Diffuse Large B-cell Lymphoma Involvement Research Articles

Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma.

We explored the utility of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) sequencing as a noninvasive diagnostic tool for detecting central nervous system (CNS) involvement in patients with diffuse large B-cell lymphoma (DLBCL). Secondary CNS involvement in DLBCL, although rare (~5% of cases), presents diagnostic and prognostic challenges during systemic disease progression or relapse. Effective treatment is impeded by the blood-brain barrier. This was a prospective cohort study (Samsung Lymphoma Cohort Study III) involving 17 patients with confirmed CNS involvement. High-throughput sequencing was conducted using targeted gene panels designed to detect low-frequency variants and copy number alterations pertinent to lymphomas in ctDNA extracted from archived CSF samples. Despite challenges such as low DNA concentrations affecting library construction, the overall variant detection rate was 76%. Detected variants included those in genes commonly implicated in CNS lymphoma, such as MYD88. The study highlights the potential of CSF ctDNA sequencing to identify CNS involvement in DLBCL, providing a promising alternative to more invasive diagnostic methods such as brain biopsy, which are not always feasible. Further validation is necessary to establish the clinical utility of this method, which could significantly enhance the management and outcomes of DLBCL patients with suspected CNS involvement.

Optimal index for detecting splenic involvement on 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging in diffuse large B-cell lymphoma.

Accurate clinical staging is important in diffuse large B-cell lymphoma (DLBCL) to adapt to optimal therapy. Splenic involvement of DLBCL has been recently more detectable with the advancement of a diagnostic scan by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). Our clinical question is whether splenic involvement was adequately diagnosed by FDG-PET/CT imaging. This retrospective study aimed to determine the optimal index for evaluating splenic involvement in patients with DLBCL. Patients with newly diagnosed DLBCL who were examined with FDG-PET/CT at diagnosis and the end of induction chemotherapy (EOI) was enrolled. The splenic involvement with the splenic FDG uptake value higher than that of the liver at diagnosis or with the decrease of splenic uptake at EOI by visual evaluation was evaluated as positive. The calculative evaluation of splenic involvement, based on the data of standardized uptake value (SUV) of the spleen, used maximum SUV (SUVmax), mean SUV (SUVmean), spleen total lesion glycolysis (spleen TLG), and spleen length. A change in each index following induction chemotherapy was expressed as an index. Receiver operating characteristic analysis was used to set the cutoff value for each index. This study included 52 patients. Spleen TLG (0.904) showed the best accuracy, followed by SUVmax (0.885) and SUVmean (0.885), among the 5 indexes for splenic involvement at diagnosis. Splenic involvement was predicted with a higher accuracy level (0.923) when selecting the cases with values higher than the cutoff level on both spleen TLG and SUVmax. The decision at EOI was more suitable by selecting both positive cases of ∆ TLG and ∆ SUVmax. Obtaining both the positive spleen TLG and SUVmax is recommended at diagnosis to predict splenic involvement. The assessment by ∆ spleen TLG and ∆ SUVmax seems to be optimal.

Diffuse large B-cell lymphoma involving the central nervous system: biologic rationale for targeted therapy.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma curable even in advanced stages. DLBCL involving the central nervous system (CNS) is more difficult to cure and fewer treatment options exist. Primary CNS lymphoma (PCNSL) refers to aggressive lymphomas confined to the CNS, and are almost always DLBCL. Standard approaches for PCNSL use high-dose methotrexate-based combinations as induction therapy and younger patients often receive dose-intensive consolidation. However, dose-intensive therapies are not suitable for all patients, and older patients have fewer effective treatment options. Patients with relapsed or chemotherapy-refractory disease have a very poor prognosis. Secondary CNS lymphoma (SCNSL) describes aggressive lymphomas involving the CNS at initial presentation or relapses within the CNS after treatment for systemic DLBCL. Isolated CNS relapse is often managed as PCNSL, but patients with synchronous involvement of DLBCL in both the periphery and the CNS pose a unique clinical challenge. Insights into the molecular circuitry of DLBCL have identified distinct genetic subtypes including cases with a predilection for CNS invasion. PCNSL and subsets of SCNSL are characterized by chronically activated B-cell receptor and NFκB signaling along with genetic evidence of immune evasion which may be exploited therapeutically. Improved mechanistic understanding of targetable pathways underpinning CNS lymphomas has led to numerous clinical trials testing targeted agent combinations and immunotherapy approaches with promising early results. Biologically rational strategies may further improve the cure rate of CNS lymphomas, either by overcoming intrinsic or acquired treatment resistance and/or by being broadly applicable to patients of all ages.

