Inter-specific parasite competition: mixed infections of Schistosoma mansoni and S. rodhaini in the definitive host.

Competition between parasite species has been predicted to be an important force shaping parasite and host ecology and evolution, although empirical data are often lacking. Using the Mus musculus-Schistosoma mansoni and Schistosoma rodhaini host-parasite systems we characterized mate choice and inter-specific competition between these two schistosome species. Simultaneous infections revealed species-specific mate preferences for both species as well as suggesting mating competition, with male S. rodhaini appearing dominant over male S. mansoni. S. rodhaini homologous pairs were also shown to have increased reproduction per paired female in the presence of a competitor in simultaneous infections. Overall total reproductive success was, however, similar between the two species under conditions of direct competition due to the greater initial infectivity of S. mansoni in comparison to S. rodhaini. Inter-specific competition was also implicated as increased parasite virulence to the host. The potential effects of such interactions on parasite and host ecology and evolution in nature are discussed.

A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma.

The role of TP53 mutation in transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL) was examined in a panel of 91 lymph node biopsies derived from 29 patients pre- and post-transformation. The entire TP53 coding sequence was screened and immunocytochemistry performed to determine expression of p53 and its key regulator MDM2. A total of 10 mutations were detected in eight patients (28%), although none were present at FL diagnosis. Mutations were not detected solely at the time of transformation; in three patients, mutated TP53 arose in at least one antecedent FL sample (6 months, 2.5 years and 4 years prior to transformation). Loss of heterozygosity at the TP53 locus occurred in 2/20 informative patients (only in t-FL samples). p53 staining was positive in 82% (9/11) of available biopsies with a missense mutation, and negative in 71% (45/63) with wtTP53. MDM2 expression was significantly higher in t-FL samples (mean 72% positive; 95% confidence interval (95% CI) 68-76%) than FL (mean 58% positive; 95% CI 54-62%) (P<0.001) but did not correlate with TP53 status. TP53 mutation has only a limited role in the transformation of FL, exerting a heterogeneous influence upon phenotypic change. In contrast, dysregulation of MDM2 is frequent and may provide a more rational therapeutic target..

Patterns of survival in patients with recurrent follicular lymphoma: a 20-year study from a single center.

PURPOSE: To examine outcome of treatment for patients with recurrent follicular lymphoma. PATIENTS AND METHODS: Two hundred twelve newly diagnosed follicular lymphoma patients were studied. One hundred seventy-nine were initially treated successfully. Recurrent or progressive lymphoma developed in 116. Treatment was given according to disease stage and current protocols, mostly with single alkylating agents. A policy of repeated lymph node and bone marrow biopsy was pursued. RESULTS: The overall median survival duration was 9 years, with a median follow-up duration of 12 years. Following recurrence, the median survival duration was 4 1/2 years. Only eight of 116 patients with recurrent disease died of causes unrelated to lymphoma. The overall response rate to first re-treatment was 78% and showed slight decline with successive recurrences, reaching 48% after the fourth treatment. The median duration of second remission was 13 months, (v 31 months for first remission), with the only significant predictive factor being quality of remission. Multivariate analysis showed only age at recurrence and number of prior treatments to correlate with survival after first recurrence. Survival after second remission was only correlated with age and quality of response: Kaplan-Meier estimates gave 53% of patients reaching second complete remission alive 10 years later, compared with 28% in partial remission. CONCLUSION: Age and previous and continuing responsiveness of follicular lymphoma to therapy are the principal determinants of survival following recurrence. Improvement in survival with new treatments will be demonstrated most readily in older patients, while more intensive approaches should be tested in younger patients in whom remission is achieved with difficulty.

Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for recurrent follicular lymphoma.

