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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: 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: 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.

Notes: Five cases of a characteristic low-grade thymic epithelial tumour are described that we suggest calling metaplastic carcinoma of the thymus.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and resultsThe patients' ages ranged from 44 to 71 (mean 56.2) years. Four of the patients were male. Three of five tumours showed invasion into mediastinal fat or pleura but, otherwise, all were well circumscribed. No metastases were present. Histologically, the tumours showed a biphasic pattern with solid carcinomatous areas merging gradually with a spindle cell component. Lymphocytes were rare. Cytological atypia and mitotic activity were variable in the solid areas, but slight or absent in the spindle cell component. On immunohistochemistry, the tumours showed expression of cytokeratin, vimentin and/or epithelial membrane antigen, both in the carcinomatous and spindle cell components. In two cases, actin expression was also present in both components. In one case, chromogranin, S100 protein, glial fibrillary acidic protein and neuron-specific enolase were expressed in at least some cells of both components. None of the patients had myasthenia gravis. All patients are alive without evidence of recurrence or metastasis.〈section xml:id="abs1-3"〉〈title type="main"〉ConclusionMetaplastic carcinoma of the thymus is a distinct clinicopathological entity that should be distinguished from the usually benign medullary thymomas and from the clinically aggressive carcinosarcomas and sarcomatoid carcinomas.

Notes: Multidrug resistance (MDR) is a major obstacle in the treatment of lymphoma. The expression of MDR-1 mRNA and P-glycoprotein (MDR-1/P-gp) has been linked to MDR. We aimed to investigate the expression of MDR-1/P-gp in B-cell lymphoma.Samples at diagnosis and relapse from 10 patients with B-cell lymphoma were obtained. We also obtained 14 unselected control cases of B-cell lymphoma at diagnosis. The expression of mRNA and protein were determined semiquantitatively by RT-PCR and immunohistochemistry. High MDR-1 and P-gp expressions were found in seven and seven of 10 samples obtained at diagnosis, eight and eight of 10 samples obtained at relapse, and three and four of 14 control cases at diagnosis, respectively. The results of RT-PCR paralleled those of immunohistochemistry. Concordance of high MDR-1/P-gp expression was noted in 27 of 34 samples (r = 0.73, P = 0.001). There were no significant changes in MDR-1/P-gp expression in all cases at relapse and during the clinical course following chemotherapy. In the 14 control cases, the average survival time was 12.7 months in MDR-1/P-gp positive cases and 29.0 months in the MDR-1/P-gp negative cases (P = 0.20).Our results showed that at least some B-cell lymphomas express MDR-1/P-gp, which could be detected by different methods, and suggested that high MDR-1/P-gp expression in tumour cells may be associated with a high probability of relapse and poor prognosis.