Primary Gastrointestinal Follicular Lymphoma Research Articles

Epidemiological features and prognosis for primary gastrointestinal follicular lymphoma.

Primary gastrointestinal follicular lymphoma (PGI-FL) is a rare extra-nodal lymphoma. Its epidemiology and prognosis remain unclear. We performed a retrospective analysis of eligible patients with 1648 PGI-FL and 34 892 nodal FL (N-FL) in the Surveillance, Epidemiology and End Results (SEER) database. The age-adjusted average annual incidence of PGI-FL was 0.111/100000. The median overall survival (OS) for PGI-FL and N-FL patients was 207 and 165 months respectively. The 5-year diffuse large B-cell lymphoma (DLBCL) transformation rates were 2.1% and 2.6% respectively. Age, sex, grade, Ann Arbor stage, primary site and radiation were independent prognostic factors (p < 0.05). Nomograms were constructed to predict 1-, 5- and 10-year OS and disease-specific survival (DSS). The receiver operating characteristic curves and calibration plots showed the established nomograms had robust and accurate performance. Patients were classified into three risk groups according to nomogram score. In conclusion, the incidence of PGI-FL has increased over the past 40 years, and PGI-FL has a better prognosis and a lower DLBCL transformation rate than N-FL. The nomograms were developed and validated as an individualized tool to predict survival. Patients were divided into three risk groups to assist clinicians in identifying high-risk patients and choosing the optimal individualized treatments.

Primary gastrointestinal follicular lymphoma

Primary gastrointestinal follicular lymphoma

Pathogenesis of Gastrointestinal Follicular Lymphomas: Consideration Based on Histopathology and Endoscopic Findings.

Gastrointestinal (GI) follicular lymphoma (FL) is the most frequently diagnosed extranodal FL; however, its pathogenesis is debatable. We investigated the distribution, endoscopic, and histopathologic findings of 366 GI FL samples obtained from 298 patients. FLs were most frequently observed in the small intestine (71%), including the duodenum (52%), but were also commonly found in the stomach (15%) and colon (12%). The proportion of granular lesions in the duodenum, terminal ileum, colon, and stomach was 74%, 39%, 24%, and 0%, respectively. Submucosal or ulcerated tumors were frequently observed in the stomach (48%) and colon (52%). Most GI FL showed grade 1 to 2 histology (89%) as well as CD10 + (93%) and BCL2 + (98%) positivity. There were no significant differences in the endoscopic or histologic findings between primary and secondary GI FLs. As known, the mucosa of the small intestine is thin and villous, while the mucosa of the stomach and colon is thicker and has a smooth surface. Granular lesions corresponding to very small FL were detected in the former but rarely in the latter. Nine (7%) patients with primary GI FL developed histologic transformation to diffuse large B-cell lymphoma (n=8) or high-grade B-cell lymphoma (n=1) 10 months to 14 years after the diagnosis of FL. Two patients died of lymphoma. In conclusion, the incidence and endoscopic findings differed, but the histopathology was similar in FLs in each site. These differences might be attributed to variations in each GI site's mucosal structure and the neoplastic follicles' size. Due to its characteristic structure, very small classic FLs might be detectable mainly in the small intestine.

Outcomes in primary gastrointestinal (GI) follicular lymphoma (FL): results from a multicenter analysis

