Predominance Hodgkin's Disease Research Articles

European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes

AbstractParaffin blocks and clinical data from 521 patients with lymphocyte predominance Hodgkin disease (LPHD) diagnosed between 1970 and 1994 were collected from 16 European and United States oncological centers to establish the pathologic and clinical characteristics of a large patient cohort, to determine how frequent T-cell–rich large B-cell lymphoma (TCRLBCL) is among LPHD, and to find differential diagnostic criteria distinguishing between the 2 lymphoma categories. For this purpose, conventionally and immunohistologically stained sections were reviewed by a panel of hematopathologists. The diagnosis of LPHD was confirmed in only 219 of the 388 assessable cases (56.5%). This low confirmation rate was due mainly to the presence of a new variant of classical Hodgkin disease (CHD), which resembled, in terms of nodular growth and lymphocyte-richness, nodular LPHD and, in terms of the immunophenotype of the tumor cells, CHD and was designated nodular lymphocyte-rich CHD (NLRCHD). The nodules of LRCHD consisted—as in nodular LPHD—predominantly of B cells but differed from those present in LPHD in that they represented expanded mantle zones with atrophic germinal centers. Clinically, patients with LPHD and NLRCHD showed similar disease characteristics at presentation but differed in the frequency of multiple relapses and prognosis after relapse. Patients with LPHD and NLRCHD clearly differed from patients with CHD with nodular sclerosis or mixed cellularity, as they presented with an earlier disease stage and infrequent mediastinal involvement. As 97% of the LPHD cases showed a complete or partial nodular growth pattern, their differentiation from TCRLBCL was a rare problem in the present series.

Expression Status of BCL-6 and Syndecan-1 Identifies Distinct Histogenetic Subtypes of Hodgkin's Disease

The tumor cells in most cases of Hodgkin's disease (HD) have been recently recognized to originate from the B-cell lineage, but their precise differentiation stage is not fully clarified. Recently, we have reported that the histogenesis of B-cell lymphomas may be assessed by monitoring the expression pattern of BCL-6, a transcription factor expressed in germinal center (GC) B cells, and CD138/syndecan-1 (syn-1), a proteoglycan associated with post-GC, terminal B-cell differentiation. In this study, we have applied these two markers to the study of HD histogenesis. We have found that in nodular lymphocyte predominance HD (NLPHD) tumor cells consistently display the BCL-6+/syn-1− phenotype, indicating their derivation from GC B cells. Conversely, classic HD (CHD) is heterogeneous because the tumor cells of a fraction of CHD display the BCL-6−/syn-1+ phenotype of post-GC B-cells, whereas another fraction of CHD is constituted by a mixture of tumor cells reflecting the GC (BCL-6+/syn-1−) or post-GC (BCL-6−/syn-1+) phenotypes. BCL-6−/syn-1+ tumor cells of CHD are mostly found surrounded by T cells expressing CD40L, consistent with the observation that CD40 signaling downregulates BCL-6 expression. These data indicate that tumor cells of NLPHD uniformly display a GC B-cell phenotype, whereas the phenotype of tumor cells of CHD appears to be modulated by the surrounding cellular background, particularly CD40L+ reactive T cells.

Outcome of Lymphocyte Predominant Hodgkin Lymphoma: A Single Institutional Analysis

Background: Nearly 5% of patients diagnosed with Hodgkin lymphoma have the nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), also known as Hodgkin paragranuloma or lymphocytic and histiocytic predominant Hodgkin disease. Given the rarity of this variant of Hodgkin lymphoma, there is no consensus on the standard of care/regimen in this subgroup of patients. Therapeutic approach has spanned from radiotherapy alone, combined chemo-radiotherapy to chemotherapy alone or observation and recently the use of Rituximab anti CD20 monoclonal antibody as these cells expresses CD20 marker. We opt to evaluate the outcome of patients with newly diagnosed NLPHL in our institution. We also reviewed outcome of NLPHL patients treated with various chemotherapy such as ABVD, CVP or RCHOP ± Radiation.Methods: We retrospectively reviewed medical records of over 300 patients [mean age 45 (13-76)] with Hodgkin Lymphoma at Beaumont Hospital, an academic community center from January 2007 - January 2017. Given the rarity of the disease, a total of 13 patients were found to have pathologically confirmed diagnosis of NLPHL. Data regarding age, sex, stage of disease, treatment and outcome was analyzed.Results: Total 13 patients with NLPHL with age range from 13 to 80 years were studied. Demographic distribution of studied patients were 8(62%) white, 4 (31%) African Americans and 1 (7.6%) Asian. Out of these, 8 (62%) were males and 5 (38%) females. A total of 9 (69%) patients have stage III disease on diagnosis while 4 (31%) patients had stage II disease on diagnosis. Out of 9 patients with stage III disease, 6 (67%) received chemotherapy alone (ABVD or CVP) whereas 3 (33%) received combined chemotherapy and radiotherapy. One patient in the chemotherapy alone arm, recurred within 24 months of treatment and received local therapy with radiation. Among those with stage II disease on diagnosis, 3 patients received radiation therapy alone while one patient was observed and did not receive any treatment. Overall, out of 13 patients studied, 12 (92%) are still alive and continues to follow with our clinic with no recorded relapse to date. One patient developed astrocytoma grade III and died of intracranial hemorrhage.CONCLUSION: Although the standard therapeutic management for patients with NLPHL remains controversial. Our data showed that regardless of the regimen selected (chemotherapy alone or combined chemo-Radiotherapy), patients with Lymphocyte predominant Hodgkin Lymphoma treated with ABVD ± Radiation have excellent outcome. Although our study represents a single institutional analysis, it concurs with recent studies that clinical outcome in patients with NLPHL is favorable with chemotherapy. DisclosuresNo relevant conflicts of interest to declare.

