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Biomedical subjects

A C Feller

Publications and source records attributed to A C Feller.

At least 37 records · Page 2Linked to original sources

Classification of malignant lymphoma.

Over the past 30 years different lymphoma classifications were used world-wide. In Europe, the Kiel classification of K. Lennert dominated the scene, it was updated 1988 and 1992. In North America the Working Formulation, primarily designed to be an instrument for translation of one classification into the other, was predominantly used. Both classifications, however, showed little correspondence with each other, which made it difficult to compare the results of randomized clinical trials on both sides of the Atlantic Ocean. In 1994 the Revised European American Lymphoma (R.E.A.L.) classification was proposed by the International Lymphomas Study Group (ILSG). In contrast to the existing classifications it abandoned the grading of malignancies. The ILSG focused on diagnostic reproducibility and on the definition of distinct clinical-pathological lymphoma entities. Similar to the Kiel classification the new classification scheme was based on cell lineage (T- and B-cell origin) and cell differentiation (precursor and mature lymphomas) and included a number of distinct extranodal lymphomas. The new WHO classification is basically identical with the R.E.A.L. scheme and exhibits only minor changes. The WHO classification includes all hematopoietic and lymphoid neoplasms. It represents the first generally accepted classification, providing hematologists and oncologists with a solid diagnostic basis for therapeutic decisions.

Europe↗

[Pathology of vasculitis: differential diagnosis and selected disorders].

The morphological diagnosis of vasculitis is a challenge for the pathologist for many reasons. Primary systemic vasculitides are rare diseases (ann. incidence 4-5/100,000 according to the Vaskulitis-Register Schleswig-Holstein), pathognomonic histopathological findings are hard to obtain in many patients even with multiple biopsies, and the nomenclature of vasculitis has long been confusing and unequivocal. The Chapel-Hill Consensus Conference (1992) is credited with the establishment of clinico-pathological definitions for primary systemic vasculitides. For the discrimination of primary systemic vasculitis from secondary vasculitis as well as pseudovasculitic syndromes, correlation with clinical data is essential; it has been facilitated by the American College of Rheumatology (ACR) classification criteria (1990). Differential diagnostic schemes for vasculitis are based on the predominant type and size of the blood vessel involved, as well as the histopathological type of inflammation and the presence or absence of immune complex deposits. However, differential diagnostic problems remain: even with the clarified nomenclature of Chapel-Hill, considerable overlap still occurs. A clinical diagnosis of vasculitis is now often established in an earlier disease stadium, in part of the cases facilitated by ANCA testing; the pathologist may therefore at first be confronted with a more subtle or abortive morphology, while in the course of disease, histopathology is modulated by immunosuppressive therapy. A number of immunopathogenic mechanisms prevailing in vasculitis can be verified with immunohistochemical and molecular biological methods, although it is frequently not known how they are initiated and perpetuated. ANCA-associated vasculitides serve as a good example to demonstrate the central role of morphology, its potentials but also its limitations in the differential diagnosis of vasculitis.

Diagnosis, Differential↗

Gain of chromosome arm 9p is characteristic of primary mediastinal B-cell lymphoma (MBL): comprehensive molecular cytogenetic analysis and presentation of a novel MBL cell line.

Primary mediastinal B-cell lymphoma (MBL) is an aggressive Non-Hodgkin's Lymphoma, which has been recognized as a distinct disease entity. We performed a comprehensive molecular cytogenetic study analyzing 43 MBLs. By comparative genomic hybridization (CGH), the most common aberrations were gains of chromosome arms 9p and Xq, which were present in 56% and 40% of cases, respectively. Based on the limited resolution of CGH, this technique may underestimate the real incidence of aberrations. Therefore, we also did an interphase cytogenetic study with eight DNA probes mapping to chromosome regions frequently altered in B-cell lymphomas. With this approach, both 9p and Xq gains were found in more than 70% of cases (75% and 87%, respectively). The findings were compared with results obtained in 308 other B-cell lymphomas. Gains in 9p were identified in only six of the 308 cases, and only one of these lymphomas with 9p gains was not primarily extranodal in origin (P < 10-(20) for CGH data and P < 10-(11) for fluorescence in situ hybridization data). We also present a novel MBL cell line, MedB-1, which carries the genetic aberrations characteristic of this entity.

Adolescent↗

[Large nodular lymphomatoid papulosis associated with parakeratosis variegata].

