Abstract
Background
Small intestine primary mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL) are relatively rare types of non-Hodgkin’s lymphoma. This study aimed to analyze the clinical characteristics and long-term prognosis of these two diseases based on the Surveillance, Epidemiology, and End Results (SEER) database.
Methods
Patients diagnosed with small intestine MALT and DLBCL from 2000 to 2021 were included. Propensity score matching (PSM) was used to minimize selection bias. The Kaplan-Meier method and Cox proportional hazards models were utilized to evaluate the effects of various clinical characteristics on overall survival (OS) and cancer-specific survival (CSS).
Results
A total of 2,748 patients were enrolled, including 2,362 with DLBCL and 386 with MALT. Compared to DLBCL patients, MALT patients were younger, had a higher proportion of females, and presented at earlier American Joint Committee on Cancer (AJCC) stages. Before PSM, the MALT cohort demonstrated significantly better OS [hazard ratio (HR) 0.54, 95% confidence interval (CI): 0.46–0.64, P<0.001] and CSS (HR 0.34, 95% CI: 0.26–0.45, P<0.001) than the DLBCL cohort. Specifically, 5-year OS rates were 80.1% for MALT and 57.6% for DLBCL, while 5-year CSS rates were 90.0% and 67.8%, respectively. Even after PSM, the MALT group maintained significantly superior OS (HR 0.55, 95% CI: 0.44–0.68, P<0.001) and CSS (HR 0.37, 95% CI: 0.26–0.52, P<0.001). Cox regression analysis identified age and AJCC stage as prognostic factors for OS in MALT patients, while race and AJCC stage were prognostic for CSS. For DLBCL patients, age, year of diagnosis, AJCC stage, chemotherapy, and marital status were significant prognostic factors for both OS and CSS.
Conclusions
Patients with small intestine MALT lymphoma have a better prognosis than those with DLBCL, and AJCC staging is a significant prognostic factor, highlighting the importance of early diagnosis and treatment.
Keywords: Small intestine, mucosa-associated lymphoid tissue lymphoma (MALT lymphoma), diffuse large B-cell lymphoma (DLBCL), clinical characteristic, long-term prognosis
Highlight box.
Key findings
• Patients with small intestine mucosa-associated lymphoid tissue (MALT) lymphoma exhibited significantly better overall and cancer-specific survival compared to those with diffuse large B-cell lymphoma (DLBCL), with American Joint Committee on Cancer (AJCC) stage being a key prognostic factor.
What is known and what is new?
• MALT lymphoma generally has a better prognosis than DLBCL, especially in gastric locations.
• This study confirms this survival advantage specifically in the rare small intestine location using a large population-based cohort and robust statistical methods.
What is the implication, and what should change now?
• Early diagnosis and accurate AJCC staging are critical for improving small intestine lymphoma prognosis. Clinical practice should prioritize enhanced detection and stage-adapted treatment strategies.
Introduction
Gastrointestinal lymphoma (GIL) originates from the lymphatic tissue within the lamina propria and submucosa of the gastrointestinal tract, with non-Hodgkin’s lymphoma (NHL) being the predominant subtype (1-3). It accounts for approximately 1% to 8% of all gastrointestinal malignancies and represents 30% to 40% of extranodal lymphomas, thereby making it the most common type of extranodal lymphoma (4,5). The incidence of GIL has increased in recent years, potentially due to the rise in microbial infections, autoimmune diseases, and secondary immune dysfunction disorders (6). In its early stages, GIL often presents with nonspecific clinical manifestations, leading to a high misdiagnosis rate and subsequently impacting treatment decisions and patient prognosis. Within the gastrointestinal tract, the stomach is the most frequent site of occurrence, accounting for 68% to 75% of all cases, followed by the small intestine (approximately 30%) and the colorectum (approximately 3%) (4,7,8). In terms of pathological classifications, diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype, followed by mucosa-associated lymphoid tissue lymphoma (MALT) (9-11).
