Gyermekkori indolens lymphomák differenciáldiagnosztikája

Összefoglaló. Bevezetés: A gyermekkorban előforduló hematológiai megbetegedések közül az indolens non-Hodgkin-lymphomák igen ritka entitásnak számítanak. A betegség általában körülírt nyirokcsomó-megnagyobbodással jelentkezik, mely jellemzően lokalizált marad, szisztémás tünetek megjelenése nélkül, a prognózis kifejezetten kedvező. Morfológiai képük igen változatos, ami miatt gyakran differenciáldiagnosztikai kihívást jelentenek. Sajátos klinikopatológiai megjelenésük és rendkívül kedvező gyógyhajlamuk miatt a 2016-os WHO klasszifikációban önálló entitásként szerepelnek, mint gyermekkori-típusú follikuláris lymphoma és gyermekkori nodális marginális zóna lymphoma. Jelen tanulmányunk célja volt átfogó képet adni a gyermekkori indolens lymphomákról, különös hangsúlyt fektetve a differenciáldiagnosztikai problematikára. Közleményünkben részletes ismertetésre kerülnek az egyes szövettani típusok, morfológiai, immunhisztokémiai, klinikai és genetikai jellemzők szerint. Summary. Introduction: Indolent non-Hodgkin lymphomas in the pediatric and young adult population are very rare. The disease usually presents as isolated, localized lymphadenopathy most often in the head and neck regions, without generalized symptoms. The histology mainly shows mature B-cell lymphoma phenotypes, distinction from reactive lymphoid hyperplasias can be often difficult. Pediatric indolent lymphomas show characteristic clinicopathological features with excellent prognosis that differ from the adult counterpart; these lymphomas can be found as a distinct entity in the 2016 WHO classification as the pediatric-type follicular lymphoma and the pediatric-type nodal marginal zone lymphoma. In this study we present the pathologic characteristics: morphology, immunophenotype and genetical features and the important differential diagnostics of these entities.

Low Mutational Burden of Extra Nodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue in Patients with Primary Sjogren's Syndrome

Background: Primary Sjogren's syndrome (pSS) is an autoimmune disease characterized by chronic inflammation of the exocrine glands. Patients with pSS are at increased risk of developing extra nodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) type, predominantly in the salivary glands. The presence of cryoglobulinemia, low C4 levels and salivary gland enlargement, are important risk factors for lymphoma development in pSS. Although lymphoma associated mutations have been described in circulating B-cells of patients with pSS associated cryoglobulinemia, it is unknown which somatic aberrations underlie the development of pSS-associated MALT lymphomas. The aim of the current study was to define the genomic landscape of pSS salivary gland MALT lymphomas. Identification of specific recurrent mutations or copy number aberrations and defining the affected pathways would help to understand the mechanisms by which intra-epithelial B-cells undergo malignant transformation. Methods: Whole exome sequencing was performed on 14 fresh frozen and 3 paraffin embedded MALT tissue samples of pSS patients at the University Medical Center Groningen (UMCG). Matched peripheral white blood cell samples were available for 12 patients and were used as germline controls. Fluorescence in situ hybridization was performed for the detection of MALT1 translocations. Results: Presence of a clonal B-cell population, indicative of a MALT lymphoma was confirmed by IgH PCR (BIOMED-2) for all patients. Whole exome sequencing resulted in a median target coverage of 130x, ranging from 84-163. More than 90% of the target regions had a coverage of >50x. In total we identified 232 somatic mutations in 184 genes. Three cases had a relatively high mutational load (>25 / case), while the median number of mutations in the remaining 14 cases was 7. Across the 17 cases there were 18 recurrently mutated genes. PRKD1, associated with malignant epithelial tumor of the salivary glands, was the most frequently mutated gene (six cases). Besides PRKD1, five additional recurrently mutated genes are also involved in epithelial surface and/or extracellular matrix (MAMDC4, COL14A1, CAMSAP3, TMEM2 and MUC4). Five genes, all with mutations in two cases, were shown to be associated with lymphomagenesis (ID3, TBL1XR1, PAX5, IGLL5, APC). A total of 18 copy number alterations (CNAs) were detected in 8 of the 14 evaluable cases, with gains of part of chromosomes 2 and 19, and loss of chromosome 6 each being detected in two cases. With respect to outcome, only 2 cases with high mutational load relapsed outside of the salivary glands, suggesting a more advanced stage of lymphoma. Conclusion: The low mutational load and lack of a clear lymphoma related gene signature suggests that localized pSS MALT lymphomas are genetically stable and most likely depend on the inflammatory state of the micro-environment. Only those cases characterized by higher mutational load showed a relapse-remitting disease, as is typical for indolent lymphoma. These observations could be translated to the clinical setting and potentially have value as biomarker for identification of patients with a more aggressive disease. Confirmation in larger cohorts are required to confirm this potential association. This study also paves way for treatment strategies targeting the micro-environment. Disclosures No relevant conflicts of interest to declare.

