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Tot, T.; Tabár, L.; Dean, P. B.
doi: 10.1007/s004280000301pmid: 11097355
Mammography screening calls for a reevaluation of the working relationship between physicians dealing with the diagnosis and treatment of breast diseases. In this new era, histologic-mammographic correlation needs to be extended to correctly describe the deceptive mammographic findings that correspond to variations in normal breast tissue. Progress in histologic-mammographic correlation can only be made by overcoming the limitations inherent to the traditional histologic technique by examining a histologic specimen of greater length, width, and depth. There are several distinct advantages to using the large-section histology technique in the diagnosis of breast diseases. The subgross (three-dimensional) histology technique serves to bridge the gap that separates the pathologist and radiologist, bringing them to a common ground for a better understanding of breast morphology. These improvements in communication between the members of the diagnostic team will serve to optimize the sensitivity and specificity of breast cancer diagnosis.
Faverly, D.; Renard, F.; Drijkoningen, M.; Scheiden, R.
doi: 10.1007/s004280000254pmid: 11097359
Education and quality assurance (QA) in breast screening pathology have been encouraged by the Europe Against Cancer programme. As a prerequisite for the set-up of a QA programme in Belgium and in the Grand Duchy of Luxembourg, an inquiry was initiated to evaluate the daily practise in breast pathology, the modalities in handling and analysing breast specimens and the willingness of the pathologists to participate in a QA scheme. Of the 278 mailed questionnaires, 109 confidential and valid questionnaires were returned, meaning a participation rate of 40%. All 109 respondents indicated their willingness to voluntarily participate in the further QA programme. Segmental resections for conservative surgery and excision biopsies ranked first and second, respectively, in examination requests. Of the respondents, 50% complained about the lack of clinical information on the pathology request form. A multidisciplinary team approach for the diagnosis of screen-detected lesions was deemed desirable by 87% of the respondents, but only 16% of them actually participate in such pre-operative meetings. Even more puzzling is that 75% of the respondents report regular unavailability of the control radiogram of the surgical specimen removed for non-palpable lesions. One-quarter to one-third of the pathologists still regularly perform frozen sections on microcalcifications or tumours smaller than 1 cm. However, 81% of the respondents estimate that pre-operative diagnosis is not appropriate for this type of lesion. The results of this inquiry show that the guidelines for the diagnosis of screen-detected breast lesions are not yet fully applied in daily practise. The development of local comprehensive breast teams involving a pathologist should improve the co-ordination between the medical disciplines, represent an important way of disseminating the guidelines on breast screening pathology and stimulate the relay unit to conduct QA programmes.
Bussolati, G.; Bongiovanni, M.; Cassoni, P.; Sapino, A.
doi: 10.1007/s004280000267pmid: 11097360
Modern classifications of ductal in situ carcinoma (DCIS) of the breast suffer from unsatisfactory reproducibility in inter-observer circulation analyses. Ducts in DCIS are markedly enlarged in the range of 360 µm in diameter. Since the diffusion of oxygen from peri-ductal vessels is limited to 100 µm, cells in the center of DCIS are poorly oxygenated and become either necrotic or remain hypoxic but viable. There is evidence that such alternative fate is dictated by the biological characteristics of the neoplastic cells. Therefore, determination of presence or absence of necrosis in ducts up to 360 µm in diameter might represent a simple, reproducible, and biologically sound criterion to classify DCIS. In the present work, following this criterion, we classified 32 cases of intra-ductal lesions as either ”necrotic” or ”hypoxic” and tested the reproducibility of such classification using K statistics. These cases had already been circulated among a group of European pathologists, who classified the lesions using five different classifications. The K statistics value obtained with the presently proposed system was extremely high (0.91). It remains to be established whether the classification ”necrotic/hypoxic” withstands large inter-observer circulation analyses, whether it is predictive of the clinical evolution of DCIS, and whether it might constitute a reproducible basis for selecting appropriate treatments.
