Extra Nodal Research Articles

Incidence, Clinical Characteristics and Survival of Malignant Lymphomas in the Province of Modena (Italy); a Population-Based Study.

The incidence of lymphomas has increased in many parts of the world in recent decades. We conducted a population-based study of peripheral lymphoma (PL) in the province of Modena (Italy). According to the international classification for lymphomas (WHO/ICD-O-3) we evaluated incidence patterns and time trends of 1,582 cases of PLs diagnosed between 1997–2003, also providing details of clinical characteristics, treatment and outcome of different entities. World Age Standardized Rates (ASR) varied substantially among lymphoid neoplasm subtypes. Overall, ASR (per 100,000) was 13.4 for B-cell lymphomas (16.5 and 10.6 for males and females respectively), 2.2 for T-cell lymphomas (3.1 and 1.5) and 3.4 for Hodgkin lymphoma. Among B-NHL the highest ASR was observed for Diffuse large B-cell lymphoma (DLBCL, 4.8) and Small lymphocytic lymphoma (CLL/SLL, 3.3). Among T-cell lymphomas, ASR was 1.4 for Mycosis fungoides/Sezary syndrome (MF/SS) and 0.4 for both Peripheral T-cell lymphoma (PTCL) and Anaplastic large cell lymphoma (ALCL). The overall annual percent change (APC) of the World ASR was 1.62 (C.I.95%: −4.32; 7.93). Extranodal (EN) involvement was observed in 49% of cases; a diagnosis of Primary EN lymphoma (PENL) was confirmed in 27.8% of cases. In addition to MF/SS, the most frequently reported PENL were marginal zone lymphomas (MZL) and DLBCL. The documented five years Overall Survival (OS) for the whole series was 61.9%, being 61.7%, 55.3% and 83% for B-NHL, T-NHL and HL, respectively. These data confirm an overall improvement when compared with available historical controls for the main European countries. In addition, using period analysis we could estimate more up-to-date survival data within our studied series (all patients vs those diagnosed after 2002): survival of patients with MZL, DLBCL and HL strongly improved during the study period. Among different lymphoma subtypes, patients with Hairy cell leukemia (HCL), HL and MF/SS had the best survival with 5-year OS of 94%, 83% and 82%, respectively. In particular, for HCL and MF/SS the analysis of the Relative Survival suggested that there was no substantial difference in survival compared with healthy population. Our study provides a comprehensive description of both epidemiological and clinical features of PL in the province of Modena, recognizing in a population-based approach, major advances in the curability of some histological subtypes.

High Grade Non-Hodgkin's Lymphoma with Tandem t(14;18) and c-MYC Rearrangement Is a Pathological Lymphoma Entity with Aggressive Clinical Presentation and Very Poor Prognosis.

Translocation t(14;18)(q32;q21) is a hallmark of follicular lymphomas (FL) and reported in 10% to 40% of diffuse large B cell lymphomas (DLBCLs). It leads to Bcl-2 over expression, a protein that opposes to mitochondrial apoptotic pathways and chemotherapy-induced cell death. c-MYC (8q24) rearrangement is a hallmark of Burkitt's lymphoma (BL) but observed in 7% to 15% of DLBCLs. c-MYC (8q24) induces over expression of c-MYC protein which promotes cell cycle and tumour proliferation. Among 70 DLBCL expected for c-MYC and t(14;18) translocation, we identified a series of 16 patients with DLBCL characterized by a tandem t(14;18) translocation and c-MYC rearrangement.Patients were 10 males, 6 females with a median age of 59 years old (36–73). At the time of diagnosis, all patients presented with poor features: B symptoms in 81%, ECOG PS > 2 in 81%, elevated LDH in 100% , stage IV in 100 % with at least one extra nodal localisation (bone marrow involvement in 87,5% and CNS involvement in 44%) and age-adjusted IPI = 3 in 81%. Lymphoma cells in blood smear was found in 50% of the cases. Three patients had a prior history of FL. All patients but one were treated with chemotherapy regiments: R-CHOP like (n=8) or Burkitt regiments (n=7). Five patients reached complete response, 7 partial response and 4 patients progressed. Five patients underwent ASCT (n=3) or allogenic bone marrow transplantation (n=2) upfront. However, disease response was dramatically short precluding planned hematopoietic-cell transplantation in most cases. Despite salvage chemotherapy, all patients progressed with a median time to progression from diagnosis of 4 months (1–10) and median overall survival of 5 months (1–16).Morphological and immunophenotypic findings were consistent with the diagnosis of DLBCL with a germinal-center (GC) profile(CD10 + and CD10−/BCl6+/Mum1−) in all cases.Combination of t(14;18) translocation and MYC rearrangement was identified by conventional cytogenetic and/or FISH analysis in all cases. Conventional cytogenetic found 3 patients with t(8;14), 3 patients with t(8;22) and one with t(2;8) translocation. We also identified a new MYC translocation variant that has never been reported in DLBCL before : t(8;9)(q24;p13) translocation in combination with t(14;18)(q32;q21) translocation. All cases assessed by cytogenetic analysis had a complex karyotype. FISH analysis for BCL6 was positive for only 3 patients.Our series shows that DLBCL with a tandem t(14;18) and c-MYC rearrangement is a particular sub-type of GC-DLBCL with aggressive initial clinical presentation and a disastrous overall survival. We conclude that patients with DLBCL with unusual aggressive clinical and biological presentation should be investigated for tandem translocation. These patients require innovative strategies and targeted therapies.