The Outcomes of Diffuse Large B-cell Lymphoma Patients with Synchronous and Early Central Nervous System Involvement: A Single-Center Experience.

Diffuse large B cell lymphoma (DLBCL) is the most commonly diagnosed subtype of non-Hodgkin's lymphoma (NHL). R-CHOP has significantly improved clinical outcomes in patients with DLBCL, however, its indication in the prevention of CNS relapse and recurrence is still inconsistent. Moreover, prophylactic methotrexate and/or cytarabine have been used prophylactically for DLBCL patients is at high risk of CNS relapse and to treat CNS DLBCL, however, their efficacy remains unclear. The aim of our retrospective study was to determine the incidence of CNS in-volvement in patients with DLBCL and to describe its risk factors and survival outcomes. A total of 406 patients with DLBCL were identified, and 17 (4.2%) of DLBCL patients had CNS involvement i.e. 9 (2.2 %) at diagnosis and 8 (~2%) at relapse. The patients were younger, had advanced stage, high CNS-IPI, and had extra nodal involvement. Seven out of the 17 patients who survived received chemotherapy and a prophylactic methotrexate. Considering the CNS-IPI, of the 146 patients with high CNS-IPI at presentation, 18 received the prophylactic HDMTX and 3 (16.7%) of them had CNS relapse. Two (1.6%) out of 128 who did not receive the prophylactic HDMTX had CNS relapse. On the other hand, of the 223 patients with intermediate CNS-IPI, 25 received the prophylactic HDMTX and 2 (8%) of them had CNS relapse and in 198 patients who did not receive the prophylactic HDMTX, 2 (1.01%) had CNS relapse. The 5-year progression-free survival and overall survival rates for the entire cohort were 73% and 84%, respectively. The median OS for those who had CNS involvement was 17 months and the 2-year OS was 40%. CNS involvement in DLBCL has a poor prognosis, thus, aggressive CNS-directed therapy should be considered, especially in young patients.

Diffuse large B-cell lymphoma and gastrointestinal Kaposi's sarcoma: a rare cause of upper gastrointestinal bleeding.

A 49-year-old man with a history of human immunodeficiency virus (HIV) infection, in a state of advanced immunosuppression and current antiretroviral therapy initiation. He was admitted to the hematology department after diagnosis of diffuse large B-cell lymphoma (DLBCL) associated with Epstein-Barr virus (EBV), disseminated cytomegalovirus (CMV) infection and cutaneous Kaposi's sarcoma (KS). During admission, he presented an episode of melena with anemization, so an urgent gastroscopy was performed. In the stomach there were multiple erythematous lesions, large and elevated, suggestive of subepithelial origin. Some of them presented an umbilicated center and other were ulcerated, covered with fibrin. The bulb and second duodenal portion showed similar involvement, large violaceous ulcerated lesions. Biopsies were taken and the anatomopathological diagnosis of the duodenal lesions was KS and of the gastric lesions KS and DLBCL associated with EBV. KS is an endothelial tumor associated with HIV. The stomach is the gastrointestinal organ most frequently affected and the typical endoscopic findings are nodular lesions. The stomach is the most common site of extranodal involvement in DLBCL. In both pathologies, the manifestation as upper gastrointestinal bleeding is exceptional and endoscopic biopsies can confirm the diagnosis.

Hepatic Involvement of Diffuse Large B-Cell Lymphoma Mimicking Antinuclear Antibody-Negative Autoimmune Hepatitis Diagnosed by Liver Biopsy

Non-Hodgkin's lymphoma (NHL) is the fifth most common hematologic disorder in the United States, and its prevalence has been rising in Western countries. Among the subtypes of NHL, diffuse large B-cell lymphoma (DLBCL) mostly involves the lymph nodes, stomach, and gastrointestinal tract, whereas hepatic involvement of DLBCL is rare. On serologic testing, elevated immunoglobulin G (IgG) levels can be observed in DLBCL; however, elevated IgG levels are mainly observed in autoimmune hepatitis. A targeted-lesion biopsy is required for the diagnosis of DLBCL. Based on a final diagnosis, the patient was treated with rituximab-based chemotherapy, including cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP). Herein, we report a case of DLBCL mimicking antinuclear antibody-negative autoimmune hepatitis, which was finally diagnosed as DLBCL involving the liver, and was confirmed by liver biopsy.

