Lugano Stage Research Articles

Primary Gastrointestinal T/NK Cell Lymphoma.

Simple SummaryPrimary gastrointestinal T/NK cell lymphoma (GI-TNKL) is a heterogeneous group including various subtypes, anatomic locations, and clinicopathologic features. GI-TNKL is difficult to diagnose due to its rarity, various subtypes, and histopathological features. We performed a retrospective analysis of 38 cases of GI-TNKL in South Korea. GI-TNKL consisted of unique subtypes showing specific characteristics of macroscopy, histology, immunophenotype, and prevalent anatomic subsites. ENKTL and MEITL were relatively common. GI-TNKL showed aggressive behavior with short PFS and OS. This clinical and pathological descriptive analysis will be helpful for accurate understanding, diagnosis, and treatment.Primary gastrointestinal T/NK cell lymphoma (GI-TNKL) is an uncommon and heterogeneous group of lymphoid malignancies. We aimed to investigate their subtype distribution, clinicopathologic characteristics, and clinical outcomes. A total of 38 GI-TNKL cases and their clinical and pathological characteristics were analyzed. GI-TNKL occurred in adults with a median patient age in the sixth decade of life and showed a slight male predominance. The most common histologic type was extranodal NK/T-cell lymphoma, nasal type (ENKTL; 34.2%), followed by monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL; 31.6%), intestinal T-cell lymphoma, NOS (ITCL, NOS, 18.4%), anaplastic large cell lymphoma, ALK-negative (ALCL, ALK-; 13.2%). The small intestine was the primary affected region. More than 90% of patients complained of various GI symptoms and cases with advanced Lugano stage, high IPI score, or bowel perforation that required emergent operation were not uncommon. GI-TNKL also showed aggressive behavior with short progression-free survival and overall survival. This thorough clinical and pathological descriptive analysis will be helpful for accurate understanding, diagnosis, and treatment.

Managing Life-Threatening Malignant Superior Mediastinal Syndrome in Pregnancy: When Benefits of Radiation and Chemotherapy Outweigh the Risks—A Case Report and Review of Literature

AbstractThere is scarce literature on managing superior mediastinal syndrome during pregnancy. We report a case of 26-year-old primigravida who presented with life-threatening superior mediastinal syndrome at 32 weeks of gestation. The diagnosis was significantly delayed and, as a result, she reached the emergency with stridor and impending respiratory failure. She was diagnosed with primary mediastinal B cell lymphoma Lugano Stage II with a bulky mediastinal mass. She was treated with chemoimmunotherapy and underwent a preterm vaginal delivery after a week. She delivered a 1.6 kg healthy child with no malformations. Later, she completed three cycles of rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone and five cycles of dose-adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, rituximab, followed by radiotherapy. She continues to be in remission at 18 months of follow-up. Delaying diagnostic imaging that involves ionizing radiation exposure and chemotherapy to avoid teratogenic and obstetric complications during pregnancy can adversely affect the prognosis in certain patients with high-grade malignancies. On the contrary, prompt multidisciplinary management can lead to a gratifying outcome.

Clinicopathological features and MYD88 L265P mutation status of intravascular large B cell lymphoma

Objective: To study the clinicopathologic features and MYD88 L265P mutation status of intravascular large B cell lymphoma (IVLBCL). Methods: Fourteen cases of IVLBCLs were diagnosed from March 2014 to December 2019 at the First Affiliated Hospital of Zhengzhou University. The clinicopathologic features and prognosis were analyzed. Epstein-Barr virus encoded RNAs and MYD88 L265P mutation status were detected using in situ hybridization and Sanger sequencing, respectively. The follow-up data were obtained by telephone interview. Results: There were 6 males and 8 females with a median age of 62 years (range: 48-73 years). The involved anatomic locations were demonstrated by positron emission tomography-computed tomography, including adrenal gland (7/14), bone (6/14), central nerve system (4/14), skin (3/14), female reproductive system (3/14), local lymph nodes (3/14), prostate (2/14), liver and spleen (2/14), sphenoid sinus (1/14), penis (1/14), bladder (1/14), and right lung (1/14). Fever was the most common symptom (7/14), followed by neurologic symptoms and lower abdominal pain (2/14 each). The reminder symptoms included rash with edema, legs weakness and numbness, or postmenopausal bleeding (1/14 each). Eleven cases were at Lugano stage Ⅳ. Four cases were associated with the hemophagocytic syndrome, while 6 cases with bone marrow involved. Microscopically, the tumor cells were generally concentrated within the small-to-medium vascular lumens or sinusoids; they had centroblast-like appearance and showed large round or oval nuclei with slightly irregularities, coarse chromatin and 1-3 distinct nucleoli. One exception was the one case with an embryoid nuclei, reminiscent of anaplastic large cell lymphoma. The mitosis was not uncommon. Extravascular neoplastic cells were seen in two cases. The neutrophils could be appreciable in most of the cases (10/14). Immunophenotyping showed that CD20 and CD79α were diffusely and strongly positive in 14 cases; 12 cases were classified as the non-GCB subtype; 6 out of the 11 cases were double expressor lymphoma; 7 out of the 12 cases were CD5-positive. Twelve cases were EBER negative. The MYD88 L265P mutation was detected in 1 case (1/10). The duration of the follow-up ranged from 0.5 to 24.0 months, and 11 patients survived and 3 died. Conclusions: IVLBCL is rare. The most common type of IVLBCL in China is Asian type with scant tumor cells. Combination of clinical and immunohistochemical features can avoid most, if not all, misdiagnoses and missed diagnoses. Some IVLBCL cases may harbor the MYD88 L265P mutation, but the prevalence of MYD88 L265P mutation in the population still warrants additional studies.