A 63 year old man suffering from lymphomatoid papulosis in association with parakeratosis variegata over a period of 20 years is presented. This case is unusual in respect to long-standing history, the rare combination of the two entities, and the extraordinary size of the nodules of lymphomatoid papulosis. Extracorporal photopheresis has induced partial remission lasting up to nine months so far.

Humans↗

Over-expression of wild-type Rad51 correlates with histological grading of invasive ductal breast cancer.

Breast cancer is a major cause of cancer-related death in women. BRCA1 tumour-suppressor function is abolished in sporadic breast cancer by down-regulation of the protein level. This down-regulation inversely correlates with tumour grading. BRCA1 is part of a multiprotein complex, which also contains the recombination factor Rad51. Here we describe that in contrast to BRCA1, histological grading of sporadic invasive ductal breast cancer significantly correlates with over-expression of wild-type Rad51. These data suggest that in addition to the absence of the tumour-suppressor protein BRCA1, over-expression of wild-type Rad51 also contributes to the pathogenesis of a significant percentage of sporadic breast cancers and that other mechanisms than mutations must be responsible for this altered expression.

BRCA1 Protein↗

Accuracy, concordance, and reproducibility of histologic diagnosis in cutaneous T-cell lymphoma: an EORTC Cutaneous Lymphoma Project Group Study. European Organization for Research and Treatment of Cancer.

OBJECTIVE: To assess the level of observer variability in the histologic identification of cutaneous T-cell lymphoma (CTCL) and its discrimination from diseases with similar histologic features. DESIGN: Cutaneous T-cell lymphoma specimens and randomly mixed controls were evaluated twice by 3 examiners. SETTINGS: The European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Project Group. PATIENTS: The study was conducted with histologic specimens from 32 patients with mycosis fungoides (MF). In addition, 13 specimens of spongiotic, lichenoid, or psoriasiform simulators of MF were blindly and randomly mixed with the CTCL specimens as controls. MAIN OUTCOME MEASURES: To evaluate the accuracy and concordance among and individual reproducibility of raters of histologic diagnoses. RESULTS: Overall, the concordance among raters was fair to moderate (range, 0.283-0.562; weighted overall kappa, 0.412). Individual reproducibility of examiners ranged from moderate to almost perfect (range, 0.473-0.896; weighted overall kappa, 0.709) and was not significantly different for the definite lymphoma (range, 0.551-0.921; overall kappa, 0.802) and nonlymphoma (range, 0.368-0.950; overall kappa, 0.793) categories. Accuracy was similarly variable among raters: sensitivity ranged from 49.3% to 78.1% (overall kappa, 0.654), and specificity (control series) ranged from 46.2% to 69.2% (overall kappa, 0.595). Adding the diagnoses of probable lymphoma to those of definite lymphoma, sensitivity ranged between 73.5% and 84.9%. Although for each examiner there was a trend toward a lower sensitivity in the detection of early lesions compared with later lesions, the difference in sensitivity between the 2 groups was not statistically significant. CONCLUSIONS: The levels of concordance and reproducibility found in this investigation were similar to those obtained with comparable studies in the most varied fields of pathology, confirming that the identification of CTCL for our observers did not cause particular problems. Our findings also revealed that pitfalls in CTCL identification are not only limited to early lymphomatous lesions, as commonly postulated.

Biopsy↗

Localized Wegener's granulomatosis: predominance of CD26 and IFN-gamma expression.

The immune response in Wegener's granulomatosis (WG) has been characterized as a predominant, potentially pathogenic Th1-like reaction by blood T cells and T-cell clones from diseased tissues. To elucidate further the immunopathogenic mechanisms, this study analysed the phenotypes of inflammatory infiltrates in frozen nasal biopsies with involvement of the upper respiratory tract only (localized or 'initial phase' WG) and with multi-organ involvement, including systemic vasculitis (generalized WG). The expression and production of Th1 and Th2 cytokines were examined in tissue specimens and peripheral blood mononuclear cells (PBMCs) of localized and generalized WG. The number of CD3+ T cells in inflammatory infiltrates ranged from 50 to 70%, together with approximately 30% CD14+ monocytes/macrophages. An average of 40% of T cells expressed CD26 in nasal biopsies of localized WG, compared with about 16% in specimens of generalized WG. In parallel, a higher number of interferon-gamma (IFN-gamma)-positive cells were detected in nasal tissue of localized than in generalized WG. PBMCs from localized WG similarly exhibited higher spontaneous IFN-gamma production in contrast to generalized WG (207 vs. 3 pg/ml, p<0.05). Interleukin-4 (IL-4) mRNA was found in higher amounts in generalized than in localized WG. IL-4 production was negligible in both disease and controls. In addition, both IL-10 mRNA and IL-10 protein levels of activated PBMCs from localized WG were elevated when compared with generalized disease (574 vs. 154 pg/ml, p<0.05) or healthy controls (574 vs. 246 pg/ml, p<0.05). It is conluded that in nasal tissues, mainly CD4+/CD26+ T cells as well as IFN-gamma-positive cells may support a polarized Th1-like immune response. Furthermore, the data suggest that this in situ immune response is already initiated and established in localized WG, accompanied by increased peripheral IFN-gamma and IL-10 production.