Поражение центральной нервной системы при диффузной В-клеточной крупноклеточной лимфоме

Introduction. Current approaches used to predict the recurrence of diffuse large B-cell lymphoma (DLBCL) with involvement of the central nervous system (CNS) need to be improved. Data from national studies on the incidence and clinical and laboratory characteristics of primary CNS DLBCL and secondary CNS involvement in systemic DLBCL are fragmentary and do not allow us to assess the overall picture. Aim. An assessment on the territory of the Siberian metropolis of data on the incidence and clinical and laboratory characteristics of DLBCL patients with primary CNS lymphoma (PCNSL) and secondary CNS involvement, as well as validation of the CNS-International Prognostic Index (CNS-IPI) on this sample. Materials and methods. The study group consisted of 47 patients with PCNSL and 35 with secondary CNS involvement in systemic DLBCL, the comparison group consisted of 202 patients with DLBCL without CNS involvement. Results. All patients with secondary CNS involvement in DLBCL belonged to the medium and high risk groups (p = 0.007) according to the CNS-IPI, which confirms its prognostic value. The risk factors for secondary CNS involvement in DLBCL were ECOG performance status ≥ 2, HIV infection, age over 60 years, a history of chronic kidney disease, ≥ 2 extranodal sites, and high expression of Ki-67 (>75% positive tumor cells), non-GCB subtype of lymphoma, and presence of anemia. When assessing the characteristics of the clinical course of the disease, a number of peculiarities of the primary and secondary CNS involvement in DLBCL were identified. In particular, in terms of overall survival, the PCNSL group had a more favorable prognosis (p = 0.051). Conclusion. The results of the study confirm the importance of the CNS-IPI as a tool of a hematologist to determine the group of patients needing prevention of recurrence of DLBCL in the CNS. New data on a higher incidence of chronic kidney disease, arterial hypertension and thyroid disorders in the group of patients with PCNSL require further study.

Prophylaxis and Management of Secondary CNS Lymphoma

Introduction Secondary CNS lymphoma (SCNSL) is CNS involvement of lymphoma either with synchronous systemic involvement or an isolated CNS relapse. SCNSL is not a specific biologic entity, but most are diffuse large B-cell lymphoma (DLBCL). CNS involvement of DLBCL at diagnosis is ~5%, but extranodal disease significantly increases the risk of CNS spread.1,2 Patient-related factors including age and performance status also correlate with CNS relapses as captured in the CNS International Prognostic Index (CNS-IPI).1

Association of Circulating Tumor DNA from the Cerebrospinal Fluid with High-Risk CNS Involvement in Patients with Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) patients with central nervous system (CNS) involvement have dismal outcomes. The detection sensitivity of conventional diagnosis of lymphoma through cerebrospinal fluid (CSF) cytology (CC) and flow cytometry (FCM) is restricted. CSF-ctDNA has shown to be an important method of liquid biopsy in patients with CNS cancers. To assess the correlation between CSF-ctDNA and CNS involvement in DLBCL, targeted mutational profiling was performed on CSF- and plasma -derived ctDNA together with matched systemic tumor tissues in 67 DLBCL patients clinically diagnosed as high risk for CNS relapse, using a validated panel of more than 400 genes. We found that ctDNA concentration in CSF but not in plasma correlated with CNS-IPI score in DLBCL patients. In CSF-positive high-risk DLBCL patients, eighty-six gene alterations(GAs) were shared between tumor tissue and CSF while ninety-five were shared between tumor tissue and plasma. Interestingly, forty-eight GAs(CSF-CNS GAs) were identified including 24 GAs exclusively in CSF and 24GAs shared by plasma which enriched in apoptosis/cell cycle related pathway and immunity-related pathway. To better screen for CNS-related molecular features in CSF, GAs in brain tumor tissue and CSF from a PCNSL-DLBCL cohort of 10 patients were sequenced and compared to that in high-risk group. Moreover, GAs in tumor samples from an additional cohort of 40 DLBCL patients clinically diagnosed as low-risk for CNS relapse were sequenced and compared to that in high-risk group to screen out non-CNS-related features. The number of alterations in five CSF-CNS genes including BTG2, PIM1, DUSP2, ETV6, CXCR4 in CSF was found to be associated with CNS risk in DLBCL patients. Our data supported the feasibility of using CSF-ctDNA as a complementary source for early detection of CNS involvement in DLBCL. The association between GAs in five CSF-CNS genes and CNS involvement deserved further investigation to determine their relevance in patient treatment and outcome. Disclosures Yu: Geneseeq Technology Inc: Current Employment. Ou:Geneseeq Technology Inc: Current Employment. Wang:Nanjing Geneseeq Technology Inc: Current Employment. Shao:Nanjing Geneseeq Technology Inc: Current Employment.

