Plasmablastic lymphoma is a rare and aggressive diffuse large B-cell lymphoma commonly associated with Epstein-Barr virus co-infection that most often occurs in the context of human immunodeficiency ...virus infection. Therefore, its immune escape strategy may involve the upregulation of immune-checkpoint proteins allowing the tumor immune evasion. However, the expression of these molecules was poorly studied in this lymphoma. We have investigated 82 plasmablastic lymphoma cases of whom half were Epstein-Barr virus positive. Although they harbored similar pathological features, Epstein-Barr virus positive plasmablastic lymphomas showed a significant increase in MYC gene rearrangement and had a better 2-year event-free survival than Epstein-Barr virus negative cases (P=0.049). Immunostains for programmed cell death-1, programmed cell death-ligand 1, indole 2,3-dioxygenase and dendritic cell specific C-type lectin showed a high or moderate expression by the microenvironment cells in 60%-72% of cases, whereas CD163 was expressed in almost all cases. Tumor cells also expressed programmed cell death-1 and its ligand in 22.5% and 5% of cases, respectively. Both Epstein-Barr virus positive and negative plasmablastic lymphomas exhibited a high immune-checkpoint score showing that it involves several pathways of immune escape. However, Epstein-Barr virus positive lymphomas exhibited a higher expression of programmed cell death-1 and its ligand in both malignant cells and microenvironment as compared to Epstein-Barr virus negative cases. In conclusion, plasmablastic lymphoma expresses immune-checkpoint proteins through both malignant cells and the tumor microenvironment. The expression of programmed cell death-1 and its ligand constitutes a strong rationale for testing monoclonal antibodies in this often chemoresistant disease.
Background
Although minimally invasive rectal surgery (MIRS) for cancer provides better recovery for similar oncologic outcomes over open approach, conversion is still required in 10% and its impact ...on short-term and long-term outcomes remains unclear. The aim of our study was to evaluate the impact of conversion on postoperative and oncologic outcomes in patients undergoing MIRS for cancer.
Methods
From June 2011 to March 2020, we reviewed 257 minimally invasive rectal resections for cancer recorded in a prospectively maintained database, with 192 robotic and 65 laparoscopic approaches. Patients who required conversion to open (Conversion group) were compared to those who did not have conversion (No conversion group) in terms of short-term, histologic, and oncologic outcomes. Univariate and multivariate analyses of the risk factors for postoperative morbidity were performed.
Results
Eighteen patients (7%) required conversion. The conversion rate was significantly higher in the laparoscopic approach than in the robotic approach (16.9% vs 3.6%,
p
< 0.01). Among the 4 reactive conversions, 3 (75%) were required during robotic resections. Patients in the Conversion group had a higher morbidity rate (83.3% vs 43.1%,
p
= 0.01) and more severe complications (38.9%, vs 18.8%,
p
= 0.041). Male sex HR = 2.46, 95%CI (1.41–4.26), total mesorectal excision HR = 2.89, 95%CI (1.57–5.320), and conversion (HR = 4.87, 95%CI 1.34–17.73) were independently associated with a higher risk of overall 30-day morbidity. R1 resections were more frequent in the Conversion group (22.2% vs 5.4%,
p
= 0.023) without differences in the overall (82.7 ± 7.0 months vs 79.4 ± 3.3 months,
p
= 0.448) and disease-free survivals (49.0 ± 8.6 months vs 70.2 ± 4.1 months,
p
= 0.362).
Conclusion
Conversion to laparotomy during MIRS for cancer was associated with poorer postoperative results without impairing oncologic outcomes. The high frequency of reactive conversion due to intraoperative complications in robotic resections confirmed that MIRS for cancer is a technically challenging procedure.
mutations, notably the recurrent gain-of-function L265P variant, are a distinguishing feature of activated B-cell like (ABC) diffuse large B-cell lymphoma (DLBCL), leading to constitutive NFκB ...pathway activation. The aim of this study was to examine the distinct genomic profiles of
-mutant DLBCL, notably according to the presence of the L265P or other non-L265P MYD88 variants.
A cohort of 361 DLBCL cases (94
mutant and 267
wild-type) was submitted to next-generation sequencing (NGS) focusing on 34 genes to analyze associated mutations and copy number variations, as well as gene expression profiling, and clinical and prognostic analyses.
