[Primary Pulmonary Diffuse Large B-cell Lymphoma Mimics Advanced Lung Cancer:Report of a Case].

Primary pulmonary diffuse large B-cell lymphoma( DLBCL) is rare, accounting for 0.4% to 1.0% of all malignant lymphomas and 0.45% of all lung malignancies. We report a case of primary pulmonary DLBCL caused by methotrexate-associated lymphoproliferative disorder (MTX-LPD). A 73-year-old man was referred to our hospital due to a growing lung nodule. Transbronchoscopic biopsy did not confirm the diagnosis, but positron emission tomography-computed tomography (PET-CT) showed an accumulation of SUVmax 28.7 in the same area and SUVmax 40.5 in the contralateral mediastinum, suggesting an advanced primary lung cancer. A partial thoracoscopic left lower lobe resection was performed in our department. Histopathological examination revealed AE1/AE3 negative, CD20 and 79a positive, bcl-2 positive, and a diagnosis of primary lung DLBCL. MTX-LPD was suspected, and discontinuation of the drug resulted in subsequent shrinkage of the residual tumor. If the diagnosis cannot be made by transbronchoscopic biopsy of an expanding nodule shadow, aggressive surgical diagnosis should be considered.

Early evaluation of CAR-T cell therapy response in R/R DLBCL patients using 18F-FDG PET/CT.

OBJECTIVE: CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy provides a durable response in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). The role of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for early evaluation of response in patients with that immunotherapy was evaluated. SUBJECTS AND METHODS: Three separate 18F-FDG PET/CT examinations of 53 patients (29 males, 24 females; median 62 years old) with R/R DLBCL were conducted; before bridging therapy [time of decision (TD)], before CAR-T (tisagenlecleucel, n=37; lisocabtagenemaraleucel, n=16) infusion [time of CAR-T infusion (IT)], and one month (M1) after CAR-T infusion. Response was evaluated based on the Deauville 5-point scale and Lugano criteria. RESULTS: Among 21 patients (39.6%) with complete metabolic response (CMR) at IT-PET, 20 were able to continue CMR, while one showed progression at M1-PET. Among 32 patients (60.4%) with non-CMR at IT-PET, 12, 8, 4, and 8 showed CMR, partial metabolic response (PMR), (non-metabolic response (NMR), and progressive metabolic disease (PMD), respectively, at M1-PET as compared with IT-PET. Evaluations of M1-PET as compared with baseline TD-PET indicated 32, 7, 5, and 9 patients with CMR, PMR, NMR, and PMD, respectively. After a median 10.1 months, 26 patients showed progression and 13 had died from DLBCL. The 32 who achieved CMR showed significantly longer progression-free (P<0.0001) and overall survival (P<0.0001) periods as compared to the 21 non-CMR patients. CONCLUSION: Fluorine-18-FDG PET/CT findings obtained one month after CAR-T cell therapy showed accuracy for early response evaluation and prediction of progression in patients with R/R DLBCL.

[A case of primary central nervous system lymphoma of the sellar region presented with panhypopituitarism].

The patient is a 41-year-old woman. She presented with vomiting and lightheadedness, and blood tests showed a generalized decrease in pituitary hormones and hyperprolactinemia. A head MRI showed increased signal intensity lesions on FLAIR image in the pituitary stalk, corpus callosum, periventricular area of the fourth ventricle, and superior cerebellar peduncle. The lesions were homogeneously enhanced, and a brain biopsy confirmed the diagnosis of primary diffuse large B-cell lymphoma of the central nervous system, and chemotherapy was started. Although the suprasellar region is a rare site for primary central nervous system lymphoma (PCNSL), it should be diagnosed early by biopsy.

Contrast-Enhanced Ultrasonography in Diagnosing Intravascular Large B-Cell Lymphoma Infiltrating Liver Sinusoids.