Clinical characteristics and survival analysis of primary intestinal extranodal NK/T-cell lymphoma, nasal type

目的回顾性研究原发肠道结外鼻型NK/T细胞淋巴瘤（ENKTL）患者的临床特征、生存及影响预后的因素。方法收集2009年1月至2019年12月就诊于空军军医大学第一附属医院诊断为肠道淋巴瘤的病例，从中筛选原发肠道ENKTL并收集患者资料进行回顾性分析。结果在210例肠道淋巴瘤患者中，原发肠道ENKTL患者34例（16.2％），其中男26例，女8例，中位年龄45（20～69）岁，年龄≤60岁者占85.3％。主要症状：腹痛（76.5％）、腹泻（20.6％）、便血（29.4％）、腹部包块（2.9％），85.3％伴B症状，73.5％血清LDH升高。病变部位：大肠（52.9％）、小肠（29.4％）、大肠及小肠均受累（17.7％）。内镜分型：隆起型（8.8％）、溃疡型（32.4％）、弥漫型（2.9％）和混合型（55.9％）。Lugano分期Ⅰ/Ⅱ期24例（70.6％），Ⅳ期10例（29.4％）。组织病理免疫组化EBER阳性者占94.1％。中位生存时间为60 d。ECOG评分、血清LDH、IPI评分及是否有并发症影响患者的OS率（P值分别为0.037、0.009、0.002和0.000）。结论原发肠道ENKTL多见于青中年男性，以腹痛最多见，常合并B症状，血清LDH多异常升高，病变多位于大肠，病灶主要呈混合型或溃疡型。IPI评分低危、无并发症者OS率较高。

R-CHOP immunochemotherapy plus surgery is associated with a superior prognosis in Chinese primary intestinal diffuse large B-cell lymphoma.

The aim of the study was to compare the therapeutic strategies and prognostic factors of patients with primary intestinal diffuse large B-cell lymphoma (PI-DLBCL). A total of 50 PI-DLBCL patients who accepted standard first-line treatment at National Cancer Center in China were included in this retrospective study. Survival analysis was performed to evaluate the prognostic risk factors. The 3-year overall survival (OS) and 3-year progression-free survival (PFS) for the entire group were 76.0% and 65.9%, respectively. Univariate analysis showed that B symptom, advanced Lugano stage, elevated LDH status, poor ECOG PS and immunochemotherapy alone were significantly correlated with a poor PFS. Elevated LDH status, poor ECOG PS, advanced Lugano stage, high IPI score and immunochemotherapy alone were significantly correlated with a poor OS. Multivariate analysis revealed that ECOG PS (P=0.035; HR=0.233; 95% CI, 0.060-0.905), LDH level (P=0.010; HR=0.223; 95% CI, 0.072-0.693) and surgery (P=0.002; HR=5.584; 95% CI, 1.883-16.563) were independent prognostic factors for OS. LDH level (P=0.035; HR=0.210; 95% CI, 0.049-0.894) and surgery (P=0.003; HR=6.410; 95% CI, 1.903-21.593) were independent risk factors for PFS in PI-DLBCL. R-CHOP immunochemotherapy combined surgery treatment was also associated with a lower rate of refractory/relapsed (R/R) disease (P=0.004). Furthermore, stratified analysis revealed that partial resection or radical resection combined with immunochemotherapy had no significantly difference which affect OS (P=0.338) and PFS (P=0.207). R-CHOP immunochemotherapy plus surgery was associated with a superior prognosis compared with R-CHOP alone in Chinese PI-DLBCL population.

PD-L1 and miR-34a are Prognostic Factors for Primary Gastric Diffuse Large B-Cell Lymphoma Patients Treated with R-CHOP.

