Different extramedullary disease shown in chemokine receptor 4 targeted PET/CT with [ 68 Ga]Ga-pentixafor in patients with Waldenström macroglobulinemia and smoldering disease.

INTRODUCTION: It is important to distinguish Waldenström macroglobulinemia from smoldering Waldenström macroglobulinemia (sWM), because only patients with Waldenström macroglobulinemia require treatment, however the distinction can be clinically complex. The aim of this study is to investigate whether [ 68 Ga]Ga-pentixafor PET/CT shows different characteristics in sWM and Waldenström macroglobulinemia patients and therefore can help to differentiate Waldenström macroglobulinemia and sWM. RESULTS: Thirty-seven patients with newly diagnosed Waldenström macroglobulinemia and 11 sWM patients were analyzed [35 men and 13 women; 64.3 ±â€…10.7 (range, 29-87) years old]. The SUV max of bone marrow disease, lymph nodes, and other extramedullary diseases on [ 68 Ga]Ga-pentixafor were significantly higher than those on 2-[ 18 F]FDG PET/CT ( P  < 0.05). On [ 68 Ga]Ga-pentixafor PET/CT, patients with Waldenström macroglobulinemia had more lymph node regions involved, significantly higher incidence of involvement in more than three lymph node regions, larger nodal disease, and higher incidence of other extramedullary disease when compared with sWM patients ( P  < 0.05). Waldenström macroglobulinemia patients showed significantly higher total lesions uptake, total lesion volume, and SUV max of extramedullary disease than sWM patients did ( P  < 0.05). None of the visual or semiquantitative indexes in 2-[ 18 F]FDG PET/CT showed significant difference between Waldenström macroglobulinemia and sWM patients. CONCLUSION: [ 68 Ga]Ga-pentixafor PET/CT had better diagnostic performance than 2-[ 18 F]FDG PET/CT in Waldenström macroglobulinemia. Patients with Waldenström macroglobulinemia presented with more extensive extramedullary disease shown in [ 68 Ga]Ga-pentixafor PET/CT than sWM patients did.

18 F-FDG PET/CT Findings in Waldenström Macroglobulinemia With Mesentery Involvement.

ABSTRACT: A 74-year-old man presented to the hospital complaining of weight loss, increasing fatigue, and blurred vision. The abdominal ultrasonography initially revealed a massive lesion in the mesentery, which was later confirmed by a contrast-enhanced CT scan. The 18 F-FDG PET/CT scan showed a single, solitary hypermetabolic mass. The patient was finally diagnosed with Waldenström macroglobulinemia with mesentery involvement by the histopathological examination.

Baseline 18 F-FDG PET/CT May Portend the Prognosis of Patients With Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma After First-Line Treatment.

PURPOSE: The outcome of patients with Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) is variable. We aim to study if baseline 18 F-FDG PET/CT has some prognostic significance in WM/LPL. METHODS: Thirty-three patients with newly diagnosed WM/LPL who underwent baseline 18 F-FDG PET/CT and received active treatment thereafter were recruited in this retrospective study. Semiquantitative indices of baseline 18 F-FDG PET/CT were measured as total lesion glycolysis (TLG), metabolic tumor volume (MTV), and SUV max . The patients were followed up for at least 3 years or until reaching the endpoint, which were defined as progression-free survival (PFS) and the time to next treatment (TTNT). RESULTS: The overall response rate of the first-line treatment in the recruited patients was 84.8% (28/33). The 3-year PFS and overall survival rates were 56.3% and 89.3%, respectively. Patients with PFS <36 months and TTNT <36 months showed TLG and MTV significantly higher than those with PFS ≥36 months and TTNT ≥36 months ( P < 0.05). SUV max in patients with PFS <36 months was significantly higher than those with PFS ≥36 months ( P = 0.033). Receiver operating characteristic analysis demonstrated that cutoff values of TLG >291.28 SUVbw * mL, MTV >108.78 mL, and SUV max >3.16 were optimal for predicting PFS <36 months. Kaplan-Meier analysis showed that TLG >291.28 SUVbw * mL and MTV >108.78 mL were predictive for shorter PFS ( P = 0.003) and TTNT ( P = 0.002). In multivariate analysis, TLG >291.28 SUVbw * mL and MTV >108.78 mL were independent predictors for shorter PFS (hazard ratio, 3.06; 95% confidence interval, 1.09-8.57; P = 0.033) and TTNT (hazard ratio, 10.01; 95% confidence interval, 2.56-39.22; P = 0.001). CONCLUSIONS: The metabolic indices of TLG and MTV in baseline 18 F-FDG PET/CT were independent prognostic factors to predict PFS and TTNT in patients with WM/LPL.

