Extranodal Origin Research Articles

An extremely rare presentation of non-Hodgkin lymphoma in the head and neck: a case report

BackgroundNon-Hodgkin lymphoma (NHL) frequently presents as extra-nodal involvement, although primary diffuse large B cell lymphoma of extra-nodal origin is a distinct entity. Different subtypes may have propensity for specific anatomic locations. In the head and neck region, diffuse large B cell lymphoma (DLBCL) is most commonly presented in the paranasal sinuses, jaws, and Waldeyer’s ring. DLBCL involving fibroadipose tissue and presenting as an extra-nodal mass is extremely unusual, particularly in the head and neck region.Case presentationWe will present a case of forehead mass as presenting features of a highly aggressive B cell lymphoma.ConclusionAlthough soft tissue DLBCL presenting as scalp mass is rare, it should be considered in differential diagnosis of every soft tissue lump.

Small Lymphocytic Lymphoma Presenting as a Breast Lump: A Rare Presentation of Non-Hodgkin's Lymphoma

Approximately one-fourth of non-Hodgkin's lymphomas (NHLs) present with an extranodal origin. Primary and secondary involvements of the breast by lymphoma are rare because of the paucity of lymphoid tissue in the breast. Primary breast small lymphocytic lymphoma (SLL) typically presents as a manifestation of widespread chronic lymphocytic leukemia (CLL). A 58-year-old female presented to our clinic with a palpable breast mass. She had no cytopenias and her absolute peripheral B lymphocyte count was less than 5000/microL. The mass was biopsied and histology with immunohistochemistry showed neoplastic cells positive for CD23 and CD5 confirming the diagnosis of small B cell lymphocytic lymphoma of the breast. Further imaging revealed extensive mediastinal and retroperitoneal lymphadenopathy. Histopathology of bone marrow biopsy revealed diffuse infiltration with SLL. The patient was treated with six cycles of fludarabine, cyclophosphamide and rituximab (FCR) with excellent clinical response. To our knowledge, this is the first case of SLL infiltration of the breast without CLL treated successfully with FCR.

Mir-671-5p, Mir-193b-5p, Mir-1307-5p Are Useful for Predicting Outcome in Diffuse Large B-Cell Lymphoma

Background: Diffuse large B-cell Lymphoma (DLBCL) is stratified histologically as GCB and ABC phenotypes based on Hans algorithm. Besides this categorization, there is a paucity of molecular markers useful for predicting response to CHOP/R-CHOP chemotherapy and outcome of DLBCL patients. We performed miRNA profiling to identify potential miRNAs for their ability to predict response to chemotherapy and outcome in DLBCL patients.Methods: A total of 41 cases of histologically and immunohistochemically confirmed DLBCL cases who received R-CHOP/CHOP were included in this study after IRB approval. The follow up ranged from 7 to 2273 days with a mean of, 874 days. Cases in sustained complete remission for ≥ 1095 days were identified as “responders” whereas cases with partial response/stable disease or primary progressive disease were identified as“non-responders”. In the first part of the study, miRNA transcriptome profiling was performed from lymph node tissue of 10 cases of DLBCL which included 3 responders and 7 non-responders (3 with refractory disease and 4 with relapse) for identification and selection of differentially expressed miRNAs. Total RNA was isolated from the biopsies, libraries constructed with ION TOTAL RNA-SEQ v2 and sequenced on S5 ION Torrent. The filtered reads were aligned to the reference genome hg19 using Bowtie. Differentially expressed miRNAs were identified by DESeq2. In the second part of the study, validation of the selected miRNAs was performed in a retrospective validation cohort of 41 cases including 17 responders and 24 non-responders by semi-quantitative qRT-PCR. ROC curves were obtained and best cut-off for the delta Ct values was selected for each of the miRNAs to distinguish the two cohorts of patients. In the third part of the study, an additional 38 cases of DLBCL were included prospectively as testing cohort, in whom mi-RNA were isolated from paired pre-treatment biopsy and plasma samples were evaluated for the expression of the selected miRNAs for prediction of response to treatment and outcome.Results: miRNA transcriptome profiling revealed a total of 30 differentially expressed miRNAs among DLBCL responders vs non-responders and the data was submitted to GEO database (GSE179760). The top 4 significantly downregulated miRNAs in non-responders selected for validation included miR-193b-5p, miR-671-5p, miR-1307-5p and miR-326 as shown in the volcano plot and heatmap in Fig.1. In-silico prediction for the interacting genes of the selected miRNAs revealed genes involved in lymphoma progression and chemoresistance . Validation by qRT-PCR revealed significant down-regulation of miR-1307-5p, miR-671-5p and miR-193b-5p in the non-responders compared to responders (Fig.2). There was no significant association of miRNA expression with disease stage, nodal or extranodal origin and the presence of B symptoms. However, the downregulation of miR-671-5p was found to be associated with the presence of B-symptoms. Downregulation of miR-193b-5p, miR-671-5p, miR-1307-5p expression showed a significant association with progression free survival as shown in Fig.3 (Spearman's correlation plot and Kaplan-Meier survival curves).In the prospective cohort of 38 DLBCL patients, all 3 miRNAs were expressed in cell free plasma and tissue but only miRNA-193b-5p showed correlation between them. Using the cut-off Ct values obtained from ROC curves of tissue miRNA levels in the validation cohort , 16/38 patients were predicted to be non-responders. The preliminary data showed that 8 of these 16 cases were correctly predicted (6 died of disease, 2 showed partial response). The remaining cases are still under follow-up. The treatment response could not be predicted on the corresponding plasma levels.Conclusion: Downregulation of miRNA-671-5p, miR-193b-5p and miR-1307-5p in pre-treatment biopsy samples is associated with poor outcome and shorter progression free survival and poor treatment response leading to refractory/relapse DLBCL, which needs confirmation in larger studies. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Multicenter Study of the Seroprevalence of Antibodies against Covid-19 in Patients with Lymphoma: An Analysis of the Oncological Group for the Treatment and Study of Lymphomas (Gotel).