IntroductionPrimary gastric diffuse large B-cell lymphoma (GDLBCL) is a heterogeneous disease in clinicopathological features and prognosis. Programmed death ligand-1 (PD-L1) and microRNA-34a (miR-34a) play crucial roles in GDLBCL progress. The purpose of this research is to explore the clinical significance of PD-L1 and miR-34a expression in GDLBCL.Patients and MethodsThe expressions of PD-L1 and miR-34a were examined by IHC and qRT-PCR in 109 patients who were diagnosed with GDLBCL and were treated with rituximab plus cyclophosphamide, doxorubicin, prednisone vincristine and prednisone chemotherapy (R-CHOP) from January 2010 to December 2018.ResultsPD-L1 level was significantly higher in tumor tissues than adjacent non-tumor tissues (60.5%, P<0.001), while the miR-34a level was just reversed (50.5%, P<0.001), which was negatively correlated (r=−0.524, P<0.001). Notably, PD-L1-positive and miR-34a-negative expressions were significantly correlated with the advanced Lugano stage of IIE-IV stage (P<0.001 and P<0.01), elevated serumal LDH levels (P<0.001 and P<0.05), B symptoms present (P<0.001 and P<0.001), non-GCB subtype (P<0.001 and P<0.001) and negative Bcl-2 expression (P<0.05 and P<0.001). PD-L1 high and miR-34a low expression groups had more patients with IPI scores of 2 or greater (P<0.001 and P<0.05) and poor R-IPI (P<0.01 and P<0.01). The complete response rate was upregulated in patients with negative PD-L1 and positive miR-34a expression after R-CHOP treatment.DiscussionPD-L1 expression and miR-34a expression were significantly associated with clinicopathological characteristics and survival prognosis; they may serve as novel prognostic markers in GDLBCL patients who were treated with R-CHOP. Immunotherapies targeting PD-L1 and miR-34a pathway may have therapeutic potential in GDLBCL.

Diffusion-weighted MRI for initial staging in Hodgkin`s lymphoma: comparison with FDG PET

PurposeTo evaluate the use of diffusion-weighted MRI (DWI) for initial staging of Hodgkin`s lymphoma and compare it to FDG PET. MethodsForty-one patients with Hodgkin`s lymphoma (14 f, 27 m, median age 39 y) were included in this retrospective study. All patients underwent FDG PET/MR for initial staging, including DWI.The Lugano classification was used to describe disease extent. A combination of follow-up imaging and histopathology served as the reference standard.Method agreement was assessed using weighted kappa (κ). The accuracy of the imaging methods was evaluated using ROC curve analysis. ResultsRegarding the Lugano stage, DWI and FDG PET had identical results in 34/41 cases (κ = 0.77). Sensitivity and specificity for nodal involvement was 89.9% and 93.8% for DWI, and 93.8% and 86.9% for FDG PET, respectively. In regard to extranodal involvement, sensitivity and specificity were 88.5% and 99.3% for DWI and 92.3% and 92.7% for FDG PET. The accuracy of both methods for nodal (p = 0.06) and extranodal involvement (p = 0.66) did not differ significantly. ConclusionDespite high sensitivity and specificity, DWI in free breathing cannot be currently recommended as an alternative to FDG PET in initial staging of Hodgkin`s lymphoma due to substantial differences in regard to therapy-determining Lugano Stage.

A comparison of clinical staging using the Lugano versus Ann Arbor classifications in Japanese patients with Hodgkin lymphoma.

The Lugano classification is a novel staging system for lymphomas established in 2014. In this staging system, 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) was formally incorporated into standard staging for FDG-avid lymphomas, including Hodgkin lymphoma (HL). We retrospectively analyzed patients with HL who were newly diagnosed and treated at our institution to evaluate the utility of the Lugano classification compared to the Ann Arbor classification in Japanese patients with this type of lymphoma. Patients newly diagnosed with HL between 2005 and 2011 were identified through our departmental database. Data from neck-chest-abdomen-pelvis CT scans, BM examinations, and FDG-PET/CT that were routinely performed for staging at our clinical practice were retrieved and analyzed. Fifty-four patients with a median age of 35.5 years (range: 15-78 years) were investigated in this retrospective study. The Lugano stage matched the Ann Arbor stage in 46 patients (85%). Six patients (11%) were upstaged while two (4%) were downstaged per the Lugano classification. Four patients (7%) were converted from early stage to advanced stage, but none was converted in the reverse. Among 11 patients (20%) with PET-positive bone/bone marrow lesions, only one (2%) exhibited biopsy-proven bone marrow involvement of HL cells. Our data revealed a high concordance rate between the Lugano and Ann Arbor staging system in Japanese patients with HL. Because of its low diagnostic value, routine bone marrow examination might be unnecessary for staging when FDG-PET/CT is used as a substitute.