Novel targeted mtLivin nanoparticles treatment for disseminated diffuse large B-cell lymphoma.

We previously showed that Livin, an inhibitor of apoptosis protein, is specifically cleaved to produce a truncated protein, tLivin, and demonstrated its paradoxical proapoptotic activity. We further demonstrated that mini-tLivin (MTV), a 70 amino acids derivative of tLivin, is a proapoptotic protein as potent as tLivin. Based on these findings, in this study we aimed to develop a venue to target MTV for the treatment of diffuse large B-cell lymphoma (DLBCL). MTV was conjugated to poly (lactide-co-glycolic acid) surface-activated nanoparticles (NPs). In order to target MTV-NPs we also conjugated CD40 ligand (CD40L) to the surface of the NPs and evaluated the efficacy of the bifunctional CD40L-MTV-NPs. In vitro, CD40L-MTV-NPs elicited significant apoptosis of DLBCL cells. In a disseminated mouse model of DLBCL, 37.5% of MTV-NPs treated mice survived at the end of the experiment. Targeting MTV-NPs using CD40L greatly improved survival and 71.4% of these mice survived. CD40L-MTV-NPs also greatly reduced CNS involvement of DLBCL. Only 20% of these mice presented infiltration of lymphoma to the brain in comparison to 77% of the MTV-NPs treated mice. In a subcutaneous mouse model, CD40L-MTV-NPs significantly reduced tumor volume in correlation with significant increased caspase-3 activity. Thus, targeted MTV-NPs suggest a novel approach to overcome apoptosis resistance in cancer.

A Phase I Study of Nivolumab and Lenalidomide in Relapsed/ Refractory B Cell Lymphoma

A Phase I Study of Nivolumab and Lenalidomide in Relapsed/ Refractory B Cell Lymphoma

3142 Atypical Presentation of an Upper Gastrointestinal (GI) Bleed Manifesting as Extranodal Involvement of Diffuse Large B-Cell Lymphoma (DLBCL) Diagnosed in a Community Setting

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most common type of Non-Hodgkin's Lymphoma (NHL), with 5.4 new cases diagnosed per 100,000 persons as of 2016. There is a male predominance, with an average age of 64.2. One extranodal site involves the GI tract, predominantly the stomach. Commonly seen are mucosa associated lymphoid tissue lymphomas and DLBCL. The majority of cases present at stage III/IV, with 40% presenting as local involvement. Here we present an unusual case of extranodal DLBCL in a patient presenting with dysphagia and an upper GI bleed. CASE DESCRIPTION/METHODS: An 85 year-old female presented for evaluation of dysphonia, ongoing for several months. The patient complained of bilateral submandibular adenopathy, dysphagia, trouble breathing, and a 15 pound weight loss over two weeks. Computed tomography of the neck revealed a nasopharyngeal mass in the left (L) nasopharynx extending into the nasal cavity, right (R) nasopharynx, and eroding into the skull. Additionally, bilateral necrotic cervical lymph nodes and L supraclavicular adenopathy were also seen. Histologic sample was consistent with DLBCL, non-germinal center type. Fluorescence in-situ hybridization was negative for MYC rearrangement, t(8:14), t(4:18), and Epstein Barr Virus, but indeterminate for BCL6 rearrangement. She was staged IIA and underwent radiation therapy without chemotherapy. During treatment, the patient was admitted for evaluation of an upper GI bleed associated with dysphagia, fatigue, and progressive weakness. She underwent an esophagogastroduodenoscopy with findings showing Los Angeles class A esophagitis, large, inflammatory nodular tissue within the lesser curvature of the stomach with associated linear ulcerations, multiple punctate ulcers throughout the gastric body and antrum, duodenitis, and a small, clean-based ulcer in the duodenal sweep. Histology of the gastric mass revealed an atypical clonal lymphoid infiltrate involving the gastric mucosa, suggestive of DLBCL, with clonal immunoglobulin heavy chain gene rearrangement. DISCUSSION: This case represents an atypical presentation of an upper GI bleed that is the result of extranodal involvement of DLBCL. An atypical presentation like this should have lymphoma in the differential for those with a history. Treatment is dependent upon the extent of disease, usually starting with the regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. If left untreated, this disease can progress rapidly and prove fatal.

