Michael Soussan

Background and Clinical Significance: Plasmablastic lymphoma (PBL) is a rare and highly aggressive B-cell neoplasm most often associated with immunodeficiency. Transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) into PBL is exceptionally uncommon, particularly in immunocompetent individuals. This paper describes a rare synchronous SLL-to-PBL transformation and summarizes current knowledge on synchronous and metachronous cases reported in the literature. Case Presentation A midle-aged immunocompetent patent presented with generalized lymphadenopathy and lumbar pain. Concurrent biopsies of an axillary lymph node and a retroperitoneal mass were obtained. Diagnostic evaluation included immunohistochemistry; fluorescent in situ hybridization (FISH); PCR-based assessment of IGH, IGK, and IGL loci; and next-generation sequencing (NGS) of IGHV to assess clonal relatedness. The patient was treated with six cycles of Dara-CHOP, followed by autologous stem cell transplantation and maintenance therapy with daratumumab and ibrutinib. The axillary node showed SLL (CD20+, CD5+, CD23+), while the retroperitoneal mass demonstrated classic features of PBL (CD138+, MUM1+, MYC+, Ki-67 ~100%, CD20−). FISH detected MYC rearrangement in the PBL component. PCR and NGS confirmed identical IGHV1-69 rearrangements, establishing clonal relatedness and Richter transformation. A review of published cases shows that both synchronous and metachronous CLL/SLL-to-PBL transformations are exceedingly rare. The patient achieved partial metabolic remission after treatment and remains in sustained metabolic response 24 months after diagnosis. Conclusions: This case highlights a rare example of synchronous CLL/SLL-to-PBL transformation in an immunocompetent patient. Integration of detailed molecular diagnostics enabled early recognition and guided a personalized treatment approach incorporating CD38-targeted therapy and BTK inhibition, resulting in an excellent long-term clinical outcome.

Background: Plasmablastic lymphoma (PBL) is a rare and highly aggressive B-cell neoplasm most often associated with immunodeficiency. Transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) into PBL is exceptionally uncommon, particularly in immunocompetent individuals. This paper describes a rare synchronous SLL-to-PBL transformation and summarizes current knowledge on synchronous and metachronous cases reported in the literature. Methods: A 46-year-old immunocompetent woman presented with generalized lymphadenopathy and lumbar pain. Concurrent biopsies of an axillary lymph node and a retroperitoneal mass were obtained. Diagnostic evaluation included immunohistochemistry, fluorescent in situ hybridization (FISH), PCR-based assessment of IGH, IGK, and IGL loci, and next-generation sequencing (NGS) of IGHV to assess clonal relatedness. The patient was treated with six cycles of Dara-CHOP, followed by autologous stem cell transplantation and maintenance therapy with daratumumab and ibrutinib. Results: The axillary node showed SLL (CD20+, CD5+, CD23+), while the retroperitoneal mass demonstrated classic features of PBL (CD138+, MUM1+, MYC+, Ki-67 ~100%, CD20–). FISH detected MYC rearrangement in the PBL component. PCR and NGS confirmed identical IGHV1-69 rearrangements, establishing clonal relatedness and Richter transformation. Review of published cases shows that both synchronous and metachronous CLL/SLL-to-PBL transformations are exceedingly rare. The patient achieved partial metabolic remission after treatment and remains in sustained metabolic response 24 months after diagnosis. Conclusions: This case highlights a rare example of synchronous CLL/SLL-to-PBL transformation in an immunocompetent patient. Integration of detailed molecular diagnostics enabled early recognition and guided a personalized treatment approach incorporating CD38-targeted therapy and BTK inhibition, resulting in an excellent long-term clinical outcome.