BACKGROUND Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal large B-cell lymphoma characterized by the selective growth of lymphoma cells within vasculature. This presents a diagnostic challenge due to non-specific symptoms and lack of tumor formation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) provides useful information in diagnosing FDG-avid lymphoma, but is not specific to  IVLBCL. Contrast-enhanced ultrasonography (CEUS) is useful in evaluating focal liver lesions; however, its efficacy in diagnosing IVLBCL involving the liver remains unknown. CASE REPORT We report the case of an 83-year-old woman presenting with fever, pancytopenia, liver dysfunction, and elevated LD and soluble interleukin-2 receptor levels. PET-CT showed multiple uptake lesions in the liver. We performed CEUS with Sonazoid® to evaluate the mass-like lesions; however, no nodular lesions were observed in B mode images. Systemic enhancement was seen in the early phase but no defect was observed in the post-vascular phase. The latter finding suggested preserved Kupffer cells function, excluding tumor-forming lymphoma and liver metastases. Suspecting IVLBCL, we performed a bone marrow examination, which showed sinusoidal infiltration of large neoplastic cells positive for CD20. The patient's condition deteriorated rapidly and she died 2 days after the examination. Autopsy revealed diffuse infiltration of lymphoma cells into liver sinusoids with preserved Kupffer cells, leading to the diagnosis of IVLBCL. CONCLUSIONS Our case shows that CEUS can distinguish IVLBCL from mass-forming lymphoma based on the absence of a defect in the post-vascular phase in a patient with clinically and radiographically suspected lymphoma involving the liver. This can assist clinicians to select appropriate lesions for biopsy.

Conventional and novel [18F]FDG PET/CT features as predictors of CAR-T cell therapy outcome in large B-cell lymphoma.

Relapse and toxicity limit the effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL), yet biomarkers that predict outcomes and toxicity are lacking. We examined radiomic features extracted from pre-CAR-T 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) scans (n = 341) of 180 patients (121 male; median age, 66 years). Three conventional (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and 116 novel radiomic features were assessed, along with inflammatory markers, toxicities, and outcomes. At both pre-apheresis and pre-infusion time points, conventional PET features of disease correlated with elevated inflammatory markers. At pre-infusion, MTV was associated with grade ≥ 2 cytokine release syndrome (odds ratio [OR] for 100 mL increase: 1.08 [95% confidence interval (CI), 1.01-1.20], P = 0.031), and SUVmax was associated with failure to achieve complete response (CR) (OR 1.72 [95% CI, 1.24-2.43], P < 0.001). Higher pre-apheresis and pre-infusion MTV values were associated with shorter progression-free survival (PFS) (HR for 10-unit increase: 1.11 [95% CI, 1.05-1.17], P < 0.001; 1.04 [95% CI, 1.02-1.07], P < 0.001) and shorter overall survival (HR for 100-unit increase: 1.14 [95% CI, 1.07-1.21], P < 0.001; 1.04 [95% CI, 1.02-1.06], P < 0.001). A combined MTV and LDH measure stratified patients into high and low PFS risk groups. Multiple pre-infusion novel radiomic features were associated with CR. These quantitative conventional [18F]FDG PET/CT features obtained before CAR-T cell infusion, which were correlated with inflammation markers, may provide prognostic biomarkers for CAR-T therapy efficacy and toxicity. The use of conventional and novel radiomic features may thus help identify high-risk patients for earlier interventions.

Hemorrhagic Presentation in Primary Central Nervous System Lymphoma: A Case Study.

BACKGROUND Primary central nervous system diffuse large B-cell lymphoma (DLBCL) is an extremely aggressive brain disease that rarely affects immunocompetent non-elderly patients, particularly with hemorrhagic presentation. Brain magnetic resonance imaging (MRI) plays an important role in the diagnosis of this entity, which typically demonstrates restricted diffusion and a T2 hypointense appearance, suggesting hypercellularity. CASE REPORT A 44-year-old man came to the emergency department with a persistent and treatment-resistant bilateral frontal headache that had been bothering him for the past 3 weeks. Upon conducting a neurological assessment, the patient displayed temporal disorientation and incoherent speech, but without any observable motor deficits. A non-contrast enhanced brain computed tomography scan was carried out, revealing a hyperattenuating, space-occupying lesion and hemorrhage in the left hemisphere of the brain. Subsequently, brain MRI demonstrated hypointense signal on T2-weighted images, restricted diffusion, and homogeneous lesional contrast enhancement, suggesting a very cellular expansive lesion with hemorrhage. To establish a definitive diagnosis, a brain biopsy was undertaken, confirming the presence of DLBCL of the primary central nervous system (germinal center phenotype). CONCLUSIONS Hemorrhagic presentation of primary central nervous system DLBCL occurs very rarely, particularly in non-elderly immunocompetent patients. Brain MRI plays an important role in the diagnosis of this entity, which allows differentiation from high-grade glial or other lesions that present more frequently with hemorrhage. Therefore, it is crucial to suspect lymphoma before surgical intervention for appropriate patient management.

