Gastrointestinal Follicular Lymphoma Research Articles

Primary Gastrointestinal Follicular Lymphoma: Characterizing Survival by Primary Site

Primary Gastrointestinal Follicular Lymphoma: Characterizing Survival by Primary Site

Tu1257 Evaluation of Capsule Endoscopy As a Diagnostic Method Before Treatment of Gastrointestinal Follicular Lymphoma

Tu1257 Evaluation of Capsule Endoscopy As a Diagnostic Method Before Treatment of Gastrointestinal Follicular Lymphoma

Diagnostic accuracy of endoscopic biopsies for the diagnosis of gastrointestinal follicular lymphoma: a clinicopathologic study of 48 patients

The purpose of this study was to reveal the diagnostic accuracy of initial pathologic assessment of biopsied samples in patients with gastrointestinal follicular lymphoma lesions. A total of 48 patients with follicular lymphoma (Lugano system stage I: n = 30; II1: n = 4; II2: n = 4; IV: n = 10) with gastrointestinal involvement who underwent endoscopic biopsy were enrolled and retrospectively reviewed. Nine (18.8%) of the 48 patients were not appropriately diagnosed as having follicular lymphoma at the initial biopsy. The initial pathological diagnosis included extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (n = 4), necrotic tissue (n = 2), duodenitis (n = 1), or suspected lymphoma of unspecified subtype (n = 2). The reasons for these inappropriate diagnoses were insufficient histopathologic analysis lacking CD10 and BCL2 staining (n = 7) and unsuitable biopsy samples taken from erosions or ulcers that contained scanty lymphoma cells or no lymphoid follicles (n = 2). In conclusion, incomplete histopathologic analysis and unsuitable biopsy samples are pitfalls in the diagnosis of gastrointestinal follicular lymphoma.

Gastrointestinal follicular lymphoma with lymphoepithelial lesions

Gastrointestinal follicular lymphoma with lymphoepithelial lesions

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

Endoscopic diagnosis of follicular lymphoma with small-bowel involvement using video capsule endoscopy and double-balloon endoscopy: a case series

The aims of this study were to compare the detection rates of gastrointestinal follicular lymphoma lesions by video capsule endoscopy (VCE) and double-balloon endoscopy (DBE), and to determine the pathologic diagnostic yields of DBE-directed biopsies. A total of 27 consecutive patients were enrolled. No significant difference in detection rates was observed in 12 patients who underwent total enteroscopy at both VCE and DBE. Pathologic diagnostic yields stratified by location were 91 % in the proximal duodenum at esophagogastroduodenoscopy, 88 % in the jejunum at antegrade DBE, 52 % in the ileum at retrograde DBE, and 57 % in the terminal ileum at colonoscopy. VCE and DBE were helpful in determining treatment in 44 % of patients.

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.

Clinical Features of Gastrointestinal Follicular Lymphoma: Comparison with Nodal Follicular Lymphoma and Gastrointestinal MALT Lymphoma

We retrospectively compared the clinicopathological features of primary intestinal follicular lymphomas (FL-GIs), nodal follicular lymphomas (FL-LNs) and gastrointestinal MALT lymphomas (MALT-GIs), and investigated the distribution and the endoscopic appearances of FL-GI to evaluate the effectiveness of treatment modality. The subjects were 28 FL-GI patients, 135 FL-LN patients and 70 MALT-GI patients. In FL-LNs the clinical stage III–IV was 83%, while in FL-GIs clinical stage I–II was 68%. In MALT-GIs clinical stage I–II was 87%. The overall survival was significantly better in MALT-GI patients than in FL-LN patients. All FL-GI patients were alive at the time of evaluation. Regarding the histological grade (WHO), grade 1 was 81% in FL-GI, whereas in FL-LN grade 2 was 28% and grade 3 was 11%. The Follicular Lymphoma International Prognostic Index was low in 61% of FL-GIs, while in FL-LNs it was equally distributed to low, intermediate and high, suggesting that the prognosis is better in FL-GIs than in FL-LNs. The clinicopathological studies revealed the FL-GI has intermediate characteristics between FL-LN and MALT-GI. We recommend a ‘watch-and-wait’ policy or chemotherapy with rituximab for the therapy of FL-GIs because the lesions are often located in broader areas from the lower duodenum to the small intestine.

