Duodenal-type follicular lymphoma (D-FL) is a newly recognized entity in the 2016 World Health Organization classification update. It has an immunophenotype similar to that of other FLs and usually carries the typical t(14;18)(q32;q21) translocation. However, unlike other FLs, D-FL is almost always diagnosed at a low stage and stays localized to the small intestine, most commonly the second portion of the duodenum, whereas the vast majority of other FLs are diagnosed at an advanced stage. Additionally, D-FL gene expression and pathogenesis appear to be more closely related to extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue than to other types of FL. Therefore, many oncologists have opted to treat this variant of FL in a “watch and wait” manner because of its excellent prognosis and the rarity of D-FL to progress even when no treatments are attempted.

Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma in the United States.1  It is graded by using the number of centroblasts per ×40 high-power field (hpf; hpf = 18-mm field of view) as grading criteria2 : grade 1 is 5 or fewer centroblasts per hpf; grade 2 is 6 to 15 centroblasts per hpf; and grade 3 is more than 15 centroblasts per hpf. Grade 3 is further subdivided into 3A (centrocytes still present) and 3B (sheets of centroblasts).3  Follicular lymphoma grades 1 and 2 have been combined into one entity because both are considered to have an indolent course.

As common as FL is, it only accounts for approximately 4% of gastrointestinal (GI) lymphomas.1,4–6  Of these, it is interesting to note that a large percentage (between 38% and 81%) arise in the duodenum.7–9  The FLs of this site are commonly localized to the intestine without nodal metastasis,9  similar to how primary cutaneous follicle center lymphoma stays localized to the skin.10  Conversely, the vast majority of patients presenting with FLs at other sites are at an advanced stage of disease.1,11  This has led the World Health Organization to recognize this entity as a distinct form of FL—duodenal-type follicular lymphoma (D-FL)—in its 2016 update.12

CLINICAL FEATURES

Most D-FLs are detected incidentally, with endoscopy being done for reasons unlikely to be related to the D-FL, because low-stage FLs rarely cause clinical symptoms. This is most likely why FLs are detected at advanced stages in the vast majority of cases. In a study performed in Europe by Schmatz et al,9  the patients usually either had some type of upper GI symptoms, the D-FL was discovered while staging for other types of malignancies, or the endoscopy was part of a preventative medical examination. However, in another study performed in Japan by Takata et al,8  the vast majority of patients presented with no symptoms, and only a small cohort had some form of abdominal symptoms. Neither study revealed a predilection for either sex, and the median age for each study was 65 and 59 years, respectively. In the Takata et al8  study, 97 of 99 patients (98%) with involvement of the second portion of the duodenum had a 5-year progression-free survival. This is compared with only 19 of 27 patients (70%) without involvement of the second portion of the duodenum who had a 5-year progression-free survival.

Regarding disease staging, although Ann Arbor staging is more commonly used for FL of other sites, it appears that the International Workshop classification (Lugano classification) is more appropriate for the clinical staging of D-FL. The reason for this is that the Lugano staging criteria are commonly used for GI lymphoma staging and, because of the multifocal nature of D-FL, it is more similar to other GI lymphomas rather than the FLs of other sites. The Takata et al8  and Schmatz et al9  studies both used the Lugano staging criteria, and of the 162 patients, none were higher than a stage II.