[The Value of Baseline PET/CT Imaging of Bone Marrow 18F-FDG Uptake Pattern in Predicting Prognosis of DLBCL].

OBJECTIVE: To investigate the prognostic value of bone marrow uptake pattern in 18F-deoxyglucose (18F-FDG) PET/CT imaging before diffuse large B-cell lymphoma (DLBCL) treatment. METHODS: The clinical data of 156 patients with DLBCL were retrospectively analyzed. All patients underwent bone marrow biopsy, bone marrow smear, flow cytometry and 18F-FDG PET/CT scan before treatment. Taking normal liver 18F-FDG uptake as the standard, the bone marrow uptake patterns of patients were divided into three types: focal increased bone marrow uptake (fPET+), diffusely increased bone marrow uptake (dPET+), and normal bone marrow uptake (nPET). Survival analysis was performed using the Kaplan-Meier method, log-rank test was used for comparison of differences between groups, and multivariate Cox regression analysis was used to identify risk factors associated with prognosis. RESULTS: Among the 156 patients, 17 cases were fPET+, 28 cases were dPET+, and 111 cases were nPET. Clinical diagnosis of bone marrow infiltration (BMI) was positive in 21 cases and negative in 135 cases. There were 62 cases of recurrence and progression, and 18 cases of death. Univariate analysis showed that Ann Arbor stage III/IV, B symptoms, NCCN-IPI score, lactate dehydrogenase (LDH), BMI+ and fPET+ were associated with progression-free survival (PFS) (all P < 0.05), while Ann Arbor stage III/IV, NCCN-IPI score, LDH, BMI+ and fPET+ were associated with overall survival (OS) (all P < 0.05). Multivariate analysis showed that Ann Arbor stage III/IV, LDH and fPET+ were independent predictors of PFS (all P < 0.05). There were no independent predictors of OS in multivariate analysis. CONCLUSION: The bone marrow uptake pattern of 18F-FDG imaging in DLBCL patients before treatment has a predictive value for DLBCL, while fPET+ is an independent risk factor for PFS.

[Intravascular Large B-cell Lymphoma Presenting with Lung Adenocarcinoma:
A Case Report and Literature Review].

Intravascular large B-cell lymphoma (IVLBCL) is an aggressive extranodal large B-cell lymphoma, cocurrence in the same organ with other malignancies is very rare, especially in the lung. Here, we report a rare case of lung adenocarcinoma with IVLBCL. The patient was admitted to the hospital due to diarrhea associated with fever and cough. A computed tomography (CT) scan of the chest showed an irregular patchy high-density shadow in the upper lobe of the right lung with ground-glass opacity at the margin. After admission, the patient was given anti-infection treatment, but still had intermittent low fever (up to 37.5 °C). The pathological diagnosis of percutaneous lung biopsy (PLB) was lepidic-predominant adenocarcinoma with local infiltration, which was proved to be invasive nonmucinous adenocarcinoma of the lung with IVLBCL after surgery. This paper analyzed the clinicopathological characteristics and reviewed the relevant literature to improve the knowledge of clinicians and pathologists and avoid missed diagnosis or misdiagnosis.
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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.

Gastrosplenic fistula due to splenic lymphoma: two case reports and review of the literature.