Hepatic infiltration helps predict outcome in dogs with multicentric large B cell lymphoma

Summary Background The five-level WHO staging system is currently the standard for canine lymphomas. In humans, staging for Non-Hodgkin lymphomas has recently evolved to the Lugano classification. In this four-level classification, the splenic infiltration does not induce stage migration from stage III, while hepatic involvement is considered as a more advanced stage together with bone marrow or non-lymphoid organs infiltration. Objective The objective of this pilot study is to evaluate the accuracy of the Lugano staging system, compared to the WHO, in predicting first remission duration (FRD) in dogs. Material and methods Thirty dogs with multicentric large B cell lymphoma, staged according to both systems, and treated with a standard chemotherapy protocol were retrospectively included. Kaplan-Meier curves were established for all stages and compared using a Log Rank test. Results The median FRD was 157 days. Factors significantly associated with shorter FRD in the univariate analysis were substage b (P = 0.024), WHO stage V (P = 0.008) and Lugano stage IV (P = 0.002). Two multivariate Cox models were then compared: the model including substage together with both WHO and Lugano staging was statistically superior to predict FRD as compared to the model including only substage and WHO staging (P = 0.014). Conclusion Taking hepatic involvement into account allows better risk stratification for canine LBCL.

136P - Helicobacter pylori-positive gastric diffuse large B-cell lymphoma: A subset with distinct prognostic features

BackgroundRecent studies indicated that Helicobacter pylori (H. pylori) exerts an oncogenic effect on the development of gastric diffuse large B-cell lymphoma (DLBCL). However, the effect of H. pylori status on prognosis of gastric DLBCL remains unconfirmed. MethodsIn the present study, H. pylori status was assessed by histologic examinations, supplemented by results from urease breath test and/or serological analyses where available. Staging tumours included a detailed medical history, physical examination which included peripheral lymph nodes and Waldeyer’s ring, complete hematological biochemical examinations containing serum lactate dehydrogenase (LDH), computed tomography (CT), gastric endoscopy, endoscopic ultrasonography, positron emission tomography (PET)/CT, and bone marrow aspiration and biopsy. Survival curves were estimated by Kaplan-Meier univariate analyses. The prognostic value of H. pylori was verified by both univariate and multivariate analyses. ResultsOne hundred and twenty-nine patients diagnosed with primary de novo gastric DLBCL in West China Hospital of Sichuan University were included from 1st January 2009 to 31st May 2016. Over a median follow-up of 45.0 months (range 2-107), mean event-free survival (EFS) was 83.1 months (95% CI 72.7-93.5) and mean overall survival (OS) was 89.9 months (95% CI 80.9-98.9) in patients infected with H. pylori, compared with 62.0 months (95% CI 50.7–73.3) and 72.2 months (95% CI 61.6–82.9), respectively, in H. pylori-negative subgroup (P = 0.010 and P = 0.020 for differences in EFS and OS between groups, respectively). Patients with H. pylori infection had significantly better 5-year EFS and OS than H. pylori-negative subgroup (5-year EFS, 71% vs 47%, P = 0.010; 5-year OS, 79% vs 58%, P = 0.020). Older age, advanced Lugano stage, higher IPI score, and negative H. pylori status were independent negative prognostic indicators of survival outcomes. ConclusionsH. pylori status in de novo gastric DLBCL can be a promising predictor of disease outcomes, and patients with negative H. pylori status should be followed up carefully since they tend to have a poor outlook. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Prognostic impact of PD-L1 expression in primary gastric and intestinal diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and the most common gastrointestinal lymphoma. The prognostic/predictive indicators among patients with gastric and intestinal DLBCL (giDLBCL) are controversial beyond their anatomical sites. We compared giDLBCL cases and investigated the clinical utility of newly emerging indicators with an emphasis on programmed cell death ligand 1 (PD-L1) expression. This retrospective study included 174 patients with primary gastric (n = 129) or intestinal (n = 45) DLBCL treated with rituximab-containing chemotherapy between 1995 and 2018. Compared with gastric DLBCL (gDLBCL) cases, patients with intestinal DLBCL (iDLBCL) had a significantly higher rate of advanced Lugano stage (71% vs 37%, P < 0.001), perforation (13% vs. 0.8%, P = 0.001), PD-L1 expression on microenvironment immune cells (miPD-L1, 70% vs 46%, P = 0.008), CD10 positivity (47% vs 28%, P = 0.027), and CD5 positivity (9% vs 1.6%, P = 0.040). The iDLBCL patients showed significantly worse progression-free survival (PFS) and overall survival (OS) than gDLBCL cases (P = 0.0338 and P = 0.0077, respectively). PD-L1 expression on tumor cells was detected in only 3 (2%) of 174 cases with early relapse and/or an aggressive clinical course; whereas, miPD-L1-positive cases had significantly better OS than the miPD-L1-negative gDLBCL and iDLBCL cases (P = 0.0281 and P = 0.0061, respectively). Multivariate analysis revealed that miPD-L1 negativity (P = 0.030) was an independent adverse prognostic factor for OS in giDLBCL. The anatomical site of disease did not influence outcome in giDLBCL cases treated with rituximab-containing chemotherapy; while, miPD-L1 expression had a favorable impact on the outcome.

