Extra Nodal Research Articles

Neck dissection for oral squamous cell carcinoma: our experience and a review of the literature.

ObjectivesThis article describes our experience with neck dissection in 10 patients with oral squamous cell carcinoma.Materials and MethodsBetween January 2007 and October 2009, 10 patients underwent primary surgery for the treatment of squamous cell carcinoma of the oral cavity. For patients with N0 disease on clinical exam, selective neck dissection (SND [I-III]) was performed. In patients with palpable cervical metastases (N+), modified radical neck dissections were performed, except in one patient in whom SND (I-III) was performed. The histopathologic reports were reviewed to assess the surgical margins, the presence of extra-capsular spread, perineural invasion, and lymphatic invasion.ResultsOn histopathologic examination, positive soft tissue margins were found in three patients, and regional lymph node metastases were present in five of the ten patients. Perineural invasion was noted in five patients, and extra nodal spread was found in four patients. Regional recurrence was seen in two patients and loco-regional recurrence plus distant metastasis to the tibia was observed in one patient. During the study period, three patients died. Seven patients remain free of disease to date.ConclusionHistopathological evaluation provides important and reliable information for disease staging, treatment planning, and prognosis. The philosophy of neck dissection is evolving rapidly with regard to the selectivity with which at-risk lymph node groups are removed. The sample size in the present study is small, thus, caution should be employed when interpreting these results.

Validation of a Prognostic Model to Assess the Risk of CNS Disease in Patients with Aggressive B-Cell Lymphoma

▪Introduction: Despite the improvement of outcome of aggressive B-cell lymphomas in the rituximab treatment era, central nervous system (CNS) relapse continues to pose a significant management problem. It remains a challenge to select patients (pts) in whom specific diagnostic procedures to identify CNS disease at diagnosis should be performed and to target a high risk group in whom a CNS prophylaxis strategy is warranted. The German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL) recently proposed a new prognostic model incorporating the 5 IPI factors (age > 60 y, LDH > N, stage 3 or 4, extranodal (EN) sites > 1) in addition to kidney/adrenal gland involvement to predict the risk of secondary CNS disease in pts with aggressive B-cell lymphoma. This model effectively stratified patients into 3 risk groups: low risk (0-1 factors, 2 y CNS relapse risk .6% (95% CI 0.0-1.2); intermediate risk (2-3 factors, 2 y CNS relapse risk 3.4 %( 95% CI 2.2-4.6)) and high risk (4-6 factors, 2 y CNS relapse risk of 10.2% (95% CI 6.3-14.1)) (Schmitz et al. Hematol. Oncol. 2013: 31, 047a). Herein, we sought to validate this model in an independent cohort of DLBCL treated with R-CHOP chemotherapy at the British Columbia Cancer Agency (BCCA).Methods: The DSHNHL dataset on which the model was initially developed was comprised of 2164 patients with aggressive B-cell lymphomas (n= 1735, 80.2% diffuse large B-cell lymphoma (DLBCL)), 18-80 years of age who were treated with rituximab with (CHO(E) P-like chemotherapy on prospective studies. The BCCA Lymphoid Cancer Database was screened to identify all patients with DLBCL treated with curative intent R-CHOP chemotherapy.Results: In total, 1597 patients were diagnosed with DLBCL at the BCCA and received at least one cycle of curative intent R-CHOP chemotherapy. The median follow-up for living patients was 4.2 years. Pts in the BCCA population-based DLBCL cohort were more likely to have poor risk features including PS >1, advanced age and a high IPI score (Table 1). Applying the 6 factor model, very similar risk groups were identified: low risk (0-1 factors 2 year CNS relapse risk .8% (95% CI 0.0-1.6%).; intermediate risk (2-3 factors 2 year CNS relapse risk 3.9% (95% CI 2.3-5.5%); and high risk (4-6 factors 2 y CNS relapse risk 12% (95% CI 7.9-16.1%) (Figure 1). The median time to CNS relapse was 6.7 months from the time of diagnosis in the BCCA group and was 7.2 months in the DSHNHL group highlighting that this event typically occurs early in the disease course. In both datasets kidney/adrenal involvement was highly associated with CNS relapse (2 year CNS risk BCCA 33%; 14% DSHNHL), the difference likely reflecting the higher risk pts in the BCCA population-based setting.Conclusions: We have validated the proposed DSHNHL prognostic model for CNS relapse in an independent dataset. The model identifies a high risk group in which diagnostic procedures to rule out CNS disease are highly recommended at diagnosis including MRI head, and cerebrospinal fluid analysis by cytology and flow cytometry and consideration of CNS-directed therapies. Kidney/adrenal involvement is consistently associated with a high risk of CNS relapse in the rituximab treatment era for which CNS prophylaxis should be incorporated into front-line therapy.Table 1Clinical factorBCCAN=1597DSHNHLN=2164Age > 60 years*Median age1035 (65%) 65 years (16-94)974 (45%) 58 years (18-80)Median follow-up4.6 years2.9 yearsMale sex915 (57%)1244 (57.5%)PS > 1*584 (37%)247 (11%)Elevated LDH1147 (53.0%)737 (49.0%)EN > 1396 (25%)479 (22%)Stage 3 or 4916 (57%)1148 (53%)IPI * 0,1234,5463 (31%) 359 (24%) 350 (23%) 329 (22%)1009 (47%) 523 (24%) 398 (18%) 231 (11%)Bulky disease > 7cm636 (41%)1027 (47.5%)*P< 0.05 [Display omitted] DisclosuresSavage:F Hoffmann-La Roche: Other. Villa:F Hoffmann-La Roche: Other. Sehn:Roche: Research Funding. Pfreundschuh:Roche: Advisory Board Other, Research Funding. Gascoyne:Hoffman La-Roche: Research Funding. Connors:Seattle Genetics, Inc.: Research Funding; Roche: Research Funding.

