Nodal Lymphoma Research Articles

Therapy of nodal Follicular Lymphoma (WHO grade 1/2) in clinical stage I/II using response adapted Involved Site Radiotherapy in combination with Obinutuzumab (Gazyvaro) - GAZAI Trial (GAZyvaro and response adapted Involved-site Radiotherapy): a study protocol for a single-arm, non-randomized, open, national, multi-center phase II trial

BackgroundLarge field irradiation had been standard for early-stage follicular lymphoma (FL) for a long time. Although involved field radiotherapy (IF-RT) was recently favored because of the toxicity of large field irradiation, smaller irradiation fields have been accompanied with an increased risk of out-of-field recurrence. The MIR (MabThera® and Involved field Radiation) trial has shown that the combination of IF-RT at a dose of 30–40 Gy with the anti-CD20 antibody rituximab has led to similar efficacy compared with large field irradiation but with markedly reduced side effects. Immune modulating radiation therapy alone using low-dose radiotherapy (LDRT) of 2 × 2 Gy has been shown to be effective in FL. The GAZAI (GAZyvaro and response Adapted Involved-site Radiotherapy) trial aims to prove the efficacy of LDRT in combination with a novel anti-CD20 therapy.Methods/designThe GAZAI trial is a non-randomized, open, non-controlled, German, multi-center phase II trial that includes patients with early-stage (I and II) nodular FL (grades 1 and 2) confirmed by central histological review. A maximum of 93 patients will be included in the trial. Patients will receive a combined approach of immunotherapy with the fully humanized anti-CD20 antibody obinutuzumab (Gazyvaro®) and involved site radiotherapy (IS-RT) with 2 × 2 Gy. The primary endpoint of the trial is the rate of metabolic complete response (CR), based on fludeoxyglucose positron emission tomography/computed tomography, after obinutuzumab and 2 × 2 Gy IS-RT in week 18. Secondary endpoints are morphologic CR rate in weeks 7 and 18 and month 6, progression-free survival, toxicity, recurrence patterns, overall survival, and quality of life. Additionally, minimal residual disease response is assessed. The risk for a potentially higher recurrence rate after LDRT will be minimized by additional salvage radiation up to the “full dose” of 40 Gy for patients who have less than a metabolic CR and morphologic partial response/CR, which will be evaluated in week 18, offering a response-adapted approach.DiscussionThe goal of this trial is a further reduction of the radiation dose in patients with nodal early-stage FL showing a good response to a combination of LDRT and anti-CD20 immunotherapy and a comparison with the currently published MIR trial.Trial registrationEudraCT number: 2016-002059-89. ClinicalTrials.gov identifier: NCT03341520.

Proliferative, pro-inflammatory, and angiogenesis regulator gene expression profile defines prognosis in different histopathological subtypes of nodal peripheral T-cell lymphoma.

Nodal peripheral T-cell lymphoma (PTCL) is an aggressive and heterogeneous malignancy with poor prognosis. We studied the prognostic impact of the expression profile of genes related to cell proliferation (CCNA2, TOP2A, and CHEK1), pro-inflammatory activity (NFkB1 and IKBkB), and angiogenesis (VEGF1) in nodal PTCL outcomes, as well as the ability of this genomic panel to discriminate different histological subtypes. We investigated the relative expression of regulator genes in 63 nodal PTCL patients. CCNA2, TOP2A, CHEK1, and NF-kB1 proteins were also assessed by immunohistochemistry. The median patient age was 47 years, 57.1% were male, 34.9% were diagnosed with PTCL-NOS, 28.6% with ALK-/ALCL, 22.2% with ALK+/ALCL, and 14.3% with AITL. The proliferative genes were associated with worse 3-year OS and PFS in PTCL-NOS and better 3-year PFS in ALK-/ALCL. Expression of CCNA2≥median and overexpression of CHEK1 protein (HR 3.793; p = 0.007) were associated with worse OS for all the cohort of nodal PTCL (HR 1.418; p = 0.001). The genomic expression profile tested in this study was not able to discriminate the different subtypes of nodal PTCL, although it showed a distinct prognostic significance between PTCL-NOS and ALCL-ALK. Overexpression of the CCNA2 gene and CHEK1 protein were associated with poor prognosis in the total nodal PTCL cohort.