A Multicenter Retrospective Analysis of Clinicopathologic Features of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma

Introduction: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a provisional entity in the 2017 WHO classifications of the lymphoid neoplasms, as it was found that features of MEITL differed from those of enteropathy-associated T-cell lymphoma. It is now considered that MEITL is more prevalent in Asia, and almost all cases of intestinal T-cell lymphoma in Asians might be MEITL. To further elucidate the clinicopathologic features of this new disease entity, we carried out a multicenter, retrospective analysis from 9 tertiary institutes in Korea.Patients and methods: A total of 38 patients who were diagnosed with MEITL between 2002 and 2017 from 9 institutes were included in the analysis. Medical records including age, sex, stage, presenting symptoms, laboratory findings, primary sites, and treatment outcomes were collected. The histopathologic diagnoses were centrally-reviewed by experienced lymphoma histopathologists. The primary end-point of the analysis was overall survival (OS).Results: The median age of the patients was 59 (range, 20 - 84) and 27 patients (71.1%) were male. None of the patients had prior history of Celiac disease. Thirty one patients (81.5%) were stage I-II by the Ann-Arbor classifications, and 28 patients (73.7%) were stage I-II1&2 by the Lugano classifications. The most frequent site of involvement was jejunum (N = 20) followed by ileum (N = 17), and 11 patients had multiple site involvement. In line with the previous reports, most cases expressed CD8 (77.1%) and CD56 (92.1%), and did not expressed CD30 (5.3%), and EBER (6.9%). T-cell intracellular antigen was positive in 14 out of 17 cases (82.4%).The median progression-free survival was 6.9 months (95% CI 4.2 - 9.6), and the median OS was 14.8 months (3.0 - 26.6). Thirty one patients (81.6%) received surgery, and 34 patients (89.5%) received chemotherapy. CHOP (N = 28) was the most frequently used regimen followed by CHOEP (N = 3), and ICE, IMVP-16, and EPOCH (N = 1 each). Complete response (CR) rate was 47.1%, and 14 patients had undergone autologous stem cell transplantation (ASCT). Relapse or progression was documented in 22 cases, and the most frequent site was the primary site (N = 20). Of note, relapse at central nervous system was found in 4 cases. Older age (≥ 55 years), advanced Lugano stage (IIE~IV), not achieving CR, and not receiving ASCT were associated with adverse OS.Conclusion: Although most patients had limited stage, the clinical outcomes of MEITL patients were dismal. While the optimal management of MEITL remains undetermined, achieving CR and consolidative ASCT seem to be essential. In addition, considering the frequent local failure, as well as the CNS relapse, novel therapeutic approaches are required to improve survival. [Display omitted] DisclosuresKim:Mundipharma: Research Funding; Merck: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Roche: Honoraria, Research Funding; Kyowa-Kirin: Research Funding; Eisai: Honoraria, Research Funding; J&J: Research Funding; Celltrion: Honoraria, Research Funding; Novartis: Research Funding.

Clinical features and prognosis of primary intestinal B-cell lymphoma: analyses of 50 cases

Objective To investigate the clinical characteristics and prognostic factors for patients with primary intestinal B-cell lymphoma. Methods The clinical data of 50 patients with primary intestinal B-cell lymphoma in Fujian Medical University Union Hospital from January 2004 to December 2013 were retrospectively analyzed. An analysis was also conducted in their clinical characteristics and related prognostic factors. Results A total of 50 patients included 35 males and 15 females with the median age of 58 years old (16-79 years old). The clinical symptoms were abdominal pain or abdominal distension [70% (35/50)]. The common origins were small intestine and ileocecus, and the most common pathological type was diffuse large B-cell lymphoma (DLBCL) [54% (27/50)]. The median survival time of 43 cases was 49.4 months. The 1-year, 3-year and 5-year overall survival (OS) rates were 79.1%, 72.1%, 58.1%, respectively. Univariate analysis indicated that hemoglobin levels, albumin levels, lactic dehydrogenase (LDH), the maximum diameter of mass, international prognostic index (IPI) score, Lugano stage, and Eastern Cooperative Oncology Group (ECOG) score were the affecting factors of OS. Multivariate analysis showed that IPI score ≥ 2 was an independent risk factor for the prognosis of intestinal B-cell lymphoma (OR= 6.766, 95% CI 1.853-24.702, P= 0.004). The efficacy analysis showed that 5-year cumulative OS rate of R-CHOP like treatment group was better than that of CHOP like treatment group (91.7% vs. 44.7%, P= 0.048). Conclusion IPI score can be used as an important indicator for clinical treatment and prognosis evaluation of primary intestinal B-cell lymphoma. Some patients with primary intestinal B-cell lymphoma can benefit from rituximab. Key words: Lymphoma, B-cell; Intestinal neoplasms; Prognosis

TREATMENT STRATEGIES AND PROGNOSTIC FACTORS OF PRIMARY GASTRIC DIFFUSE LARGE B CELL LYMPHOMA: A RETROSPECTIVE STUDY OF 303 CASES FROM CHINA LYMPHOMA PATIENT REGISTRY

