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Notes: Abstract: Some connective tissue diseases are characterised by specific autoantibodies. Although anticentromere or antikinetochore antibodies (ACA), and antitopoisomerase-I or anti-Scl-70 antibodies (ATA), have disease-specific meanings for systemic sclerosis and its CREST variant, respectively, the clinical significance of their concurrent existence has not been clarified. We investigated this condition in our case and with reference to the literature. For this purpose published reports between 1980 and 1998, where both ACA and ATA were measured simultaneously, were analysed by a MEDLINE search. In 10 papers 24 patients had both antibodies. In a further 25 reports, covering 3509 subjects who had either ACA or ATA, no concurrent existence was found. Prevalences of ACA (P(ACA)) and ATA (P(ATA)) in exclusive cases varied from 8.8% to 54.5%, and from 11.8% to 87.5%, respectively, whereas P(ACA) varied from 20.0% to 56.6%, and P(ATA) from 16.8% to 63.7% in the reports with patients positive for both. The actual prevalence of simultaneous presence was between 0.7% and 5.6%, significantly lower than the expected probabilities if both antibodies were to occur independently (p〈0.005). In concurrently positive cases visceral involvement was characteristic, especially affecting the vascular system, with deterioration of oesophageal function and cutaneous lesions. We suggest that ATA and ACA do not coexist by chance, and that clinical characteristics with coexistence have a significance for the classification of scleroderma.

Notes: By means of Monte Carlo simulations of a lattice model, microphase separation transition of symmetric diblock-copolymer melts confined in the thin-film geometry between parallel hard walls is studied. We impose a surface field which acts repulsively only on one of the two species, to stabilize lamellar order parallel to the surfaces. However, interplay between two characteristic lengths, that is, the natural thickness of the lamellar l and the thickness of the film D, causes complicated behavior. In case that the two lengths are compatible with each other, clear lamellar order parallel to the surfaces is observed at temperatures lower than the bulk transition temperature, as expected. On the other hand, tilted or deformed lamellar structure, or even coexistence of lamellae in different orientations are found in cases of strong conflict. In both cases, lamellae are fully established. Even at temperature higher than the bulk transition temperature, weak order is induced by the surface field, and a gradual transition between such surface-induced order and bulklike order is observed. Film thickness and temperature dependence of the ordered structure is discussed, as well as a density reduction near the walls and in the interfaces between the segregated regions.

Notes: Aims:  Lymphomatous polyposis (LP) is considered to represent mantle cell lymphoma (MCL) of the gastrointestinal (GI) tract. However, a few reports have suggested that some are follicular lymphoma (FL) or mucosa-associated lymphoid tissue (MALT) lymphomas. In this study, we analysed 35 patients and clarified the clinicopathological features of LP.Methods and results:  Paraffin-embedded tissue samples were stained immunohistochemically and analysed by tissue-fluorescence in situ hybridization (T-FISH) for IGH/CCND1 (cyclin D1) and IGH/BCL2. The average age of the patients was 58.3 years. Over half of the cases showed gastric, duodenal, small intestinal, ileocaecal and sigmoid colonic lesions (15, 19, 15, 16 and 16 cases, respectively). Phenotypically, cases were classified into three types of MCL (cyclin D1+ CD5+ CD10–) (n = 12), FL (cyclin D1– CD5– CD10+) (n = 14) and MALT (cyclin D1– CD5– CD10–) (n = 9). T-FISH identified 11 of the 11 examined cases with MCLs to have IGH/CCND1, while seven of 10 cases with FL had IGH/BCL2, and none of the MALT cases were positive for IGH/CCND1 or IGH/BCL2. At the study endpoint, five of 12 patients with MCL were dead, two of 14 with FL and one of nine with MALT were dead of other disease. Event-free survival analysis showed significantly poorest outcome in MCL, followed by FL, while MALT was associated with a favourable outcome (P = 0.0040).Conclusions:  Our study emphasizes the importance of differentiating MCL, FL and MALT of LP in evaluating prognosis and hence the most suitable therapeutic regimen.