Clinical features and possible prognostic factors in patients with Marginal Zone Lymphoma: Retrospective analysis from two centers

Objectives Marginal zone lymphoma accounts 5%-17% of all non-Hodgkin lymphomas and has an indolent clinical course. The parameters that predict prognosis and the need for treatment are still unclear. The aim of the current study was to examine the impact of parameters on the course of disease and the need for treatment in marginal zone lymphoma. Methods A retrospective study was conducted with marginal zone lymphoma patients in the two centres between 2010 and 2018. The demographic and disease characteristics, and also hematological and biochemical parameters at the time of diagnosis were examined. The effect of the parameters on overall survival and need for treatment were analyzed. Results During the follow-up, 25 patients required treatment and 15 patiens were followed up without treatment. Overall survival was significantly higher in patients with nodal marginal zone lymphoma than in extranodal and splenic marginal zone lymphoma patients. overall survival of patients who required treatment was 92.9 months while untreated patients was 58.4 months and there was no significant difference among the groups. The platelet count of untreated patients at the time of diagnosis were significantly higher than patients who received treatment. No significant relationship was found between any parameter and overall survival. Conclusions We demonstrated platelet count at the time of diagnosis as a predictive factor for future treatment need. It is an objective and simple blood test that may be helpful to predict the course of the disease although further studies are warranted.

Treatment outcomes of stage IE intestinal extra-nodal marginal zone lymphoma: A National Cancer Database study.

e19530 Background: Extra-nodal marginal zone lymphoma is a rare, indolent non-Hodgkin lymphoma. Classically it involves the gastric mucosa and is associated with chronic infection, but it can also be found in the lower gastrointestinal (GI) tract. No standard therapy has been established for early stage disease in the small intestine, colon or rectum though multiple strategies have been employed. Little is known regarding the natural history and long-term outcomes of this disease when confined to the lower GI tract. We used the National Cancer Database (NCDB) to evaluate this patient population based upon treatment modality and disease site. Methods: Patients meeting the inclusion criteria were extracted from the 2017 Extra-Nodal Non-Hodgkin’s Lymphoma NCDB. Patients were grouped by primary treatment or observation status. Clinical and demographic factors were compared between the treatment groups via chi-square, Fisher’s exact and the Kruskal-Wallis tests. Comparison of Overall Survival (OS) between groups utilized either univariable log-rank comparison of the Kaplan-Meier estimator or multivariable Cox proportional hazards regression modelling, with patients censored at date of last contact. All analyses were performed with the SAS software suite, version 9.4. Results: 775 patients were identified with stage IE extra-nodal marginal zone lymphoma of the small intestine, colon or rectum with treatment and follow-up data. Prevalence increased over time. Median age at diagnosis was 65, with a ten-year overall survival for the entire cohort of 74.8% (69.8% - 79.0%). Location of disease was small intestine in 286 patients (36.9%), colon in 361 patients (46.6%) and rectum in 128 patients (16.5%). Ten-year overall survival was significantly worse for a small intestine primary site compared to colon and rectum primary sites (64.9% (55.6% - 72.6%) vs 81.5% (74.9% - 86.5%) and 80.9% (68.5% - 88.8%) respectively; p-value 0.013). Initial treatment was surgery in 361 patients (46.6%), radiation in 99 patients (12.8%), chemotherapy and/or immunotherapy in 120 patients (15.5%), and observation in 195 patients (25.1%). No significant differences in 5-year or 10-year survival were seen between treatment groups. Conclusions: Observation is a reasonable management strategy in patients with stage IE lower intestinal tract extra-nodal marginal zone lymphoma; survival is similar to those who received surgery, radiation or systemic therapy. Those with small intestine primary site had worse overall survival, irrespective of treatment modality, when compared to colon and rectum disease sites.