Introduction: Primary gastric diffuse large B cell lymphoma (PGDLBCL) is the common primary extranodal DLBCL, with higher incidence in Asian than in Western countries. However, the optimal treatment for PGDLBCL remains controversial. We thus conducted a retrospective analysis of 303 cases to evaluate present treatment strategies and prognostic factors of PGDLBCL. Methods: From three centers of the China Lymphoma Patient Registry (CLAP), 303 PGDLBCL cases from January 1994 to December 2015 were retrospectively analyzed. Patients were classified into four groups: chemotherapy (C, 192 cases), surgery (S, 21 cases), chemotherapy + surgery (C + S, 78 cases), and watch and wait (12 cases). Results: The 3-year progression-free survival (PFS) and 3-year overall survival (OS) of the entire cohort were 75.3% and 80.3% (median follow-up time: 42 months). PFS (p = 0.122) and OS (p = 0.451) were similar among the four treatment groups. In the chemotherapy-treated cohort, group C + S had higher PFS than group C (83.7% vs. 71.8%, p = 0.013). Its OS was also relative higher, even without statistical significance (86.6% vs. 78.5%, p = 0.097). The inclusion of radiotherapy during initial treatment (23 cases) in this cohort did not improve PFS (57.9% vs. 76.2%, p = 0.017) or OS (73.7% vs. 81.1%, p = 0.220). Rituximab did not show significant clinical benefit in our study (PFS: 78.1% vs. 71.1%, p = 0.205; OS: 83.9% vs. 75.7%, p = 0.052). Treatment-related complications included gastrointestinal bleeding (22 cases), perforation (4 cases), and obstruction (4 cases), which correlated with poorer outcomes (PFS: 50.7% vs. 78.1%, p = 0.005; OS: 59.2% vs. 83.3%, p < 0.001). Glucocorticoid in chemotherapy increased incidence of complications (p = 0.035). The univariate analysis revealed prognostic factors as age, Lugano stage, ECOG, B symptom, International Prognosis Index, LDH, HGB, ESR, β2-MG, lesion in cardia, prior gastrointestinal bleeding, and complications. The multivariate analysis showed that B symptom (Relative rate (RR) = 2.82, p = 0.016), lesion in cardia (RR = 2.86, p = 0.039), LDH (RR = 4.65, p < 0.001) and gastrointestinal bleeding before treatment (RR = 3.08, p = 0.005) were highly predictive for poor PFS, and the latter two factors also predicted poor OS (RR = 4.08, p = 0.004; RR = 3.18, p = 0.001). Conclusions: Our results indicated that chemotherapy + surgery is a considerable choice to improve the survival of PGDLBCL. The inclusion of radiotherapy during initial treatment did not improve survival in our study. Due to elevated risk of complication, glucocorticoid could be removed from chemotherapy. B symptom, lesion location, LDH, and gastrointestinal bleeding before treatment are independent predictors of poor outcomes. This retrospective, multicenter analysis provides the largest sample size study for PGDLBCL, but the future prospective trial is warranted. Keywords: extranodal lymphomas.

Utility of baseline assessment with FDG‐PET‐CT compared with CT Scanning in people with diffuse large B‐cell lymphoma (DLBCL)

Introduction: We sought to establish whether a baseline FDG-PET-CT offers increased sensitivity compared to a baseline CT scan in people with diffuse large B-cell lymphoma (DLBCL) with Lugano stage II disease or above and to assess whether this might affect subsequent clinical decision making. Methods: We retrospectively reviewed all patients with newly diagnosed DLBCL over a 4-year period who had both an FDG-PET-CT and conventional CT scanning prior to any treatment. Discordance between the two studies was noted and the potential impact of this on clinical decision making was assessed, according to current British or international guidelines, specifically relating to the selection of primary treatment and the decision to offer therapy to prevent relapse in the central nervous system. Results: Between 2012 and 2016, there were 101 patients, M:F 59:42, aged 20 to 89 (median 54), who had a confirmed diagnosis of DLBCL (de novo DLBCL NOS 91; primary mediastinal B-cell lymphoma 4; previous low grade lymphoma with histological transformation to DLBCL 6) and had undergone both FDG-PET CT and a CT scan, which were available. In 39 cases (38%), there was discordance between the two imaging modalities. Anatomical sites detected by FDG-PET-CT but not by CT included: bone (13), spleen (5), adrenal gland (3), lymph nodes that were normal by size criteria but strongly tracer-avid (3), liver (2), and mediastinal soft tissue (2). Assessed by CT alone, 14 patients would have met formal criteria for the application of methotrexate via the parenteral or intrathecal route. With the information gleaned from FDG-PET-CT, a further 4 patients would have met criteria for this intervention. In addition, 3 patients who were assessed as having limited stage disease by CT had evidence of advanced-stage disease by FDG-PET CT scanning (splenic uptake, lymph nodes that were normal by size-criteria on CT that were clearly abnormal on FDG-PET-CT). This migration of their stage meant they would have received standard chemotherapy rather than being considered for combined modality therapy. FDG-PET-CT identified areas not related to lymphoma determined either on biopsy or clinical follow-up, thyroid disease (3), and nonspecific intestinal uptake for which no cause was found (2). Conclusions: In many patients, FDG-PET-CT identifies abnormalities not detected on CT scanning, even when the latter is reported by an expert lymphoma radiologist. Only a small number of these discordant findings result in a change in patient management, but these may have significant impact on individual patient outcomes. Therefore, we agree with the Lugano classification recommendation, published by Cheson et al, that FDG-PET CT should be applied at diagnosis in all patients with DLBCL. A biopsy or close clinical follow-up of atypical findings discovered on FDG-PET-CT is important, as findings other than lymphoma may produce a false-positive scan. Keywords: diffuse large B-cell lymphoma (DLBCL); positron emission tomography (PET)

