Primary Intestinal Grade 2 Follicular Lymphoma (Stage IIIB, FLIPI 3): Diagnostic Challenges and Therapeutic Management with Bendamustine and Rituximab

Primary gastrointestinal follicular lymphoma (PGI-FL) is a rare subset of extranodal non-Hodgkin lymphoma, traditionally characterized by localized, indolent lesions in the second portion of the duodenum. However, primary jejunal involvement presenting with advanced-stage disease (Stage IIIB) and high-risk stratification (FLIPI 3) represents a far more aggressive and rare clinical entity. Because low-grade lymphomas often present with non-specific abdominal complaints, their diagnosis is frequently delayed or confounded by benign clinical presentations and inconclusive minimally invasive biopsies.

We present a rare case of advanced primary jejunal Follicular Lymphoma (Grade 2, Stage IIIB, FLIPI 3) in a 64-year-old female who initially presented with vague chronic dyspepsia, underwent a non-diagnostic fine-needle aspiration biopsy, and ultimately required surgical small bowel resection to establish a definitive diagnosis before initiating immunochemotherapy.

A 64-year-old female presented with a six-month history of dyspepsia. Initial abdominal imaging revealed incidental mesenteric lymphadenopathy, but fine-needle aspiration biopsy was non-diagnostic, demonstrating only atypical lymphoid proliferation. Staging PET/CT demonstrated hypermetabolic mesenteric and para-aortic lymphadenopathy. The patient underwent exploratory laparotomy, segmental jejunal resection, and primary stapled anastomosis. Histopathology and immunohistochemistry established a diagnosis of Grade 2 Follicular Lymphoma with subserosal, omental, and regional lymph node involvement (CD20+, CD10+, BCL2+, BCL6+, Ki-67 10-15%). The disease was classified as Stage IIIB with a high-risk FLIPI score of 3. Patient has active chronic Hepatitis B infection (HBV DNA 5,810 IU/mL) treated with Tenofovir alfenamide. Cycle 1 of Rituximab-Bendamustine (RB) immunochemotherapy was successfully initiated alongside viral and antimicrobial prophylaxis without immediate complications.

Primary gastrointestinal follicular lymphoma (PGI-FL) comprises less than 4% of primary GI non-Hodgkin lymphomas. While the vast majority of PGI-FL cases present as localized, highly indolent lesions confined to the second portion of the duodenum, extensive small bowel (jejunal) involvement with advanced nodal spread (Stage IIIB) and a high-risk score (FLIPI 3) is exceptionally uncommon.

Low-grade B-cell neoplasms, particularly Follicular Lymphoma, rely heavily on evaluating intact lymph node architecture and immunophenotypic grading.

In this patient, FNAB showed atypical lymphoid proliferation, initially leading to observation. It was only through high-resolution PET/CT and subsequent surgical excision that an adequate specimen was secured, allowing immunohistochemistry (CD20+, CD10+, BCL2+, BCL6+, Ki-67 10-15%) to confirm Grade 2 Follicular Lymphoma with subserosal and omental invasion.

Unlike standard duodenal FL, which often remains stable under a "watch-and-wait" approach or responds to localized radiotherapy, primary jejunal FL extending into the subserosa, omentum, and regional nodes behaves more like systemic nodal follicular lymphoma.

B-cell depletion with Rituximab severely impairs anti-HBV immunity, posing a high risk of fulminant viral reactivation, hepatic failure, and death in patients with active baseline viremia (HBV DNA 5,810 IU/mL; HBsAg reactive). In this patient, Tenofovir alfenamide 25 mg/tablet once a day was started 2 weeks prior initiation of chemotherapy and clearance from gastroenterologist was secured.

When clinical and radiological suspicion of lymphoma is high, a negative or non-conclusive FNAB should never rule out malignancy, and tissue excisional biopsy remains the gold standard. Crucially, early Tenofovir Alafenamide prophylaxis enables the safe delivery of anti-CD20 immunochemotherapy in high-risk patients with concurrent chronic Hepatitis B.