The Impact of Immunophenotypic Subtypes and Treatment Regimens on Patient Outcomes in Monomorphic Post-Transplant Lymphoproliferative Disorders (Diffuse Large B-Cell Lymphoma)

Introduction: Post-Transplant Lymphoproliferative Disorders (PTLD) are a group of heterogeneous disorders that arise as a consequence of iatrogenic immunosuppression for solid organ or allogeneic bone marrow/stem cell transplantation. Though they all arise in a common clinical context, different types of PTLD differ with respect to their underlying biology, clinical presentation and treatment. The aims of this study were to: (1) Define the cell of origin (COO) of monomorphic Diffuse Large B-cell Lymphoma (DLBCL) PTLD and evaluate their impact on clinical presentation and survival and (2) assess the impact of different Rituximab containing treatment regimens on survival outcomes in monomorphic DLBCL PTLD patients.Methods: We conducted a retrospective review of our institutional databases to identify all the cases of monomorphic PTLD (DLBCL) diagnosed and treated at our medical center from 2000-2013. COO classification into germinal center B-cell like (GCB) and non-germinal center B-cell like (non-GCB) type was performed by immunohistochemistry using the Hans algorithm.Results: Cell of origin: 40 cases of monomorphic PTLD (DLBCL) were diagnosed during the study interval. Tissue material for COO subtyping was available for 25 patients. By immunohistochemistry 16/25 (64%) were non-GCB and 9/25 (36%) were GCB subtype, median age of presentation being 46 years (range 3-75) and 48 years (range 3-64), respectively. A trend towards EBV positivity (by in situ hybridization for EBV encoded RNA) was noted in the non-GCB group (75% vs. 33%) [p=0.09]. Non-GCB DLBCL PTLD presented earlier post-transplant at a median 1.5 years (range 0.2-15) vs. 3.9 years (range 0.7-17) for GCB cases. When comparing immunosuppressive therapy at the time of PTLD presentation, an association between Tacrolimus therapy and non-GCB phenotype was identified [p=0.03]. Non-GCB DLBCL PTLD demonstrated a trend towards higher rates of extra nodal involvement (88% vs. 44%) [p=0.06] and advanced stage disease (Stage III/IV 75% vs. 33%) [p=0.09]. No significant differences in organ transplanted, LDH, ECOG performance and IPI were observed. While acknowledging the heterogeneity of therapies administered, no significant differences in Progression Free Survival (PFS) (median PFS non-GCB = 17 months vs. GCB = 15 months [p=0.36]) and Overall Survival (OS) (median OS non-GCB = 33 months vs. GCB = 27 months [p=0.22]) were identified.Impact of Treatment: 35 adults (age≥18) were treated at our center. The four most common first line therapies administered were R-CHOP (14), R-EPOCH (7), Palliative Care (5) and Rituximab monotherapy (4). Five patients were given 4 other different therapies. In patients given Rituximab monotherapy, two patients presenting with stage I disease responded while two with stage IV disease progressed. When focusing on patients who commenced R-CHOP or R-EPOCH as their initial therapy, no significant differences in age, stage, LDH, extra nodal disease, ECOG performance status, IPI and immunosuppression therapy was identified between the groups. The complete response (CR) rate for R-CHOP was 50% vs. 71% for R-EPOCH. Primary refractory disease was present in 29% of patients receiving R-CHOP vs. 14% with R-EPOCH. Death during first line therapy occurred equally in both groups (14%). All four primary refractory disease patients in the R-CHOP arm died, while the one patient who was primary refractory to R-EPOCH is alive 3 years post autologous stem cell transplant. R-EPOCH demonstrated prolonged PFS (median PFS R-CHOP = 15 months vs. R-EPOCH not reached [p=0.049]) and prolonged OS (Figure 1) [p=0.036].Conclusions: (1) In monomorphic PTLD (DLBCL), the non-GCB subtype predominates and is associated with the use of Tacrolimus. It commonly presents with advanced stage disease and extra nodal involvement however, no difference in PFS and OS was noted when compared to GCB DLBCL PTLD. (2) R-EPOCH demonstrated prolonged PFS and OS when compared to R-CHOP. The survival differences reflect the higher rates of primary refractory disease in the R-CHOP group and the inability to salvage patients once they become relapse/refractory. Given the retrospective nature of our analysis, further studies in a larger cohort of patients are ongoing to validate these results. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Post Transplant Lymphoproliferative Disorders (PTLD) after Solid Organ Transplant: Cleveland Clinic Experience

