Primary gastric lymphomas are rare. Although their incidence rate is increasing, they comprise less than 10% of gastric malignancies. Despite this rarity, stomach accounts for more than two-third of all extranodal non-Hodgkin lymphomas. Because of its multiple subtypes and low prevalence, its treatment is not so clear cut. More than 30 types, with different biological and clinical characteristics, have been recognized by the WHO classification. Two main subtypes are MALT and DLCL with different behaviors and treatments. Other less frequent subtypes are follicular, mantle, and T-cell lymphoma [
Previously, the main treatment for gastric lymphomas was supposed to be surgery. Older studies pointed to the important role of surgery in treatment of the disorder [
In general, the prognosis depends on multiple factors, such as patient’s age and performance status, histologic subtype, treatment, lactate dehydrogenase (LDH) serum levels, and disease related factors [
The present retrospective study was conducted on the patients with gastric lymphoma in our referral radiotherapy center between 1998 and 2010. All the patients had presented with gastrointestinal complaint, and lymphoma diagnosis was made by endoscopy biopsy first. The patients’ demographic characteristic, disease factors (size, location, histology, etc.), performance status, treatment (operation, radiotherapy/chemotherapy technique, and dose), and outcome (disease-free survival and overall survival) were obtained from their records and by phone if needed. We searched “PubMed” using “gastric and lymphoma” or “stomach and lymphoma” to find the related papers.
This study was conducted on 54 cases with biopsy proven diagnosis of primary gastric NHL who had been treated and followed up at our ward during 1998 to 2010. The performance status (PS) was determined according to the World Health Organization (WHO) scale. Only the patients who had initially presented with gastric lymphoma were classified as gastric lymphoma, and those with secondary gastric involvement with lymphoma were excluded from the study. The patients were staged according to the Ann Arbor staging system at the time of diagnosis. All the patients had undergone endoscopy and location of tumor was mentioned at reports. However, no information was available regarding
Clinical investigation included history, physical examination, complete blood count, erythrocyte sedimentation rate, kidney function test, liver function test, serum LDH, abdomen and pelvic ultrasonography, Computed Tomography (CT) scan, chest X ray, bone marrow aspiration, and biopsy.
All the patients were treated with curative intent. Overall, 44 patients (81.5%) had undergone gastrectomy followed by adjuvant chemotherapy and/or radiotherapy, whereas 10 ones (18.5%) had been treated with chemotherapy alone or with radiotherapy (see Table
Distribution of treatment schedules and histopathologic types in 54 patients with primary gastric lymphoma.
Treatment | Histopathology | |||||
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DLBCL | MALT lymphoma | Follicular lymphoma | T-cell lymphoma | Mantel cell lymphoma | Total | |
Sur → RT | 0 | 2 | 0 | 0 | 0 | 2 |
Sur → RT → ChT | 3 | 2 | 0 | 0 | 0 | 5 |
Sur → ChT → RT | 19 | 6 | 1 | 0 | 1 | 27 |
Sur → ChT → RT → ChT | 1 | 1 | 0 | 0 | 0 | 2 |
Sur → ChT | 5 | 1 | 0 | 2 | 0 | 8 |
ChT → RT | 6 | 1 | 0 | 0 | 0 | 7 |
ChT → RT → ChT | 1 | 1 | 0 | 0 | 0 | 2 |
ChT alone | 1 | 0 | 0 | 0 | 0 | 1 |
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Total |
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DLBCL: diffuse large B-cell lymphoma; Sur: surgery; RT: radiotherapy; ChT: chemotherapy.
Disease- or progression-free survival was calculated as the duration from the date of histological diagnosis to the date of relapse or disease progression or censored at the date of the last followup. In addition, OS was calculated as the duration from the date of histological diagnosis to the date of death resulting from any cause or censored at the date of the last followup. Univariate analysis for DFS and OS rates were performed using the Kaplan–Meier method and the prognostic factors were compared using the log-rank test. Besides, multiple-covariate analysis was performed using the stepwise regression hazards regression model. The Hazard Ratio (HR) for death, with the 95% Confidence Interval (CI), was calculated for the variable groups. The stratified log-rank test was used to compare the treatment results in each variable group. A
A total of 54 patients with primary gastric lymphoma were reviewed. The patients’ median age was 50 (17–75) years, and 28 patients (51%) were 50 years old or younger. Besides, the peak age was during the sixth decade of life in both sexes. The WHO performance status was 0 or 1 in approximately 83% of the patients, while 2 or 3 in 13%. Epigastric pain and discomfort (83%), anorexia and weight loss (41%), and postprandial vomiting (28%) were the most common presenting signs and symptoms. B symptoms occurred in 33% of the patients. In addition, bulky disease (primary tumor size more than 10 cm in the greatest diameter) was documented in 20 patients (37%). According to the pathologic, imaging, and clinical findings, 36 (59%), 16 (30%), 5 (9%), and 1 (2%) patients were in stages I, II, III, and IV, respectively. Diffuse large B-cell lymphoma (67%) and Mucosa Associated Lymphoid Tissue (MALT) lymphoma (26%) were the most common histological types. Table
All the potential prognostic variables, including the WHO performance status, age, sex, Ann Arbor stage of disease, primary tumor size and location, B symptoms, histologic grade, serum LDH level, treatment modality, dose of radiation, and International Prognostic Index (IPI), were analyzed to find out their impacts on disease-free survival and overall survival of the patients with gastric lymphoma (Table
Univariate analysis of prognostic factors for clinical outcome.