Introduction: GI FL is a rare disease, accounting for less than 5% of GI non-Hodgkin’s lymphomas (NHL). We formed a consortium to clarify baseline features, common practices and survival outcomes in primary GI FL. Methods: A retrospective analysis of 182 patients (pts) with primary GI FL from 8 institutions was conducted. Overall survival (OS) and progression-free survival (PFS) were assessed. Cox regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Results: Median age at diagnosis (dx) was 60 years (yrs) (IQR: 51–68). 89% (n = 141) of pts had low-grade FL by histology, and most presented with a low-risk score by FLIPI (68%, n = 111) or FLIPI-2 (76%, n = 103). At presentation, 18% (n = 32) of pts were asymptomatic, and 71% (n = 124) had at least one GI symptom, most commonly abdominal pain (40%, n = 70). 5% (n = 9) of pts presented with overt GI bleeding, and 9% (n = 15) with bowel obstruction. The most common first-line strategy was observation (33%, n = 59), of which 36% (n = 21) underwent surgical resection at dx. Other regimens included single-agent rituximab (R) (22%, n = 39), chemoimmunotherapy (CI) with R-bendamustine (18%, n = 32) or R-CHOP (11%, n = 19), and radiation therapy (5%, n = 9). The remainder received other CI combinations or R-lenalidomide. For those observed, median time to first treatment (tx) was 4.6 yrs. For those treated, overall response rate was 83% (95% CI, 76%–89%), and median time to second-line tx was 3.7 yrs. With median follow-up of 5.7 yrs, median OS was not reached. 5-yr PFS and OS were 71% (95% CI, 64%–79%) and 93% (95% CI, 89%–98%), respectively. Relevant factors that did not show a significant effect on PFS/OS included advanced disease by Paris and Ann Arbor staging systems, high-risk disease by FLIPI or FLIPI-2, B symptoms, GI symptoms, location of disease within the GI tract, and bone marrow involvement. Patients who were initially observed had similar OS to those who were treated up-front; PFS/OS did not improve significantly with use of maintenance rituximab. Factors that significantly impacted PFS and/or OS are outlined in Table 1. Conclusion: This multi-institutional analysis describes characteristics of the largest cohort of pts with GI FL to date. Observation or tx with rituximab ± chemotherapy were common initial approaches. Patients in this cohort had a good overall prognosis. While some factors including age, grade and BCL-2 expression by immunohistochemistry (IHC) predicted survival, traditional prognostic indices and staging systems did not. The research was funded by: No funding to disclose. Keyword: Extranodal non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. T. Alrifai Consultant or advisory role: Previous independent consultancy for MJH Life Sciences; completed in June of 2022. J. Kline Employment or leadership position: Speaker for Kite Pharma, Inc./Gilead. B.A.D Consultant or advisory role: Advisory boards for Merck, Kite Pharma, Inc./Gilead, Seattle Genetics, and Verastem Oncology Honoraria: Has received advisory board fees from Janssen, Sanofi, and consulting fees from COTA Healthcare. Research funding: Research support from Merck, iTeos, and Verastem Oncology R. Karmali Employment or leadership position: Speakers Bureau: AstraZeneca, BeiGene, Morphosys Consultant or advisory role: Advisory Board: BMS, Gilead Sciences/Kite Pharma, Janssen, Pharmacyclics, Morphosys, Epizyme, Genentech/Roche, Calithera, Miltenyi, Lilly Oncology Research funding: Grants/Research Support: BMS, Takeda, BeiGene, Gilead Sciences/Kite, Calithera

Ibritumomab Tiuxetan Radioimmunotherapy for Primary Gastrointestinal Follicular Lymphoma.

Primary gastrointestinal follicular lymphoma (PGIFL) is characterized by localized involvement of the gastrointestinal (GI) tract. PGIFL usually runs an indolent course. External beam radiation therapy is curative in a substantial proportion of localized follicular lymphomas, but GI toxicities may discourage its use in PGIFL. Ibritumomab tiuxetan radioimmunotherapy (RIT) is a radioimmunoconjugate of anti-CD20 monoclonal antibody linked to chelator tiuxetan and radioisotope. RIT delivers confined high-intensity radiation with short path length specifically targeting lymphoma cells and sparing normal tissue. In this case series report, we included six cases of PGIFL treated with RIT. All patients had low-risk, localized, and nonbulky disease. All patients responded completely and were relapse-free for the duration of follow-up. Hematologic toxicities were seen, but none were serious. RIT is a potentially curative treatment option in PGIFL with a tolerable toxicity profile.