The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) coronavirus has generated a pandemic, in which there are population groups at higher risk and who are potentially fatal victims of the disease. Cancer patients have been considered a group with special susceptibility, particularly patients with lung tumour involvement and haematological neoplasms. The Spanish Lymphoma Oncology Group (GOTEL) carried out a multicenter study of SARS-CoV-2 seroprevalence in patients with lymphoma. Results: A total of 150 patients were included between 22 May and 11 June 2020. The mean age was 65 years (range 17–89), 70 women (46.5%) and 80 men (53, 5%). At the time of diagnosis of lymphoma, 13 cases were stage I (9%), 27 (18%) stage II, 37 (24.5%) stage III, and 73 (48.5%) stage IV, while 6.6% had a primary extranodal origin. A total of 10 cases with positive serology for SARS-CoV-2 were identified, which is a prevalence of 6% in this population. None of the patients required intensive care unit management and all fully recovered from the infection. Conclusion: IgG antibody seroprevalence in lymphoma patients appears similar to that of the general population and does not show greater aggressiveness.

Multiple recurrent follicular dendritic cell sarcoma: A case report.

Tumors of the follicular dendritic cells (FDC-Sarcoma) represent a rare entity with only about 200 cases reported worldwide. The majority (60%) of cases arise primarily in cervical, abdominal or axillar lymph nodes, but extra nodal origin from secondary lymphatic tissue like the tonsils, Waldeyer's ring or MALT is also common (40%). The current report presents a characteristic course of a cervical FDC-Sarcoma, with its challenges in establishing the initial diagnosis and the struggle for therapeutic options. The FDC-Sarcoma presented recurrently for four times. Three different university hospitals in Germany were involved in the patients' treatment. Due to the patients' refusal, no adjuvant therapy was applied. In the end, a neck dissection was performed. The patient was closely followed up and has been recurrence-free for 10 years. This case suggests operative resection in combination with a neck dissection as a curative therapy for FDC-Sarcoma of the head and neck.

Diagnosis-to-Treatment Interval As a Prognostic Factor in Aggressive T-Cell Lymphomas