Bone Marrow Biopsy Is Still Indispensable for Evaluating Bone Marrow Involvement in DLBCL Patients Even in the PET/CT Era

Background: Initial staging by positron emission tomography/computed tomography (PET/CT) is recommended for lymphoma of fluorodeoxyglucose (FDG)-avid histology, such as diffuse large B-cell lymphoma (DLBCL). Although both PET/CT and bone marrow biopsy (BMB) are usually performed to determine the bone marrow involvement in DLBCL, whether PET/CT alone is sufficient remains controversial. While previous reports discussing this point have used data based on medical records, here we performed a systematic review of untreated DLBCL patients, for whom a radiologist and a hematopathologist separately performed blind reviews. Methods: The subjects had DLBCL diagnosed between 2008 and 2017 for which both PET/CT and BMB were performed for staging before initiation of treatment. We excluded cases in which BMB specimens were qualitatively and/or quantitatively insufficient to determine the presence or absence of bone marrow involvement. To exclude follicular lymphoma, we did not include patients whose diagnostic specimens of lymphoma included any degree of nodular growth pattern. All PET/CT scans were performed in a single institution. In PET/CT, cases with score 4 or 5 in the Deauville criteria in bone marrow were classified as positive. In the review of BMB, we used both hematoxylin-eosin staining and CD20 immunostaining specimens in all cases to determine the involvement. We treated the presence of bone marrow involvement by BMB as a reference, and the involvement type was classified as either concordant or discordant pattern. Survival curves were compared by the log-rank test. A P-value less than 0.05 was considered to indicate a significant difference. Results: The study included 87 untreated patients with DLBCL (82 DLBCL, NOS; 3 intravascular large B-cell lymphoma; and 2 primary mediastinal large B-cell lymphoma), comprising 46 males and 41 females. The median age at the time of diagnosis was 71 (range, 19 to 87 years). The number of positive cases in PET/CT and BMB was 17 (20%) and 24 (28%), respectively (Table). Nine (10%) cases had both positive results. Among BMB-positive cases, there were18 concordant and 6 discordant involvements. When considering BMB results as a reference, PET/CT showed 38% sensitivity and 87% for specificity. The positive and negative predictive values were 53% and 79%, respectively. In 61 patients initially treated with R-CHOP, there was no significant difference in progression-free survival (PFS) between positive and negative cases in PET/CT (P = 0.16) , but PFS was significantly worse for BMB-positive cases than BMB-negative cases (P = 0.03). Conclusion: BMB is still mandatory in patients with untreated DLBCL and predicts outcome in the era of PET/CT. Routine CD20 immunostaining might be helpful in detecting lymphoma involvement in BMB specimens. DisclosuresNo relevant conflicts of interest to declare.

