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Notes: Background:  Criteria for distinguishing between cutaneous lymphoid hyperplasia (CLH) and low-grade B-cell lymphoma are not well defined. We examined the hypothesis that the presence of a clonal B-cell population in heavy multinodular lymphoid infiltrates correlates with clinical presentation and outcome.Methods:  We identified 29 patients with skin lesions characterized histologically by a heavy dermal lymphocytic infiltrate with a multinodular architecture and extension into deep dermis and subcutaneous fat. Clonality was assessed immunophenotypically by light-chain restriction and also by analysis for IgH-gene rearrangement using PCR on DNA extracted from paraffin blocks.Results:  Follow-up (mean 80 months; median 45 months) was obtained in all patients. Twenty-four patients (83%) presented with a solitary lesion: only four had solitary recurrences, and none developed multiple synchronous lesions or systemic B-cell lymphoma. However, 9/24 of these solitary lesions (38%) were clonal by light-chain restriction or IgH PCR; 5/29 patients (17%) presented with multiple recurrent lesions and continued to develop lesions during the period of follow-up; 3/5 patients (60%) with multiple lesions demonstrated a B-cell clone. No patient developed systemic B-cell lymphoma.Conclusions:  Heavy, multinodular cutaneous lymphoid infiltrates have an excellent prognosis. Multiple lesions at presentation are the best predictor of recurrent multiple lesions confined to the skin. The presence of a clonal B-cell population does not correlate with clinical presentation or histology, nor does it predict development of further lesions or systemic lymphoma.

Notes: The generic term aggressive B-cell lymphoma includes a variety of entities, each with particular diagnostic and therapeutic issues. To define these entities better and to help confront such issues, a workshop was organized by the European Association of Haematopathology (EAHP) and the Society of Haematology during the XI Meeting of the EAHP, held in Italy in May 2002. Participants were asked to submit cases under various categories and all cases submitted were examined and reviewed by the panel members. The panel's diagnoses formed the basis for discussion at the workshop and a limited number of cases were selected to be presented in more detail and discussed during the workshop. After the workshop the panel met again to discuss the outcome, summarized in this report, which describes the panel's proposals regarding diagnostic criteria, terminology, the definition of new entities and evaluation of biological differential and new prognostic parameters.

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: Abstract Background: Lymphomas of mucosa associated lymphoid tissue (MALT) are a special type of extranodal lymphoma, possibly related to chronic antigenic stimulation. Increased cancer susceptibility may also contribute to the development of MALT lymphoma (MALToma). It has been suggested that patients with MALToma have an increased incidence of other malignancies. Patients and methods: We retrospectively reviewed the histology and clinical records of 147 patients with MALToma, including 51 cases of gastric MALToma. The incidence of any second malignancy was confirmed with a provincial registry. The relative rates of cancer, excluding MALToma, were calculated relative to the background population of the same age group and secular year. Results: A total of 41 tumors occurred in 32 patients (21%), including 22 solid tumors. The incidence of solid tumors in the gastric MALToma group was 15%. Seven patients had two or more second malignancies. Cancer occurred before diagnosis of MALToma in 29 cases, concurrent with MALToma in three, and after MALToma in nine. Follow-up of the surviving patients is short (median 17.6 months). The relative rate from birth of a second malignancy was 0.86 in the whole group (90% confidence interval (CI): 0.62–1.16) and 0.95 (90% CI: 0.55–1.54) in the gastric MALToma group. The rates were roughly the same if skin cancers were excluded. Conclusions: The incidence of second cancers in this series is similar to previous reports. However, when compared to an age-matched population followed for the same period of time, MALToma patients do not appear to have a statistically significant increased rate of cancers.

Notes: Abstract Background:Allogeneic bone marrow transplantation (BMT) has beenused in patients with low-grade lymphoma (LGL) and chronic lymphocyticleukemia (CLL) with the goal of achieving long-term disease-free survival. Patients and methods:Twenty-nine patients with these diagnoses(LGL = 19, CLL = 10) received allogeneic BMT between September 1995 andJanuary 1999. Median age was 42 (range 20–52) years. Twenty-three oftwenty-nine patients (79%) were Ann Arbor or Rai stage IV at the timeof transplant; twenty-four (83%) had never achieved complete remission(CR). Donor source was HLA-matched sibling (20), unrelated (8) and syngeneic(1). Results:Seventeen patients are currently alive, a median of 29months (range 1–85) post-BMT with a median KPS of 90%.Twenty-three of twenty-seven evaluable patients (85%) achieved CRpost-BMT. Six patients had refractory/recurrent disease. Death occurredrelated to transplant complications in eight patients and underlying diseasein four. Overall and event-free survival for the whole group is 51% and44%, respectively. Conclusions:Allogeneic BMT for young patients with advanced stageLGL or CLL is a feasible strategy that can result in achievement of long-termdisease-free survival.

