Eosinophilic folliculitis: an important differential diagnosis after allogeneic bone-marrow transplant.

Eosinophilic folliculitis (EF) is a descriptive histopathological term applied to a heterogeneous group of disorders. In EF, the characteristic histopathological features are eosinophilic spongiosis and pustulosis involving the infundibular region of the hair follicle. EF may be seen in association with bacterial and fungal infection, drug reactions and haematological disorders. However, in those conditions, the histopathological changes are rarely restricted to the infundibula but in most cases include a moderate to dense perifollicular or even diffuse dermal infiltrate of lymphocytes, or eosinophilic or neutrophilic granulocytes. We present two cases of EF after mini-allogeneic bone-marrow transplantation (BMT) in order to highlight this rare and perhaps under-recognized clinical association.

The ins and outs of EBV infection.

Epstein-Barr virus (EBV) infects almost the entire adult population of the world. The success of this virus appears to be based on its ability to infect the B cell, rather than any other cell type. We review EBV B-cell tropism, and discuss the mechanisms by which the virus may gain access to, and egress from, B cells in the normal host.

Epstein-Barr virus and Hodgkin's disease: further evidence for the three disease hypothesis.

The epidemiology of Hodgkin's disease suggests that it is a heterogeneous condition comprising more than one disease entity. The Epstein-Barr virus (EBV) is present in the Reed-Sternberg cells of a proportion of cases and is likely to play a role in the pathogenesis of these cases. In this study we show that EBV association rates vary with age at diagnosis. We suggest that Hodgkin's disease can be divided into three disease entities on the basis of EBV association and age, thereby providing biological support for the multiple aetiology hypothesis proposed by MacMahon (Cancer Res 1966; 26: 1189-1290).

Criteria for the definition of Epstein-Barr virus association in Hodgkin's disease.

There is a clear association between the Epstein-Barr virus (EBV) and Hodgkin's disease (HD). EBV is not, however, detectable within the affected tissues of all cases. The proportion of positive cases varies from 15-79% depending on the assay used to detect EBV. The techniques utilised vary not only in sensitivity but in their ability to detect viral DNA, RNA, or protein and in their ability to demonstrate the cellular localisation of the virus. Thus, the biological significance of a positive result will vary depending on the method of analysis. In the present study, four different methods of detecting EBV were compared. RNA in situ hybridization was found to be the most practical method of detecting EBV in tumour cells. Using this assay EBV was detected in the Reed-Sternberg cells of 33% and 45% of the two series of HD cases examined in this study. We believe that these cases should be considered EBV-associated.

CHOP-based chemotherapy is as effective as alternating PEEC/CHOP chemotherapy in a randomised trial in high-grade non-Hodgkin's lymphoma. Scotland and Newcastle Lymphoma Group.

The aim of this study was to test whether survival for patients with high-grade non-Hodgkin's lymphoma (NHL) can be improved with a non-cross-resistant regimen as compared to a CHOP-based regimen. This is a multicentre study comprising 325 adult patients, median age 58 years, with high-grade non-Hodgkin's lymphoma: patients of any age and performance status were eligible provided they were able to receive the drugs in the regimens. Patients were randomised to either B-CHOP-M (bleomycin, cyclophosphamide, doxorubicin, vincristine, prednisolone and methotrexate) or PEEC-M (methylprednisolone, vindesine, etoposide, chlorambucil and methotrexate) alternating with B-CHOP-M. At a median follow-up of 9 years, there was no significant difference in overall survival or disease-free survival between the two arms. Toxicities for the two regimens were equivalent. This study confirms that for relatively unselected patients with high-grade non-Hodgkin's lymphoma, an alternating multidrug regimen does not improve upon the results obtained with B-CHOP-M.

Paraffin section immunophenotyping of non-Hodgkin's lymphoma, using a panel of monoclonal antibodies.

The monoclonal antibodies F8-11-13, 4KB5, MB1, and MB2 recognize largely B-cell-restricted antigenic determinants that resist routine processing. Similarly, MT1, MT2, and UCHL1 react with fixation-resistant T-cell-restricted antigens. In order to evaluate the diagnostic potential of these antibodies, the authors have assessed their immunoreactivity with a series of 81 formalin-fixed and paraffin-embedded non-Hodgkin's lymphomas (48 B-cell, 33 T-cell) encompassing a wide variety of histologic subtypes, which had been fully characterized by frozen-section immunophenotyping. Ninety-six percent of B-cell lymphomas reacted with one or more of the B-cell-associated antibodies, whereas 100% of T-cell lymphomas reacted either with MT1, UCHL1, or both antibodies. MT2 was of no value in distinguishing between B- and T-cell lymphomas. None of the antibodies was entirely lineage specific; furthermore, a proportion of cases failed to react with one or more of the B- or T-cell-associated antibodies. Although these antibodies provide useful information in distinguishing between T- and B-cell lymphomas, the authors suggest that a panel of these antibodies is necessary for accurate determination of the histogenesis of these tumors. As with any immunohistochemical marker, interpretation of the immunostaining must be in the context of the morphologic features.