Notes: Aims:  A micropapillary pattern (MPP) in lung adenocarcinoma, characterized by papillary structures with epithelial tufts lacking a central fibrovascular core, has been reported to be a new pathological marker of poor prognosis. However, its clinicopathological and prognostic significance in small lung adenocarcinomas (≤20 mm) remains undetermined. A new histological classification of small lung adenocarcinoma proposed by Noguchi et al. has been found to be useful since it has defined surgically curable bronchioloalveolar carcinoma (BAC)-type tumours (Noguchi's type A and B) based on the absence of active fibroblastic proliferation. However, BAC-type tumours with active fibroblastic proliferation (Noguchi's type C), which is adenocarcinoma with mixed subtypes including BAC and invasive carcinoma in the new World Health Organization (WHO) classification, account for most of the small adenocarcinomas and represent a heterogeneous group ranging from minimal to overtly invasive cancer with variable prognoses. Therefore, in this study the aim was to investigate whether MPP can be an additional histological marker(s) to subclassify this heterogeneous group in small lung adenocarcinoma.Methods and results:  One hundred and twenty-two cases of small lung adenocarcinomas (≤20 mm in maximum dimension) classified according to the new WHO classification and Noguchi's proposal were analysed with reference to the presence of MPP. Of the 122 cases, 67 (55%) were MPP-positive and 55 (45%) were MPP-negative. Lymph node metastasis and pleural invasion were significantly more frequent in the MPP-positive group: 74% and 66% in the positive group versus 26% and 34% in the negative group, respectively. The 5-year survival of the MPP-positive group was 54%, whereas that of the MPP-negative group was 81% (P = 0.024). The 5-year survival rates of BAC (Noguchi's type A and B) (n =14), mixed BAC and invasive adenocarcinoma (Noguchi's type C) (n = 85) and invasive adenocarcinoma (Noguchi's type D and F) (n = 23) were 100%, 68% and 36%, respectively. In patients with mixed BAC and invasive adenocarcinoma (Noguchi's type C tumours), the 5-year survival of the MPP-positive group (n = 51) was 54%, significantly lower than that of the MPP-negative group (n = 23) of 100% (P = 0.02).Conclusions:  MPP is a simple and distinct pathological marker to subclassify tumours with a significantly poor prognosis within small (≤20 mm) mixed BAC and invasive adenocarcinoma (Noguchi's type C tumours).

Notes: We examined apoptosis in 33 gastric carcinomas using the terminal deoxynucleotydil transferase mediated dUTP-digoxigenin nick end labelling technique (TUNEL). Of the tumours, nine were well-differentiated, 13 moderately differentiated and 11 poorly differentiated. In addition, we also analysed MIB-1, a cell proliferation antigen. Morphologically, apoptotic tumour cells were more frequently observed in well-differentiated tumours. In addition, apoptotic signals of the TUNEL method were seen even in the nuclei of tumour cells which did not show apoptosis. The nick end labelling index was 51.0 ± 26.3 in the well-differentiated and moderately differentiated tumours and 28.0 ± 18.8 in poorly differentiated tumours. The mean of apoptotic body index and nick end labelling index were both significantly higher in well-differentiated and moderately differentiated tumours than in the poorly differentiated type (P 〈 0.0001, P = 0.008). The MIB-1 labelling index and higher in poorly differentiated tumours than in the well-differentiated or moderately differentiated tumours, and labelled cells were more numerous in the superficial region than in the middle and deep regions of tumours. No apparent correlation was found between the nick end labelling index and the MIB-1 labelling index. The high number of apoptotic cells (the high Nick end labelling index) and low proliferation potentiality (the low MIB-1 labelling index) in well-differentiated gastric carcinomas may thus be related to their natural tendency to demonstrate slow growth.

Notes: Twenty-one patients with CD30 (Ki-1) positive lymphoma were studied from a group of 91 patients with adult T-cell leukaemia/lymphoma. The patients were grouped into three types: diffuse CD30 positive anaplastic large cell lymphoma in 11 patients (group 1); pleomorphic type lymphoma with diffuse CD30 expression in five patients (group 2); and pleomorphic type lymphoma with positive CD30 expression in large cells but negative in medium-sized and small cells in five patients (group 3). The patients with diffuse CD30 positive lymphomas (groups 1, 2) frequently presented with extranodal tumours (68.8%) and lymph node enlargement greater than 2 cm in diameter (50%), and rarely with leukaemic changes, bone marrow involvement and hypercalcaemia (one case of each). Patients in group 3 rarely had extranodal tumours, but had frequent leukaemic changes. Expression of intercellular adhesion molecule (ICAM-1; CD54) by the lymphoma cells in 13 patients (81.3%) with diffuse CD30 positive lymphomas, was significantly higher than that in 33 patients (9.1%) with CD30 negative adult T-cell leukaemia/lymphomas. No positive reaction for epithelial membrane antigen (EMA) was found in the lymphoma cells of CD30 positive cases. The overall survival in patients with diffuse CD30 positive lymphomas was better than that of CD30 negative adult T-cell leukaemia/lymphoma patients, but showed no significant difference. These findings suggest that diffuse CD30 positive adult T-cell leukaemia/lymphoma has unusual clinical and immunohistological findings. It is also speculated that local tumour formation and leukaemic changes in such diffuse CD30 positive cases are influenced by CD54 (ICAM-1) expression by the lymphoma cells.

