Prognostic value of the combination of volume, massiveness and fragmentation parameters measured on baseline FDG pet in high-burden follicular lymphoma.

The prognostic value of radiomic quantitative features measured on pre-treatment 18F-FDG PET/CT was investigated in patients with follicular lymphoma (FL). We conducted a retrospective study of 126 FL patients (grade 1-3a) diagnosed between 2006 and 2020. A dozen of PET/CT-derived features were extracted via a software (Oncometer3D) from baseline 18F-FDG PET/CT images. The receiver operating characteristic (ROC) curve, Kaplan-Meier method and Cox analysis were used to assess the prognostic factors for progression of disease within 24 months (POD24) and progression-free survival at 24 months. Four different clusters were identified among the twelve PET parameters analyzed: activity, tumor burden, fragmentation-massiveness and dispersion. On ROC analyses, TMTV, the total metabolic tumor volume, had the highest AUC (0.734) followed by medPCD, the median distance between the centroid of the tumors and their periphery (AUC: 0.733). Patients with high TMTV (HR = 4.341; p < 0.001), high Tumor Volume Surface Ratio (TVSR) (HR = 3.204; p < 0.003) and high medPCD (HR = 4.507; p < 0.001) had significantly worse prognosis in both Kaplan-Meier and Cox univariate analyses. Furthermore, a synergistic effect was observed in Kaplan-Meier and Cox analyses combining these three PET/CT-derived parameters (HR = 12.562; p < 0.001). Having two or three high parameters among TMTV, TVSR and medPCD was able to predict POD24 status with a specificity of 68% and a sensitivity of 75%. TMTV, TVSR and baseline medPCD are strong prognostic factors in FL and their combination better predicts disease prognosis.

End-of-treatment 18[F]-FDG PET can predict early progression in patients receiving bendamustine-rituximab for follicular lymphoma in first relapse: a prospective West Japan hematology Study Group (W-JHS) NHL01 trial.

Response determined by 18[F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)-CT after induction therapy can predict progression-free survival (PFS) in follicular lymphoma (FL). However, little prospective research has examined the significance of PET after second-line therapy. We conducted a prospective multicenter phase II trial (W-JHS NHL01) of bendamustine plus rituximab (BR) without rituximab maintenance for FL in first relapse. This study aimed to evaluate the usefulness of end-of-treatment (EOT)-PET for predicting PFS in FL patients in first relapse. EOT-PET examinations were performed between 6 and 8 weeks from the start of the last BR cycle. The primary endpoint was 1-year PFS. Key secondary endpoints were overall response rate (ORR), complete response rate (CRR), and 1-year overall survival (OS). Seventy-five patients were enrolled, and 8 were excluded from analysis. ORR was 86.6% and CRR was 59.7%. One-year PFS was 88.9% (95% confidence interval [CI] 80.7-94.3%) and 1-year OS in 75 patients was 97.3% (95% CI 89.6-99.3%). One-year PFS was significantly inferior in EOT-PET-positive patients (n = 9) compared with PET-negative patients (n = 58) (77.8% vs. 93.1%; p = 0.02). We confirmed that EOT-PET after second-line BR therapy could predict early progression in FL patients in first relapse.

PET/CT in a 65-Year-Old Woman With Epstein-Barr Virus-Associated Smooth Muscle Tumor After Chemotherapy for Follicular Lymphoma.

ABSTRACT: The Epstein-Barr virus-associated smooth muscle tumor (SMT) is an uncommon neoplasm. It arises mainly in 3 immunosuppression settings: HIV-associated SMT; drug-related immunosuppression in transplant recipients; and congenital immunodeficiency disorder-associated SMT. We present 18 F-FDG PET/CT findings of an adrenal Epstein-Barr virus-associated SMT in a 65-year-old woman with a history of follicular lymphoma after chemotherapy.

Metabolic tumor volume predicts outcome in patients with advanced stage follicular lymphoma from the RELEVANCE trial.