PURPOSE: To assess myeloablative therapy with autologous bone marrow transplantation (ABMT) in younger patients with follicular lymphoma in the hope of prolonging remission duration and survival. PATIENTS AND METHODS: Since June 1985, 64 patients with follicular lymphoma have received cyclophosphamide (CY) 60 mg/kg x 2 and total-body irradiation (TBI) 2 Gy x 6 supported by ABMT as consolidation of second or subsequent remission. The marrow mononuclear cell (MNC) fraction was treated in vitro with three cycles of the monoclonal antibody (MAb) anti-CD20 and baby rabbit complement before cryopreservation. At the time of treatment, 34 patients were in complete remission (CR), and 30 had residual disease present. RESULTS: The median time to engraftment was 28 days (range, 15 to 46) for both a neutrophil count greater than 0.5 x 10(9)/L and a platelet count greater than 20 x 10(9)/L. Engraftment did not occur in one patient who died at 12 weeks, and three patients (excluded from the range) have had delayed recovery (> 6 months) of RBCs and platelets. Fifty two patients are alive; three died as a consequence of the transplant procedure, two died in remission from other causes, and seven died of recurrent lymphoma. There was a significant correlation between survival and the total number of episodes of treatment required during the course of the illness (< or = to three v > three, P = .01). With a median follow-up duration of 3 1/2 years, 35 patients continue in remission between 1 and 8 years, and 24 have developed recurrent lymphoma, five with evidence of transformation to high-grade histology. Freedom from recurrence did not correlate with the time from diagnosis, the number of previous treatments, the presence or absence of residual disease at the time of treatment, or during which specific remission the treatment was given (second v > second). However, comparison with an age-matched, remission-matched, historical control group shows a significant advantage in favor of treatment with CY plus TBI plus ABMT (P = .001); currently, there is no difference in survival. CONCLUSION: These results are encouraging, although preliminary; it remains to be established whether this treatment prolongs survival.

Role of image-guided core-needle biopsy in the management of patients with lymphoma.

PURPOSE: The results of 106 radiologically guided core needle biopsies in 96 patients were analyzed retrospectively to evaluate the accuracy, safety, and role of this technique in the management of patients with lymphoma and to determine factors predictive of success. PATIENTS AND METHODS: Biopsies were performed in 51 patients with low-grade non-Hodgkin's lymphoma (NHL), 24 with high-grade NHL, 16 with previously diagnosed Hodgkin's disease (HD), and 15 with no previous history of lymphoma. Disease was infradiaphragmatic in 92 patients and supradiaphragmatic in 14. Computed tomography (CT) guidance was used in 98 biopsies and ultrasonography (US) in eight. RESULTS: The biopsy was diagnostic and yielded information on the basis of which treatment was started in 88 of 106 patients. The procedure was well tolerated and there were no major complications. Small size of the sample or inappropriate tissue sampled were the main causes of failure. The technique was equally successful in the diagnosis of HD and both high-grade and low-grade NHL as in nonlymphoproliferative disorders. The procedure was equally successful at diagnosis as at suspected recurrence or progression. In 33 of 80 cases in which the biopsy was performed at the time of recurrence or progression, the histology had changed; in 31 of 33, this influenced treatment. The technique was efficient at diagnosing transformation of follicular NHL in 16 of 18 patients, which allowed early adjustment of treatment at recurrence. CONCLUSION: At St Bartholomew's Hospital (SBH), image-guided core-needle biopsy has proven to be a quick, safe, and efficient alternative to excisional biopsy in the evaluation of lymphoproliferative disorders at presentation, recurrence, or progression. It should become the procedure of choice for histologic sampling in the absence of peripheral lymphadenopathy.

High-dose therapy and autologous stem-cell support for chemosensitive transformed low-grade follicular non-Hodgkin's lymphoma: a case-matched study from the European Bone Marrow Transplant Registry.

PURPOSE: To assess the outcome of high-dose therapy with autologous stem-cell support in patients with histologic transformation of low-grade follicular non-Hodgkin's lymphoma (NHL) and identify significant prognostic factors, as well as to compare survival of these patients with that of patients with matched low-grade and de novo high- or intermediate-grade NHL undergoing the same procedure. PATIENTS AND METHODS: Fifty patients with transformed low-grade NHL have been reported to the European Bone Marrow Transplant registry. Outcome from high-dose therapy and significant prognostic factors were analyzed. Their survival was also compared with that of 200 patients with matched low-grade NHL and 200 patients with matched de novo high- or intermediate-grade NHL by a case-matched analysis. RESULTS: The procedure-related death rate among the 50 transformed NHL patients was 18%. Overall survival (OS) and progression-free survival (PFS) rates were 51% and 30% at 5 years, respectively. Median PFS time was 13 months. Raised lactate dehydrogenase levels at transformation (P =.0031) was identified as the only adverse significant predictor of PFS on multivariate analysis. A subgroup of patients with residual chemosensitive disease who attained complete remission after high-dose therapy had the best outcome, with an OS at 5 years of 69%. A comparison with matched patients with low-grade disease and with de novo high- or intermediate-grade lymphoma showed no significant difference in OS (P =.939 and P =.438, respectively). CONCLUSION: Patients with chemosensitive transformed lymphoma should be seriously considered for high-dose therapy and autologous stem-cell support.

