By Dr Victoria Gomez & Dr Katherine Mejia-Perez

A 65-year-old man with long-standing symptoms of gastroesophageal reflux disease was referred for a diagnostic EGD. Endoscopy was unrevealing with the exception of a mucosal abnormality that appeared to arise from the periampullary region detected upon slow withdrawal within the duodenum. A diagnostic duodenoscope was inserted, with findings of a distorted major papilla with diffuse whitish nodularity, with extension to the periampullary area (Fig. 1A). The differential dia gnosis of the lesion at that time included primary ampullary adenoma/carcinoma versus a pancreatic lesion. The patient was referred for EUS for further evaluation. A linear array endoscopic ultrasound (EUS) demonstrated an 18 mm polypoid mucosal lesion in the major papilla, without involvement of the muscularis propria or pancreas parenchyma (Fig. 1B). The bile and pancreatic ducts were spared. Mucosal biopsies were obtained. Histopathological and immunohistochemical evaluation showed nodular and diffuse proliferation of atypical lymphocytes in the submucosa and lamina propria, which stained positive for CD20, BCL-6, BCL-2, and CD10 (Fig. 1C); with a low proliferative rate by Ki-67 (5-20%). The diagnosis of follicular lymphoma, World Health Organization (WHO) grade 1 of 3 of the periampullary region was made.

The patient was referred for an oncologic consultation. NM PET/CT demonstrated no foci of abnormal metabolic activity. Five weekly sessions of induction chemotherapy with rituximab were administered. A surveillance EGD post-treatment was performed and demonstrated complete resolution of the lesion (Fig. 1D). Biopsies of the ampulla and periampullary region were obtained, showing no evidence of lymphoma.

Figure 1.  A, Whitish nodular lesion of the ampulla detected on upper endoscopic evaluation. B, Linear array EUS view, showing 18-mm polypoid lesion involving the major papilla, confined to the mucosa. C, Pathologic specimen stained with H&E, showing neoplastic follicles in the duodenal lamina propria and submucosa, (blue arrow, orig. mag. x10). D. Repeat upper endoscopy with duodenoscope post-chemotherapy, showing complete resolution of the lesion.

Figure 1.
A, Whitish nodular lesion of the ampulla detected on upper endoscopic evaluation. B, Linear array EUS view, showing 18-mm polypoid lesion involving the major papilla, confined to the mucosa. C, Pathologic specimen stained with H&E, showing neoplastic follicles in the duodenal lamina propria and submucosa, (blue arrow, orig. mag. x10). D. Repeat upper endoscopy with duodenoscope post-chemotherapy, showing complete resolution of the lesion.

Discussion

Primary follicular lymphoma is the rarest histologic subtype of the lymphomas affecting the gastrointestinal tract, with a frequency of 1-3.6%. The duodenum is the most commonly affected location (1–4). It is mainly an asymptomatic condition, which usually represents an incidental diagnosis during GI endoscopy (5). The most common reported finding consists of multiple small mucosal whitish nodules or polyps. Endoscopic ultrasound most often reveals mucosal and submucosal thickening, with multiple hypoechogenic nodules, which represent lymphocyte proliferation (1,4). We decided not to perform biopsies on first upper endoscopic evaluation because the primary origin of the lesion, as well as its extent into the intestinal wall, was unknown.

Diagnosis is confirmed with microscopic examination and immunostaining (5). Microscopy reveals neoplastic cells invading the lamina propria, being confined to the submucosal layer. Within the GI tract, immunostaining of follicular lymphoma shows expression of pan B cell markers, such as CD19 and CD20, and, the anti-apoptotic protein, BCL-2. They are also positive for BCL-6 and CD10 (2,5).

Due to its low prevalence and absence of guidelines, treatment of ampullary lymphomas is very heterogenous: watch and wait, monotherapy with rituximab, chemotherapy with R-CHOP and R-CHOP-like regimens, surgery, radiotherapy and Helicobacter pylori eradication. Regarding prognosis, which tends to be favorable, some reports have shown no difference in prognosis among the different types of therapy strategies, (2,4,6). In our particular case, monotherapy with a biologic agent was successful.

In conclusion, primary gastrointestinal lymphoma is a rare tumor, mostly asymptomatic and incidentally diagnosed on upper gastrointestinal examination. Endoscopists play an important role in its detection, diagnosis and initial management. Careful examination of the major papilla during routine upper endoscopy should always be performed with a careful, meticulous withdrawal. Subtle lesions can often times be properly recognized and further evaluated.