BACKGROUND: We investigated the prognostic value of baseline positron emission tomography (PET) parameters for patients with treatment-naïve follicular lymphoma (FL) in the phase III RELEVANCE trial, comparing the immunomodulatory combination of lenalidomide and rituximab (R2) versus R-chemotherapy (R-chemo), with both regimens followed by R maintenance therapy. PATIENTS AND METHODS: Baseline characteristics of the entire PET-evaluable population (n = 406/1032) were well balanced between treatment arms. The maximal standard uptake value (SUVmax) and the standardized maximal distance between tow lesions (SDmax) were extracted, the standardized distance between two lesions the furthest apart, were extracted. The total metabolic tumor volume (TMTV) was computed using the 41% SUVmax method. RESULTS: With a median follow-up of 6.5 years, the 6-year progression-free survival (PFS) was 57.8%, the median TMTV was 284 cm3, SUVmax was 11.3 and SDmax was 0.32 m-1, with no significant difference between arms. High TMTV (>510 cm3) and FLIPI were associated with an inferior PFS (P = 0.013 and P = 0.006, respectively), whereas SUVmax and SDmax were not (P = 0.08 and P = 0.12, respectively). In multivariable analysis, follicular lymphoma international prognostic index (FLIPI) and TMTV remained significantly associated with PFS (P = 0.0119 and P = 0.0379, respectively). These two adverse factors combined stratified the overall population into three risk groups: patients with no risk factors (40%), with one factor (44%), or with both (16%), with a 6-year PFS of 67.7%, 54.5%, and 41.0%, respectively. No significant interaction between treatment arms and TMTV or FLIPI (P = 0.31 or P = 0.59, respectively) was observed. The high-risk group (high TMTV and FLIPI 3-5) had a similar PFS in both arms (P = 0.45) with a median PFS of 68.4% in the R-chemo arm versus 71.4% in the R2 arm. CONCLUSIONS: Baseline TMTV is predictive of PFS, independently of FLIPI, in patients with advanced FL even in the context of antibody maintenance.

Endoscopic observation of a rare duodenal tumor

A 30-year-old young previously healthy man presented to our hospital with middle and upper abdominal discomfort. Abdominal computerized tomography (CT) showed no significant abnormalities. White light endoscopy showed the local mucosa in the descending part of the duodenum had granuloid uplift, some of which were fused into pieces with red color, and some other areas showed fading tone. Magnifying endoscopy with indigo-carmine staining and narrow-band imaging showed a finger-like, loose villous structure with irregular microvessels on the surface. Pathological examination of biopsy specimens showed that lymphocytes were diffused and dispersed in the mucosa with relatively simple morphology, no lymphoid follicles were observed, and local compression was obvious. Immunohistochemical staining revealed a lymphoid population highly positive for CD20 and CD10. These results were consistent with duodenal-type follicular lymphoma (D-FL). (AU)

Primary esophageal follicular lymphoma: a rare entity / Linfoma folicular esofágico primario: una entidad rara

A 63-year-old woman presented with dyspepsia de novo. An esophagogastroduodenoscopy revealed a 30 mm flat yellowish esophageal lesion, 28 cm from the incisors (Fig. 1a), with the stomach and duodenum without any lesion. Helicobacter pylori infection was excluded. Histological examination was suggestive of a lymphoproliferative process (Fig. 1b). Immunohistochemistry showed diffuse positivity for CD20 (Fig. 1c) and BCL-2 (Fig. 1d), dim CD10 and BCL-6 staining, a Ki-67 of 20-25%, no CD21 or cyclin D1 expression, all these features compatible with low-grade follicular lymphoma. Physical examination was unremarkable. Computed tomography of the neck, chest, and abdomen revealed no lymph node enlargement, hepatosplenomegaly or metastasis. Blood routine tests and tumor markers were at normal levels. Bone marrow biopsy showed no involvement by lymphoma. Therefore, a diagnosis of primary follicular lymphoma of the esophagus was made. The patient opted for a watch-and-wait strategy and there is no evidence of disease progression after four years of follow-up.(AU)

Biliary obstruction secondary to duodenal follicular lymphoma with papillary involvement.