[Recurrent Bing-Neel syndrome with mixed intracranial involvement. A diagnostic challenge]. / Síndrome de Bing-Neel con afectación intracraneal mixta recidivante. Un reto diagnóstico.

TITLE: Síndrome de Bing-Neel con afectación intracraneal mixta recidivante. Un reto diagnóstico.

Chemokine Receptor 4-Targeted 68Ga-Pentixafor PET/CT in Response Assessment of Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma: Comparison to 18F-FDG PET/CT.

PURPOSE: 68Ga-pentixafor PET/CT was reported to have a high sensitivity in detecting tumor involvement of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) in our previous study. We aimed to further investigate its value in response assessment in WM/LPL. PATIENTS AND METHODS: Fifteen patients with WM/LPL were recruited in a prospective cohort study and underwent both 68Ga-pentixafor and 18F-FDG PET/CT at baseline and posttreatment. PET/CT-based responses were analyzed with visual assessments and compared with clinical response. RESULTS: At baseline, all of the 15 patients had a positive 68Ga-pentixafor PET/CT scan, whereas 18F-FDG PET/CT was positive in 11/15 patients. After chemotherapy, the overall response rate was 86.7% (13/15), and 68Ga-pentixafor PET/CT showed different degree of tumor response from baseline in these patients. In the 2 patients with progressive disease, 68Ga-pentixafor PET/CT detected new lesions or remarkable increase of 68Ga-pentixafor uptake in tumor involvements. However, 18F-FDG PET/CT failed to detect the improvement of disease in 6/13 patients and missed disease progression in 1 of the 2 patients. CONCLUSIONS: 68Ga-pentixafor PET/CT outperformed 18F-FDG PET/CT in response assessment of WM/LPL.

Clinical Relevance of the High Prevalence of MYD88 L265P Mutated Vitreoretinal Lymphoma Identified by Droplet Digital Polymerase Chain Reaction.

Purpose: To investigate the frequency and clinical relevance of missense mutation at position 265 changing leucine to proline in the myeloid differentiation factor 88 gene (MYD88 L265P) in the vitreous of Chinese patients with vitreoretinal lymphoma (VRL) using droplet digital polymerase chain reaction (ddPCR).Methods: Vitreous fluid (VF) from 29 eyes of 20 VRL patients at the North Huashan Hospital were included. MYD88 L265P analysis of VF was performed using ddPCR. Associations between clinicopathologic characteristics and MYD88 mutation were analyzed using t-test or Fisher's exact test.Results: MYD88 L265P mutations were detected in 22 of 29 samples from 14 patients with diffuse large B-cell lymphomas and one patient with lymphoplasmacytoid lymphoma. However, no significant associations were found between MYD88 L265P mutation status and age, sex, lymphoma subtype or location of the primary lesion.Conclusion: The high prevalence of MYD88 L265P identified by ddPCR suggests that this method of evaluating the frequency of MYD88 L265P is a promising tool for accurate diagnosis of VRL.

Detection of Residual Tumor With 68Ga-Pentixafor PET/CT in a Patient With Waldenström Macroglobulinemia and Concurrent John Cunningham Virus-Related Progressive Multifocal Leukoencephalopathy.

A 75-year-old man diagnosed with Waldenström macroglobulinemia (WM) complained of neurological symptoms. Baseline F-FDG PET/CT showed diffusely increased radioactivity in the bone marrow and decreased FDG uptake in the right cerebellum. After rituximab-containing immunochemotherapy, the patient had clinically partial response of WM, but the cerebellar lesion was enlarged. Repeated F-FDG PET/CT was similar to the baseline. Ga-pentixafor PET/CT detected residual tumor of WM in occipital bone and cervical lymph nodes, but there was no uptake in the cerebellar lesion. Finally, John Cunningham virus-related progressive multifocal leukoencephalopathy was confirmed.

Spectral-domain optical coherence tomography of retinal vessels in Waldenström's macroglobulinemia.

