Duodenal-type Follicular Lymphoma Research Articles

Clinical characteristics and outcomes of Brazilian patients with duodenal-type follicular lymphoma: a multicenter retrospective study

Duodenal-type follicular lymphoma (DFL) is a rare subtype classified by the 5th edition of the WHO and international consensus classifications of lymphoid neoplasms, typically presenting as localized disease with favorable outcomes. This multicenter retrospective study examines 53 Brazilian DFL patients with a median age of 58.2 years (33–85), with males comprising 50% (n = 27). According to Lugano GI tract classification, 40 patients (75%) were stage I. Median follow-up was 2.9 years (range 0.1–11). Incidental diagnosis occurred in 28 patients (52.8%) during routine endoscopy; 24 patients (45%) presented mild gastrointestinal symptoms. Treatments included watchful waiting (32 patients, 60.4%), rituximab monotherapy (15 patients, 28.3%), radiotherapy (three patients, 5.7%), and chemoimmunotherapy (three patients, 5.7%). Three patients experienced disease progression; watchful waiting showed three spontaneous remissions. No deaths occurred during follow-up. This study, the first from Latin America, demonstrates a good prognosis across treatments, highlighting Watchful waiting’s effectiveness.

Duodenal-type follicular lymphoma: comprehensive insights into disease characteristics and established treatment strategies.

This review aims to detail the characteristics and outcomes of duodenal-type follicular lymphoma (DTFL), a rare lymphoma variant. It focuses on integrating recent reports in treatment modalities and highlights emerging insights into the unique biological features of the disease. Recent studies confirm the indolent nature of DTFL, with extended follow-up periods showing favorable outcomes under watchful waiting strategies and a notable proportion of patients experiencing spontaneous remission. Additionally, advancements in understanding the disease's biology revealed that the tumor microenvironment is marked by specific genomic expressions indicative of chronic inflammation. The observations of spontaneous resolution and the generally favorable progression of DTFL call for a conservative approach in initiating treatment. Clinical management should judiciously consider the disease's typically benign course against the potential risks of intervention, promoting customized treatment protocols tailored for cases with clinical necessity. Additionally, the discovery of an inflammatory tumor microenvironment and molecular evidence suggesting an antigen-driven process highlight critical areas for future research.

Clinicopathological characteristics of duodenal-type follicular lymphoma: A case report

Clinicopathological characteristics of duodenal-type follicular lymphoma: A case report

Studies on clinicopathological features of duodenal-type follicular lymphoma of 18 patients

To investigate the clinical and pathological characteristics of duodenal-type follicular lymphoma (D-FL), and to deepen the understanding of Duodenal-type follicular lymphoma. The clinical symptoms, endoscopic features, pathologic features, immunophenotype, molecular pathological features and treatment follow-up of 18 D-FL patients diagnosed in Department of Pathology, Beijing Tiantan Hospital affiliated to Capital Medical University between January 2020 and July 2023 were summarized. A total of 18 patients with D-FL were included, including 10 males and 8 females. The median age was 49 (32-69) years respectively. Most of the patients were found during gastroenteroscopy or presented with the common gastrointestinal symptoms of stomach pain, acid reflux, vomiting and diarrhea. Most endoscopic findings were multiple small gray and white polyposis. In the pathological morphology, the mucous layer and submucous layer showed lymphoid follicular structures with full and strained follicles. The immunophenotype showed that the tumor cells strongly expressed CD20 and BCL2 and had low proliferation activity. Immunoglobulin clonal analysis of 1 case showed IgK monoclonal rearrangement (1/1). FISH showed 1 case of BCL2 gene rearrangement (1/3). All patients did not receive targeted chemotherapy and adopted a wait-and-see strategy. Median follow-up was 12 (2-34) months. This study shows that D-FL is an indolent lymphoma, which tends to occur in the duodenum and has a good prognosis.

Frequent CDKN2B/P15 and DAPK1 methylation in duodenal follicular lymphoma is related to duodenal reactive lymphoid hyperplasia.