Adolescent↗

T-cell/natural killer cell lymphoblastic lymphoma with an unusual coexpression of B-cell antigens.

Lymphoblastic lymphomas are usually B- or T-cell neoplasms. There exists a small group of T-cell lymphomas additionally coexpressing cytotoxic or natural killer (NK)-cell markers, supporting the hypothesis of a common T/NK-cell precursor and respective neoplasms. Clinically, lymphatic neoplasms of T/NK-cell phenotype are either extranodal lymphomas or acute leukemias. The clinical course of these T/NK neoplasms cannot be predicted by morphology and/or phenotype alone. However, the expression of a heterogeneous (T + NK or myeloid) marker profile or of "early" antigens (such as TdT, CD10, RAG1, RAG2) render them more likely to be in the acute leukemia group. We present a case of a 63-year-old woman with a bone marrow infiltrate, enlarged lymph nodes, and B-symptoms. A cervical lymph node biopsy showed a monomorphic blastic infiltrate with a T-cell phenotype, coexpressing NK markers (CD56, CD57, NK1) and B-cell antigens (CD20, CD79). To the best of our knowledge, this is a newly recognized phenotype that has not been reported before. T/NK-cell lymphomas, including blastic NK-cell leukemia/lymphoma and T-lymphoblastic lymphomas, have to be included in the differential diagnosis. Both groups have a different clinical behavior and prognosis. In particular, T/NK-cell lymphomas associated with an Epstein Barr virus infection are clinically very aggressive neoplasms.

Antigens↗

[Angiomyolipoma of the lung].

We present a case of a 48 year old man who complained of progressive dyspnoea. Radiograph revealed a large tumor in the left lung. Biopsy was performed and revealed beneath a normal bronchial epithelium polymorph tumor cells admixed with some histiocytes. These tumor cells were strongly pigmented and expressed HMB-45 and protein S-100 immunohistochemically. Malignant melanoma of the bronchus was included in the differential diagnosis. A thoracotomy and left lower lobe resection was performed. Histology revealed an angiomyolipoma. The lung is an uncommon localisation of angiomyolipoma with so far three reported cases. Lipoma, leiomyoma and lymphangioleiomyomatosis have to be included in the differential diagnosis. The peculiarity of this case is the presence of multiple pigmented tumor cells that express HMB-45. This has not been reported yet.

Angiomyolipoma↗

An animal model for anaplastic large cell lymphoma in the immunocompetent syngeneic C57Bl/6 mouse.

We report on the analysis of a murine anaplastic lymphoid cell line TS1G6, established recently by interleukin (IL)-9 transfection. TS1G6 revealed a highly characteristic pattern of large anaplastic cells with mononuclear, binuclear, or multinuclear cells resembling Hodgkin (H) or Sternberg-Reed (SR) cells. This cell line is tumorigenous after injection of as few as 10(4) lymphoma cells into nude or immunocompetent C57Bl/6 mice and leads to death from progressive disease of all treated animals within a few weeks. The histological analysis of these tumors revealed a diffuse large cell malignant lymphoma that is morphologically almost identical to human anaplastic large cell lymphoma (ALCL). The lymphoma cells did not show overexpression of the anaplastic lymphoma kinase (ALK) gene, which is found in about 50% of the cases of human ALCL. Thus, this model may be an animal model for an important subset of human ALCL. The cytokine profile, which is of the T helper 2 type, showed strong parallels to the human lymphoma counterpart. Mice suffering from such lymphomas could not be cured with a regimen using high dose cyclophosphamide similar to many ALCL patients. Such an animal model for ALCL has not yet been recognized, but may provide the basis for investigating new antitumor immunotherapies in a fully immunocompetent host.