MALT lymphoma originates from the marginal zone B-cells within the mucosa-associated lymphoid tissue, predominantly affecting the stomach but also occasionally involving the small intestine. Extensive research has elucidated the clinical manifestations and prognostic factors of gastric MALT lymphoma, emphasizing the crucial role of chronic inflammation, particularly Helicobacter pylori (HP) infection, in its etiology. HP eradication typically results in a favorable prognosis for these patients (12-15). In contrast, DLBCL can arise in various extranodal sites, including the small intestine. Unlike MALT lymphoma, the pathogenesis of DLBCL is complex, involving genetic alterations, immune suppression, viral infections, and other factors, and is not linked to chronic inflammation (16). Previous studies have shown that chemotherapy, specifically the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen, is effective in improving the prognosis of patients with gastric DLBCL (17,18). However, due to the rarity of small intestine lymphomas, there is a scarcity of large-scale studies on small intestine MALT lymphoma and DLBCL, with most of the existing literature consisting of case reports or studies with small sample sizes (19-22). Furthermore, data on the prognosis of small intestine DLBCL are limited (23,24). Currently, there is a notable lack of population-based research examining the clinical characteristics and long-term outcomes of small intestine MALT lymphoma and DLBCL. To address this knowledge gap, our study utilizes the latest Surveillance, Epidemiology, and End Results (SEER) database and employs advanced statistical techniques, including multiple imputation (MI) and propensity score matching (PSM), to conduct a comprehensive analysis of the clinical features and prognostic factors of patients with small intestine MALT lymphoma and DLBCL. Our goal is to provide a detailed understanding of these diseases, ultimately informing clinical decision-making and improving patient outcomes. We present this article in accordance with the STROBE reporting checklist (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-1213/rc).
Methods
Patient selection
The study focused on individuals diagnosed with small intestine MALT and DLBCL from 2000 to 2021, using data from the SEER database (available at http://seer.cancer.gov). Patients were identified based on the International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3): 9680/3 for DLBCL, NOS, and 9699/3 for extranodal marginal zone lymphoma of mucosal-associated lymphoid tissue-MALT. Individuals without definitive pathological diagnoses or incomplete survival data were excluded from the analysis. Figure 1 displays a flowchart outlining the research methodology. Various factors such as age, diagnosis year, gender, race, American Joint Committee on Cancer (AJCC) stage, surgical intervention, chemotherapy treatment, marital status, cancer-specific death rate, overall survival (OS) status, and follow-up period were examined. Using X-tile software, as shown in Figure S1, patients were divided into two age groups: those aged 65 years or younger (non-elderly) and those older than 65 years (elderly). Race was classified as white, black, or other (including American Indian/Alaska Native and Asian/Pacific Islander). Marital status was categorized as either married or unmarried, where the latter category included individuals who were divorced, separated, single, or widowed. The aim of this research was to evaluate the clinical characteristics and outcomes related to small intestine MALT and DLBCL. OS and cancer-specific survival (CSS) were calculated from the date of MALT and DLBCL diagnosis until the earliest occurrence of death, cancer-related death, or the end of follow-up. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.
Figure 1.
Flow chart of the study. DLBCL, diffuse large B-cell lymphoma; MALT, mucosa-associated lymphoid tissue; PSM, propensity score matching.
Statistical analysis
Categorical variables were presented as frequencies and percentages, and the Chi-squared test was utilized for group comparisons. For continuous variables that did not follow a normal distribution, the median and interquartile range (IQR) were used for descriptive purposes, and the Mann-Whitney U test was employed for group comparisons. A comprehensive strategy combining MI with the random forest algorithm was implemented to strengthen the statistical analysis, especially in handling missing data in the SEER dataset. To ensure comparability between the MALT and DLBCL cohorts, a 1:1 PSM was applied, incorporating factors such as age, diagnosis year, gender, race, AJCC stage, surgical treatment, chemotherapy, and marital status, with a caliper width of 0.01. Survival outcomes, including OS and CSS, were assessed using the Kaplan-Meier method, and differences between groups were examined with the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from both univariate and multivariate Cox proportional hazards models. Variables that were statistically significant (P<0.05) in the univariate analysis were included in the multivariate analysis. All statistical analyses were conducted using R software (version 4.1.0), with statistical significance determined by a P value of less than 0.05.
Results
Patients’ characteristics
A total of 2,748 individuals participated, including 2,362 diagnosed with DLBCL and 386 with MALT lymphoma. Among the DLBCL cohort, males outnumbered females (63.4% vs. 36.6%), there were more older patients than younger ones (57.8% vs. 42.2%), and those with AJCC stage I/II exceeded those with stage III/IV (74.4% vs. 25.6%). Similarly, in the MALT group, there were more males than females (54.1% vs. 45.9%), the elderly population was about equal to the non-elderly (50.8% vs. 49.2%), and patients with AJCC stage I/II were more numerous than those with stage III/IV (88.1% vs. 11.9%). In comparison to DLBCL patients, MALT patients were generally younger, had a higher proportion of females, and were diagnosed at earlier AJCC stages. Table 1 presents a detailed summary of the clinical characteristics for both MALT and DLBCL patients affecting the small intestine. Table S1 outlines the distribution of MALT and DLBCL across various primary sites within the small intestine. Table S2 provides a thorough examination of the patients’ clinical profiles before experiencing a MI, highlighting that race data was missing in 0.7% of cases, AJCC stage in 44.7% of cases, surgical intervention details in 0.5% of cases, and marital status in 4.6% of instances.
