcomas in premenopausal patients.

The correlations of sex with various histologic factors in soft tissue sarcomas (STS) were studied in 142 adult patients over the age of 20 years. They included 63 with malignant fibrous histiocytomas, 20 with liposarcomas, 20 with synovial sarcomas, 11 with malignant Schwannomas and 28 with other forms of STS. These were divided into four groups, according to age (20-49 years and greater than or equal to 50 years) and sex. Survival rates in female patients were better than those in male patients, and the difference was significant between the 20-49 year groups (p less than 0.01). The relative frequencies in distribution of each histologic type were similar among male and female patients in both age groups. Among histological factors, mitotic counts showed a significant correlation (P less than 0.04) with sex, followed by cellularity. STS in female patients aged 20-49 years had lower mitotic counts than in patients in other groups, where it occurred with a higher frequency of low and intermediate grade tumors. The findings suggested estrogen, either directly to indirectly, to have a favorable effect on STS prognosis in premenopausal female patients.

Adult↗

Immunohistochemical detection of high endothelial venules in extranodal B-cell lymphomas.

The hypothesis that extranodal malignant lymphomas, such as thyroid, stomach, rectum, ileum and uterus, eventuate from long-standing inflammation is essentially tested using a monoclonal antibody (HECA-452) to an endothelial-associated antigen selectively expressed by the high endothelim of post-capillary venules (HEVs) normally present in lymph nodes, tonsils and mucosa-associated lymphoid tissues. The presence of HEVs was examined on freshly prepared specimens from 16 cases of extranodal lymphoma of the B-cell type (eight thyroid, three stomach, two rectum, one ileum, one uterus, one tonsil). Control cases included reactive lymph nodes, nodal lymphoma of T-cell type, epithelial neoplasia, bone and soft tissue sarcomas, glioblastoma, thyroid affected by chronic lymphocytic thyroiditis (CLTH), thyrotoxicosis (Grave's disease) or nodular goiter, and salivary gland affected by Sjogren's syndrome (SS). HECA+ HEVs were present in reactive lymph nodes, nodal lymphoma, and all but one case of thyroid, all cases of stomach and all cases of rectal lymphoma, together with all CLTH and SS, both known to be autoimmune diseases. No thyroid, ileal or uterine lymphoma cases had any HECA positive venules. HECA+ venules were present in extranodal lymphomas, either adjoining the lymphoid follicles observed in several cases or in the diffusely proliferating tumor cells. Previous studies have shown that HEVs appeared in association with long-standing inflammation. The present study therefore, suggested that extranodal lymphomas of the thyroid, stomach and rectum evolve in long-standing inflammation, forming HEVs.

Antibodies, Monoclonal↗

Very high incidence of germ cell tumorigenesis (seminomagenesis) in human papillomavirus type 16 transgenic mice.

Human papillomavirus type 16 (HPV16) is frequently found in carcinomas and precancerous lesions of the uterine cervix and is thought to be closely associated with carcinogenesis in these regions. However, the transforming activity of the E6 and E7 genes in vivo has not been characterized. To investigate this function, we produced transgenic mice carrying HPV16 E6 and E7 open reading frames. We obtained five transgenic founders and established three transgenic lineages. We observed testicular tumors of germ cell origin in mice of all three lineages. Morphological studies showed that these tumors were a type of seminoma. Both testes of all tumor-bearing mice were affected with this type of tumor. Strikingly, in one lineage, all of the male mice developed this tumor. On Northern (RNA) analysis, a high level of expression of HPV mRNA was detected in these tumors. These results suggest that transforming genes of HPV16 have transforming activity in vivo and preferential effects on germ cells in the testis.

Animals↗

Immunologic and immunohistochemical studies on chronic lymphocytic thyroiditis with or without thyroid lymphoma.

The local immunologic phenomena in the thyroid gland of 16 patients with chronic lymphocytic thyroiditis (CLTH) were investigated; 5 of these cases were associated with thyroid non-Hodgkin's lymphomas (NHL). All patients were admitted because of struma, growing slowly in patients with CLTH alone and rapidly in those with associated thyroid NHL. CLTH was confirmed by histologic findings, including the presence of lymphoid follicles or thyroid autoantibodies in the serum in all 16 patients. Immunologic study revealed that all thyroid NHL were of the B cell type. Surface maker study of suspended cells showed that the percentages of E-rosette-forming cells in patient with CLTH and thyroid NHL (38.0 +/- 10.0%) and in patients with CLTH alone (45.0 +/- 11.9%) were between those of B cell NHL of lymph node and B cell hyperplasia reported by others. Immunohistochemical studies confirmed the reactive nature of lymphoid follicles. Subset distribution of T and B lymphocytes in patients with CLTH and thyroid NHL markedly contrasted with that in patients with CLTH alone: an increased ration of CD8+ cells (suppressor/cytotoxic cell) to CD4+ cells (helper/inducer cell). There was a marked increase in the number of immunosuppressive acidic-protein(IAP)-containing macrophages in the thyroid lesion and serum IAP level in patients with thyroid NHL. These findings provide evidence of a difference in the local immunologic conditions in CLTH alone compared to CLTH complicated by thyroid NHL.

Adult↗

Prognostic factors for pleural lymphoma patients.