Prognostic factors | Patients’ number | 5-year DFS (%) |
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5-year OS (%) |
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WHO performance score | |||||
0-1 | 45 | 73.9 | <0.001 | 76.2 | <0.001 |
2 | 5 | 00.0 | 00.0 | ||
3 | 4 | 00.0 | 00.0 | ||
Sex | |||||
Female | 29 | 61.8 | 0.742 | 66.8 | 0.923 |
Male | 25 | 68.1 | 67.3 | ||
Age | |||||
≤50 years | 28 | 73.9 | 0.097 | 79.6 | 0.034 |
>50 years | 26 | 55.2 | 49.1 | ||
Ann Arbor stage | |||||
I | 33 | 73.2 | 0.071 | 75.1 | 0.027 |
II | 15 | 59.5 | 70.1 | ||
III | 5 | 40.0 | 25.0 | ||
IV | 1 | 00.0 | 00.0 | ||
Histology | |||||
DLBC | 36 | 61.2 | 0.645 | 59.5 | 0.405 |
MALT | 14 | 71.4 | 77.9 | ||
Others | 4 | 100.0 | 100.0 | ||
Primary tumor size | |||||
1–5 cm | 13 | 61.5 | 0.412 | 75.0 | 0.182 |
6–9 cm | 21 | 72.8 | 75.9 | ||
≥10 cm | 20 | 58.9 | 50.5 | ||
B symptoms | |||||
No | 36 | 78.8 | 0.001 | 77.8 | 0.013 |
Yes | 18 | 36.4 | 40.6 | ||
Serum LDH level | |||||
Normal | 34 | 93.1 | <0.001 | 92.6 | <0.001 |
Elevated | 20 | 28.7 | 34.0 | ||
Histological grade | |||||
I | 27 | 64.0 | 0.977 | 66.4 | 0.951 |
II | 13 | 69.2 | 76.2 | ||
III | 14 | 64.3 | 61.9 | ||
Treatment modality | |||||
Surgery + CT ± RT | 44 | 61.5 | 0.387 | 64.7 | 0.606 |
CT and/or RT | 10 | 80.0 | 80.0 | ||
Radiation dose | |||||
No RT | 7 | 34.3 | 0.236 | 41.7 | 0.169 |
<30 Gy | 11 | 61.4 | 47.7 | ||
30–40 Gy | 26 | 75.4 | 80.7 | ||
>40 Gy | 10 | 60.0 | 60.0 | ||
IPI | |||||
0-1 risk factor | 35 | 84.4 | <0.001 | 89.2 | <0.001 |
2 risk factor | 6 | 33.3 | 25.0 | ||
≥3 risk factor | 13 | 16.2 | 13.6 | ||
Location | |||||
Proximal | 27 | 67.3 | 0.791 | 72.1 | 0.623 |
Distal | 24 | 61.4 | 61.7 | ||
Diffuse involvement | 3 | 66.7 | 66.7 | ||
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All patients |
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DFS: disease-free survival; OS: overall survival; CT: chemotherapy; RT: radiotherapy; IPI: International Prognostic Index.
The stratified log-rank test analysis of prognostic factors for histologic subtypes.
