Introduction

Follicular lymphoma primarily or secondarily occurs in the gastrointestinal tract¹. The disease entity of intestinal follicular lymphoma was established in the last two decades and is now formally considered a distinct subcategory of follicular lymphomas in the classification of tumors of hematopoietic and lymphoid tissues published by the World Health Organization (WHO)². Multiple white, polypoid lesions in the duodenum, which are incidentally found during esophagogastroduodenoscopy, are the typical endoscopic features of intestinal follicular lymphoma. Among the patients with follicular lymphoma with intestinal involvement, 66.7–100% have multiple follicular lymphoma lesions in the jejunum and/or ileum. Because of the widespread involvement of the small intestine, radiotherapy is not feasible even in cases of localized stage intestinal follicular lymphoma. Although treatment strategies have not yet been standardized, the watch-and-wait approach is often preferred in clinical settings. However, because of the rarity of this disease, the long-term outcomes of patients who are managed with this approach have not been sufficiently investigated. Therefore, in the current study, we analyzed the outcomes of 73 patients with primary intestinal follicular lymphoma who were diagnosed before 2016 and managed using the watch-and-wait approach.

Aims & Methods

Patients with primary intestinal follicular lymphoma who were diagnosed before 2016 and managed with the watch-and-wait approach in 20 institutions were enrolled. We retrospectively investigated the overall, disease-specific, and event-free survival rates as well as the rate of spontaneous regression.

Results

Among the 248 patients with follicular lymphoma with gastrointestinal involvement, 124 had localized disease (stage I or II₁). We analyzed the data of 73 patients who were managed using the watch-and-wait approach. During the mean follow-up period of 8.3 years, the follicular lymphoma had spontaneously resolved in 16.4% of the patients. The 5-year and 10-year overall survival rates were 92.9% and 87.1%, respectively. With disease progression (n = 7), initiation of therapy (n = 7), and histologic transformation to aggressive lymphoma (n = 0) defined as events, the 5-year and 10-year event-free survival rates were 91.1% and 86.9%, respectively. No patient died of progressive lymphoma. Thus, both 5-year and 10-year disease-specific survival rates were 100%.

Conclusion

An indolent long-term clinical course was confirmed in the patients with primary intestinal follicular lymphoma. The watch-and-wait strategy is a reasonable approach for the initial management of these patients.

References

1. Harris, N.L., et al. Follicular lymphoma. In: Swerdlow, S.H., et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC, 220–226 (2008).
2. Yoshino, T., Chott, A. Duodenal-type follicular lymphoma. In: WHO Classification of Tumours Editorial Board, editors. WHO Classification of Tumours of Digestive System Tumours. Lyon: IARC, 383–385 (2019).

Disclosure

No

Clinical Case Summary

Duodenal-Type Follicular Lymphoma (DTFL) is a rare form of non-Hodgkin’s lymphoma, accounting for <4% of gastrointestinal lymphomas. Though generally indolent, misdiagnosis can lead to delayed diagnosis in progressive cases. We present a case highlighting the importance of awareness for early detection. A 53-year-old woman with persistent epigastralgia underwent esophagogastroduodenoscopy (EGD) three times over five years at different hospitals. Only the latest EGD revealed multiple whitish nodular lesions in the first portion of the duodenum. Biopsies showed follicular proliferation confined to the mucosa, composed of small cleaved lymphoid cells. Immunohistochemistry confirmed a B-cell phenotype (CD20+, CD79a+, CD3-, CD5-), a germinal center phenotype (CD10+, Bcl6+), Bcl2 expression and low Ki-67. Blood tests were unremarkable, and viral serology was negative. CT scans revealed only reactive submandibular lymph nodes, with a normal bone marrow biopsy. PET scan showed uptake limited to the duodenum, confirming stage I disease (Lugano classification). Given its indolent course, a watch-and-wait strategy was adopted, with stable findings at a six-month follow-up EGD. DTFL is often incidentally detected during endoscopy and can be mistaken for benign conditions. Although typically localized, it may spread beyond the duodenum. Awareness is crucial to avoid unnecessary interventions and ensure timely diagnosis. Immunohistochemistry is key to distinguishing DTFL from reactive lymphoid hyperplasia and other low-grade lymphomas. While treatment options vary, active surveillance remains the most common approach due to its favorable prognosis. This case highlights DTFL as a rare but clinically significant entity that is frequently misdiagnosed, leading to unnecessary procedures. Recognizing its endoscopic and histologic features is essential for early diagnosis and appropriate management.

