Primary intestinal NHL accounts for a major proportion of cases of extranodal lymphoma. Although its prognosis is poor compared to gastric lymphoma, there are few studies analyzing the clinical features and survival outcomes of primary intestinal NHL according to primary site of involvement and histologic subtype. In this study, we analyzed data for 581 patients, making ours the largest sample among studies investigating primary gastrointestinal lymphoma. The clinical features of our study were similar to those described in previous studies, and revealed that primary intestinal NHL occurs more frequently in male patients and predominantly presents as a localized disease (Table ).
Summary of published results of prospective and retrospective studies
The incidence of B-cell lymphoma was much that of higher than T-cell lymphoma, and DLBCL was the main subtype. This is consistent with the observation that the majority of gastrointestinal tract NHL is of B-cell origin, including DLBCL and MALT lymphoma [2
]. However, the proportion of DLBCL (n = 386, 66.4%) was significantly higher than MALT (n = 64, 10.6%) in our study. This is different from gastric lymphoma, in which MALT lymphoma accounts for approximately 40% of all cases [15
]. This high frequency of DLBCL might be associated with the worse prognosis of intestinal lymphoma compared to gastric lymphoma [1
]. The relatively higher incidence of T-cell lymphoma may be another cause of the poor prognosis for intestinal NHL. Our study showed the occurrence of three subtypes of T-cell lymphoma including PTCL-U, EATL and ENKTL with a frequency of 13.2%. Although the proportion of T-cell lymphomas varied according to the type of study and number of patients [5
], our proportion was comparable to previous studies with a relatively large number of patients [1
]. Patients with T-cell lymphomas more frequently presented with advanced disease and constitutional B symptoms, and their overall response rate to treatment was inferior to that of B-cell lymphomas. This resulted in significantly worse survival outcomes for T-cell lymphoma compared to B-cell lymphoma in our study, which is consistent with previous results [7
]. The comparison of survival outcomes based on subtypes of NHL demonstrated that MCL did not show a survival curve plateau. This reflects MCL has higher risk of relapse resulting in worse OS and PFS than other subtypes (Figure ) in consistent with previous results [25
]. The 5-year OS of PTCL-U in our study was inferior to previously reported 5-year OS of nodal PTCL-U, suggesting a poor prognosis for intestinal T-cell lymphoma [28
The ileocecal region was the most common site of involvement, accounting for approximately 40% of primary sites in this study (Table ). However, this region was mainly affected by B-cell lymphomas (95.7%). The frequent occurrence of B-cell lymphomas in the ileocecal region was associated with high proportions of DLBCL (Table ). T-cell lymphomas were extremely rare in the ileocecal region (4.3%), while involvement of the jejunum was more common in T-cell lymphomas (12.5%) than in B-cell (3.6%). This relatively high incidence of T-cell lymphomas in the small intestine, especially the jejunum, was also noted in previous studies [3
]. Like previous studies reporting high proportions of MALT lymphoma in the duodenum and rectum in East Asian samples [6
], the high proportion of B-cell lymphoma in the duodenum and rectum in this study was also associated with frequent occurrence of MALT lymphoma.
A comparison of survival outcomes based on primary site of involvement revealed that involvement of the ileocecal region was associated with better survival rates than involvement of the small and large intestine. Patients with multiple intestinal involvements had the worst survival outcomes. A previous study reported that the overall survival of ileocecal lymphoma was similar to that of gastric lymphoma and superior to that of small intestinal lymphoma [4
]. There are several possible explanations for the superior survival outcomes of patients with involvement in the ileocecal region. First, T-cell lymphoma rarely occurs in the ileocecal region compared to the small and large intestine. Thus, the proportion of T-cell lymphoma in our study (4.3%) was similar to that of a previous study reporting 4% in the ileocecal region [4
]. Second, lymphomas in the ileocecal region often presented with complications, such as obstructions requiring surgical intervention. Thus, more than 50% of patients with lymphoma in the ileocecal region underwent immediate surgery [1
]. Our study also showed that the percentage of patients who underwent surgery in the ileocecal region (64.1%) was significantly higher than the percentage of patients who required surgery in the small and large intestines (45.7% and 39.2%, respectively, Table ). Previous studies reported that primary surgical treatment had a favourable influence on the prognosis of intestinal lymphoma, especially for localized disease [7
]. Thus, the fact that many of our patients received surgery might explain the better survival of patients with ileocecal lymphoma in our study as compared to other studies.
The optimal treatment strategy for intestinal lymphoma is still unclear. Although conservative treatment is preferred to surgery in localized gastric lymphomas, the same is not true for intestinal lymphomas because surgery in combination with chemotherapy has proven superior to any other treatment combination [1
]. In a previous study, we compared the outcomes of surgery followed by chemotherapy, and chemotherapy alone in intestinal DLBCL, and found that surgery followed by chemotherapy led to better survival outcomes [32
]. Consistent with these findings, surgical resection was associated with survival benefits in patients with B-cell lymphoma in the present study (P < 0.001, Figure ). Considering the fact that more than 90% of patients received chemotherapy, this result may be interpreted to reflect a survival advantage of surgery plus chemotherapy. However, the survival benefit was not observed in patients with T-cell lymphoma (P = 0.460, Figure ), possibly due to the high proportion of Lugano stage IV cases in our sample. Thus, need for surgery failed to show independent prognostic value in the multivariate analysis for OS (Table ). The results of our multivariate analysis demonstrated that age, performance status, serum LDH, Lugano stage, B symptoms, and T-cell immunophenotype were all independently prognostic for OS in patients with intestinal NHL.
Although this is the largest series of primary intestinal NHL, our study has some limitations. First, patients included in this analysis were not consecutively diagnosed because of its retrospective study in nature. Second, we could not provide the results of PET/CT scan because PET/CT scan was not widely used before 2006 in Korea.