Background: Post transplant lymphoproliferative disorders (PTLD) are rare pathologically and clinically heterogeneous diseases arising in the setting of immunosuppression following hematopoietic stem cell and solid organ transplants (SOT). Our understanding of PTLD is restricted by its low incidence and heterogeneous treatment approaches, resulting in paucity of data. We sought to further describe characteristics and outcomes in PTLD patients who underwent treatment at our institution.Methods and Patients: We performed a retrospective study to describe our institutional experience in a relatively large cohort of PTLD patients after SOT. Patient and disease characteristics were examined and prognostic factors for survival were determined using univariate and multivariate Cox analysis.Results: Between May 1987 to January 2014, 98 patients with a confirmed diagnosis of PTLD underwent treatment at our institution. Median time from SOT to PTLD diagnosis was 60 months with median follow of 68 months from PTLD diagnosis. Baseline characteristics include male gender 77%, ECOG performance status (PS) 0-1 in 61%, and stage III-IV 69% with a median age at diagnosis of 47 years. Most common transplanted organ included heart 30%, lung 24%, kidney 20% and liver 19% and median time from SOT to PTLD diagnosis was 60 months. Most cases had monomorphic histology (81%) and were EBV+ (82%). Graft involvement and rejection were observed in 32% and 43% respectively. Of the 84% with extranodal (EN) involvement, gastrointestinal tract (37%) and lung (27%) were the common sites, while 3.2% had bone marrow (BM) involvement. Central nervous system (CNS) was involved in 11% of the cases. Only 58% received rituximab as part of the initial therapy, as significant part of our cohort was treated prior to rituximab era. Reduction in immunosuppression (73%), chemotherapy (40%), radiation (11%) and surgery (8%) were utilized either as single modality or in combination for treatment. Of the 66 patients with response data, 59% had complete response (CR) and 14% had progressive disease (PD). Relapse occurred in 23% of cases. Median overall survival (OS) from diagnosis of PTLD was 6 years (Figure 1), but in rituximab treated patients it was 8 years. On univariate analysis, higher age at diagnosis (HR 1.19, 95% CI 1.01-1.40, p=0.033), lung transplant (HR 2.42, 95% CI 1.36-4.33, p=0.003), higher IPI (HR 1.83, 95% CI 1.40-2.39, p=<0.001), decreased PS (HR 2.43, 95% CI 1.70-3.48, p=<0.001), and platelet count <200,000 (HR 2.84, 95% CI 1.27-6.33, p=0.011) were associated with lower OS, whereas liver transplant (HR 0.24, 95% CI 0.09-0.68, p=0.007) and GI involvement (HR 0.47, 95% CI 0.24-0.95, p=0.036) predicted better OS. Rituximab treatment (Figure 2) and achieving CR were associated with better OS. Histology, EN involvement, and EBV status were not significant predictors for survival. On multivariate analysis only lung transplant, IPI, and PS were predictive for OS. Lung transplant patients had a higher risk of mortality compared to other SOT (HR 2.63, 95% CI 1.39-4.95, p=0.003). Both higher IPI (HR 1.66, 95% CI 1.18-2.32, p=0.003) and poor PS (HR 1.94, 95% CI 1.27-2.96, p=0.002) were associated with inferior OS.Conclusions: In this large cohort of PTLD patients after SOT, lung transplants, higher IPI and poor PS were identified as poor prognostic factors for OS on both univariate and multivariate analysis. Rituximab treatment was a favorable prognostic factor for OS that resulted in prolonged survival observed in this cohort. [Display omitted] [Display omitted] DisclosuresHill:Millenium: Research Funding; Novartis: Research Funding.

Lack of Influence of Rituximab and CNS Directed Prophylactic Therapy on CNS Relapse in High-Risk Diffuse Large B Cell Lymphoma

Abstract Background/method: Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) although uncommon, can be devastating. Conflicting reports have been published regarding the reduction in incidence of CNS relapse in post-rituximabera.We retrospectively identified all the patients with DLBCL who has received rituximab-based chemotherapy at initial presentation in our institute between 2004 and 2014. Patients were divided into two groups, ‘high risk’ group and ‘standard risk’ group, based on following definition. High risk group will have at least one of the following risk factors 1) LDH ≥ 650 U/L 2) Age adjusted International Prognostic Index (IPI) of ≥ 4 3) Involvement of &gt; 1 extra nodal site 4) Involvement of testis 5) Breast 6) Bones 7) Kidneys 8) Adrenal glands 9) Retroperitoneal lymph nodes 10) Para-meninges or 11) Bone marrow. Patients without any of these risk factors were deemed standard risk. Descriptive statistics were used to analyze the incidence of CNS relapse, patient and disease characteristics. Historically reported incidence rates were used for comparison. Results:One hundred and forty two consecutive patients with DLBCL were included in our study. One hundred and twenty two patients received rituximab-based therapy at the initial diagnosis. Forty-nine patients (40%) met the criteria for ‘high risk’ based on the above definition. Seventy-three patients (60%) qualified for standard risk group. Standard risk group received no CNS directed prophylaxis and none of these patients had CNS relapses. Thirty-one of 49 ‘high risk’ patients received CNS prophylaxis, mainly intrathecal methotrexate. Total 5 patients (4.09%) developed CNS relapse. CNS relapse in high-risk group was 10.2% (5/49). Median age at diagnosis in patients with CNS relapse was 53 years. Median time to relapse was 8.76 months. Median survival after the CNS relapse was 9.16 months. Four out of 5 patients received CNS prophylaxis with intrathecal methotrexate or systemic methotrexate or systemic cytarabine or a combination of them. Average number of doses of prophylaxis received by each patient was 3.2 (range 1-7). Only one patient who developed CNS relapse did not receive any CNS directed therapy as prophylaxis. Conclusion:No significant reduction in the incidence of CNS relapse was noted with upfront use of rituximab. Our study confirms that majority of the DLBCL patients do not need CNS directed therapy. For high risk DLBCL patients, we not only need to develop better predictive markers for CNS relapse but also need better CNS directed therapies to prevent this fatal complication of highly curable disease. Disclosures No relevant conflicts of interest to declare.

