Primary follicular lymphoma of the gastrointestinal tract: effect of stage, symptoms and treatment choice on outcome

Th e gastrointestinal (GI) tract is the most common extranodal site of non-Hodgkin lymphoma, but primary follicular lymphoma (FL) of the GI tract is rare and accounts for less than 7% of GI lymphomas [1,2]. Recent studies suggest that FL of the GI tract is particularly indolent and may represent a distinct localized variant of FL [3 – 7]. In a study of 63 patients with stage I FL of the duodenum, Schmatz et al . reported that 38% of patients were observed, with no transformation and only two cases of progressive disease [4]. Th erefore, observation was suggested as the most sensible treatment strategy. Other management strategies have included radiation therapy (similar to the approach for stage I nodal FL), chemotherapy (most commonly rituximab) and surgery [4 – 10]. It is unknown whether patients with stage II FL of the GI tract (involving the abdominal lymph nodes) have similar outcomes to patients with stage I disease. We hypothesize that, since stage II disease is not truly localized, it may behave more like nodal FL with higher rates of recurrence and progression. Th erefore, we compared outcomes in patients with stage I and stage II FL of the GI tract after observation or various treatment regimens. Th rough our institutional pathology database, 40 patients were identifi ed with stage I or stage II FL of the GI tract diagnosed between 1980 and 2010. Th e diagnosis of FL was made by endoscopic biopsy with histologic and immunohistologic criteria as defi ned by the World Health Organization (WHO). Initial staging included computed tomography (CT) of the chest, abdomen and pelvis in 95%, positron emission tomography (PET) in 70% and bone marrow biopsy in 83%. Stage was classifi ed according to the Lugano system for GI lymphomas. Twenty-eight patients had stage I disease (confi ned to the GI tract with single or multiple sites), and 12 patients had stage II disease (involving the mesenteric nodes in nine and the mesenteric and paraaortic nodes in three). Notably, lymph nodes were rarely sampled, and most patients were clinically staged. Th e median axial size of involved nodes was 1.6 cm (range, 1.0 – 4.6 cm). Histologic grade was 1 in 60%, 2 in 35% and 3A in 5%. Th e median age was 58 years (range, 35 – 75 years), and the male:female ratio was 19:21. Th e most common subsite of FL of the GI tract was the duodenum (63%), as seen in previous studies [4 – 7]. Other subsites included the jejunum (23%), ileum (25%), colon (23%), rectum (5%) and stomach (8%). Most patients (75%) had multifocal disease, usually consisting of a cluster of polyps or plaques within a single GI subsite. Th irty-three percent of patients had involvement of multiple GI subsites, but this may have been underestimated, because only 30% of patients underwent pan-endoscopy [11,12]. Reasons for initial endoscopy and biopsy included upper GI symptoms (abdominal pain and/or nausea) in 45%, GI bleeding in 20%, screening in 30% and workup for lymphadenopathy in 5%. Symptoms were thought to be related to lymphoma in 38% of patients, and there was no diff erence in symptoms of stage I versus stage II disease. Other causes of symptoms included gastroesophageal refl ux, gastritis and ulcer disease. Six patients received antibiotics for possible Helicobacter pylori infection, but this did not induce regression of lymphoma in any patients. Th e follicular lymphoma international prognostic index (FLIPI) was low risk in 93% of patients, intermediate risk in 5% and high risk in 2%. FLIPI did not predict for outcome in this study, and all patients with stage II disease were in the low-risk category. Patients were followed for a median of 4.8 years after diagnosis (range, 0.9 – 18 years). Typical follow-up consisted of a physician evaluation and endoscopy every 6 months for 1 year and then annually. Kaplan – Meier methods were used to estimate progression-free survival, and this was measured from the date of diagnosis to the date of recurrence, progression or the last oncologic evaluation. Comparisons were made using the log-rank test. Out of 40 patients, 16 (40%) were managed by observation, including 11 with stage I disease and fi ve with stage II disease [Table I, Figure 1(a)]. Over the period of follow-up, 10 of L eu k L ym ph om a D ow nl oa de d fr om in fo rm ah ea lth ca re . c om b y U ni ve rs ity O f R oc he st er S ch oo l O f M ed ic i n e & D en tis tr y on 0 5/ 01 /1 3