References

Figure 1: Upper endoscopy shows nodularity with whitish spots in the second portion of the duodenum (D2)
Figure 2: Endoscopic view showing a whitish polypoid lesion approximately 3 cm from the papilla
Figure 3: Duodenal mucosa with nodular lymphoid infiltrate, suggestive of duodenal-type follicular lymphoma

1 - Marks E, Shi Y. Duodenal-Type Follicular Lymphoma: A Clinicopathologic Review. Arch Pathol Lab Med. 2018 Apr;142(4):542-547.
DOI: 10.5858/arpa.2016-0519-RS
2 -Junga Z, Stratton A, Laczek J. Primary Multifocal Small Bowel Follicular Lymphoma Discovered Incidentally on Diagnostic Endoscopy. Clin Gastroenterol Hepatol. 2017 Aug;15(8):A27-A28.
DOI: 10.1016/j.cgh.2017.03.007
3 -Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-2390.
DOI: 10.1182/blood-2016-01-643569

Clinical Case Summary

The gastrointestinal tract is the most common site for primary extranodal non-Hodgkin lymphoma (NHL), with small intestinal and ileocecal NHL accounting for 8.6% and 7.0%, respectively. However, primary ileal diffuse large B-cell lymphoma (DLBCL) presenting as a submucosal tumor (SMT)-like lesion is exceedingly rare. We report a case of primary ileal DLBCL resected via endoscopic mucosal resection (EMR).
A 67-year-old woman presented with intermittent left abdominal pain for six days. Initial abdominal CT suggested partial intestinal obstruction and eccentric thickening of the terminal ileum, with enlarged adjacent lymph nodes. Colonoscopy revealed an SMT-like lesion in the terminal ileum with smooth surface mucosa, measuring approximately 10 × 10 mm. Endoscopic ultrasound (EUS) showed a hypoechoic lesion originating from the muscularis mucosae. After obtaining informed consent from the patient and her family, endoscopic EMR was performed. Histopathology revealed a small round cell tumor, raising suspicion of lymphoma. Immunohistochemistry confirmed the diagnosis of B-cell non-Hodgkin lymphoma. Molecular testing showed no BCL2 or C-MYC rearrangement, leading to a final diagnosis of non-germinal center B-cell-like (non-GCB) DLBCL. Bone marrow biopsy demonstrated normal marrow without infiltration. PET-CT confirmed localized disease, and the patient received R-CHOP chemotherapy.
Primary ileal DLBCL presenting as an SMT-like lesion is extremely rare, and accurate diagnosis is challenging with current endoscopic techniques such as EUS and magnifying endoscopy with narrow-band imaging. Endoscopic resection can be employed for both diagnostic and therapeutic purposes. In this case, timely detection, rapid intervention, definitive diagnosis, and effective multidisciplinary collaboration (involving imaging, endoscopy, pathology, and chemotherapy) provided the patient with optimal treatment, resulting in a favorable prognosis.

Introduction

In the European Society of Gastrointestinal Endoscopy guidelines (updated 2022), obscure gastrointestinal bleeding (OGIB) should be reserved for patients not found to have a source of bleeding by small-bowel evaluation. Herein, OGIB was defined as P0 (no bleeding potential) or P1 (less likely to bleed), based on the P classification using small-bowel capsule endoscopy (CE). We aimed to clarify the long-term outcomes of patients with OGIB.

