Lymphocyte 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.

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.

Coincident merkel cell carcinoma and B‐cell lymphoma: A report of two cases evaluated by cytology

Diagnostic CytopathologyVolume 42, Issue 9 p. 819-822 Letter to the Editor Coincident merkel cell carcinoma and B-cell lymphoma: A report of two cases evaluated by cytology Trisha M. Shattuck M.D., Ph.D., Corresponding Author Trisha M. Shattuck M.D., Ph.D. Department of Pathology, Duke University Medical Center, Durham, North CarolinaCorrespondence to: Trisha M. Shattuck, M.D., Ph.D., Duke University Medical Center, Box 3712, Durham, NC 27710, USA. E-mail: trisha.shattuck@duke.eduSearch for more papers by this authorMichael S. Waugh M.D., Michael S. Waugh M.D. Department of Pathology, Duke University Medical Center, Durham, North CarolinaSearch for more papers by this authorClaudia K. Jones M.D., Claudia K. Jones M.D. Department of Pathology, Duke University Medical Center, Durham, North CarolinaSearch for more papers by this author Trisha M. Shattuck M.D., Ph.D., Corresponding Author Trisha M. Shattuck M.D., Ph.D. Department of Pathology, Duke University Medical Center, Durham, North CarolinaCorrespondence to: Trisha M. Shattuck, M.D., Ph.D., Duke University Medical Center, Box 3712, Durham, NC 27710, USA. E-mail: trisha.shattuck@duke.eduSearch for more papers by this authorMichael S. Waugh M.D., Michael S. Waugh M.D. Department of Pathology, Duke University Medical Center, Durham, North CarolinaSearch for more papers by this authorClaudia K. Jones M.D., Claudia K. Jones M.D. Department of Pathology, Duke University Medical Center, Durham, North CarolinaSearch for more papers by this author First published: 11 June 2013 https://doi.org/10.1002/dc.23011Citations: 3Read the full textAboutRelatedInformationPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessClose modalShare 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 Citing Literature Volume42, Issue9September 2014Pages 819-822 RelatedInformation RecommendedT-cell/histiocyte-rich large B-cell lymphoma is a disseminated aggressive neoplasm: differential diagnosis from Hodgkin's lymphomaM Fraga, A García-Rivero, L Sánchez-Verde, J Forteza, M A Piris, HistopathologyMultilobated B‐cell lymphoma, a variant of centroblastic lymphoma. Report of four casesJ.K.C. CHAN, C.S. NG, S. TUNG, HistopathologyT-cell-rich B-cell lymphoma and lymphocyte-predominant Hodgkin's disease: two closely related entities?U. SCHMIDT, K. A. METZ, L.-D. LBDER, British Journal of HaematologyComposite marginal zone B-cell lymphoma and classical Hodgkin's lymphoma: a clinicopathological study of 12 casesA Zettl, T Rüdiger, A Marx, H K Müller-Hermelink, G Ott, Histopathology

Lymphocyte-predominant Hodgkin Disease

Lymphocyte-predominant Hodgkin disease is a rare form of Hodgkin lymphoma that is recognized as a separate histopathological entity. This disease tends to have multiple relapses, but has an overall good prognosis. Owing to its rarity, and the prolonged time period between recurrence and transformation events, there is no consensus regarding optimal management. However, the National Comprehensive Cancer Network guidelines indicate that for early stages, appropriate treatment is radiotherapy. Several management options have been reported including observation, radiation, chemotherapy, combined chemoradiotherapy, and anti-CD20 antibody therapy. Salvage therapy remains effective in inducing prolonged remission in patients with relapsed/refractory disease.

A coincidence of renal cell carcinoma and hematological malignancies

Hematological malignancies with renal cell carcinoma (RCC) are rarely seen. We reported here two cases of coincidence of RCC with multiple myeloma (MM) and Hodgkin's disease (HD). A 69-year-old male patient with tumor that was located at the upper pole of left kidney was admitted to our clinic. Partial tumoral resection was performed and stage-I RCC was diagnosed after the histopathological examination of tumor. Moreover, he was diagnosed with IgG kappa stage-IIA MM as a result of bone marrow examination and serum immunofixation electrophoresis. Radiotherapy, combination chemotherapy, and autologous stem cell transplantation (ASCT) were performed. The patient is still alive who achieve a complete remission. A 53-year-old male patient suffered from cervical lymphadenopathy. He has a story of right radical nefrectomy that has been performed 4 years ago. Stage II-B lymphocyte-predominant HD was diagnosed. Combination chemotherapy was started, but relapse occurred 25 months later. ASCT was not planned due to cardiovascular problems and the patient died. Clinicians should keep in mind the coincidence of RCC with MM and HD.