Notes: Abstract Purpose: To define both the natural history of and prognostic factors affecting outcome post relapse from a complete response in advanced stage diffuse large-cell lymphoma. Patients and methods: A total of 468 patients aged 17–74 years received the 12-week duration chemotherapy regimens MACOP-B, VACOP-B and ACOP-12 between 1 April 1981 and 31 December 1995 for advanced stage diffuse large, mixed or immunoblastic lymphoma. Of these 402 entered a complete remission, 97 (24%) of whom subsequently relapsed. Initial staging data, follow-up, and relapse information were analyzed to define the natural history of relapse and also subjected to univariate and multivariate correlation with overall (OS) and failure free survival (FFS). Results: Eleven percent of the relapses were low grade. All other relapses were of intermediate grade with 75% occurring within the first two years, the remainder up until the eleventh year. Median and five-year OS from the time of relapse for intermediate grade relapse were 12 months and 20%; for FFS they were eight months and 18% respectively. Adverse independent factors, for both OS and FFS were: less than one year to relapse, decreasing performance status at relapse, and more than three nodal sites at relapse. Conclusions: Low-grade relapse is not uncommon in patients who initially presented with diffuse large cell lymphoma. As the management of low- and intermediate grade disease is so different biopsy proof of the nature of the relapse is of value. The prognostic factors identified need to be taken into consideration when analyzing results from trials of secondary treatment so as to avoid erroneous conclusions about comparative treatment efficacy.

Notes: Abstract Objectives: To determine the prevalence of hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin's lymphoma (NHL) in British Columbia. Design: A cross-sectional analysis. Setting: The British Columbia Cancer Agency (BCCA), a Canadian provincial tertiary oncology referral center. Subjects: Consecutive patients with B-cell NHL registered onto the BCCA lymphoma database in 1996 and part of 1997 and a control group of patients with T-cell NHL registered on the database from 1995 through 1997. Patients with HIV infection were excluded from the analysis. A second control group (n = 1085) consisted of health-care workers tested for HCV infection following a needle-stick injury. Interventions: Stored sera from patients with B-cell NHL (n= 88) and T-cell NHL (n = 37), identified from the database, were tested for the presence of HCV infection with commercially available serologic tests. Main outcome measures: HCV seropositivity in the B-cell lymphoma group compared to the control groups (T-cell NHL and health-care workers). Results: 2.3% of the B-cell NHL group, none of the T-cell NHL group and 1% of the health-care worker control group were positive for HCV infection. These results were not statistically significantly different. Conclusion: Patients in British Columbia with B-cell NHL do not have an increased prevalence of HCV infection. These data suggest that the lymphotrophism of HCV may differ by regional, racial and genotypic variations around the world.

Notes: Abstract Background: Low grade malignant lymphomas arising from mucosa associated lymphoid tissue (MALT) represent a distinct clinicopathological entity. The cytogenetic findings and molecular genetics of MALT lymphomas remain minimally defined. Cytogenetic studies infrequently constitute part of the diagnostic work-up of MALT lymphomas, most commonly due to small biopsy size and their extranodal localization. Only 28 MALT cases with a clonal karyotype have been published to date. A number of chromosomal abnormalities have been observed with the majority of the cases featuring trisomy of chromosome 3 which is present in up to 78% of the cases. Materials and methods: A total of 116 cases of MALT lymphoma were diagnosed at BCCA between 1988 and 1997. Eleven cases of pathologically confirmed MALT lymphomas were subjected to cytogenetic analysis at the time of the initial evaluation. Eight of 11 cases yielded successful cultures and the presence of a clonal karyotype using standard cytogenetic methodology. In addition, a single case of orbital MALT lymphoma with a clonal karyotype has been obtained through our consultative practice from University of Nebraska Medical Center. These nine cases of MALT lymphoma with a clonal karyotype are the subject of this report. Results and conclusion: In this study we report nine cytogenetically studied MALT lymphomas, three of which feature a novel t(11;18)(q21;q21) translocation which has also been observed in five other MALT cases described in the literature. This recurrent translocation is the most common translocation associated with MALT lymphomas being present in 33% (three of nine) of our cases and 18% (five of 28) of the previously published cases. The results suggest that a potentially important gene located at one of these breakpoints may be involved in the pathogenesis of MALT lymphomas.

Notes: Abstract Despite advances in immunohistochemistry and molecular biology, the distinction between classical Hodgkin's lymphoma and related diseases such as nodular lymphocyte-predominant Hodgkin's disease, T-cell rich large B-cell lymphoma or anaplastic large cell lymphoma has remained difficult in rare cases. Lack of clear-cut diagnostic criteria represents a problem for both the pathologist and the clinician. To delineate this 'grey zone' between classical Hodgkin's lymphoma and non-Hodgkin's lymphoma (NHL) and to develop criteria for classification of such cases, 12 expert hematopathologists each submitted one to five borderline cases to a workshop. Cases were reviewed and classified at a multiheaded microscope and criteria were established for the diagnosis of questionable cases. Well established entities such as classical Hodgkin's lymphoma, anaplastic large-cell lymphoma and TCRBCL were defined more strictly and cases with unusual morphology or antigen expression could be identified. A distinctive subset of cases representing mediastinal large B-cell lymphomas with features of Hodgkin's lymphoma was identified.