A number of monoclonal antibodies (MAbs) that recognize human follicular dendritic cells (FDCs) have been identified. Although some of them have already been applied individually in routine immunolabeling using formalin-fixed paraffin sections for diagnostic and experimental purposes, many antibodies are still employed only for immunolabeling using cryostat sections or particularly processed sections because they have been thought unsuitable for routine sections. A comprehensive examination re-evaluating their suitability in paraffin sections has not been reported. Accordingly, there is limited ability to examine the immunopathological contribution or diagnostic value of FDCs using routinely processed specimens or archived materials. In this study a broad panel of antibodies was systematically applied to the immunolabeling of paraffin sections of reactive tonsils or lymph nodes, in combination with advanced antigen retrieval (AR) techniques. Several antibodies, including Ki-M4p, X-11, 12B1, CNA.42, 1F8/BU32 (anti-CD21), BU38/1B12 (anti-CD23), Ber-MAC-DRC/To5 (anti-CD35), 1.4C3 (anti-CD106), NGFR5 (anti-nerve growth factor receptor p75), IIH6 (anti-CD55), 55K-2 (anti-fascin), and anti-S100 protein alpha-chain, were found to label FDCs in routine sections when combined with suitable AR techniques. Our results are easily adaptable for routine practice and provided useful suggestions concerning the immunopathological behavior and diversity of the particular cells.
Several authors have reported cases of patients with malignant lymphoma with unique characteristics, designated nasal-type T/NK cell lymphoma, which expresses the natural killer (NK) cell marker and shows frequent extra-nodal involvement and poor prognosis. We report 2 cases of this type of lymphoma which were CD56-positive and showed a histopathologically angiocentric pattern with cutaneous and subcutaneous tumorous lesions. Patient 1 had extensive invasion of skin, underlying skeletal muscle, spleen and bone marrow, and died of sepsis 34 months after onset. Patient 2 had multiple subcutaneous nodules and invasion to mammary gland, lung, lymph node and spleen at the time of her first visit. She died of a rapid invasion of lymphoma cells to the liver 5 months after onset. Both patients showed similar immunophenotypes of tumor cells (CD2+, CD3-, CD4-, CD8-, CD20-, CD56+) and germ line configuration of the heavy chain of immunoglobulin (JH), T-cell receptor C beta-1 subunit DNA and T-cell receptor J gamma subunit DNA. Epstein-Barr virus early regions RNA was demonstrated in the nuclei of tumor cells of both patients with in situ hybridization. The histopathological examination of the skin lesions of both patients revealed the features of angiocentric lymphoma. The detection of CD56 in the tumor cells of cutaneous lymphomas should be routinely performed for the early diagnosis of this type of lymphoma with extremely poor prognosis.
756 CLASSLFICATION OF MALIGNANT LYMPHOMA Acta Path. Jap.form no clear-cut pattern but rather monotonous diffuse masses of round cells which appear to differ only in size. It should be a great hazard not only for treatment of the patients but also for statistical, epidemiological and various other studies on lymphomas that the diagnosis on one tumor would vary according to pathologists who examine it or hospitals where a patient is treated.It is therefore very important to evaluate the general situation on lymphoma diagnosis, to investigate the cause of diagnostic diversity, and to find objective measures to improve the accuracy and reproducibility of lymphoma diagnosis.As seen in the other reports of this symposium, new theoretical and technical approaches based on the recently acquired knowledges on basic immunology have greatly advanced the study of malignant lymphoma.50 It is now apparent that the Rappaport classification (AFIP Atlas, 1966)45 whose clinical usefulness had been widely recognized has some theoretical as well as practical drawbacks. Several different new classifications for non-Hodgkin's lymphomas have been proposed by leading scholars of this field in U.S.A. and E~rope,4,~~,16,16,~~35 and they are a t present being critically evaluated in the project for the international classification of non-Hodgkin's lymphoma sponsored by the National Cancer Institute of U.S.A.It was established through the U.S. -Japan seminars on malignant diseases of hematopoetic system held twice in 1967 and 19712, that the geographic difference between U.S.A. and Japan in various aspects of malignant lymphoma notably in the relative incidence of its subtypes was quite a p~a r e n t .~~~~' In order to contribute to the clarification of the problems of lymphoma diagnosis, and to obtain useful findings for a new classification suited for the lymphomas in Japan, a collaborative study was made by organizing a study group consisting of 16 members of different schools and different length of experience in the pathology of lymphoma. This study consisted of two parts namely I) the study of the consistency and reliabily of the histopathological diagnosis, and 11) the correlation between histological appearances and immunological characters of the lymphoma cells.
A 54-year-old man was admitted because of right supraclavicular lymphadenopathy of some weeks duration. Computed axial tomography revealed a large multinodular lesion in a supraclavicular lymph node. The patient then had a supraclavicular lymph node biopsy. Light microscopy showed a tumor whose structure was suggestive of an interdigitating cell sarcoma. Enzyme and immunohistochemical analysis showed that the tumor cells possessed membranous adenosine triphosphatase activity, intracytoplasmic S100 protein, surface CD1a and CD4 antigens, and HLA-DR antigen. Ultrastructural examination showed that the cells exhibited many interdigitating cytoplasmic extensions, but no Birbeck granules. DNA content analysis of the tumor cells proved that the cells were malignant. These data are consistent with derivation from a lymph node interdigitating cell.
Left cervical lymphadenopathy developed in a 50-year-old male who had a history of adult-onset Still's disease for the preceding 18 months. Still's disease is characterized by rash, fever, and leukocytosis. Lymphadenopathy has been reported in about 60% of the patients, and most histopathologic studies have shown non-specific reactive hyperplasia. However, in this case, an open biopsy of the cervical node revealed a histology of diffuse large B-cell lymphoma. The B-cell malignant lymphoma that developed may have resulted from a sequential progression of a previous stage of benign lymphoproliferative lesion. Our case suggests that the pathophysiology of adult-onset Still's disease involves the stimulation of lymphoid systems to the point of progression towards lymphoma. Malignant lymphoma should be added to the list of life-threatening complications which, although rare, are associated with this disease.
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