Duodenal type follicular lymphoma (DFL), a rare entity of follicular lymphoma (FL), is clinically indolent and is characterized by a low histological grade compared with nodal follicular lymphoma (NFL). Our previous reports revealed that DFL shares characteristics of both NFL and mucosa-associated lymphoid tissue (MALT) lymphoma in terms of clinical and biological aspects, suggesting its pathogenesis may involve antigenic stimulation. In contrast to NFL, the genomic methylation status of DFL is still challenging. Here, we determined the methylation profiles of DNAs from patients with DFL (n = 12), NFL (n = 10), duodenal reactive lymphoid hyperplasia (D-RLH) (n = 7), nodal reactive lymphoid hyperplasia (N-RLH) (n = 5), and duodenal samples from normal subjects (NDU) (n = 5) using methylation specific PCR of targets previously identified in MALT lymphoma (CDKN2B/P15, CDKN2A/P16, CDKN2C/P18, MGMT, hMLH-1, TP73, DAPK, HCAD). DAPK1 was frequently methylated in DFL (9/12; 75%), NFL (9/10; 90%), and D-RLH (5/7; 71%). CDKN2B/P15 sequences were methylated in six DFL samples and in only one NFL sample. Immunohistochemical analysis showed that p15 expression inversely correlated with methylation status. Genes encoding other cyclin-dependent kinase inhibitors (CDKN2A/P16, CDKN2C/P18) were not methylated in DFL samples. Methylation of the genes of interest was not detected in DNAs from D-RLH, except for DAPK1, and the difference in the extent of methylation between NDU and D-RLH was statistically significant (P = 0.013). Our results suggest that D-RLH serves as a reservoir for the development of DFL and that methylation of CDKN2B/P15 plays an important role in this process.

Endoscopic submucosal dissection for duodenal-type follicular lymphoma.

Duodenal-type follicular lymphoma (D-FL) is a special type of follicular lymphoma, which tends to occur in the descending segment of the duodenum. The lesion is mostly limited to the mucosal layer. The treatment approach for D-FL has not been clearly established and the watch and wait (WW) approach is generally recommended as a major option. Since D-FL may be transformed into a more serious type of lymphoma, it is of clinical significance to explore active treatment methods. We diagnosed and successfully treated a case of D-FL with Endoscopic submucosal dissection (ESD). Because D-FL is limited to mucosa in the descending segment of the duodenum, ESD can completely dissect the lesion to achieve the purpose of complete resection. Compared with the WW, the method of WW after endoscopic therapy is more active, safe and effective.

Endoscopic and Histopathological Characteristics of Gastrointestinal Lymphoma: A Multicentric Study.

Background: Extranodal non-Hodgkin lymphoma (NHL) is more prevalent in the gastrointestinal (GI) tract than in other sites. This study aimed to determine the endoscopic characteristics of primary gastrointestinal non-Hodgkin lymphomas. Methods: We investigated 140 patients from three tertiary referral hospitals with primary malignant lymphoma of the gastrointestinal tract. Characteristics of the lesions were evaluated and analyzed using image-enhanced endoscopy, endoscopic ultrasound, and histopathology. Results: The median age was 60.5 (range: 11-99), and 59 (42.1%) were female. The most frequent complaint was abdominal pain (74.3%), followed by bloody feces (10%) and diarrhea (2.9%). B symptoms were observed in 15 (10.7%) patients. GI obstruction was the most common complication (10.0%), followed by hemorrhage (7.9%) and perforation (1.5%). Regarding endoscopic findings, the identified sites were the following: the stomach (61.4%), colon (10%), small intestine (10%), ileocecum (8.6%), rectum (6.4%), and duodenum (3.6%). Diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma are most prevalent in the stomach. Helicobacter pylori was identified in 46 cases (39.0%), with MALT lymphoma being the most infected subtype. Nearly all gastrointestinal non-Hodgkin lymphomas manifested as superficial type (25-59.6%) and ulcer type (15.6-50%) under endoscopy. We found that fungating type and protruding with ulcer type were more frequent types of aggressive lymphomas (diffuse large B-cell lymphoma, mantle cell lymphoma, and T-cell lymphoma) compared to the indolent types (MALT lymphoma, follicular lymphoma, duodenal-type follicular lymphoma, and small lymphocytic lymphoma) (p < 0.05). Conclusions: This study showed that most subtypes of gastrointestinal non-Hodgkin lymphomas exhibited same endoscopic features (superficial type and ulcer type). Aggressive gastrointestinal non-Hodgkin lymphomas (diffuse large B-cell lymphoma, mantle cell lymphoma, and T-cell lymphoma) were highly suspected when fungating lesions and protruding with ulcer lesions were encountered under endoscopy. Endoscopists should be aware of the connection between enhanced endoscopic characteristics and histological varieties of gastrointestinal lymphoma to improve diagnosis.