Prognostic factors | Patients’ number | 5-year OS (%) |
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DLBC | MALT | |||
WHO performance score | ||||
0-1 | 45 | 67.0 | 90.9 | <0.001 |
2 | 5 | 00.0 | 00.0 | |
3 | 4 | 00.0 | 50.0 | |
Sex | ||||
Female | 29 | 59.8 | 72.9 | 0.985 |
Male | 25 | 58.6 | 83.3 | |
Age | ||||
≤50 years | 28 | 74.9 | 88.9 | 0.021 |
>50 years | 26 | 36.2 | 60.0 | |
Ann Arbor stage | ||||
I | 33 | 64.7 | 90.0 | 0.039 |
II | 15 | 73.3 | 50.0 | |
III-IV | 6 | 00.0 | 50.0 | |
Primary tumor size | ||||
1–5 cm | 13 | 57.1 | — | 0.107 |
6–9 cm | 21 | 72.1 | — | |
≥10 cm | 20 | 63.6 | 57.1 | |
B symptoms | ||||
No | 36 | 73.2 | 81.8 | 0.025 |
Yes | 18 | 35.4 | 66.7 | |
Serum LDH level | ||||
Normal | 34 | 94.7 | 87.5 | <0.001 |
Elevated | 20 | 21.4 | 66.7 | |
Treatment modality | ||||
Surgery + CT ± RT | 44 | 53.8 | 82.5 | 0.502 |
CT and/or RT | 10 | 87.5 | 50.0 | |
IPI | ||||
0-1 risk factor | 35 | 87.0 | 90.9 | <0.001 |
2 risk factor | 6 | 20.0 | — | |
≥3 risk factor | 13 | 00.0 | 33.3 | |
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All patients |
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DFS: disease-free survival; OS: overall survival; CT: chemotherapy; RT: radiotherapy; IPI: International Prognostic Index.
This retrospective study has been conducted at the Nemazee hospital, the referral center in south of Iran. This study is the first report on GL in Iran. In this study multiple factors, including gender, age, grade, surgery, and LDH level (Table
Survival rates and prognostic factors in patients with primary gastric lymphoma in the literature.
Author [ref] | Patients’ number | 5-year DFS (%) | 3-year OS (%) | 5-year OS (%) | Prognostic factor |
---|---|---|---|---|---|
Medina-Franco et al. [ |
41 | 52.5 | — | 71.2 | LDH serum level, PS |
Danzon et al. [ |
361 | — | 63 | 61 | Age |
Park et al. [ |
214 | — | — | — | Age, LDH serum level, gender, ascites |
Bani-Hani et al. [ |
19 | — | — | 48.2 | Age, stage |
Economopoulos et al. [ |
29 | — | — | 58 | Stage, size |
Tanaka et al. [ |
95 | — | 81.7 | — | Stage, LDH serum level |
Huang et al. [ |
83 | 52 | — | 59 | PS, stage, modified IPI |
Muller et al. [ |
45 | — | — | 40 | Grade, stage |
Mäkelä et al. [ |
32 | — | — | 56 | Stage, radical surgery, age |
Xue et al. [ |
83 | — | — | 77.8 | Lymph node involvement and clinical stage |
Brincker and D'Amore [ |
106 | — | — | 67 | LDH serum level, fever |
Luo et al. [ |
68 | 75.7 | 78.2 | 75.7 | Surgery |
Barreda et al. [ |
169 | — | 61.34 | — | IPI, HDL, remission, treatment, location |
Durr et al. [ |
35 | 90 | — | — | Grade |
Shaw et al. [ |
62 | — | — | — | Weight loss, invasion of adjacent organs, nonsurgical treatment |
Al-Bahrani et al. [ |
32 | — | — | — | Stage, resectability |
Salvagno et al. [ |
525 | — | — | 65.4 | Surgery |
Jaser et al. [ |
66 | — | — | — | Stage |
Present study | 54 | 64.7 | — | 67 | IPI, LDH serum level |
Mean age in our study was 50 (17–75) years. As seen in Table
Characteristics of some major reported series of primary gastric lymphoma in the literature.