Diffuse Large B Cell Lymphoma in an Adolescent: A Challenging Case with Intracerebral and Retinal Involvement

Diffuse large B-cell lymphoma (DLBCL) is a rare lymphoma type in pediatric patients with usually good prognosis. We present the difficult diagnostic procedure and the complicated course in an adolescent patient with DLBCL.Case report: The 16-year-old female patient presented with a history of fever episodes during the past 3 weeks, hepatosplenomegaly, leukopenia, anemia, hypertriglyceridemia, massive hyperferritinemia and elevation of lactate dehydrogenase. Leukemia was excluded by bone marrow puncture. Initially, no significant lymph node enlargement was detected by imaging of the mediastinum and the abdomen but a pathological signal of the bone marrow could be observed in magnetic resonance imaging (MRI). Hemophagocytic lymphohistiocytosis (HLH) was diagnosed and the patient was treated with prednisone 0.5 mg/kg per day. The overall condition and the laboratory values improved but deteriorated on cessation of the steroid treatment. The result of the bone marrow biopsy then revealed an infiltration of a malignant B-cell lymphoma. Diagnosis of a DLBCL, Non-GCB-type with a BCL6-break was subsequently made in a biopsy of a lymphnode which had shown increased uptake in PET scan. Treatment according to the current NHL-BFM registry including administration of Rituximab was started. The course of disease was complicated by HLH symptoms with persistent fever and pancytopenia, renal failure, severe Methotrexate excretion failure requiring Carboxypeptidase treatment and Herpes virus encephalitis. After recovery progression of DLBCL was found and the treatment was switched to DA-EPOCH regimen and repeated systemic Rituximab administrations. Five months after diagnosis the girl suffered from visual impairment and convulsions. Ophthalmoscopy revealed retinal lesions and intracerebral lesions were detected by MRI but no abnormalities of cerebrospinal fluid (CSF) were found. Biopsy of a brain lesion confirmed cerebral involvement of DLBCL. Intensified treatment included high- dose steroids, cranio-spinal irradiation, high-dose Cytarabin and intrathecal Rituximab. Response of the cerebral lesions but no improvement of the visual impairment was found. Salvage treatment with Gemcitabin, Cisplatin and Rituximab was administered because of persistent nodal and extranodal lymphoma manifestations. The patient finally died due to refractory disease and severe bone marrow failure.Conclusion: This case of DLBCL in an adolescent girl is extraordinary in many ways. DLBCL, especially the non-GCB type, is a rare disorder in pediatric patients. Predominant bone-marrow involvement has been described in only few older patients with non-GCB-type DLBCL and mostly aggressive clinical course. HLH as a presenting feature is rather observed in T- or NK-cell lymphoma than in DLBCL. Finally, central nervous system (CNS) relapse occurs in only about 6% of adults with DLBCL regardless of CNS prophylaxis. Retinal and intraparenchymal CNS involvement without abnormalities in the CSF has been typically described for primary CNS lymphoma in adults. All these conditions have contributed to the adverse outcome in our patient. DisclosuresNo relevant conflicts of interest to declare.

Diagnostic Accuracy of Immunoglobulin Heavy Chain Rearrangement, FDG-PET/CT and Unilateral Bone Marrow Trephination for Detecting Bone Marrow Involvement in Diffuse Large B Cell Lymphoma