Advanced Stage Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) in Children and Adolescents : Retrospective Study from Sfce and Ukccssg

Background: Advanced stage nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) in children and adolescents is a very rare entity and therefore few data about their treatment and outcome are available.Aim of the study: To describe the clinical characteristics and evolution of advanced stage NLPHL in children and adolescentsMethods:A retrospective analysis of clinical data of patients treated in the SFCE and UK CCLG centersPatients and Results: 32 patients with NLPHL according to the REAL/WHO classification with disease stage ≥ IIB were recorded between 1998 and 2013. Two patients had composite NLPHL and B cell non-Hodgkin lymphoma at diagnosis. Median age was 12 years (range 4-17) and the majority were boys [n=28; 88%]. Stage distribution was: IIB =2 ( 6%), III =25 (71%) & stage IV =5 (15%). Twenty-seven patients had cervical node involvement while mediastinum involvement was seen in 11 (34% ) patients. B symptoms were seen in 2 and eight patients had ESR >30 mm. Sites of extra nodal localisation were bone, bone marrow, liver and lungs.Standard Hodgkin chemotherapy regimens (CT) were used in 26 patients (81%), combined with rituximab (R) in 5 children (3 to 6 doses) and along with 20Gy involved field radiotherapy in 6 children. NHL chemotherapy regimens were used in 5 patients; R-CHOP [n=3], LMB 01 regimen [n=1] and other regimen [n=1]. One patient received rituximab alone (4 doses) and 1 child had no treatment [watch and wait strategy]. Median follow up is 45 months (5 – 162).Outcome: Overall survival is 96% and cumulative incidence of an event is 25%. Eight patients relapsed with a median delay of 15 months (5-73), and 3 had a second relapse 9,11 and 48 months respectively after first relapse. One patient treated with chemotherapy alone developed Ewing’s sarcoma and died 2 years later. The only patient treated with rituximab alone relapsed at 22 months. Of note, no relapses were observed in patients who had chemotherapy and rituximab.Conclusion: Our report shows that while advanced stage NLPHL in children and adolescents is rare, their clinical outcome is very good. Additionally, this report may inform the basis of future treatment of advanced stage NLPHL in children and adolescents. DisclosuresNo relevant conflicts of interest to declare.

Prognostic Role of Serum Albumin Level in DLBCL before and during the Rituximab Era. Retrospective GISL Study over 738 Cases

