Extranodal Diffuse Large B-cell Lymphoma Research Articles

IMMUNOCHEMORADIOTHERAPY OR IMMUNOCHEMOTHERAPY ONLY IN PATIENTS WITH EXTRANONAL DIFFUSE LARGE B‐CELL LYMPHOMA OF STOMACH

Introduction: Radiation therapy (RT) is an effective method for treating indolent lymphomas of the stomach (Yahalom, 2006), but the results proving its role in patients with extranodal diffuse large B-cell lymphoma with predominant lesions of the stomach during chemoradiation treatment are few and conflictive (Metijharissi et al., 2017, Mehmood, 2017). The purpose of the study: is to evaluate the effectiveness of immunochemoradiotherapy (ICT + RT) compared with only ICT in patients with extranodal diffuse large B-cell lymphoma of the stomach. Methods: The study included 66 primary patients aged 25-90 years (mean age - 59 years), who received and completed in the period 2006-2017. ICT + RT (26 patients) or ICT only (40 patients). Of these, men - 32; women - 34; Stage I - 6, II - 30; III - 3; IV - 27. The average observation period of the group - 45 months. 63 patients received 4-8 cycles of ICT R-CHOP-21, 3 patients - DA-EPOCH-R. RT was performed after ICT at doses of 30-40 Gy for the entire volume of the stomach and in perigastric lymph nodes. In 10 patients before treatment, 3 weeks after ICT (20 patients) and 4 weeks after RT (15 patients), a full body PET scan with 18F-FDG was performed. The groups were comparable in terms of the main prognostic factors for the IPI criteria. Patients, who received surgical treatment were not included into the study. Five patients from the ICT group with a lack of efficacy of R-CHOP-21 were treated with 2 therapy lines, 1 - the third line of therapy. Results: A complete response after R-CHOP-21 was established in 48 of 66 (73%) patients. After subsequent RT in all 26 patients of the group of ICT + RT, complete remission was achieved in terms from 7 to 93 months. (average - 50 months.). In the group of ICT only, 5 patients died (4 of them in stage IV), including 4 from the underlying disease advance, 1 - from relapse in the central nervous system. The average follow-up period for this group was 42 months, the deceased patients — 10 months. The overall 5-year survival rate of the combined treatment group is 100%, ICT is 72%. In patients with PET positive results after PCT after irradiation, the metabolic activity of the tumour was not detected. Conclusion: ICT+RT is the optimal method of treating patients with extranodal aggressive lymphoma with gastric lesions. Keywords: diffuse large B-cell lymphoma (DLBCL); extranodal lymphomas.

Primary central nervous system lymphoma: A curable disease.

Primary central nervous system lymphoma is a rare subtype of non-Hodgkin lymphoma that is confined to the brain, leptomeninges, or the eye and is associated with a relatively poor prognosis compared to other extranodal diffuse large B-cell lymphomas. However, methotrexate-based induction chemotherapy followed by consolidative chemotherapy or high-dose therapy and autologous stem cell transplantation is associated with improved survival and reduced neurotoxicity. Aberrant activation of B-cell receptor signaling and activation of nuclear factor kappa beta is a frequent genetic alteration and offers opportunities for targeted therapies in this lymphoma subtype.

Clinical features and outcomes of diffuse large B-cell lymphoma based on nodal or extranodal primary sites of origin: Analysis of 1,085 WHO classified cases in a single institution in China.