Partners In Health Generalist/Specialist Twinning: A Health Delivery Model Used in Treating Childhood Lymphoma in Rural Rwanda,

Abstract 4222In the developed world approximately 80% of children with lymphoma can be cured. As global health initiatives have broadened to address noncommunicable diseases the approach to cancer care for children in resource poor settings becomes of increasing concern. Traditional models of tertiary care provision will not be applicable as there is not an adequate number of existing pediatricians subspecializing in oncology to provide for the world’s children. At Rwinkwavu, a Partners In Health (PIH) supported government district hospital in rural Rwanda, a small cohort of children with lymphoma have received therapy over the past 4 years using a unique approach to care delivery. Each case is managed by a team consisting of a Rwandan physician with no specialty training, a Rwandan nurse coordinator focused on oncology patients, a Rwanda-based US trained pediatrician and a US- based pediatric oncologist. Biopsies and radiologic staging studies were obtained in Rwanda but all pathologic diagnoses were made at Brigham and Women’s Hospital, a Harvard teaching hospital, through a formal arrangement. A treatment plan for each patient was formulated with the consulting pediatric oncologist and a road map was generated. Chemotherapy was administered by nurses in the Rwinkwavu pediatric ward under the daily supervision of the local generalist and with the support of the pediatrician. Blood counts and broad spectrum antibiotics were available but blood cultures could not be performed. If radiation therapy was required patients were transported to Uganda for the treatments. Ten patients aged 3–15 (median age 9.5 years) have been treated using this approach. 5 (50%) have completed therapy - Hodgkin’s Disease (HD) n =2, HIV-associated large cell lymphoma (HIV LCL) n =2, Burkitt’s Lymphoma (BL) n=1. They received either CHOP (cyclophosphamide, adriamycin, vincristine, prednisone), n=3 or ABVD (adriamycin, bleomycin, vincristine, dacarbazine), n=1; 1 patient with Stage 1 Lymphocyte Predominant HD is being observed without adjuvant therapy after complete surgical excision. All 5 have no evidence of disease recurrence 4 months - 4 years following completion of therapy (median = 14 months). 2 patients are currently on therapy (recurrent HD, HIV LCL) and are in remission. 2 patients succumbed to treatment complications (HD- died from cardiomyopathy, BL- died from transverse myelopathy) and 1 patient (BL) died of progressive disease while receiving chemotherapy. We can not determine the number of pediatric patients with lymphoma who died before a diagnosis was made or before receiving appropriate therapy. In the developing world lymphoma is one of the most common oncologic diseases in children. These data suggest that chemotherapy can be administered with curative intent to a subset of these patients in the setting of a confirmed pathological diagnosis. This approach provides a platform for models of care that rely on local physicians acting in concert with trained consultants from the developed countries to deliver subspeciality care in resource poor settings. Disclosures:No relevant conflicts of interest to declare.

Lymphocyte-predominant Hodgkin lymphoma—clinical features and treatment outcomes from a 30-year experience

Background: Lymphocyte-predominant Hodgkin disease (LPHD) is a rare subtype of Hodgkin lymphoma, for which there is limited evidence regarding the presentation, natural history and treatment outcomes.Patients and methods: We conducted a single-institution retrospective review all of patients diagnosed with LPHD over a 30-year period.Results: Eighty-eight patients were included. Median follow-up was 13 years. Local radiotherapy or chemoradiotherapy resulted in durable disease control in patients with stage I or II disease. Advanced stage at presentation, presence of B symptoms, low albumin, and either partial response or stable disease to first treatment were associated with worse treatment outcomes. Relapse rate for the entire cohort was 44%, with an 8% rate of transformation to large-cell lymphoma. Rituximab in combination with chemotherapy resulted in durable remission in a heavily pretreated subgroup. Outcomes with autologous transplant are discussed.Conclusion: Our series has the longest follow-up of any report, includes the only series of patients treated with autologous transplant, and has the largest group of patients treated with rituximab and chemotherapy in this indication.