Duodenal-type follicular lymphoma is a clinical variant of follicular lymphoma located in the intestine, presenting as multiple small polyps. The estimated frequency is 1/7000 people and extraduodenal involvement is rare. It predominantly affects middle-aged women, although some cases of young patients have been published in the literature. They are usually located in the second periampullary portion of the duodenum. It is diagnosed incidentally or after performing an imaging test due to non-specific digestive symptoms (abdominalgia, diarrhea or hyporexia). The prognosis is usually favorable without specific treatment5.

Disease surveillance evaluation of primary small-bowel follicular lymphoma using capsule endoscopy images based on a deep convolutional neural network (with video).

BACKGROUND AND AIMS: Capsule endoscopy (CE) is useful in evaluating disease surveillance for primary small-bowel follicular lymphoma (FL), but some cases are difficult to evaluate objectively. This study evaluated the usefulness of a deep convolutional neural network (CNN) system using CE images for disease surveillance of primary small-bowel FL. METHODS: We enrolled 26 consecutive patients with primary small-bowel FL diagnosed between January 2011 and January 2021 who underwent CE before and after a watch-and-wait strategy or chemotherapy. Disease surveillance by the CNN system was evaluated by the percentage of FL-detected images among all CE images of the small-bowel mucosa. RESULTS: Eighteen cases (69%) were managed with a watch-and-wait approach, and 8 cases (31%) were treated with chemotherapy. Among the 18 cases managed with the watch-and-wait approach, the outcome of lesion evaluation by the CNN system was almost the same in 13 cases (72%), aggravation in 4 (22%), and improvement in 1 (6%). Among the 8 cases treated with chemotherapy, the outcome of lesion evaluation by the CNN system was improvement in 5 cases (63%), almost the same in 2 (25%), and aggravation in 1 (12%). The physician and CNN system reported similar results regarding disease surveillance evaluation in 23 of 26 cases (88%), whereas a discrepancy between the 2 was found in the remaining 3 cases (12%), attributed to poor small-bowel cleansing level. CONCLUSIONS: Disease surveillance evaluation of primary small-bowel FL using CE images by the developed CNN system was useful under the condition of excellent small-bowel cleansing level.

A Case of Adenomyosis Showing Size Reduction in a Follicular Lymphoma Patient Receiving Chemotherapy With R-Bendamustine.

ABSTRACT: We describe a case of adenomyosis that reduced in size in a patient with lymphoma on receiving chemotherapy. A 48-year-old woman with worsening left flank pain was diagnosed with follicular lymphoma. [ 18 F]FDG PET/CT revealed multiple hypermetabolic lymph nodes in the bilateral cervical, axillary, mediastinal, mesenteric, retroperitoneal, iliac, and inguinal regions. In addition, adenomyosis with mild hypermetabolism was demonstrated on [ 18 F]FDG PET/CT. The size and metabolism of adenomyosis decreased after chemotherapy with R-bendamustine; in addition, along with decrease in estradiol levels, the patient experienced amenorrhea and hot flushes. The patient was diagnosed with chemotherapy-induced early menopause.

[A case of gastric follicular lymphoma with rapid deterioration and transformation].

A 79-year-old male patient underwent esophagogastroduodenoscopy, which revealed a reddish lesion, 10mm in diameter, presenting as a surface recess in the angular incisure. He was diagnosed with gastric follicular lymphoma. Positron emission tomography-computed tomography revealed metastasis to the mediastinal lymph node, although the tumor size was small. Hence, we did not administer any treatment and continued following up. After 8 months, multiple enlarged lymphoma lesions in the stomach and a mass with ulceration on the oral side of the duodenal papilla were observed. The tumor had transformed into diffuse large B-cell lymphoma; therefore, chemotherapy was initiated. The patient has remained recurrence-free for 55 months after treatment.