Anaplastic Lymphoma Kinase↗

Efficacy of histologic criteria for diagnosing early mycosis fungoides: an EORTC cutaneous lymphoma study group investigation. European Organization for Research and Treatment of Cancer.

The correct classification of lymphoproliferative disorders provides valuable information regarding subsequent clinical evolution of the disease. The ability of pathologists to distinguish such lesions is generally low, especially when dealing with minimal lymphoid infiltrates. To improve the efficacy of histopathology in the diagnosis of early lesions of mycosis fungoides (MF), we reviewed 24 skin biopsies from 18 patients with patch stage lesions of MF early in the course of their disease and 13 slides of lichenoid, spongiotic, or psoriasiform simulators of MF as a control series. A series of cytoarchitectural features was assessed, and differences in the distribution of histopathologic parameters between the two groups (early MF lesions and MF simulators) were evaluated by the chi-square test and Fisher's exact test. For these parameters, sensitivity and specificity also were calculated. A multivariate log-linear analysis was performed to estimate which of the morphologic parameters yielded independent diagnostic information. We found that the most important feature for the diagnosis of lymphoma was the presence of lymphocytes with extremely convoluted, medium-large (7-9 microm in diameter) nuclei (medium-large cerebriform cells), singly or clustered in the epidermis and in small sheets in the dermis. Additional significant histologic features were epidermotropism as single cells lined up along the basal keratinocytes of the dermal-epidermal junction, absence of significant papillary dermis fibrosis, and absence of significant numbers of dermal blastlike cells. We conclude that the efficacy of single histopathologic features in the diagnosis of early MF is generally poor. Only the presence of medium-large cerebriform cells in the epidermis or in clusters in the dermis proved to be a highly reliable feature. However, the histopathologic diagnosis of early MF lesions and their discrimination from inflammatory simulators can be achieved using the constellation of cytoarchitectural parameters proposed.

Biopsy↗

Deciduoid pleural mesothelioma affecting a young female without prior asbestos exposure.

Pleural mesothelioma is commonly associated to asbestos exposure. A 40-year-old woman is described who presented with shortness of breath. She had a smoking history but no history of asbestos exposure. Chest radiography and computed tomography showed a large tumour on the right lower lung. An open pleural biopsy was performed. A metastatic adenocarcinoma of the pleura was primarily diagnosed. The tumour progressed and after surgical excision an accurate histological and immunohistochemical examination was performed. It revealed a pleural mesothelioma with a deciduoid differentiation that has not been described before.

Adenocarcinoma↗

[New immunotherapeutic approaches for the treatment of anaplastic large cell lymphoma in a mouse model].

As there is still a high mortality of the large cell anaplastic non Hodgkin lymphoma (ALCL) (between 40-70%, depending on prognostic factors) there is a need for new therapeutic approaches. Therefore, we studied different strategies for cancer immunotherapy in an immunogenic ALCL tumor model system: A murine IL-9 dependent T cell line was transfected with IL-9 cDNA, resulting in an autonomous growing T cell line designated G6BB, which had a high tumor incidence after injecting of as few as 10(4) cells subcutaneously into syngeneic C57Bl/6 mice. Tumor growth, dissemination, histology, and immunohistochemistry were similar to human ALCL. This mouse model provides an immunogenic in vivo system to investigate antitumor immunotherapies. In order to increase antigen recognition by T cells and T cell activation, we administered tumor bearing mice cell-based cancer vaccines with irradiated tumor cells alone or in combination with immunostimulating CpG-Oligonucleotides, a combination of Th1 cytokines and Th2 cytokine antibodies (IL-12, IFN-gamma, GM-CSF, Anti-IL-10) (after detecting a Th2 cytokine profile in G6BB), or the recall antigens diphtheria, pertussis, and tetanus.

Animals↗

Detection of Chlamydia pneumoniae but not cytomegalovirus in occluded saphenous vein coronary artery bypass grafts.