Background: We aimed to evaluate the prognostic value of imaging biomarkers on 18F-FDG PET/CT in extensive-stage small-cell lung cancer (ES-SCLC) patients undergoing first-line chemo-immunotherapy. Methods: In this multicenter and retrospective study, we considered two cohorts, depending on the type of first-line therapy: chemo-immunotherapy (CIT) versus chemotherapy alone (CT). All patients underwent baseline 18-FDG PET/CT before therapy between June 2016 and September 2021. We evaluated clinical, biological, and PET parameters, and used cutoffs from previously published studies or predictiveness curves to assess the association with progression-free survival (PFS) or overall survival (OS) with Cox prediction models. Results: Sixty-eight patients were included (CIT: CT) (36: 32 patients). The median PFS was 5.9:6.5 months, while the median OS was 12.1:9.8 months. dNLR (the derived neutrophils/(leucocytes-neutrophils) ratio) was an independent predictor of short PFS and OS in the two cohorts (p < 0.05). High total metabolic tumor volume (TMTV^high if > 241 cm³) correlated with outcomes, but only in the CIT cohort (PFS for TMTV^high in multivariable analysis: HR 2.5; 95%CI 1.1–5.9). Conclusion: Baseline 18F-FDG PET/CT using TMTV could help to predict worse outcomes for ES-SCLC patients undergoing first-line CIT. This suggests that baseline TMTV may be used to identify patients that are unlikely to benefit from CIT.

VEXAS (vacuoles, E1 enzyme, X-LINKED, autoinflammatory, somatic) syndrome is a complex inflammatory disease associated with somatic mutations of the ubiquitin-like modifier activating enzyme 1 (UBA1) gene. A 75-year-old man with a medical history of thrombophlebitis, leukocytoclastic vasculitis, chronic inflammatory arthralgia, elevated inflammatory markers, and anemia was diagnosed with VEXAS syndrome. ¹⁸F-FDG PET/CT showed thoracic aortitis, a rare involvement during VEXAS syndrome. Corticosteroid therapy monitored with ¹⁸F-FDG PET/CT led to a complete metabolic response.

Background: Epicardial adipose tissue (EAT) is considered a novel diagnostic marker for cardiometabolic disease. This study aimed to evaluate whether EAT volume was associated with stress-induced myocardial ischemia in asymptomatic people living with diabetes—independently of confounding factors—and whether it could predict this condition. Methods: We included asymptomatic patients with diabetes and no coronary history, who had undergone both a stress a myocardial scintigraphy to diagnose myocardial ischemia, and a computed tomography to measure their coronary artery calcium (CAC) score. EAT volume was retrospectively measured from computed tomography imaging. Determinants of EAT volume and asymptomatic myocardial ischemia were evaluated. Results: The study population comprised 274 individuals, including 153 men. Mean (± standard deviation) age was 62 ± 9 years, and 243, 23 and 8 had type 2, type 1, or another type of diabetes, respectively. Mean body mass index was 30 ± 6 kg/m², and mean EAT volume 96 ± 36 cm³. Myocardial ischemia was detected in 32 patients (11.7%). EAT volume was positively correlated with age, body mass index and triglyceridemia, but negatively correlated with HbA1c, HDL- and LDL-cholesterol levels. Furthermore, EAT volume was lower in people with retinopathy, but higher in men, in current smokers, in patients with nephropathy, those with a CAC score > 100 Agatston units, and finally in individuals with myocardial ischemia (110 ± 37 cm³ vs 94 ± 37 cm³ in those without myocardial ischemia, p < 0.05). The association between EAT volume and myocardial ischemia remained significant after adjustment for gender, diabetes duration, peripheral macrovascular disease and CAC score. We also found that area under the ROC curve analysis showed that EAT volume (AROC: 0.771 [95% confidence interval 0.683–0.858]) did not provide improved discrimination of myocardial ischemia over the following classic factors: gender, diabetes duration, peripheral macrovascular disease, retinopathy, nephropathy, smoking, atherogenic dyslipidemia, and CAC score (AROC 0.773 [0.683–0.862]). Conclusions: EAT may play a role in coronary atherosclerosis and coronary circulation in patients with diabetes. However, considering EAT volume is not a better marker for discriminating the risk of asymptomatic myocardial ischemia than classic clinical data.