Predictive Factors for Developing Venous Thrombosis during Cisplatin-Based Chemotherapy in Testicular Cancer

Background: Malignancies and cisplatin-based chemotherapy are both known to correlate with a high risk of venous thrombotic events (VTT). In testicular cancer, the information regarding the incidence and reason of VTT in patients undergoing cisplatin-based chemotherapy is still discussed controversially. Moreover, no risk factors for developing a VTT during cisplatin-based chemotherapy have been elucidated so far. Patients and Methods: We retrospectively analyzed 153 patients with testicular cancer undergoing cisplatin-based chemotherapy at our institution for the development of a VTT during or after chemotherapy. Clinical and pathological parameters for identifying possible risk factors for VTT were analyzed. The Khorana risk score was used to calculate the risk of VTT. Student t test was applied for calculating the statistical significance of differences between the treatment groups. Results: Twenty-six out of 153 patients (17%) developed a VTT during chemotherapy. When we analyzed the risk factors for developing a VTT, we found that Lugano stage ≥IIc was significantly (p = 0.0006) correlated with the risk of developing a VTT during chemotherapy. On calculating the VTT risk using the Khorana risk score model, we found that only 2 out of 26 patients (7.7%) were in the high-risk Khorana group (≥3). Conclusion: Patients with testicular cancer with a high tumor volume have a significant risk of developing a VTT with cisplatin-based chemotherapy. The Khorana risk score is not an accurate tool for predicting VTT in testicular cancer.

The Lymphocyte-Monocyte Ratio and the Platelet-Lymphocyte Ratio at Diagnosis as Independent Prognostic Factors in Primary Gastrointestinal Diffuse Large B Cell Lymphoma.

To study the role of the absolute lymphocyte count (ALC), absolute monocyte count (AMC), platelet count (PLT), lymphocyte-monocyte ratio (LMR) and the platelet-lymphocyte ratio (PLR) in the prognosis of primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL). We retrospectively analyzed the prognostic value of the ALC, AMC, PLT, LMR, PLR at diagnosis in 173 PGI-DLBCL patients through histopathological examination from March 2009 to February 2015. In total, 173 patients with histopathological diagnosis of PGI-DLBCL in this study, the median age was 51years (range 12-90years), median follow-up time was 44months (range 7-89months). In univariate analysis, age <60years, B symptoms, Lugano stage I-II, low international prognostic index (IPI) or low age-adjusted international prognostic index (aaIPI), normal lactate dehydrogenase (LDH), normal β2-microglobulin (β2m), Hb≥11g/dL, ALC≥1.5×109/L, AMC≤0.50×109/L, LMR≥2.5, PLR≤170 were related with superior overall survival (OS) and progression-free survival (PFS) (p≤0.05). Multivariate analysis suggested that ALC, LMR, LDH were related with PFS (p≤0.05). Similarly, age and LMR were related with OS (p≤0.05). The parameters (ALC, AMC, LMR, PLR) may be valuable prognostic factors in PGI-DLBCL patients. LMR, PLR at diagnosis are expected to be independent prognostic factors for PGI-DLBCL patients.

A retrospective analysis of clinical pathological characteristics and prognosis of 82 patients of primary intestinal lymphoma