Table 1. Comparison of the demographic and clinical characteristics of patients before and after PSM.
| Variables | Before PSM | After PSM | ||||||
|---|---|---|---|---|---|---|---|---|
| Total (n=2,748) | DLBCL group (n=2,362) | MALT group (n=386) | P value | DLBCL group (n=386) | MALT group (n=386) | P value | ||
| Age, years | 0.009* | 0.83 | ||||||
| ≤65 | 1,186 (43.2) | 996 (42.2) | 190 (49.2) | 193 (50.0) | 190 (49.2) | |||
| >65 | 1,562 (56.8) | 1,366 (57.8) | 196 (50.8) | 193 (50.0) | 196 (50.8) | |||
| Year of diagnosis | 0.92 | 0.72 | ||||||
| 2000–2010 | 1,338 (48.7) | 1,151 (48.7) | 187 (48.4) | 192 (49.7) | 187 (48.4) | |||
| 2011–2021 | 1,410 (51.3) | 1,211 (51.3) | 199 (51.6) | 194 (50.3) | 199 (51.6) | |||
| Sex | <0.001* | 0.83 | ||||||
| Male | 1,707 (62.1) | 1,498 (63.4) | 209 (54.1) | 212 (54.9) | 209 (54.1) | |||
| Female | 1,041 (37.9) | 864 (36.6) | 177 (45.9) | 174 (45.1) | 177 (45.9) | |||
| Race | 0.26 | 0.28 | ||||||
| White | 2,313 (84.2) | 1,999 (84.6) | 314 (81.3) | 329 (85.2) | 314 (81.3) | |||
| Black | 151 (5.5) | 126 (5.3) | 25 (6.5) | 23 (6.0) | 25 (6.5) | |||
| Others | 284 (10.3) | 237 (10.0) | 47 (12.2) | 34 (8.8) | 47 (12.2) | |||
| AJCC stage | <0.001* | 0.74 | ||||||
| I/II | 2,098 (76.3) | 1,758 (74.4) | 340 (88.1) | 343 (88.9) | 340 (88.1) | |||
| III/IV | 650 (23.7) | 604 (25.6) | 46 (11.9) | 43 (11.1) | 46 (11.9) | |||
| Surgery | 0.32 | 0.45 | ||||||
| Yes | 2,153 (78.3) | 1,858 (78.7) | 295 (76.4) | 304 (78.8) | 295 (76.4) | |||
| No | 595 (21.7) | 504 (21.3) | 91 (23.6) | 82 (21.2) | 91 (23.6) | |||
| Chemotherapy | <0.001* | 0.94 | ||||||
| Yes | 1,698 (61.8) | 1,582 (67.0) | 116 (30.1) | 115 (29.8) | 116 (30.1) | |||
| No/unknown | 1,050 (38.2) | 780 (33.0) | 270 (69.9) | 271 (70.2) | 270 (69.9) | |||
| Marital status | 0.59 | 0.83 | ||||||
| Married | 1,643 (59.8) | 1,417 (60.0) | 226 (58.5) | 223 (57.8) | 226 (58.5) | |||
| Unmarried | 1,105 (40.2) | 945 (40.0) | 160 (41.5) | 163 (42.2) | 160 (41.5) | |||
| Survival months | 48.0 (8.0, 113.0) | 41.0 (7.0, 109.0) | 80.0 (31.0, 136.0) | <0.001* | 27.0 (3.0, 105.0) | 80.0 (31.0, 136.0) | <0.001* | |
Data are presented as n (%) or median (IQR). *, P<0.05. Others: American Indian, Alaska Native, Asian/Pacific Islander. AJCC, American Joint Committee on Cancer; DLBCL, diffuse large B-cell lymphoma; IQR, interquartile range; MALT, mucosa-associated lymphoid tissue; PSM, propensity score matching.
Survival analysis of patients with small intestine MALT and DLBCL
Before PSM, the OS rates at 1, 3, 5, and 10 years for individuals with small intestine MALT lymphoma were 90.4%, 84.9%, 80.1%, and 61.1%, respectively, whereas the CSS rates for these timeframes were 93.6%, 92.1%, 90.0%, and 84.0%. For those with small intestine DLBCL, the OS rates were 72.5%, 62.8%, 57.6%, and 44.4%, and the CSS rates were 77.7%, 70.9%, 67.8%, and 63.0%, respectively. After PSM, the OS rates for DLBCL patients were adjusted to 69.4%, 61.0%, 55.2%, and 47.8%, and the CSS rates were 77.9%, 72.3%, 68.9%, and 67.6%, respectively (Table S3). Before PSM, the MALT group had significantly higher OS (HR 0.54, 95% CI: 0.46–0.64, P<0.001) (Figure 2A) and CSS (HR 0.34, 95% CI: 0.26–0.45, P<0.001) (Figure 2B) compared to the DLBCL group. Even after PSM, the MALT cohort maintained a significantly better OS (HR 0.55, 95% CI: 0.44–0.68, P<0.001) (Figure 2C) and CSS (HR 0.37, 95% CI: 0.26–0.52, P<0.001) (Figure 2D).