Orbital soft tissue composite lymphoma presenting as recurrence of a nodal lymphoma with mantle and follicular cell components: A case report, literature review and guideline for the treatment of patients

Composite lymphoma with mantle and follicular cell components is a challenging diagnosis. Flow cytometry, immunohistochemistry and molecular genetics are required to distinguish the two components, as often the more aggressive one is predominant and masks the other. A 58-year-old man with history of nodal composite lymphoma presented with right exophthalmos and diplopia. A head CT scan showed an orbital tumor. A biopsy of the tumor revealed a mantle cell lymphoma predominating over a follicular lymphoma. Immunoglobulin heavy chain and light chain rearrangements analysis by PCR proved that both components of the orbital tumor were recurrences of the same nodal composite lymphoma diagnosed two years earlier. The nodal lymphoma was composed of a follicular lymphoma and an in situ mantle cell neoplasia. Consensus view is that dominant lymphoma should be treated when needed but taking into account if the mantle cell lymphoma is an in situ neoplasia and if it expresses CD5 and SOX11.

Primary hyaline vascular Castleman disease of the kidney: case report and literature review

BackgroundCastleman’s disease (CD) is an uncommon type of benign proliferation of the lymphoid tissue, characterized by local or systemic lymphadenopathy that most frequently appears in the mediastinum; involvement of the kidney is uncommon, and proliferation originating from the kidney is extremely rare. Herein, we report a rare case of hyaline vascular Castleman’s disease (HV-CD) in a 56-year-old male patient and discuss its morphological characteristics and differential diagnoses including mantle cell lymphoma (MCL), follicular lymphoma (FL), and nodal marginal zone lymphoma (NMZL).Case presentationA right upper-middle renal mass was detected after physical examination in a 56-year-old man without any clinical symptoms and a previous partial resection of the right kidney. Microscopically, the lymphoid follicles were increased in number and had expanded mantle zones and atrophic germinal centers. Vascular proliferation and hyalinization in the interfollicular zones were observed. Immunohistochemical staining showed CD20-positive cells in the mantle zones; CD21 and CD35 were expressed in the dendritic cells, CD3 was positive in a small number of T cells, and CD38 and CD138 were positive in the plasma cells. Additionally, Ki-67 expression was positive in the follicle centers. In contrast, staining for Bcl-2 in the germinal centers and cyclin D1 were negative. The immunohistochemical analysis combined with the morphological results supported the diagnosis of HV-CD. The patient recovered well after surgery.ConclusionsPrimarily renal HV-CD without lymph node hyperplasia or clinical symptoms is extraordinarily rare and different from the multicentric-type CD (MCD) with kidney involvement. Therefore, it is extremely important to improve the awareness of this diagnosis. Attention should be paid to the difference between HV-CD and common lymph node reactive hyperplasia, MCL, FL, NMZL, and so on. To avoid misdiagnosis as a renal malignant tumor requiring radical resection, distinguishing these diseases is crucial.

Spectrum of histopathological diagnosis of lymph node biopsies and utility of immunohistochemistry in diagnosis of lymphoma: A 5 year retrospective study from a tertiary care Centre in South India

Spectrum of histopathological diagnosis of lymph node biopsies and utility of immunohistochemistry in diagnosis of lymphoma: A 5 year retrospective study from a tertiary care Centre in South India - IJPO- Print ISSN No: - 2394-6784 Online ISSN No:- 2394-6792 Article DOI No:- 10.18231/j.ijpo.2019.083, Indian Journal of

Expression and clinical significance of neuropilin-1 in Epstein-Barr virus-associated lymphomas.

The expression of neuropilin-1 (NRP-1) in Epstein-Barr virus (EBV)-associated lymphomas and its relationships with clinicopathological parameters was investigated. The researchers compared 111 cases of patients with lymphoma to 20 cases of reactive lymphoid hyperplasia. In situ hybridization was applied to observe the expression of EBV-encoded RNA (EBER) in lymphomas, and immunohistochemistry was used to detect the NRP-1 expression in lymphoma tissues and lymph node tissues with reactive hyperplasia. In these 111 cases, the EBER of 62 cases (55.9%) appeared positive. NRP-1 was relatively highly expressed in lymphomas (P= 0.019). Further, NRP-1 showed higher expression in lymphomas with positive EBER than in negative ones. A comprehensive analysis revealed that NRP-1 was differently expressed in NK/T-cell lymphoma, Hodgkin's lymphoma, diffuse large B-cell lymphoma, and anaplastic large cell lymphoma (P= 0.027). Moreover, highly expressed NRP-1 was found to be a useful independent prognostic factor in assessing overall survival and progression-free survival rates in cases of non-Hodgkin's lymphoma (NHL). NRP-1 exhibited higher expression in lymphomas, and it was positively expressed in EBV-positive lymphomas. Moreover, highly expressed NRP-1 can be used as an undesirable independent prognostic factor in NHL.