Aims & Methods

We retrospectively examined 796 consecutive patients with OGIB who underwent CE at the Hiroshima University Hospital between March 2014 and October 2021. Of the eligible patients, 302 were excluded because of small-bowel bleeding (148 patients), incomplete observation of the small-bowel (85 patients), a bleeding source located outside the small-bowel (67 patients), or equipment failure (2 patients). Therefore, a total of 494 patients with OGIB and negative CE findings were included in this study. Of these, 33 could not be followed up for more than 1 year. Thus, a final total of 461 patients were enrolled in this study (257 males, median age: 70 years, median observation period: 654 days, and median hemoglobin value: 8.4 g/dL). These were classified into P0 and P1 groups according to CE findings, and we examined rebleeding rates and predictive factors.

Results

Of the 461 patients, 224 (49%) had P0 and 237 (51%) had P1 findings. There were no significant differences between the two groups in terms of sex, age, observation period, hemoglobin value, and bleeding pattern. Nor were there any significant differences in the use of antiplatelet agents, anticoagulants. In terms of comorbidities, the incidences of liver cirrhosis (15% vs. 33%, P < 0.001) and diabetes mellitus (16% vs. 28%, P = 0.002) were significantly higher among patients in the P1 group than those among patients in the P0 group. Rebleeding was observed after CE in 57 of the 461 patients (12.4%), specifically, 20 of the 224 patients (8.9%) in the P0 group and 37 of the 237 patients (15.6%) in the P1 group. Two patients in the P0 group and 15 patients in the P1 group were rebleeding from small-bowel. The rate of rebleeding from the small-bowel was significantly lower in the P0 group than that in the P1 group (0.9% vs. 6.6%, P = 0.002), as was the cumulative rebleeding rate (P = 0.005). According to the multivariate analysis, post-endoscopic treatment of small-bowel lesions (hazard ratio (HR) = 13.028, 95% confidence interval (CI):4.448–38.160, P < 0.001) and P1 CE findings (HR = 10.000, 95% CI:2.154-46.438, P = 0.003) were independent predictive factors for rebleeding from the small-bowel.

Conclusion

Rebleeding may occur in patients with OGIB. Patients with P1 CE findings or post-endoscopic treatment of small-bowel lesions may experience rebleeding from the small-bowel, suggesting the need for careful follow-up.

Introduction

Short bowel syndrome (SBS) is the most common cause of intestinal failure (IF) in children and is generally managed using parenteral nutrition and/or intravenous fluids (PN/IV). Long-term PN/IV can cause potentially life-threatening complications. Patients may receive teduglutide (TED) to encourage adaptation of the remaining intestine and to reduce dependence on PN/IV. Short-term studies have shown that TED is effective and has an acceptable safety profile in children and adults with SBS-associated IF (SBS-IF). However, assessment of long-term treatment with TED in paediatric patients with SBS-IF is limited.

Aims & Methods

We report real-world long-term safety and effectiveness data of TED from a paediatric cohort enrolled in the prospective, multinational SBS Registry (NCT01990040; EUPAS7973). Data were analysed cumulatively for up to 6 years between enrolment and interim data cut-off (June 23, 2014 to June 30, 2023). Patients were categorised based on whether they received TED (ever-treated; received ≥1 dose of TED 0.05 mg/kg/day [median]) or never received TED (never-treated; received PN/IV for ≥6 months before study entry). Safety endpoints included: occurrence of colorectal cancer in patients with any remnant colon; other malignancy; colorectal polyps; and adverse events (AEs). Effectiveness endpoints included clinical response (≥20% reduction in PN/IV volume from baseline) and change from baseline in volume of PN/IV (per weight [L/kg]) and number of days/week receiving PN/IV.