Immunocytoma: a retrospective analysis from St Bartholomew's Hospital-1972 to 1996.

PURPOSE: To analyze the presentation features and outcome for patients with immunocytoma (IMC) managed at St Bartholomew's Hospital (SBH), London, United Kingdom, between 1972 and 1996. Outcome was compared with that of patients with small lymphocytic lymphoma (SLL)/B-cell chronic lymphocytic leukemia (B-CLL) treated at SBH during the same period. PATIENTS AND METHODS: One hundred twenty-six patients with newly diagnosed IMC were identified. Patients were subclassified (using the Kiel classification) as having lymphoplasmacytoid (n =92), lymphoplasmacytic (n = 24), polymorphous (n = 9), or undetermined (n = 1) IMC. Six patients (5%) had stage I to IIE disease; the rest had advanced disease. Treatment was given according to disease stage. Seven patients were managed expectantly. RESULTS: Eighty-two (69%) of 119 patients responded to treatment, but complete remission was seen in only 15 (13%) of 119. Treatment failed in 29 (24%) of 119 patients. There were three treatment-related deaths; five patients were not assessable for response. When survival of patients with IMC was compared with that of patients with B-CLL/SLL, a significant difference was found (P <. 01); this difference was maintained when only patients in whom the diagnosis was based on lymph node biopsy were considered (P =.01). A comparison of the three IMC subgroups showed that there was a trend (P =.06) toward a difference between B-CLL/SLL and the lymphoplasmacytoid subtype. CONCLUSION: Patients diagnosed with IMC are generally older and present with advanced disease. Conventional therapies usually result in incomplete responses of short duration. Overall, these results support the proposed World Health Organization reclassification of IMC to include lymphoplasmacytoid lymphoma (Kiel classification) as a variant of B-CLL/SLL.

Multicenter phase II study of fludarabine phosphate for patients with newly diagnosed lymphoplasmacytoid lymphoma, Waldenström's macroglobulinemia, and mantle-cell lymphoma.

PURPOSE: Fludarabine phosphate (F-AMP) has significant activity in follicular lymphoma and in B-cell chronic lymphatic leukemia, where it has demonstrated high complete response (CR) rates. Lymphoplasmacytoid (LPC) lymphoma, Waldenstrom's macroglobulinemia (WM), and mantle-cell lymphoma (MCL) also present with advanced-stage disease and are incurable with standard alkylator-based chemotherapy. A phase II trial was undertaken to determine the activity of F-AMP in patients newly diagnosed with these diseases. PATIENTS AND METHODS: Between 1992 and 1996, 78 patients (aged 18 to 75 years) received intravenous F-AMP (25 mg/m2/d for 5 days, every 4 weeks) until maximum response, plus two further cycles as consolidation. The primary end point was response rate; secondary end points included time to progression (TTP), duration of response, and overall survival (OS). RESULTS: Forty-four (62%) of 71 assessable patients had a response to F-AMP (LPC lymphoma, 63%; WM, 79%; MCL, 41%); the CR rate was 15%. At a median follow-up of 1.5 years, 19 of 44 responding patients have had progression of lymphoma; the median duration of response was 2.5 years. The median survival has not yet been reached. There was no significant difference in the duration of response or OS between patients with different histologies; TTP was shorter in patients with MCL (P = .015). Myelosuppression was relatively common, and the treatment-related mortality (TRM) was 5%, mostly associated with pancytopenia and infection. CONCLUSION: Single-agent fludarabine phosphate is active in previously untreated LPC lymphoma and WM, with only moderate activity in MCL. However, the CR rate is low, and the TRM is relatively high. Its role in combination chemotherapy remains to be demonstrated.

High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow-up.