A Rare Case of Primary Gastrointestinal Follicular Lymphoma Presenting as Dyspepsia

A Rare Case of Primary Gastrointestinal Follicular Lymphoma Presenting as Dyspepsia

A Rare Case of Primary Gastrointestinal Follicular Lymphoma Detected After Thorough Evaluation of the Duodenum

A Rare Case of Primary Gastrointestinal Follicular Lymphoma Detected After Thorough Evaluation of the Duodenum

Primary Gastrointestinal Follicular Lymphoma: When Lymphoid Infiltrate is not Benign

Background Primary gastrointestinal follicular lymphoma is a rare variant of follicular lymphoma. The most common location of involvement is the second portion of the duodenum and detection is often incidental during upper endoscopy. The clinical course is usually indolent. Dissemination is rare and transformation into high-grade lymphoma almost never occurs even without treatment. Histologically, diagnosis can be difficult, appearing as a benign lymphoid infiltrate prior to immunohistochemical staining. We present the case of a patient with a rare primary gastrointestinal follicular lymphoma. Case A 54-year-old Caucasian female previously healthy was referred for evaluation of intermittent epigastric pain associated with reflux. There were no fevers, chills or weight loss. Upper endoscopy performed at an outside facility was significant for a nodular duodenal mucosa in the bulb and second portion with biopsy showing atypical lymphoid infiltrate. A repeat upper endoscopy at our facility had identical endoscopic findings with extensive duodenal biopsy showing lymphoid infiltrate. A second pathologic opinion noted lymphoid nodules with small and large cells that were CD20 positive B-cells which co-expressed Bcl-2, Bcl-6 and CD10 consistent with follicular lymphoma. Staging position emission tomography scan showed no hypermetabolic areas and bone marrow biopsy showed no lymphoma but did note an incidental chronic lymphocytic leukemia. Discussion Follicular lymphoma comprises only 1-3% of primary gastrointestinal lymphomas. When follicular lymphoma does involve the gastrointestinal tract, the duodenum is most often affected (89% of cases). Endoscopically, follicular lymphoma usually manifests as multiple white nodules < 10 mm in size. The diagnosis of follicular lymphoma requires identification of a neoplastic infiltrate forming nodular follicles. The majority of primary gastrointestinal follicular lymphomas express Bcl-2 and CD-20. Treatment options include: watch and wait, radiation, rituximab monotherapy or chemotherapy with or without radiation. Conclusions Primary gastrointestinal follicular lymphoma is a rare, indolent neoplasm that may appear as a benign lymphoid infiltrate. Immunohistochemical staining is critical in making the diagnosis particularly in the setting of atypical lymphoid infiltrates that are nodular. In patients with localized disease, clinical outcomes are excellent even without therapy.Figure: Follicular lymphoma duodenal bulb.

A Rare Case of Primary Gastrointestinal Follicular Lymphoma With Exclusive Involvement of the Mucosal Layer of Duodenum

58-year-old woman with a past medical history of GERD presented with indigestion and bloating. Vital signs, physical exam, and routine labs were unremarkable. She underwent an EGD which revealed a 15-mm frond-like lesion in the second portion of the duodenum along the lateral wall. Biopsy was obtained and pathology showed a lymphoid infiltrate with prominent germinal centers concerning for a lymphoproliferative disorder. However the specimen was inadequate. She therefore underwent an EGD/EUS which revealed a 15-mm sessile polypoid lesion in the same location. The lesion was noted to be limited to the mucosa with normal appearance of all the other duodenal wall layers. No abnormal appearing lymph nodes were seen surrounding the examined portion of the duodenum. The lesion was resected by endoscopic mucosal resection (EMR). Pathology showed frequent intramucosal follicular aggregates of lymphocytes. Immunostains showed the follicles to be positive for pan B-cell antigens CD20 and CD79a. Numerous associated T cells were positive for CD3 and CD5. Cyclin D1 was negative and CD10 was positive consistent with follicular center cells and follicles were positive for BCL-2 consistent with neoplastic follicles. Diagnosis was consistent with indolent grade 1-2 follicular lymphoma stage IE. A body CT scan showed heterogenous attenuation pattern within the vertebral bodies. No lymphadenopathy or splenomegaly were present. She is scheduled to undergo a spine MRI with plans for a bone marrow biopsy if bone marrow replacement is detected. Primary GI FL accounts for only 1-3% of the GI lymphomas. It predominantly affects middle-aged females. The duodenum accounts for the majority of small intestinal FL. Endoscopic findings include isolated follicles, single or multiple polyps, plaques and nodularity of mucosa. Histopathologic features include predominant involvement of lamina propria and to a lesser extent, submucosa. Isolated mucosal involvement such as in our case is extremely rare. EUS can assess the size and depth of the lesion as well as detect locoregional spread. Endoscopic biopsies may not always provide adequate diagnostic material. In such situations, EMR could be considered to enhance the diagnostic yield as well as to diagnose the infiltrative type of lymphoma. We hereby report a rare presentation of primary GI FL that exclusively involved the mucosal layer, using a combination of advanced endoscopic techniques.Figure: EGD showing polypoid lesion within the duodenum.Figure: EUS showing no lesion within the deeper duodenum layer.