Bone marrow involvement (BMI) has important clinical implication in diffuse large B cell lymphoma (DLBCL) as a component of staging and International Prognostic Index (IPI). However, there are some limitations of BMI assessment using iliac bony trephination, such as low sensitivity to patchy or focal lymphomatous involvement, inter-observers variability, inappropriately obtained specimens in terms of technical problem. This study investigated that whether the combined evaluation with 18F-FDG PET/CT and molecular analysis of monoclonal Immunoglobulin heavy chain (IgH) rearrangement could increase the diagnostic accuracy of BMI at the time of diagnosis in DLBCL.MethodsThis observational study conducted in 100 patients with newly diagnosed DLBCL from January 2017 to May 2018 from single institution. The specimens for IgH rearrangement polymerase chain reaction (PCR) to detect the clonality were obtained by fine-needle aspiration and unilateral trephination biopsy. In addition, 18F-FDG PET/CT assessment was performed at the time of diagnosis and classified into two patterns (focal vs diffuse) based on the type of bony FDG uptakes. The section specimens were reviewed by hematopathologists according to the World Health Organization (WHO) classification.Results53 patients were diagnosed with advanced stage and 9 patients (9%) were confirmed morphologic BMI (mBMI) by section biopsy. IgH monoclonality (IgH BMI) was detected in 17 patients (17%) and bony involvement on PET/CT assessment (PET BMI) was observed in 16 patients (16%), respectively. All nine patients with mBMI were linked together with either IgH BMI or PET BMI. Of 17 patients with IgH BMI, 6 patients (35.2%) were concordant with mBMI. Overall diagnostic accuracy of IgH BMI for detection of mBMI was 86%, and it's sensitivity and specificity was 66.7% and 87.9% with 96.4% of negative predictve value (NPV), respectively. In addition, among the patients with PET BMI, 11 patients were sub-classified into focal type (68.8%, 11/16) with median 7.9 of SUVmax compared to diffuse type with median 5.6 of SUVmax. 5 patients (31.3%, 5/16) were concordant with mBMI. Two of these five concordant cases were focal type. PET/CT assessment showed 85% of diagnostic accuracy with 55.6% of sensitivity, 87.9% of specificity and 95.2% of NPV, respectively. However, the combination of IgH rearrangement with PET/CT assessment resulted in 100% of sensitivity and 79.1% of specificity with 100% of NPV, respectively. Total 28 patients had positive results either IgH rearrangement or PET BMI. 11 patients showed only PET BMI, and another 12 showed only IgH BMI.ConclusionEach PET/CT assessment and PCR-technique for IgH rearrangement was associated with low sensitivity and high NPV for detecting mBMI. However, combined evaluation with IgH monoclonality and initial PET/CT could give more information to predict bone marrow involvement of DLBCL [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Lumen Obstructive Primary B-Cell Lymphoma of the Colon: A Rare Masquerader of Colorectal Carcinoma

Although gastrointestinal (GI) tract is the most common site involved by extra-nodal lymphoma, primary GI involvement is rare. An 85 year-old hispanic man presented with 2-month history of generalized abdominal pain, and altered stool consistency/frequency. At presentation, the laboratory workup was largely unremarkable, except hemoglobin of 11.5g/dL. Patient endorsed a history of colon polyps, last colonoscopy being 10 years ago. Colonoscopy revealed a large, friable mass in descending colon/splenic flexure, occluding 90% of the lumen, preventing further advancement of the scope (Figure). Given high suspicion for malignancy, multiple biopsies were obtained. CT of abdomen/pelvis with oral and intravenous contrast demonstrated a 4.5x4.2x5.8cm partially obstructive apple-core mass near splenic flexure, with pericolonic fat stranding suggestive for mesocolon extension. No bowel dilation or air-fluid levels were observed, suggesting non-obstructive colon. Additionally posterior mediastinal, mesenteric root, periportal and para-aortic lymphadenopathy were seen. Pathology established ALK positive diffuse large B-cell lymphoma (DLBCL), with immunohistochemistry negative for CD20, CMV and HHV8. Peripheral blood flow cytometry did not reveal abnormal T or B-cell populations or blast cells. Bone marrow biopsy determined no evidence of DLBCL involvement. Multiple hypermetabolic mediastinal and periesophageal lymph nodes were seen on PET-CT along with multiple focal hypermetabolic liver lesions, consistent with liver metastases. Considering patient's age, high cardiovascular risk, and other co-morbidities, surgical intervention was not indicated. Patient was started on chemotherapy regimen with CEPP (Cyclophosphamide, Etoposide, Procarbazine and Prednisone). The stomach is the most common location of GI lymphomas (50-60%) followed by small bowel (20-30%) and colorectal (10-20%). In the colon, lymphomas are commonest in the cecum, given relative abundance of lymphatic tissue. The etiology of colonic DLBCL is unknown, but immunodeficiency states and inflammatory bowel disease are recognized as predisposing conditions. The symptoms are non-specific, and endoscopic appearance may vary from fungating to ulcerative and/or infiltrative lesions. Radiologically, DLBCL is often indistinguishable from other benign and malignant tumors. The treatment of colorectal DLBCL includes chemotherapy, radiation, surgical treatment or a combination of these approaches.1523 Figure 1. Large, friable mass in descending colon/splenic flexure, occluding 90% of the lumen.

