Acute left ventricular insufficiency in a Burkitt Lymphoma patient with myocardial involvement and extensive local tumor cell lysis: a case report

BACKGROUND: Burkitt lymphoma (BL) is a rare disease with the sporadic variant accounting for less than 1% of adult non-Hodgkin lymphomas. BL usually presents with an abdominal bulk, but extranodal disease affecting the bone marrow and central nervous system is common. Cardiac manifestations, however, are exceedingly rare, with less than 30 cases reported in the literature. CASE PRESENTATION: We report on a 54-year-old male patient with a six week-long history of paranasal sinus swelling, fatigue and dyspnea on exertion. Stage IV sporadic BL with extensive lymphonodal and cardiovascular involvement was diagnosed. Manifestations included supra- and infradiaphragmatic lymphadenopathy as well as infiltration of the aortic root, the pericardium, the right atrium and the right ventricle. EBV-reactivation was detected, which is uncommon in the sporadic subtype. After initial full-dose chemotherapy with very good BL control, the patient developed acute, but fully reversible cardiac insufficiency. Myocardial lymphoma involvement receded completely during the following two therapy cycles, while cardiac function periodically deteriorated shortly after chemotherapy administration and quickly recovered thereafter. Interestingly, the decline in cardiac function lessened with decreasing myocardial lymphoma manifestation. Once the cardiovascular BL infiltration was resolved, cardiac function remained stable throughout further treatment. Following seven cycles of chemotherapy and mediastinal radiation, the patient is now in continued complete remission. CONCLUSIONS: Although rare, cardiac involvement in BL can quickly become life-threatening due to rapid lymphoma doubling time and should therefore be considered at initial diagnosis. This case suggests an association between myocardial infiltration, chemotherapy associated tumor cell lysis and transient deterioration of cardiac function until the damage caused by the underlying lymphoma could be restored. While additional studies are needed to further elucidate the mechanisms of acute cardiac insufficiency due to lymphoma lysis in the infiltrated structures, prompt BL control and full recovery of the patient supports courageous treatment start despite extensive cardiovascular involvement

Comorbidities rather than older age define outcome in adult patients with tumors of the Ewing sarcoma family

BACKGROUND: Ewing family of tumors (EFT) is rarely diagnosed in patients (pts) over the age of 18 years (years), and data on the clinical course and the outcome of adult EFT pts is sparse. METHODS: In this retrospective analysis, we summarize our experience with adult EFT pts. From 2002 to 2020, we identified 71 pts of whom 58 were evaluable for the final analysis. RESULTS: Median age was 31 years (18-90 years). Pts presented with skeletal (n = 26), and extra-skeletal primary disease (n =32). Tumor size was ≥8 cm in 20 pts and 19 pts were metastasized at first diagnosis. Between the age groups (≤25 vs. 26-40 vs. ≥41 years) we observed differences of Charlson comorbidity index (CCI), tumor origin, as well as type and number of therapy cycles. Overall, median overall survival (OS) was 79 months (95% confidence interval, CI; 28.5-131.4 months), and median progression-free survival (PFS) 34 months (95% CI; 21.4-45.8 months). We observed a poorer outcome (OS, PFS) in older pts. This could be in part due to differences in treatment intensity and the CCI (<3 vs. ≥3; hazard ratio, HR 0.334, 95% CI 0.15-0.72, p = 0.006). In addition, tumor stage had a significant impact on PFS (localized vs. metastasized stage: HR 0.403, 95% CI 0.18-0.87, p = 0.021). CONCLUSIONS: Our data confirms the feasibility of intensive treatment regimens in adult EFT pts. While in our cohort outcome was influenced by age, due to differences in treatment intensity, CCI, and tumor stage, larger studies are warranted to further explore optimized treatment protocols in adult EFT pts

Flow cytometry can reliably capture gut microbial composition in healthy adults as well as dysbiosis dynamics in patients with aggressive B-cell non-Hodgkin lymphoma

Modulation of commensal gut microbiota is increasingly recognized as a promising strategy to reduce mortality in patients with malignant diseases, but monitoring for dysbiosis is generally not routine clinical practice due to equipment, expertise and funding required for sequencing analysis. A low-threshold alternative is microbial diversity profiling by single-cell flow cytometry (FCM), which we compared to 16S rRNA sequencing in human fecal samples and employed to characterize longitudinal changes in the microbiome composition of patients with aggressive B-cell non-Hodgkin lymphoma undergoing chemoimmunotherapy. Diversity measures obtained from both methods were correlated and captured identical trends in microbial community structures, finding no difference in patients' pretreatment alpha or beta diversity compared to healthy controls and a significant and progressive loss of alpha diversity during chemoimmunotherapy. Our results highlight the potential of FCM-based microbiome profiling as a reliable and accessible diagnostic tool that can provide novel insights into cancer therapy-associated dysbiosis dynamics

Combination therapy with Olaratumab/doxorubicin in advanced or metastatic soft tissue sarcoma -a single-Centre experience