Incidental Findings of Duodenal-Type Follicular Lymphoma by Endoscopic Screening: A Case Report

Introduction: Follicular Lymphoma (FL) is a B-cell neoplasm arising from the germinal center. Gastrointestinal FL is a rare case, accounting for less than 4% of all primary lymphoma of the gastrointestinal tract. Duodenal-type Follicular Lymphoma (DTFL) was included in an entity of primary intestinal FL. However, in the 2017 World Health Organization (WHO) Classification, this entity was included in a specific variant called DTFL. In this article, we report a case of DTFL in a 56-year-old man which was incidentally found during upper gastrointestinal endoscopy Case Presentation: : We report a case of incidentally found DTFL in a 56-year-old man during an endoscopy. The endoscopic finding showed a small, hypertrophic, or nodular lesion on part two duodenum. Microscopic evaluation of duodenal mucosa consists of proliferative atypical lymphoid cells arranged in follicular architecture. The lesion was confined to the lamina propria. The atypical lymphoid cells were dominated by monotonous centrocyte-like cells, small-sized, with scant cytoplasm, and cleaved nuclei. There were some scattered larger centroblast-like cells with multiple nucleoli. No mantle zone and tingible body macrophage were found. The immunohistochemical evaluation showed positivity for CD 20, CD 10, Bcl-6, and Bcl-2 in the follicular structure. CD 21 was dominantly stained at the periphery of the follicular structure, and Ki-67 was low. Conclusions: According to clinical data, endoscopic findings, and histopathological and immunohistochemical findings, the patient was diagnosed with DTFL.