Extranodal NHL- A retrospective review of clinico-pathologic features and outcome and comparison with nodal NHL. Single institution experience years: 1988–2004

17542 Background: Non-Hodgkin’s lymphoma (NHL) arising in an extra nodal (EN) site is not uncommon and its natural history and treatment is clearly characterized in the literature. Data on EN-NHL and comparison with N-NHL with relation to survival and prognostic factors is scarce in our part of the world. The primary objective of this study was to analyze the anatomic distribution, clinical features and outcome of DLBCL patients according to the primary site with applicability of International Prognostic Index (IPI). Methods: From 1988 to 2004, 557 patients were analyzed for the clinico-pathologic characteristics, treatment outcome and prognostic factors affecting overall survival. Results: Median age was 48.7 ± 15.3 years ; the M: F ratio was 2:1. The distribution according to the primary site was: lymph node, 322 cases (58%) of these 145 cases (44%) stage IV, 76 cases (23%) Stage III, 60 cases (18%) stage II and 47 cases(15%) stage I ; and EN sites, 235 (42%), including GIT (44%) followed by upper aerodigestive tract (19%), bones (08%), spine (05%), and 3% each as breast, CNS, testis,lungs. The median survival rate was 4.8 and 6.3 years in NL and ENL respectively vary according to primary site/stage of the lymphoma. In the univariate analysis age less than 60 years, early stage I-II, extra nodal involvement primarily gastric or bone, 0–1 extra nodal site, 0–1 PS, lack of B symptoms, normal LDH level has been associated with good prognosis. In the multivariate analysis age, PS, stage and level of LDH were the main variables to predict OS; no nodal or extranodal site maintained their prognostic value. Conclusion: Our data correspond with series from west increasing incidence extranodal lymphoma due to improved diagnostic techniques and superior results with chemotherapy by preserving the organ. Few patients with bowel obstruction or cord compression lymphoma required surgery for diagnosis or relief of symptoms. There is significant difference from western data in histologies DLBC-NHL is the most common histologies in our study. Overall survival patients with EN-NHL were similar to nodal NH-Lymphoma but largely depended on IPI. No significant financial relationships to disclose.

Primary gastrointestinal Non Hodgkin′s lymphoma chemotherapy alone an effective treatment modality: Experience from a single centre in India

Gastrointestinal tract (GI) is the most frequently involved extra nodal site in non-Hodgkin's lymphoma (NHL). Surgery, radiotherapy and chemotherapy (CT) have been used mostly in various combinations, but lately chemotherapy alone has emerged as an effective option. The purpose of this study is to evaluate efficacy of CT alone in treatment of primary GI-NHL and to compare the results with combined CT+surgery. Retrospective analysis of case records of GI NHL patients. Over a 15-year period (1986-2000), 77 new cases of primary GI-NHL were registered at our center. GI-NHL was defined according to standard criteria. All patients received chemotherapy. The median age was 32 years (Range 9-80). Endoscopy / CT guided biopsies were performed in 42% (32) of patients for the purpose of diagnosis. Laparotomy was done in 58% (45) of patients to establish a diagnosis or as primary or debulking treatment. Stomach and intestines were involved in 47% (36) and 53% (41) patients respectively. Early stage disease was present in 37% (29). Seventy eight percent of tumors were intermediate to high grade, 43% (33) received only CT while 57% (44) received CT+surgery. Five years EFS and OS were: 72% and 65% for all patients; 72% and 67% for CT only group; 60% and 64% for CT+surgery group (P=.05). Four patients died of neutropenic infection. Organ-preservation strategy using chemotherapy alone (CT) can be successfully employed in a significant number of patients with primary GI-NHL.