BACKGROUND: The antibody targeting platelet-derived growth factor receptor alpha (PDGFRA), olaratumab, was approved in 2016 for metastatic soft tissue sarcoma (STS) in combination with doxorubicin based on promising results of a phase Ib/II trial by the Food and Drug Administration (FDA). However, recently the phase III ANNOUNCE trial could not confirm the additional value of olaratumab in this context. METHODS: Here, in a retrospective analysis we share our single-centre experience with olaratumab/doxorubicin in STS by including n = 32 patients treated with olaratumab/doxorubicin between 2016 and 2019. RESULTS: Median progression-free survival (PFS) in the overall cohort was 3.1 months (range 0.6-16.2). A response [complete remission (CR), partial remission (PR) or stable disease (SD)] was seen in n = 11 (34%) cases, whereas n = 21 (66%) patients showed progressive disease (PD). In n = 9 patients surgery was performed subsequently in an individual therapeutic approach. Out of n = 5 patients receiving additional regional hyperthermia, n = 3 achieved PR or SD. CONCLUSIONS: This single-centre experience does also not support the promising phase Ib/II results for olaratumab/doxorubicin in STS. However, our findings do not preclude that olaratumab combination therapy could be valuable in a neoadjuvant setting. This warrants further exploration also taking into account the heterogeneous nature of STS

Impact of a specialised palliative care intervention in patients with advanced soft tissue sarcoma - a single-centre retrospective analysis

BACKGROUND: Soft tissue sarcomas (STS) account for less than 1% of all malignancies. Approximately 50% of the patients develop metastases with limited survival in the course of their disease. For those patients, palliative treatment aiming at symptom relief and improvement of quality of life is most important. However, data on symptom burden and palliative intervention are limited in STS patients. AIM: Our study evaluates the effectiveness of a palliative care intervention on symptom relief and quality of life in STS patients. DESIGN/SETTING: We retrospectively analysed 53 inpatient visits of 34 patients with advanced STS, admitted to our palliative care unit between 2012 and 2018. Symptom burden was measured with a standardised base assessment questionnaire at admission and discharge. RESULTS: Median disease duration before admission was 24 months, 85% of patients had metastases. The predominant indication for admission was pain, weakness and fatigue. Palliative care intervention led to a significant reduction of pain: median NRS for acute pain was reduced from 3 to 1 (p < 0.001), pain within the last 24 h from 5 to 2 (p < 0.001) and of the median MIDOS symptom score: 18 to 13 (p < 0.001). Also, the median stress level, according to the distress thermometer, was reduced significantly: 7.5 to 5 (p = 0.027). CONCLUSIONS: Our data underline that specialised palliative care intervention leads to significant symptom relief in patients with advanced STS. Further efforts should aim for an early integration of palliative care in these patients focusing primarily on the identification of subjects at high risk for severe symptomatic disease

TFE3 activation in a TSC1-altered malignant PEComa: challenging the dichotomy of the underlying pathogenic mechanisms

Perivascular epithelioid cell tumors (PEComas) form a family of rare mesenchymal neoplasms that typically display myomelanocytic differentiation. Upregulation of mTOR signaling due the inactivation of TSC1/2 (Tuberous Sclerosis 1 and 2) is believed to be a key oncogenic driver in this disease. Recently, a subgroup of PEComas harboring TFE3 (Transcription Factor E3) rearrangements and presenting with a distinctive morphology has been identified. TSC1/2 and TFE3 aberrations are deemed to be mutually exclusive in PEComa, with two different pathogenic mechanisms assumed to lead to tumorigenesis. Here, we challenge this dichotomy by presenting a case of a clinically aggressive TCS1-mutated PEComa displaying a TFE3-altered phenotype. FISH analysis was suggestive of a TFE3 inversion; however, RNA and whole genome sequencing was ultimately unable to identify a fusion involving the gene. However, a copy number increase of the chromosomal region encompassing TFE3 was detected and transcriptome analysis confirmed upregulation of TFE3, which was also seen at the protein level. Therefore, we believe that the TSC1/2-mTOR pathway and TFE3 overexpression can simultaneously contribute to tumorigenesis in PEComa. Our comprehensive genetic analyses add to the understanding of the complex pathogenic mechanisms underlying PEComa and harbor insights for clinical treatment options

4f mixing in ternary metallic cerium systems

The results of LIII-edge X-ray absorption, bremsstrahlung-isochromat spectroscopy, and valence-band photoemission measurements are reported for the series of compounds CeX2Si2 (with X=Fe, Co, Ni). In view of the known lattice-constant anomalies of these compounds, it is concluded that the Ce-4f electrons hybridize with ligand orbitals

Cell-to-cell variability in JAK2/STAT5 pathway components and cytoplasmic volumes defines survival threshold in erythroid progenitor cells.

Survival or apoptosis is a binary decision in individual cells. However, at the cell-population level, a graded increase in survival of colony-forming unit-erythroid (CFU-E) cells is observed upon stimulation with erythropoietin (Epo). To identify components of Janus kinase 2/signal transducer and activator of transcription 5 (JAK2/STAT5) signal transduction that contribute to the graded population response, we extended a cell-population-level model calibrated with experimental data to study the behavior in single cells. The single-cell model shows that the high cell-to-cell variability in nuclear phosphorylated STAT5 is caused by variability in the amount of Epo receptor (EpoR):JAK2 complexes and of SHP1, as well as the extent of nuclear import because of the large variance in the cytoplasmic volume of CFU-E cells. 24–118 pSTAT5 molecules in the nucleus for 120 min are sufficient to ensure cell survival. Thus, variability in membrane-associated processes is sufficient to convert a switch-like behavior at the single-cell level to a graded population-level response