Background: Recent studies (Maurer et al., JCO 2018, Olszewski et al., BJH 2018) have identified short diagnosis-to-treatment interval (DTI) of less than 15 days as a high-risk feature in B-cell lymphomas, independently of other clinical factors. T-cell lymphomas (TCL) pose a challenge because of their heterogeneity, rarity, and poor outcomes. Patients who respond to initial induction chemotherapy frequently proceed to consolidative high-dose chemotherapy with stem cell transplantation (SCT). Our objective was to examine the association between short DTI, receipt of SCT, and survival in 4 most common types of aggressive NK/TCL: peripheral TCL not otherwise specified (PTCL), angioimmunoblastic TCL (AITL), anaplastic large-cell TCL (ALCL), and extranodal NK-/T-cell lymphoma, nasal type (ENKTL).Methods: From the National Cancer Data Base, a registry containing >80% of lymphomas diagnosed in the US, we selected patients age 18 to 70, diagnosed with PTCL, AITL, ALCL, or ENKTL in 2004-2014, who received multi-agent chemotherapy within 120 days of diagnosis. Short DTI was defined as less than 15 days from diagnosis to start of chemotherapy. We analyzed the use of SCT as part of first course of treatment (before relapse) in a hierarchical logistic model adjusting for age, sex, race/ethnicity, TCL histology, stage, extranodal origin, and type of hospital (academic or community), reporting adjusted odds ratios (OR) with 95% confidence intervals (CI). Overall survival (OS) from start of chemotherapy was examined using Cox models adjusting for the same variables, reporting adjusted hazard ratios (HR). To investigate the differential impact of early mortality, we conducted sensitivity analyses in pre-specified subgroups excluding patients who died within 3 or 6 months of starting chemotherapy, and in the subset who underwent SCT (after presumably favorable response to initial chemotherapy).Results: Among 8,194 patients (Table; median age 54 years, 38% women), median DTI was 22 days (interquartile range, 11 to 38). The proportion undergoing SCT (11% overall) varied by histology, and was higher in academic centers (17%) compared with other types of hospitals (7%, P<.001). DTI of less than 15 days was associated with a significantly lower likelihood of undergoing SCT overall (OR, 0.71; 95%CI, 0.60-0.85, P=.0002), and this association was present in every histologic subtype except for ALCL, where the use of SCT was altogether rare. The association between short DTI and less frequent SCT persisted in the subset of patients surviving >3 months from the start of chemotherapy (OR, 0.78; 95%CI, 0.65-0.94, P=.012).With a median follow-up of 10.1 years, survival varied by histology, and was significantly worse for patients with short DTI in PTCL, ALCL and ENKTL, but not in AITL (Fig. A-D). Worse prognosis with short DTI persisted in the subsets patients who survived >3 months (overall HR, 1.32; 95%CI, 1.14-1.33; P<.0001) or >6 months (overall HR, 1.14; 95%CI, 1.04-1.25; P=.005) from the start of chemotherapy. However, in the subgroup of patients who successfully underwent SCT, a short DTI was no longer prognostic (Fig. E; HR, 0.91; 95%CI, 0.66-1.26; P=.57).Conclusions: Patients with TCL who need to start chemotherapy within 15 days of diagnosis have a lower likelihood of undergoing subsequent SCT. This association is not fully explained by early mortality, and may reflect a more aggressive biology, including worse response to standard chemotherapy-a hypothesis supported by the fact that achievement of SCT nullifies the poor prognostic value of short DTI. Short DTI is thus a novel risk factor in TCL that identifies a high-risk population well suited to experimental treatment strategies, and clinical researchers should strive to enroll these patients. Outcomes from clinical trials in which subjects start therapy after a screening period lasting >15 days from diagnosis should not be uncritically extrapolated to patients who start urgent chemotherapy in general practice. Further research should examine molecular characteristics and response rates to chemotherapy among patients with TCL who require immediate treatment upon diagnosis. [Display omitted] DisclosuresReagan:Takeda Oncology: Research Funding; Alexion: Honoraria; Pfizer: Research Funding. Olszewski:Genentech: Research Funding; Spectrum Pharmaceuticals: Consultancy, Research Funding; TG Therapeutics: Research Funding.

Clinical characteristics and treatment strategies for early-stage primary gastric diffuse large B-cell lymphoma

Objective: Primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is the most common non-Hodgkin lymphoma (NHL) of extranodal origin. Most patients with PG-DLBCL had localized disease (stage Ⅰ or Ⅱ) at presentation, and will achieve complete response (CR) after induction chemotherapy. However, there has been little consensus regarding whether optimal treatment is provided by chemotherapy alone or chemotherapy plus radiotherapy, nor the treatment outcome from the addition of rituximab in localized-stage PG-DLBCL. Methods: Patients with Stage ⅠE and ⅡE PG-DLBCL were retrospectively analyzed. Patients have not undergone surgery, have received at least 3 cycles of R-CHOP or CHOP-like chemotherapy as initial therapy, and achieved CR or partial response (PR) were enrolled. Results: A total of 91 patients were studied. The median age was 51 years, included 47 males and 44 females. Fifty-two patients were at Stage ⅠE and 39 at Stage ⅡE, 64 (70.3%) patients received R-CHOP-like regimens, and 27 (29.7%) received CHOP-like regimens, the median chemotherapy cycle was 6 (3-8). Among the 91 patients, 80 (87.9%) patients achieved CR from induction chemotherapy, 11(12.1%) was evaluated PR. Of CR patients, 48 patients (60%) underwent consolidating radiotherapy and 32 patients (40%) did not receive radiotherapy; all PR patients received salvage radiotherapy. CR patients with and without radiation therapy had 4-year progression-free survival (PFS) rates of 96.4% and 96.7%, respectively (χ(2) = 0.546, P=0.46); 7/11 (63.6%) PR patients achieved CR after radiotherapy, with a median follow-up of 41 months, they were all disease free. For patients treated with R-CHOP or CHOP-like regimens, the 4-year PFS was 93.2% and 89.7%, respectively (χ(2)=0.096, P=0.757). Conclusions: Consolidation radiotherapy failed to improve the outcome for early-stage PG-DLBCL, while for PR patients, salvage radiotherapy increased CR rate and improved survival. The addition of rituximab to CHOP did not improve the efficacy.