Marked Improvement in Detecting the Number of Involved Nodal Areas in Lymphoma, Using 18 F- FDG - PET and CT Scan.

Positron emission tomography (PET) imaging with 18-fluoro-2-deoxiglucose (FDG) is used increasingly for the initial evaluation and staging of patients with Hodgkin's lymphoma (HL) and non- Hodgkin's lymphoma (NHL). However, the degree of concordance of PET and TAC scanning for each nodal and extra nodal site are not well defined. The number of nodal areas involved is a new prognostic factor in follicular lymphomas as was demonstrated in the Follicular Lymphoma (FL) International prognostic index (FLIPI), and their use may be useful for the LNH and HL. In this study, we examined the performance of CT versus FDG-PET scanning, comparing each one of the nodal and extra nodal areas, as it is described in the FLIPI, in a retrospective cohort of lymphoma patients (pts) with HL and NHL. We reviewed the charts of 56 patients with diagnosis of HL and NHL in the initial and relapse staging, in a single tertiary care center. All patients had FDG-PET imaging study, clinical examination and CT scans. The Ann Arbor stage, each nodal site (cervical, mediastinal, axillary, mesenteric, para aortic, inguinal), and extra nodal sites were evaluated on the basis of FDG-PET scanning and were compared with the findings derived from CT. Bone marrow biopsy results were excluded from this initial analysis. The histopathological diagnoses included diffuse large B-cell Lymphomas in 20/56 pts (36%), HL 15/56 pts (27%), anaplastic large cell lymphoma 8/56 pts (14%), FL 5/56 pts (9%), peripheral T-cell Lymphoma 4/56 (7%) and others 7%. Among the 56 pts, 22 (39%) had discordant results between FDG-PET scanning and CT scanning, that lead to a change in stage assignment. Among the discordant cases FDG-PET resulted in upstaging in 18/56 pts (32%), and down staging in 4/56 pts (7%). Forty for pts (79%) had discordant results in the number of nodal areas, among the discordant cases FDG-PET detected more nodal areas in 36/56 pts (64%) and CT in 8/56 pts (14%). The discordant cases were distributed as it is shown in the table.In conclusion Pet and CT in combination detects more involved nodal areas than each method by itself.Summary of PET/CT correlation with nodal areasNodal areasCervical(n)Axillar (n)Mediastinal(n)Paraaortic(n)Inguinal (n)positive total4026262417Only Positive FDG-PET161213711Only Positive CT73221Positive FGD-PET + CT171111155

Analysis of Clinical Characteristics and Prognostic Variables of Hodgkin's Lymphoma: A Single Center Experience.

Background: Hodgkin's disease is a curable malignant disease. Despite advances in the management of this disease entity, there are groups of patients who suffer relapse and identification of prognostic variables and adaptation of treatment to individual risk remains a major challenge. Emphasized in this study are the clinicopathological characteristics and outcome of Hodgkin's lymphomas.Materials and Methods: A retrospective analysis of 245 adult patients treated for Hodgkin's lymphoma between October 1990 and Dec 2004 was done. An analysis of the most important variables was made in terms of both disease free and overall survival. Spectrums of pretreatment factors were evaluated including International Prognostic Factors, extranodal disease symptoms, histology, and bulky disease. Patients were treated with chemotherapy, radiotherapy either alone or in combinations at the beginning and relapses was treated with various salvage regimes combined with radiotherapy and stem cell transplant.Results: The median age in this study group was 32 years (14–72) and 156(63.67%) were male. Distribution by stages were: stage I-43, stage II-113, stage III-44, and stage IV-45.Pathological subtypes were Nodular sclerosis-128, Mixed cellularity-56,Lymphocyte rich classical-13,Lymphocyte depletion-7,and nodular lymphocyte predominance-29,not specified in 12.B symptoms observed in 95,bulky in 72 and Extra nodal involvement in 63 patients. Complete remission was achieved in 226 patients with first line management (92.24%).Primary chemo refractory (19) and relapses were observed in 72 patients, and subsequent salvage chemotherapy including stem cell transplant (28 patients) resulted CR in 41.With the median follow up of 41months (1-374), OS was 95% and DFS was 87%.Twelve patients died out of which 8 due to disease recurrence or progression.Conclusions: Achieving a complete remission shows a favorable prognosis for prolonged DFS. StageIV, bulky disease,B symptoms, extra nodal involvement and NS histology were associated with inferior OS and DFS. Additional factors for poor DFS were male sex, hypoalbumenemia and anemia. Age and leucocytosis did not affect the outcome. Identifying the pretreatment risk factors may be useful in designing clinical trials for the treatment of relapsed and refractory Hodgkin's disease and in making individual therapeutic decisions.