PURPOSE: To evaluate the long-term results of high-dose therapy (HDT) in follicular lymphoma, with specific emphasis on the prognostic significance of polymerase chain reaction (PCR)-detectable Bcl-2/IgH rearrangements. PATIENTS AND METHODS: Between June 1985 and October 1995, 99 patients with follicular lymphoma received HDT as consolidation of second or subsequent remission. Bone marrow was treated in vitro with anti-B-cell antibodies and complement. RESULTS: Sixty-five patients remained alive, 49 treatment-failure free, with a median follow-up of 5.5 years (range, 1.5 to 12.5 years). Four "early" and 10 "late" deaths occurred from treatment-related causes; seven of the latter were due to secondary myelodysplasia (s-MDS) or secondary acute myeloblastic leukemia. Overall, 12 (12%) of the 99 patients developed s-MDS or acute myeloblastic leukemia. Kaplan-Meier estimates of freedom from recurrence (FFR) and survival rates at 5 years were 63% (95% confidence interval [CI], 52% to 72%) and 69% (95% CI, 58% to 78%), respectively. For all 99 patients, in multivariate analysis, absence of the Bcl-2/IgH rearrangement at the time of diagnosis (hazards ratio [HR], 0.39; P =.04) and three or fewer treatment episodes before HDT (HR, 0.03; P =.001) were significant prognostic factors for improved survival. For patients bearing Bcl-2/IgH rearrangements, in univariate and multivariate analyses, absence of a PCR-detectable Bcl-2/IgH rearrangement during follow-up was associated with a significantly lower risk of recurrence (adjusted HR, 0.13; P <.001) and death (HR, 0.25; P =.02), whereas the PCR status of the reinfused bone marrow did not correlate with outcome. CONCLUSION: Prolonged FFR can be achieved in patients with follicular lymphoma after HDT, but as yet there is no survival advantage compared with conventional treatment. These results confirm that elimination of cells bearing the Bcl-2/IgH rearrangement is highly desirable and should be attempted. The incidence of s-MDS is of increasing concern in this setting.

Tositumomab and iodine I 131 tositumomab for recurrent indolent and transformed B-cell non-Hodgkin's lymphoma.

PURPOSE: An open-label phase II study was conducted at two centers to establish the efficacy and safety of tositumomab and iodine I 131 tositumomab at first or second recurrence of indolent or transformed indolent B-cell lymphoma. PATIENTS AND METHODS: A single dosimetric dose was followed at 7 to 14 days by the patient-specific administered radioactivity required to deliver a total body dose of 0.75 Gy (reduced to 0.65 Gy for patients with platelets counts of 100 to 149 x 10(9)/L). Forty of 41 patients received both infusions. RESULTS: Thirty-one of 41 patients (76%) responded, with 20 patients (49%) achieving either a complete (CR) or unconfirmed complete remission [CR(u)] and 11 patients (27%) achieving a partial remission. Response rates were similar in both indolent (76%) and transformed disease (71%). The overall median duration of remission was 1.3 years. The median duration of remission has not yet been reached for those patients who achieved a CR or CR(u). Eleven patients continue in CR or CR(u) between 2.6+ and 5.2+ years after therapy. Therapy was well tolerated; hematologic toxicity was the principal adverse event. Grade 3 or 4 anemia, neutropenia, and thrombocytopenia were observed in 5%, 45%, and 32% of patients, respectively. Secondary myelodysplasia has occurred in one patient. Four patients developed human antimouse antibodies after therapy. Five of 38 assessable patients have developed an elevated thyroid-stimulating hormone; treatment with thyroxine has been initiated in one patient. CONCLUSION: High overall and CR rates were observed after a single dose of tositumomab and iodine I 131 tositumomab in this patient group. Toxicity was modest and easily managed.

p53 protein expression in Reed-Sternberg cells of Hodgkin's disease.

Hodgkin's disease (HD) is perceived to be a malignant disease of the lymphoid system. One of the main obstacles into the investigation of the cell biology of Hodgkin's disease is the relative paucity of Reed-Sternberg cells (or variants), the presumed neoplastic component of this condition, which often make up less than 1% of the total cell number.

Inhibition of the adrenocorticotropin response to surgery in humans: interaction between dexamethasone and fentanyl.

