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Notes: Summary Skin biopsy specimens from normal skin and from 115 patients with benign dermatoses, pre- or pseudo-malignant disorders or malignant cutaneous lymphomas have been examined immunohistologically for expression of the Reed-Sternberg cell associated antigen CD30 detected by monoclonal antibodies Ki-1 and Ber-H2. The antibodies stained the atypical cells in lymphomatoid papulosis, a proportion of the neoplastic cells in some cases of mycosis fungoides and most of the neoplastic cells in six large cell anaplastic/pleomorphic non-Hodgkin's lymphomas. The lymphoid cells in all other specimens were Ki-1- and Ber-H2-negative. In all cases, expression of the Ki-1/Ber-H2 antigen was accompanied by expression of activation and proliferation associated markers (i. e., HLA-DR, IL-2 receptor, transferrin receptor and the Ki-67 nuclear antigen). These data indicate the value of antibodies Ki-1 and Ber-H2 in distinguishing between lymphomatoid papulosis and other types of pre- or pseudo-malignant disorders and support the view that lymphomatoid papulosis, Hodgkin's disease and some types of non-Hodgkin's lymphoma constitute a spectrum of related disorders, originated from activated lymphoid cells.

Notes: The aetiology of the ampicillin rash is uncertain although numerous theories have been proposed–mainly immunological. One such concerns the presence of anti-epithelial antibodies which have received conflicting reports in the literature. In this study, skin biopsies from three patients with a maculopapular ampicillin-rash were studied by immunofluorescence to investigate the presence of anti-epithelial antibodies. However immunofluorescence for IgG, IgM, IgA and C3 was completely negative so that we were unable to provide any support for this particular hypothesis.

Notes: CD 3 antigen expression was studied in a series of 98 T-cell lymphomas, using polyclonal antibodies which recognize this molecule in routinely processed, paraffin-embedded, tissue. We identified 40 cases in which CD3 was present on only a proportion of the neoplastic cells. This phenomenon of heterogeneous CD3 expression was commonest in pleomorphic T-cell lymphomas (22/42 cases) and in CD30 (Ki-1)-positive lymphomas (5/11 cases), and was less frequently observed in mycosis fungoides (4/18 cases) and not seen in T-cell lymphoblastic lymphoma (0/9 cases). CD3 expression was often related to cell morphology, with CD3 antigen being present on the smaller neoplastic cells but absent from the larger ones. The diagnostic significance of these observations is that, on occasion, it may be possible to diagnose a lymphoma as being of T-cell origin in paraffin sections by demonstrating a minor subpopulation of CD3-positive neoplastic cells.

Notes: The prognostic value of immunophenotyping lymphomas was assessed by studying 51 cases of high-grade non-Hodgkin's lymphoma for which long term clinical follow-up (14–28 years) was available. Using antibodies which identify T- and B-cell-related antigens in formalin-fixed, paraffin-embedded material, 43 were shown to be of B-cell and eight of T-cell phenotype. In terms of survival, cases of high-grade T-cell lymphoma fared significantly worse (P 〈 0.05) than cases of high-grade B-cell subtype. These findings support the belief that T-cell lymphomas have a more aggressive clinical course than their B-cell counterparts.

Notes: In an immunocytochemical study of 41 human lung tumours we have shown that Langerhans cells can be reliably identified using the anti-CD1 monoclonal antibody NA1/34. Langerhans cells are present in all the main varieties of human lung tumour although they are infrequent in both small cell carcinoma and carcinoid tumour. There is considerable variation in numbers of Langerhans cells in both adenocarcinomas and squamous cell carcinomas. In this study tumours were divided into those with high numbers of Langerhans cells (〉 2 per high power field) and those with low numbers (〈 2 per high power field). Analysing these results against patient survival showed a markedly worse survival in those tumours with a high number of Langerhans cells for all the tumours as a single group and for squamous cell carcinoma as a single entity.