ObjectiveTo explore the clinicobiologic features and outcomes of diffuse large B-cell lymphoma (DLBCL) patients in China according to the primary site.MethodsA total of 1,085 patients diagnosed with DLBCL in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during a 6-year period were enrolled. Their clinical characteristics and outcomes were analyzed according to the primary site.ResultsIn the 1,085 patients, 679 (62.6%) cases were nodal DLBCL (N-DLBCL) and 406 cases (37.4%) were extranodal DLBCL (EN-DLBCL). The most common sites of N-DLBCL were lymphonodus (64.8%), Waldeyer’s ring (19.7%), mediastinum (12.8%) and spleen (2.7%), while in EN-DLBCL, stomach (22.4%), intestine (16.0%), nose and sinuses (8.9%), testis (8.4%), skin (7.9%), thyroid (6.9%), central nervous system (CNS) (6.4%), breast (5.7%), bone (3.4%), and salivary gland (2.7%) were most common. N-DLBCL patients tend to present B symptoms, bulky disease, and elevated LDH more often, while age >60 years, extranodal sites >1, Ann Arbor stage I or II, bone marrow involvement, and Ki-67 index >90% were usually seen in EN-DLBCL. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate for all patients were 62.5% and 54.2%. The 5-year OS rate for patients with N-DLBCL and EN-DLBCL were 65.5% and 56.9% (P=0.008), and the 5-year PFS were 57.0% and 49.0% (P=0.020). Waldeyer’s ring originated DLBCL possessed the highest 5-year OS rate (83.6%) and PFS rate (76.9%) in N-DLBCL. The top five EN-DLBCL subtypes with favorable prognosis were stomach, breast, nose and sinuses, lung, salivary gland, with 5-year OS rate: 70.3%, 69.6%, 69.4%, 66.7% and 63.6%, respectively. While CNS, testis, oral cavity and kidney originated EN-DLBCL faced miserable prognosis, with 5-year OS rate of 26.9%, 38.2%, and 42.9%.ConclusionsIn our study, primary sites were associated with clinical characteristics and outcomes. Compared with EN-DLBCL, N-DLBCL had better prognosis.

Immune evasion-related extranodal large B-cell lymphoma: A report of six patients with neoplastic PD-L1-positive extranodal diffuse large B-cell lymphoma.

We identified six patients with Epstein-Barr virus (EBV)-negative extranodal diffuse large B-cell lymphoma (DLBCL) and immunohistochemical expression of PD-L1 on their tumor cells by examining 283 DLBCL cases with the PD-L1 SP142 clone between 2015 and 2017. They consisted of two men and four women with a median age of 71 years, and were examined in an autopsy (n = 1) and biopsies from the adrenal gland (n = 2), skin (n = 1), pelvic cavity (n = 1), and kidney (n = 1). All showed a monomorphic population of large transformed B-cells leading to diagnoses of DLBCL with two intravascular large B-cell lymphoma (IVLBCL) and one de novo CD5+ type and were featured by an invariable immunephenotype: CD3-, CD20+, BCL-2+, and MUM1+. In addition, CD5 and CD10 were each detected in one case. All cases expressed PD-L1 on >10% to >90% of tumor cells, which was confirmed with two other PD-L1 antibodies (E1J2J and 28-8). Three untreated patients had a rapid, lethal clinical course within 7 months after diagnosis; while, the remaining three achieved complete remission after treatment and were alive at the last follow-up. We suggest immune evasion-related extranodal large B-cell lymphoma should be recognized beyond the currently identified entities of IVLBCL and de novo CD5+ DLBCL.

Expressions of p53, p63 and PIM1 proteins in nodal or extranodal diffuse large B-cell lymphoma and their prognostic significance

Expressions of p53, p63 and PIM1 proteins in nodal or extranodal diffuse large B-cell lymphoma and their prognostic significance

Primary Extranodal Diffuse Large B-Cell Lymphomas Are Enriched for Mutations in MYD88 and CD79B.

Introduction: Diffuse large B-cell lymphomas (DLBCLs) with mutations in MYD88 and CD79B are a distinct molecular subentity according to recent analysis (“MCD-type” according to R. Schmitz et al., N Engl J Med 2018; and partially “cluster 5” according to B. Chapuy et al., Nature Medicine 2018). Both mutations were found particularly in specific anatomical localizations.Methods: To evaluate the incidence of MYD88 and CD79B mutations in primary extranodal DLBCL, we analyzed 111 tumor specimens of 99 patients. We performed targeted resequencing analysis to detect MYD88, CD79B, CARD11 and BTK mutations.Results:MYD88 mutations were frequently found in primary CNS lymphoma (67%), lymphoma of Waldeyer´s ring and paranasal sinuses (ENT) (44%), breast (75%), testicular (60%) and cutaneous (50%); the majority of mutations (89%) were located on L265P. CD79B mutations were frequent in CNS lymphoma (57%), lymphoma of ENT (52%) and breast lymphoma (50%). Both mutations occur simultaneously in CNS lymphoma (48%) and ENT lymphoma (33%). CARD11 mutations were frequently found in CNS lymphoma (33%) and in ENT lymphoma (26%). BTK mutations were found rarely, with the highest frequency (11%) in ENT lymphoma.Conclusion: Both, mutations in CD79B and MYD88 are frequent in primary extranodal lymphoma particularly in CNS lymphoma, lymphoma of Waldeyer's ring and paranasal sinuses, testicular, cutaneous and breast lymphoma. These findings may contribute to establish targeted therapeutic intervention of B-cell signaling in this subentity. [Display omitted] DisclosuresWeissinger:Bristol-Myers Squibb: Research Funding. Viardot:BMS: Consultancy, Honoraria; Gilead Kite: Consultancy, Honoraria; Amgen: Consultancy; Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.

