Leukemia & Lymphoma
ISSN: 1042-8194 (Print) 1029-2403 (Online) Journal homepage: http://www.tandfonline.com/loi/ilal20
Dissemination pattern of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue Yoshimi Ishii, Naoto Tomita, Taisei Suzuki, Yasufumi Ishiyama, Kumiko Kishimoto, Eri Yamamoto, Satoshi Koyama, Yukako Hattori, Yuki Nakajima, Kenji Motohashi, Hirotaka Takasaki, Rika Kawasaki, Chizuko Hashimoto, Sachiya Takemura, Katsumichi Fujimaki, Hiroyuki Fujita, Rika Sakai, Shin Fujisawa, Shigeki Motomura & Yoshiaki Ishigatsubo To cite this article: Yoshimi Ishii, Naoto Tomita, Taisei Suzuki, Yasufumi Ishiyama, Kumiko Kishimoto, Eri Yamamoto, Satoshi Koyama, Yukako Hattori, Yuki Nakajima, Kenji Motohashi, Hirotaka Takasaki, Rika Kawasaki, Chizuko Hashimoto, Sachiya Takemura, Katsumichi Fujimaki, Hiroyuki Fujita, Rika Sakai, Shin Fujisawa, Shigeki Motomura & Yoshiaki Ishigatsubo (2015) Dissemination pattern of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, Leukemia & Lymphoma, 56:9, 2750-2752, DOI: 10.3109/10428194.2015.1010161 To link to this article: http://dx.doi.org/10.3109/10428194.2015.1010161
View supplementary material
Accepted author version posted online: 03 Feb 2015. Published online: 06 Mar 2015.
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Article views: 40
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ilal20 Download by: [University of Cambridge]
Date: 05 November 2015, At: 22:01
Leukemia & Lymphoma, September 2015; 56(9): 2750–2752 © 2015 Informa UK, Ltd. ISSN: 1042-8194 print / 1029-2403 online DOI: 10.3109/10428194.2015.1010161
Letter to the Editor
Dissemination pattern of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue Yoshimi Ishii1,2, Naoto Tomita1, Taisei Suzuki3, Yasufumi Ishiyama4, Kumiko Kishimoto2, Eri Yamamoto1, Satoshi Koyama1, Yukako Hattori5, Yuki Nakajima1, Kenji Motohashi2, Hirotaka Takasaki5, Rika Kawasaki6, Chizuko Hashimoto7, Sachiya Takemura8, Katsumichi Fujimaki6, Hiroyuki Fujita9, Rika Sakai5, Shin Fujisawa2, Shigeki Motomura5 & Yoshiaki Ishigatsubo1
Downloaded by [University of Cambridge] at 22:01 05 November 2015
1Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine,
Yokohama, Japan, 2Department of Hematology, Yokohama City University Medical Center, Yokohama, Japan, 3Department of Hematology, Shizuoka Red Cross Hospital, Shizuoka, Japan, 4Department of Hematology, Yokosuka City Hospital, Yokosuka, Japan, 5Department of Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan, and 6Department of Hematology/ Immunology, Fujisawa City Hospital, Fujisawa, Japan, 7Department of Hematology/Oncology, Yamato Municipal Hospital, Yamato, Japan, 8Department of Internal Medicine, Yokohama Ekisaikai Hospital, Yokohama, Japan and 9Department of Hematology, Saiseikai Yokohama Nanbu Hospital, Yokohama, Japan
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) was first described by Isaacson and Wright in 1983 [1]. MALT lymphoma, an extranodal lymphoma composed of morphologically heterogeneous small B cells, is a common subtype of non-Hodgkin lymphoma, constituting 7–8% of all B cell lymphomas and up to 50% of primary gastric lymphomas [2]. In addition to the stomach, MALT lymphomas can arise in various nongastrointestinal (GI) sites, including the salivary gland, conjunctiva, thyroid, orbit, lung, larynx, breast, liver, skin and dura mater. Patients with MALT lymphoma usually have an indolent course with a long disease-free and overall survival, associated with a slow dissemination rate of the disease [3–6]. There is no consensus on the best approach to manage this disease, and treatment decisions are often made on a caseby-case basis according to the disease dissemination pattern. Approximately 30–40% of patients present with advancedstage disease at diagnosis [3,5,7,8], and extensive staging is generally recommended to determine the best treatment in such patients [9]. We also previously reported the importance of full staging in patients with MALT lymphoma with advanced disease, given the significant proportion (5/16 [31%]) of patients with primary pulmonary MALT lymphoma with gastric involvement [10]. The dissemination pattern in patients with MALT lymphoma still remains unknown. Here, we present an analysis of the dissemination pattern in 184 cases of newly diagnosed MALT lymphoma. Between May 1998 and September 2013, 184 patients were newly diagnosed with MALT lymphoma and were treated in
Yokohama City University Hematology Group. The diagnosis was determined by institutional pathologists according to the World Health Organization classification criteria [2]. A central pathological review was not performed. Before the initiation of therapy, all 184 patients underwent a full staging, briefly consisting of physical examination, hematological and biochemical tests, chest radiography, computed tomography (CT) or positron emission tomography (PET)/CT from the cervix to the pelvis, and bone marrow aspiration and biopsy. Staging was performed according to the Ann Arbor classification [11]. Patient management varied and consisted of chemotherapy, radiotherapy, chemoradiotherapy, surgery, Helicobacter pylori eradication and watch-and-wait. Management decisions were made on a case-by-case basis according to clinical stage. Patients underwent follow-up CT or PET/CT every 6 months for at least 5 years. The median follow-up time was 50 months for surviving patients (range, 2–155 months). Overall survival (OS) was calculated from the date of diagnosis to the date of death or last follow-up assessment, whichever occurred first. Fisher’s exact test was used to calculate the differences between the two groups. Survival curves were constructed using the Kaplan–Meier method and compared using the log-rank test. A p-value 0.05 was considered statistically significant. All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University), which is a graphical user interface for R software (R Foundation for Statistical Computing). This study was approved by the institutional review board of Yokohama City University Hospital.