Abstract 2513: Mutational and transcriptional landscape of nodal marginal zone lymphoma

Abstract Nodal marginal zone lymphoma (NMZL) is a rare B-cell neoplasm lacking disease-defining markers. In this study, we aimed to determine the mutational profile of Asian NMZLs and report novel genetic features of this disease. We performed WES on FFPE samples of eight Korean NMZLs and two matched non-neoplastic tissue samples. For unmatched cases, additional variant filtering was performed to minimize germline contamination. RNAseq was performed on six NMZL FFPE samples with acceptable samples quality. A total of 394 non-synonymous variants in 370 genes were found with the mean number of variants per case of 49.3 (range 14 – 98). We selected 93 candidate NMZL genes (CNGs) based on the following criteria: (i) genes with mutations in ≥ 2 patients; (ii) genes with mutations in either of two cases with matched control; (iii) genes with mutations in at least one case and reported to have biological roles in B-cell lymphomas. Mutations in genes involved in chromatin remodeling including KMT2D (25%), HIST1H1E (25%), and HIST1H1B (13%) were observed, which was consistent with previous studies. Genes encoding key components of B-cell receptor (BCR) signaling and related pathways were also affected, including CD79B (25%), CARD11 (13%) and BCL6 (13%). Of note, NFKBIE (c.759_762delTTAC) frameshift mutation was found in one patient; this mutation was proven to be loss-of-function in nature, resulting in deregulation of NF-κB signaling. Identical mutation was reported in Hodgkin lymphoma and primary mediastinal B-cell lymphoma, however, this is the first report of this mutation in NMZL. Genes involved in immune response including MYD88 (13%), PIM1 (13%), CD70 (13%) and TNFRSF14 (13%) were also mutated, suggesting the linkage between immune dysregulation and NMZL pathogenesis. At the transcriptome level, three samples were consistently clustered together. This group of patients was characterized by higher Ki-67 proliferation index compared to the others, and was associated with older age, higher serum LDH level and higher IPI score. Gene set analysis (GSA) based on lymphoma-specific gene sets from SignatureDB (https://lymphochip.nih.gov/signaturedb/) showed significant association between XBP1 target genes and these high Ki-67 group (P = 0.024). In summary, this study showed high prevalence of mutations in chromatin remodeling and BCR signaling pathway, readdressing the importance of these pathways in NMZL. Several novel genetic alterations in NMZL were found including NFKBIE c.759_762delTTAC, warranting further validation to clarify the significance of these alterations. We also found that NMZLs with high Ki-67 index were associated with specific gene expression profile, providing clue to the explanation for the heterogeneity of NMZLs. Citation Format: Jiwon Koh, Seongmin Choi, Insoon Jang, Sehui Kim, Cheol Lee, Jin Ho Paik, Kwangsoo Kim, Yoon Kyung Jeon. Mutational and transcriptional landscape of nodal marginal zone lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2513.