Ibrutinib Can Induce Complete Remissions and Sustained Responses in Refractory Cutaneous or Leg-Type Diffuse Large B-Cell Lymphoma

Background: Primary cutaneous diffuse large B-cell lymphoma, leg-type (LT-DLBCL) is an extremely aggressive DLBCL subtype typically occurring at lower extremities and with very poor prognosis due to early relapses and refractory (R/R) disease. Previous studies have shown increased BCR dependence in DLBCL being observed in association with the mutation status of BCR associated genes and MYD88.Aim: Primary goal was to assess the clinical course in patients with primary cutaneous DLBCL and to elucidate the potential of alternative treatments with regard to molecular characteristics.Methods: We identified 16 patients with cutaneous DLBCL treated at our center of which 8 patients had typical localization and were histologically confirmed as LT-DLBCL. The other 8 patients showed cutaneous DLBCL at other anatomic sites (DLBCL-OS) and were classified as DLBCL/DLBCL NOS. Three R/R patients received ibrutinib as off-label individual treatment attempt (420 mg daily). We extended the clinical and molecular analysis for the ibrutinib exposed DLBCL by 1 R/R oropharyngeal DLBCL. Specimen from R/R ibrutinib exposed and 3 other patients were analyzed for CD79B, MYD88, CARD11 and BTK mutations by targeted resequencing analysis. PD-1/PD-L1 expression was assessed in 2 cases with relapse after ibrutinib. Treatment was initiated after signed informed consent.Results: The median age at diagnosis was 51 years in DLBCL-OS and 80 years in LT-DLBCL (total range 37-91). Patients received a median of 2 (0-7) treatments and response to last chemotherapy was different for DLBCL-OS (6 complete remissions (CR), 2 R/R) and LT-DLBCL (2CR, 5R/R). One LT-DLBCL patient showed stable disease (SD) without treatment. LT-DLBCL patients showed a significantly shorter median overall survival (OS) (21,5 months vs. not reached, p=0.009). After ibrutinib treatment we observed 1 ongoing CR for 10 months till date for a DLBCL-OS with CD79B p.Y197S and MYD88 L273P mutation and 1 CR for 6 months in a LT-DLBCL being WT for all sequenced genes. However, this patient relapsed with a highly proliferative disease and died shortly after. The 3rd patient with LT-DLBCL had an isolated MYD88 L265P mutation and showed a PR for 1 month. Samples from patients with indolent clinical course showed a MYD88 p.S251N and BTK p.P385S mutation (LT-DLBCL with SD) or were WT for all sequenced genes (2 patients with DLBCL-OS and ongoing CR). The patient with R/R oropharyngeal DLBCL had a MYD88 L265P and CD79B c.587A mutation, 4 prior treatment regimen and fulminant progression during the last 2 treatments. Initial response to ibrutinib was rapid with a drop of LDH levels from 2200 U/L to 620 U/L within 7 days and consecutive decrease to 323 U/L. However, this patient relapsed after 30 days of treatment.Immunomodulatory effects of ibrutinib and potential synergistic treatment with checkpoint inhibitors have previously been suggested. We specifically investigated PD-1/PD-L1 expression in tissues obtained from the two patients progressing after ibrutinib treatment. Remarkably, we observed increased expression for PD-1 (moderate) and PD-L1 (strong) in non-tumor bystander cells. Treatment with nivolumab was initiated in 1 patient with early clinical benefit. However, the patient refused the continuation of this treatment.Conclusion: Patients with LT-DLBCL are older and show a poor clinical course compared to cutaneous DLBCL at other anatomic sites. MYD88 L265P mutations were observed only in chemo-refractory cases with extranodal DLBCL. Ibrutinib can induce complete remissions and sustained responses in chemo-refractory extranodal DLBCL but relapses may be more aggressive and disseminated. Mutational patterns and ibrutinib response were in line with previous hypothetical models for sensitivity to BCR inhibition. Combining ibrutinib and checkpoint inhibitors may be considered in future trials for LT-DLBCL patients. DisclosuresWeissinger:Bristol-Myers Squibb: Research Funding. Viardot:Roche: Consultancy, Honoraria; Amgen: Consultancy; Gilead Kite: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.