Positron emission tomography to detect bone marrow involvement for patients with follicular lymphoma: a systematic review and meta-analysis.

Detection of bone marrow involvement (BMI) for patients with follicular lymphoma (FL) is of great significance for staging and treatment. The clinical value of positron emission tomography/computed tomography (PET/CT) in assessing BMI is still under debate and investigation. PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify studies evaluating PET/CT in detecting BMI in FL patients. Data extraction and quality evaluation were independently conducted by two reviewers, and nine eligible studies were selected as final quantitative analysis. Nine studies comprising 1119 FL patients were included. The pooled sensitivity was 0.67 (95% CI, 0.38-0.87), and the pooled specificity was 0.82 (95% CI, 0.75-0.87). The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 3.7 (95% CI, 2.1-6.3), 0.4 (95% CI, 0.18-0.91), and 9 (95% CI, 2-33), respectively. The area under the curve of PET/CT to detect BMI in FL patients was 0.83 (95% CI, 0.8-0.86). Current evidence suggests that PET/CT cannot replace bone marrow biopsy to detect BMI, but it is still of partial clinical significance for the prognosis of patients with follicular lymphoma.

Primary esophageal follicular lymphoma: a rare entity.

A 63-year-old woman presented with dyspepsia de novo. An esophagogastroduodenoscopy revealed a 30 mm flat yellowish esophageal lesion, 28 cm from the incisors (Fig. 1a), with the stomach and duodenum without any lesion. Helicobacter pylori infection was excluded. Histological examination was suggestive of a lymphoproliferative process (Fig. 1b). Immunohistochemistry showed diffuse positivity for CD20 (Fig. 1c) and BCL-2 (Fig. 1d), dim CD10 and BCL-6 staining, a Ki-67 of 20-25%, no CD21 or cyclin D1 expression, all these features compatible with low-grade follicular lymphoma. Physical examination was unremarkable. Computed tomography of the neck, chest, and abdomen revealed no lymph node enlargement, hepatosplenomegaly or metastasis. Blood routine tests and tumor markers were at normal levels. Bone marrow biopsy showed no involvement by lymphoma. Therefore, a diagnosis of primary follicular lymphoma of the esophagus was made. The patient opted for a watch-and-wait strategy and there is no evidence of disease progression after four years of follow-up.

Prognostic value of interim 18F-FDG PET/CT in adult follicular lymphoma treated with R-CHOP.

PURPOSE: The prognostic value of interim 18F-FDG PET/CT (I-PET) for follicular lymphoma (FL) is controversial, and may be related to the lack of strict standards in terms of age, chemotherapy regimen, and evaluation criteria in previous studies. This study aimed to investigate the prognostic value of I-PET in adult FL patients treated with R-CHOP. METHODS: I-PET was performed in 30 adult FL patients after treatment with 3-5 cycles of R-CHOP. PET/CT images were assessed using the Deauville 5-point scale (D-5PS) criteria. Baseline PET/CT (B-PET) was performed in 24 of the patients with FL before treatment. The PET/CT image parameters, such as the SUVmax, TLG, and tMTV, were recorded. The prognostic values of sex, age, grade, Ann Arbor stage, LDH level, and I-PET were evaluated. RESULTS: Kaplan-Meier analysis and Cox regression showed that sex, age, grade, Ann Arbor stage, LDH, and I-PET using the D-5PS criteria could not predict the PFS of adult patients with FL treated with R-CHOP (P>0.05). ROC curve analysis evaluated the predictive values of SUVmax, TLG, and tMTV in B-PET and I-PET and showed that none of them was predictive of PFS in adult FL patients (P>0.05). However, the variation in SUVmax (∆SUVmax) was predictive of PFS in adult FL patients (AUC=0.83, P=0.040), and the cutoff threshold was 4.85. CONCLUSIONS: I-PET using the D-5PS criteria cannot predict the PFS of adult FL patients treated with R-CHOP. However, the ∆SUVmax between B-PET and I-PET is applicable for the prognosis of adult patients with FL.

