Plasmablastic lymphoma: 2024 update on diagnosis, risk stratification, and management.

DISEASE OVERVIEW: Plasmablastic lymphoma (PBL) is a rare CD20-negative aggressive lymphoma with a poor prognosis under standard treatment options. Though PBL is associated with human immunodeficiency virus infection and other immunosuppressed states, it can also affect immunocompetent individuals. DIAGNOSIS: The diagnosis requires a high clinical suspicion and pathological confirmation. EBER expression and MYC gene rearrangements are frequently detected. The differential diagnosis includes EBV+ diffuse large B-cell lymphoma, extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B-cell lymphoma, among others. RISK STRATIFICATION: Age ≥60 years, advanced clinical stage, and high intermediate and high International Prognostic Index scores are associated with worse survival. MANAGEMENT: Combination chemotherapy regimens, such as EPOCH, are recommended. The addition of bortezomib, lenalidomide, or daratumumab might improve outcomes. Including PBL patients and their participation in prospective clinical trials is warranted.

A single-center analysis of patients with extranodal marginal zone lymphoma of the breast.

Breast extranodal marginal zone lymphoma (EMZL) is a rare malignancy. We performed the largest published to date single-center retrospective analysis of 13 patients with breast EMZL focusing on clinical characteristics and treatment-related outcomes. The rarity of this disease at our center was concordant with the prevalence reported in the literature, with breast EMZL comprising 2% of 654 MZL cases. Most patients presented with stage I-II disease however four (30.8%) patients had stage IV disease mostly due to occult bone marrow (BM) involvement. Interestingly, EMZL was frequently non-FDG avid (66.7%) on staging PET/CT. With a median follow-up of 3.1 years (range 5 months to 10.2 years), the 3-year progression free survival was 68.7% (95%CI 30.2%-88.9%) and overall survival 80.2% (95%CI 40.3%-94.8%). No patient experienced higher-grade transformation. Herein we show that localized breast EMZL can be effectively treated with radiation therapy providing long term disease control.

Marginal zone lymphoma of the colon: case series from a single center and SEER data review.

Colon extranodal marginal zone lymphoma (EMZL) is poorly characterized in the literature. We performed a retrospective review of patients with colon EMZL at our institution and from the Surveillance Epidemiology and End Results (SEER) database. Eight patients were identified in our institution with majority (88%) presenting with stage-I disease. Initial management included active surveillance, polypectomy followed by surveillance, and surgical resection followed by chemotherapy. One patient with concurrent prostate carcinoma received radiation to the rectum. Initial therapy led to complete remission in five out of six treated patients with four of them maintaining remission at 88 months. SEER database identified 361 patients with stage-I colon EMZL. Overall survival for this cohort was 73.9% at 10 years with no significant difference in outcomes between treatment groups. Our single institution experience and the SEER data analysis emphasize indolent nature of colon EMZL and need for non-aggressive therapeutic approaches.

Treatments and Outcomes in Stage I Extranodal Marginal Zone Lymphoma in the United States.

A considerable number of patients with extranodal marginal zone lymphoma (EMZL) are diagnosed with stage I disease. Information on treatments and survival by primary location remains limited. We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database to assess treatment, primary location, and survival of patients with stage I EMZL. Results show that 7961 patients met inclusion criteria. Observation (no treatment) was the most common approach (31%) followed by radiation therapy (RT, 23%). The median overall survival (OS) was 17.3 years (95%CI 16.3 to 18.3). Shorter survival was observed in patients with stage I EMZL compared to expected survival in a cohort derived from the general U.S. population matched by sex, age, and calendar year at diagnosis. However, similar survival was observed in RT-treated patients. We identified age ≥ 60 years (SHR = 4.00, 95%CI 3.10-5.15; p < 0.001), higher grade transformation (SHR = 4.63, 95%CI 3.29-6.52; p < 0.001), and primary lung EMZL (SHR = 1.44, 95%CI 1.05-1.96; p = 0.022) as factors associated with shorter lymphoma-specific survival (LSS). Conversely, primary skin location (SHR = 0.50, 95%CI 0.33-0.77; p = 0.002) was associated with longer LSS. Our results support the use of RT as the preferred approach in localized EMZL.

Survival analysis in treated plasmablastic lymphoma patients: a population-based study.