Author [ref] | Country | Year | Patients’ number | Median age (range) | Male/female ratio | Most frequent histological type |
---|---|---|---|---|---|---|
Medina-Franco et al. [ |
Mexico | 1990–2000 | 41 | 52.6 | 0.86 | Large cell lymphoma |
Danzon et al. [ |
France | 1989–1997 | 361 | — | 1.24 | High grade |
Park et al. [ |
Republic of Korea | 1990–2004 | 214 | 55 (21–81) | 1.27 | Only high grade |
Bani-Hani et al. [ |
Jordan | 1991–2002 | 19 | — | — | DLCL |
Economopoulos et al. [ |
Greece | 1977–1983 | 29 | 55 (21–74) | 2.2 | Diffuse histiocytic |
Huang et al. [ |
China | 2001–2008 | 83 | 52 (15–81) | 1.18 | DLCL |
Muller et al. [ |
UK | 1973–1992 | 45 | 65 (25–84) | 1.5 | High grade |
Luo et al. [ |
China | 1990–2003 | 68 | 50 (25–82) | 1.93 | — |
Barreda et al. [ |
Peru | 1995–2000 | 169 | — | 0.83 | DLCL |
Durr et al. [ |
USA | 1975–1991 | 35 | 63 | — | DLCL |
Lybeert et al. [ |
The Netherlands | 1982–1992 | 81 | 69.7 (30–88) | — | Intermediate grade |
Parvez et al. [ |
Saudi Arabia | 1990–1998 | 22 | — | — | DLCL |
Schmidt et al. [ |
Germany | 1985–2000 | 92 | 60 (29–85) | — | DLCL |
Shaw et al. [ |
New Zealand | 1969–1987 | 62 | — | 0.87 | — |
Takahashi et al. [ |
Japan | 1974–1996 | 85 | 60.5 | 1.07 | — |
Aoyagi et al. [ |
Japan | 1980–1994 | 25 | 59.6 (26–89) | 0.92 | — |
Waisberg et al. [ |
Brazil | 1973–2001 | 16 | 62.8 (40–83) | 3 | Low grade |
Koch et al. [ |
Germany | 1996–2004 | 398 | 63.2 (20–83) | 1.2 | DLCL |
Al-Bahrani et al. [ |
Iraq | 1965–1978 | 32 | 42.6 (12–70) | 2.5 | PDLL |
Present study | Iran | 1998–2012 | 54 | 50 (17–75) | 0.86 | DLBCL |
DLCL: diffuse large cell lymphoma; DLBCL: diffuse large B-cell lymphoma; PDLL: poorly differentiated lymphocytic lymphoma; DFS: disease-free survival; OS: overall survival; LDH: lactic dehydrogenase.
Extranodal lymphoma consists of 25–40% of all lymphomas. The most common location for extranodal lymphoma is the gastrointestinal tract which consists of 30–40% of the extranodal lymphoma [
In general, GL more frequently involves antrum, corpus, and cardia [
Rise in LDH level, BM involvement, and B symptoms are less frequent in GL [
IPI consists of some prognostic factors, such as age > 60 years, stage > II2, high LDH level, ECOG PS > 2, and more than one Extranodal Site (EN) of disease. Our study results indicated a significant relationship between IPI and survival. IPI has been proposed as the strongest prognostic factor [
The most common subtype in our study was DLCL followed by MALT. T-cell, mantle, and follicular lymphomas totally were detected in 4 cases. Survivals in different subtypes were not statistically different. Up to now, over 30 subtypes of GL with various prognoses have been recognized by the WHO classification, and the disease treatment is guided by the subtype [
Major reports on gastric MALT.
Author | Country | Stage | Years | Number | Median age (range) | M/F | Survival |
---|---|---|---|---|---|---|---|
Andriani et al. [ |
Italy | I-II | 1993–2006 | 60 | 60 (23–80) | 1.2 | 94.7 (74.6)% 5 y |
Gisbert et al. [ |
Spain | I–IV | 1991–2005 | 37 | 61 | 1.63 | NM |
Park et al. [ |
Republic of Korea | I | 1998–2002 | 11 | 55.7 (36–73) | 0.83 | NM |
Stathis et al. [ |
Italy | I-II | 1990–2006 | 105 | 64 (20–94 ) | 1.05 | 92% |
Present study | Iran | I–IV | 1998–2010 | 14 | 47.50 (17–75) | 0.75 | 77.9 5 Y DFS |
NM: not mentioned.
Major reports on gastric DLCL.
Author | Country | Stage | Years | Number | Median age (range) | M/F | Survival |
---|---|---|---|---|---|---|---|
Tanaka et al. [ |
Japan | I–IV | 1995–2009 | 95 | 68 (32–86) | 1.11 | — |
Leopardo et al. [ |
Italy | I–IV | 2000–2007 | 30 | 58 | 1.5 | 100% 5 y DFS |
30 | 73.3% | ||||||
Ibrahim et al. [ |
Saudi Arabia | I–IV | 1982–1998 | 185 | 54 (17–94) | 1.34 | 68% 5 y OS |
Spectre et al. [ |
Israel | I–IV | 1990–2005 | 73 | 57 (20–80) | 1.28 | 62% 3OS |
Present study | Iran | I–IV | 1998–2010 | 36 | 49 (17–74) | 1.0 | 59.5 5 Y DFS |
GL treatment is not so clear and multiple strategies have been proposed in this regard; however, it is not known which one is more beneficial [
Rituximab is a monoclonal antibody against CD20 on B-cell lymphoma. It is widely used and is effective in overall survival as well as disease-free survival in nodal lymphoma. Studies on the effectiveness of rituximab in gastric DLCL have revealed improvement in the response rate and survival [
GL is a diverse category according to its subtypes and associated prognostic factors. Thus, further prospective studies according to each subtype may open the horizons.
The Research Improvement Center of Shiraz University of Medical Sciences and Ms. A. Keivanshekouh are appreciated for improving the use of English in the paper.