Outcome of Lymphocyte Predominant Hodgkin Lymphoma

BACKGROUND: Lymphocyte predominant Hodgkin Lymphoma (LPHL) , also known as Hodgkin paragranuloma or lymphocytic and histiocytic predominant Hodgkin disease. It accounts for 5% of the lymphoma in the western world Since LPHL is a rare type of lymphoma different treatment modalities used to treat it including radiotherapy alone, combined chemotherapy and radiotherapy, chemotherapy alone and recently the use of Rituximab anti CD20 monoclonal antibody as LPHL expresses CD20 marker . The results are variable. Patients of LPHL also have frequent relapses beyond 5 years of treatment as compared to cHL and high rates of transformation to DLBCL .OBJECTIVE:To review outcome of LPHL patients treated with various chemotherapy regimens ( ChlVpp/ABVD) and (ABVD/COPDac) alone or in combination with radiotherapy.METHODS AND MATERIALS: Data of total 301 patients reviewed . Out of which 15 were of LP Hodgkin (4.98%). Retrospective review of 15 patients of LP Hodgkin Lymphoma patients enrolled between January 2006 to December 2013 was done. Data regarding age, sex, stage of disease , treatment and outcome was analyzed.RESULTS: Total 15 LP HD patients with age range from 2 to 18 years were included from 2006 to 2013. Mean age of patients was 10 years. Median was 9. Out of these 13 (86.7% ) were males and 2 (13.3%) females, most of them are of stage III (40%). Majority , 9 patients (60 %). were treated with ChlVpp/ABVD protocol. XRT was given to 5 patients (33.3%). Total 12 (80%) are still on follow up and 3 (20%) relapsed.CONCLUSION: Patients of Lymphocyte predominant Hodgkin Lymphoma treated with chemotherapy had a better outcome . DisclosuresNo relevant conflicts of interest to declare.

Lymphome de Hodgkin nodulaire à prédominance lymphocytaire chez l’enfant: présentation clinique, biologique et prise en charge actuelle

Nodular lymphocyte predominant Hodgkin disease (NLPHL) differs clearly from classical Hodgkin lymphoma (cHL) by clinical presentation and more favorable outcome. Patients often present with early stage IA or IIA. Extranodal disease and B-symptoms are uncommon. Histologically, NLPHL is characterized by the presence of atypical “lymphocyte predominant cells” (LP cells) or “pop-corn” cells in a non-neoplastic and reactionnal nodular background of small mature B-lymphocytes. LP cells are negative for CD30 and positive for CD20, BCL6 and EMA (in half of the cases). FDG-PET plays an important role in evaluation of cHL and NLPHL for staging, therapy assessment and relapse. Historically, patients with NLPHL have been treated like patients with cHL, but their very favorable prognosis and the risk of late complications of chemotherapy and/or radiotherapy have led to a de-escalation in recent years. Patients with early stage could be treated by surgical adenectomy alone or associated with not intensive chemotherapy. Currently, there is no consensus regarding to the optimal treatment of patients with advanced stage. Rituximab used as monotherapy or in association with chemotherapy has achieved complete or partial responses. The outcome of NLPHL is singular by the frequent occurrence of late relapses and the risk of transformation into aggressive B lymphoma justifying an extended follow-up. Further prospective studies are needed to optimize treatment of these advanced and recurrent forms.