Prognostic factors in 47 patients with pleural lymphocytic lymphoma developing in chronic tuberculous pyothorax were evaluated using Cox's proportional hazards model. There were 41 men and six women, aged 44-80 (median 61) years. Approximately 70% of the patients had localized disease in Stages I and II, and 30% advanced disease in Stages III and IV. Histologically, 27 patients had the diffuse large, immunoblastic type and 12 had others. In the other seven patients, histological subtyping of the lymphocytic lymphoma was impossible because of degenerative or necrotic changes in the histologic specimens. A diagnosis of lymphocytic lymphoma of B-cell type was made in one case using combined cytologic and surface maker findings on a cell suspension. In addition, immunologic and immunohistochemical studies revealed another 40 cases to be proven B-cell lymphomas. Poor performance status and elevated levels of BUN and GPT were significantly associated with shortened survival in a Cox's proportional hazards model. A poor performance status and high levels of serum BUN and GPT suggested a marked deterioration in a patient's condition. When compared with previous literature describing prognostic factors in patients with B-cell lymphomas and with lymphocytic lymphomas with unfavorable histologies or associated with long-standing inflammations, the only common prognostic factors was performance status. The significance of primary site in predicting survival from lymphocytic lymphoma is discussed.

Adult↗

Lymphoproliferative diseases of the lung in Japan: review of thirty-six patients with an immunohistochemical study.

Thirty-six cases of primary lymphoproliferative disease of the lung, collected from hospitals in Japan, have been reviewed. Histologically they were divided into three groups: definite lymphoma (DL) showing monomorphous proliferation of medium to large cells (17 cases), small lymphoid cell proliferation (SLP) frequently containing lymphoid follicles (11 cases), and pseudolymphoma showing lymphoid follicular hyperplasia (LFH) (six cases) or mixed diffuse infiltration of small lymphocytes and macrophages (two cases). In some DL cases, lymphoid follicles were present in or near the tumors. Pulmonary lesions in SLP and LFH patients were frequently detected at their medical checkups. Immunohistochemistry revealed that proliferating cells in 15 out of 17 DL and all SLP cases were B cells with restricted expression of the immunoglobulin light chain, all lambda type, in three DL and four SLP cases. From morphologic and immunologic findings, 10 SLP cases were diagnosed as intermediate lymphocytic lymphoma (ILL) and one as being of lymphoplasmacytic type. Two DL cases with convoluted nuclei proved from immunohistochemistry to be of T-cell type, showing a much lower frequency of T-cell type than that found in the USA (approximately 50%).

Antigens, Differentiation↗

[Adult T cell leukemia/lymphoma with hyperprolactinemia: successful treatment by OK432 and PSK].

A 48-year-old woman was admitted in September 1987, because of lumbago and galactorrhea. Peripheral blood analysis showed neutrophilia and eosinophilia without abnormal lymphocytes. The antibody to adult T-cell leukemia (ATL) virus-associated antigen was detected and a hyperprolactinemia was observed. The blastogenic responses to PHA, ConA and PWM were lowered. Brain CT and MRI scannings showed no abnormalities in the hypophysis and hypothalamus, but abdomen CT revealed markedly enlarged abdominal lymph nodes. Two months after the administration of OK432 and PSK, the lymph node swellings disappeared and the responses to PHA, ConA and PWM were normalized, but hyperprolactinemia and galactorrhea persisted. After four months of the remission period, the patient developed lymph node swellings again, and was diagnosed from the biopsy specimen of the retroperitoneal lymph node as having malignant lymphoma of diffuse mixed cell type. Southern blot analysis showed a monoclonal integration of HTLV-I proviral DNA. Despite repeated combination chemotherapies, she died of pneumonia in February 1989. Autopsy revealed marked infiltrations of lymphoma cells in the liver, spleen and lungs, but no abnormality accounting for hyperprolactinemia was detected in the suprasellar regions. This case was of interest in that immunotherapy was effective in achieving a remission and in normalizing immuno-parameters in ATLL.

Adjuvants, Immunologic↗

Malignant lymphoma of the central nervous system in Japan: histologic and immunohistologic studies.

Ninety-seven Japanese patients with so-called primary non-Hodgkin's lymphoma of the central nervous system (CNS-NHL), unrelated to the acquired immunodeficiency syndrome (AIDS) or organ transplantation, were reviewed. The patients' ages ranged from 1 to 87 years (median: 58 years) with a male to female ratio of 1.77:1. The most frequent past histories were acute appendicitis (appendectomy), head injury, uveitis or iritis, and gastritis or gastric ulcer. These patients presented with symptoms suggesting an expanding intracranial lesion with no signs of extracranial lymphomatous disease. Combined computed tomographic scans, angiography, and findings at surgery or autopsy showed that the cerebrum was the commonest site of involvement, 87% of all cases, with the frontal to temporal region being the most commonly involved. Histologically, the diffuse large-cell type was most frequent and 26% of lymphomas were of high-grade malignancy as defined by the Working Formulation. The reported frequency of high-grade CNS-NHLs in AIDS patients in the United States is much higher (over 60%). Immunohistochemistry on paraffin-embedded sections revealed a B-cell nature of the present series of tumors. In 16% of the cases, large numbers of small lymphoid cells with a positive reaction predominantly for anti-T lymphocyte antibodies surrounded the tumors or aggregated around the capillaries. The tumors which were infiltrated by small lymphoid cells showed more favorable prognosis than those which were not, suggesting a host reaction to tumor growth in these patients.

Acquired Immunodeficiency Syndrome↗