We examined the plasma ACTH and cortisol responses to surgery in 25 patients with atherosclerotic heart disease undergoing myocardial revascularization. The patients were all premedicated with diazepam, and general anesthesia was induced with thiopental. They were randomly assigned to one of four groups: I) no dexamethasone (DEX), enflurane anesthesia, II) 40 mg DEX, iv, 45-60 min before sternotomy, enflurane anesthesia, III) no DEX, fentanyl [N-(1-phenethyl-4-piperidyl)propionanilide] anesthesia (50-100 micrograms/kg), and IV) DEX, fentanyl anesthesia. Isokalemic hemodilution of significant magnitude occurred during cardiopulmonary bypass. All groups had significant increases in plasma ACTH during surgery, which returned to control levels 22 h after the bypass. Group I (no DEX, no fentanyl) and group III (no DEX, fentanyl) patients had large similar increases in plasma ACTH, which peaked 2-4 h postbypass [400 +/- 83 (+/- SEM) pg/mL; 88 +/- 18 pmol/L]. The group II (DEX, no fentanyl) patients also had large increases in ACTH which were similar to those in groups I and III, except 2-4 h postbypass (183 +/- 91 pg/mL; 40 +/- 20 pmol/L). The group IV (DEX, fentanyl) patients had a significantly attenuated ACTH response to surgery; the mean plasma ACTH level 2-4 h postbypass was only 54 +/- 21 pg/mL (12 +/- 5 pmol/L). Therefore, although DEX or fentanyl alone had a minimal effect on the ACTH response to surgery, a significant attenuation occurred when DEX and fentanyl were used in combination. We conclude that glucocorticoids and morphine agonists exert interactive inhibitory effects on ACTH release in humans, probably by virtue of their suppression of CRH release from the hypothalamus.

Fludarabine in low-grade lymphoma.

During the last 4 years, 88 patients with low-grade non-Hodgkin's lymphoma have received fludarabine, 25 mg/m2 daily for 5 days, repeated every 3 to 4 weeks. Fifty-one patients received fludarabine at recurrence or when the disease was deemed resistant to conventional treatment, 21 patients received the drug in the context of "minimal residual disease" in the hope of complete remission being achieved with a view to proceeding to myeloablative therapy (cyclophosphamide and total body irradiation) with autologous bone marrow transplantation, and 16 newly diagnosed patients received fludarabine as first-line therapy. Myelosuppression was the predominant toxicity, with 55% and 31% of previously treated and newly diagnosed patents, respectively, becoming neutropenic (neutrophils < or = 1.0 X 10(9)/L). The response rate (complete and partial response) was 44% for both patients with recurrent/resistant disease (20 of 45 evaluable patients) and for those with "minimal residual disease" (nine of 20 evaluable patients). In newly diagnosed patients, the response rate was 69% (11 of 16 patients). Five patients died of infection while neutropenic. These results confirm the activity of fludarabine in low-grade non-Hodgkin's lymphoma. Its precise role remains to be determined.

Antigen preservation in infarcted lymphoid tissue. A novel approach to the infarcted lymph node using monoclonal antibodies effective in routinely processed tissues.

We studied 11 cases of malignant lymphoma diagnosed concurrently with or following lymph node infarction. Cases included seven B-cell lymphomas, three T-cell lymphomas, and one case of Hodgkin's disease. Sections of viable and infarcted tissue were immunostained in parallel using a panel of antibodies effective in routinely processed, wax-embedded tissue. The panel included anti-leucocyte-common antigen (CD45), T-cell-associated antigens (UCHL1, MT1), B-cell-associated antigens (MB1, 4KB5 (CD45R), MT2, LN1), a B-cell-specific antigen (L26), C3D-1 (CD15), and BER-H2 (CD30). Antibodies to intermediate filament cytoskeletal proteins, epithelial membrane antigen, and Factor VIII-related antigen were also used. In eight cases, staining of the infarcted material gave evidence of a lymphoid proliferation of either T- or B-cell type; an in the case of Hodgkin's disease, the results supported this diagnosis. The immunophenotype derived in the infarcted tissue mirrored the findings in the viable material in these eight cases of non-Hodgkin's lymphoma. A case of testicular infarction with concurrent intraosseous lymphoma was also examined. Staining in this case provided evidence of infarcted lymphoma. Thus, immunostaining of infarcted lymphoid tissue with these novel antibodies provides valuable information that conventional light microscopy cannot offer.

True histiocytic lymphoma: a morphologic, immunohistochemical, and molecular genetic study of 13 cases.