Lymphohematopoietic Cancers in the United Farm Workers of America (UFW), 1988–2001

Agricultural risk factors for lymphohematopoietic cancers (LHC) in Hispanic farm workers in California were examined in a nested case-control study embedded in a cohort of 139,000 ever members of a farm worker labor union in California. Crop and pesticide exposures were estimated by linking county/month and crop specific job history information from union records with California Department of Pesticide Regulation pesticide use reports during the 20-year period prior to cancer diagnosis. A total of 131 LHC diagnosed in California between 1988 and 2001 were included in the analysis. Analyses were conducted by gender and subtype of non-Hodgkins lymphoma (nodal, extra nodal) and by leukemia histology (lymphocytic, granulocytic). Odds ratios were calculated by stratification and by unconditional logistic regression. Risk for all LHC was elevated in workers cultivating vegetables (OR = 1.67, 95% CI = 1.12-2.48). Risk of leukemia was associated with exposure to the pesticides mancozeb (OR = 2.35, 95% CI = 1.12-4.95) and toxaphene (OR = 2.20, 95% CI = 1.04-4.65) while NHL risk was increased in association with 2,4-D (OR = 3.80, 95% CI=1.85-7.81). Risk of leukemia was particularly elevated among female workers and for granulocytic versus lymphocytic leukemia for several chemicals. No associations were noted for multiple myeloma. California farm workers employed where mancozeb and toxaphene were used had an increased risk of leukemia compared to farm workers employed elsewhere. Employment in farms using 2,4-D was associated with an increased risk of NHL.

How to define intermediate stage in Hodgkin's lymphoma?

Intermediate or unfavourable stage Hodgkin's lymphoma (HL) definition relies upon at least three different scoring systems defined by cooperative groups (EORTC, GHSG and Canadian-ECOG). We aimed to investigate their efficacy and their correlation with International Prognostic Score (IPS) for advanced HL. We studied a population of 1156 patients with localized stage HL treated prospectively within GELA centres in H8 (518 patients) and H9 (638 patients) protocols. Median age: 30 yr, 18%, Female 50%; stage I: 25%; stage II: 75%. According to scoring systems 70% had 0-1 EORTC factors; 60% 0-1 GHSG factors and 82% 0-1 Canadian factors. The IPS for advanced stages was available only in H9 study with 64% 0-1 factor. Survival curves according to each of the different scoring systems could significantly discriminate the subgroup populations. When a multivariate Cox analysis was performed for overall survival (OS) including all the scoring system variables: age > 45 yr, sex male, Haemoglobin < 10.5 g/dL, lymphocytes < 600/microL, B symptoms with elevated ESR, extra nodal sites did retain an independent significant value. Probability of OS was 99%, 98%, 92%, 82% and 73% for patients with 1-5 factors, respectively P < 0.0001. These factors are similar for most of them with those described in the IPS when stages III and IV are replaced by extra nodal localization. This new score should be validated in other prospective trials, as it will simplify the Hodgkin prognostic scoring systems for localized and advanced stages.

Cutaneous CD56 positive natural killer and cytotoxic T-cell lymphomas

We report two cases of CD56 positive natural killer (NK) cell and cytotoxic T-cell cutaneous lymphomas and review the literature on these rare forms of non-Hodgkin's lymphoma. The first case was diagnosed to have extra nodal NK/T-cell lymphoma, nasal-type. She had a rapid downhill clinical course and died within 3 months of presentation. She had been started on systemic chemotherapy but did not respond. The second case was diagnosed as subcutaneous panniculitis-like T-cell lymphoma, CD56 positive variant. She presented with skin nodules that were quiescent for 10 years. Then the course of the disease suddenly changed and progressed rapidly. She had systemic chemotherapy and initially had a complete response, but she relapsed within 1 month of completion of chemotherapy. She then had partial response with further chemotherapy but relapsed rapidly. She died within 15 months of her lymphoma changing to its aggressive form. These cases illustrate the often poor prognosis of cutaneous CD56 positive lymphomas.