Introduction.Serum albumin (SA) has been shown to be a prognostic marker in many hematological malignancies, and in diffuse large B-cell lymphoma (DLBCL) before the introduction of rituximab. SA may be a surrogate for age, comorbid status, and disease severity. Here, we aimed to assess the role of SA as prognostic marker for overall survival (OS) in patients with newly diagnosed DLBCL treated with and without rituximab (R) containing regimens (CHOP and CHOP-like).Patients and methodWe collected 738 patients complete for IPI factors [age, LDH, extra nodal sites, stage and performance status (PS)] and SA recorded in the GISL database from 1998 to 2012. OS was estimated using the Kaplan-Meier method, with Cox proportional hazard model used to identify potential risk factors for time-to-event data. Optimal cut-off for SA was calculated by means of ROC curve at 5 years of follow-up. Stability of the cut-point was analyzed using bootstrap techniques. The role of SA was explored interacting SA with R and adjusting by IPI. The strength of SA as prognostic factor was evaluated counting the bootstrap frequency of inclusion (BIF, 1000 re-samples) of SA, adjusted by the IPI factors, in Cox PH regression.ResultsOf the 738 patients included in the study 322 (44%) were treated with R-CHOP and 416 (56%) were treated without regimens containing R. The median age at diagnosis was 60 years (range 21-89) and 45%, 25% and 30% were categorized in IPI 0-1, 2 and 3/5 respectively; and the median SA was 3.8 g/dL (range 1.0-6.4). Patients treated with R showed a greater % of high IPI 3/5 (43%) compared to those not treated with R (20%, P<0.001) and a lower SA level (3.7 vs 3.9 g/dL, P=0.001). SA showed correlation with IPI (4.0, 3.8 and 3.5 g/dL in IPI 0-1, 2 and 3/5, respectively, P=0.0001).Overall, the median follow-up was 64 months (range 1-157) with 241 dead. The 5-ys OS was 66% (95 CI 62-70) and the best cut-off for SA was 3.7 g/dL with ROC=68.5%. OS at 5-yrs in patients not treated with R was 74% and 52% for SA ≥3.7 and <3.7 g/dL, respectively (P<0.001). In patients treated with R the 5-yrs OS was 78% and 50% for SA ≥3.7 and <3.7 g/dL (P<0.001). The SA <3.7 g/dL, interacted by R and adjusted by IPI, had HR = 1.71 (95 CI 1.22-2.40, P=0.002) and HR = 1.99 (95 CI 1.31-3.01, P=0.001) in cases not treated and treated with R, and the HRs did not vary between treatments (P=0.582). The BIF of SA<3.7 g/dL adjusted by IPI factors was 88% and 79% in patients without and with R chemotherapy.ConclusionThe SA is a simple variable collected from the clinical-chemistry, that showed a good prognostic property in DLBCL. Although correlated with the IPI, SA has maintained a strong prognostic value both before or during the rituximab era. The biologic role of SA over the survival is unclear. It has been hypothesized that low level of SA may be associated with 1) increased inflammatory response to the tumor, 2) increased cytokine release and 3) poor nutritional status, and due to this condition the patients would not be able to receive the full cycles of chemotherapy. DisclosuresNo relevant conflicts of interest to declare.

Combined Modality Approach for Early Stage Unfavorable Hodgkin Lymphoma- Can We Avoid Radiation Therapy Based on Interim PET Imaging?

Background: Prior studies have demonstrated the utility of involved field radiation therapy to reduce relapse rates and improve local control in Hodgkin Lymphoma (HL). The standard treatment for early stage unfavorable HL is combined modality approach with chemotherapy and radiation therapy (XRT). Despite reduction in the fields of XRT, long term adverse outcomes are associated with the combined modality approach. Recent clinical trials have focused on adapting therapy based on interim PET scans. There is, however, limited data evaluating patient outcomes with chemotherapy alone in unfavorable, bulky HL patients.Methods: Two hundred and fifteen patients diagnosed with HL at our institution were included in our retrospective analysis after obtaining IRB approval. Statistical analysis was performed by chi-square analysis, Wilcoxon signed rank sum test and Kaplan-Meier plots using SPSS.19 software.Results: Of the 215 patients, 48 had early stage unfavorable HL and were included in this analysis. Unfavorable HL was defined as bulky disease (>10cm or >1/3 thoracic diameter), ESR >50 or >3 extra nodal sites involvement at presentation. The median age at diagnosis was 31 years (range 17-58). Twenty-two patients (46%) were male. All patients had an Eastern Cooperative Oncology Group performance status of either 0 or 1. Nineteen patients (40%) presented with B symptoms. The majority (83%) of patients were treated with 4-6 cycles of ABVD as first line therapy, while the remainder were treated with COPP/ABV, Stanford V, ABV or MOPP/ABV. Approximately half of the patients received XRT (54%), which was determined by physician choice. Forty-six patients (96%) were alive at the time of analysis. Seven patients (15%) underwent autologous stem cell transplantation for either disease relapse or for an incomplete response. Interim PET data was missing in 8 patients, who were excluded from subsequent analysis. Interim PET was positive in 13 of the remaining 40 patients, 9 of whom received consolidative radiation therapy and 4 of whom received high dose therapy followed by autologous stem cell transplantation. Among the 27 patients with negative interim PET, 12 received XRT. The median overall survival (OS) of all patients was 38.8 months. In patients with negative interim PET scan, the PFS was 83% and 80% in patients who received chemotherapy with and without XRT, respectively. The OS was 83% and 100% in patients who received chemotherapy with and without XRT, respectively. The differences in PFS and OS were not statistically significant between the two groups. Two patients died in the group that received combined modality treatment after negative interim PET, one from pre-existing cardiomyopathy and one from progression of disease. No death was related to XRT. In a subgroup analysis, eleven of the 27 patients with negative interim PET had bulky disease, 8 of whom received XRT. The PFS in this subgroup was 75% and 100% in patients who received chemotherapy with and without XRT, respectively. The OS in this subgroup was 88% and 100% in patients who received chemotherapy with and without XRT, respectively.Conclusion: Our data suggests that radiation therapy can be avoided based on interim PET scan in early stage unfavorable HL without compromising OS. The high overall survival of these patients may be accounted for by the fact that many who fail initial treatment can be salvaged with high dose chemotherapy and autologous stem cell transplantation. Given the potential for reduction in radiation related adverse outcomes, we encourage participation in ongoing prospective, PET-adapted, clinical trials investigating the need for consolidative XRT following chemotherapy in patients with unfavorable, bulky disease. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Distribution of Ki67 proliferative indices among WHO subtypes of non-Hodgkin's lymphoma: association with other clinical parameters.