Intravascular lymphoma forming massive aortic tumors complicated with sarcoidosis and focal segmental glomerulosclerosis: a case report and literature review

BackgroundIntravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal diffuse large B-cell lymphoma characterized by proliferation of B cells within small vessels. Herein, we report a case of a 77-year-old man who presented with IVLBCL and massive tumor formation on the aortic wall who was previously diagnosed with sarcoidosis and focal segmental glomerulosclerosis (FSGS). To our knowledge, this is the first reported case of an IVLBCL with aortic tumor formation.Case presentationA 77-year-old ambulatory man with sarcoidosis and FSGS had neurological symptoms for nine months. The patient presented to the emergency department with sudden left leg pain, and was diagnosed with acute femoral artery occlusion. Emergency thrombectomy was performed subsequently. Pathological evaluation of the thrombi revealed that its surface was filled with large atypical B cells. Bone marrow biopsy showed infiltration of large atypical B cells within the small vessels. IVLBCL was suspected and further examination was planned, but the patient died due to sudden respiratory and cardiac arrest on hospital day twelve. Autopsy revealed intravascular tumors adherent to the aortic arch, left ventricle, and the abdominal aorta. All enlarged lymph nodes and the ventricular septum of the heart showed hyalinized lesions with granular formation consistent with sarcoidosis. The patient was diagnosed with IVLBCL with aortic tumor formation complicated with sarcoidosis and FSGS.ConclusionsIVLBCL may present with tumor formation on the aortic wall. Although the cause of its affinity to the aortic wall is yet unknown, autopsy findings imply that arteriosclerosis may have contributed to the tumor formation. The literature suggests that T-cell abnormalities could possibly be the common etiology of intravascular lymphoma, sarcoidosis, and FSGS.

Calcium Independent Effect of Orai1 and STIM1 in Non-Hodgkin B Cell Lymphoma Dissemination.

Ca2+ release-activated Ca2+ channels, composed of Orai1 and STIM1 (stromal interaction molecule 1) proteins, are the main Ca2+ entry mechanism in lymphocytes. Their role in cell migration and metastasis is demonstrated in solid cancers but it remains elusive in malignant hemopathies. Diffuse large B cell lymphoma (DLBCL) is characterized by the dissemination of neoplastic B cells throughout the organism which is under the control of chemokines such as Stromal Derived Factor 1 (SDF-1) and its receptor CXCR4. CXCR4 activation triggers a complex intracellular signaling including an increase in intracellular Ca2+ concentration whose role is still unclear. Using pharmacological and genetic approaches, we revealed that STIM1 and Orai1 were responsible for Ca2+ influx induced by SDF-1. Furthermore, we provide in vitro and in vivo evidence that they are necessary for basal or SDF-1-induced DLBCL cell migration which is independent of Ca2+ entry. We identify that they act as effectors coupling RhoA and ROCK dependent signaling pathway to MLC2 phosphorylation and actin polymerization. Finally, we revealed an alteration of Orai1 and STIM1 expression in extra-nodal DLBCL. Thus, we discovered a novel Ca2+-independent but Orai1 and STIM1-dependent signaling pathway involved in basal and CXCR4 dependent cell migration, which could be relevant for DLBCL physiopathology.