WEO Newsletter.

WEO Newsletter.

Primary gastrointestinal follicular lymphoma of the small intestine with massive hemorrhage: a report of three cases

Primary gastrointestinal follicular lymphoma (FL) has an indolent clinical presentation and many of cases are diagnosed incidentally during routine endoscopic examinations. Herein, we present 3 cases with FL of the small intestine developed massive intestinal hemorrhage that necessitated blood transfusion. In all three patients, upper and lower endoscopic examinations failed to detect the bleeding sites. Eventually, video capsule endoscopies identified ulcerative lesions in the jejunum and biopsies using single- or double-balloon endoscopy confirmed the FL diagnosis in our three cases. The respective clinical stages according to the Lugano system were I, II-1 and II-1. PET-CT did not play a significant role in identifying the gastrointestinal lesions. Two patients received rituximab monotherapy and achieved a complete response. The other remains under observation after termination of antiplatelet drug therapy. Generally, the macroscopic appearance of multiple whitish nodules and the absence of symptoms represent the typical clinical picture of gastrointestinal FL. However, this study demonstrates that patients with ulcerative lesions may be at risk for massive bleeding. Further discussion is required to determine the optimal indications for total endoscopic examination of the small intestine.

Diagnosis of follicular lymphoma of the gastrointestinal tract: A better initial diagnostic workup.

Due to an increasing incidence and more frequent recognition by endoscopists, gastrointestinal follicular lymphoma has been established as a variant of follicular lymphoma. However, due to its rarity, there are no established guidelines on the optimal diagnostic strategy for patients with primary gastrointestinal follicular lymphoma or secondary gastrointestinal involvement of systemic follicular lymphoma. This review offers an overview and pitfalls to avoid during the initial diagnostic workup of this disease entity. Previously reported case reports, case series, and retrospective studies are reviewed and focus on the disease's endoscopic and histological features, the roles of computed tomography and positron emission tomography scanning, the clinical utility of the soluble interleukin-2 receptor, and the possible pathogenesis.

Primary Gastrointestinal Follicular Lymphoma: Characterizing Survival by Primary Site

Primary Gastrointestinal Follicular Lymphoma: Characterizing Survival by Primary Site