Utilization of radiation therapy in early-stage Hodgkin disease and its impact on survival

8511 Background: Despite numerous randomized trials confirming the benefit of consolidation radiation therapy (RT) in the management of early stage Hodgkin disease (HD), utilization of RT in this setting remains variable. We performed a population-based analysis to assess the utilization of RT and its impact on overall and cause specific survival. Methods: The surveillance, epidemiology and end results (SEER) registry was used to identify patients aged 15–75 years diagnosed between 1990–2004 with early stage (stage I-IIA/B) HD, excluding nodular lymphocyte predominant HD. Kaplan-Meier analysis was performed to evaluate the effect of RT on overall survival (OS) and cause-specific survival (CSS). Subgroup survival analyses were also performed by era of treatment (1990–1997 and 1998–2004), sex, and patient age (<30, 30–50, and >50 years). Results: A total of 9729 patients met inclusion criteria. Median age of all patients was 34 years. The majority (71.3%) had nodular sclerosis (NS) type HD. By clinical stage, 3399 (34.9%) were stage I, and 6330 (65.1%) were stage II. 5352 patients (55%) received RT. RT was more likely to be employed during the early era of treatment, in younger patients, females, non-Blacks, and in NS, mixed cellularity and lymphocyte-rich HD. For the entire cohort, RT was associated with a significant (p<0.001) improvement in OS and CSS (hazard ratio of 0.537 and 0.437, respectively). The benefit of RT for OS and CSS remained significant for all subgroups analyzed including the era of treatment, sex, and age (p≤0.001). Conclusions: In this large population-based series of early stage HD patients, the use of RT is associated with a significant OS and CSS benefit across all subgroups. Current efforts in clinical trials have aimed at decreasing the utilization of RT among this patient population. This shift in practice is reflected in the data presented here. The omission of RT from the treatment paradigm, however, appears to be related with diminished survival. No significant financial relationships to disclose.

Recurrent cerebral venous thrombosis revealing paraneoplastic angiitis in Hodgkin’s lymphoma

Recurrent cerebral venous thrombosis (CVT), as a manifestation of paraneoplastic angiitis and revealing of nodular lymphocyte predominant Hodgkin's disease (NLPHD), is an extremely rare condition. We herein report a 55-year-old man who developed recurrent CVT despite efficacious anticoagulant therapy and subsequent stenting of the superior longitudinal sinus. Progressive neurological deterioration ensued and a body scan revealed axillary lymph nodes. Pathological analysis led to a diagnosis of NLPHD. Conventional angiography showed CVT and multiple arterial narrowings. A paraneoplastic primary cerebral angiitis with prominent venous structure involvement was suspected. Immunotherapy using rituximab and steroids provided a dramatic recovery. This case of CVT due to paraneoplastic cerebral angiitis is a rare condition and represents a new, very rare manifestation of nodular lymphocyte predominant Hodgkin's disease.

Results of a Prospective Phase II Trial of Limited and Extended Rituximab Treatment in Nodular Lymphocyte Predominant Hodgkin's Disease (NLPHD).

Background: NLPHD represents a unique clinical entity characterized by limited peripheral nodal disease, an indolent behavior with a frequent relapse pattern following radiotherapy or chemotherapy, and late treatment-related effects. Distinct from classical HD, the malignant cells of NLPHD are universally CD20+ and we therefore postulated that rituximab may have activity with fewer adverse effects.Methods: In this prospective phase II trial, patients (pt) with untreated or relapsed CD20+ NLPHD and measurable disease were eligible to receive four weekly doses of rituximab at 375 mg/m2. Restaging studies after completion of all treatment were performed at 1, 3 and 6 months (mo), and every 6 mo thereafter to progression. Endpoints were estimated response rate, freedom from progression (FFP) and safety. We previously reported that FFP was less than 1 year despite the fact that all patients responded to a limited, weekly × 4 treatment (Ekstrand et al. Blood 101:4285, 2003). The protocol was then modified to repeat 4 weekly 375 mg/m2 doses at 6 mo intervals for 2 yr. One patient received an extended rituximab course after progression on the limited course.Results: Pt received limited (n=23, 12 previously untreated) or extended (n=16, 9 previously untreated) rituximab. Median age at treatment was 44 yr (17–71) with 26 males. Among 21 previously untreated pt, stages were I (6), II (8), or III (7). Median follow-up is 60 months (mo) for all pt, 72 mo for limited and 30 mo for extended treatment pt. Treatment-related adverse events were minimal and no grade 3 or 4 toxicities were reported. All but 1 pt responded (OR 97%) with CR/CRu in 27 (69%), and PR in 11 (28%) and SD in 1 (3%). CR/CRu was achieved in 56% limited and 88% extended rituximab pt (p=0.08). No difference was observed in previously treated v untreated pt. To date, 17 progressions (15 limited, 2 extended rituximab) have been recorded. Median FFP was 24 mo for limited and not reached for extended rituximab (p=0.03). FFP at 30 months was estimated at 52% for limited rituximab and 88% for extended rituximab pt. Four pt transformed to large cell lymphoma (one after multiple relapse treatments). Three deaths occurred, one each due to colon cancer, acute leukemia (pt heavily pre-treated with radiation and MOPP), and large cell lymphoma. For all 38 pt, median follow-up from diagnosis is 7.5 yr (range (<1–38) and survival from diagnosis is estimated at 97% at 10 yr and 85% at 20 yr.Conclusions: Rituximab is an effective treatment in de novo or recurrent NLPHD that may be associated with fewer adverse effects than conventional therapy. FFP is prolonged with an extended treatment but additional follow-up is needed to better assess the duration of benefit.