Extra Nodal NK/T-Cell Lymphoma Nasal Type that Responded to DeVIC Combination Chemotherapy

We report a 76-year-old woman with extra nodal NK/T-cell lymphoma nasal type (ENKL). She had large tumors on her left leg with inguinal lymphadenopathy and gastric tumors. The tumor cells showed angiocentric growth with necrosis. Immunohistologically, the tumor cells from the skin lesion expressed CD2, cytoplasmic CD3, CD56, and T-cell intracellular antigen-1 (TIA-1), but not surface CD3, CD19, and TdT. The gastric tumor cell, also expressed cytoplasmic CD3, CD45RO and CD56. She was diagnosed as having ENKL (stage IV of Ann Arbor). The tumors responded remarkably well to radiation therapy followed by multi-drug resistance independent DeVIC (carboplatin, etoposide, ifosfamide, and dexamethasone) combination therapy. After two series of this therapy, no tumors were detected in clinical, histopathological, endoscope and computerized tomogram (CT) examinations. However, she suddenly died of brain stem metastasis three months later. Although there may be a limitation of effects on metastasis of tumors in the central nervous system, radiation and DeVIC combination therapy is a potent therapeutic method for ENKL.

Prognostic Factors in Localized Hodgkin's Lymphoma: How To Define Intermediate/Unfavourable Disease?.

Actually, the prognosis of localized Hodgkin's lymphoma (HL) patients may be assessed by different scoring systems. Although many similar characteristics have been identified, these scoring systems are not easy to relate to advanced stage HL. The aim of the present study was to refine the assessment of risk using the published scoring systems and to construct a statistical model for predicting risk of death. We report here the results of the EORTC, GHSG and Canadian-ECOG scoring systems obtained in 1156 patients for whom hematological data were available among the 1390 patients with localized HL prospectively treated within GELA centres in H8 (518 pts) and H9 (638 pts) trials. The International prognostic score (IPS) was available only for the H9 subset. All patients have been treated with radio-chemotherapy of different intensity or duration according to their prognostic factors. Median age was 30 yr [14–69] and age≥45yr.: 18%, female 50%; stage 1: 25%; stage 2: 75%; B symptoms with elevated ESR: 40%; number of nodal sites 1–2: 52%; ≥3: 48%; extra nodal involvement: 8%, bulky mediastinum> 0.35, 28%; elevated ESR> 50:33%; Hb< 10.5 g/dl: 7%; Lymphocytes < 600/μl: 6%; WBC > 15000/μl:11 %; albumin< 40g/l: 37%. With the EORTC scoring system 36% of patients had favourable HL, with GHSG 35% and with Canadian-ECOG 38%. The IPS was 0 in 19% and 1 in 45%. With a median follow up of 42 months, 54 patients died. Survival curves according to the different scoring systems significantly discriminated favourable and unfavourable patients outcomes (5 yrs OS 95% vs 92%, p=0.01). By multivariate Cox analysis, age > 45yr (RR=2.0), sex male (RR=2.5), haemoglobin <10.5g/dl (RR=2.3), lymphocytes < 600/μL (RR=3.6), B symptoms with elevated ESR (RR=3.6), extra nodal sites (RR=1.2) retained a significant prognostic value. The 5 yrs OS was 99%, 98%, 92%, 82%, 73% for patients with 0,1, 2, 3, 4–5 factors respectively (p< 0.0001, see figure). 10% of the patients had 3–5 factors. The covariates selection was validated by the bootstrap method. The introduction of albumin< 40g/l in the H9 subset population did not bring more significant information. In conclusion, these factors are similar with those described in the IPS when stages 3–4 are replaced by extra nodal (E) localization. They should be validated in other prospective trials because such a scoring system could unify the assessment of the prognosis for HL patients and facilitate the treatment choice. [Display omitted]

Clinical Significance of Bcl-2 and Ki67 Protein Expression in Agrressive Non-Hodgkin Lymphoma.