Figure 2.
OS and CSS were compared before and after PSM between small intestine MALT group and DLBCL group. (A) OS before PSM; (B) CSS before PSM; (C) OS after PSM; (D) CSS after PSM. CSS, cancer-specific survival; DLBCL, diffuse large B-cell lymphoma; MALT, mucosa-associated lymphoid tissue; OS, overall survival; PSM, propensity score matching.
Subgroup analysis
To assess the disparities in clinical features between individuals diagnosed with small intestine MALT and DLBCL, we performed subgroup analyses encompassing age, year of diagnosis, gender, race/ethnicity, AJCC stage, surgical intervention, chemotherapy administration, and marital status. Prior to PSM, our findings indicated that MALT demonstrated superior OS compared to DLBCL across all subgroups, with the exception of those identified as black or other races, where OS was comparable between the two groups (Figure S2). Likewise, with regard to CSS, MALT exhibited superiority over DLBCL in all subgroups except for the black or other race categories, where CSS was similar (Figure S3). Following PSM, we noted that OS was equivalent between MALT and DLBCL in the black or other race subgroups, as well as in those who did not undergo surgical treatment and those who received chemotherapy. In contrast, MALT retained its OS advantage over DLBCL in all remaining subgroups (Figure 3). Furthermore, CSS was comparable between MALT and DLBCL in patients aged 65 years or younger, those of black or other races, those who did not undergo surgery, and those who received chemotherapy. In all other subgroups, MALT demonstrated superior CSS compared to DLBCL (Figure 4).
Figure 3.
Subgroup analysis of OS between small intestine MALT group and DLBCL group after PSM. AJCC, American Joint Committee on Cancer; CI, confidence interval; DLBCL, diffuse large B-cell lymphoma; HR, hazard ratio; MALT, mucosa-associated lymphoid tissue; OS, overall survival; PSM, propensity score matching.
Figure 4.
Subgroup analysis of CSS between small intestine MALT group and DLBCL group after PSM. AJCC, American Joint Committee on Cancer; CI, confidence interval; CSS, cancer-specific survival; DLBCL, diffuse large B-cell lymphoma; HR, hazard ratio; MALT, mucosa-associated lymphoid tissue; PSM, propensity score matching.
Univariate and multivariate cox regression
The initial univariate Cox regression analysis highlighted age, AJCC stage, and marital status as predictors of OS in small intestine MALT patients. Subsequently, the multivariate Cox regression analysis pinpointed age and AJCC stage as independent predictors of OS in this cohort (Table 2). Likewise, the univariate analysis revealed race and AJCC stage as factors influencing CSS in small intestine MALT patients. The multivariate analysis then solidified race and AJCC stage as independent determinants of CSS for these patients (Table 3). In the case of small intestine DLBCL patients, the univariate Cox regression analysis suggested that age, year of diagnosis, AJCC stage, chemotherapy, and marital status were all associated with reduced OS. The multivariate analysis further validated these variables as independent prognosticators of OS in this patient group (Table 4). Finally, the univariate analysis indicated that age, year of diagnosis, AJCC stage, chemotherapy, and marital status were all linked to decreased CSS in small intestine DLBCL patients. The subsequent multivariate analysis confirmed these factors as independent predictors of CSS in this population (Table 5).
Table 2. Univariate and multivariate Cox regression to analyze the overall survival of patients with small intestine MALT.