Studies on blood lymphocytes of patients with nodular poorly differentiated lymphocytic lymphoma.

T and B lymphocytes were measured in pretreatment blood samples from patients wih nodular poorly differentiated lymphocytic lymphoma (NPDLL). There were significant differences in T cell values between control groups and patients with NPDLL. In 13 out of 20 cases of NPDLL blood lymphocytes showed abnormalities of immunoglobulin light chain expression and were considered to show an abnormal clonal expansion of B lymphocytes. The abnormal clone of B cells in the blood reflected that found in lymph nodes and could be detected in the absence of bone marrow involvement or blood lymphocytosis.

Metastatic thymoma: a case report and immunohistological analysis.

A patient with metastatic lymphocyte predominant thymoma was studied and an immunohistological analysis of frozen and paraffin sections was performed. The immunophenotype of the lymphoid cells was similar to that of primary thymomas and T cell lymphoblastic lymphomas. The epithelial cells reacted with an anticytokeratin monoclonal antibody. The results have diagnostic implications for the histopathologist using immunohistochemistry as a diagnostic aid and it is concluded that a panel of monoclonal antibodies against both lymphoid and epithelial markers should be used for immunohistological typing of tumours of uncertain histogenesis.

Immunophenotype analysis of malignant histiocytosis of the intestine.

Five cases of malignant histiocytosis of the intestine and one case of true histiocytic lymphoma were studied using immunohistological techniques. In paraffin sections tumour cells in all cases were shown to contain alpha-1-antitrypsin and to express the leucocyte common antigen. Four of the five cases of malignant histiocytosis of the intestine and the case of histiocytic lymphoma expressed the epithelial membrane antigen. Cryostat sections in four cases of malignant histiocytosis of the intestine showed that most tumour cells reacted with anti-T cell monoclonal antibodies. Only a minority expressed a typical monocyte macrophage phenotype.

T and B lymphocyte markers in effusions of patients with non-Hodgkin's lymphoma.

T and B cells were sought in effusion fluids of 13 patients with lymphoma. In T cell lymphomas (four cases) morphologically abnormal cells that formed E rosettes were present. In B cell lymphomas (nine cases) morphologically abnormal cells were present in only two cases, however immunological studies showed a reduction in T cells and monoclonal light chain immunoglobulin expression in six of nine cases.

Detection of Epstein-Barr virus genomes in Hodgkin's disease: relation to age.

An investigation as to whether any particular subgroup of patients with Hodgkin's disease was particularly likely to be Epstein-Barr virus (EBV) genome positive was made on samples from 95 patients. These were grouped according to age and Hodgkin's disease subtype, and analysed using Southern blot analysis. Most samples from children or adults aged 50 years or over contained detectable EBV genomes; samples from young adults were only rarely positive. The differences in EBV positivity by age were highly significant, but there was no significant association between EBV and histological subtype after allowing for the effect of age. The results support the hypothesis that Hodgkin's disease in different age groups may have different aetiologies, and suggest that EBV does have a pathogenetic role in Hodgkin's disease in children and older age groups.

The Scotland and Newcastle epidemiological study of Hodgkin's disease: impact of histopathological review and EBV status on incidence estimates.

AIMS: The epidemiological and pathological features of Hodgkin lymphoma (HL) are complex. The Epstein-Barr virus (EBV) is consistently associated with a proportion of cases, and these cases are thought to represent a distinct aetiological subgroup of HL. The aim of the present analysis was to determine the age and sex specific incidence of EBV associated and non-associated HL, analysed separately, using data derived from a population based study-the Scotland and Newcastle epidemiological study of Hodgkin's disease (SNEHD). This study also provided a unique opportunity to evaluate accuracy in the current diagnosis and classification of HL. METHODS: SNEHD analysed consecutive cases of HL diagnosed in the study area between 1993 and 1997. Diagnostic biopsy material was retrieved, EBV status of tumours was determined, and histological review was performed. RESULTS: In total, 622 cases were eligible for the study, and EBV studies and histopathological review were performed on biopsy material from 537 and 549 cases, respectively. Accuracy in the overall diagnosis of HL and classification of nodular sclerosis HL was good, but diagnosis of HL in the elderly and classification of other subtypes was less reliable. One third of classic HL cases were EBV associated, and age specific incidence curves for EBV associated and non-associated cases were distinct. CONCLUSIONS: Comparison of age specific incidence curves for EBV associated and non-associated HL supports the hypothesis that these are two distinct aetiological entities. Accuracy in the diagnosis of HL is generally good, but certain subgroups of cases continue to present diagnostic difficulties.