Role of neutrophil to lymphocyte ratio in addition to revised international prognostic index (R-IPI) in patients with extranodal diffuse large B-cell lymphoma of head and neck.

e19032 Background: Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin lymphoma (NHL). One third of DLBCLs cases have a primary extranodal origin and head and neck localization is second most common localization after gastrointestinal tract. The Revised-International Prognostic Index (r-IPI) is commonly used as prognostic tool, but there is growing evidence that neutrophil to lymphocyte ratio (NLR) also has prognostic significance in DLBCL. Methods: We retrospectively reviewed all cases of extranodal DLBCLs diagnosed between 2006 and 2016 at a single academic institution. Collected data included race, gender, primary site, baseline laboratory data, IPI score, pathology, treatment and survival. Results: A total of 33 patient were included, with 18 (54.5%) being females. Median age at diagnosis was 68 (range 28-92). 15% of patients had a r-IPI of 0, 30% a r-IPI of 1-2, 12% a rIPI of 3-5 and 36% a not evaluable (NE) r-IPI. Twelve (36%) patients had germinal center B cell subtype (GCB) and 17 (51%) patients had activated B cell subtype (ABC) by immunohistochemistry. Among all patients, 13 (39%) had pretreatment NLR equal or more than 3.5 and 11 (33%) patients had NLR less than 3.5 and 9 patients had a NE NLR. . Among deceased patients, 5 (56%) of them had NLR of more that 3.5 (p =0.011). Nine (27%) patients had pretreatment monocyte count less than 700/mm3 and 14 (42%) patients had monocyte count at least 700/mm3 (p=0.611). The 2-year overall survival was 77% (95% CI 0.61 - 0.93). Conclusions: (R-IPI) is the most common tool to predict outcome in DLBCL and our study showed that pretreatment NLR can be used as additional poor prognosis marker for patients with extranodal DLBCL of the head and neck. [Table: see text]

Improved survival with rituximab-based chemoimmunotherapy in older patients with extranodal diffuse large B-cell lymphoma

Using the Surveillance, Epidemiology, and End Results (SEER)–Medicare database, we investigated the relative benefits of adding rituximab to CHOP chemotherapy in diffuse large B-cell lymphoma (DLBCL) of extranodal origin, and found similar advantage for nodal and extranodal lymphomas. Hazard ratio for overall survival was 0.64 for nodal, and 0.70 for extranodal DLBCL. Hazard ratios for lymphoma-related death were 0.62 and 0.57, respectively. The advantage was largest for DLBCL of the spleen, liver and lung. Conversely, it was not evident for thyroid or testicular lymphomas. Compared with nodal DLBCL, spleen was the only site with significantly better prognosis after R-CHOP.

Differences In Clinical-Biological Features and Outcome Between Diffuse Large B-Cell Lymphomas Of HIV-Infected and Non-HIV-Infected Patients Treated With RCHOP In The CART Era