Immunohistochemical distinction of ABC and GCB in extranodal DLBCL is not reflected in mutation patterns

Gene expression profiling (GEP) separated diffuse large B-cell lymphoma (DLBCL) in two different entities, i.e. activated B cell-like (ABC) and germinal center B cell-like (GCB) lymphomas with ABC lymphomas demonstrating a less favorable outcome. NF-kB pathway activating mutations in MYD88, CD79A/B and CARD11 are predominantly found in ABC type lymphomas. Targeted therapies affecting NF-kB pathways have shown therapeutic potential in this subtype. Immunohistochemistry algorithms have been developed as a tool for distinguishing these entities in routine clinical diagnostics. To test whether this immunohistochemistry classifier would detect the biological differences between the entities 147 DLBCLs were subtyped into ABC and GCB using the Visco-Young algorithm. Mutation analysis demonstrated mutations in MYD88 or CD79 A/B in 21% (10/47) of non-GCB type but only in 3% (1/31) of GCB lymphomas (p = 0.012) in nodal lymphomas. In primary extra nodal lymphomas, however, 17.5% (4/23) of GCB type and 37.5% (15/40) of non-GCB lymphomas carried mutations in MYD88 and CD79 A/B. While the Visco-Young algorithm was sufficient to detect biological differences (i.e. mutation patterns) in nodal DLBCL it did not distinguish GCB and non-GCB type lymphomas of primary extranodal sites. Here, the morphological sites of the lymphomas seem to be more important for their molecular pattern than their immunohistochemical status.

Effects of Concurrent Expression of Myc and Bcl-2 on the Treatment and Prognosis in Extranodal Diffuse Large B Cell Lymphoma

Aim: We aimed to investigate the effects of immunohistochemical and molecular presence of double-hit lymphomas (DHL) (combined expression of myc and bcl-2) on overall and progression-free survival rates of patients with extranodal diffuse large B-cell lymphoma (DLBCL). Methods: A total of 31 patients (17 female, 14 male; mean age 57 years) with diagnosis of extranodal DLBCL were included into the study. Patients transforming from low grade B cell lymphoma, and patients with HIV positivity were not included. In a retrospective manner, patient characteristics were noted (age at diagnosis, sex, sites of extranodal involvement, stage, high-risk group, histopathological diagnosis, IPI score, LDH level at diagnosis, bone marrow involvement, and treatment modalities). Histopathological specimens underwent immunohistochemical (bcl-6, bcl-2, myc, CD10, Mum-1) and molecular (bcl-2 and myc, by means of PCR) analysis. All patients was treatment with R-CHOP protocol. Results: DHL was observed immunohistochemically in only one patient, while molecular studies found 6 cases. Three-month overall survival rates were 50% and 88% in DHL positive and negative groups, respectively. Six-month overall survival rates were 16% and 76% in DHL positive and negative groups, respectively. Progression-free 3-month survival rates were 51% and 88% in DHL positive and negative groups, respectively. Progression-free 6-month survival rates were 33% and 76% in DHL positive and negative groups, respectively. No relation with histopathological type of the disease was noted. Conclusion: We conclude that DHL presence in patients with extranodal DLBCL was an independent factor leading to shortened overall or progression-free survival.

Primary extranodal diffuse large B-cell lymphomas: Many sites, many entities? Clinico-pathological, immunohistochemical and cytogenetic study of 106 cases

We analyzed the clinicopathological, immunohistochemical and cytogenetic features of 106 extranodal (EN) diffuse large B-cell lymphomas (DLBCLs) from stomach (34 cases), intestine (10), cervico-cephalic region (11), central nervous system (13), testes (21), skin (8), and miscellaneous sites (9).Hans’ algorithm and the immunohistochemical double expressor score (DES) for MYC and BCL2 were applied to all cases. A subset of fifty-eight cases were analyzed with fluorescent in situ hybridization (FISH) with specific break apart probes for BCL6, MYC, BCL2, CCND1, BCL10 and MALT1 genes. Clinical records were available for all patients.The immunohistochemical study showed that, in our series of EN-DLBCLs, the Hans’ subgroup and the DES differed significantly according to the site of origin. At FISH analysis, BCL6 and BCL2 were the most commonly rearranged genes in non-GC and in GC cases, respectively. Gastrointestinal lymphomas displayed the highest rate of gene rearrangements, often with MYC involvement. One testicular DLBCL showed BCL2/MYC double hit. At survival analysis, cerebral and testicular origin was associated with poor prognosis. In addition, Hans’ subgroup and other immunohistochemical markers influenced patients’ outcome.In conclusion, our data suggest that immunophenotypic, genetic and survival characteristics of EN-DLBCL are related to the specific primary site of the disease.