Translocation t(14;18)/IGH‐BCL2 in gastrointestinal follicular lymphoma

Chromosomal translocation t(14;18)(q32;q21) involving the immunoglobulin heavy chain gene (IGH) and the BCL2 gene (t[14;18][q32;q21]/IGH-BCL2) is present in 60% to 90% of nodal follicular lymphomas. To the authors' knowledge, the prevalence and clinical significance of this translocation have not been examined previously in gastrointestinal follicular lymphomas. Clinicopathologic and molecular features were investigated in 48 patients who had gastrointestinal follicular lymphoma. The site of involvement was the duodenum in 54% of patients, the jejunum in 52%, the ileum in 52%, the stomach in 29%, and the colorectum in 15%. The presence of the t(14;18)/IGH-BCL2 translocation was detected by interphase fluorescence in situ hybridization. Treatment modalities included surgical resection (n = 16), rituximab plus chemotherapy (n = 13), rituximab alone (n = 6), antibiotics (n = 5), and watchful waiting (n = 8). Complete remission (CR) of lymphoma was achieved in 31 patients (65%). The overall survival and event-free survival rates after 5 years were 93% and 68%, respectively. The t(14;18)/IGH-BCL2 was detected in 39 patients (81%). The involvement of multiple sites (69% vs 0%), manifestation of the lymphomatous polyposis type (72% vs 22%), and histologic grade 1 or 2 tumors (92% vs 56%) were more frequent in the t(14;18)-positive group than in the negative group. In addition, the CR rate was lower in the t(14;18)-positive group than in the negative group (56% vs 100%; P = .0179), and a trend was observed toward poorer event-free survival in the positive group (P = .089). The t(14;18)/IGH-BCL2 chromosomal translocation occurred frequently in gastrointestinal follicular lymphomas. The current results indicated that this translocation may be a predictor of an adverse clinical course.

Colonic Perforation Following Polypectomy of a Gastrointestinal Follicular Lymphoma Masquerading as a Colon Polyp

The gastrointestinal (GI) tract is the predominant site for primary extranodal non-Hodgkin lymphomas (NHL), accounting for 5-10% of all extranodal disease. A 74-year-old man underwent colonoscopy for a positive fecal occult blood test. Colonoscopy revealed a 3.5-cm polyp in the descending colon and was removed by snare cautery polypectomy. Post-polypectomy site showed a 0.3-0.5-cm mucosal defect. Five endoclips were applied to close the mucosal defect. The patient remained stable during subsequent intensive monitoring and never required surgical intervention. Pathology of the polyp revealed follicular lymphoma (FL) involving the lamina propria of the mucosa with extension into the submucosa. The patient had no systemic symptoms, and staging for NHL with contrast computerized tomography of the chest, abdomen, and pelvis revealed no evidence suggestive of lymphoma. Approximately 6-20% of all primary GI-NHL are in the colon. The frequency of GI-FL accounts for 1-3.6% of all GI-NHL. After a search of the current literature, there have been no cases of a follicular lymphoma presenting solely as an isolated colon polyp. Likewise, bowel perforation due to polypectomy of such polyps has never been cited. Retrospectively, the diagnosis and extent of the polyp could have been established using endoscopic end-to-end forceps biopsy and/or endoscopic ultrasound with a radial scanning catheter probe and fine-needle aspiration of the lesion. Such a diagnosis could have changed the strategy for endoscopic removal of the polyp. Our case is interesting because it is the first report of a follicular lymphoma presenting as a single isolated colon polyp involving all layers of the colonic mucosa.

Colonic Perforation Following Polypectomy of a Gastrointestinal Follicular Lymphoma Masquerading as a Colon Polyp

Colonic Perforation Following Polypectomy of a Gastrointestinal Follicular Lymphoma Masquerading as a Colon Polyp

Gastrointestinal follicular lymphoma: review of the literature

Gastrointestinal follicular lymphoma (GI-FL) is a relatively rare disease, accounting for only 1%-3.6% of gastrointestinal non-Hodgkin's lymphoma. Although the duodenum and terminal ileum are considered to be the most common sites of origin, the development of wireless capsule endoscopy and double-balloon enteroscopy has increased the detection of GI-FL in every part of the small intestine. Approximately 70% of patients with GI-FL are estimated to have multiple lesions throughout the entire gastrointestinal tract. FL is a low-grade lymphoma that usually develops very slowly. If the lymphoma causes no symptoms, immediate treatment may not be necessary. Standard therapy has not yet been established for GI-FL, but chemotherapy, radiotherapy, monoclonal antibody therapy, or a combination of these therapies, is sometimes performed based on the therapeutic regimens for nodal FL. Regimens including conventional chemotherapy with rituximab, which achieve high response rates in nodal FL, are commonly used for GI-FL. The long-term clinical outcome of GI-FL is unclear. The results of a few series on the long-term outcomes of patients with GI-FL treated with conventional therapy indicate a median relapse-free time ranging from 31 to 45 months. On the other hand, in patients with GI-FL who were followed without treatment, the median time to disease progression was 37.5 months. Thus, whether to initiate aggressive therapy or whether to continue watchful waiting in patients with GI-FL is a critically important decision. Ongoing research on biomarkers to guide individualized GI-FL therapy may provide invaluable information that will lead to the establishment of a standard therapeutic regimen.