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.

Rituximab in Lymphocyte-Predominant Hodgkin Disease

Background: Lymphocyte-predominant Hodgkin disease (LPHD) differs in biology and clinical behaviour from classic Hodgkin disease. Almost 100% of LPHD neoplastic cells express CD20 and thus rituximab could be effective; yet limited data are available. Patients and Methods: We performed a retrospective analysis on patients with LPHD who were treated with rituximab at our institution to determine the magnitude of benefit offered by this drug. Results: Seven patients were identified; 4 received the drug as single agent while the rest received it in combination with chemotherapy. All except 2 received the drug in the salvage setting. Response rate was 100% with 6 of 7 patients achieving complete remission. At a median follow-up of 2 years, 4 patients are still disease free while the rest relapsed at a median time of 27 months. Conclusion: Rituximab is effective in LPHD and should be considered; however, the optimal schedule remains to be determined.

Treatment of CD 20+ Hodgkin Lymphoma (Lymphocyte Predominant) with Monoclonal Antibody Rituximab after First-Line Treatment Is Effective and Might Improve the Outcome

Lymphocyte-predominant Hodgkin disease (LPHD) presents as early-stage disease with slow disease progression and excellent initial response to conventional chemotherapy. Although 96% of LPHD patients experience a complete remission (CR) upon first line treatment, many relapses occur. Residual tumor cells in Hodgkin's patients can survive standard therapy and cause relapse. Thus, the elimination of minimal residual disease after first line treatment might improve the outcome in Hodgkin disease. CD20+ is strongly expressed by malignant cells in LPHD, but so far there is limited information regarding the efficacy of Rituximab in this patient population. A 66 year-old woman presented with bilateral inguinal lymphadenopathy in 2004 and complained on malaise and weight loss. Lymph node biopsy confirmed a diagnosis of LPHD and immunohistochemistry confirmed that CD20 antigen was expressed on more than 30% of malignant cells. Staging revealed II B disease. There were lymph node enlargements in the pelvis on CT. Her blood count, erythrocyte sedimentation rate, and albumin were normal with elevation of and lactate dehydrogenase and alkaline phoshatase. She was treated with ABVD regiment 8 cycles and CR was achieved. After standard chemotherapy patient with CD20+ LPHD received four weekly doses of Rituximab at 375 mg/m2 and maintenance therapy with additional four doses of Rituximab every three months for the next year. Treatment was well tolerated without any complications. Evaluation of disease assessment included physical examination and computed tomography, bone marrow biopsy and routine analyses, after the end of treatment and every 3 months after for the first two years, and on six months for the following year. There were no abnormalities on CT after the end of the treatment. Patient was in complete remission. CT after 36 months showed no detectible tumor mass. Patient remains still in complete remission three years after chemotherapy without detectible tumor mass.Our case report suggests that Rituximab is both safe and effective in patients with CD20+ LPHD. The optimal treatment for patients with LPHD remains uncertain. Current research aims to identify alternative treatment approaches that possess significant activity but less toxicity. Radiotherapy for early-stage patients and chemotherapy or combined modality treatment for advanced-stage patients remains to be standard of care. Initial observed benefit of Rituximab treatment in this group of patients suggests that there is a role for monoclonal antibodies in optimal treatment approach, especially in improving the outcome. Further studies with Rituximab are warranted in this patient population.

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.

A B-cell lymphoma–associated chromosomal translocation in a progressive transformation of germinal center

Progressive transformation of germinal center (PTGC) is a pattern of lymph node reactive hyperplasia. It can also be the predominant pattern in a hyperplastic lymph node known as florid PTGC. It is characterized histologically by the expansion of the mantle zone lymphocytes into both the adjacent sinusoids and germinal centers. The lymphocytes destroying the germinal centers are predominantly B cells, with a minor population of T cells. Morphologically, it can be confused with nodular lymphocyte-predominant Hodgkin disease (NLPHD) because of its nodular pattern and because of the presence of large cells that can be incorrectly identified as lymphocytic and histiocytic cells. A relationship between PTGC and NLPHD remains unclear, and many authors have suggested that PTGC can represent a precursor lesion of NLPHD. Here we report the first karyotype obtained in PTGC, in a 12-year-old boy. It shows a t(3;22)(q27;q11) translocation, probably involving the BCL6 gene. This translocation has previously been described in diffuse large B-cell lymphomas and in NLPHD with BCL6 rearrangement. This finding offers an insight into a possible tumorigenic pathway from PTGC to NLPHD. Further studies will be required to confirm this hypothesis.