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence.

Diffuse large B cell lymphoma (DLBCL) arises from extranodal organs in about 30% of cases. Its prognosis and risk of recurrence in the central nervous system (CNS) vary according to the primary site of origin. Recent studies begin to clarify these differences using molecular classification. Testicular, breast, and uterine DLBCL (as well as possibly primary cutaneous DLBCL, leg-type) share a high prevalence of the non-germinal center B cell (non-GCB) phenotype and the MYD88/CD79B-mutated (MCD) genotype. These biologic features, which resemble primary CNS lymphoma, may underlie their stage-independent propensity for CNS involvement. Management of these lymphomas should involve CNS prophylaxis, preferably using systemic high-dose methotrexate to prevent intraparenchymal recurrence. Involvement of the kidneys, adrenal glands, ovary, bone marrow, lung, or pleura usually indicates disseminated disease, conferring worse prognosis. Involvement of these sites is often associated with high CNS-International Prognostic Index (IPI), concurrent MYC and BCL2 or BCL6 rearrangements, or intravascular lymphoma-risk factors warranting CNS prophylaxis. In contrast, craniofacial, thyroid, localized bone, or gastric lymphomas have a variable prevalence of the non-GCB phenotype and lack MYD88 mutations. Their outcomes with standard immunochemotherapy are excellent, and the risk of CNS recurrence is low. We recommend individualized consideration of CNS prophylaxis based on the CNS-IPI score and anatomical proximity in cases of epidural, orbital, or skull involvement. Rituximab-containing immunochemotherapy is a standard approach for all extranodal DLBCLs. Surgery is no longer required for any primary site, but routine consolidative radiation therapy is recommended for testicular lymphoma. Radiation therapy also appears to be associated with better progression-free survival in primary bone DLBCL. Future studies should better distinguish primary from secondary sites of extranodal involvement, and investigate the association of newly identified genotypes with the risk of CNS or systemic recurrence.

Analysis of survival and treatment outcome of patients with primary diffuse large B cell lymphoma in reproductive system

Objective: To analyze clinical feature and treatment outcome of patients with primary diffuse large B cell lymphoma(DLBCL) in reproductive system. Methods: A total of 26 patients with DLBCL in reproductive system were retrospectively analyzed, and the clinical features, laboratory data were included in Kaplan-Meier and prognostic analysis. Results: In our center, the incidence of primary diffuse large B cell lymphoma in reproductive system was 3.5% in all DLBCL patients, and the median age was 62.0 years. Male are more common with unilateral testicular involvement, and 38.5% patients belong to Ⅲ and Ⅳstage while 84.6% patients belong to non-germinal center B cell-like subgroup. The overall response rate(ORR) for the whole group was 88.5%. The complete response rate was 76.9%. The 3, 5-year progression free survival rate was 70.5% and 62.7% , and the 3, 5-year overall survival rate was 83.5% and 69.6%, respectively. The most common recurrent sites were contralateral testis and central nervous system. Rituximab can improve the survival of patients and combined with contralateral irradiation can furtherly improve progression free survival of patients(P=0.047). Clinical stage, B symptom, IPI, the level of LDH, and CRP, age>60 years, and initial treatment outcome were predictive of overall survival. Conclusion: Primary diffuse large B cell lymphoma in reproductive system is a rare type of extranodal DLBCL which occurs in older men with aggressive features. The most common sites of recurrence were contralateral testis and central nervous system. Surgery, rituximab , radiotherapy and prophylactic intrathecal injection can improve the survival of patients and may be the first-line treatment.