Primary splenic large cell anaplastic lymphoma associated with HIV infection.

We report a case of primary splenic B-cell CD30 positive large cell anaplastic lymphoma developing in an HIV positive patient. The tumour cells expressed Epstein-Barr virus-associated antigens.

T-cell lymphoma in children and young adults: clinical, immunological and pathological features.

The clinical, pathological and immunological features in 5 cases of T-cell lymphoma without overt marrow involvement are described. Classification of this distinct sub-group of lymphoma on morphological and clinical criteria alone has been shown to be unreliable, and precise recognitionr equires additional information from cytochemical and immunological marker studies of peripheral blood and lymph nodes. Valuable information may also be obtained from analysis of pleural fluid. The accurate identification of this sub-group assumes new clinical relevance in the light of the considerable improvement in prognosis reported with treatment schedules that are effective in acute lymphoblastic leukaemia.

Expression of MHC class II antigens in human B-cell leukaemia and non-Hodgkin's lymphoma.

In this review we have summarized our experiences of serological analysis of MHC class II antigen expression in human B cell malignant disease. Cells from a large number of cases of B-cell chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL) have been examined for expression of class II antigens. Using a number of monoclonal antibodies which in some cases are specific for class II subregion products (DP, DQ and DR), MHC class II antigens were detected by indirect immunofluorescence and fluorescent activated cell sorter analysis in CLL and by immunohistochemical staining in NHL. At the cell surface in many cases of B cell malignant disease, products of the different class II subregion genes are non-coordinately expressed. The most commonly occurring pattern of non-coordinate expression of class II molecules is of expression of DP and DR antigens in the absence of detectable DQ expression. These findings are in contrast to normal B lymphocytes where DP, DQ and DR antigens are expressed together at the cell surface. There is considerable heterogeneity among cases comprising individual histopathological categories of B cell malignancy, and in many instances heterogeneous class II phenotypes are also found on cells from the same tumour. In chronic lymphocytic leukaemia, class II antigen expression is inducible in vitro by treating the cells with the phorbol ester TPA. CLL cells treated with TPA have much increased levels of class II antigen expression at the cell surface and much increased steady state levels of class II specific mRNA transcripts detectable with complementary DNA probes. Aberrant class II antigen expression may be involved in the pathogenesis of B cell malignant disease.

Detection of t(14;18) in British follicular lymphoma using cytogenetics, Southern blotting and the polymerase chain reaction.

Cytogenetics, Southern blotting and PCR were used to detect t(14;18) in 72 British patients with follicular lymphoma. The overall incidence of the translocation was 76%. Cytogenetics was the most successful technique, but 10-30% of translocations detected karyotypically were missed by molecular methods, presumably due to break-points falling outside the range of probes and primers used here. Reliance on molecular detection alone may considerably underestimate the incidence of t(14;18) and it is therefore essential to use the most comprehensive range of probes and primers available.

Lymphocytes in pseudomembranes of late prosthetic joint failure.

The pseudomembrane formed in association with late aseptic prosthesis failure contains a mixed giant cell and histiocytic infiltrate with variable numbers of lymphocytes. Immunolabelling with a panel of antibodies on paraffin sections was undertaken to define the nature of the lymphoid infiltrate in 19 cases. In all cases, the predominant lymphoid cell was a memory (CD45RO+, CD45RA-) T-cell. B-cells were rare. Tissue from patients with rheumatoid arthritis (RA) contained greater numbers of T-cells when compared with patients with osteoarthritis (OA), suggesting that the intensity of the lymphoid infiltrates reflects the underlying joint disease rather than necessarily being part of a hypersensitivity response to wear debris.

Demonstration of clonality in T-cell lymphoma using an anti-T-cell receptor variable region antibody panel.

Frozen sections from 35 T-cell lymphomas were stained with the Diversi-T alpha beta T-Cell Receptor panel which includes seven antibodies to T-cell receptor variable region gene products. In five cases a monoclonal population of T-cells could be demonstrated (one case V beta 5+, three cases V beta 8+ and one case V beta 6+) and in a further case a biclonal population (V beta 5+ and V beta 8+). We conclude that this antibody panel is of limited usefulness for the demonstration of clonality in T-cell lymphoma.