DUODENAL‐TYPE FOLLICULAR LYMPHOMA, A RARE ENTITY: CLINICAL ASPECTS, TREATMENT AND OUTCOMES OF BRAZILIAN PATIENTS

Introduction: Duodenal-type follicular lymphoma (DFL) is a rare entity, presented mostly as localized disease and excellent long-term outcomes. Its pathogenesis and peculiar predilection for the duodenum is not clear. Wide use of endoscopy for several reasons seems to highlight this disease and increase its diagnosis, since many patients are asymptomatic. Environment aspects, such as diet and local infections, could play a role in its clinical presentation and evolution. Methods: We evaluated 53 patients with diagnosis of DFL based on the current WHO classification on lymphoid neoplasms. Reference Brazilian centers in hematology reported their cases to this retrospective analysis. Cases were reviewed in electronic charts after ethical approval by each center. Results: The median follow-up of the whole cohort was 2.9 years (range 0.1–11). Median age at diagnosis was 58.2 y (33–85). Using the Lugano TGI classification, 75% (n = 40) were stage I. There were 2 patients with concomitant involvement of the jejunum and 1 with colonic infiltration of follicular lymphoma. Endoscopic lesions were mainly nodules (56%) and in the second portion of the duodenum (85%). Bone marrow involvement (BMi) was present in 4 cases. Close to half of the population (51%) was asymptomatic and had the diagnosis after a screening endoscopy, while 45% had some form of mild gastrointestinal symptom that preclude the exam. Only one patient had constitutional symptoms. FLIPI 0-1 in 81% of patients, with LDH elevated in 3 patients (mean of 262.8, range 116–487). Most patients were followed with regular observation (watch and wait in 60.4%), rituximab monotherapy was administered for 15 patients (28.3%) and radiotherapy for 3 (5.7%). Only 3 patients received chemotherapy (one consolidated with radiotherapy). GI symptoms were the major cause (n = 8) for starting treatment, followed by nonspecific cause in 7 cases (many described by patient anxiety). Rituximab maintenance was performed in 9 patients, 7 treated with rituximab monotherapy and 2 with rituximab plus chemotherapy. Three patients had progression of disease (1 after watch and wait, 1 treated with rituximab monotherapy and no maintenance and 1 progressed after receiving chemotherapy for advanced disease). Within these patients, 2 had BMi. Table 1 summarize the main findings. No patient died. Within the watch and wait group, most patients didn’t perform a follow up endoscopy however three patients had a spontaneous complete remission observed by endoscopy. Conclusions: This is the first cohort of Brazilian or Latin American patients with DFL published so far. Most patients were asymptomatic or with mild gastrointestinal symptoms at diagnosis. Small multiple nodules in the second portion of the duodenum were the principal appearance. Patients tended to have low FLIPI, localized disease and good prognosis. Watch and wait strategy seems safe and spontaneous CR can occur. Keyword: indolent non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Clinical Research Advances of Duodenal-Type Follicular Lymphoma--Review

Duodenal-type follicular lymphoma (DFL) is a unique subtype of follicular lymphoma (FL), which often involves the second portion of duodenum (descending part of duodenum). Due to its specific pathological features, such as lack of follicular dendritic cells meshwork and disappearance of activation-induced cytidine deaminase expression, DFL presents an inert clinical course and is often confined to the intestinal tract. Inflammation-related biomarkers suggest that the microenvironment may play a likely role in the pathogenesis and favorable prognosis of DFL. Since patients generally have no obvious clinical symptoms and low progression rate, the treatment regimen for DFL is mainly observation and waiting (W&W) strategy. This study will review the latest research progress of epidemiology, diagnosis, treatment and prognosis of DFL in recent years.

Genetic and Microenvironment Features Do Not Distinguish Follicular Lymphoma Patients Requiring Immediate or Deferred Treatment.

Genetic and Microenvironment Features Do Not Distinguish Follicular Lymphoma Patients Requiring Immediate or Deferred Treatment.

Follicular Lymphoma in the 5th Edition of the WHO-Classification of Haematolymphoid Neoplasms-Updated Classification and New Biological Data.

The conceptual description of Follicular lymphoma (FL) in the 5th edition of the World Health Organization (WHO) classification of haematolymphoid tumors (WHO-HAEM5) has undergone significant revision. The vast majority of FL (85%) with a follicular growth pattern are composed of centrocytes and centroblasts, harbor the t(14;18)(q32;q21) translocation and are now termed classic FL (cFL). They are set apart from three related subtypes, FL with predominantly follicular growth pattern, FL with unusual cytological features (uFL) and follicular large B-cell lymphoma (FLBCL). In contrast to the revised 4th edition of the WHO classification of haematolymphoid tumors (WHO-HAEM4R), grading of cFL is no longer mandatory. FL with a predominantly diffuse growth pattern had been previously recognized in WHO-HAEM4R. It frequently occurs as a large tumor in the inguinal region and is associated with CD23 expression. An absence of the IGH::BCL2 fusion and frequent STAT6 mutations along with 1p36 deletion or TNFRSF14 mutation is typical. The newly introduced subtype of uFL includes two subsets that significantly diverge from cFL: one with "blastoid" and one with "large centrocyte" variant cytological features. uFL more frequently displays variant immunophenotypic and genotypic features. FLBCL is largely identical to WHO-HAEM4R FL grade 3B and renaming was done for reasons of consistency throughout the classification. In-situ follicular B-cell neoplasm, pediatric-type FL, duodenal-type FL and primary cutaneous follicle center lymphoma are categorized as discrete entities. In addition, novel findings concerning underlying biological mechanisms in the pathogenesis of early and systemic follicular lymphoma will be presented.