Results

In total, 398 paediatric patients were enrolled: 266 never-treated, 132 ever-treated (per-protocol set, n=397; 266 never-treated, 131 ever-treated). Patients had a mean (standard deviation [SD]) age of 5.4 (4.01) years (ever-treated 6.8 [4.12] years; never-treated 4.8 [3.80] years) and the majority were male (63.7%; ever-treated 68.7%; never-treated 61.3%). The median (range) length of exposure in ever-treated patients was 29.0 (1.15–106.61) months.
No new cases of colorectal cancer or new/worsening colorectal polyps were reported between baseline and interim cut-off. New/worsening malignancies were reported for one never-treated patient. A greater proportion of ever-treated patients reported AEs (87.0% vs 74.4%) and serious AEs (SAEs; 72.5% vs 59.0%) than never-treated patients. AEs and SAEs related to TED were reported in 15.3% and 6.1% of ever-treated patients, respectively. There were no allergic or hypersensitivity reactions to TED. The most common TED-related AEs were vomiting (3.8%) and abdominal pain (2.3%). Fatal events were recorded for one ever-treated and three never-treated patients.
A greater proportion of ever-treated patients had achieved a clinical response (year 1, 18/30, 60.0%; year 3, 11/17, 64.7%) than never-treated patients (year 1, 23/100, 23.0%; year 3, 17/82, 20.7%). Ever-treated patients had a greater mean (SD) reduction from baseline in PN/IV volume (L/kg; ever-treated: year 1, −39.4% [35.97], n=19; year 3, −61.6% [23.64]; n=7; never-treated: year 1, −21.1% [50.70], n=80; year 3, −34.4% [36.83], n=49) and number of days/week receiving PN/IV (ever-treated: year 1, −1.6 [2.16], n=30; year 3, −1.5 [1.77], n=17; never-treated: year 1, −1.0 [2.22], n=100; year 3, −0.6 [1.51]; n=82) than never-treated patients.

Conclusion

This 6-year interim analysis of real-world data from a large cohort of paediatric patients with SBS-IF supports that the safety profile of TED is consistent with the previous 5-year follow-up and suggests that TED improves intestinal adaptation in paediatric patients with SBS-IF over a 3-year period.

Disclosure

Palle B Jeppesen: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; commercial relationships as consultant and speaker with Albumedix, ArTara Therapeutics, Baxter, Coloplast, Ferring Pharmaceuticals, Fresenius Kabi, GLyPharma Therapeutic, Ironwood Pharmaceuticals, Naia Pharmaceuticals, NorthSea Therapeutics, Novo Nordisk Foundation, Protara Therapeutics, Takeda, Therachon, VectivBio and Zealand Pharma.
Martina Kohl-Sobania: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; study investigator for NPS Pharmaceuticals and Takeda; honoraria from Aposan, Takeda and Tauro-Implant as a speaker; advisory board member for Takeda.
Francisca Joly: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; study investigator for NPS Pharmaceuticals, Takeda, VectivBio and Zealand Pharma; advisory board member for Alira Health, ArTara Therapeutics, Baxter, M3E Solutions, Takeda, Therachon, VectivBio and Zealand Pharma; commercial relationships as consultant and speaker for Baxter, B. Braun, Fresenius Kabi, Nestlé Health Sciences, Takeda, Therachon and Théradial.
Joel B Mason: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; research support from Takeda as a site for the study; compensation from Care/of, a producer of nutritional supplements; honoraria from UpToDate, a web-based medical information platform, for authoring chapters.
Johane P Allard: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; fees from Takeda as a consultant and speaker, and research support from Takeda as a study site principal investigator (PI); research support from Fresenius Kabi and OMS as a PI; honoraria from Baxter as a speaker and consultant; research support from Zealand Pharma as a site PI.
Ulrich-Frank Pape: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; honoraria from Takeda as a consultant and speaker, and research support from Takeda, VectivBio and Zealand Pharma as a study site PI.
Loris Pironi: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; advisory board member for Baxter, NorthSea Therapeutics and Takeda.
Gabriel E Gondolesi: speaker for Takeda; compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; received investigator-initiated research grant from Takeda.
Lauren K Schwartz: compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; speaker for Bristol Myers Squibb; advisory board member for Takeda.
Pinggao Zhang, Sasan Sabrdaran and Yi Wen Huang: employees of Takeda Pharmaceuticals U.S.A., Inc. and receive stock and/or stock options.
André Gabriel: former employee of Takeda Pharmaceuticals U.S.A., Inc. who received stock and/or stock options.

Acknowledgements: This study was funded by Takeda Pharmaceuticals U.S.A., Inc., MA, USA. Medical writing support, funded by Takeda Pharmaceuticals U.S.A., Inc., was provided by Elizabeth Coe, PhD of PharmaGenesis Cardiff, Cardiff, UK.