Non-hodgkin lymphoma (NHL) is a diverse group of disease encompassing divergent tumor types with contrasting clinical behaviors. We aimed to evaluate the usefulness of Ki67 index in segregating indolent from aggressive NHL and its association with clinical parameters. During a study period of 4.5 years, a total of 215 cases of lymphomas were diagnosed among of which 172 cases were NHL. Ki67 immunohistochemical staining was performed by the DAKO envision method. Average proportion of tumor cells stained was calculated to determine the proliferative index. The mean age at diagnosis was 46.2 years +19.8 (3-81) with a male to female ratio of 1.5:1. Mean Ki67 index for indolent NHL included 23% for small cell, 25% for mantle cell, 28.5% for marginal zone and 34.6% for follicular lymphoma. On the other hand, mean Ki67 index for aggressive lymphomas were 66.4%, 66.9%, 80.3%, 83.3% and 94.4% for diffuse large B cell, T cell (NOS), anaplastic large cell, lymphoblastic and burkitts lymphoma respectively. No significant correlation was found between Ki67 index and other clinical parameters like age and extra nodal involvement. Ki67 index is a valuable IHC marker to distinguish indolent from aggressive lymphomas especially in small needle biopsies where exact typing may not be possible.

English

INTRODUCTION: Rosai-Dorfman disease (RDD) is a rare proliferative histiocytic disorder of unknown etiology. RDD typically presents with generalized lymphadenopathy and polymorphic histiocytic infiltration of the lymph node sinuses; however, occurrences of extranodal soft tissue RDD may rarely occur. We are presenting a case that presented as a subcutaneous swelling. CONCLUSION: RDD is a rare inflammatory lesion that should be considered in the differential diagnosis of a soft tissue tumor. Differentiation of extra nodal RDD from more common soft tissue tumors such as soft tissue sarcoma or inflammatory my fibroblastic tumor is difficult and usually requires definitive surgical excision with histopathological examination. The optimal treatment for extra nodal RDD is surgical excision and is usually curative.

PO-0162 Clinical Profile And Outcome Of Children With Anaplastic Large Cell Lymphoma

Background Anaplastic large cell lymphoma (ALCL) in children is usually ALK positive and is characterised by advanced disease at presentation with a high incidence of extra nodal involvement. We present the clinical profile, treatment and outcome of a small cohort of children with ALCL treated at our centre between January 2004 and June 2013. Results 19 children, 14 boys and 5 girls, aged 18 months to 14 years, with ALCL. 16/19 had lymphadenopathy and 14/19 had fever. Thirteen had high risk, 5 had standard risk and one had low risk disease. 16/19 ALK positive. 17/19 were treated according to the NHL-BFM 90 protocol. Fourteen completed treatment. Three died during treatment; 2 due to infection and 1 had progressive disease. All 3 had high risk disease and were ALK positive. All thethree children with ALK negative disease relapsed; one died on relapse treatment, another was lost to follow up a year after completion of relapse therapy and the third with primary cutaneous disease, is alive and well. Of the 11 ALK positive children who completed treatment, only one relapsed and died. The remaining 10 are alive and well with a mean follow up of 17 months (range 8–93 months). Conclusion The majority of our patients are ALK positive and have high risk disease at presentation. 55% of children with high risk disease are alive and well after a mean follow up of 17 months. The overall survival was 65% and event free survival 58% at the time of this analysis.

Epidemiology of Post-Transplant Lymphoproliferative Disorders in Solid Organ Transplant Recipients in a Single Canadian Centre.

Objective: Many epidemiologic studies of post-transplant lymphoproliferative disorder (PTLD) in solid organ transplant (SOT) populations have limited follow-up, incomplete pre-transplant viral serology and PTLD histology, and study only adults or children. We describe a single center study of the PTLD cases in all adult and pediatric (ped) SOT recipients from January 1, 1984 to June 30, 2013. Methods: Patients (n=4750, 475 age < 18, 4275 age ≥ 18) included 724 heart (15.2%), 551 lung or heart/lung (11.6%), 1298 liver (27.3%), 2099 kidney (44.2%), 66 pancreas or kidney/pancreas (1.4%), and 12 multivisceral or small bowel (.3%). Yearly cumulative incidence (CI) was calculated using the patient-year variant of the incidence definition: number of cases/amount of patient-time at risk each year. PTLD risk factors were analyzed using univariate Cox regression analyses, ped and adult patients were analyzed separately. Results: 134 cases of PTLD occurred over a median follow-up (FU) of 5.98 yrs (standard error (SE) 0.09, range 0-29.5 yrs). Ped SOT recipients developed more early lesions and polymorphic PTLD than adults (44 vs. 10%); adults had more monomorphic PTLD (68 vs. 38%). CI of PTLD was 1.31% PY at 1 year, 2.25% PY at 5 years, 3.04% at 10 years, and 3.93% PY at 20 years. Median overall survival (OS) of the entire cohort was 13.8 years (SE .36); PTLD adversely impacted OS in adult (p=.000, HR 1.3 (95% C.Int. 1.1-1.4), but not ped recipients (p=.23). Factors that significantly increased PTLD risk were: younger age at transplant, less time post-transplant, REBV -, and RCMV- (adult only). Risk of early (≤ 1 year) and late (> 1 year) PTLD, early/late EBER+ PTLD, and PTLD localized to CNS, GI, allograft and >1 extranodal (EN) site decreased with increased age at transplant. Risk of early PTLD and allograft PTLD in adults was higher from 1984-1991 compared to 2002-13. Being REBV- conferred significantly higher risk of early and late PTLD, early and late EBER+ PTLD, and PTLD localized in the CNS, GI tract, allograft, and over 1 EN site in adults. Conclusions: PTLD cases continued to arise 20 yrs post-transplant, and risk was increased by younger age, shorter duration post-transplant, and negative EBV serology. Negative EBV serostatus also increased risk of all PTLD subgroups in adults, including CNS involvement.