Primary gastrointestinal follicular lymphoma with histological transformation

Dear Editor, Primary gastrointestinal follicular lymphoma (GI-FL) accounts for 30 to 40 % of primary extranodal FL [1]. The disease usually manifests as multiple small polyps in the duodenum or terminal ileum. Histological grade at presentation is low in most cases (95.8 %) and histological transformation (HT) is very rare [2]. Moreover, primary GI-FL is not visualized by fluorodeoxyglucose (FDG)-positron emission tomography (PET), which is in sharp contrast to nodal FL [1, 3]. Here, we describe a case of primary GI-FL with HT at initial presentation. A 45-year-old male was referred to our institution for evaluation of epigastralgia. Gastroduodenoscopy detected multiple and homogeneous small polyps without mass formation in the descending portion of the duodenum (Fig. 1a). A total of seven specimens were randomly taken from the polyps. Among them, six specimens showed proliferation of atypical lymphocytes with follicle formation (Fig. 1b). The immunophenotypes were CD3−, CD10+, CD20+, and bcl-2+. Fluorescence in situ hybridization analysis disclosed a BCL2-IGH fusion signal. These findings were consistent with FL. One specimen, however, showed transformation to large cell lymphoma with the same immunophenotype (Fig. 1c). FDG-PET combined with computed tomography scan was unremarkable including the descending duodenum (Fig. 1d). There was no evidence of bone marrow involvement. Finally, we made the diagnosis of primary GI-FL with HT. The patient underwent six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy plus rituximab. Gastroduodenoscopy after the treatment confirmed complete regression of the polypoid lesion. In the present case, aggressive biopsy led to an unexpected detection of HT. A study by Shia et al. demonstrated that 4 (15 %) of 26 primary GI-FL cases were found to have large cell lymphoma admixed with FL at initial diagnosis [4]. Therefore, HT within a GI-FL lesion at initial presentation is a recurrent phenomenon, although it has not been reconfirmed in later studies [2, 5]. Clinical features of the Shia's cases and ours provide important clues to characterize primary GI-FL with HT. Firstly, three (75 %) of four cases manifested as multiple nodules without mass formation on endoscopic examination. It is therefore likely that HT in primary GI-FL cannot be suspected by mere morphology. Secondly, all the patients were alive at 5 to 102 months after treatment with standard chemotherapy. HT inGI-FLmight be associatedwith a less aggressive outcome than HT in usual FL. S. Hangai : F. Nakamura :Y. Kamikubo :M. Ichikawa : M. Kurokawa Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan

Primary Follicular Lymphoma of the Duodenum Relapsing 11 Years after Resection

A 52-year-old Japanese woman was diagnosed with primary follicular lymphoma of the duodenum that was curatively resected by pancreatoduodenectomy. She remained in complete remission until 11 years after the surgery, when multiple enlarged intra-abdominal lymph nodes were demonstrated by computed tomography scans and positron emission tomography scans. Two years later, jejunal lesions were detected by endoscopy, and biopsy samples confirmed a recurrence of follicular lymphoma. This case indicates that primary gastrointestinal follicular lymphoma has a potential of relapse after an extended period of time, and thus patients must be followed up for over 10 years after complete remission.

Primary Gastrointestinal Follicular Lymphoma: Single-Center 12 Year Experiences

Primary gastrointestinal follicular lymphoma (GI-FL) is very rare and its natural course is barley known. This study aimed to evaluate the clinical characteristics of primary gastrointestinal follicular lymphoma (GI-FL). From May 1996 to October 2008, the records of five patients diagnosed with primary GI-FL were retrieved from pathological files and retrospectively analyzed in terms of characteristics of endoscopic and clinical findings. The five patients consisted of 3 males and 2 females with a median age of 52 years. Abdominal pain was the most common (n=4, 80%) symptom. The most frequent site was the terminal ileum in the small bowel (n=3, 60%). Endoscopic findings were 3 of mass forming type, 1 of irregular ulcer type and 1 of whitish granular type. Three cases (60%) had a component of diffuse large B cell lymphoma. All cases received chemotherapy. While complete remission occurred in every patient, relapse occurred in the two patients with a higher grade and more advanced stage than the other cases. At a median follow-up time of 37 months (range, 27-58 months; mean, 38.8 months), four patients (80%) were disease free and one patient had died of cardiovascular disease. In South Korea, primary gastrointestinal follicular lymphoma is very rare and symptomatic. Endoscopic findings were variable from early whitish granular lesions to advanced mass forming lesions.

Primary gastrointestinal follicular lymphoma involving the duodenal second portion is a distinct entity: A multicenter, retrospective analysis in Japan

We conducted a multicenter, retrospective study to determine the anatomical distribution and prognostic factors of gastrointestinal (GI) follicular lymphoma (FL). This study included 125 patients with stage I and II(1) GI-FL. Of the 125 patients, the small intestine was examined in 70 patients, with double-balloon endoscopy and/or capsule endoscopy. The most frequently involved GI-FL site was the duodenal second portion (DSP) (81%), followed by the jejunum (40%); 85% of patients with involvement of the DSP also had jejunal or ileal lesions. The absence of abdominal symptoms and macroscopic appearance of multiple nodules were significantly present in the DSP-positive group. During a median follow up of 40 months, six patients showed disease progression. Patients with involvement of the DSP had better progression-free survival (PFS) than those without such involvement (P = 0.001). A multivariate analysis revealed that male sex, the presence of abdominal symptoms, and negative involvement of the DSP were independently associated with poor PFS. In conclusion, most patients with GI-FL have duodenal lesions associated with multiple jejunal or ileal lesions. Gastrointestinal follicular lymphomas involving the DSP might be a distinct entity showing a favorable clinical course.