PURPOSE: To image retinal blood vessels in patients with Waldenström's macroglobulinemia using optical coherence tomography (OCT). METHODS: Retrospective case series examining fundus photographs and OCT scans of 16 eyes in eight patients with Waldenström's macroglobulinemia. Analyses included intravascular OCT reflectivity profiles and vessel diameters, and their relation to total immunoglobulin M (IgM) levels. RESULTS: In six out of eight patients, cross-sectional OCT scans of larger retinal vessels (diameter > 100 µm) showed normal intravascular reflectivity and retrovascular shadowing. In two patients with the highest total IgM > 60 g/l, altered intravascular reflectivity, distinct anterior and posterior vessel wall reflexes, and retrovascular hyposhadowing were seen. Normalization of the OCT reflectivity in these patients occurred after reduction of total IgM to < 17 g/l and was accompanied by decreasing venous tortuosity and disappearance of retinal haemorrhages and cotton wool spots. CONCLUSION: This study found that Waldenström's macroglobulinemia and total IgM > 60 g/l were associated with abnormal intravascular reflectivity and retrovascular shadowing on OCT. Awareness of these signs of hyperviscosity could potentially enable earlier detection of critical conditions in patients with Waldenström's macroglobulinemia and improve the assessment of severity and treatment effect.

CXCR4-targeted PET imaging using 64Cu-AMD3100 for detection of Waldenström Macroglobulinemia.

Objective:  Waldenström Macroglobulinemia (WM) is a rare B-cell malignancy characterized by secretion of immunoglobulin M and cancer infiltration in the bone marrow. Chemokine receptor such as CXCR4 and hypoxic condition in the bone marrow play crucial roles in cancer cell trafficking, homing, adhesion, proliferation, survival, and drug resistance. Herein, we aimed to use CXCR4 as a potential biomarker to detect hypoxic-metastatic WM cells in the bone marrow and in the circulation by using CXCR4-detecting radiopharmaceutical.Methods: We radiolabeled a CXCR4-inhibitor (AMD3100) with 64Cu and tested its binding to WM cells with different levels of CXCR4 expression using gamma counter in vitro. The accumulation of this radiopharmaceutical tracer was tested in vivo in subcutaneous and intratibial models using PET/CT scan. In addition, PBMCs spiked with different amounts of WM cells ex vivo were detected using gamma counting.Results: In vitro, 64Cu-AMD3100 binding to WM cell lines demonstrated a direct correlation with the level of CXCR4 expression, which was increased in cells cultured in hypoxia with elevated levels of CXCR4, and decreased in cells with CXCR4 and HIF-1α knockout. Moreover, 64Cu-AMD3100 detected localized and circulating CXCR4high WM cells with high metastatic potential.Conclusions: In conclusion, we developed a molecularly targeted system, 64Cu-AMD3100, which binds to CXCR4 and specifically detects WM cells with hypoxic phenotype and metastatic potential in the subcutaneous and intratibial models. These preliminary findings using CXCR4-detecting PET radiopharmaceutical tracer indicate a potential technology to predict high-risk patients for the progression to WM due to metastatic potential.

How we manage Bing-Neel syndrome.

Bing-Neel syndrome (BNS) is an uncommon presentation of Waldenström macroglobulinaemia (WM), seen during the course of the disease in about 1% of patients. BNS occurs when WM cells gain access to the central nervous system (CNS) causing neurological deficits. The diagnosis of BNS is suggested by the presence of radiological abnormalities, such as leptomeningeal enhancement on magnetic resonance imaging and confirmed by the presence of clonal lymphoplasmacytic cells and MYD88 L265P in the cerebrospinal fluid. The treatment of BNS requires agents with good penetration into the CNS, such as fludarabine, methotrexate and cytarabine. The novel Bruton Tyrosine Kinase inhibitor ibrutinib has shown CNS-penetrating properties, and recent data suggest a therapeutic role in BNS. In this review, we will discuss the clinical and pathological features, diagnostic criteria, treatment options and outcomes of patients with BNS.

Imaging of Waldenström Macroglobulinemia: A Comprehensive Review for the Radiologist in the Era of Personalized Medicine.

OBJECTIVE. We describe the range of organ systems involved and the spectrum of imaging findings seen in Waldenström macroglobulinemia (WM). CONCLUSION. Although imaging is not mandatory in the initial workup of a patient with WM, a multimodality imaging approach can lead toward the diagnosis of a lymphoproliferative disorder, establish the tumor burden, identify sites of involvement, and thus explain the clinical presentation, help in determining prognosis and monitoring response to therapy, and help identify treatment-induced toxicity.

18F-FDG PET/CT in the Evaluation of Bing-Neel Syndrome.

Waldenström macroglobulinemia is an indolent B-cell lymphoproliferative disorder. When there is involvement of the central nervous system, Waldenström macroglobulinemia is known as Bing-Neel syndrome. We present a case of Bing-Neel syndrome in a patient who presented with confusion and left orbital pain. 18F-FDG PET/CT was utilized in making the diagnosis.