Impact of positron emission tomography - computed tomography status on progression-free survival for relapsed follicular lymphoma patients undergoing autologous stem cell transplantation.

The optimum management approach for patients with relapsed or refractory follicular lymphoma remains uncertain. Autologous stem cell transplantation (autoSCT) is considered a standard option in suitable, younger patients with relapsed follicular lymphoma. AutoSCT is associated with very durable remissions in a minority of subjects, but also with significant, well-established toxicities. Although positron emission tomography (PET) status prior to autoSCT is an established prognostic factor in diffuse large B-cell lymphoma and Hodgkin lymphoma, no data exist in follicular lymphoma. We describe survival outcomes according to pre-transplant PET status, classified by the Lugano criteria into complete metabolic remission (CMR) versus non-CMR, in 172 patients with relapsed or refractory follicular lymphoma within a national, multicenter, retrospective British Society of Blood and Marrow Transplantation and Cellular Therapy registry study. The median number of lines of therapy prior to SCT was three (range, 1-6). The median follow-up after SCT was 27 months (range, 3-70). The median progression-free survival for all patients after autoSCT was 28 months (interquartile range, 23- 36). There was no interaction between age at transplantation, sex, number of months since last relapse, Karnofsky performance status or comorbidity index and achieving CMR prior to autoSCT. Superior progression-free survival was observed in 115 (67%) patients obtaining CMR versus 57 (33%) non-CMR patients (3-year progression-free survival 50% vs. 22%, P=0.011) and by pre-SCT Deauville score (continuous variable 1-5, hazard ratio [HR]=1.32, P=0.049). PET status was independently associated with progression-free status (non-CMR HR=2.02, P=0.003), overall survival (non-CMR HR=3.08, P=0.010) and risk of relapse (non-CMR HR=1.64, P=0.046) after autoSCT by multivariable analysis. Our data suggest that pre- SCT PET status is of clear prognostic value and may help to improve the selection of patients for autoSCT.

Primary small bowel follicular lymphoma: the role of balloon-assisted enteroscopy in diagnosis and follow-up.

An asymptomatic 38-year-old male with no significant previous medical history performed routine laboratory studies that revealed iron-deficiency anemia. Esophagogastroduodenoscopy and colonoscopy were unremarkable and he undergone videocapsule endoscopy that revealed multiple small polyps along jejunum and ileum. Double-balloon enteroscopy confirmed the presence of scattered small whitish nodules and small polyps carpeting segments of jejunal mucosal and sometimes forming conglomerates with a nodular appearance. Histopathological examination showed lamina propria expansion by neoplastic follicles, predominantly composed by small lymphoid cells that, by immunohistochemistry, showed expression of CD20, CD10 and bcl-2. Computed tomography scan of abdomen and pelvis did not reveal systemic involvement, consistent with primary small bowel follicular lymphoma. Chemotherapy was started and, at reevaluation enteroscopy, although nodular jejunal segments persisted, biopsies did not show involvement by lymphoproliferative disease, which was interpreted as complete remission. Periodic clinical and biochemical evaluation and annual enteroscopic surveillance was maintained and, after three years, local recurrence of low-grade follicular lymphoma was detected. As previously, there was no evidence of systemic involvement and the decision was to maintain close surveillance. After one year, the patient remains asymptomatic and without evidence of disease progression. This case illustrates the essential role of balloon-assisted enteroscopy for diagnosis and surveillance of primary small bowel follicular lymphoma.

FDG-PET/CT-guided rebiopsy may find clinically unsuspicious transformation of follicular lymphoma.