Ultrasound Guided Core Biopsy of the Spleen in Lymphoma Diagnosis.

Patients with clinical or radiological splenic abnormalities are frequently referred to the lymphoma service for assessment. Previously diagnosis would require open biopsy or diagnostic splenectomy, with significant associated morbidity. Cytological examination of fine needle aspiration biopsy material is insufficient for accurate diagnosis and classification of lymphoma. Concerns regarding the risk of splenic core biopsy have limited its application. We report our experience with an ultrasound (US) guided technique, with particular reference to diagnostic yield, accuracy and complication rate. Sixty-two procedures were performed in 57 patients, 28 males and 34 females, median age 61 years (range 18–84). Biopsy was requested for diagnosis of isolated splenic abnormalities (n=28) or where the spleen represented the primary clinical or radiographic abnormality (n=34). Splenic abnormalities evaluated by US or computed tomography were defined as diffuse (n=26), multiple focal (n=24) or solitary focal (n=12) lesions. Using a subcostal or intercostal approach, a cutting needle was passed under US guidance during tidal respiration. Seven patients received platelet transfusion prior to biopsy for platelet counts <100 × 109/L. Coagulation screening tests were normal in all cases. A median of two cores (range 1–4) was obtained. The complication rate was very low. Only 1 patient suffered a significant haemorrhage despite a normal platelet count. This was managed conservatively and no patient required surgical intervention. Eight patients experienced local discomfort requiring analgesia before discharge. Pathological samples adequate for diagnosis were obtained from 59/62 (95%) procedures. Of these 59 specimens, malignant diagnoses were reached in 34 (31 lymphoma, 3 metastatic adenocarcinoma), from patients with both diffusely abnormal spleens (n=14) and focal splenic lesions (n=20). Fourteen specimens revealed benign pathology (including extramedullary hemopoiesis, granulomas and chronic inflammation) whilst 11 were normal. Sufficient material was obtained for immunohistochemistry to be performed on all 31 lymphoma biopsies allowing sub-classification in all but one case. Lymphoma diagnoses were diffuse large B cell lymphoma (DLBCL) (n=17), splenic marginal zone lymphoma (n=8), nodular lymphocyte predominant hodgkin's disease (n=2), hodgkin's lymphoma (n=1), mantle cell lymphoma (n=1), lymphoplasmacytoid lymphoma (n=1), low grade non-hodgkin's lymphoma (n=1). In 5 patients with DLBCL the spleen was the only site of disease. Subsequent therapeutic splenectomy was performed in 14 patients (17 prior biopsies) and demonstrated no false positives and 1 false negative core biopsy result. The 20 remaining patients with normal or benign spleen histology on core biopsy have reached a median follow-up of 21 months (range 3–157). No further false negative results have been identified by alternative tissue biopsy (n=10) or clinical evaluation. The 1 false negative core biopsy was followed immediately by splenectomy due to high clinical suspicion and a diagnosis of hepatosplenic T cell lymphoma was reached. US guided core biopsy of the spleen is a safe procedure with high accuracy. It allows a spleen conserving approach and we recommend it as a technique in the diagnosis or exclusion of splenic lymphoma.

HAEMACARE Project: Reclassifing Hematologic Neoplasias According Morphological Data.