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).

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.

S3443 Multifocal Duodenal-type Follicular Lymphoma Found Incidentally on Diagnostic Endoscopy

Introduction: Follicular lymphoma (FL) accounts for approximately 4% of gastrointestinal (GI) lymphomas (1). Of the follicular lymphomas found in the GI tract, duodenal-type follicular lymphoma (D-FL) make up 38-81% of cases (2-4). D-FL is often incidentally discovered, lack invasion into deeper layers of the GI tract, and are indolent in nature (5). The clinical stage at time of diagnosis often predicts probability of disease progression (6). Given the excellent prognosis and rare occurrence of progression to high stage FL or transformation to diffuse large B cell lymphoma, a “wait and see” therapeutic approach is often taken (4,7). We report a case of D-FL here. Case Description/Methods: A 39-year-old female with no pertinent past medical history presented with refractory acid reflux. Her endoscopy was notable for gastritis, duodenal atrophy, and three 5-mm pale nodules in the second part of the duodenum (Figure 1A-1C). Initial biopsy of these polyps showed atypical lymphoid follicular aggregates. Outside pathologists’ subsequent review noted atypical lymphoid cells positive for CD10, BCL-2, BCL-5, and CD20 markers, consistent with duodenal follicular lymphoma. Further workup with small bowel enteroscopy to the mid-jejunum and colonoscopy were normal. LDH, SPEP with immunofixation, HIV, hepatitis serologies, and full body CT were unremarkable. The patient was diagnosed with stage I D-FL per the Lugano staging system for gastrointestinal lymphomas, and a “wait and wait” approach was recommended by oncology. Discussion: D-FL typically presents with multiple low-stage, white nodules in the second portion of the duodenum, as in our case. Because lesions are rarely solitary in 78-85% D-FL cases, thorough small bowel assessment with enteroscopy or capsule endoscopy is warranted (3,4). Radiation has been shown to be effective in limited disease and is the most common form of treatment (8-10). Chemotherapy, Rituximab, and surgery can also used as monotherapy or in combination therapy (4). However, the “watch and wait” approach has been found to be equally effective and is the most common approach amongst oncologists in the United States (11).Figure 1.: Endoscopic images of the duodenal second portion. Three distinct 5-mm pale nodules were seen and biopsies. First, second, and third lesions are seen in figure 1A, 1B, and 1C, respectively.

Duodenal-type follicular lymphoma more than 10 years after treatment intervention: A retrospective single-center analysis.

BACKGROUNDDuodenal-type follicular lymphoma (D-FL) has been recognized as a rare entity that accounts for approximately 4% of primary gastrointestinal lymphomas. D-FL follows an indolent clinical course compared with common nodal FL and is generally considered to have a better prognosis. Therefore, the “watch and wait” approach is frequently adopted as the treatment method. Alternatively, there is an option to actively intervene in D-FL. However, the long-term outcomes of such cases are poorly understood.AIMTo clarify the clinical outcomes after long-term follow-up in cases of D-FL with treatment intervention.METHODSWe retrospectively analyzed patients who met the following criteria: the lesion was confirmed by endoscopy, the diagnosis of D-FL was confirmed histopathologically, and the patient was followed-up for more than 10 years after the intervention at our center.RESULTSWe identified 5 cases of D-FL. Two patients showed a small amount of bone marrow involvement (Stage IV). Rituximab was used as a treatment for remission in all 5 patients. It was also used in combination with chemotherapy in 2 Stage IV patients as well as for maintenance treatment. Radiation therapy was performed in 2 cases, which was followed by complete remission (CR). Eventually, all 5 patients achieved CR and survived for more than 10 years. However, 3 patients experienced recurrence. One patient achieved a second CR by retreatment, and in another case, the lesion showed spontaneous disappearance. The remaining patient had systemic widespread recurrence 13 years after the first CR. Biopsy results suggested that the FL lesions were transformed into diffuse large B-cell lymphoma. The patient died 4 years later despite receiving various chemotherapies.CONCLUSIONIn this study, the treatment for patients of D-FL in Stage IV was successful. In the future, criteria for how to treat “advanced” D-FL should be established based on additional cases. This study of patients with D-FL indicates that whole-body follow-up examinations should continue for a long time due to a fatal recurrence 13 years after reaching CR.