Abstract 4634: Mouse model for nodal marginal zone lymphoma

Abstract Introduction: Indolent B-Cell Non-Hodgkin’s Lymphoma (i-NHL) represents a heterogeneous group of lymphoproliferative malignancies, encompassing 40% of NHL, that remains largely incurable. The B-cell receptor signaling pathway is activated in B-cell malignancy and mediates its activity mainly through the Phosphoinositide 3-kinase (PI3K) pathway. Furthermore, novel PI3K inhibitors, such as idelalisib and copanlisib, have shown impressive clinical activity in several indolent lymphomas including marginal zone lymphoma (MZL). This further supports the important role of the PI3K pathway in these tumors. Methods We generated a genetically engineered mouse model carrying heterozygous knockout alleles of both the tumor suppressor genes Phosphatase and Tensin Homolog (PTEN) and Liver Kinase B1 (LKB1), leading to over-activation of the PI3K-mTOR pathway in all mouse tissues. We closely monitored these mice for tumor formation by at least weekly physical examinations for several months. Upon tumor detection, tumor size was recorded weekly using calipers, with an experimental endpoint of 15-20mm in any dimension. One half of the tumor was immediately preserved in a 4% paraformaldehyde solution and prepared for sectioning, H&E and immunohistochemical staining. Results: Thirty mice died or were sacrificed due to disease progression, defined as either lymph node enlargement and/or splenomegaly. All mice showed either abnormal lymphadenopathy or splenomegaly. By Kaplan-Meier analysis, we saw a steady decrease in both tumor-free and overall survival after 3 months of age. Utilizing the product limit method, the median survival time was 6 months (95% CI: 6, 8). A total of 51 lymph nodes were sent for IHC and pathological identification. Of the 51 nodes, 61.5% (N=32) showed indolent Non-Hodgkin’s Lymphoma, 25% (N=13) were atypical, and 11.5% (N=6) were reactive. All lymph nodes with indolent NHL were Marginal Zone subtype. In order to generate a more specific model of B cells, we used the Cre/LoxP system with CD19-Cre. We detected an increase in the average portion of MZL B cells in the spleen of the homozygous mice compared to wild type (38.3% vs 4.9%, p=0.0216). Conclusion: Nodal marginal zone lymphoma remains an incurable indolent lymphoma that lacks preclinical models. As novel agents become available, it is important to have a better understanding of the underlying pathogenesis of this malignancy and be able to model it in an immunocompetent mouse with a preserved microenvironment. Our data provides, for the first time, a proof of concept on the role of the PI3K-mTOR pathway in the pathogenesis of nodal marginal zone lymphoma and paves the way for future studies understanding the biology of this disease, and developing rational therapies for this incurable malignancy. Note: This abstract was not presented at the meeting. Citation Format: Victor Yazbeck, Ian McConnell, Joseph Lownik, Ariel Sindel, Roy Sabo, Alden Chesney, Guanhua Lai, Adolfo Mauro, Jamal Zweit, Rebecca Martin, Daniel Conrad, Steven Grant, Jolene Windle, Steven Grossman. Mouse model for nodal marginal zone lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4634.

Actualités dans les lymphomes à petites cellules non folliculaires

Non-follicular small cell lymphomas include several entities whose clinical and pathological descriptions have been refined in the last 20 years. MALT lymphoma, developed at the expense of lymphoid tissue associated with the mucosa, is usually localized to a given organ, but can also disseminate. Some patients with MALT lymphoma can be treated by eradicating the associated infectious agent, whereas local treatment should be preferred for other cases; disseminated forms and relapsed patients are eligible for anti-CD20 antibodies associated with cytotoxic agents. Patients with mantle cell lymphoma have benefited from many advances, including the use of cytarabine and bendamustine, anti-CD20 antibodies, intensive treatments (autograft) and recently targeted therapy (ibrutinib, inhibitor or the Bruton tyrosine kinase). Patients with splenic nodal marginal zone lymphomas should be evaluated for different options, of which immunochemotherapy remains important. For all these entities, the implementation of treatments may be delayed by several years for certain groups of patients. Although considered as incurable, the prognosis of these pathologies has improved significantly and the majority of patients will be able to live for many years with often treatment-free intervals.

Additional therapy improves outcomes in completely resected, limited-stage follicular lymphoma

Patients with early-stage nodal follicular lymphoma (FL) may be rendered free of detectable disease by a diagnostic excisional biopsy. We reviewed the management and outcomes of 48 patients with FL, diagnosed from 2003–2013, treated at a single institution. The primary endpoints were local control (LC) and progression-free survival (PFS).Median age at diagnosis was 54.5 years (range 15–74 years). Forty-seven patients were stage I (97.9%); 15 patients (31.3%) had grade 3 disease. Initial management consisted of observation (12 patients; 25.0%), radiation therapy (RT) alone (12 patients; 25.0%), systemic therapy alone (9 cases; 18.8%), or both (15 patients; 31.3%). Median follow-up was 4.92 years (range 0.5–13.83 years). 4-year PFS and OS were 80.9% and 97.1%, respectively. Patients treated with additional therapy experienced significantly better 4-year LC (100% vs. 81.8%; p = .012) and 4-year PFS (86.7% vs. 63.6%; p = .006).Patients with completely resected limited-stage FL would benefit from therapy beyond excisional biopsy alone.