BackgroundThe use of combination antiretroviral therapy (CART) has improved the prognosis of HIV-related diffuse large B cell lymphoma (DLBCL). In the pre-CART era, HIV-infected individuals usually presented DLBCL of primary extranodal origin and advanced stage, unlike non-HIV-infected individuals. In the CART era, studies conducted before the introduction of immunochemotherapy pointed outcomes of HIV-infected patients to be approaching those of non-HIV-infected patients. Recently, studies have reported the lack of influence of HIV-infection in the prognosis of Burkitt's lymphoma treated with immunochemotherapy. Nevertheless, there is scarce information comparing the clinical presentation and outcome of DLBCL treated with immunochemotherapy between non-HIV-infected patients and HIV-infected patients in CART era. MethodsWe retrospectively studied two series of DLBCL patients treated with RCHOP; 81 HIV-infected patients included in a Spanish multicentre trial and 84 non-HIV-infected patients diagnosed in our institution between 2002 and 2010. Demographic, HIV-infection, and DLBCL data on each case were collected. DLBCL cases were classified in nodal and extranodal according to a previously reported definition (JCO 2005). Continuous and categorical variables are presented using descriptive statistics. Survival analyses were performed using the Kaplan-Meier method, and compared using the log-rank test. P-values of less than 0.05 were considered statistically significant. ResultsThe median follow-up of HIV-infected patients was 6.5 years and of non-HIV-infected patients was 4.6 years. Non-HIV-infected patients were older at the time of DLBCL diagnosis than HIV-infected patients, median age (range) 62 years (24-80) and 44 years (24-74) respectively; (P<0.001). HIV-infected series had a higher percentage of males (81%) than non-HIV-infected (52%); (P<0.001). There were differences between HIV-infected patients and non-HIV-infected patients regarding the following features: B-symptoms (53% vs. 26%; P<0.001), III and IV Ann Arbor stages (71% vs. 52%; P=0.011), and ECOG performance status higher than 2 (51% vs. 26%; P=0.001). There was a trend for more HIV-infected patients (61%) to have high LDH levels at DLBCL diagnosis than non-HIV-infected patients (45%); P=0.057. On the other hand, the percentage of patients with intermediate-high/high International Prognostic Index, two or more extranodal involvement, and bulky disease was similar in both HIV-infected and non-HIV-infected patients. No differences were observed between HIV-infected and non-HIV-infected series in terms of nodal and extranodal presentation. HIV-infected patients were classified according to the time of CART onset; before immunochemotherapy (69%) and concomitantly with RCHOP (31%). More patients receiving CART prior to immunochemotherapy presented undetectable viral load at lymphoma diagnosis (43%) than patients to whom CART was initiated with DLBCL treatment (4%); P=0.001. Time of CART onset had no effect on the presentation of the remaining clinical features, as well as in CD4-lymphocyte counts at DLBCL diagnosis. Non-HIV-infected patients tended to have a better complete response (CR) rate than HIV-infected patients (81% vs. 69%; P=0.071). Within HIV-infected patients the time of CART onset did not influence the achievement of CR to RCHOP. The overall survival (OS) was better in non-HIV-infected patients (5-year OS 74%; 95%CI: 64-84%) than in HIV-infected patients (5-year OS 56%; 95%CI: 45-67%); P=0.009. No differences in disease free survival (DFS) were observed between HIV-infected (5-year DFS 72%; 95%CI: 60-84%) and non-HIV-infected patients (5-year DFS 73%; 95%CI: 62-84%). In HIV-infected patients time of CART onset neither had impact in OS nor in DFS. Nodal and extranodal DLBCL cases showed similar OS and DFS. ConclusionsIn the CART era, DLBCL of HIV-infected patients still have aggressive features but the incidence of extranodal involvement equalizes that of non-HIV-infected patients. The prognosis of DLBCL treated with RCHOP is worse in HIV-infected than in non-HIV-infected patients.Supported in part by grants EC11-041 and RD12/0036/0029 RTICC from Instituto Carlos III, Spain. Disclosures:No relevant conflicts of interest to declare.

Are there any significant variations in the clinical or histological presentation of lymphoid pathologies over the course of time in Spain?

Little data is available concerning variations in the clinical characteristics of lymphoid neoplasms at presentation. We decided to investigate whether any variations in these characteristics had occurred in Spain during the last few years. The GOTEL group database is an archive of all new lymphoma cases, regardless of their histological subtype, diagnosed in the hospitals within the group. An analysis was made of all the records between 1 January 1999 and 1 January 2009. Though the number of hospitals submitting data has changed over the course of time, data were provided by 26 hospitals from 16 Spanish provinces. A total of 3651 cases of lymphoma were recorded during this period. Grouped by clinical features, 42.8% (1561 patients) had low-grade lymphoma, 30.4% (1110 patients) intermediate-grade lymphoma and 15.2% (556 patients) Hodgkin's lymphoma; 208 patients had T lymphoma (5.7%), 111 patients high-grade lymphoma (3%) and 105 patients (2.9%) suffered lymphomas that were difficult to classify. A total of 6.3% of the diagnoses (231 patients) were made prior to 1999, 29.5% between 2000 and 2001, 25.7% between 2002 and 2003, 19.7% between 2004 and 2005, 11.2% between 2006 and 2007, and there were 200 entries from 2008 to the close of the study period, corresponding to 1.5% of the complete database. The median age at diagnosis was 60 (range 7-105 years), by percentiles: 25 corresponded to 44 years old, 50 to 60 years old and 75 to 71. Distribution by gender was 53.1% male and 46.9% female. An analysis was made of all the clinical variables collected, comparing their behaviour during the different diagnostic periods. The periods, gender, ECOG, stage, LDH, ß2 microglobulin, Hodgkin's or non- Hodgkin's type neoplasm, B lymphoma vs. Hodgkin's, NK or T, nodal or extra-nodal origin, median age at diagnosis and histological type by region of origin did not show any statistically significant differences in their distribution over the course of time. In our experience, there are no significant variations in clinical presentation or histological type in lymphomas diagnosed over the course of time in Spain.