Aggressive Non-Hodgkin lymphoma (NHL) is heterogeneous group with respect to clinical, histopatological and evaluative features. The International Prognostic Index (IPI) has provided a widely accepted prognostic set of criteria to design therapy. However, IPI dose not determine whether routine phenotypic features, beside IPI, may influence survival. We evaluate the prognostic significance of Bcl-2 and Ki67 protein expression in relation to clinical presentation and outcome.In the period 1989–2002,two hundred eleven patients with newly diagnosed aggressive NHL were recorded in our Department. In this study we included patients with available biopsy sample. Protein expression was analyzed on paraffin embedded tumor tissue by imunohistochemistry in relation to clinical factor and outcome. The expression of more than 20% of neoplastic cell was considered positive for bcl-2, and more than 60% for Ki-67. Comparison was made by x2 test. Survival curves were considered by Kaplan-Meyer method and compared by the long-rank test. Sixty seven patients were recorded and their characteristic were: median age 53 years, stage III and IV, 67%; present B symptoms 44%,; bone marrow infiltration 29%, elevated LDH 58%, performas status more then 1– 26%; extra nodal sites more than 2 –34%. All 62 patients received antracyclin based combination chemotherapy, 72% CHOP regiment.Overall survival was 52% with a follow up 6–183 months. Bcl-2 expression was observed in 35,5% (22pts) and Ki67 positivity over 60% in 20 pts (30%). Overall survival was influenced by bcl-2 and Kli67 expression. Bcl-2 positive cases were significantly associated with lower overall survival (20% vs. 58%; p<0.01). Overall survuval was significantly worse in patients with Ki67 positivity over 60% (27% vs. 49%; p<0.05)Bcl-2 and Ki67 monoclonal antibody immunostaging appears to be a simple and reproducible method of determining biological potential of tumor cells and provides useful prognostic information in patients with aggressive NHL.

Extra nodal growth as a prognostic factor in malignant melanoma

Aim Extra nodal growth (ENG) in lymph-node metastases may be an additional indicator for poor prognosis and increased loco-regional recurrence in patients with a cutaneous malignant melanoma (CMM). Most studies analyzing prognostic factors lack a proper definition or description of the histological criteria for extra nodal growth. The objective of this study was to evaluate this factor. Methods Retrospectively 94 patients with CMM and clinically lymph-node metastases were analysed. Metastatic lymph-nodes were evaluated for ENG and if present grouped in microscopic (<2 mm) or macroscopic (>2 mm) ENG. ENG was defined as metastatic tumour which clearly extends histologically through the nodal capsule into the perinodal fatty tissue or tumour involvement in the hilar region with interruption of the smooth outline of the (presumed) capsule. Results Ninety-four patients, median age 52 (6–92) years with CMM, median Breslow thickness 2.8 (0.2–11.0) mm. In 50 patients ENG was present (macroscopic: 32, microscopic: 18). The median follow-up was 59 (range 5–325) months. The number of loco-regional recurrence was 10; 4 in the group with and 6 in the group without ENG (n.s.). Five years survival of patients with ENG was 42% and without ENG 50% (n.s.). There was no significant difference in survival or loco-regional recurrence between microscopic or macroscopic ENG. Conclusion ENG of lymph-node metastases of CMM is of no prognostic value and has no clinical impact.

La maladie de Rosai-Dorfman extra-ganglionnaire : à propos d’une localisation thyroïdienne

Extra nodal involvement by Rosaï-Dorfman disease (RDD) is not rare but remains poorly described clinically and microscopically. We report a case of RDD involving the thyroid and revealed by a 15 mm cold nodule developed on an ancient goiter. The patient was a 53 year old North African woman. She also presented an involvement of cervical lymph nodes, respiratory tract and right kidney. Microscopic analysis of thyroid revealed a diffuse and dense infiltrate of large pale histiocytes with few features of lymphophagocytosis. To the best of our knowledge, this is the fifth case reported in the literature. In previous reported cases, thyroid RDD was associated to constant lymph node involvement (massive lymphadenopathy in 3 cases and occult in one case) and no other extra nodal localization except the respiratory tract in one case. The characteristic features of lymphophagocytosis must be searched with great care.

Linfonodos cervicais: um dilema para o ultra-sonografista

A análise dos linfonodos cervicais é um assunto complexo, na medida em que obtemos, por vezes, padrões de imagens superponíveis para os processos benignos - reacionais (infecciosos específicos e inespecíficos) - e para os malignos - doenças neoplásicas (linfoproliferativas e metastáticas). O seguimento adequado das linfadenopatias também requer do examinador detalhamento topográfico e descrição dos aspectos ecográficos relevantes. Realizamos revisão literária com os objetivos de ressaltar os critérios ultra-sonográficos mais significantes (modo-B e dúplex-Doppler colorido) e fazer analogia aos reparos anatômicos utilizados na tomografia computadorizada, para uniformizar a descrição topográfica dos níveis linfonodais por meio da ultra-sonografia. Os aspectos avaliados ao modo-B foram: número (se agrupados ou isolado), forma, hilo ecogênico central, ecotextura/ecogenicidade, presença de calcificações, necrose e/ou hemorragia interna, dimensões, contornos (disseminação extracapsular). Ao dúplex-Doppler colorido os aspectos avaliados foram: padrão de vascularização e análise espectral - índice de resistividade e índice de pulsatilidade. Existem padrões ultra-sonográficos freqüentemente descritos nos linfonodos malignos como morfologia globosa, hipoecogenicidade marcada, vascularização predominantemente periférica e índice de resistividade elevado, porém a análise deve ser multifatorial, levando-se em conta os parâmetros ao modo-B e ao dúplex-Doppler colorido.