Primary lymphomas of the intraabdominal solid organs and the gastrointestinal tract: spectrum of imaging findings with histopathological confirmation.

Unlike nodal lymphoma, primary lymphomas of the intraabdominal organs are uncommon neoplasms whose diagnosis may be challenging in certain clinical circumstances. Despite this difficulty for imaging diagnosis, there are several imaging features on ultrasonography, computed tomography, magnetic resonance imaging, and positron emission tomography that may suggest the correct diagnosis. The scope of this review is to describe and illustrate the imaging features of primary lymphoma of intraabdominal organs providing clues to the diagnosis, together with their pathological correlations.

Cytology and the cell block method in diagnostic characterization of canine lymphadenopathy and in the immunophenotyping of nodal lymphoma.

Minimally invasive techniques used to evaluate canine peripheral lymphadenopathy (PLN), including fine needle aspiration biopsy with cytological evaluation (FNAB-C) and flow cytometry (FC), have benefits and limitations. The cell block (CB) method is an alternate processing technique in which fine needle aspirate biopsy samples are concentrated, fixed, and embedded in paraffin for routine histological processing/staining. Utilizing three observers, we determined the diagnostic value of the CB in evaluating canine PLN across six categories (non-diagnostic, reactive, inflammatory/infectious, probable lymphoma and lymphoma, metastatic neoplasia) and correlated findings to immunophenotypic and clonal antigen receptor rearrangement results in canine nodal lymphoma. Eighty-five paired FNAB-C and CB samples were evaluated from canine patients presenting to the University of Minnesota Veterinary Oncology or Internal Medicine services. Diagnostic quality samples were obtained in 55/85 (65%) CB and 81/85 (95%) FNAB-C samples, respectively, and nodal pathology impacted CB diagnostic yield. Overall percent agreement between diagnostic-quality FNAB-C and CB samples was 86%, but increased to 95% if the categories of lymphoma and probable lymphoma were combined. There was 100% agreement for both the diagnoses of metastatic neoplasia and reactive lymph nodes and 92% agreement for the diagnosis of lymphoma/probable lymphoma. Using immunohistochemistry (IHC), CB samples correctly immunophenotyped 22/23 (96%) cases of B-cell lymphoma, but only 1/6 (17%) cases of T-cell lymphoma. IHC was not completed on nine cases of lymphoproliferative disease because of insufficient cellularity. When the CB method (CBM) yielded diagnostic quality samples there was good to excellent agreement with FNAB-C samples and CB samples were suitable for some IHC tests.

Differentiation of lymphomatous, metastatic, and non-malignant lymphadenopathy in the neck with quantitative diffusion-weighted imaging: systematic review and meta-analysis.

To perform a systematic review and meta-analysis of literature comparing average apparent diffusion coefficient (ADC) for differentiating lymphomatous, metastatic, and non-malignant cervical lymphadenopathy. We performed a comprehensive literature search of Ovid MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science Core Collection. Studies comparing average ADC of lymphomatous, metastatic, and non-malignant neck lymph nodes were included. The standardized mean difference and 95% confidence interval (CI) was calculated using random-effects models. In subgroup analysis of those studies applying ADC threshold for differentiation of cervical lymphadenopathy, pooled diagnostic odds ratio (DOR) and summary receiver operating characteristics (sROC) area under the curve (AUC) were determined. A total of 27 studies with 1165 patients were included, pooling data from 225 lymphomatous, 1162 metastatic, and 1333 non-malignant cervical lymph nodes. The average ADC values were lower in lymphomatous compared to metastatic nodes, and in metastatic compared to non-malignant nodes with a standardized mean difference of - 1.36 (95% CI: - 1.71 to - 1.01, p < 0.0001) and - 1.61 (95% CI: - 2.19 to - 1.04, p < 0.0001), respectively. In subgroup analysis, applying ADC threshold could differentiate lymphomatous from metastatic lymphadenopathy with DOR of 52.07 (95% CI 25.45-106.54) and sROC AUC of 0.936 (95% CI 0.896-0.979) and differentiate metastatic from non-malignant nodes with DOR of 39.45 (95% CI 16.92-92.18) and sROC AUC of 0.929 (95% CI 0.873-0.966). Quantitative assessment of ADC can help with differentiation of suspicious cervical lymph nodes, particularly in those patients without prior history of malignancy or unknown primary cancer site.

