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Harald Stein – One of the best experts on this subject based on the ideXlab platform.

  • plasmacellular differentiation in extranodal marginal zone b cell lymphomas of the ocular Adnexa an analysis of the neoplastic plasma cell phenotype and its prognostic significance in 136 cases
    British Journal of Ophthalmology, 2005
    Co-Authors: Sarah E. Coupland, Ioannis Anagnostopoulos, Martin Hellmich, Claudia Auwhaedrich, Harald Stein


    Aim: To determine (a) the expression of plasma cell related antigens in extranodal marginal zone B cell lymphomas (EMZL) of the ocular Adnexa; and (b) the prognostic value of plasmacellular differentiation in these tumours.

    Methods: A consecutive case series of 136 ocular Adnexal EMZL obtained from three ocular pathology centres over 20 years was analysed retrospectively. An extensive immunohistochemical panel, including the plasma cell related antigens VS38c, CD38, CD138, multiple myeloma oncogene-1-protein (MUM1/IRF4), and CREB binding protein (CBP) was performed. EMZL were defined as “plasmacellular differentiated” on the basis of morphological features, evidence of cytoplasmic immunoglobulin, negativity for BSAP/PAX5, and expression of at least one of the investigated plasma cell related antigens. Controls included normal or hyperplastic lymphatic tissues. Detailed clinical data were collected for most patients, and compared with the results of immunohistochemistry. The end points considered for statistical analysis were development of local tumour recurrence, development of systemic disease, and lymphoma related death.

    Results: 57 (42%) of the 136 ocular Adnexal EMZL showed a plasmacellular differentiation; 45 of these plasmacytoid cases were primary tumours. In contrast with most admixed normal plasma cells, which displayed co-expression of MUM1/IRF4, Vs38c, CD38, CD138, and CBP, the plasmacellular differentiated EMZL tumour cells demonstrated co-expression of all five plasma cell related antigens in only six of 57 (11%) plasmacellular differentiated ocular Adnexal EMZL. The most commonly expressed plasma cell related antigen was MUM1/IRF4, immunoreactivity being seen in 56/57 (98%) plasmacellular differentiated EMZL examined. Although the association of plasmacellular differentiation in primary ocular Adnexal EMZL and disseminated disease was statistically significant on univariate analysis (p = 0.042), this was weaker on multivariate analysis.

    Conclusion: Plasmacellular differentiated tumour cells in EMZL demonstrate an aberrant immune profile for plasma cell related antigens when compared with normal plasma cells. On multivariate analysis, plasmacellular differentiation in ocular Adnexal EMZL was not significantly associated with local recurrence, the development of systemic disease, or with lymphoma related death.

  • immunoglobulin vh gene expression among extranodal marginal zone b cell lymphomas of the ocular Adnexa
    Investigative Ophthalmology & Visual Science, 1999
    Co-Authors: Sarah E. Coupland, Ioannis Anagnostopoulos, Hans Dieter Foss, Michael Hummel, Harald Stein


    PURPOSE. Most lymphomas of the ocular Adnexa are primary extranodal non-Hodgkin’s lymphomas of the B-cell type, with the most common lymphoma subtype being the extranodal marginal-zone B-cell lymphoma (EMZL). Analysis of somatic mutations in the variable (V) region of the Ig heavy (H)-chain gene segment suggests that EMZL development in other locations is dependent on antigen stimulation. The purpose of this study was to analyze the presence of somatic hypermutations in clonally rearranged Ig H-chain V genes of this lymphoma entity in the ocular Adnexa and to estimate whether the mutation pattern is compatible with antigen selection. METHODS. Twenty-six eases of EMZL of the ocular Adnexa were diagnosed on the basis of morphology, histology, and immunohistology. A nested polymerase chain reaction (PCR) was performed on DNA extracted from paraffin sections. The isolated PCR products were sequenced and compared with published V H germline segments to determine the number of somatic mutations in the complementarity-determining region (CDR) 2 and framework (FW) region 3. RESULTS. The number of somatic mutations in the cases of EMZL varied between 0 and 24: Five cases involved 0 to 3 somatic mutations, and the remaining 21 cases involved 4 to 24 mutations. Based on the ratio of replacement (R) to silent (S) mutations in the CDR2 or FW3 regions, antigen selection seems to have occurred in 60% of ocular Adnexal EMZL. The V H 3 family was the most commonly expressed germline V H family (54%), followed by V H 4 (23%), with biased usage of the latter. Some germline V H genes used included DP-8, DP-10, DP-53, DP-63 (V H 4.21), and DP-49, which are frequently used by autoantibodies (e.g., rheumatoid factors) and natural autoantibodies. CONCLUSIONS. EMZLs of the ocular Adnexa have an Ig H-chain mutation pattern that supports the concept that they represent a clonal expansion of post-germinal-center memory B-cells in most instances. In two thirds of cases, antigen selection may have occurred, and autoantibodies may have a role in their development.