Primary extra-nodal diffuse large B-cell lymphoma: A prognostic analysis of 141 patients.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma. Approximately 40% of DBLCL originates from extra-nodal sites, but the diversity of clinical presentations and the genetic and molecular alterations indicate that extra-nodal DLBCLs may be distinct disease entities. The aim of the present study was to highlight the various aspects of primary extra-nodal DLBCL (PE-DLBCL) based on a single center cohort. The data from 141 patients with PE-DLBCL treated at Peking Union Medical College Hospital were retrospectively evaluated. The primary extra-nodal sites involved were the gastrointestinal tract (n=42), central nervous system (CNS; n=38), breast (n=19), adrenal gland (n=15), female genital system (FGS; n=12), thyroid (n=8) and bone (n=7). The median overall survival rate was 28 months (range, 1–116). Multivariate analysis demonstrated that an International Prognostic Index (IPI) ≤2 (P=0.049), complete remission (CR) achieved following first-line therapy (P=0.001) and chemotherapy combined with rituximab (P<0.001) were positive prognostic factors. Patients with DLBCL with primary adrenal gland or female genital system (FGS) involvement exhibited a significantly higher risk of CNS recurrence (P<0.05). Rituximab treatment may have reduced the likelihood of CNS recurrence (P=0.005), whereas prophylaxis with intrathecal injection alone was not sufficient for prevention (P>0.05). In conclusion, IPI >2 and the lack of a CR following first-line therapy were independent prognostic risk factors for PE-DLBCL. Patients with primary adrenal gland or FGS involvement exhibited a higher risk of CNS relapse. Rituximab had a positive impact on the survival of patients with PE-DLBCL, also reducing the likelihood of CNS relapse.

Extranodal diffuse large B-cell lymphomas: A retrospective case series and review of the literature.

Non-Hodgkin lymphomas commonly show extranodal involvement (25-30%) but primary diffuse large B-cell lymphomas (DLBCL) with extranodal localization represent clinically and molecularly distinct entities. The present study involved retrospective analysis of case records of 4 patients who were diagnosed with extranodal DLBCL between 2010 and 2016 at the Medical Oncology and Hematology Departments of the Ioannina University Hospital, Greece. Median age of presentation was 69 years (range 60-77 years). There were 2 males and 2 females. The sites of DLBCL involvement included adrenal gland, mandible, cervix uteri, and ileum. Two patients had B symptoms while none had bone marrow involvement. After staging workup, all the patients fell into IE stage. The treatment approach included chemotherapy combined with rituximab (R), whereas one patient received additionally irradiation therapy. Post-treatment positron emission tomography-computed tomography scan was performed in 3 patients. In terms of the outcome, 3 patients are alive in complete response, whereas one was lost in follow-up. Further prospective data analyses are required so as to better elucidate the biology and course of extranodal DLBCL.

Concurrent Abdominal and Thyroid Lymphoma: A Case Report

ABSTRACT Objective: Thyroid lymphoma constitutes a rare presentation of extranodal, diffuse, large B-cell lymphoma (DLBCL) and represents a small proportion of thyroid cancers. In this article, we present a case report of extranodal DLBCL presenting with simultaneous thyroid, abdominal, and retroperitoneal involvement. We also review the relevant epidemiologic literature and treatment modalities of thyroid lymphoma as well as providing a potential pathophysiologic mechanism. Methods: A literature search was conducted using the databases PubMed and Google Scholar for primary thyroid lymphoma and extranodal lymphoma involving the thyroid. Publications were selected based upon size of patient cohorts, treatment modalities investigated, quality of the data, as well as subsequent citation frequency. Articles most recently published, and therefore belonging to the post-rituximab era, were favored. Results: Thyroid lymphoma in the presence of concurrent abdominal disease usually presents with goiter with or with...

Clinicopathological and fluorescence in situ hibridisation analysis ofprimary testicular diffuse large B-cell lymphoma: asingle-centre case series.

Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) represents arare and aggressive extranodal non-Hodgkin's lymphoma (NHL) with some specific features that differ from other NHLs. Formalin fixed, paraffin wax embedded (FFPE) samples of21 PT-DLBCLs and 30 comparative patients with DLBCL were analysed. All PT-DLBCL patients were treated with rituximab-containing regimens, intrathecal prophylaxis (10 patients), and irradiation ofthecontralateral testis (9 patients). FFPE samples were additionally analysed by immunohistochemistry (Bcl-2, c-Myc protein expression) and fluorescence in situ hybridisation (FISH) (BCL2 and MYC). The patients with PT-DLBCL (median age 48.5 years), had low frequency of B symptoms (28.6%) and were often diagnosed in I and II Ann Arbor clinical stage (66.0%). Themajority ofPT-DLBCL (80.9%) had anon-germinal centre B-cell-like immunophenotype. Immunohistochemical staining showed increased c-Myc protein expression in thePT-DLBCL group compared to thecontrol group (p=0.016). MYC rearrangement was detected in 1 of14 (7.0%), and MYC amplification in 3 of14 (21.0%) patients. One ofthe14 cases (7.0%) in thePT DLBCL group showed BCL2 rearrangement, and four of14 (28.05%) cases showed BCL2 amplification. Complete remission (CR) was achieved in 75.0% ofPT-DLBCL patients who had superior survival compared to those who did not achieve CR (median 48 vs. 21 months, p=0.012). Patients with PT-DLBCL express some immunohistochemical, biological, and clinical features that might differentiate them from nodal and extranodal DLBCL patients, indicating theneed for amore personalised treatment approach.

Estrogen receptor beta expression and prognosis of diffuse large B cell lymphoma

ABSTRACTObjectives: Estrogen receptor beta (ERβ)-selective agonists inhibited B cell lymphoma growth in animal models. However, a recent study found that higher ERβ expression in tissue from diffuse large B cell lymphoma (DLBCL) patients indicated a poorer survival. This study aimed to determine the ERβ expression in DLBCL tissue using immunohistochemistry and correlate with clinical outcomes.Methods: Diagnostic tissues from newly diagnosed adult DLBCL patients treated with Rituximab-Cyclophosphamide/Doxorubicin/Vincristine/Prednisolone were counted for ERβ1-expressing cells. Nodal lymphoma (N = 41) was analyzed separately from extra-nodal DLBCL (N = 31).Results: On immunohistochemistry, ERβ1 was expressed in 73.6% of cases with the median expressing cells of 20%. For nodal lymphoma, high ERβ expression (≥25%) was associated with poorer event free survival (EFS) independent of the international prognostic index with the adjusted hazard ratio (HR) of 2.49 (95% Confidence interval (CI) 1.03–6.00, P = 0.042). On the contrary, high ERβ expression (≥25%) was associated with superior outcomes in extra-nodal DLBCL with the adjusted HR of 0.25 (95% CI 0.09–0.75, P = 0.013) for EFS and adjusted HR of 0.29 (95% CI 0.10–0.85, P = 0.024) for overall survival in multivariate analyses.Conclusion: ERβ1 protein expression represented opposite prognostic factors in nodal vs. extra-nodal DLBCL.

A rare case of an extranodal head and neck lymphoma primarily diagnosed as sarcoma

Diffuse large B-cell lymphomas-not otherwise specified (DLBCL-NOS) are a common lymphoid malignancy, being the most common form of non-Hodgkin lymphoma (NHL). Typically, DLBCL-NOS arises in lymph nodes, however primarily extranodal involvement is possible, and it can present itself in various clinical and morphological types, posing a diagnostic challenge. In some cases, extranodal lymphomas may mimic non-lymphoid tumours, among them sarcomas. Treatment of DLBCL may involve chemotherapy, immunotherapy, radiotherapy and autologous stem cell transplant, while in the care of sarcomas surgery is an important modality of treatment. A-36-year-old male patient presented with a tumour of the left angle of the mandible which appeared a few days after a tooth extraction. It was first diagnosed as inflammation and treated with antibiotics. Afterwards, a biopsy indicated liposarcoma. A repeated biopsy and histopathological examination at an oncology centre revealed extranodal diffuse large B-cell lymphoma- not otherwise specified (DLBCL-NOS). The patient was successfully treated with chemotherapy with rituximab and radiotherapy. Complete remission was achieved and the patient remains DLBCL-NOS free for over six years. It is vital for extranodal lymphomas to be thoroughly differentiated from other malignancies by experienced oncology centres, since a false diagnosis may lead to a dramatic mistreatment.