- Email: [email protected]
Keynote Lecture
Immune Reaction and Degeneration . 305
Keynote Lecture
113 ATYPICAL GLANDULAR FORMATIONS OF THE PROSTATE B. Helpap Institut fur Pathologie, Hegau-Klinikum, Singen A variety of small acinar lesions of the prostate ~an mimi~ pro~ate cancer in punch biopsies and transurethral resection material. First, differential diagnostic problems of the central and transition zone, including atypical adenomatous hyperplasia of the prostate, atrophic processes, sclerosing adenosis, basal cell hyperplasia, ~d I~w gra?e adenocarcinoma are discussed. The second part deals With differential diagnostic problems in the peripheral zone: prostatic intraepith~Iial neoplasia (PIN) postatrophic hyperplasia, Cowper's glands, semmal vesicles and ductal and intraductal carcinoma. Finally, atypical small acinar proliferations (ASAP) are described. A possible relationship between ASAP and low grade carcinoma, as it is already well documented in high grade PIN and high grade carcinoma is discussed.
Keynote Lecture 114 Update on the Pathology of Malignant Lung Tumors K.-M. MOller Institute of Pathology - BG Hospital Bergmannsheil - Ruhr-Universily Bachum - P.O. Bax 10 0250 - 0-44702 Bochum, Germany - EMAil [email protected]
The "new" 3 nJ WHO classification of lung tumors 1999 is described in nine groups of malignant broncho-pulmonary neoplasias. In recent years, our knowledge of the quite variable biology of tumors has been significantly increased by the use of immunohistochemical methods ond moleculor biology. These methods facilitated an improved qualitative and quantitative characterization of heterogeneously differentiated lung tumors (e.g., neuroendocrine I blastomatoid portions etc.]. The detection of genetic alterations of tumor suppressors (Rb / p53 / FIHT / TGFBR2 etc.) and oncogenes (e.g., myc / fos / blc-2 / ras / erbB etc.) is, at the moment, only of scientific interest. The genetic heterogeneity of tumors is emphasized by results obtained with the comparative genomic hybridization (CGH). In small-cell carcinomas of the lung more than seven voriable chromosomal alterations - especially loss of genetic material in the regions 3p, 10q, and 4q - can be detected in a tumor. Adenocorcinornos show losses of genetic material on chromosomes 9 and 19, and/or gains on chromosome 1. Squamous cell carcinomas frequently exhibit losses on chromosome 2 and gains on chromosome 3. A connection between the detected genetic anomalies and histomorphological growth pafferns can not be seen. At the present time, the validity of individual findings for a correlation between operability, tumor progress, chemotherapy and prognosis is not sufficiently elucidated by investigations nor secured. The histopathogical, immunohistochemical, and genetic characterization of specimens of, mostly advanced, lung tumors that show voriable phenotypes in biopsies of just 1·2 mm does not allow conclusions regarding causal factors (e.g., smoking, radon, asbestos etc.) or further progress of the disease. Therapeutical approach and the still unfavorable prognosis remain essentially, as in the last thirty years, to be choracterized by TNM and performance status of the individual patient and, to a lesser extent, by the main histological type of tumor.
Oral Presentation: Immune Reaction and Degeneration
115 Kiittners Tumour: an autoimmune driven process? Tiemann M, Teymoortash A, Schrader C, Seifert G*, Donath K*, Parwaresch R, Kloppel G Institut fur Pathologie, Christian-Albrechts-Universitat zu Kiel *Institut fur Pathologie, Universitat Hamburg Introduction: So called sclerosing sialadenitis is a chronic inflammation of the submandibular glands, the pathogenesis of which is unknown. Patients and methods:We analysed 22 biopsy specimens from the files of the salivary gland registry in Hamburg and the Dept. of Hematopathology in Kiel. Paraffin embedded tissue was immunostained with antibodies against CD3, CD4, CD8 for T cells, CD68 for macrophages and related subpopulations, CD20 and Ki-B3 for B-cells, and Granzyme b for cytotoxic cells. Moleculargenetical analysis was done with a seminested PCR for the hypervariable region CDRIII of the immunoglobulin heavy chain (lGH) and two multiplex PCR for detection of rearrangements of the T cell receptor (TCR) gamma chain. Results: In 13/22 cases intraepithelial macrophages were seen. In 9/22 cases, there were also plasmacytoid macrophages. Intraductal stones were not seen; one case showed a small necrosis. Number and distribution of macrophages was strongly related to the grade of fibrosis. In each case there were large numbers ofCD3 and CD8 positive intraepithelial T cells. Peri ductal foci of cytotoxic T cells with expression of granzyrne B were also seen, occasionally with epithelial damage. In 21 cases, Iymphoepithelial invasion by B cells was found. 20/22 cases showed germinal centre formation. Rearrangement studies revealed oligoclonal TCR rearrangements in 14/22 cases. Monoclonal IGH rearrangements were lacking; oligoclonal rearrangement patterns were seen in 5 cases. Conclusion: The demonstration of oligoclonal populations of cytotoxic T cells suggests, that sclerosing sialadenitis might result from an autoimmune process. Non 'Hodgkin's lymphoma seems not to be associated.