Follicular dendritic cell sarcoma of the tonsil

Follicular dendritic cells (FDCs) are non-phagocytic, non-lymphoid cells of immune system, which are necessary for antigen presentation and regulation of the reactions in the germinal centers of lymph node. Follicular dendritic cell sarcoma (FDCS) is unusual and those with an extranodal origin in the head and neck region are extremely rare. Here, we report a case of FDCS of the left tonsil in a 27-year-old male patient. The patient presented with swelling of the left tonsil and resultant difficulty in swallowing for last three months. The tumor was excised and was sent for histopathologic examination. Microscopic examination and immunohistochemical analysis proved the case to be FDCS. After the diagnosis, the patient received post-operative radiotherapy. The patient is on six months follow-up which is uneventful.

Biological Characterization of Nodal versus Extranodal Presentation of Diffuse Large B-Cell Lymphoma using Immunohistochemistry

Diffuse large B cell lymphoma (DLBCL) of primary nodal (PN) or primary extranodal (PEN) origin may differ immunophenotypically, in that PEN lymphoma cells may originate from activated rather than germinal center B (GCB) cells. We evaluated the relationship between DLBCL clinicopathological features, including expression of B-cell differentiation markers, and primary tumor site. Expression of CD10, Bcl-6, Bcl-2, and MUM1 was determined in paraffin-embedded tissues from 123 patients with DLBCL. Of the 123 patients with DLBCL, 40 (32.5%) had the GCB and 83 (67.5%) had the non-GCB phenotype. Fifty-one patients (42%) showed disease involvement at PEN sites, including 29 with disease in the gastrointestinal (GI) tract (14 in the stomach, 15 in the intestine). Of these 51 patients, 16 (31.4%) were classified with the GCB and 35 (68.5%) with the non-GCB subtype. There were no differences in the frequencies of GCB and non-GCB subtypes among primary sites. Of the 72 patients with PN DLBCL, 22 (31%) had the GCB and 50 (69%) had the non-GCB subtype. There were no differences in the frequencies of GCB and non-GCB subtypes between patients with PN and PEN DLBCL. Although lactate dehydrogenase (LDH) concentration > normal, stage >II, and rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) treatment were independent predictors of overall survival (OS), GCB subtype, and presence of PEN disease failed to predict survival upon multivariate analysis. There was no difference in GCB and non-GCB phenotypes between patients with PN and PEN DLBCLs. Additional studies are needed to further assess molecular differences between the two groups.

Variations in the clinical or histologic presentation of lymphoid pathologies over the course of time.

e18539 Background: Little data is available concerning variations in the clinical characteristics of lymphoid pathologies at presentation. We decided to investigate whether any variations in these aspects had occurred in our environment during the last few years. Methods: The GOTEL group database is an archive of all new lymphoma cases, regardless of their histological subtype, diagnosed in the hospitals within the group. An analysis was made of all the records between 1st January 1999 and 1st January 2010. The number of hospitals submitting data has changed over the course of time, however data has been provided by 26 hospitals from 16 Spanish provinces. Results: A total of 3,651 cases of lymphoma were recorded within this period. Grouped by clinical features, 42.8% (1,561 patients) presented low-grade lymphomas, 30.4% (1,110 patients) intermediate-grade lymphomas, 15.2% (556 patients) Hodgkin’s lymphomas, there were 208 patients with T lymphoma (5.7%), 111 patients with high-grade lymphomas (3%), and 105 patients (2.9%) with lymphomas that were difficult to classify. A total of 6.3% of the diagnoses (231 patients) were performed prior to 1999, 29.5% between 2000 and 2001, 25.7% between 2002 and 2003, 19.7% between 2004 and 2005, 11.2 % between 2006 and 2007, and 200 entries from 2008 to the close of the study period, corresponding to 1.5% of the complete database. The median age at diagnosis was 60 years (range 7-105 years), by percentiles: 25 correspond to 44 years, 50 to 60 years and 75 to 71 years. The distribution by gender was 53.1% male, and 46.9% female. An analysis was made of all the clinical variables collected, comparing their behaviour during the different diagnostic periods. Neither the periods, gender, ECOG, stage, LDH, β2 microglobulin, Hodgkin’s or non Hodgkin’s type neoplasia, B Lymphoma versus Hodgkin’s, NK or T, nodal or extra-nodal origin, median age at diagnosis nor histological type by region of origin, showed any statistically significant differences in their distribution over the course of time. Conclusions: In our experience, there are no significant variations in the clinical presentation or histological type in lymphomas diagnosed over the course of time in Spain.