BACKGROUND: Gastrosplenic fistula is a rare and potentially fatal complication of various conditions. Lymphoma is the most common cause. It can occur spontaneously or after chemotherapy. Gastrosplenic fistula diagnosis can be confused with a splenic abscess because of the presence of air into the mass. The computed tomography identification of the fistulous tract is the key to a right diagnosis. Treatment modalities include surgical resection, chemotherapy, or a combination of both. CASE PRESENTATION: Here we report two patients with gastrosplenic fistula due to diffuse large B cell lymphoma. The first patient was a 54-year-old Caucasian woman with an enormous primary splenic diffuse large B cell lymphoma leading to the development of a spontaneous fistula in the stomach. The second patient was a 48-year-old Caucasian male patient with an enormous splenic diffuse large B cell lymphoma complicated by fistula after chemotherapy. Both patients died of septic shock several days after surgery. CONCLUSION: Gastrosplenic fistula is a rare complication with a poor-prognosis, for which surgery is currently the preferred treatment.

Characterization of primary small intestinal lymphoma: a retrospective study based on double balloon endoscopy.

BACKGROUND: The diagnosis of primary small intestinal lymphoma (PSIL) is difficult. This study aimed to evaluate the clinical, radiological and endoscopic characteristics of PSIL and provide clue for diagnosis. METHODS: A total of 30 patients diagnosed with PSIL who underwent double balloon endoscopy (DBE) in the First Affiliated Hospital of Zhejiang University were retrospectively analyzed. Clinical, radiological and endoscopic data were collected. Univariate analysis was used to determine significant indicators for differentiating three main subtypes of PSIL. Cox regression analysis was performed to assess the risk factors for survival. RESULTS: In this study, 10 patients were pathologically diagnosed as diffuse large B-cell lymphoma (DLBCL), 11 were indolent B-cell lymphoma (BCL) and 9 were T-cell lymphoma (TCL). Compared with DLBCL patients, the body mass index (BMI) of TCL patients was significantly lower (p = 0.004). Meanwhile, compared with patients with DLBCL, the patients with indolent BCL had lower levels of C-reactive protein, lactate dehydrogenase (LDH), fibrinogen and D-Dimer (p = 0.004, p = 0.004, p = 0.006, and p = 0.002, respectively), and lower proportion of thicker intestinal wall and aneurysmal dilation in CT scan (p = 0.003 and p = 0.020, respectively). In terms of ulcer morphology, patients with DLBCL had significantly higher proportion of deep ulcers than patients with indolent BCL (p = 0.020, respectively). Cox regression analysis showed that drink (p = 0.034), concomitant colonic ulcers (p = 0.034) and elevated LDH (p = 0.043) are risk factors for mortality in patients with PSIL. CONCLUSIONS: This study provides clinical characteristics of patients with PSIL. Thicker intestinal wall and aneurismal dilation detected on CT scan and deeper ulcer on DBE examination helps to establish a diagnosis of DLBCL.

The potential value of ultrasound in predicting local refractory/relapse events in primary thyroid lymphoma patients.

BACKGROUND: Primary thyroid lymphoma (PTL) is a rare malignant disorder, and ultrasound plays an important role in PTL diagnosis and follow-up surveillance. Prediction of refractory/relapse events in PTL patients is an essential issue, yet no ultrasonic PTL features have been discovered to be related to refractory/local relapse events. METHODS: From January 2008 to September 2022, newly diagnosed PTL patients in our center who underwent standard first-line treatment and received an ultrasound examination before treatment were enrolled. Data regarding patients' clinical and sonographic features, as well as their therapeutic responses were collected. Subjects with an ideal prognosis were compared to those with refractory/relapse events. RESULTS: In total, 37 PTL patients were analyzed, including 26 with diffuse large B-cell lymphoma, 2 with follicular lymphoma and 9 with mucosa-associated lymphoid tissue lymphoma. During the median follow-up of 25 months, 30 patients obtained a complete response, 4 were refractory patients, and 3 experienced local relapse. No significant difference was detected in the baseline clinical characteristics between patients with an ideal prognosis and those with refractory/local relapse events. In terms of sonographic features, however, an event-free survival (EFS) curve comparison revealed that patients with bilobar enlargement (defined as an anterior-posterior diameter > 2.5 cm on both sides of thyroid lobes) had a poorer EFS than those without (P < 0.0001), and patients with diffuse type had a poorer EFS than those with mixed/nodular types (P = 0.043). No significant difference was observed in EFS between patients with or without signs of suspicious cervical lymph node metastasis, rich blood signal distribution or symptoms of trachea compression. CONCLUSIONS: PTL patients with an anterior-posterior diameter > 2.5 cm for both thyroid lobes or PTL patients of the diffuse ultrasound type could be prone to refractory/local relapse events.