We describe the morphologic, immunohistologic, and genotypic characteristics of 13 cases of true histiocytic lymphomas. Six cases presented with primary gastrointestinal involvement, five with lymphadenopathy, the other sites involved being the bone marrow and the skin. The neoplastic cells displayed large abundant eosinophilic cytoplasm, occasionally vacuolated with folded or bizarre-shaped nuclei with prominent nucleoli. Mitotic figures were numerous. Multinucleated cells were common. The pattern of growth was usually diffuse and noncohesive. Spindle cell sarcoma-like areas were evident in five cases, with a prominent foam cell component in four cases. All cases expressed histiocyte-associated markers (CD68, lysozyme, alpha-1-antitrypsin), CD45 or CD45RO, and were negative for CD1a, epithelial, and B- and T-cell lineage-specific markers. Reactivity for S-100 was observed in a variable proportion of cells in 11 cases. The proliferation fraction varied from 3 to 88%. Genotypic analysis for T-cell receptor or immunoglobulin gene rearrangement demonstrated a germline configuration in all cases. We demonstrate that true histiocytic lymphoma is a rare distinctive pathologic entity that may be defined by immunohistochemical criteria and that recognition among histiocytic disorders is important for clinical and prognosis reasons.

Primary lymphoma of the small intestine. A clinicopathological study of 119 cases.

Small bowel lymphomas account for 20 to 40% of primary gut lymphomas in Western populations and are among the most common malignant tumours of the small bowel. We studied 119 cases of primary small bowel lymphoma presenting over 4 decades. Two thirds of the patients were men with a peak age incidence in the 7th decade. Common presenting features included abdominal pain, weight loss, small bowel obstruction, and acute abdomen. Tumours were classified using the Kiel European Association for Haematopathology Geneva Workshop scheme and phenotyped on paraffin sections; 66% were B cells, and 34% were T cell. In all cases, the antibodies L26 and polyclonal CD3 reliably distinguished between B- and T-cell tumours. Of the B-cell lymphomas, 62% were diffuse high grade, 20% were low-grade lymphomas of mucosa-associated lymphoid tissue, 11% had both low- and high-grade components, and 7% were other low-grade types. Of the T-cell lymphomas, 83% were high grade, and 49% were enteropathy associated. Most T-cell lymphomas were ulcerated plaques or strictures in the proximal small bowel; B-cell lymphomas tended to be annular or polypoid masses in the distal and terminal ileum. Survival data showed that low-grade B-cell lymphomas had the best outcome and T-cell lymphomas the worst. Adverse prognostic features included perforation, high-grade histology, multiple tumours and advanced stage.

Granulocyte and HLA-D region specific monoclonal antibodies in the diagnosis of Hodgkin's disease.

Tissue sections embedded in paraffin and fixed in formalin from 32 patients with Hodgkin's disease, representing the major histological subtypes, were studied using two granulocyte specific monoclonal antibodies (Leu-M1 and 3C4) and an HLA-D region specific monoclonal antibody (TAL-IB5). Reed-Sternberg cells were stained with one or other of the antigranulocyte antibodies in the nodular sclerosing and lymphocyte depleted subtypes. Reed-Sternberg cells in all but three cases of mixed cellularity Hodgkin's disease were positive with both Leu-M1 and 3C4. One case stained with only Leu-M1, and two cases were consistently negative with both antibodies. HLA-DR was widely expressed in the Reed-Sternberg cells of all three subtypes. In the four cases of lymphocyte predominant Hodgkin's disease the multinucleated Reed-Sternberg cells did not stain with either antigranulocyte antibody but were strongly positive with anti-HLA-DR. Twenty five cases of non-Hodgkin's lymphoma, in which there were multinucleated giant cells resembling Reed-Sternberg cells, were studied in a similar way. These cases included pleomorphic T cell and B cell lymphomas, histiocytic lymphomas, and malignant histiocytosis of the intestine. In none of these did the multinucleated cells stain with either antigranulocyte antibody, but in most cases the multinucleated cells stained with anti-HLA-DR. In two cases of the tumour stage of mycosis fungoides dot like intracytoplasmic staining was shown in the tumour cells with both antigranulocyte markers. The monoclonal antigranulocyte antibodies Leu-M1 and 3C4 are of considerable value in both the diagnosis and the differential diagnosis of Hodgkin's disease and are particularly valuable in that they can be applied to tissue fixed in formalin and embedded in paraffin. Antibody to HLA-DR, while useful, is of less value.

Monoclonal antibody L26: an antibody that is reactive with normal and neoplastic B lymphocytes in routinely fixed and paraffin wax embedded tissues.