Favourable IGCCCG subgroups of stage II NSGCT patients may require less chemotherapy if TNM staging is included

4532 Background: When the IGCCCG prognostic factor analysis was performed there were few stage II cases included in this analysis of chemotherapy cases. Patients were not included from centres which used primary retroperitoneal lymph node dissection followed either by 2 courses of adjuvant chemotherapy or 3 courses at relapse. Primary surgery is the standard of care in North America but not in Europe where primary chemotherapy is used. To investigate this issue the impact of nodal (stage II) versus extra nodal (stage IV) metastases in each of the IGCCCG sub-groups has been examined in an audit of 447 patients treated in centres where chemotherapy rather than RPLND was primary management for stage 2 non-seminoma. Methods: Clinicians from 7 centres (St Barts, Oldchurch, Southend, Colchester, Ipswich, Norwich and Cambridge) have prospectively registered cases in a central data base at St Barts and notes review and follow up has been co-ordinated. Results: Between 1982 and 2002 447 patients were registered and survival analysis performed. Stage II cases comprised 63% of IGCCCG good-risk group (N=298), 42% of intermediate and 10% of poor risk patients. With median FU of 60 months there was no significant difference in survival for good-risk patients 92% of stage II (i.e. N+, n=156); 85% of stage IV (i.e. M+, n=94). In contrast survival was significantly influenced in intermediate and poor risk cases with 79% of stage II (N+, n=29) patients alive compared to 60% of stage IV (M+, n=92) (x2 4.05p = <0.05). There was no difference in survival between patients having 3 or 4 courses of treatment and no relapses in 8 who stopped treatment after two courses because of extenuating circumstances. Conclusions: Extralymphatic spread (stage IV) is prognostically significant within intermediate and poor risk IGCCCG. This influence is not seen in good risk patients and the observation that there may be N+ patients in whom it is possible to reduce treatment to 2 courses should be explored further. No significant financial relationships to disclose.

Favourable IGCCCG subgroups of stage II NSGCT patients may require less chemotherapy if TNM staging is included

4532 Background: When the IGCCCG prognostic factor analysis was performed there were few stage II cases included in this analysis of chemotherapy cases. Patients were not included from centres which used primary retroperitoneal lymph node dissection followed either by 2 courses of adjuvant chemotherapy or 3 courses at relapse. Primary surgery is the standard of care in North America but not in Europe where primary chemotherapy is used. To investigate this issue the impact of nodal (stage II) versus extra nodal (stage IV) metastases in each of the IGCCCG sub-groups has been examined in an audit of 447 patients treated in centres where chemotherapy rather than RPLND was primary management for stage 2 non-seminoma. Methods: Clinicians from 7 centres (St Barts, Oldchurch, Southend, Colchester, Ipswich, Norwich and Cambridge) have prospectively registered cases in a central data base at St Barts and notes review and follow up has been co-ordinated. Results: Between 1982 and 2002 447 patients were registered and survival analysis performed. Stage II cases comprised 63% of IGCCCG good-risk group (N=298), 42% of intermediate and 10% of poor risk patients. With median FU of 60 months there was no significant difference in survival for good-risk patients 92% of stage II (i.e. N+, n=156); 85% of stage IV (i.e. M+, n=94). In contrast survival was significantly influenced in intermediate and poor risk cases with 79% of stage II (N+, n=29) patients alive compared to 60% of stage IV (M+, n=92) (x2 4.05p = <0.05). There was no difference in survival between patients having 3 or 4 courses of treatment and no relapses in 8 who stopped treatment after two courses because of extenuating circumstances. Conclusions: Extralymphatic spread (stage IV) is prognostically significant within intermediate and poor risk IGCCCG. This influence is not seen in good risk patients and the observation that there may be N+ patients in whom it is possible to reduce treatment to 2 courses should be explored further. No significant financial relationships to disclose.