| Variables | Univariate | Multivariate | |||||
|---|---|---|---|---|---|---|---|
| HR | 95% CI | P value | HR | 95% CI | P value | ||
| Age, years | |||||||
| ≤65 | 1 | Reference | 1 | Reference | |||
| >65 | 4.71 | 3.17, 6.99 | <0.001* | 4.50 | 3.03, 6.70 | <0.001* | |
| Year of diagnosis | |||||||
| 2000–2010 | 1 | Reference | – | – | – | ||
| 2011–2021 | 0.84 | 0.57, 1.23 | 0.37 | – | – | – | |
| Sex | |||||||
| Male | 1 | Reference | – | – | – | ||
| Female | 0.86 | 0.62, 1.20 | 0.38 | – | – | – | |
| Race | |||||||
| White | 1 | Reference | – | – | – | ||
| Black | 1.54 | 0.78, 3.04 | 0.21 | – | – | – | |
| Others | 1.56 | 0.94, 2.61 | 0.09 | – | – | – | |
| AJCC stage | |||||||
| I/II | 1 | Reference | 1 | Reference | |||
| III/IV | 1.86 | 1.22, 2.83 | 0.004* | 1.53 | 1.01, 2.34 | 0.048* | |
| Surgery | |||||||
| Yes | 1 | Reference | – | – | – | ||
| No | 0.82 | 0.54, 1.25 | 0.36 | – | – | – | |
| Chemotherapy | |||||||
| Yes | 1 | Reference | – | – | – | ||
| No/unknown | 1.13 | 0.79, 1.63 | 0.50 | – | – | – | |
| Marital status | |||||||
| Married | 1 | Reference | 1 | Reference | |||
| Unmarried | 1.41 | 1.02, 1.97 | 0.041 | 1.35 | 0.97, 1.89 | 0.07 | |
*, P<0.05. Others: American Indian, Alaska Native, Asian/Pacific Islander. AJCC, American Joint Committee on Cancer; CI, confidence interval; HR, hazard ratios; MALT, mucosa-associated lymphoid tissue.
Table 3. Univariate and multivariate Cox regression to analyze the cancer specific survival of patients with small intestine MALT.
| Variables | Univariate | Multivariate | |||||
|---|---|---|---|---|---|---|---|
| HR | 95% CI | P value | HR | 95% CI | P value | ||
| Age, years | |||||||
| ≤65 | 1 | Reference | – | – | – | ||
| >65 | 1.64 | 0.94, 2.87 | 0.08 | – | – | – | |
| Year of diagnosis | |||||||
| 2000–2010 | 1 | Reference | – | – | – | ||
| 2011–2021 | 0.73 | 0.40, 1.33 | 0.30 | – | – | – | |
| Sex | |||||||
| Male | 1 | Reference | – | – | – | ||
| Female | 0.73 | 0.42, 1.29 | 0.28 | – | – | – | |
| Race | |||||||
| White | 1 | Reference | 1 | Reference | |||
| Black | 1.93 | 0.69, 5.43 | 0.21 | 2.26 | 0.80, 6.38 | 0.13 | |
| Others | 2.44 | 1.21, 4.95 | 0.01 | 2.34 | 1.16, 4.73 | 0.02 | |
| AJCC stage | |||||||
| I/II | 1 | Reference | 1 | Reference | |||
| III/IV | 3.89 | 2.17, 6.97 | <0.001* | 3.93 | 2.19, 7.06 | <0.001* | |
| Surgery | |||||||
| Yes | 1 | Reference | – | – | – | ||
| No | 1.31 | 0.71, 2.42 | 0.40 | – | – | – | |
| Chemotherapy | |||||||
| Yes | 1 | Reference | – | – | – | ||
| No/unknown | 0.65 | 0.37, 1.13 | 0.13 | – | – | – | |
| Marital status | |||||||
| Married | 1 | Reference | – | – | – | ||
| Unmarried | 1.03 | 0.58, 1.80 | 0.93 | – | – | – | |
*, P<0.05. Others: American Indian, Alaska Native, Asian/Pacific Islander. AJCC, American Joint Committee on Cancer; CI, confidence interval; HR, hazard ratios; MALT, mucosa-associated lymphoid tissue.
Table 4. Univariate and multivariate Cox regression to analyze the overall survival of patients with small intestine DLBCL.