Detection performance and prognostic value of initial bone marrow involvement in diffuse large B-cell lymphoma: a single centre 18F-FDG PET/CT and bone marrow biopsy evaluation study.

BACKGROUND: Detection of bone marrow involvement (BMI) in diffuse large B-cell lymphoma (DLBCL) typically relies on invasive bone marrow biopsy (BMB) that faces procedure limitations, while 18F-FDG PET/CT imaging offers a noninvasive alternative. The present study assesses the performance of 18F-FDG PET/CT in DLBCL BMI detection, its agreement with BMB, and the impact of BMI on survival outcomes. PATIENTS AND METHODS: This retrospective study analyzes baseline 18F-FDG PET/CT and BMB findings in145 stage II-IV DLBCL patients, evaluating both performance of the two diagnostic procedures and the impact of BMI on survival. RESULTS: DLBCL BMI was detected in 38 patients (26.2%) using PET/CT and in 18 patients (12.4%) using BMB. Concordant results were seen in 79.3% of patients, with 20.7% showing discordant results. Combining PET/CT and BMB data, we identified 29.7% of patients with BMI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT for detecting DLBCL BMI were 88.4%, 100%, 100%, 95.3%, and 96.5%, respectively, while BMB showed lower sensitivity (41.9%) and NPV (46.8%). The median overall survival (OS) was not reached in any gender subgroup, with 5-year OS rates of 82% (total), 84% (female), and 80% (male) (p = 0.461), while different International Prognostic Index (IPI) groups exhibited varied 5-year OS rates: 94% for low risk (LR), 91% for low-intermediate risk (LIR), 84% for high-intermediate risk (HIR), and 65% for high risk (HR) (p = 0.0027). Bone marrow involvement did not impact OS significantly (p = 0.979). CONCLUSIONS: 18F-FDG PET/CT demonstrated superior diagnostic accuracy compared to BMB. While other studies reported poorer overall and BMI 5-year OS in DLBCL, our findings demonstrated favourable survival data.

Implications of Sarcopenia and Glucometabolism Parameters of Muscle Derived From Baseline and End-of-Treatment 18F-FDG PET/CT in Diffuse Large B-Cell Lymphoma.

OBJECTIVE: We previously found that the incidence of sarcopenia increased with declining glucose metabolism of muscle in patients with treatment-naïve diffuse large B-cell lymphoma (DLBCL). This study aimed to investigate the relationship between sarcopenia and muscle glucometabolism using 18F-FDG PET/CT at baseline and end-of-treatment, analyze the changes in these parameters through treatment, and assess their prognostic values. MATERIALS AND METHODS: The records of 103 patients with DLBCL (median 54 years [range, 21-76]; male:female, 50:53) were retrospectively reviewed. Skeletal muscle area at the third lumbar vertebral (L3) level was measured, and skeletal muscle index (SMI) was calculated to determine sarcopenia, defined as SMI < 44.77 cm²/m² and < 32.50 cm²/m² for male and female, respectively. Glucometabolic parameters of the psoas major muscle, including maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean), were measured at L3 as well. Their changes across treatment were also calculated as ΔSMI, ΔSUVmax, and ΔSUVmean; Δbody mass index was also calculated. Associations between SMI and the metabolic parameters were analyzed, and their associations with progression-free survival (PFS) and overall survival (OS) were identified. RESULTS: The incidence of sarcopenia was 29.1% and 36.9% before and after treatment, respectively. SMI (P = 0.004) was lower, and sarcopenia was more frequent (P = 0.011) at end-of-treatment than at baseline. The SUVmax and SUVmean of muscle were lower (P < 0.001) in sarcopenia than in non-sarcopenia at both baseline and end-of-treatment. ΔSMI was positively correlated with ΔSUVmax of muscle (P = 0.022). Multivariable Cox regression analysis showed that sarcopenia at end-of-treatment was independently negatively associated with PFS (adjusted hazard ratio [95% confidence interval], 2.469 [1.022-5.965]), while sarcopenia at baseline was independently negatively associated with OS (5.051 [1.453-17.562]). CONCLUSION: Sarcopenic patients had lower muscle glucometabolism, and the muscular and metabolic changes across treatment were positively correlated. Sarcopenia at baseline and end-of-treatment was negatively associated with the prognosis of DLBCL.