Hitting a Moving Target: Successful Management of Diffuse Large B-cell Lymphoma Involving the Mesentery With Volumetric Image-guided Intensity Modulated Radiation Therapy

IntroductionWe report successful treatment of mesenteric diffuse large B-cell lymphoma (DLBCL) using localized involved site radiation therapy (ISRT), intensity modulated radiation therapy (IMRT), and daily computed tomography (CT)-image guidance. Patients and MethodsPatients with mesenteric DLBCL treated with RT between 2011 and 2017 were reviewed. Clinical and treatment characteristics were analyzed for an association with local control, progression-free survival (PFS), and overall survival. ResultsTwenty-three patients were eligible. At diagnosis, the median age was 52 years (range, 38-76 years), and 57% (n = 13) had stage I/II DLBCL. All patients received frontline chemotherapy (ChT) (R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone], n = 19; dose-adjusted R-EPOCH [rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin], n = 4) with median 6 cycles. Prior to RT, salvage ChT for refractory DLBCL was given to 43% (n = 10) and autologous stem cell transplantation was administered in 13% (n = 3). At the time of RT, positron emission tomography-CT revealed 5-point scale of 1 to 3 (48%; n = 11), 4 (9%; n = 2), and 5 (44%; n = 10). All patients received IMRT, daily CT imaging, and ISRT. The median RT dose was 40 Gy (range, 16.2-49.4 Gy). Relapse or progression occurred in 22% (n = 5). At a median follow-up of 37 months, the 3-year local control, PFS, and overall survival rates were 80%, 75%, and 96%, respectively. Among patients treated with RT after complete metabolic response to frontline ChT (n = 8), the 3-year PFS was 100%, compared with 61% for patients with a history of chemorefractory DLBCL (n = 15; P = .055). Four of the 5 relapses occurred in patients with 5-point scale of 5 prior to RT (P = .127). ConclusionMesenteric involvement of DLBCL can be successfully targeted with localized ISRT fields using IMRT and daily CT-image guidance.

Diffuse large B-cell lymphoma with pulmonary and cerebral involvement: A case report.

Primary diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma; however, the involvement of the lung and central nervous system (CNS) in patients with DLBCL is rare. Furthermore, patients with DLBCL rarely exhibit specific clinical symptoms, which may delay definitive diagnosis. The present study reports the case of a 42-year-old man suffering from primary DLBCL with concurrent pulmonary and cerebral involvement. The patient suffered from human immunodeficiency virus infection and presented with symptoms including dry cough, thoracalgia, intermittent mild fever and mild headache. Thoracic computed tomography scans revealed multiple pulmonary masses, and brain magnetic resonance imaging scans revealed nodules in the left frontal cortex and bilateral basal ganglia. A percutaneous lung needle biopsy test confirmed the diagnosis of DLBCL. In addition, positron emission tomography revealed the involvement of other parts of the body in DLBCL. The aim of the present study was to present the clinical, radiological and histological characteristics of the patient, which may aid physicians in diagnosing pulmonary and CNS involvement in DLBCL.

Hypothalamic involvement in diffuse large B-celllymphoma

Hypothalamic involvement in diffuse large B-celllymphoma

MicroRNAs as predictors for CNS relapse of systemic diffuse large B-cell lymphoma.

Systemic diffuse large B-cell lymphoma (DLBCL) is a potentially curable disease using current regimen of immunochemotherapy. Central nervous system (CNS) relapse is a complication that occurs in approximately 5% of DLBCL patients and is associated with a high fatality rate. Early identification of molecular markers for CNS involvement may serve for the highly needed accurate stratification of patients into risk groups regarding CNS relapse. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and are known to be involved in DLBCL pathophysiology. In this study, we utilized miRNA multiplex reading of systemic newly diagnosed DLBCL samples obtained from patients with clinical risk factors for CNS involvement whose disease course was distinguished by the presence or absence of subsequent CNS relapse. The analysis detected two differentially expressed miRNAs, miR-20a and miR-30d, that predict for CNS involvement. Replication of these results in different samples was used for validation. We performed bioinformatics miRNA-target enrichment analysis to reveal a number of putative mechanisms for these miRNAs regulation of CNS relapse, including neuronal plasticity and WNT signaling pathway. Altogether, we show that the expression level of two miRNAs may have valuable information that may refine stratification for patients-at-risk for relapse with CNS involvement in DLBCL. Further larger scale studies are needed to shed light on the pathways involved in this disease.