Notes: Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases Neoplasms of histiocytes and dendritic cells are rare, and their phenotypic and biological definition is incomplete. Seeking to identify antigens detectable in paraffin-embedded sections that might allow a more complete, rational immunophenotypic classification of histiocytic/dendritic cell neoplasms, the International Lymphoma Study Group (ILSG) stained 61 tumours of suspected histiocytic/dendritic cell type with a panel of 15 antibodies including those reactive with histiocytes (CD68, lysozyme (LYS)), Langerhans cells (CD1a), follicular dendritic cells (FDC: CD21, CD35) and S100 protein. This analysis revealed that 57 cases (93%) fit into four major immunophenotypic groups (one histiocytic and three dendritic cell types) utilizing six markers: CD68, LYS, CD1a, S100, CD21, and CD35. The four (7%) unclassified cases were further classifiable into the above four groups using additional morphological and ultrastructural features. The four groups then included: (i) histiocytic sarcoma (n=18) with the following phenotype: CD68 (100%), LYS (94%), CD1a (0%), S100 (33%), CD21/35 (0%). The median age was 46 years. Presentation was predominantly extranodal (72%) with high mortality (58% dead of disease (DOD)). Three had systemic involvement consistent with `malignant histiocytosis'; (ii) Langerhans cell tumour (LCT) (n=26) which expressed: CD68 (96%), LYS (42%), CD1a (100%), S100 (100%), CD21/35 (0%). There were two morphological variants: cytologically typical (n=17) designated LCT; and cytologically malignant (n=9) designated Langerhans cell sarcoma (LCS). The LCS were often not easily recognized morphologically as LC-derived, but were diagnosed based on CD1a staining. LCT and LCS differed in median age (33 versus 41 years), male:female ratio (3.7:1 versus 1:2), and death rate (31% versus 50% DOD). Four LCT patients had systemic involvement typical of Letterer–Siwe disease; (iii) follicular dendritic cell tumour/sarcoma (FDCT) (n=13) which expressed: CD68 (54%), LYS (8%), CD1a (0%), S100 (16%), FDC markers CD21/35 (100%), EMA (40%). These patients were adults (median age 65 years) with predominantly localized nodal disease (75%) and low mortality (9% DOD); (iv) interdigitating dendritic cell tumour/sarcoma (IDCT) (n=4) which expressed: CD68 (50%), LYS (25%), CD1a (0%), S100 (100%), CD21/35 (0%). The patients were adults (median 71 years) with localized nodal disease (75%) without mortality (0% DOD). In conclusion, definitive immunophenotypic classification of histiocytic and accessory cell neoplasms into four categories was possible in 93% of the cases using six antigens detected in paraffin-embedded sections. Exceptional cases (7%) were resolvable when added morphological and ultrastructural features were considered. We propose a classification combining immunophenotype and morphology with five categories, including Langerhans cell sarcoma. This simplified scheme is practical for everyday diagnostic use and should provide a framework for additional investigation of these unusual neoplasms.

Notes: Ki67 protein: the immaculate deception? This article updates our previous review of Ki67 published in Histopathology 10 years ago. In this period the numbers of papers published featuring this antibody has increased 10-fold from 338 to 3489 indicating the considerable enthusiasm with which this antibody has been studied. This review attempts to provide an update on the characterization of the Ki67 protein, its function and its use as a prognostic or diagnostic tool.

Notes: Tissue from 86 cases of Hodgkin's disease, fixed in formalin and embedded in paraffin, was immunostained for the T-cell marker CD3. Of these cases, 20 were selected on the basis of previous reactivity of Reed-Sternberg cells for T-cell associated antigens in frozen sections whilst the remaining 66 were retrieved from the routine pathology files. Five of the 20 selected cases and 22 of the retrieved cases showed predominantly cytoplasmic positivity in a subpopulation of Hodgkin and Reed-Sternberg cells. CD3 positive cells were present in all subtypes of Hodgkin's disease including three of nine lymphocyte predominance cases. It therefore appears that some Hodgkin and Reed-Sternberg cells can express the major T-cell antigen CD3. Although these findings are open to other interpretations, they are consistent with the hypothesis that at least some cases of Hodgkin's disease arise from activated T-cells.

Notes: There has recently been much interest in the patterns of follicular dendritic reticulum cells (DRC) in pathological lymph nodes, particularly in relation to the phenomenon of DRC break-up (thought to be pathognomonic of AIDS-related lymphadenopathies) and to progressive transformation of germinal centres (as a possible precursor of lymphocyte predominant Hodgkin's disease). In the present study we have immunostained twenty-nine reactive lymph nodes and five tonsils with monoclonal antibody R4/23 (DAKO-DRC) in order to evaluate the frequency of such changes in lymphoid tissue unaffected by AIDS or Hodgkin's disease. Most of the specimens contained typical secondary follicles with clearly defined germinal centres and mantle zones. There were two variants in lymph nodes showing follicular hyperplasia characterized by (i) progressive transformation of germinal centres and (ii) inclusions of nests of small lymphocytes within germinal centres. In each of these types of follicles the compact evenly-distributed meshwork of DRCs, as previously described, was seen. However there were considerable variations in DRC meshwork in each category (the pattern could not be predicted from the morphology) with examples in all three of the DRC break-up previously considered specific for the AIDS related lymphadenopathy. Since none of the lymph nodes and tonsils studied had any known relationship to either Hodgkin's disease or AIDS it is argued that none of the changes in the DRC meshwork observed are specific for these conditions.