Extranodal lymphomas

The assessment of extranodal lymphomas poses considerable challenges to general surgical histopathologists and specialist haematopathologists alike. The breadth of lymphoma subtypes that may occur at extranodal sites, the variation in morphology, immunophenotype, genetics and clinical features within and between these entities, the difficulties in distinguishing these lymphomas from reactive lymphoid infiltrates or other neoplasms, and the different clinical significance of lymphomas with primary versus secondary involvement of extranodal sites, all contribute to these challenges. In this review, I will discuss several lymphomas defined by extranodal origin (in particular extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue/MALT lymphoma, and enteropathy-associated T cell lymphoma) and aspects of selected others likely to be encountered at extranodal sites, with an emphasis on practical histopathological assessment. Lymphomas of the spleen, skin, bone marrow and thymus are not covered, as these are comprehensively reviewed in companion articles.

Follicular Dendritic Cell Sarcoma of the Tonsil

Follicular dendritic cell sarcoma (FDCS) is unusual, and those with an extranodal origin in the head and neck region are extremely rare. To date, no cases of tumors featuring the characteristics of follicular dendritic cells were reported in Korea. We report a new case of FDCS of the tonsils in a 65-year-old man. A diagnostic tonsillectomy was performed. Based on histopathologic and immunohistochemical findings, the patient was diagnosed with FDCS. Adjuvant radiotherapy was performed due to a high mitotic count. The patient survived with a 2-year disease free period. The differential diagnosis of a tonsillar mass must include FDCS. In cases in which FDCS is suspected on histopathologic examination, an immunohistochemical study is essential for the diagnosis

Tissue Microarrays in Diffuse Large B-Cell Lymphomas

Diffuse large B-cell lymphomas (DLBCL) can be divided into different subgroups (germinal center B-cell-like [GCB] and non-GCB) according to their gene expression profiles. Immunohistochemistry has been proposed as a surrogate for identifying these subgroups, but data about its efficacy in providing prognostic information are conflicting. This study retrospectively analyzed a series of 105 DLBCL, defined as GCB and non-GCB according to CD10, bcl-6, and MUM1 expression. All patients received a first-line anthracycline-based (CHOP-like) chemotherapy. A total of 50 patients (48%) were identified as GCB and 55 (52%) as non-GCB. The overall response rate was 89% (94/105), with 62 (59%) complete response. Disease progressions were equally distributed between the 2 subgroups and were not significantly different (P = .756) considering the primary site of involvement (nodal or extranodal). The median follow-up was 62 months (range 5-126 months). Overall survival at 5 years was not significantly different between the groups (P = .3468) and was 72.3% and 66.6% for GCB and non-GCB, respectively. The results do not support the prognostic value of GCB and non-GCB immunohistochemical categories in DLBCL of both nodal and extranodal origin. Furthermore, a limited number of antigens may be not sufficient to identify the same patterns defined by cDNA microarray. Prospective studies are warranted to address this issue.

A cytomorphological and immunohistochemical profile of aggressive B-cell lymphoma: high clinical impact of a cumulative immunohistochemical outcome predictor score

We analyzed morphological and immunohistochemical features in 174 aggressive B-cell lymphomas of nodal and extranodal origin. Morphological features included presence or absence of a follicular component and cytologic criteria according to the Kiel classification, whereas immunohistochemical studies included expression of CD10, BCL-2, BCL-6, IRF4/MUM1, HLA-DR, p53, Ki-67 and the assessment of plasmacytoid differentiation. Patients were treated with a CHOP-like regimen. While the presence or absence of either CD10, BCL-6 and IRF4/MUM1 reactivity or plasmacytoid differentiation did not identify particular cytomorphologic or site-specific subtypes, we found that expression of CD10 and BCL-6, and a low reactivity for IRF4/MUM1 were favourable prognostic indicators. In contrast, BCL-2 expression and presence of a monotypic cytoplasmic immunoglobulin expression was associated with an unfavourable prognosis in univariate analyses. Meta-analysis of these data resulted in the development of a cumulative immunohistochemical outcome predictor score (CIOPS) enabling the recognition of four distinct prognostic groups. Multivariate analysis proved this score to be independent of the international prognostic index. Such a cumulative immunohistochemical scoring approach might provide a valuable alternative in the recognition of defined risk types of aggressive B-cell lymphomas.