Aims: The European Project HAEMACARE (VI Frame Research Program), is working in the reclassification of hematological neoplasias included in population based Cancer Registries of 13 European countries with the objective to improve and standardize morphological data validation.Patients and methods: a multidisciplinary research group of the I+CS integrated by epidemiologists, hematologists, pathologists is working in the reclassification of Hodgkin disease (HD) included in the population based Cancer Registry of Zaragoza (CRZ) in order to reclassify according to WHO and ICD-O classifications and identify the non other specification (NOS) cases. From January 1995 to December 2000, a total of 141 patients diagnosed as Hodgkin disease are included. The sources of data were: Zaragoza population based Cancer Registry, Aragon hematological malignancies Registry (FEHHA) and from the records of public Hospitals and the National Deaths Index. All cases were identified from the CRZ and 35 cases (24.8%) NOS were re-studied by the hematologists and pathologists and reclassified according histological and morphological subtypes of WHO classification. Diagnostic criteria were set for LRCHD: scattered Hodgkin-Reed-Sternberg cells with a classical immunophenotype in a background of small lymphocytes without admixture of eosinophils and neutrophils and without sclerosis nodular lymphocyte predominant HD (NLPHD), mixed cellular (MCD) and lymphocyte-rich classical HD (LRCHD). In 24.8% of cases were necessary to process the samples again or review smears and applied immunochemistry techniques in order to establish accurate diagnosis according the new sub-classification in NLPHD or CHD and distinguish some cases of T-cell rich large B-cell lymphoma. In addition we have calculated the estimated survival according specific morphological subtypes.Results:Hodgkin Disease. Histological distributionICD-0-3No%malesfemalesmean age(y)mean surv(y)No deaths (%)NOS*3524.8152043.75.813 (34.3)CHD6445.4392539.37.619 (29.7)MCD2114.915646.37.74 (19.0)LRCHD117.89251.16.75 (45.5)NLPHD107.06451.28.32 (20.0)Total141845743.27.143 (30.5)*non other specificationThe estimated survival analysis showed a mean of 7.6 years (95% CI: 6.7–8.4) for all cases, median not reached.Comments: In our study has been necessary to reclassify the 24.8% of cases according WHO criteria. The incidence peaks are classical. The overall survival is similar to describe previously.

O55 Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL): Clinicopathological characteristics and outcome of a rare entity

Twenty-four years after apparently successful treatment for nodular lymphocyte predominant Hodgkin's disease (nLPHD), a 41-year old male developed “B” symptoms and extensive adenopathy. A right axillary lymph node biopsy showed two distinct regions including (1) histiocyte-rich B-cell lymphoma and (2) diffuse small T-cell lymphoma. A clonal rearrangement of the gene for the T-cell receptor beta chain confirmed the presence of a T-cell neoplasm, and this was further confirmed by selective polymerase chain reaction (PCR) on this morphologic zone. PCR on the morphologic B-cell lymphoma confirmed the presence of an immunoglobulin gene rearrangement. These two regions were separated by a less-defined zone containing a mixture of small CD57 positive T lymphocytes, small B lymphocytes, and rare lymphocytic and histiocytic (L&H) cells, highly suggestive of recurrent LPHD. The development of composite B-cell and T-cell lymphoma in this patient raises the speculation that nLPHD may be a neoplasm of lymphoid cells, which can differentiate in both B- and T-cell directions, with the “L&H” cells constituting their B-cell progeny.

High-Dose Chemotherapy Followed by Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Lymphocyte Predominant Hodgkin's Disease.

Lymphocyte Predominant Hodgkin's Disease (LPHD) is a B-cell lymphoma that may require different treatment and may have a different natural history than classical Hodgkin's disease. Although AHSCT is accepted therapy for patients with relapsed and refractory classical Hodgkin's disease, there is little information regarding transplantation for LPHD. We performed a retrospective analysis of 19 patients who were treated with AHSCT for relapsed or refractory LPHD at the University of Nebraska Medical Center between April, 1987 and October, 2002. Biopsies of all LPHD patients were reviewed to confirm the diagnosis according to the WHO classification. Patients with a prior or concurrent diagnosis of classical Hodgkin's disease or non-Hodgkin's lymphoma were excluded. There were 18 men and 1 woman. Median age was 33 years (range 19–52). Thirteen patients (68%) received 1–2 chemotherapy regimens prior to AHSCT, and 6 patients (32%) received 3 or more regimens. Nine patients (47%) received radiation therapy prior to AHSCT. Five patients (26%) had extranodal disease at the time of AHSCT. Five patients (26%) were transplanted with autologous bone marrow, and 14 patients (74%) received peripheral blood stem cells. Six patients (32%) were transplanted with BEAM (carmustine, etoposide, cytarabine, melphalan), and 13 patients (68%) were treated with CBV (cyclophosphamide, carmustine, etoposide). The results of AHSCT for the 19 patients with LPHD were compared with 229 patients in our database who received AHSCT for relapsed and refractory nodular sclerosis Hodgkin's disease during the same time period. The characteristics of the groups were similar with respect to age, disease status at the time of AHSCT, stage at AHSCT, amount of treatment prior to AHSCT, and interval between diagnosis and AHSCT. Patients with LPHD were more likely to be males (p<0.001), less likely to have received radiation prior to AHSCT (p=0.06), and more likely to have been transplanted with peripheral blood stem cells (p=0.05). The actuarial 5-year progression-free survival following AHSCT for patients with LPHD and nodular sclerosis Hodgkin's disease was 40% (95% CI 18% to 61%) and 39% (95% CI 33% to 45%), respectively (p=0.30). The actuarial 5-year overall survival following AHSCT for patients with LPHD and classical Hodgkin's disease was 56% (95% CI 30% to 75%) and 53% (95% CI 46% to 59%), respectively (p=0.36). A multivariate analysis comparing patients with LPHD and those with nodular sclerosis Hodgkin's disease was performed. The relative risk of treatment failure following AHSCT for patients with nodular sclerosis histology was 1.14 (95% CI 0.62 to 2.12; p=0.67), and the relative risk of death was 1.22 (95% CI 0.62 to 2.41; p=0.56). These results demonstrate that long-term progression-free survival and overall survival can be achieved following high-dose therapy and AHSCT for patients with LPHD. Furthermore, no significant differences in progression-free survival and overall survival were identified when results of AHSCT for LPHD and nodular sclerosis Hodgkin's disease were compared. Although none of the LPHD patients were treated with newer agents such as gemcitabine or rituximab prior to AHSCT, this analysis suggests that high-dose therapy followed by AHSCT may be used for patients with relapsed and refractory LPHD as well as classical Hodgkin's disease.