Background: The SwiftScan solution (General Electric Healthcare) combines a new low-energy high-resolution sensitivity collimator and a tomographic step-and-shoot continuous (SSC) mode acquisition. The purpose of this study is to determine whether SSC mode can be used in clinical practice with shorter examination times, while preserving image quality and ensuring accurate semi-quantification. Twenty bone scan and 10 lung scan studies were randomly selected over a period of 2 months. Three sets of image datasets were produced: step-and-shoot (SS) acquisition, simulated 25% count reduction using the Poisson resampling method (SimSS), and SimSS continuous acquisition (SimSSC), where SimSS was summed with counts acquired during detector head rotation. Visual assessment (5-point Likert scale, 2 readers) and semi-quantitative evaluation (50 focal uptake from 10 bone studies), assessed by SUV_mean, coefficient of variation (COV), and contrast-to-noise ratio (CNR), were performed using t test and Bland-Altman analysis. Results: Intra-reader agreement was substantial for reader 1 (k = 0.71) and for reader 2 (k = 0.61). Inter-reader agreement was substantial for SS set (k = 0.93) and moderate for SimSSC (k = 0.52). Bland-Altman analysis showed a good interchangeability of SS and SimSSC SUV values. The mean CNR between SS and SimSSC was not significantly different: 42.9 ± 43.7 [23.7–62.1] vs. 43.1 ± 46 [22.9–63.3] (p = 0.46), respectively. COV values, assessing noise level, did not deviate significantly between SS and SimSSC: 0.20 ± 0.08 [0.18–0.23] vs. 0.21 ± 0.08, [0.18–0.23] (p = 0.15), respectively, whereas a significant difference was demonstrated between SS and SimSS: 0.20 ± 0.08 [0.18–0.23] vs. 0.23 ± 0.09 [0.20–0.25] (p < 0.0001), respectively. Conclusions: SSC mode acquisition decreases examination time by approximately 25% in bone and lung SPECT/CT studies compared to SS mode (~ 2 min per single-bed SPECT), without compromising image quality and signal quantification. This SPECT sensitivity improvement also offers the prospect of more comfortable exams, with less motion artifacts, especially in painful or dyspneic patients.

Background: We aimed to assess the clinical utility of a previously published score combining the total metabolic tumor volume (TMTV) on baseline FDG-PET/CT and pretreatment derived from the neutrophils to lymphocytes ratio (dNLR) for prognostication in NSCLC patients undergoing first-line immunotherapy (IT). Methods: In this multicenter retrospective study, 63 advanced NSCLC patients with a PD-L1 tumor proportion score (TPS) ≥50%, who underwent FDG-PET/CT before first-line IT, treated from January 2017 to September 2019, were enrolled. Associations between this score and the progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and overall response rate (ORR) were evaluated. Results: The median (m) PFS and mOS were 7.7 (95% CI 4.9–10.6) and 12.1 (8.6–15.6) months, respectively, and DCR and ORR were 65% and 58%, respectively. mOS was 17.9 months (14.6 not reached) for the good group versus 13.8 (95%CI 8.4–18.9) and 6.6 (CI 2.0–11.2) months for the intermediate and poor groups, respectively. mPFS was 15.1 (95%CI 12.1–20.0) months for the good group versus 5.2 (1.9–8.5) and 1.9 (95%CI 1.3–2.5) months for the intermediate and poor groups, respectively. The poor prognosis group was associated with DCR and ORR (p < 0.05). Conclusions: The metabolic score combining TMTV on the baseline FDG-PET/CT scan and pretreatment dNLR was associated with the survival and response in a cohort of advanced NSCLC patients with ≥50% PD-L1 receiving frontline IT.

BACKGROUND: Sentinel node and occult lesion localization (SNOLL) calls for a combination of two specific procedures: intraoperative detection of sentinel lymph node (SLN) and radio-guided occult lesion localization (ROLL). The safety and benefits of radio-guided localization in the surgical treatment of non-palpable breast cancer have been confirmed. The aim of this study was to evaluate the potential role for an intra-operative handheld tumor resection gamma camera (TReCam) in SNOLL procedures. METHODS: Fifteen patients were enrolled. The SNOLL procedure was performed in all patients with conventional lymphoscintigraphy (LS). TReCam was used to obtain nuclear imaging in the operating theater. Concordance between LS and TReCam images, duration of use and assessment of difficulties in data acquisition with TReCam were reported. RESULTS: Concordance for tumor localization between single-detector gamma probe and TReCam was excellent (15/15). The number of radioactive SLNs visualized between LS and TReCam was equivalent in 53.3% of cases (8/15). TReCam was considered to be very easy-to-use (12/15) or easy-to-use (3/15). Average duration of acquisition with TReCam was 4 minutes and 45 seconds for the SLN procedure, and 2 minutes and 10 seconds for lumpectomy. CONCLUSIONS: This study suggests that TReCam is easy-to-use and does not increase operative time. Its exact role in radio-guided surgery needs to be clearly defined in a larger study. However, its usefulness and benefits in radio-guided breast surgery seem to be promising.