| Variables | Univariate | Multivariate | |||||
|---|---|---|---|---|---|---|---|
| HR | 95% CI | P value | HR | 95% CI | P value | ||
| Age, years | |||||||
| ≤65 | 1 | Reference | 1 | Reference | |||
| >65 | 3.22 | 2.83, 3.66 | <0.001* | 2.77 | 2.44, 3.16 | <0.001* | |
| Year of diagnosis | |||||||
| 2000–2010 | 1 | Reference | 1 | Reference | |||
| 2011–2021 | 0.87 | 0.78, 0.99 | 0.030* | 0.89 | 0.79, 0.99 | 0.049* | |
| Sex | |||||||
| Male | 1 | Reference | – | – | – | ||
| Female | 1.03 | 0.92, 1.16 | 0.58 | – | – | – | |
| Race | |||||||
| White | 1 | Reference | – | – | – | ||
| Black | 1.06 | 0.82, 1.35 | 0.67 | – | – | – | |
| Others | 0.90 | 0.74, 1.10 | 0.32 | – | – | – | |
| AJCC stage | |||||||
| I/II | 1 | Reference | 1 | Reference | |||
| III/IV | 2.66 | 2.37, 2.98 | <0.001* | 3.02 | 2.68, 3.40 | <0.001* | |
| Surgery | |||||||
| Yes | 1 | Reference | – | – | – | ||
| No | 1.00 | 0.87, 1.15 | >0.99 | – | – | – | |
| Chemotherapy | |||||||
| Yes | 1 | Reference | 1 | Reference | |||
| No/unknown | 2.65 | 2.37, 2.96 | <0.001* | 2.89 | 2.57, 3.24 | <0.001* | |
| Marital status | |||||||
| Married | 1 | Reference | 1 | Reference | |||
| Unmarried | 1.22 | 1.09, 1.37 | <0.001* | 1.15 | 1.03, 1.29 | 0.01* | |
*, P<0.05. Others: American Indian, Alaska Native, Asian/Pacific Islander. AJCC, American Joint Committee on Cancer; CI, confidence interval; DLBCL, diffuse large B-cell lymphoma; HR, hazard ratios; MALT, mucosa-associated lymphoid tissue.
Table 5. Univariate and multivariate Cox regression to analyze the cancer specific survival of patients with small intestine DLBCL.
| Variables | Univariate | Multivariate | |||||
|---|---|---|---|---|---|---|---|
| HR | 95% CI | P value | HR | 95% CI | P value | ||
| Age, years | |||||||
| ≤65 | 1 | Reference | 1 | Reference | |||
| >65 | 2.38 | 2.03, 2.79 | <0.001 | 1.89 | 1.61, 2.22 | <0.001 | |
| Year of diagnosis | |||||||
| 2000–2010 | 1 | Reference | 1 | Reference | |||
| 2011–2021 | 0.76 | 0.66, 0.88 | <0.001 | 0.79 | 0.68, 0.92 | 0.002 | |
| Sex | |||||||
| Male | 1 | Reference | – | – | – | ||
| Female | 0.98 | 0.85, 1.14 | 0.80 | – | – | – | |
| Race | |||||||
| White | 1 | Reference | – | – | – | ||
| Black | 1.04 | 0.76, 1.42 | 0.83# | – | – | – | |
| Others | 0.92 | 0.71, 1.18 | 0.50# | – | – | – | |
| AJCC stage | |||||||
| I/II | 1 | Reference | 1 | Reference | |||
| III/IV | 3.88 | 3.36, 4.48 | <0.001 | 4.61 | 3.97, 5.36 | <0.001 | |
| Surgery | |||||||
| Yes | 1 | Reference | – | – | – | ||
| No | 1.02 | 0.86, 1.22 | 0.79 | – | – | – | |
| Chemotherapy | |||||||
| Yes | 1 | Reference | 1 | Reference | |||
| No/unknown | 2.75 | 2.39, 3.17 | <0.001 | 3.29 | 2.84, 3.83 | <0.001 | |
| Marital status | |||||||
| Married | 1 | Reference | 1 | Reference | |||
| Unmarried | 1.42 | 1.23, 1.63 | <0.001 | 1.26 | 1.09, 1.45 | 0.002 | |
# indicates no statistically significant difference between the two groups. Others: American Indian, Alaska Native, Asian/Pacific Islander. AJCC, American Joint Committee on Cancer; CI, confidence interval; DLBCL, diffuse large B-cell lymphoma; HR, hazard ratios.
Survival analysis of patients with small intestine MALT and DLBCL in AJCC stage
A multivariate Cox regression analysis, accounting for numerous variables, underscored the pivotal role of AJCC stage in predicting both OS and CSS among patients with small intestine MALT and DLBCL. Following this, we assessed the prognostic significance of AJCC stage in these patient cohorts. Our findings revealed that patients with small intestine MALT who had AJCC stage III/IV experienced markedly reduced OS and CSS compared to those with stage I/II, with HRs and 95% CIs of 1.86 (1.22–2.83) for OS (P=0.004) and 3.89 (2.17–6.97) for CSS (P<0.001), respectively, as depicted in Figure S4A,S4B. Likewise, for patients with small intestine DLBCL, those with AJCC stage III/IV also exhibited significantly worse OS and CSS compared to stage I/II patients, with HRs (95% CIs) of 2.66 (2.37–2.98) for OS (P<0.001) and 3.88 (3.36–4.48) for CSS (P<0.001), respectively, as shown in Figure S4C,S4D.