Loss of CD19 expression in B‐cell neoplasms

To investigate whether an antibody against an intracellular epitope can detect CD19 in routine biopsy specimens and thus to document in detail its expression in human lymphomas. A polyclonal antibody to the C terminus of CD19 was used to immunostain paraffin-embedded samples of normal and neoplastic lymphoid tissues. CD19 was widely expressed in normal B cells and in extramedullary plasma cells. It was found in most B-cell neoplasms, but expression in follicular lymphoma was weak (33/69) or negative (four cases). Similarly, CD19 expression in diffuse large B-cell lymphomas was weak (28/56) or negative (eight cases). In T-cell-rich B-cell lymphomas, CD19 was also weak (4/10) or negative (three cases). CD19 was often absent in post-transplant B lymphoproliferative disease, classical Hodgkin's disease and plasma cell neoplasms. An unexpected finding was the frequent absence of CD19 in the neoplastic cells in lymphocyte predominant Hodgkin's disease. CD19 can now be detected in routine biopsy specimens. In contrast to the classical pan-B marker CD20, CD19 is not always strongly expressed in B-cell neoplasms. Furthermore, the lymphocytic and histiocytic (L&H) cells of lymphocyte predominant Hodgkin's disease (which express most B-cell-associated markers) commonly lack CD19.

Rituximab in Relapsed Lymphocyte Predominant Hodgkin's Disease (LPHD). Long-Term Results of a Phase-II Study from the German Hodgkin Lymphoma Study Group (GHSG).

Introduction: LPHD is a rare disease which accounts for 3–8% of all Hodgkin cases. Patients with LPHD relapse frequently and freedom from treatment failure is not significantly improved by intensification of polychemotherapy or radiotherapy. The malignant cells of LPHD are CD20+ and therefore the anti-CD20 antibody rituximab (R) may have activity with fewer adverse late effects.Methods: This phase-II trial was initiated by the German Hodgkin Lymphoma Study Group (GHSG) to evaluate rituximab in patients with LPHD at first or higher relapse or progressive disease after at least one standard treatment. Histological slides were reviewed by a reference panel. Pts received 375mg/m2 of the anti-CD20 antibody rituximab once weekly for four weeks given as intravenous infusion in saline solution.Results: Between 1999 and 2004 we treated twenty-one pts. with CD20-positive Hodgkin's lymphoma according to the study protocol. Fourteen patients had stage I/II disease at the time of study entry and all patients were in their first to third relapse (median 2). The initial diagnosis of LPHD was confirmed in 17/21 cases. The remaining cases were reclassified as HD transformed to T-cell rich B-cell lymphoma (2) or CD20-positive classical HD (2). The overall response rate was 90%. Time to progression was 31 months (ms). The median follow-up 58 ms. Both T-cell rich B-cell lymphoma are in continous remission (PR 51ms+, CR 61ms+).Conclusion: Single-agent therapy with rituximab is safe and showed high efficacy in relapsed LPHD. Therefore rituximab might be a non-toxic and efficient alternative treatment strategy compared to intensified chemo-and/or radiotherapeutic protocols in this young group of patients.

Expression of X-Linked Inhibitor of Apoptosis Protein in Reactive Lymphoid Tissues, Non-Hodgkin's Lymphomas, and Hodgkin's Disease.