BACKGROUND: A causal relation between atherosclerosis and chronic infection with Chlamydia pneumoniae and/or cytomegalovirus (CMV) has been suggested. Whether the unresolved problem of venous coronary artery bypass graft occlusion is related to infection with C pneumoniae and/or CMV has not been addressed. METHODS AND RESULTS: Thirty-eight occluded coronary artery vein grafts and 20 native saphenous veins were examined. Detection of C pneumoniae DNA was performed by use of nested polymerase chain reaction (PCR). Homogenisates from the specimen were cultured for identification of viable C pneumoniae. Both conventional PCR and quantitative PCR for detection of CMV DNA were applied. Differential pathological changes (degree of inflammation, smooth muscle cell proliferation [MIB-1]) were determined and correlated to the detection of both microorganisms. C pneumoniae DNA could be detected in 25% of occluded vein grafts. Viable C pneumoniae was recovered from 16% of occluded vein grafts. Except for 1 native saphenous vein, all control vessels were negative for both C pneumoniae detection and culture. All pathological and control specimens were negative for CMV DNA detection. Pathological changes did not correlate with C pneumoniae detection. CONCLUSIONS: Occluded aorto-coronary venous grafts harbor C pneumoniae but not CMV. The detection of C pneumoniae in occluded vein grafts warrants further investigation.

Adult↗

Wegener's granulomatosis associated with renal cell carcinoma.

OBJECTIVE: To determine the frequencies and types of malignant neoplasms occurring before or simultaneously with the diagnosis of Wegener's granulomatosis (WG), and to test for the presence of "Wegener's autoantigen," proteinase 3 (PR3), in malignant tissues from WG patients to ascertain whether an association exists between malignancy and WG. METHODS: A retrospective statistical analysis was performed on the medical records of 477 patients with WG as compared with a control group of 479 patients with rheumatoid arthritis (RA). A murine monoclonal antibody was used to test malignant tissues for the presence of PR3. RESULTS: A malignant neoplasm was found in 23 patients in the WG group and in 18 patients in the control group. The odds ratio for malignant neoplasm in the WG group was 1.79 (P = 0.0876, 95% confidence interval [95% CI] 0.92-3.48). Seven patients with renal cell carcinoma were found in the WG group compared with 1 patient in the control group, for an odds ratio of 8.73 (P = 0.0464, 95% CI 1.04-73.69). Simultaneous occurrence of cancer and WG was observed in 14 patients with WG compared with 1 control patient, for an odds ratio of 18.00 (P = 0.0059, 95% CI 230-140.67). Furthermore, the diseases occurred simultaneously in 5 of the 7 patients with both WG and renal cell carcinoma, but not in the single patient in the control group with RA and renal cell carcinoma. PR3 could not be detected in any of the 8 malignant tissue samples (4 renal cell carcinomas) investigated in the patients from the WG group. CONCLUSION: The close temporal association between renal cell carcinoma and WG suggests that malignancy is, in some cases, a trigger for the development of WG. However, since PR3 was not found in malignant tissues from the WG patients, the immunopathologic mechanisms leading to autoimmunity and vasculitis remain unclear.

Adult↗

[Comparative analysis of various standard immunohistochemical procedures].

Immunohistochemical staining techniques, such as the APAAP, ABC, EnVision and Immuf1p4x methods, play a leading role in the search to solve the questions arising in clinical diagnosis. With the increase in number of techniques for diagnostic examination, the sarch for suitable method is becoming more and more important. The goal of this study was to compare these different treatments with regard to sensitivity and specificity. Furthermore, an analysis of time and cost was made. The primary antibodies used were CD20, CD30 and IgM, as well as receptor antibodies estrogen and progesterone. The variable costs of each technique were calculated based on selected examples. The APAAP method required the most time and was, at the same time, by far the most expensive treatment. The EnVision method required the least time and showed very good staining results, which were comparable to those of the ABC and ImmunoMax techniques. The staining costs could be reduced by about 95% and the staining intensity improved substantially by using expensive receptor antibodies in combination with the Immuno-Max method. This study illustrates the importance of knowing different examination techniques, as well as the costs arising by their usage.

Antigens, CD20↗

[Malakoplakia of the colon].

We report on a 62-year-old female patient with melena in which polypoid lesions of the cecum were discovered endoscopically. Histological examination of mucosal biopsies revealed an inflammatory process with lots of histiocytes and so-called Michaelis-Gutmann bodies, leading to the diagnosis of a malakoplakia of the colon. No other organs were found affected. In the course of an antibiotic therapy, there was no melena detectable over a period of six months. Malakoplakia, an inflammation usually affecting the urogenital tract, is rarely found in the colon, with only 35 cases published until now. It is frequently associated with other diseases like neoplastic or inflammatory disorders, immune defect syndromes or heroin abuse. This spectrum is expanded by our report in which a long-standing alcohol abuse was found as an attendant disease.

Alcohol-Related Disorders↗