116 MOLECULAR ANALYSIS OF IgVH-GENES SUGGESTS THAT ANTIGENS INVOLVED IN SYNOVlALITIS OF OSTEOARTHROSIS AND RHEUMATOID ARTHRITIS ARE DIFFERENT V. Krenn, H-J. Kim, C. Berek, M.M. Souto Cameiro, F. Hensel, G. Ristow, A. Konig, H.K. Muller-Hermelink Institutut fur Pathologie, Orthopad, Klink Wurzburg, ORFZ Berlin Aims: B-lymphocytes and plasma cells participate in chronic synovialitis of osteoarthrosis (OA) and rheumatoid arthritis (RA). In order to understand the pathogenesis of synovialitis it would be interesting to know, how B-cells are activated in these two different diseases. Methods: IgVH gene repertoires were determined from RNA (OA, n~5) prepared from tissue cryosections and from isolated Blymphocytes and plasma cells (Pic) by micromanipulation. The data were compared with RA (rr-S), The B-cell environment was analysed immunhistochemically by detecting pic (wU2, IgM, IgG, IgA), Blymphocytes (C020) and follicular dendritic cells ~FDCs (Ki-M4) . Results: In small perivascular infiltrates of OA which are devoid of FDCs somatically highly mutated IgVH genes R\S:CDR~ LR!LS~5,3; FR LR!LS~2,0) could be detected which exhibited higher RlS ratios when compared to the large lymphatic follicular infiltrates with FDC networks of RA (R\S:CDR~LR!LS~3,4;FRLR!LS~1,7). B-Iympho cytes of OA exhibited higher numbers of somatic mutations (mean14,8) when compared to RA (mean- 4,35). Conclusions: The unexpected finding of highly mutated IgVH-genes in lymphocytic aggregates of OA synovial tissue which are devoid of FOCs suggests that already experienced B-lymphocytes (~memory Bcells) migrate into the synovial tissue. In OA patients the immune system is obviously dealing with already known antigens while in RA new antigens induce a local B-cell response leading to large lymphatic follicles with FOC networks. It is therefore suggested that antigens triggering synovialitis in OA and RA are different.
Keynote Lecture
113 ATYPICAL GLANDULAR FORMATIONS OF THE PROSTATE B. Helpap Institut fur Pathologie, Hegau-Klinikum, Singen A variety of small acinar lesions of the prostate ~an mimi~ pro~ate cancer in punch biopsies and transurethral resection material. First, differential diagnostic problems of the central and transition zone, including atypical adenomatous hyperplasia of the prostate, atrophic processes, sclerosing adenosis, basal cell hyperplasia, ~d I~w gra?e adenocarcinoma are discussed. The second part deals With differential diagnostic problems in the peripheral zone: prostatic intraepith~Iial neoplasia (PIN) postatrophic hyperplasia, Cowper's glands, semmal vesicles and ductal and intraductal carcinoma. Finally, atypical small acinar proliferations (ASAP) are described. A possible relationship between ASAP and low grade carcinoma, as it is already well documented in high grade PIN and high grade carcinoma is discussed.
Keynote Lecture 114 Update on the Pathology of Malignant Lung Tumors K.-M. MOller Institute of Pathology - BG Hospital Bergmannsheil - Ruhr-Universily Bachum - P.O. Bax 10 0250 - 0-44702 Bochum, Germany - EMAil [email protected]
The "new" 3 nJ WHO classification of lung tumors 1999 is described in nine groups of malignant broncho-pulmonary neoplasias. In recent years, our knowledge of the quite variable biology of tumors has been significantly increased by the use of immunohistochemical methods ond moleculor biology. These methods facilitated an improved qualitative and quantitative characterization of heterogeneously differentiated lung tumors (e.g., neuroendocrine I blastomatoid portions etc.]. The detection of genetic alterations of tumor suppressors (Rb / p53 / FIHT / TGFBR2 etc.) and oncogenes (e.g., myc / fos / blc-2 / ras / erbB etc.) is, at the moment, only of scientific interest. The genetic heterogeneity of tumors is emphasized by results obtained with the comparative genomic hybridization (CGH). In small-cell carcinomas of the lung more than seven voriable chromosomal alterations - especially loss of genetic material in the regions 3p, 10q, and 4q - can be detected in a tumor. Adenocorcinornos show losses of genetic material on chromosomes 9 and 19, and/or gains on chromosome 1. Squamous cell carcinomas frequently exhibit losses on chromosome 2 and gains on chromosome 3. A connection between the detected genetic anomalies and histomorphological growth pafferns can not be seen. At the present time, the validity of individual findings for a correlation between operability, tumor progress, chemotherapy and prognosis is not sufficiently elucidated by investigations nor secured. The histopathogical, immunohistochemical, and genetic characterization of specimens of, mostly advanced, lung tumors that show voriable phenotypes in biopsies of just 1·2 mm does not allow conclusions regarding causal factors (e.g., smoking, radon, asbestos etc.) or further progress of the disease. Therapeutical approach and the still unfavorable prognosis remain essentially, as in the last thirty years, to be choracterized by TNM and performance status of the individual patient and, to a lesser extent, by the main histological type of tumor.