Gastric follicular lymphoma with mediastinal lymph node dissemination detected by FDG-PET

We read with great interest the article by Higuchi et al., ”Impact of double-balloon endoscopy on the diagnosis of jejunoileal involvement in primary intestinal follicular lymphomas: a case series“ [1]. There is no doubt that, as they concluded, double-balloon endoscopy is useful for evaluating the spread of jejunoileal lesions in patients with gastrointestinal follicular lymphoma (GI-FL). In their report, however, the authors stated that fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) was not useful for the clinical assessment of GI-FL. To show the impact of [18F]FDG-PET on the staging of GI-FL, we report a patient with GI-FL in whom distant dissemination was detected using [18F]FDG-PET.

Treatment strategies for nodal and gastrointestinal follicular lymphoma: Current status and future development

In recent years, therapies for follicular lymphoma (FL) have steadily improved. A series of phase III trials comparing the effect of rituximab with chemotherapy vs chemotherapy alone in treating FL have indicated significant improvements in progression-free survival (PFS) and overall survival. Recent studies have found that prolonged response durations and PFS were obtained with maintenance therapy using rituximab or interferon after completion of first line therapy. For patients with relapsed or refractory FL, phase II studies have assessed the effectiveness of combination therapies using a Toll-like receptor-9 agonist (1018ISS), oblimersen sodium (a Bcl-2 antisense oligonucleotide), bendamustine, and rituximab, as well as veltuzumab, a new humanized anti-CD20 antibody, and epratuzumab. In addition, the effectiveness of yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab as radioimmunotherapies has been reported. Furthermore, three phase III studies on an idiotype vaccine are near completion. Unfortunately, these vaccines, which appeared highly effective in phase I and II trials, do not appear to result in prolonged PFS. This report will summarize the current knowledge on therapies for treatment of FL, and will conclude with a brief discussion of feasible future options for effective treatments. Lastly, we added descriptions of the management of gastrointestinal FL, which is considered to be controversial because it is rare.

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.

Endoscopic Findings of Follicular Lymphoma of the Gastrointestinal Tract: The Efficacy of a Double Balloon Enteroscopy for the Diagnosis

Endoscopic Findings of Follicular Lymphoma of the Gastrointestinal Tract: The Efficacy of a Double Balloon Enteroscopy for the Diagnosis Kentaro Moriichi, Jiro Watari, Yusuke Saitoh, Chisato Ishikawa, Yuhei Inaba, Takahiro Itoh, Kotaro Okamoto, Katsuya Ikuta, Hiroki Tanabe, Kazuya Sato, Tokiyoshi Ayabe, Toshifumi Ashida, Yoshihiro Torimoto, Yutaka Kohgo Background/Aims: Follicular lymphoma is an uncommon and poorly defined disease of the gastrointestinal (GI) tract in which mucosa-associated lymphoid tissue lymphoma arises most frequently. Recently, the double-balloon method, a novel method for enteroscopy, was developed for the diagnosis and treatment of the disease of the small intestines. We investigated the endoscopic findings of GI follicular lymphoma and the usefulness of the new enteroscopy for the diagnosis. Materials and Methods: From 1999 to 2004, six patients with follicular lymphoma of the GI tract were diagnosed in our unit. All patients were histologically diagnosed as follicular lymphoma with H&E and immunohistochemical stains positive for B-cell markers and Bcl-2 protein, including rearrangement of IgH and Bcl-2 gene. We performed GIF-XQ230 and XQ240 for upper endoscopy and CF-240I and 240AI for colonoscopy with chromoendoscopy, respectively (Olympus Optical co., Tokyo, Japan). A double balloon enteroscopy was used with EM450-P5 and T5 (Fujinon Toshiba ES Systems Co., Ltd. Tokyo, Japan). For the diagnosis of lesion in the small intestine, small bowel enema was performed instead. Results: 1) Endoscopic findings of the duodenum and the small intestines revealed as follows two types: multiple lymphomatous polyposis (MLP) (A type, n Z 2) and multiple white small polyps and elevated plaques (B type, n Z 3). One patient had gastric lesions shown as verrucous lesions that are not present in the duodenum and small intestines. 2) All the lesions of the colorectum showed an obscure mucosa with the disappearance of transparency of the mucosal vessel. 3) Interestingly, colorectal lesions were detected only in patients with A type and gastric lesions. 4) A double balloon enteroscopy was performed in two patients with B type, and both cases were endoscopically and histologically diagnosed as follicular lymphoma by the enteroscopy. 5) Out of the four patients who received small bowel enema, the lesions were demonstrated radiographically in three patients. In the fourth case, the lesions in the small intestines were detected only by a double balloon enteroscopy. Conclusions: Endoscopic findings of follicular lymphoma of the GI tract showed two distinct categories. The cases that showed MLP type and gastric lesions may also have concomitant colorectal lesions with minute findings. A double balloon enteroscopy is considered to be a useful procedure and provides Abstracts