Formalin fixed and paraffin wax embedded tissue from 85 well characterised cases of non-Hodgkin's lymphoma and Hodgkin's disease were studied using the avidin-biotin-peroxidase complex technique. Among the non-Hodgkin's lymphomas all cases of B cell lymphoma were reactive with L26, a monoclonal antibody which is as yet an unclustered pan B cell reagent, with the exception of pre-B cell acute lymphoblastic leukaemia and malignant lymphoma plasmacytic. Eighteen well characterised cases of T cell lymphoma, selected to include tumours previously shown to exhibit cross reactivity with antibodies to fixation resistant B cell related antigens, were similarly studied. Neoplastic cells in all but one case were unstained by L26. Twenty seven cases of Hodgkin's disease were also examined. In five cases all Reed-Sternberg cells and their variants were strongly stained by L26; only a proportion of Reed-Sternberg cells and their variants were recognised in a further five cases. Monoclonal antibody L26 promises to be a valuable reagent for the diagnosis of malignant lymphoma in routinely fixed and paraffin wax embedded tissues. Its advantage lies in its sensitivity and greater B cell specificity than any of the B cell related reagents currently available for the study of malignant lymphoma in fixed tissues.

Malignant lymphoma of the urinary bladder: a clinicopathological study of 11 cases.

AIM: To report the clinical and histological features and outcome of primary and secondary malignant lymphomas of the urinary bladder. METHODS: Eleven cases of malignant lymphoma of the urinary bladder were obtained from the registry of cases at St Bartholomews and the Royal London Hospitals. The lymphomas were classified on the basis of their morphology and immunophenotype, and the clinical records were reviewed. RESULTS: There were six primary lymphomas: three extranodal marginal zone lymphomas of mucosa associated lymphoid tissue (MALT) type and three diffuse large B cell lymphomas. Of the five secondary cases, four were diffuse large B cell lymphomas, one secondary to a systemic follicular follicle centre lymphoma, and one nodular sclerosis Hodgkins disease. Four patients with secondary lymphoma for whom follow up was available had died of disease within 13 months of diagnosis. Primary lymphomas followed a more indolent course. In one case, there was evidence of transformation from low grade MALT-type to diffuse large B cell lymphoma. The most common presenting symptom was haematuria. Cystoscopic appearances were of solid, sometimes necrotic tumours resembling transitional cell carcinoma, and in one case the tumours were multiple. These cases represented 0.2% of all bladder neoplasms. CONCLUSIONS: Diffuse large B cell lymphoma and MALT-type lymphoma are the most common primary malignant lymphomas of the bladder. Lymphoepithelial lesions in MALT-type lymphoma involve transitional epithelium, and their presence in high grade lymphoma suggests a primary origin owing to transformation of low grade MALT-type lymphoma. Primary and secondary diffuse large B cell lymphomas of the bladder are histologically similar, but the prognosis of the former is favourable.

Monoclonal antibody (UCHL1) that recognises normal and neoplastic T cells in routinely fixed tissues.

UCHL1 is a murine monoclonal antibody that recognises a 180-185 kD determinant on CD4 (72%) and CD8 (36%) positive T cells. This antibody is effective in formalin fixed and paraffin embedded tissues, using the immunoperoxidase method. One hundred and forty three cases of malignant lymphoma were examined. Neoplastic cells in 100% of cases of Mycosis fungoides (n = 10), 83% of cases of peripheral T cell lymphoma (n = 25), and 78% of cases of (T-ALL) T acute lymphoblastic lymphoma (n = 9) were stained by this antibody. In addition, staining was seen in 100% of cases of malignant histiocytosis of the intestine (n = 13), a condition now thought to be a T cell lymphoma. Two cases of true histiocytic lymphoma were also positive. This antibody stained neither the neoplastic cells in a wide range of B cell lymphomas (n = 62) nor Reed-Sternberg cells in 16 cases of Hodgkin's disease. UCHL1 also stained neoplastic cells in four cases of granulocytic sarcoma. A panel of normal tissues was similarly studied. Staining was seen in normal T cells and mucosal intraepithelial lymphocytes, macrophages, mature myeloid cells, and endometrial stromal granulocytes. UCHL1 is a monoclonal antibody that identifies T cells in formalin fixed paraffin embedded tissues, and should prove useful for diagnosing T cell lymphomas, especially when only formalin fixed tissue is available for diagnosis.