Oral Presentation: Immune Reaction and Degeneration
115 Kiittners Tumour: an autoimmune driven process? Tiemann M, Teymoortash A, Schrader C, Seifert G*, Donath K*, Parwaresch R, Kloppel G Institut fur Pathologie, Christian-Albrechts-Universitat zu Kiel *Institut fur Pathologie, Universitat Hamburg Introduction: So called sclerosing sialadenitis is a chronic inflammation of the submandibular glands, the pathogenesis of which is unknown. Patients and methods:We analysed 22 biopsy specimens from the files of the salivary gland registry in Hamburg and the Dept. of Hematopathology in Kiel. Paraffin embedded tissue was immunostained with antibodies against CD3, CD4, CD8 for T cells, CD68 for macrophages and related subpopulations, CD20 and Ki-B3 for B-cells, and Granzyme b for cytotoxic cells. Moleculargenetical analysis was done with a seminested PCR for the hypervariable region CDRIII of the immunoglobulin heavy chain (lGH) and two multiplex PCR for detection of rearrangements of the T cell receptor (TCR) gamma chain. Results: In 13/22 cases intraepithelial macrophages were seen. In 9/22 cases, there were also plasmacytoid macrophages. Intraductal stones were not seen; one case showed a small necrosis. Number and distribution of macrophages was strongly related to the grade of fibrosis. In each case there were large numbers ofCD3 and CD8 positive intraepithelial T cells. Peri ductal foci of cytotoxic T cells with expression of granzyrne B were also seen, occasionally with epithelial damage. In 21 cases, Iymphoepithelial invasion by B cells was found. 20/22 cases showed germinal centre formation. Rearrangement studies revealed oligoclonal TCR rearrangements in 14/22 cases. Monoclonal IGH rearrangements were lacking; oligoclonal rearrangement patterns were seen in 5 cases. Conclusion: The demonstration of oligoclonal populations of cytotoxic T cells suggests, that sclerosing sialadenitis might result from an autoimmune process. Non 'Hodgkin's lymphoma seems not to be associated.
116 MOLECULAR ANALYSIS OF IgVH-GENES SUGGESTS THAT ANTIGENS INVOLVED IN SYNOVlALITIS OF OSTEOARTHROSIS AND RHEUMATOID ARTHRITIS ARE DIFFERENT V. Krenn, H-J. Kim, C. Berek, M.M. Souto Cameiro, F. Hensel, G. Ristow, A. Konig, H.K. Muller-Hermelink Institutut fur Pathologie, Orthopad, Klink Wurzburg, ORFZ Berlin Aims: B-lymphocytes and plasma cells participate in chronic synovialitis of osteoarthrosis (OA) and rheumatoid arthritis (RA). In order to understand the pathogenesis of synovialitis it would be interesting to know, how B-cells are activated in these two different diseases. Methods: IgVH gene repertoires were determined from RNA (OA, n~5) prepared from tissue cryosections and from isolated Blymphocytes and plasma cells (Pic) by micromanipulation. The data were compared with RA (rr-S), The B-cell environment was analysed immunhistochemically by detecting pic (wU2, IgM, IgG, IgA), Blymphocytes (C020) and follicular dendritic cells ~FDCs (Ki-M4) . Results: In small perivascular infiltrates of OA which are devoid of FDCs somatically highly mutated IgVH genes R\S:CDR~ LR!LS~5,3; FR LR!LS~2,0) could be detected which exhibited higher RlS ratios when compared to the large lymphatic follicular infiltrates with FDC networks of RA (R\S:CDR~LR!LS~3,4;FRLR!LS~1,7). B-Iympho cytes of OA exhibited higher numbers of somatic mutations (mean14,8) when compared to RA (mean- 4,35). Conclusions: The unexpected finding of highly mutated IgVH-genes in lymphocytic aggregates of OA synovial tissue which are devoid of FOCs suggests that already experienced B-lymphocytes (~memory Bcells) migrate into the synovial tissue. In OA patients the immune system is obviously dealing with already known antigens while in RA new antigens induce a local B-cell response leading to large lymphatic follicles with FOC networks. It is therefore suggested that antigens triggering synovialitis in OA and RA are different.