Herein we analyzed survival outcomes in chemotherapy-treated patients with plasmablastic lymphoma (PBL) diagnosed between 2010 to 2016 (n = 248). Data was acquired from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database (April 2019 release based on November 2018 submission). The majority of patients were male (81.9%) and younger than 60 years (71.0%). Oral and gastrointestinal (GI) sites were the most frequent primary extranodal locations (23% and 19.4%, respectively). Oral primary location was inversely associated with presence of B symptoms and advanced Ann-Arbor stage. The 3-year and 5-year overall survival (OS) rates of treated PBL patients were 54% (95% CI: 46.5%-60.8%) and 52.8% (95% CI: 45.2%-59.8%). Three-year conditional survival for 2-year and 3-year survivors were 90.3% and 97.8%, overlapping the survival of a general population matched by age, sex and calendar year. In a multivariable analysis, oral primary location was associated with not only better OS (HR 0.43; 95% CI: 0.21-0.88, P = .021) but also better lymphoma-specific survival (LSS) (SHR 0.36; 95% CI: 0.15-0.86, P = .022); age ≥60 years was associated with shorter LSS (SHR 1.73; 95% CI: 1.02-2.96, P = .043). Seven registries granted access to HIV status (n = 93) where HIV infection was detected in 52.7% of cases. The HIV status did not affect survival outcomes in unadjusted and adjusted analyses. We identified clinical characteristics associated with survival and showed that treated PBL patients may achieve long-term survival.

Splenic marginal zone lymphoma: A US population-based survival analysis (1999-2016).

BACKGROUND: Splenic marginal zone lymphoma (SMZL) is a rare tumor without a uniform treatment approach. The authors describe a large population-based study evaluating survival outcomes of patients with SMZL according to the treatment received. METHODS: From the Surveillance, Epidemiology, and End Results database, patients were selected who had SMZL diagnosed from 1999 to 2016. Observation, splenectomy, chemotherapy, and splenectomy with chemotherapy were the evaluated treatment strategies. Cox and Fine and Gray regression models were used to evaluate overall and SMZL-specific survival, respectively. RESULTS: In total, 1671 patients were selected for the analysis. Most patients were aged >60 years (71.3%), White (89.7%), and non-Hispanic (91.7%). Transformation to diffuse large B-cell lymphoma (DLBCL) occurred in 71 patients (4.2%), and the 10-year transformation rate was 8.6% (95% CI, 6.6%-10.9%). In multivariable analysis, shorter SMZL-specific survival was associated with age ≥60 years (subdistribution hazard ratio [SHR], 1.85; 95% CI, 1.40-2.45; P < .001), Hispanic ethnicity (SHR, 1.50; 95% CI, 1.06-2.13; P = .023), DLBCL transformation (SHR, 2.10; 95% CI, 1.48-2.97; P < .001), and the presence of B-symptoms (SHR, 1.67; 95% CI, 1.23-2.27; P < .001). Compared with splenectomy, observation (SHR, 0.92; 95% CI, 0.67-1.28; P = .636), chemotherapy only (SHR, 1.28; 95% CI, 0.93-1.76; P = .127), and splenectomy plus chemotherapy (SHR, 1.43; 95% CI, 0.96-2.13; P = .089) showed no significant differences in SMZL-specific survival. Predictors of shorter overall survival were age ≥60 years (hazard ratio, 2.98; 95% CI, 2.37-3.76; P < .001) and the presence of B-symptoms (hazard ratio, 1.33; 95% CI, 1.06-1.67; P = .014). CONCLUSIONS: There were no significant differences in overall or SMZL-specific survival by treatment strategy. Older age, Hispanic ethnicity, DLBCL transformation, and B-symptoms were associated with a worse prognosis.

Low Frequency of Mutation Testing in the United States: An Analysis of 3866 GIST Patients.