  • lymphoproliferative lesions of the ocular Adnexa analysis of 112 cases
    Ophthalmology, 1998
    Co-Authors: Sarah E. Coupland, L Krause, Henrijacques Delecluse, Ioannis Anagnostopoulos, Hans Dieter Foss, Michael Hummel, Norbert Bornfeld, William R Lee, Harald Stein


    Abstract Objective Lymphoproliferative lesions of the ocular Adnexa were analyzed to examine (1) the suitability of the Revised European-American Lymphoma (REAL) classification for the subtyping of the lymphomas in these sites; (2) the predictive value of the REAL classification for the evolution of these tumors; and (3) the frequency and prognostic impact of tumor type, location, proliferation rate (Ki-67 index), p53, and CD5 positivity and the presence of monoclonality within these tumors. Design Retrospective review. Methods The clinical, histomorphologic, immunohistochemical, and molecular biologic (polymerase chain reaction [PCR]) features of lymphoid proliferations of the ocular Adnexa were studied. Study materials The ocular Adnexal lymphoproliferative lesions were located as follows: orbit in 52 patients (46%), conjunctiva in 32 patients (29%), eyelid in 23 patients (21%), and caruncle in 5 patients (4%). Results Reactive lymphoid hyperplasia was diagnosed in 12 cases and lymphoma in 99 cases; 1 case remained indeterminate. The five main subtypes of lymphoma according to the REAL classification were extranodal marginal-zone B-cell lymphoma (64%), follicle center lymphoma (10%), diffuse large cell B-cell lymphoma (9%), plasmacytoma (6%), and lymphoplasmocytic lymphoma (5%). Age, gender, and anatomic localization of the lymphomas did not have prognostic significance during a follow-up period of 6 months to 16.5 years (mean, 3.3 years). Extent of disease at time of presentation was the most important clinical prognostic factor: advanced disease correlated with increased risk ratios of having persistent disease at the final follow-up and with lymphoma-related death ( P P P P P Conclusion The REAL classification is suitable for the subdivision of the ocular Adnexal lymphomas. The MIB-1 proliferation rate and p53 positivity may aid the prediction of disease stage and disease progression, whereas PCR can support the diagnosis and reduce the number of histologically indeterminate lesions.

Steven H Swerdlow – One of the best experts on this subject based on the ideXlab platform.

  • use of similar immunoglobulin vh gene segments by malt lymphomas of the ocular Adnexa
    Modern Pathology, 2009
    Co-Authors: David W Bahler, Philippe Szankasi, Sucheta Kulkarni, Raymond R Tubbs, James R Cook, Steven H Swerdlow


    Extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue type (MALT lymphomas) develop from acquired reactive infiltrates directed against external or autoantigens. Although some European cases of ocular Adnexal MALT lymphoma have been associated with Chlamydia psittaci infections, C. psittaci has not been detected in large studies of US-based cases. To evaluate whether the growth of US-based ocular Adnexal MALT lymphomas may be promoted by a similar antigen, we identified and analyzed the expressed immunoglobulin VH genes in 10 cases. Interestingly, the VH genes in two cases used the same VH1 family V1-2 gene segment, and three cases used the same VH4 family V4-34 gene segment. The other five cases all used different gene segments V4-31, V5-51, V3-23, V3-30, and V3-7. All of the VH genes were mutated from germ line, with percent homologies ranging between 96.9 and 89.0%. The distribution of replacement and silent mutations within the VH genes was nonrandom consistent with the maintenance of immunoglobulin function and also strongly suggestive of antigen selection in the six VH genes with highest mutation loads. The CDR3 sequences in two of three VH-34 cases were the same size (15 amino acids) and had similar sizes in the two VH1-2 cases (18 and 16 amino acids). In conclusion, US-based MALT lymphomas of the ocular Adnexa preferentially express a limited set of VH gene segments not frequently used by other MALT lymphomas and consistent with some recognizing similar antigens. Analysis of somatic mutations present within the VH genes is also consistent with antigen binding stimulating the growth of these lymphomas.

Gabriel Oelsner – One of the best experts on this subject based on the ideXlab platform.

  • Minimal surgery for the twisted ischaemic Adnexa can preserve ovarian function
    Human Reproduction, 2003
    Co-Authors: Gabriel Oelsner, Shlomo B. Cohen, David Soriano, Dahlia Admon, Shlomo Mashiach, Howard Carp