Prospect and guideline update of sentinel lymph node biopsy for patients with early-stage breast carcinoma

Axillary lymph nodes are the most common and initial site of metastasis of breast carcinoma. Precise axillary staging of breast carcinoma before initial treatment is crucial as it allows efficient identification for local and systemic treatment options, and provides prognostic information. Sentinel lymph node biopsy (SLNB) is an accurate minimally invasive technology for axillary staging. Although top evidence of high-quality clinical trials showed that SLNB could safely and effectively replace axillary lymph node dissection (ALND) for axillary negative patients with decrease in complications and improvement in quality of life, there are specific indications and contraindications for SLNB. Clinicians should balance the compliance of guideline and native clinical practice, especially for the circumstance of multifocal/multicentric lesion, breast biopsy history, and neoadjuvant chemotherapy. With the accumulation of clinical practice and new results of clinical trials, axillary therapy has changed from unique surgery to patient-tailored multi-disciplinary intervention, although ALND should be recommended traditionally if SLNB is positive. Intensive and accurate preoperative axillary staging is gradually valued by clinicians. Development of imaging modality especially ultrasonography and ultrasound-guided biopsy can identify some extra lymph node positive patients directly to ALND with avoidance of unnecessary SLNB. Thus, the positive rate of SLNB will decline significantly. It seems possible that axillary management will step into a noninvasive era abandoning SLNB in some patients with small breast cancer. In this article we review the prospect and guideline update of SLNB for patients with early-stage breast cancer.

Extra nodal ENT tuberculosis

IntroductionTuberculosis (TB) of the head and neck is one of the rarer forms of extrapulmonary tuberculosis but still poses a significant clinical and diagnostic challenge. PurposeThe aim of this study is to discuss diagnostic problems of the extra nodal ENT TB and to analyze its epidemiological and clinical specificities. Patients and methodsWe report a study of 21 cases of extra-nodal locations of TB managed in the ENT department of the Habib Thamer Hospital of Tunis between 2003 and 2012. ResultsThe disease affected the nasopharynx in 13 cases, the tonsils in 3 cases and the larynx in 2 cases. The parotid gland, the thyroid gland and the rhinosinus were compromised in one case each. The clinical signs as well as radiology and endoscopy are not specific. Diagnosis was based on histopathological examination. All our patients received anti-tubercular chemotherapy. The evolution was favorable with 12months average outcome. ConclusionThere are no pathognomonic features indicative of this disease. It is important for otolaryngologists to mention TB as a differential diagnosis in head and neck malignancies and other chronic non infective and infective pathological conditions. Early diagnosis and therapy may prevent needless and risky surgery.

Changing trend of HIV-associated PCNSL over 15 years: A single-center experience.

2049 Background: Primary central nervous system lymphoma (PCNSL) is a rare form of extra nodal non Hodgkin lymphoma, accounting for approximately 3-4% of primary brain tumors and approximately 1% o...

Multifocal Primary Non- Hodgkin’s Lymphoma of the Oral Cavity: Report of Three Cases and Review of the Literature

Objective: Oral non- Hodgkin’s lymphoma (NHL) is a relatively rare neoplasm that may develop in the soft tissues or jaw bones, with or without node or marrow involvement. Oral lymphomas are often difficult to diagnose as there are no characteristic clinical features and usually appear as non- tender swellings.Case: We describe clinical, radiographic, histopathological and immunohistochemical findings of three cases of multifocal NHLs presenting in the oral cavity.Conclusion: If the oral lesion is multifocal, extra nodal lymphoma must be considered in the differential diagnosis.