Notes: To investigate the relationship of Epstein-Barr virus (EBV) and angioimmunoblastic lymphadenopathy with dysproteinemia, we performed DNA analysis using the polymerase chain reaction (PCR), Southern blot, in situ hybridization, and immunohistochemical analysis of lymph nodes in five patients who were followed up and biopsied more than once. In the course of the disease, nodal architecture diminished, cellular atypia worsened, and clear cells increased in number. In the DNA analysis of the receptor genes, the clonal population increased in number. EBV nucleic acid sequences were found by either PCR or in situ hybridization in all examined nodes. The number of EBV-positive cells varied widely among the cases and throughout the course of the disease in the same patients. The analysis of EBV terminal repeats or lymphocyte-determined membrane antigen genes showed polyclonal populations of EB-infected cells. EBV-positive cells possessed intermediate- to large-sized nuclei, and the cells with large nuclei, especially, expressed latent membrane protein of EBV. These large cells varied in number among the cases. Double-labelling immunohistochemistry/in situ hybridization studies demonstrated that most of the EBV-positive cells expressed B-cell antigen (CD20). The presence of EBV seems to be associated with the selective defects of the immune system, rather than with the direct pathogenesis of angioimmunoblastic lymphadenopathy.

Notes: Summary We report a case of primary cutaneous T-cell lymphoma with an angiocentric growth pattern. The lesions had been confined for about 2.5 years to the skin, but there had been a gradual progression of the disease both clinically and histologically. We assessed the neoplastic clonality and the presence of Epstein-Barr (EB) virus genome in this case using immunohistochemistry. Southern blot analysis and RNA in situ hybridization. Clonal proliferation of a CD4+αβT-cell phenotype was demonstrated. In addition, the clonal population harboured the EB virus genome, which suggested that the virus was involved in the pathogenesis of the disease. The patient has remained in remission for 10 months, and has received treatment with cyclophosphamide and prednisone.

Notes: Aim:  To study the clinicopathological and immunohistochemical features of 143 cases of primary small and large intestinal non-Hodgkin's lymphoma (NHL) in Japanese patients who presented between 1981 and 2000.Methods and results:  The new World Health Organization (WHO) classification was used to classify NHL. The patients included 109 males and 34 females, with an average age of 54.1 years. Tumour sites were as follows: ileocaecal (n = 51, 35.7%), ileum (n = 29, 20.3%), rectum (n = 13, 9.1%), and duodenum (n = 11, 7.7%). Macroscopically, 124 cases (86.7%) were classified as tumorous type, 12 (8.4%) as diffuse infiltration type (erosion, superficial ulceration), five (3.5%) as polyposis type, and only two cases (1.4%) as ulceration type. Immunohistochemically, 122 lesions (85.3%) were of B-cell phenotype and 21 lesions (14.7%) were of T-cell phenotype. According to the WHO classification, of the B-cell lymphomas, 84 cases (68.9%) were large cell, 16 (13.1%) were Burkitt, 10 (8.2%) were marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT), and seven (5.7%) were mantle cell tumours. Among the T-cell lymphomas, 15 (71.4%) were of unspecified type, two (9.5%) were natural killer type, two were anaplastic large-cell lymphomas, one was lymphoblastic, and one was an adult T-cell leukaemia lymphoma. The survival rate for T-cell lymphomas was poorer than for B-cell lymphomas. Among the B-cell lymphomas, mantle cell lymphoma tended to have a poorer prognosis, whereas MALT lymphomas had a better prognosis than other B-cell tumour types.Conclusions:  Our retrospective study of patients with primary malignant lymphomas in the small and large intestines has illustrated the clinical features and outcomes of patients with this disease.