AIM: The purpose of the study was to evaluate the clinical impact of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) followed by a new biopsy from the site with maximum standardized uptake value (SUVmax) in case of high maximal SUV values, in detecting clinically unsuspected histologic transformations (HT) of follicular lymphoma (FL). METHODS: This retrospective study included all the patients who had undergone FDG-PET/CT during primary diagnosis or relapse of FL between 2010 and 2020 at Oulu University Hospital. RESULTS: The diagnosis changed from an indolent disease to a transformed lymphoma in >10% (7/63) of the patients who underwent diagnostic FDG-PET/CT. The HT risk associated with high SUVmax (>10) was 24% (7 of 29 performed biopsies). Four out of these seven patients with verified HT had no previous clinical suspicion of transformation. CONCLUSION: Our results suggest that a rebiopsy based on a high SUVmax in diagnostic FDG-PET/CT is valuable in detecting clinically unsuspected HT of FL.

Accuracy and prognostic impact of FDG PET/CT and biopsy in bone marrow assessment of follicular lymphoma at diagnosis: A Nation-Wide cohort study.

BACKGOUND: In the workup of follicular lymphoma (FL), bone marrow biopsy (BMB) assessment is a key component of FLIPI and FLIPI2, the most widely used outcome scores. During the previous decade, several studies explored the role of FDG-PET/CT for detecting nodal and extranodal disease, with only one large study comparing both techniques. METHODS: The aim of our study was to evaluate the diagnostic accuracy and the prognostic impact of both procedures in a retrospective cohort of 299 FL patients with both tests performed at diagnosis. In order to avoid a collinearity bias, FLIPI2 was deconstructed in its founding parameters, and the bone marrow involvement (BMI) parameter separately included as: a positive BMB, a positive PET/CT, the combined "PET/CT and BMB positive" or "PET/CT or BMB positive". These variables were also confronted independently with the POD24 in 233 patients treated with intensive regimens. RESULTS: In the total cohort, bone marrow was involved in 124 and 60 patients by BMB and PET/CT, respectively. In terms of overall survival, age > 60 y.o. and the combined "PET/CT or BMB positive" achieved statistical independence as a prognostic factor. In patients treated with an intensive regimen, only the combined "PET/CT or BMB positive" added prognostic value for a shorter overall survival, when confronted with the POD24. CONCLUSION: Our results show that in FL both BMB and PET/CT should be considered at diagnosis, as their combined assessment provides independent prognostic value in the context of the most widely use clinical scores.

Characteristic multimodal imaging of palatal follicular lymphoma: a case report on effectiveness of CT, diffusion-weighted MR imaging and intraoral ultrasonography.

Oral lymphomas are relatively uncommon. Follicular lymphoma is the second most common subtype of non-Hodgkin lymphoma. We report characteristic multimodal imaging of palatal follicular lymphoma, especially CT, diffusion-weighted MR imaging (DWI) and intraoral ultrasonography. A 67-year-old woman presented with swelling on the right side of the palate within 2 months. On clinical examination, an approximately 35 × 20 mm mass lesion with elastic soft was found to overlay the right side of the palate. Contrast-enhanced CT image showed a mass with homogeneous enhancement on the right side of the palate, and bone tissue algorithm CT showed focal erosion of the right posterior maxilla. Regarding MR imaging, on T1-weighted image, the mass showed low signal intensity and homogeneous enhancement, and T2-weighted and STIR images revealed intermediate and high signal intensity, respectively. Furthermore, DWI and apparent diffusion coefficient (ADC) map showed high and low signal intensity, respectively. ADC value of the mass was 0.60 × 10-3 mm2s-1. On intraoral ultrasonography, the mass showed clear boundary, hypoechoic echogenicity, homogeneous internal architecture, vascular signals using color Doppler imaging and heterogeneous hard using strain elastography. A partial biopsy of the palatal region was performed. Histopathological diagnosis was follicular lymphoma. This case suggests that multimodal imaging, especially CT, DWI with ADC map and intraoral ultrasonography with color Doppler imaging and strain elastography, could be effective for evaluating palatal lesions.