    BACKGROUND: Recently detorsion has replaced salpingo-oophorectomy as treatment for the twisted ischaemic Adnexa. This paper asssess whether the ovary resumes normal function after preservation by detorsion. METHODS: The results of detorsion performed between January 1988 and December 2001 were retrospectively analysed. Post-operative complications and subsequent ovarian function were assessed including: ultrasound monitoring of follicular development, Adnexal appearance during subsequent surgery, and the outcome of IVF. RESULTS: A total of 102 detorsions were performed; 67 by laparoscopy, 35 by laparotomy. No patient developed thromboembolism. Post-operative fever occurred in 15% of patients after laparoscopy and 29% after laparotomy (P < 0.01). Patients were hospitalized for a mean (6 SD) of 2.1 6 1.2 and 7.4 6 1.5 days after laparoscopy and laparotomy respectively (P < 0.001). Ultrasound showed normal follicular development in 93 and 91% of patients after detorsion by laparoscopy and laparotomy respectively. At subsequent surgery, the Adnexa appeared normal in nine out of nine patients after laparoscopy and in four out of five patients after laparotomy. Four patients of the laparoscopy group and two patients of the laparotomy group underwent subsequent IVF. In all six patients oocytes retrieved from the previously ischaemic ovary were fertilized. CONCLUSIONS: Detorsion with Adnexal sparing is the treatment of choice for twisted ischaemic Adnexa, and preferably performed by laparoscopy.

  • laparoscopy versus laparotomy for detorsion and sparing of twisted ischemic Adnexa
    Jsls-journal of The Society of Laparoendoscopic Surgeons, 2003
    Co-Authors: Shlomo B. Cohen, Dahlia Admon, Shlomo Mashiach, Mordechai Goldenberg, Daniel S. Seidman, Arnaud Wattiez, Gabriel Oelsner


    BACKGROUND Torsion of the ovary is an urgent event for fertile women. Until recent years, the common treatment for twisted ischemic ovaries was salpingo-oophorectomy. We have demonstrated in the past that the ovary can be salvaged provided detorsion is performed. We studied the outcome of women undergoing minimal surgery for ischemic ovaries versus the extended procedure including cystectomy in respect of ovarian function and fertility performance. METHODS We retrospectively studied 102 women who underwent surgery for torsion of the ovary in which the macroscopic appearance of black-bluish ischemic Adnexa was encountered during surgery. Detorsion without removal of the Adnexa or the ovary was performed by laparoscopy in 67 patients and by laparotomy in 35 patients. Patients’ files were reviewed for immediate and late outcomes. Patients were examined postoperatively with vaginal ultrasound for ovarian follicular function. Data concerning patients’ further surgeries or in vitro fertilization were retrieved from the charts as well. RESULTS Febrile morbidity was approximately 15% and 29% in the laparoscopy and laparotomy groups, respectively. Hospital stay was 2.1 +/- 1.2 and 7.4 +/- 1.5 days in the laparoscopy and laparotomy groups, respectively (P<0.001). Ultrasound follow-up was available in 60 of 67 patients who underwent laparoscopy and in 32 of 35 patients treated by laparotomy. Normal-sized ovaries with follicular development were encountered in the detorsed side in 93% and 91%, respectively. Normal macroscopic appearance of the Adnexa at subsequent surgeries was reported in 9 of 9 patients in the laparoscopy group and in 4 of 5 patients in the laparotomy group. Four patients from the laparoscopy group and 2 from the laparotomy group underwent subsequent in vitro fertilization. In all 6 patients, oocytes retrieved from the previously detorsed ovary were fertilized. In both groups, none of the patients developed clinical signs of pelvic or systemic thromboembolism. CONCLUSIONS Torsion of the ischemic Adnexa should be treated laparoscopically by detorsion and Adnexal sparing.

  • Laparoscopic detorsion allows sparing of the twisted ischemic Adnexa.
    Journal of The American Association of Gynecologic Laparoscopists, 1999
    Co-Authors: Shlomo B. Cohen, Gabriel Oelsner, Dahlia Admon, Shlomo Mashiach, Daniel S. Seidman, Mordechai Goldenberg


    Abstract Study Objective. To determine the safety and outcome of laparoscopic detorsion in the management of the twisted ischemic, hemorrhagic Adnexa. Design. Retrospective chart review and prospective follow-up (Canadian Task Force classification II-2). Setting. University-affiliated hospital. Patients. Fifty-eight women with twisted black-bluish ischemic Adnexa encountered at laparoscopy. Intervention. Laparoscopic detorsion with Adnexal sparing. Measurements and Main Results. All patients had a benign immediate postoperative course. Transient temperature elevation occurred in seven women (12.1%). No signs of pelvic or systemic thromboembolism were detected in any patient. Long-term follow-up included transvaginal ultrasound, which revealed follicular development in the previously twisted Adnexa in 54 women; normal macroscopic appearance at incidental subsequent surgery in 9; and in vitro fertilization with retrieval of oocytes from the previously twisted side in 4. Conclusion. Laparoscopic detorsion of the twisted ischemic, hemorrhagic Adnexa is a safe procedure with minimal postoperative morbidity and a potential for the ovary to recuperate fully with preservation of normal function. Laparoscopic Adnexa-sparing procedures should be performed in place of traditional salpingo-oophorectomy in women with this disorder who desire future fertility.