Opportunities and challenges of active immunotherapy in dogs with B-cell lymphoma: a 5-year experience in two veterinary oncology centers

BackgroundPet dogs spontaneously develop lymphoma. An anthracycline-based multidrug chemotherapy regimen represents the treatment cornerstone; however, cure is rarely achieved. We have been treating dogs with B-cell lymphoma with an autologous vaccine (APAVAC®) and CHOP-based chemotherapy since 2011.MethodsTo better characterize the safety and efficacy of APAVAC®, and to find the best candidates for immunotherapy, we designed a retrospective study on all dogs treated with chemo-immunotherapy to date and compared them with those dogs treated with chemotherapy only. All dogs were completely staged and re-staged at the end of treatment. The primary endpoint was the effectiveness of chemo-immunotherapy, measured as time to progression (TTP), lymphoma-specific survival (LSS), and 1-, 2-, and 3-year survival rates. The secondary objective was safety.ResultsThree hundred dogs were included: 148 (49.3%) received chemotherapy and 152 (50.7%) chemo-immunotherapy. Overall, the latter survived significantly longer (median LSS, 401 vs 220; P < 0.001).Among dogs with diffuse large B-cell lymphoma, the 1-, 2- and 3-year survival rates were 20, 13 and 8% for chemotherapy, and 51, 19 and 10% for chemo-immunotherapy. The benefit of chemo-immunotherapy was particularly relevant in dogs with concurrent high serum LDH, stage V, substage a disease and not previously treated with steroids (median LSS, 480 vs 85 days; P < 0.001). Among dogs with nodal marginal zone lymphoma, those having at least 3 of the aforementioned characteristics significantly benefited from chemo-immunotherapy (median LSS, 680 vs 160 days, P < 0.001). The 1-, 2- and 3-year survival rates were 30, 16 and 10% for chemotherapy, and 55, 28 and 10% for chemo-immunotherapy. Among dogs with follicular lymphoma, lack of immunotherapy administration was the only variable significantly associated with increased risk of tumor-related death. Chemo-immunotherapy was remarkably well tolerated, with no local or systemic adverse events.ConclusionsOverall, the addition of immunotherapy to a traditional CHOP protocol is associated with improved outcome in dogs with B-cell lymphoma, regardless of histotype and evaluated prognostic factors. Moreover, the identikit of the best candidate for immune-therapy was delineated for the most common histotypes. The study also confirms the excellent tolerability of the vaccine.