Clinicopathologic Characterization of Diffuse-Large-B-Cell Lymphoma with an Associated Serum Monoclonal IgM Component

Recently, diffuse-large-B-cell lymphoma (DLBCL) associated with serum IgM monoclonal component (MC) has been shown to be a very poor prognostic subset although, detailed pathological and molecular data are still lacking. In the present study, the clinicopathological features and survival of IgM-secreting DLBCL were analyzed and compared to non-secreting cases in a series of 151 conventional DLBCL treated with R-CHOP. IgM MC was detected in 19 (12.5%) out of 151 patients at disease onset. In 17 of these cases secretion was likely due to the neoplastic clone, as suggested by the expression of heavy chain IgM protein in the cytoplasm of tumor cells. In IgM-secreting cases immunoblastic features (p<.0001), non-GCB-type (p = .002) stage III-IV(p = .003), ≥2 extra nodal sites (p<.0001), bone-marrow (p = .002), central-nervous-system (CNS) involvement at disease onset or relapse (p<.0001), IPI-score 3–5 (p = .009) and failure to achieve complete remission (p = .005), were significantly more frequent. FISH analyses for BCL2, BCL6 and MYC gene rearrangements detected only two cases harboring BCL2 gene translocation and in one case a concomitant BCL6 gene translocation was also observed. None of the IgM-secreting DLBCL was found to have L265P mutation of MYD88 gene. Thirty-six month event-free (11.8% vs 66.4% p<.0001), progression-free (23.5% vs 75.7%, p<.0001) and overall (47.1% vs 74.8%, p<.0001) survivals were significantly worse in the IgM-secreting group. In multivariate analysis IgM-secreting (p = .005, expB = 0.339, CI = 0.160-0.716) and IPI-score 3–5 (p = .010, expB = 0.274, CI = 0.102–0.737) were the only significant factors for progression-free-survival. Notably, four relapsed patients, who were treated with salvage immmunochemotherapy combined with bortezomib or lenalidomide, achieved lasting remission. Our data suggests that IgM-secreting cases are a distinct subset of DLBCL, originating from activated-B-cells with terminally differentiated features, prevalent extra nodal dissemination and at high risk of CNS involvement.

Testicular swelling: A rare manifestation of chronic lymphocytic leukemia presenting with Richter′s syndrome

Richter syndrome (RS) represents the clinico-pathologic transformation of indolent lymphomas to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. Majority of the patients have a previous diagnosis of Chronic Lymphocytic Leukemia and the median time to transformation is 2-4 years. De novo RS is extremely uncommon. RS frequently arises in the lymph nodes or bone marrow and rarely presents with extra nodal involvement, common sites being the gastrointestinal tract, eye, central nervous system, lung and kidney. Involvement of testis by RS is extremely rare and we came across only one such reported case in the literature. We are reporting this case as our patient presented with de novo RS at an extremely uncommon extra nodal site, testis.

Transformation and additional malignancies are leading risk factors for an adverse course of disease in marginal zone lymphoma

Marginal zone lymphoma (MZL) is a non-Hodgkin lymphoma that occurs as extra nodal, nodal, or splenic. While MZL is generally considered an indolent disease, a substantial percentage of patients follow an unfavorable course. The objective of this retrospective analysis was to identify predictors for a reduced overall survival (OS), or conversely an increased OS. One hundred and ninety-seven MZL patients were analyzed. Apart from assessing previously published risk factors, concomitant morbidity at diagnosis, transformation into aggressive lymphoma, and occurrence of additional malignancies were evaluated. Next to the known risk factors, i.e. above 60 years of age and elevated serum lactate dehydrogenase (LDH), we demonstrate that transformation into aggressive lymphoma, as well as additional malignancies, are important independent risk factors for a shortened OS in a multivariate analysis, irrespective of the MZL localization. Impressively, in the group of patients lacking LDH elevation, transformation, and/or additional malignancies, only 1 of 63 patients died during follow-up compared with 37 of 87 patients in the high-risk group (HR = 22.8; 95% confidence interval 3.1-167.0; P = 0.002). Our analysis proposes novel risk factors and warrants for a continuous follow-up to detect the occurrence of transformation and additional malignancies early on.

Extranodal diffuse large B-cell lymphoma: Experience from a tertiary care oncology center in South India

Aims: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma (NHL) with frequent extra nodal (EN) presentation. The overall occurrence of lymphomas has been increasing; however, those of EN-NHL have been increasing much more rapidly. There is limited data found on EN-DLBCL in the Indian population and hence we carried out this retrospective observational study of primary EN-DLBCL at our center in Southern India. Materials and Methods: A total of 90 consecutive cases diagnosed as EN-DLBCL (according to the standard criteria) by tissue biopsy confirmed by immunohistochemistry between 2007 and 2011 were included. Staging workup including computed tomography of neck, thorax and abdomen and pelvis, bone marrow aspiration and biopsy was done and International Prognostic Index (IPI) calculated. Staging was according to Cotswold's modification of Ann Arbor. The actuarial survival analysis was performed by Kaplan-Meier. Data were analyzed using the SPSS (version 16) statistical software. Results: The median age in this study was 49 years (18-88) with results showing EN-DLBCL to be 1.36 times more common in males. Advanced stages were seen in 15 subjects (16.6%) and bulky disease in 13 subjects (14.4%). CD20 was positive in 89 (98.8%) while 32 had high serum lactate dehydrogenase. According to the IPI most were low-risk-56 (66.6%). Overall response rate for the various combination chemotherapies was 85.7% with complete response in 62.3%. The overall survival range spanned from 2 to 123 months. Univariate analysis showed only bulky disease was associated with inferior survival. Conclusions: EN-DLBCL was present at an early age compared to nodal DLBCL, present more often in early stage and low IPI score. Chemoimmunotherapy with radiotherapy to the EN or bulky site is the standard treatment at present.