Positron emission tomography in the evaluation of lymphoma

Positron emission tomography (PET) using 18F-fluoro-deoxyglucose (FDG) has emerged in recent years as an important tool for the evaluation of lymphoma patients during their course of disease. At diagnosis, FDG imaging is capable of detecting nodal and extra nodal sites of disease and provides accurate staging. FDG-PET is superior to computed tomography, during and at the end of first-line treatment or salvage therapeutic regimens, as a tool for monitoring therapeutic response. PET enables the differential diagnosis of residual viable tumor versus a remnant fibrotic or necrotic mass. PET also provides prognostic data of high clinical significance for both Hodgkin’s disease and non-Hodgkin’s lymphoma. Results of this metabolic imaging modality, interpreted in view of the pretherapy risk profile of the individual patient, are predictive of the immediate success of a certain therapeutic strategy, as well as of overall and disease-free survival. PET appears to play also an important role in the detection of lymphoma relapse. Data comparing 67Gallium scintigraphy and FDG-PET indicate the latter as the functional imaging modality of choice for assessment of lymphoma patients. Preliminary studies show an additional value of fused PET/computed tomography imaging for further improved diagnosis, staging and definition of status of lymphoma.

Dendritic cell sarcoma of the oral cavity

Sarcomas derived from immune accessory cells are uncommon malignancies, most of them occurring in lymph nodes while extra nodal sites are very rarely affected. Based on the immune profile, the cells that give origin to these neoplasms are currently divided in: follicular dendritic cell (FDC), interdigitating dendritic cell (IDC), indeterminate cell and Langerhans cell. A case of a dendritic cell sarcoma arising in the alveolar ridge mucosa in a 50-year-old female is reported here. The lesion presented as a nodular mass without defined borders and covered by reddish mucosa. Histologically, the tumour was composed of spindle-shaped cells with large nuclei and abundant cytoplasm, arranged in variable patterns as storiform and whorled and revealing interspersed lymphocytes. No capsule could be seen and the neoplasm extended up to the lining epithelium. Immunohistochemically, the spindle cells were positive for vimentin, S-100 protein, CD1a, factor XIIIa and focally to smooth-muscle actin, but were negative for CD21, CD35, CD23 and caldesmon—all markers of follicular dendritic cells. In conclusion, the present case has morphologic pattern of dendritic cell sarcoma and the immunophenotype is compatible with IDC cells or with intermediate dendritic cells and demonstrates the overlap of features among these entities.

Posttransplant lymphoproliferative disorder associated with an Epstein-Barr-related virus in cynomolgus monkeys.

Human posttransplant lymphoproliferative disorder (PTLD) has been shown to be associated with Epstein-Barr virus (EBV) infection. Primate animal models of PTLD and the use of molecular markers in its diagnosis have not been reported. This study was designed to evaluate the frequency, pathology, and molecular characteristics of PTLD in cynomolgus kidney allograft recipients. Over a 5-year period (January 1995 to November 2000), 160 primate renal transplants were performed at the Massachusetts General Hospital (MGH). Of these, all cases (n=9) that developed PTLD were included. H&E stained paraffin sections of all available tissue samples from the cases were evaluated for the presence of PTLD. Immunoperoxidase staining for T cells (CD3), B cells (CD20), kappa and lambda light chains as well as EBV nuclear antigens (EBNA2) and latent membrane proteins (EBV LMP-1) was done on paraffin sections using standard immunohistochemical (IHC) methods. In situ hybridization for EBV encoded RNA (EBER) was performed in all tissue samples with atypical lymphoid proliferations, using a novel EBER nucleotide probe based on consensus gene sequences from EBV and the related herpes lymphocryptoviruses (LCV) infecting baboons and rhesus macaques. Of 160 consecutive primate renal transplants performed at MGH, 5.6% developed PTLD 28-103 days after transplantation. In all cases, the lymph nodes were involved and effaced by an atypical polymorphous lymphoid proliferation of EBER+ B cells, diagnostic for PTLD. Focal staining for EBNA-2 was noted in tumor cells. In 67% (six of nine) the PTLD infiltrates were present in extra nodal sites, notably liver (56%), lung (44%), heart (44%), renal allograft (44%), and native kidney (22%). The spleen was involved by PTLD in all four animals that had not undergone a pretransplant splenectomy. The PTLD morphology was similar in all cases and predominantly of the polymorphous type, however, some of these showed areas that appeared minimally polymorphous. No cases of monomorphic PTLD were seen. By in situ hybridization, expression of the RNA product, homologous for EBV-encoded RNA (EBER) was identified in the PTLD tumor cells of all cases, indicating latent primate EBV- related infection. This report identifies a novel animal model of EBV associated PTLD in the setting of kidney transplantation, with valuable implications for managing and understanding human PTLD and oncogenesis.