18-F FDG-PET in the staging of lymphocyte-predominant Hodgkin's disease

This bicentric study assessed retrospectively the usefulness of 18 F-FDG-PET in the staging of 31 patients with lymphocyte-predominant Hodgkin's disease (LPHD). FDG-PET and conventional explorations (CE) were performed for initial disease (n=25) or recurrence (n= 6). All the 68 involved sites were detected by PET including 5 extra-nodal lesions. Only 43 nodal sites (68%) and one splenic focus were detected by CE. PET changed staging in 9 patients (7 upstaged, 2 downstaged) and radiation fields in 3 patients. These results showed the potential role of PET in the staging of LPHD.

Clinical Presentation and Outcomes of Lymphocyte-predominant Hodgkin Disease at the University of Florida

To examine the clinical presentation and treatment outcomes of lymphocyte-predominant Hodgkin disease (LPHD) at the University of Florida over a 37-year period. A retrospective review of the clinical presentation and treatment outcomes in 34 patients with LPHD treated at the University of Florida from 1968 to 2005 was conducted. The end points of absolute survival, cause-specific survival, and relapse-free survival were assessed and late treatment sequelae were identified. Ninety-six percent of patients presented with stage I/II disease. None had mediastinal disease, 4 (12%) had bulky disease (>6 cm in maximum tumor dimension), and only 1 (3%) had B symptoms. Eighty percent of patients were treated with radiation therapy (RT) alone and 20% with RT and chemotherapy. At 5, 10, and 15 years, absolute survival was 97%, 85%, and 76%; cause-specific survival was 100%, 95%, and 95%; and relapse-free survival was 93%, 81%, and 74%. No patients died with Hodgkin disease, but 1 patient's death was attributed to treatment-related late sequelae. There were 6 treatment failures, including 2 within the RT field; all failures were successfully salvaged. The median time to relapse was 5.8 years (range, 2.9-14.6 years). Three secondary malignancies were observed. LPHD patients typically present at an early stage without B symptoms, mediastinal, or bulky disease. First-line treatment with RT alone yields excellent results in appropriately selected patients and remains the standard of care. Relapses often occur late and long-term follow-up is needed to successfully diagnose and treat late relapses.

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.

Komplette Remission eines rezidivierenden Hodgkin-Lymphoms vom Mischzelligen Typ nach Rituximab-Therapie

Anamnese und klinischer Befund: Ein 55-jähriger Patient stellte sich aufgrund einer zervikalen Lymphknotenschwellung vor. Histologisch wurde ein Hodgkin-Lymphom (HL) vom Mischzelligen (MZ)-Typ, Stadium IV A (Ann-Arbor-Klassifikation) diagnostiziert. Eine komplette Remission (CR) konnte nach 6 Zyklen Chemotherapie COPP/ABVD (Cyclophosphamid, Vincristin, Procarbazin, Prednisolon/ Doxorubicin, Bleomycin, Velbe, Dacarbazin) erreicht werden. 12 Monate später erlitt der Patient ein Rezidiv. Eine Dexa-BEAM-Behandlung (Dexamethason, BCNU (Bis-Chlorethyl-Nitrosourea), Etoposid, Cytarabin und Melphalan) mit einer anschließenden autologen peripheren Stammzelltransplantation wurde durchgeführt. 7 Jahre nach Erstdiagnose erlitt der Patient ein histologisch gesichertes Rezidiv des HL im Stadium IV A. Eine partielle Remission konnte mit 2 Zyklen Dexa-BEAM erreicht werden. 4 Monate später kam es zum Progress des HL. Eine Therapie mit Gemcitabine erbrachte kein Ansprechen.

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.