Prognostic value of the peripheral blood lymphocyte/monocyte ratio combined with 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma.

OBJECTIVE: To explore the prognostic value of the peripheral blood lymphocyte/monocyte ratio (LMR) combined with 18F-FDG PET/CT for diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 203 patients with primary DLBCL who were hospitalized to the First People's Hospital of Lianyungang between January 2017 and December 2022 were retrospectively analyzed. Before and after three courses of treatment, PET/CT was performed on forty DLBCL patients. The subject operating characteristic (ROC) curve has been employed to determine the most effective LMR cutoff points. According to the criteria for assessing the efficacy of Lugano lymphoma, the PET/CT findings after 3 courses of treatment were specified as complete remission (CR), partial remission (PR), stable disease (SD) and disease progression (PD). The CR group, PR+SD group, and PD group were the three groups created from the four outcomes. Results were analyzed using the Cox proportional risk model, the Kaplan-Meier method (K-M), and the log-rank test. RESULTS: An optimal cutoff point of 3.00 for the LMR in 203 patients was determined by the SPSS 26 software ROC curve. When LMR≥3.00, the 1-year, 3-year, and 5-year OS (Overall Survival) rates are 98%, 88%, and 64% respectively, and the PFS (Progression-free Survival) rates are 90%, 75%, and 56% respectively. When LMR <3.00, the 1-year, 3-year, and 5-year OS rates are 96%, 72%, and 28% respectively, and the PFS rates are 83%, 60%, and 28% respectively. A lower LMR was substantially related with shorter OS, and PFS, according to a K-M survival analysis (P<0.005). LMR<3.00 was an independent predictor of OS, based on a multifactorial Cox analysis (P=0.037). K-M survival analysis of the 18F-FDG PET/CT results of 40 patients revealed that both OS and PFS were statistically significant (P<0.001). Patients were separated into 3 groups combining LMR and 18F-FDG PET/CT: PET/CT CR patients with LMR≥3.00, PET/CT PD patients with LMR<3.00, and others. The Kaplan-Meier analysis revealed that there were significant differences in OS and PFS for each of the three groups (P<0.001). ROC curves showed that the area under the curve (AUC) of the combined testing of the two was 0.735, and the combined testing of the two was better compared to testing alone (PET/CT AUC=0.535, LMR AUC=0.567). This indicates that combining both PET/CT and LMR is a favorable prediction for DLBCL. CONCLUSION: A decreased LMR at initial diagnosis suggests an unfavorable prognosis for DLBCL patients; For patients with DLBCL, combining 18F-FDG PET/CT and the LMR has a better predictive value.

HoLy-Net: Segmentation of histological images of diffuse large B-cell lymphoma.

Over the last years, there has been large progress in automated segmentation and classification methods in histological whole slide images (WSIs) stained with hematoxylin and eosin (H&E). Current state-of-the-art (SOTA) techniques are based on diverse datasets of H&E-stained WSIs of different types of predominantly solid cancer. However, there is a scarcity of methods and datasets enabling segmentation of tumors of the lymphatic system (lymphomas). Here, we propose a solution for segmentation of diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin's lymphoma. Our method applies to both H&E-stained slides and to a broad range of markers stained with immunohistochemistry (IHC). While IHC staining is an important tool in cancer diagnosis and treatment decisions, there are few automated segmentation and classification methods for IHC-stained WSIs. To address the challenges of nuclei segmentation in H&E- and IHC-stained DLBCL images, we propose HoLy-Net - a HoVer-Net-based deep learning model for lymphoma segmentation. We train two different models, one for segmenting H&E- and one for IHC-stained images and compare the test results with the SOTA methods as well as with the original version of HoVer-Net. Subsequently, we segment patient WSIs and perform single cell-level analysis of different cell types to identify patient-specific tumor characteristics such as high level of immune infiltration. Our method outperforms general-purpose segmentation methods for H&E staining in lymphoma WSIs (with an F1 score of 0.899) and is also a unique automated method for IHC slide segmentation (with an F1 score of 0.913). With our solution, we provide a new dataset we denote LyNSeC (lymphoma nuclear segmentation and classification) containing 73,931 annotated cell nuclei from H&E and 87,316 from IHC slides. Our method and dataset open up new avenues for quantitative, large-scale studies of morphology and microenvironment of lymphomas overlooked by the current automated segmentation methods.