Importantly, we highlighted different genomic profiles for MYD88 L265P and MYD88 non-L265P-mutant DLBCL, shedding light on their divergent backgrounds. Clustering analysis also segregated subgroups according to associated genetic alterations among patients with the same
mutation. We showed that associated
and MYD88 L265P mutations act synergistically to increase NFκB pathway activation, although the majority of MYD88 L265P-mutant cases harbors downstream NFκB alterations, which can predict BTK inhibitor resistance. Finally, although the MYD88 L265P variant was not an independent prognostic factor in ABC DLBCL, associated
mutations significantly improved the survival of MYD88 L265P-mutant ABC DLBCL in our cohort.
This study highlights the relative heterogeneity of
-mutant DLBCL, adding to the field's knowledge of the theranostic importance of
mutations, but also of associated alterations, emphasizing the usefulness of genomic profiling to best stratify patients for targeted therapy.
.
Primary gastrointestinal follicular lymphomas (PGFL) are very rare. Our aim was to analyze the clinical features, management, and long-term outcomes in a prospective series of patients diagnosed with ...PGFL.
All adult patients with PGFL, consecutively enrolled into the multicenter French study between 1990 and 2017, were evaluated and followed up prospectively after undergoing a complete work-up. Clinical, pathological and endoscopic features, as well as treatment outcomes, were analyzed.
Thirty-one patients (16 men, median age 62 years, range 33 to 79 years) with PGFL were included. The median follow-up was 92 months (range, 6 to 218 months). In the majority of patients (n=14), lymphoma was incidentally diagnosed during endoscopy. Otherwise, the most frequent circumstances of diagnosis were abdominal pain (n=7) and dyspepsia (n=5). The duodenum was the most common site of involvement (n=19) and multifocal localizations were seen in seven patients (22%). The most frequent first line strategy was surveillance applied in 22 patients (71%), of whom nine reached spontaneous, complete remission and 11 had stable disease. Seven patients (23%) received chemotherapy as first line treatment, and two underwent resection. Of seven patients who received chemotherapy, four achieved complete remission. In three patients, transformation into a high-grade lymphoma occurred.
The diagnosis of PGFL is frequently fortuitous. The most common localization is in the duodenum. The disease has an indolent course and a good prognosis, however, rare cases of transformation into aggressive high-grade lymphoma may occur. An appropriate characterization and follow-up of these lymphomas is mandatory for their optimal management.
We aimed to assess the prognostic significance of follicular lymphoma-associated macrophages in the era of rituximab treatment and maintenance.
We applied immunohistochemistry for CD68 and CD163 to ...two large tissue microarrays (TMA). The first TMA included samples from 186 patients from the BC Cancer Agency (BCCA) who had been treated with first-line systemic treatment including rituximab, cyclophosphamide, vincristine, and prednisone. The second contained 395 samples from PRIMA trial patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and randomized to rituximab maintenance or observation. Macrophage infiltration was assessed using Aperio image analysis. Each of the two cohorts was randomly split into training/validation sets.
An increased CD163-positive pixel count was predictive of adverse outcome in the BCCA dataset 5-year progression-free survival (PFS) 38% vs. 72%, respectively, P = 0.004 in the training cohort and 5-year PFS 29% vs. 61%, respectively, P = 0.004 in the validation cohort. In the PRIMA trial, an increased CD163 pixel count was associated with favorable outcome (5-year PFS 60% vs. 44%, respectively, P = 0.011 in the training cohort and 5-year PFS 55% vs. 37%, respectively, P = 0.030 in the validation cohort).
CD163-positive macrophages predict outcome in follicular lymphoma, but their prognostic impact is highly dependent on treatment received.
The utility of (18)Ffluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in assessing response at the end of induction therapy is well documented in Hodgkin's and ...diffuse large B-cell lymphomas, but its role in follicular lymphoma (FL) remains undetermined. We investigated the prognostic significance of PET-CT performed after first-line therapy in patients with FL treated in the prospective Primary Rituximab and Maintenance (PRIMA) study.
Results of PET-CT scans performed after induction immunochemotherapy were recorded retrospectively. Patients went on to either observation or rituximab maintenance per protocol independent of the PET-CT result. Patient characteristics and outcomes were then evaluated.
Of 122 PET-CT scans performed at the end of the induction immunochemotherapy, 32 (26%) were reported as positive by the local investigator. Initial demographic or disease characteristics did not differ between PET-CT-positive (PET-positive) and PET-CT-negative (PET-negative) patients. PET status correlated with conventional response criteria (P < .001). Patients remaining PET positive had a significantly (P < .001) inferior progression-free survival at 42 months of 32.9% (95% CI, 17.2% to 49.5%) compared with 70.7% (95% CI, 59.3% to 79.4%) in those who became PET negative. PET status, but not conventional response (complete response or complete response unconfirmed v partial response) according to IWC 1999, was an independent predictive factor for lymphoma progression. The risk of death was also increased in PET-positive patients (hazard ratio 7.0; P = .0011).