Riethdorf, L.; O’Connell, J. T.; Riethdorf, S.; Cviko, A.; Crum, C. P.
doi: 10.1007/s004280000273pmid: 11097361
The expression of mucin genes in the normal glandular epithelium of the endocervix has been well characterized. However, mucin gene expression in neoplastic or particular non-neoplastic glandular cervical lesions has not been addressed. This immunohistochemical study was carried out to analyze the expression of MUC2 and MUC5AC in neoplastic and non-neoplastic glandular lesions of the cervix. Monoclonal antibodies were used on paraffin-embedded sections from 41 adenocarcinomas, 2 adenosquamous carcinomas, 13 adenocarcinomas in situ (ACIS), 3 glandular dysplasias, 8 endometrioses, 5 tubal metaplasias, 17 squamous metaplasias, 3 microglandular hyperplasias and normal tissue of the endocervix, endometrium and fallopian tube. The patterns of expression of MUC2 and MUC5AC were different and in principle contrary. Focal MUC2 expression was observed almost exclusively in neoplastic lesions (36%) and not in normal epithelia and non-neoplastic lesions, the one notable exception being immature metaplasia. In contrast, strong expression of MUC5AC was observed in both normal endocervical epithelium (100%) and neoplastic lesions (73%). The expression of MUC5AC, however, was diminished in most neoplastic glandular lesions. Co-expression of MUC2 and MUC5AC was consistently documented in the lesions with intestinal differentiation. In contrast, cases of tubal metaplasia and endometriosis were negative for MUC2 and MUC5AC. These results indicate that discrimination of mucin gene expression may be helpful in discriminating lesions of the cervix.
Greiner, A.; Neumann, M.; Stingl, S.; Waßink, S.; Marx, A.; Riechert, F.; Müller-Hermelink, H. K.
doi: 10.1007/s004280000258pmid: 11097362
A new monoclonal antibody, Wue-1, which specifically recognizes normal and malignant plasma cells, is characterized. Biochemical studies showed that monoclonal antibodies (mAbs) recognize a protein of 94 kDa. Using triple-staining flow cytometry and double-labeling immunohistochemical techniques, two populations of plasma cells, i.e. lymphoplasmocytoid plasma cells located in the germinal center of lymphoid organs and reticular plasma cells at the paracortex or medullary cords of secondary lymphoid tissues, were distinguished. Wue-1 is expressed when B-cell markers become lost and secretory activity with plasma cell morphology appears. Cell surface markers were identified on normal plasma cells and compared with their malignant counterpart in vivo. Terminal plasma–cellular differentiation of malignant low- and high-grade B-cell lymphoma and anaplastic plasmacytoma, otherwise difficult to identify with conventional B-cell markers on tissue sections or fluorescence-activated cell sorter analyses, were detectable by Wue-1. In cell culture, Wue-1 enhanced the proliferation of myeloma cell lines but not normal plasma cells in a dose-dependent manner. Since Wue-1-induced proliferation was increased by interleukin (IL)-6, Wue-1 recognizes a so far unidentified antigen with functional properties. Therefore, Wue-1 represents a useful new tool for therapy and for the in vivo and in vitro studying of B-cell lymphomas and the mechanisms of B-cell differentiation.
Huss, R.; Haas, C.; Herrmann, M.; Kalden, J. R.; Löhrs, U.
doi: 10.1007/s004280000256pmid: 11097363
Systemic lupus erythematosus (SLE) is characterized by a variety of autoantibodies and other immune abnormalities indicative of an immunological hyperactivity. Antibodies against native DNA, however, are a disease-specific marker and play a major role in the pathogenesis of systemic or organ-specific disease manifestations. Nevertheless, the mechanisms causing the appearance of autoantibodies and immune complexes in SLE are not yet understood. Here, we report that chromosomal DNA and other forms of nucleic acids are usually cleared from circulation by binding to a yet unidentified receptor-like protein on the surface membrane of erythrocytes, independently from complement or antibodies. The binding kinetics of DNA and other nucleic acids to erythrocytes are significantly altered in SLE patients, showing an overall reduced binding capability and presaturated binding kinetics. Significant amounts of chromosomal DNA can be isolated from erythrocytes of SLE patients but not from normal controls. Electron microscopy shows electron-dense particles on the surface of SLE erythrocytes (approximate size 20–40 nm). Comparative genomic hybridization reveals that the nucleic acid isolated from erythrocytes of SLE patients is of genomic and random origin, leading to an accumulation of ”free” nucleic acids in the periphery, which eventually induces a B-cell immune response.
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