Evolution in the Definition of Follicular Lymphoma and Diffuse Large B-Cell Lymphoma: A Model for the Future of Personalized Medicine

The definitions of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are evolving in the era of personalized medicine. Early stages of the evolution of FL have been recognized. Two histological manifestations of early lesions are in situ follicular neoplasia and duodenal type FL. Additionally, FL frequently undergoes histological transformation, the most common form being DLBCL. High-grade B-cell lymphoma with double hit, with translocations involving BCL2 and MYC are important clinically. Rarer forms of transformation include classic Hodgkin lymphoma (CHL) and histiocytic sarcoma. In addition to conventional FL associated with the BCL2 translocation, alternative forms of BCL2-negative FL have been observed. These are heterogenous clinically and genetically. A distinctive group of B-cell lymphomas of follicle cell derivation arise in young patients and include pediatric type FL, testicular FL and a large B-cell lymphoma with IRF4 rearrangement. Historically DLBCL was separated into only two histological variants, centroblastic and immunoblastic. In 2017 the WHO classification recommended (1) the segregation of activated B cell and germinal center B cell derived DLBCL, (2) the identification of high-grade B-cell lymphoma with double hit, and (3) the recognition of an aggressive lymphoma that may resemble Burkitt lymphoma, currently designated in the International Consensus Classification as Large B-cell lymphoma with 11q aberration. Today we appreciate greater genomic complexity among aggressive B-cell lymphomas. Recent studies with NGS and mutational profiling have identified clinically significant genetic subgroups. It is hoped that these data ultimately will lead to targeted therapy based on the genetic profile.

Clinical features and outcomes of duodenal-type follicular lymphoma: A single-center retrospective study.

Duodenal‐type follicular lymphoma (FL) is a rare and newly recognized disease. Few data are available on the outcomes and treatment strategies for patients with duodenal‐type FL. We aimed to investigate the clinical features and outcomes of duodenal‐type FL. We defined duodenal‐type FL as involvement of the duodenum, without nodal or extranodal lesions other than intestinal lesions, pathologically diagnosed as FL. We reviewed 26 patients with duodenal‐type FL between January 2011 and December 2020 at Kobe City Hospital Organization, Kobe City Medical Center General Hospital. In particular, patients were selected for the watch and wait (WW) strategy and followed up with regular esophagogastroduodenoscopy about once a year at our institution. The patient characteristics were as follows: median age 63.5 years (range: 42–78), sex (male, 15; female, 11), stage (I, 26), and grade (I, 26). Regarding treatment strategies, 23 patients were selected for the WW strategy, and three patients received initial rituximab therapy. The median follow‐up period was 65.5 months (range: 0.2–109). Five‐year progression‐free survival and 5‐year overall survival rates were 86.3% and 100%, respectively. Among the 23 patients selected for the WW strategy, six had spontaneous complete regression, and 14 had stable disease, and three had progressive disease, including one with histologic transformation. The WW strategy for patients with duodenal‐type FL could be an appropriate and safe treatment option. However, in several cases, disease progression was documented, and regular follow‐up is important.

A long-term follow-up study with pathological analysis of histological transformation in duodenal-type follicular lymphoma

A long-term follow-up study with pathological analysis of histological transformation in duodenal-type follicular lymphoma

Favorable response of duodenal-type follicular lymphoma to single-agent rituximab

Favorable response of duodenal-type follicular lymphoma to single-agent rituximab