Discussion
In this study, we investigated the clinical characteristics and long-term prognosis of primary MALT lymphoma and DLBCL in the small intestine using data from the SEER database. A total of 2,748 patients, including 2,362 with DLBCL and 386 with MALT, diagnosed between 2000 and 2021, were included. PSM was employed to mitigate selection bias. Our analysis revealed that MALT patients were younger, had a higher proportion of females, and presented at earlier AJCC stages compared to DLBCL patients. Kaplan-Meier survival analysis demonstrated significantly better OS and CSS for the MALT cohort both before and after PSM. Specifically, 5-year OS and CSS rates were higher for MALT (80.1% and 90.0%, respectively) than for DLBCL (57.6% and 67.8%, respectively). Cox regression analysis identified age and AJCC stage as prognostic factors for OS in MALT patients, while race and AJCC stage were prognostic for CSS. For DLBCL patients, age, year of diagnosis, AJCC stage, chemotherapy, and marital status were significant prognostic factors for both OS and CSS. These findings suggest that patients with small intestine MALT lymphoma have a more favorable prognosis than those with DLBCL, emphasizing the importance of early diagnosis and appropriate treatment strategies.
In a small-sample retrospective analysis conducted by Korean researchers comparing the clinical outcomes of duodenal and gastric MALT lymphomas, a higher male-to-female patient ratio was observed (25). Similarly, Castro et al. (26) utilized extensive data from German cancer registries and the U.S. SEER database to compare the prognosis of gastric MALT and DLBCL, finding a higher proportion of male patients. Wang et al. (23) developed prognostic models for small intestinal and colonic DLBCL using the SEER database, which included 1,613 patients, 63.9% of whom were male. Another study, combining SEER data with data from a Chinese hospital, also reported a male predominance (24). In alignment with these findings, our study likewise identified a higher proportion of male patients compared to female patients in both small intestinal MALT and DLBCL. Several potential explanations for this gender disparity are proposed. First, males may encounter greater occupational stress, which could adversely affect the immune system and increase lymphoma risk. Prior research supports the notion that immune system impairment elevates the risk of GIL (27,28). Second, males may be more frequently engaged in communal dining practices, potentially exposing them to a higher risk of HP infection and, consequently, MALT lymphoma. Multiple cohort studies have documented a higher prevalence of HP infection in males compared to females (29-31). Furthermore, gender-specific differences in hormone levels, genetic predisposition, dietary patterns, and other factors may also contribute to the development of GIL (1,4,32). Nonetheless, some studies utilizing SEER data have reported comparable proportions of male and female patients among gastric MALT lymphoma cases (12,33). The discrepancies observed between these studies and the aforementioned ones may stem from variations in sample size, geographical location, and racial composition. Hence, future large-scale studies encompassing diverse regions, time periods, and racial groups are warranted to further elucidate the gender distribution of small intestinal lymphoma.
The AJCC staging system is of paramount importance in the diagnosis, treatment planning, and prognostic evaluation of cancer. In the context of small intestinal lymphoma, the AJCC stage incorporates factors including primary tumor size, depth of invasion, regional lymph node involvement, and distant metastasis, thereby stratifying the disease into standardized stages I, II, III, and IV (34-36). Cancers at varying stages demonstrate distinct biological features and prognostic profiles, guiding the choice of appropriate therapeutic interventions based on staging outcomes. For instance, early-stage cancers (e.g., stages I and II) may be optimally managed with surgical resection, whereas advanced-stage cancers (e.g., stages III and IV) may require a multimodal approach incorporating chemotherapy, radiotherapy, and immunotherapy. Our study revealed that the AJCC stage is a significant predictor of prognosis in patients with small intestinal MALT and DLBCL, with patients at advanced stages experiencing markedly poorer outcomes compared to those at earlier stages. This finding aligns with the work of Sun et al. (37), who also identified the AJCC stage as a key prognostic factor in their investigation of a prognostic nomogram for primary gastrointestinal NHL. Furthermore, we noted that a substantial proportion of patients with small intestinal MALT and DLBCL were diagnosed at early stages, specifically 88.1% of MALT patients and 74.4% of DLBCL patients. The indolent nature of small intestinal MALT lymphoma, originating from mucosa-associated lymphoid tissue, characterized by slow growth, low invasiveness, and frequent localization to the primary site with infrequent distant metastases, contributes to the higher proportion of early-stage diagnoses (38,39). Additionally, advancements in imaging modalities [such as computed tomography (CT), magnetic resonance imaging, positron emission tomography-CT, etc.] and pathological examination techniques have enabled more precise assessment of tumor characteristics, including size, invasion depth, lymph node involvement, and distant metastasis, leading to an increased detection of DLBCL at early stages (40-43). Furthermore, the evolution of small intestinal endoscopy and capsule endoscopy has further enhanced the detection of early-stage MALT and DLBCL, facilitating earlier diagnosis (41,44). Consequently, our study demonstrated that the 5-year OS rate and 5-year CSS rate for small intestinal MALT patients were 80.1% and 90.0%, respectively. Despite DLBCL being a more aggressive NHL, it exhibited 5-year OS and CSS rates of 57.6% and 67.8%, respectively. This conclusion is consistent with that of Calomino et al. (45), indicating that the prognosis of DLBCL is relatively poorer, which may be associated with its more aggressive nature.