Primary Follicular Dendritic Cell Sarcoma of the Thyroid Gland Coexisting With Hashimoto’s Thyroiditis

Follicular dendritic cell (FDC) sarcoma, especially of extranodal origin, is an extremely rare malignancy of FDC origin, with only 1 case previously documented in the thyroid. The authors report the case of a 58-year-old female who presented with a painless mass in her neck. The neoplastic cells expressed monocyte/macrophage-specific marker CD68 (KP-1) and lysozymes and the dendritic cell-associated antigens CD35 and Fascin but was negative for CD1a, CD21, and CD23, most consistent with a diagnosis of FDC sarcoma. BIOMED-2 multiplex polymerase chain reaction analysis showed B-cell clonality in both tumor and its adjacent coexisting Hashimoto's thyroiditis. To the authors' knowledge, this is the first report of a rare entity of FDC sarcoma primarily involving the thyroid gland coexisting with Hashimoto's thyroiditis.

No Benefit from Rituximab Containing Regimens in Patients with Primary Extranodal Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous category of lymphoid tumors that comprises different clinical forms not fully recognized in the WHO classification. In this regard, extranodal (EN) DLBCLs have particular clinicobiological features and outcome, sometimes related to the specific site where the lymphoma arises. Nowadays, rituximab plus chemotherapy (CT) is the gold-standard in the treatment of DLBCL. However, the superiority of rituximab-CT (R-CT) over CT alone has not been addressed for all the clinical subsets of the disease and, in fact, the clinical role of the new therapies might be different for primary nodal or EN DLBCLs. The aim of this study was to assess the impact of rituximab in patients suffering from nodal or EN DLBCL. Two-hundred and thirty non-immunocompromised patients (112M/118F; median age, 61 years) diagnosed with CD20+DLBCL in a single institution between 1997 and 2006 (five years before and after establishing R-CT as the standard treatment in DLBCL) and treated with adriamycin-containing regimens were the subject of the present study. The series included 148 primary nodal and 82 EN DLBCL. Patients with primary CNS lymphoma were excluded and lymphomas arising at Waldeyer ring were considered as nodal DLBCL. The main EN sites were GI (n=26), bone (n=13), soft tissue (n=13), lung/pleura (n=9), liver (n=9), and other (n=12). Main clinico-biological and evolutive variables were analyzed. One hundred nineteen patients received only CT and 111 R-CT. Eighty-seven cases with available information were assigned to germinal center B-cell-like (GCB) (41%) or non-GCB (59%) groups according to the Hans method (Blood 2004; 103:275–82) based on CD10, BCL6 and MUM1 expression. Main initial features, including the primary nodal or EN origin, international prognostic index (IPI), and GCB/non-GCB categories were similar for CT and R-CT groups. No correlation was observed between the GCB/non-GCB groups and the primary site of the tumor, although nodal lymphomas more frequently expressed MUM1 than EN (69% vs. 31%, respectively; p=0.01). CR rate and 5-year overall survival (OS) according to the treatment arm (CT vs. R-CT) is detailed for the whole series and for the nodal and EN groups in the table and OS curves depicted in the figure. In the whole series, variables predicting poor OS in the multivariate analysis were high-risk IPI (RR 2.5; p<0.001), primary nodal involvement (RR 1.6; p=0.04) and no R-CT treatment (RR 1.9; p=0.002). In the nodal group, IPI and no R-CT maintained the prognostic value, whereas in the primary EN only IPI predicted OS. Moreover, no difference in OS was observed according to the nodal or EN origin in those patients receiving R-CT. Biological subtypes GCB vs. non-GCB did not add predictive information neither in the whole series nor in the nodal or EN groups. In conclusion, patients with primary EN DLBCL seem to have little benefit from the use of R-CT. Nevertheless, this intriguing observation should be confirmed in further prospective studies.Complete response CR (%)5-years OS (%)CTR-CTCTR-CTAll cases (n=230)5979*4670*Primary nodal (n=148)5478*3471*Primary extranodal (n=82)68787069*p<0.002 R-CT vs. CT [Display omitted]