OBJECTIVE: The objective of this study was to determine whether there were survival differences associated with KIT mutation testing, type of KIT mutations, and other clinical variables in patients with localized or metastatic gastrointestinal tumor (GIST). METHODS: Adult patients with GIST were extracted from the Surveillance Epidemiology and End Results (SEER) database from 2010 to 2015 with follow-up through 2016. Overall survival (OS) and cancer-specific survival (CSS) were the designated endpoints. RESULTS: A total of 3866 patients met inclusion criteria. Metastatic disease was found in 656 patients (17%), whereas localized disease was present in 3210 patients (83%). KIT mutation testing was performed in 1033 patients (26.7%) with equal distribution in localized and metastatic disease (27% and 26.6%, respectively). Multivariate analysis was performed in localized and metastatic GIST. In localized GIST, black race showed worse OS (hazard ratio [HR]=1.57; 95% confidence interval [CI]: 1.26-1.96), whereas higher mitotic rate (>5/50 HPF) demonstrated poor OS (HR=1.59; 95% CI: 1.24-2.05) and CSS (HR=3.07; 95% CI: 2.07-4.54); tumor size (>10 cm) showed poor CSS (HR=5.73; 95% CI: 2.37-13.8). In metastatic GIST, black race showed poor OS (HR=1.42; 95% CI: 1.04-1.93) and CSS (HR=1.73; 95% CI: 95% CI: 1.18-2.54), while KIT testing was associated with better OS (HR=0.64; 95% CI: 0.47-0.87) and CSS (HR=0.66; 95% CI: 0.44-0.97); treatment with tyrosine kinase inhibitors showed better OS (HR=0.67; 95% CI: 0.51-0.88). Surgical resection was associated with better OS (HR=0.56; 0.47-0.67) and CSS (HR=0.55; 95% CI: 0.42-0.72) both in localized and metastatic GIST. CONCLUSIONS: The minority of GIST patients have their tumor tested for any KIT mutation. Yet, KIT testing and therapy with tyrosine kinase inhibitors were associated with better survival in GIST patients with metastatic disease. Surgery, potentially curative for localized GIST, shows benefit in the metastatic setting.

Ventilator Settings Can Substantially Impact Patients' Comfort.

BACKGROUND: With increasing realization that sedatives may complicate care of mechanically ventilated patients, greater emphasis might turn to promoting comfort by titration of ventilator settings. HYPOTHESIS: Patients with acute on chronic respiratory failure (ACRF) with underlying chronic obstructive pulmonary disease (COPD) demonstrate different levels of comfort in response to varying ventilator settings compared to those with underlying obesity hypoventilation syndrome (OHS). METHODS: Patients recovering from ACRF with underlying COPD or OHS were randomized to varying combinations of ventilator modes (assist control and pressure support), tidal volumes, and inspiratory flows for 3 minutes/setting. For each ventilator setting, physiologic variables were recorded and patients indicated their level of comfort using a 10-point Borg scale. RESULTS: In all, 20 patients, aged 68 ± 13 years (standard deviation) and ventilated for 4.9 days, were enrolled. Of 20 patients, 13 had COPD and 7 had OHS. No ventilator mode, flow, or tidal volume provided consistently greater comfort between the groups, but patients reported substantial ranges of comfort (up to 8 Borg points) across the ventilator settings studied. There were no significant differences in heart rate, blood pressure, or airway pressures within patients across ventilator settings or between the groups, but patients with OHS were more tachypneic compared to patients with COPD while breathing on assist control of 6 mL/kg (constant flow 60 L/min) and 8 mL/kg (decelerating flow 40 L/min). There was no correlation between comfort and systolic blood pressure, heart rate, or respiratory rate. CONCLUSION: Ventilator parameters may impact patients' comfort substantially. Future studies may help identify evidence-based methodology for gauging comfort following changes in ventilator settings and the settings that are most likely to positively impact various groups of patients.

Anti-GBM disease and ANCA during dengue infection.

Anti-glomerular basement membrane (GBM) disease is a severe inflammatory renal disorder due to pathogenic autoantibodies directed mainly against the α3 chain of type IV collagen. In ~1/4 of patients with anti-GBM disease, antineutrophil cytoplasmic antibodies (ANCA) predominantly with myeloperoxidase (MPO) specificity can be detected. Although the inciting stimuli leading to the development of an immune response against the type IV collagen and neutrophils are unknown, evidence indicates that both genetic and environmental factors play a role. Of note, molecular mimicry between self-antigens and nonself-antigens such as antigenic determinants of microorganisms has been implicated in the pathogenesis of anti-GBM disease and ANCA-associated vasculitis. A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue can be complicated by acute renal failure, proteinuria, hematuria and glomerulonephritis. We present a 66-year-old woman who was diagnosed with dengue infection and rapidly progressive glomerulonephritis during an outbreak of dengue in Honduras in the summer of 2013. Renal biopsy revealed severe crescentic glomerulonephritis. Immunofluorescence examination demonstrated strong linear IgG deposition along glomerular capillary walls. Serologic tests demonstrated antibodies against GBM, MPO and platelet glycoproteins. The patient was diagnosed with anti-GBM disease associated with p-ANCA with MPO specificity. Despite heavy immunosuppression and plasmapheresis, IgG titers against dengue virus continued to rise confirming the diagnosis of acute dengue infection. We present the first reported case of anti-GBM disease associated with p-ANCA with MPO specificity during dengue infection. This report calls for a heightened awareness of autoimmunity leading to crescentic glomerulonephritis in patients with dengue infection.