Comparison of Lugano Criteria Versus RECIL and PERCIST as Prognostic Factors in Diffuse Large B-Cell Lymphoma.

OBJECTIVE: This study aimed to compare the criteria of the Lugano, RECIL, and PERCIST for prognosis in patients with diffuse large B-cell lymphoma. PATIENTS AND METHODS: We retrospectively evaluated 335 patients with diffuse large B-cell lymphoma. All patients underwent baseline 18 F-FDG PET/CT. Among them, 252 and 213 patients underwent interim PET/CT (I-PET/CT) and end-of-treatment PET/CT (EoT-PET/CT), respectively. Scans were interpreted by 2 nuclear medicine physicians using Lugano, RECIL, and PERCIST. RECIL and PERCIST were compared with Lugano for predicting progression-free survival (PFS) and overall survival (OS). RESULTS: All 3 response criteria could be used to predict PFS and OS. In I-PET/CT, the concordance index of Lugano in predicting PFS and OS was higher than that of RECIL (both P = 0.043) or PERCIST ( P = 0.008 and P = 0.034, respectively). In EoT-PET/CT, the concordance index of Lugano for predicting PFS and OS was similar to RECIL and not significantly different from PERCIST ( P = 0.597 and P = 0.231, respectively). CONCLUSIONS: For I-PET/CT, using the Lugano criteria is more accurate than RECIL or PERCIST in predicting PFS and OS. However, for EoT-PET/CT, the PERCIST criteria are minimally better.

Tumor Location Relative to the Spleen Is a Prognostic Factor in Lymphoma Patients: A Demonstration from the REMARC Trial.

Baseline [18F]FDG PET/CT radiomic features can improve the survival prediction in patients with diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to investigate whether characterizing tumor locations relative to the spleen location in baseline [18F]FDG PET/CT images predicts survival in patients with DLBCL and improves the predictive value of total metabolic tumor volume (TMTV) and age-adjusted international prognostic index (IPI). Methods: This retrospective study included 301 DLBCL patients from the REMARC (NCT01122472) cohort. Physicians delineated the tumor regions, whereas the spleen was automatically segmented using an open-access artificial intelligence algorithm. We systematically measured the distance between the centroid of the spleen and all other lesions, defining the SD of these distances as the lesion spread (SpreadSpleen). We calculated the maximum distance between the spleen and another lesion (Dspleen) for each patient and normalized it with the body surface area, resulting in standardized Dspleen (sDspleen). The predictive value of each PET/CT feature for progression-free survival (PFS) and overall survival (OS) was evaluated through univariate and multivariate time-dependent Cox models and Kaplan-Meier analysis. Results: In total, 282 patients (mean age, 68.33 ± 5.41 y; 164 men) were evaluated. The artificial intelligence algorithm successfully segmented the spleen in 96% of the patients. SpreadSpleen, Dspleen, and sDspleen were correlated neither with TMTV (Pearson ρ < 0.23) nor with IPI (Pearson ρ < 0.15). When median values were used as the cutoff, SpreadSpleen, Dspleen, and sDspleen all significantly classified patients into 2 risk groups for PFS and OS (P < 0.001). They complemented TMTV and IPI to classify the patients into 3 risk groups for PFS and OS (P < 0.001). Integrating SpreadSpleen, Dspleen, or sDspleen into a Cox model on the basis of TMTV, IPI, and TMTV combined with IPI significantly improved the concordance index for PFS and OS (P < 0.05). Conclusion: Baseline PET/CT features that characterize tumor spread and dissemination relative to the spleen strongly predicted survival in patients with DLBCL. Integrating these features with TMTV and IPI further improved survival prediction.