Background: To evaluate the histological type, clinical presentation, treatment and prognosis of primary intestinal lymphoma (PIL). Methods: From 2003 to 2015, in a single institution in China, 82 patients with a diagnosis of PIL were enrolled in our study. According to World Health Organization (WHO) classification and Lugano staging system for gastrointestinal lymphoma, we divided patients into different subtypes and stages. Results: Male to female ratio was 1.8:1 and the median age was 59.5 years. Of the 82 patients, 68 patients (82.9%) suffered from intestinal B-cell lymphoma (IBCL) and 14 patients (17.1%) suffered from intestinal T-cell lymphoma (ITCL). Diffuse large B cell lymphoma (DLBCL) was the predominant histological subtype (59.8%) in all of the PIL cases. Mucosa-associated lymphoid tissue-type lymphoma (MALT) was the second most common subtype (15.9%). From the study we also concluded that PIL mostly occurred in the small intestine (45.1%), followed by colon and rectum (26.8%). The univariate prognosis analysis revealed that Lugano stage I/II, B-cell phenotype and treatment based on surgery plus chemotherapy were independent prognostic factors (P=0.003, 0.000 and 0.000, respectively). According to multivariate analysis, age of onset, Lugano stage, immunophenotype and the method of treatment were significant predictive factors for better survival (P=0.005, 0.005, 0.000 and 0.000, respectively). Conclusions: The patients with younger age of onset, B cell lymphoma, earlier stages, and treatment based on surgery plus chemotherapy have a better prognosis. To ensure the diagnosis of PIL to be made as soon as possible, we should make efforts to select the proper laboratory parameters and imaging findings of PIL.

Efficacy of surgery and rituximab in primary gastric diffuse large B-cell lymphoma

目的探讨手术联合化疗与单纯化疗对原发胃弥漫大B细胞淋巴瘤（PGDLBCL）患者生存的影响，并分析化疗过程中联合应用利妥昔单抗（R）对其预后的影响。方法回顾性分析83例PGDLBCL患者的临床资料，并分析外科手术及利妥昔单抗对患者生存的影响。结果83例患者中男43例，女40例，中位年龄52 (20~76）岁，中位随访时间为36 (4~59）个月。手术联合化疗组（40例）和单纯化疗组（43例）患者的5年总生存（OS）率分别为68.4%、85.9%（P=0.117），疾病无进展生存（PFS）率分别为66.7%、82.6%（P=0.258），差异均无统计学意义。手术联合化疗患者中R-CHOP方案组（23例）和CHOP方案组（17例）患者的5年OS率分别为73.6%、64.2%（P=0.113），PFS率分别为71.2%、62.5%（P= 0.147）；单纯化疗患者中R-CHOP方案组（24例）和CHOP方案组（19例）患者的5年OS率分别为85.7%、83.5%（P=0.152），PFS率分别为83.4%、81.8%（P=0.307）。单纯化疗组和手术联合化疗组Lugano分期早期（Ⅰ~Ⅱ1期）患者的5年OS率分别为86.4%、78.7%，差异无统计学意义（P=0.283）；晚期（Ⅱ2~Ⅳ期）患者分别为74.6%、58.5%，差异有统计学意义（P=0.040）。多因素分析显示IPI评分是影响预后的独立因素（RR=0.370，95% CI 0.089~3.537，P=0.015）。结论单纯化疗或手术联合化疗对PGDLBCL患者长期生存的影响差异无统计学意义，但由于手术可能造成患者生存质量的下降，因此对于无手术指征者更倾向于推荐单纯化疗。本研究中利妥昔单抗的联合应用未能使大部分这类患者的生存显著获益，但这需要进一步多中心、大样本的研究来证实。

Clinicopathological characteristics and prognostic analysis of primary intestinal diffuse large B-cell lymphoma

To analyze the clinicopathological characteristics, treatment protocls and prognostic factors in patients with primary intestinal diffuse large B-cell lymphoma (DLBCL). The clinical data of 54 patients with DLBCL who were treated in Cancer Hospital of Chinese Academy of Medical Sciences in the period from August 2003 to November 2012 were retrospectively analyzed, and the relevant prognostic factors of DLBCL were analyzed. Of the 54 patients, there were 43 males and 11 females (male∶female ratio was 3.91∶1), with a median age of onset of 49 (7-76) years. Most patients (64.8%) were in Lugano stage Ⅰ-Ⅱ. Of all the patients, 50 were followed up for a median of 49 (1-118) months. The 1-, 3- and 5-year overall survival (OS) rates were 82.0%, 69.9% and 60.7%, respectively; the 1-, 3- and 5-year progression-free survival (PFS) rates were 68.0%, 58.0% and 53.4%, respectively. Univariate analysis showed that the factors affecting prognosis of DLBCL patients included Lugano stage, B symptom, International Prognostic Index (IPI) score, lactate dehydrogenase level, β2-microglobulin level, tumor size, and treatment protocols (all P<0.05). The 5-year OS rate was 67.1% in the patients treated with surgery plus chemoradiotherapy, and 40.0% in those treated with surgery or chemotherapy alone (P<0.05). In the patients treated with chemotherapy combined with rituximab, the 5-year OS rate was higher than in those treated with chemotherapy alone (71.2% vs 47.6%, P<0.05). Multivariate analysis indicated that tumor size (RR=7.686, P=0.022) and lactate dehydrogenase level (RR=10.131, P=0.017) were independent prognostic risk factors affecting OS. Primary intestinal DLBCL is a highly heterogeneous malignancy. Surgery combined with chemoradiotherapy and rituximab may help improve the overall prognosis of DLBCL patients.