(18)FFDG PET-CT status at the end of immunochemotherapy induction in patients with FL is strongly predictive of outcome and should be considered a meaningful clinical end point in future studies.
Summary
Lymphoma‐associated haemophagocytic syndrome (LAHS) accounts for most cases of secondary haemophagocytic syndrome (HS) and has been extensively described in Asian populations. However, little ...is known about the epidemiology of LAHS in Western countries. We herein report a case series of 71 LAHS patients in which the lymphomas were mainly of the aggressive type. Diagnoses included non‐Hodgkin B cell lymphoma (46·5%) including human herpes virus 8‐associated non‐Hodgkin lymphoma (12·7%), T cell lymphoma (28·2%) and Hodgkin lymphoma (23·9%). An underlying immunodeficiency was described in 30 patients (42·3%). Early mortality within the 30 days following HS diagnosis was observed in 26·8% of cases. The overall survival was estimated at 45·7% 95% confidence interval, CI (35·4–59·0) at 6 months, and 34·3% 95% CI (24·8–47·4) at 2 years. Concurrent infection, age over 50 years, ethnicity and etoposide treatment were independently associated with mortality. While it appears that certain types of lymphomas were more prone to trigger HS, LAHS were not restricted to a few types of lymphoma. The overall prognosis was poor, with a particularly high rate of early mortality, highlighting the importance of both early recognition and choice of initial therapeutic management.
Mediastinal gray zone lymphoma, B-cell lymphomas with intermediate features between classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, have not been well described in the literature. ...We report the clinical characteristics and outcomes of a large retrospective series of 99 cases centrally reviewed by a panel of hematopathologists, with a consensus established for the diagnosis. Cases were defined as classical Hodgkin lymphoma-like morphology (64.6%) with primary mediastinal B-cell lymphoma immunophenotype, primary mediastinal B-cell lymphoma-like morphology (30.3%) with classical Hodgkin lymphoma or composite (5.1%) (synchronous occurrence of classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma). The median age was 32 years (13-83 years); 55% were women. Thirteen of 81 evaluable cases (16%) were Epstein-Barr virus-positive. Twenty-eight percent of patients presented primary refractory disease (progression under first-line treatment or relapse within one year). The 3-year event-free and overall survival rates were 63% and 80%, respectively. Patients treated with a standard regimen (RCHOP/ABVD) had worse event-free survival (P=0.003) and overall survival (P=0.02) than those treated with a dose-intensive chemotherapy (high-dose RCHOP/escalated BEACOPP). Rituximab added to chemotherapy was not associated with better event-free survival (P=0.55) or overall survival (P=0.88). Radiotherapy for patients in complete remission had no impact on event-free survival. In multivariate prognostic analysis, ECOG-PS and anemia were the strongest factors associated with a shorter event-free survival and overall survival, respectively. In conclusion, this report describes the largest series of mediastinal gray zone lymphoma. Our data suggest that a dose-intensive treatment might improve the outcome of this rare and aggressive disease.
The roles of the inflammatory response and production of a proliferation-inducing ligand (APRIL) cytokine in gastric mucosa-associated lymphoid tissue (MALT) lymphomagenesis induced by Helicobacter ...species infection are not clearly understood. We characterized the gastric mucosal inflammatory response associated with gastric MALT lymphoma (GML) and identified APRIL-producing cells in two model systems: an APRIL transgenic mouse model of GML induced by Helicobacter infection (Tg-hAPRIL) and human gastric biopsy samples from Helicobacter pylori-infected GML patients. In the mouse model, polarization of T helper 1 (tbet), T helper 2 (gata3), and regulatory T cell (foxp3) responses was evaluated by quantitative PCR. In humans, a significant increase in april gene expression was observed in GML compared to gastritis. APRIL-producing cells were eosinophilic polynuclear cells located within lymphoid infiltrates, and tumoral B lymphocytes were targeted by APRIL. Together, the results of this study demonstrate that the Treg-balanced inflammatory environment is important for gastric lymphomagenesis induced by Helicobacter species, and suggest the pro-tumorigenic potential of APRIL-producing eosinophils.
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