X-linked inhibitor of apoptosis protein (XIAP) is an important regulator of apoptosis which binds to and inhibits caspases-3, -7 and -9, blocking the caspase 9-mediated apoptosis pathway. This pathway is activated by p53 and DNA damage and may be an important determinant of responsiveness to chemotherapy. Apoptosis also plays a major role in the regulation of follicle center B-cell proliferation and BCL2-mediated inhibition of apoptosis is a key factor in B-cell lymphomagenesis. In this study we examined the expression of XIAP in 65 reactive and neoplastic lymphoid proliferations utilizing a monoclonal antibody to XIAP (#610763 BD Biosciences, San Jose, CA) and immunohistochemistry with avidin-biotin-complex immunoperoxidase technique on formalin-fixed, paraffin-embedded sections. In reactive lymph nodes and tonsils, expression of XIAP was limited to large noncleaved cells in follicle centers (5 of 6 cases). XIAP was absent in plasmacytoma (3 cases) and small lymphocytic lymphoma/chronic lymphocytic leukemia (1 case). XIAP was expressed in follicular lymphoma, predominantly in large noncleaved cells (6 of 9 cases) and in diffuse large B cell lymphoma (11 of 16 cases), including cases of T-cell/histiocyte-rich diffuse large B cell lymphoma (2 cases), primary mediastinal large B cell lymphoma (1 case), and posttransplantation diffuse large B cell lymphoma (1 case). XIAP was consistently expressed in Burkitt and Burkitt-like lymphoma (3 of 3 cases) and anaplastic large cell lymphoma (3 of 3 cases) and in one case of adult T cell leukemia/lymphoma. XIAP was variably expressed in marginal-zone B cell lymphoma, predominantly in large blasts (2 of 4 cases) and in mantle cell lymphoma (2 of 3 cases). XIAP was not detected in peripheral T cell lymphoma, unspecified (1 case), extranodal NK/T cell lymphoma, nasal type (1 case), precursor B cell lymphoblastic leukemia (1 case), or granulocytic sarcoma (1 case). XIAP was consistently expressed in the Reed-Sternberg and mononuclear Reed-Sternberg-variant cells of classical Hodgkin disease (9 of 9 cases) and the L+H Reed-Sternberg-variant cells of nodular lymphocyte predominance Hodgkin disease (3 of 3 cases). XIAP is expressed across a broad range of lymphoproliferative disorders, including classical and nodular lymphocyte predominance Hodgkin disease, diffuse large B cell lymphoma, follicular lymphoma, Burkitt lymphoma, marginal-zone and mantle cell lymphoma, and anaplastic large cell lymphoma. XIAP appears to be selectively expressed in the proliferating elements of these lymphomas. The possible prognostic and therapeutic significance of XIAP expression needs to be determined.

1245 POSTER Experience with treatment of lymphocyte predominance Hodgkin's disease in children

1245 POSTER Experience with treatment of lymphocyte predominance Hodgkin's disease in children

Composite follicular lymphoma and nodular lymphocyte predominance Hodgkin's disease

Composite follicular lymphoma and nodular lymphocyte predominance Hodgkin's disease

Special issues in pediatric Hodgkin's disease

Childhood Hodgkin's disease (HD) is not a biologically unique disease; it differs from adult HD primarily in the relative incidence of disease histology. Preadolescent children are more likely to have Mixed Cellularity and nodular lymphocyte predominant HD. Adolescent and young adult HD is indistinguishable, with a predominance of nodular sclerosing (NS) HD. Nonetheless, treatment paradigms have diverged over the years as pediatric oncologists responded first to developmental issues in the young child, and later to the long-term treatment consequences in all young survivors. The latter concerns are of equal relevance to the young adult with HD. The increasing convergence of treatment approaches in the past decade is therefore most appropriate. Reproductive potential, risk of secondary malignancy and cardiopulmonary consequences of therapy have driven the pediatric treatment paradigm of care. Chemotherapy with low dose, limited field radiation is standard, with low-stage patients often treated by chemotherapy alone. Algorithms tailor therapy to response. The prognostic importance of very early chemotherapy response rather than end-of-chemotherapy response has led the Children's Oncology Group to use early response (after 6 wk) to titrate individual therapy and dense regimens to maximize the early response rates. Although the dose dense regimens of adult groups are similar, the pediatric algorithms emphasize using the enhanced efficacy to limit cumulative therapy. This review intends to address the special issues of childhood HD, with the intent of further encouraging understanding that will foster convergence of pediatric and adult treatment paradigms.