In the investigation by Liu et al. (24) on the clinical characteristics and prognostic outcomes of small intestine DLBCL patients, it was determined that age, marital status, disease stage, surgical intervention, and chemotherapy were independent risk factors for OS. Similarly, our research identified age, year of diagnosis, AJCC stage, chemotherapy administration, and marital status as independent predictors of OS in these patients. Specifically, individuals aged above 65 years, those diagnosed in earlier periods, patients with advanced AJCC stages, those not receiving chemotherapy, and unmarried patients exhibited poorer OS rates. In addition to analyzing OS, our study also explored CSS among small intestine DLBCL patients. We observed that the factors influencing OS were also predictive of CSS. Consistent with the findings of Liu et al. (24), our results indicated a worse prognosis for elderly patients, potentially due to physiological decline and diminished medication tolerance in this demographic. Furthermore, we noted an improved prognosis for patients diagnosed in more recent years, which might be attributable to advancements in diagnostic and therapeutic methodologies (38,41). Additionally, we found that unmarried patients had a poorer prognosis, possibly because married patients may receive greater social support, family care, and emotional backing, aiding in maintaining a positive mindset and treatment adherence, thereby potentially enhancing their prognostic outcomes (46). Nonetheless, the evidence supporting these assertions remains limited, and further research is imperative to validate these findings. Given the rarity of small intestine MALT lymphoma, large-scale studies on this subject are scarce, and the existing literature predominantly consists of case reports or small-sample studies (19,20). Our study marks the initial population-based investigation into the risk factors affecting OS and CSS in individuals with small intestine MALT lymphoma. The results indicate that age and AJCC stage are determinants of OS, with older patients and those at more advanced stages experiencing worse outcomes. Additionally, race and AJCC stage were found to be predictors of CSS, where patients belonging to other races (such as American Indian, Alaska Native, Asian/Pacific Islander) had poorer prognoses compared to Caucasians, hinting at potential racial differences in the prognosis of small intestine MALT lymphoma. Further exploration is required to uncover the underlying causes of these disparities.
Our study has several limitations. Firstly, although we utilized the SEER database, which provides a large and diverse patient population, the retrospective nature of the study limits our ability to control for all potential confounding factors. This could introduce bias into our findings, despite our efforts to minimize selection bias through PSM. Secondly, the SEER database relies on administrative data, which may not capture all relevant clinical details, such as specific treatment regimens, comorbidity status, or genetic markers, that could influence patient outcomes. Thirdly, the relatively small sample size of the MALT lymphoma cohort, compared to the DLBCL cohort, may have limited our statistical power to detect small differences in survival outcomes or to identify all potential prognostic factors. Fourthly, the racial disparities observed in our study require further investigation, as the SEER database does not provide detailed information on socioeconomic status, access to healthcare, or other factors that could contribute to these disparities. Finally, our study focused on OS and CSS, but did not explore other important outcomes, such as quality of life or treatment-related toxicity, which are also crucial in the management of these patients. Future studies with larger sample sizes, prospective designs, and more comprehensive data collection are needed to address these limitations and to further refine our understanding of the clinical characteristics and prognosis of small intestine MALT lymphoma and DLBCL.
Conclusions
In summary, our study reveals distinct clinical characteristics and prognosis between small intestine MALT lymphoma and DLBCL, with MALT patients demonstrating a more favorable outcome. The significant impact of AJCC staging on prognosis underscores the necessity of timely diagnosis and intervention. Future research should delve deeper into the biological differences between these lymphomas, refine prognostic models, and explore novel therapeutic strategies to further improve patient outcomes, particularly for those with DLBCL who face a less favorable prognosis.
Supplementary
The article’s supplementary files as
Acknowledgments
None.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.
Footnotes
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-1213/rc
Funding: This study was supported by the Changshu Science and Technology Program (No. CY202339), the Suzhou Youth Science and Technology Project for the Advancement of Science, Education, and Health (No. KJXW2023067), and the Suzhou 23rd Batch of Science and Technology Development Plan (Clinical Trial Institution Capability Enhancement) Project (No. SLT 2023006).
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-1213/coif). The authors have no conflicts of interest to declare.
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