PB2060 THE UTILITY OF VARIABLE LEVELS OF CD39 EXPRESSION BY FLOW CYTOMETRY TO DISTINGUISHING B CELL LYMPHOMA SUBTYPES

Background:B lymphocytes were considered to be positive regulators of humoral immune responses. Recently B‐cell subsets named “regulatory B cells” (Bregs) have been describe. These subsets negatively regulate immune responses by inhibiting the activity of the effector T lymphocytes (Teff) and favoring that of the regulators T (Treg). The Bregs have been linked to not only inflammatory and autoimmune diseases, but also malignancies via suppressing anti‐tumour immunity. It emerged that B‐cells have regulatory properties having the ability to produce the immunosuppressive adenosine (ADO) via CD39, an ectoenzyme expressed on cells that cooperates to metabolize exogenous ATP to ADO. Studies have experimented that CD39 is upregulated (CD39high) in subset of activated immunosuppressive B‐cells. Unlike T and NK, greater than 90% of normal B‐cells express CD39, while the neoplastic B‐cells have an heterogeneous expression of CD39.Aims:The aim of this study was to assess the expression of CD39 in neoplastic B cells of nodal Follicular lymphomas (FL) and Diffuse Large B Cell Lymphomas (DLBCL). Moreover, these were compare with background non‐malignant B cells, when present.MethodsWe investigated the intensities of CD39 (CD39all,CD39hight) by flow cytometry (FC) in cell suspensions from dissociated tissues of 17 DLBCL, 22 FL and 10 normal lymph node (N‐LN). According Hans algorithm, among DLBCL 8 case were classified as Germinal Center B (GCB) subtypes and 9 as non‐GCB. The FL are subdivided according to the histological grade: 2 cases G1, 8 G2 and 12 G3.Results:For CD39all there was no difference in expression between DLBCL and N‐LN (p = 0,68), while there are significant differences between DLBCL and FL (p = 0,02) and between FL and N‐LN (p = 0,019). There were statistical differences for CD39high expression in DLBCL compared with N‐LN (p = 0,02) and with FL (p = 0,002). On the contrary, there were no statistically differences between FL and N‐LN (p = 0,9). Within the DLBCL the two subgroups were similar for CD39all (p = 0,1) but presented different results for CD39high: non‐GCB subtypes had a stronger expression compared to GCBs (p = 0,01). In FL subgroups CD39 expression showed high heterogeneity with a trend to a greater intensity of the marker as the histological grade increases, although there is not a statistically significant differenceSummary/Conclusion:Analysis of CD39 by FC could be an useful tool to distinguishing between FL and DLBCL. In particular, in FLs the intensity of expression could be related to the histological grade. Furthermore, CD39high seems to differentiate GCB from non‐GCB DLBCL, confirming in the latter the origin from activated B cell. The variable levels of CD39 by FC could contribute to orient in the defining entities that are not always easily and clearly differentiated. In addition, a variation of CD39 expression between neoplastic and normal cells was noted, particularly when clonal elements differ by FC for different sizes according to Side and Forward Scatter. Given that in Breg there is a variable levels of CD39 as a function of their immunosuppressive activity, it could be hypothesized that even in neoplastic B cells the different intensity of expression of the marker could suggest an active role of the B clone in producing immunosuppressive molecules and in characterizing the microenvironment favorable to the same lymphoma. Acknowledgments: This work was supported by Associazione Italiana contro le leucemie‐linfomi e mieloma (AIL) Trevisoimage

Rare mature B‐cell lymphomas in children and adolescents

Pediatric-type follicular lymphoma (PTFL), pediatric nodal marginal zone lymphoma (pnMZL), and large B-cell lymphoma (LBCL) with IRF4 rearrangement have been introduced into the current World Health Organization (WHO) classification. They account for 5% to 10% of mature B-cell lymphomas in children and adolescents. Both PTFL and pnMZL predominantly affect male adolescents and usually present with localized lymphadenopathy in the head and neck region. The cells within the follicles of PTFL typically show high-grade cytology, IGH monoclonality and lack the t(14;18) chromosomal alteration. In contrast, pnMZL is characterized by progressive transformation of germinal center (PTGC)-like features and interfollicular proliferation of the cells with expansion of the marginal zones with diffuse areas. Watch and wait after complete resection seems an adequate therapy with chemotherapy restricted to incompletely resected disease. All children with PTFL and pnMZL reported, so far, survived. B-cell lymphomas presenting in the Waldeyer's ring are characterized by the expression of IRF4/MUM1 and often associated with IRF4 rearrangements. Because of the frequent diffuse component, treatment often follows current protocols for mature B-NHL. The prognosis is excellent.

UTILITY OF ULTRASONOGRAPHY DIAGNOSIS FOR CERVICAL LYMPHADENOPATHY IN CENTRAL INDIAN POPULATION- A HOSPITAL BASED OBSERVATIONAL STUDY

Background: Cervical lymph nodes are frequently involved in a number of disease conditions. The most commonly seen causes of cervical lymphadenopathy are tuberculosis, distant metastasis and lymphoma.&#x0D; Objective: To assess the usefulness of ultrasonography in the differential diagnosis of cervical lymphadenopathy.&#x0D; Methods: ultrasonography of cervical lymph nodes was performed with a real-time linear scanner using a 7.5- or 11-MHz probe. Ultrasonography findings were retrospectively reviewed in 432 lymphnodes of 120 patients. USG findings were reevaluated by FNAC, CECT neck, MRI and core needle biopsy wherever required.&#x0D; Results: out of 432 lymphnodes; 108 tuberculous lymphadenitis, 46 metastatic, 59 lymphoma, 114 inflammatory and 105 normal lymph nodes were observed. Ultrasonography features were found to be stronger in tubercular, metastatic and lymphomatous lymphnodes. Hypoechoic center was prominently observed in tubercular and metastatic form. In most of the patients, FNAC result was equivocal and a subsequent excision biopsy of the lymph node was carried out to confirm the diagnosis. Lymphadenitis was diagnosed with a sensitivity of 100% and a specificity of 100%.&#x0D; Conclusion: This study concluded that cervical group of lymph nodes with ultrasonography features such as round shape, absence of hilar echo, sharp nodal borders, Hypoechoic internal echogenicity and presence of intranodal necrosis were highly suggestive of metastatic cervical lymph nodes. Ultrasonography along with other radiological and histopathological parameters can be very effective in early diagnosis of high risk diseases.&#x0D; Keywords: Ultrasonography; Tuberculous Lymphadenitis; Malignant Lymphoma; Metastatic Node