Impact of double-balloon endoscopy on the diagnosis of jejunoileal involvement in primary intestinal follicular lymphomas: a case series

In recent years, primary gastrointestinal follicular lymphoma has been increasingly detected in the duodenum on esophagogastroduodenoscopy (EGD). Primary gastrointestinal follicular lymphomas are frequently distributed to multiple sites in the gastrointestinal tract. Therefore, investigation into the spread of follicular lymphomas in the small bowel is important in order to determine the most appropriate treatment strategy. The performance of double-balloon endoscopy (DBE) in the diagnosis of jejunoileal follicular lymphoma lesions has not been fully evaluated. We aimed to investigate the value of DBE in addition to computed tomography (CT) and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) in the diagnosis of jejunoileal follicular lymphoma. DBE with biopsy was performed in seven patients with primary duodenal follicular lymphoma diagnosed by EGD, in order to investigate jejunoileal involvement. Jejunoileal follicular lymphoma lesions were detected by DBE in six out of the seven patients (three in the jejunum and three in the jejunum and ileum), whereas CT and (18)F-FDG-PET failed to detect the existence of these lesions. Endoscopic findings of the jejunoileal lesions revealed multiple white nodules and white villi, which were similar to those of duodenal lesions. DBE was more useful for the diagnosis of jejunoileal involvement in primary intestinal follicular lymphoma than CT and (18)F-FDG-PET. The use of DBE will become important for determining the most appropriate treatment for gastrointestinal follicular lymphoma.

Primary Gastrointestinal Follicular Lymphoma: A Clinicopathologic Study of 13 Cases From Taiwan

Follicular lymphoma (FL) is a common nodal lymphoma. Primary gastrointestinal follicular lymphoma (GIFL) is rare and most commonly occurs in the elder women with indolent clinical course, mainly in the duodenum and terminal ileum. We conducted this study to characterize GIFL in Taiwan. A total of 13 cases were retrospectively collected in 4 hospitals in southern and eastern Taiwan up to 2006. Pathology review and immunohistochemistry were performed and the clinical data were obtained from chart review. There were 5 men and 8 women with a median age of 58 years (range, 31 to 74; mean, 55). The most frequent site was ileum (7/13, 54%) with 4 tumors in the terminal ileum and the most common symptom was abdominal pain (8/13, 62%). Multiple lymphomatous polyposis was present in 6 patients (46%). Five (45%) of 11 tumors with surgical resection showed transmural involvement. Most of the cases revealed a predominantly follicular pattern (7/13, 54%) and low-grade disease (grades 1 and 2; 10/13, 77%). The tumors expressed CD10 (62%), Bcl-2 (77%), Bcl-6 (77%), and MUM1 (38%). Five patients (38%) were at stage IE and 8 (62%) at stage IIE. Treatment included surgery with or without chemotherapy. All patients achieved complete remission and relapse occurred in 3 patients. At a median follow-up time of 51 months (range, 3 to 180; mean, 63), 11 patients (85%) were disease free and no patient died of lymphoma. We characterized the clinicopathologic features of the first series of GIFL in Taiwan. These tumors frequently involved ileum with a favorable prognosis.

Intramucosal follicular lymphoma in the terminal ileum with nodal involvement

Primary gastrointestinal follicular lymphoma (FL) is rare, and there is only one previously reported case with lymphoma cells confined within the mucosa, a stage IE disease. We present the second case of primary intramucosal FL located in the terminal ileum, with focal nodal involvement in a 47-year-old male. This unusual case demonstrates that even an intramucosal FL exhibits the potential for nodal spread, which is evidence of lymphocytic trafficking within the lymphoid system.