Case of relapsed CD20(+) mixed‐cellularity Hodgkin disease treated with sequential rituximab and radiotherapy

American Journal of HematologyVolume 77, Issue 4 p. 418-419 Letters and CorrespondenceFree Access Case of relapsed CD20(+) mixed-cellularity Hodgkin disease treated with sequential rituximab and radiotherapy Michalis V. Karamouzis, Michalis V. Karamouzis 1st Department of Medical Oncology, St. Savvas Anticancer-Oncologic Hospital, Athens, GreeceSearch for more papers by this authorNikiforos Apostolikas, Nikiforos Apostolikas Department of Pathology, St. Savvas Anticancer-Oncologic Hospital, Athens, GreeceSearch for more papers by this authorChara Georganta, Chara Georganta 1st Department of Medical Oncology, St. Savvas Anticancer-Oncologic Hospital, Athens, GreeceSearch for more papers by this authorGiorgos Lainakis, Giorgos Lainakis 1st Department of Medical Oncology, St. Savvas Anticancer-Oncologic Hospital, Athens, GreeceSearch for more papers by this authorKostas Kandylis, Kostas Kandylis 1st Department of Medical Oncology, St. Savvas Anticancer-Oncologic Hospital, Athens, GreeceSearch for more papers by this authorGerasimos Rigatos, Gerasimos Rigatos 1st Department of Medical Oncology, St. Savvas Anticancer-Oncologic Hospital, Athens, GreeceSearch for more papers by this author Michalis V. Karamouzis, Michalis V. Karamouzis 1st Department of Medical Oncology, St. Savvas Anticancer-Oncologic Hospital, Athens, GreeceSearch for more papers by this authorNikiforos Apostolikas, Nikiforos Apostolikas Department of Pathology, St. Savvas Anticancer-Oncologic Hospital, Athens, GreeceSearch for more papers by this authorChara Georganta, Chara Georganta 1st Department of Medical Oncology, St. Savvas Anticancer-Oncologic Hospital, Athens, GreeceSearch for more papers by this authorGiorgos Lainakis, Giorgos Lainakis 1st Department of Medical Oncology, St. Savvas Anticancer-Oncologic Hospital, Athens, GreeceSearch for more papers by this authorKostas Kandylis, Kostas Kandylis 1st Department of Medical Oncology, St. Savvas Anticancer-Oncologic Hospital, Athens, GreeceSearch for more papers by this authorGerasimos Rigatos, Gerasimos Rigatos 1st Department of Medical Oncology, St. Savvas Anticancer-Oncologic Hospital, Athens, GreeceSearch for more papers by this author First published: 18 November 2004 https://doi.org/10.1002/ajh.20224Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL REFERENCES 1Ekstrand BC, Lucas JB, Horwitz SM, et al. Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial. Blood 2003; 101: 4285– 4289. 2Rehwald U, Schulz H, Reiser M, et al. German Hodgkin Lymphoma Study Group (GHSG). Treatment of relapsed CD20+ Hodgkin lymphoma with the monoclonal antibody rituximab is effective and well tolerated: results of a phase 2 trial of the German Hodgkin Lymphoma Study Group. Blood 2003; 101: 420– 424. 3Ibom VK, Prosnitz RG, Gong JZ, et al. Rituximab in lymphocyte predominance Hodgkin's disease: a case series. Clin Lymphoma 2003; 4: 115– 118. 4DeVita VT Jr. Hodgkin's disease—clinical trials and travails. N Engl J Med 2003; 348: 2375– 2376. 5Aleman BMP, Raemaekers JMM, Tirelli U, et al. European Organization for Research and Treatment of Cancer Lymphoma Group. Involved-field radiotherapy for advanced Hodgkin's lymphoma. N Engl J Med 2003; 348: 2396– 2406. Citing Literature Volume77, Issue4December 2004Pages 418-419 ReferencesRelatedInformation

Expression pattern of FCRL (FREB, FcRX) in normal and neoplastic human B cells

FCRL (also known as FREB and FcRX) is a recently described member of the family of Fc receptors for immunoglobulin G (IgG). In the present study we analysed its expression in normal and neoplastic lymphoid tissue using immunohistochemical techniques. FCRL was preferentially expressed in a proportion of germinal centre cells and, more weakly, in mantle zone B cells. In addition, strong labelling was observed in marginal zone B cells in the spleen, representing one of the few markers for this cell type. The majority of cases of small B-cell lymphoma, diffuse large B-cell lymphoma and lymphocyte predominance Hodgkin's disease were positive for FCRL. However, the number of positive cells varied widely, and in consequence we could not define a cut-off that distinguished subsets of diffuse large B-cell lymphoma. Our results also showed that FCRL tended to be negative in T-cell-rich B-cell lymphoma and in classical Hodgkin's disease. FCRL may therefore represent a novel marker for normal B cells (e.g. splenic marginal zone cells) and may also be useful as a potential marker of B-cell neoplasms.