Paediatric nodal marginal zone lymphoma: a clinicopathological study of seven cases

Objective: To investigate the pathological features and clinical manifestation of pediatric nodal marginal zone lymphoma(NMZL). Methods: Histological morphology and immunophenotype of 7 cases of pediatric NMZL were retrospectively reviewed at Beijing Friendship Hospital Affiliated to Medical University between January 2008 to October 2018. Clonal rearrangement analysis was performed. Clinical information including patient follow-up data were analyzed. Results: All 7 patients were male with a median age of 15 years aged from 10 to 26 years. All patients presented with only lymph node enlargement without B symptoms, including cervical lymph node (5 cases), preauricular lymph node (1 case) and retroauricular lymph node (1 case). Histologically, all cases showed irregular large follicles on the edges with widened marginal areas and intervesicular areas, and lesional cells were uniform with progressive transformation of germinal center centers along with a small amount of intrinsic lymphoid tissue. All 7 cases showed diffuse CD20 positivity both follicle and interfollicular region along with 30%-40% positivity in the interfollicular region (pathological region). Markers of other B-cell lymphomas werenot expressed. All 7 cases were positive for immunoglobulin(Ig) gene rearrangement. None of the patients showed no recurrence up on after follow-up for an average of 13 months. Conclusions: Pediatric NMZL is a rare type of lymphoma that has a unique morphology and occurs almost exclusively in male children and young adults and often in head and neck lymph nodes. It has an excellent prognosis. Therefore, awareness of the disease with accurate diagnosis is important.

Synchronous Presentation of Ovarian Adenocarcinoma with Follicular Lymphoma in pelvic lymph nodes (Collision tumor) in a Postmenopausal Female patient: A Rare Case

Synchronous Presentation of Ovarian Adenocarcinoma with Follicular Lymphoma in pelvic lymph nodes (Collision tumor) in a Postmenopausal Female patient: A Rare Case

Early Stage Extranodal Follicular Lymphoma: Characteristics, Management, and Outcomes

IntroductionExtranodal follicular lymphoma (E-FL) is a rare entity that has distinct characteristics and outcomes compared with nodal follicular lymphoma. Patients and MethodsThis cohort comprised 37 patients with stages I/II E-FL, diagnosed from 2003 to 2013. Outcomes included progression-free survival (PFS), and overall survival (OS). Survival outcomes were calculated using Kaplan–Meier methods. ResultsMedian age was 60 years (range, 37-84 years). Disease was stage I in 29 (78.4%). The Follicular Lymphoma International Prognostic Index score was 0 to 1 in 31 (83.8%), 2 in 2 (5.4%), 3 in 1 (2.7%), and missing in 3 (8.1%). Sites of involvement included the gastrointestinal (GI) tract in 22 (59.5%), and non-GI sites in 15 (40.5%). Initial management consisted of chemotherapy (CHT) alone in 21 (56.8%), radiation therapy (RT) alone in 2 patients (5.4%), RT and rituximab in 1 (2.7%), CHT and RT in 7 (18.9%), and observation in 6 (16.2%). RT was to a median dose of 30.6 Gy (range, 23.4-44.0 Gy). At a median follow-up of 69 months (range, 8-157 months), 5-year PFS and OS were 70.4% and 94.4%, respectively. Although the 5-year PFS of those observed was worse than for those who received therapy (33.3% vs. 77.6%; P = .011), that did not translate into an OS difference. Patients who received RT as part of upfront management had a 100% local control (LC) rate and a trend toward improved 5-year PFS (90% vs. 62.2%; P = .067). ConclusionEarly stage E-FL is an indolent disease and is associated with excellent OS. Treatment strategies should be individualized with RT prioritized when LC is a significant goal.