Correspondence: Dr. Naoto Tomita, Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa, Yokohama 236-0004, Japan. Tel: 81-45-787-2800. Fax: 81-45-786-3444. E-mail: [email protected] Received 20 September 2014; revised 13 January 2015; accepted 17 January 2015
2750
Downloaded by [University of Cambridge] at 22:01 05 November 2015
Letter to the editor 2751
Human immunodeficiency virus infection was not observed in any of the 184 patients. The median age was 69 years (range, 25–94 years). Eighty-three patients (45%) were male and 101 patients (55%) were female (male/female ratio, 0.82). The stage distribution was as follows: stage I, 112 patients (61%); stage II, 28 patients (15%); stage III, two patients (1%); and stage IV, 42 patients (23%). Thirty-three patients (18%) presented with 1 extranodal site, whereas 151 patients (82%) had only one extranodal site. According to International Prognostic Index (IPI) criteria, 67%, 22%, 10% and 1% of patients were in the low-, low-intermediate, high-intermediate and high-risk groups, respectively. Thirty-seven patients (20%) had nodal involvement. The serum lactate dehydrogenase (LDH) level was elevated in 28 patients (15%). Six patients (3%) had bone marrow involvement. Five patients (3%) had B symptoms. Two patients (1%) had Eastern Cooperative Oncology Group performance status 2–4. Soluble interleukin-2 receptor (sIL-2R) level was 1000 U/mL in 13 patients (7%). Male patients were diagnosed at a more advanced clinical stage compared with female patients (p 0.015). Advanced clinical stage was correlated with sIL-2R 1000 U/mL (p 0.003). In the 184 patients, a total of 259 lesions (including nodal and extranodal sites) were detected. The lesion sites are summarized in Figure 1. This figure shows the organ that MALT lymphoma tended to involve. Most patients (149/184 [81%]) presented with single-organ involvement. Thirty-five patients (19%) had multiorgan involvement. Of these patients, four (2%) had GI involvement and 31 (17%) had multiorgan involvement outside the GI tract. Twelve patients (7%) had both GI tract and non-GI tract involvement. Five patients (3%) had both lung and gastric involvement. The number of patients with multiorgan involvement was higher in patients with extragastric lymphoma than in patients with gastric lymphoma (28/107 [26%] patients vs. 7/77 [9%]; p 0.004).
Additional lymphoma localization at diagnosis and rate of stage according to initial presentation are summarized in Table I. Two patients had bilateral orbital lesions, and one patient had bilateral salivary gland lesions. Four of 23 (17%) with primary pulmonary involvement had additional gastric lesions. Two patients with orbital lymphoma had bone marrow involvement and one had a pulmonary lesion. Nine patients died. Death was related to lymphoma progression in three patients (33%), whereas the other six patients died of various causes including secondary acute myeloid leukemia (one patient), colon cancer (one patient), breast cancer (one patient), hepatitis (one patient), progressive multifocal leukoencephalopathy (one patient) and unknown reason (one patient). The 4-year OS rate was 96.2%. Four-year OS rates were similar between patients with disseminated and localized disease (96.1% vs. 95.5%; p 0.77). The 4-year OS rate was not significantly different between patients with gastric lymphoma and patients with extragastric lymphoma (95.5% vs. 96.7%; p 0.207). Fouryear OS rates were not different according to primary MALT site. In univariate analysis, elevated LDH, IPI, B symptoms, advanced stage, performance status 3–4, nodal involvement, age 65 and primary site did not influence the OS rate. Bone marrow involvement and 1 extranodal site were unfavorable prognostic factors, but not unfavorable factors through multivariate analysis. In our study, we evaluated 184 patients with newly diagnosed MALT lymphoma. Seventy-seven patients (42%) had primary gastric lymphoma and 104 patients (58%) had primary extragastric lymphoma, similar to other published data [9]. Raderer et al. reported that 15 (25%) of 61 patients with gastric MALT lymphoma had multifocal involvement and 37 (47%) of 79 patients with extragastric lymphoma had multiorgan involvement [9]. We also found that multiorgan involvement occurred more frequently in patients with primary
Figure 1. Lesion sites in 184 patients with MALT lymphoma. A total of 259 lesions were detected.
2752
Y. ishii et al.
Table I. Additional lymphoma localization at diagnosis and rate of stage according to primary site. Primary lesion (n) (stage at diagnosis; n)
Downloaded by [University of Cambridge] at 22:01 05 November 2015
Orbita (30) (I; 21, II; 4, III; 1, IV; 4) Salivary gland (3) (I; 1, II; 1, IV; 1) Waldeyer’s ring (4) (I; 3, II; 1) Thyroid (12) (I; 6, II; 5, IV; 1) Lung (23) (IV; 23) Stomach (77) (I; 59, II; 11, III; 1, IV; 6) Intestinal (17) (I; 14, II; 1, IV; 2)
Lymph Bone node marrow Orbita 5
2
1
1
1
Salivary Waldeyer’s gland ring Lung Stomach Liver Spleen Adrenal Intestinal Soft tissue
2
1
1
1
1 1
1
5
1
5 15
2
3
1
extragastric lymphoma than in patients with primary gastric lymphoma (28/107 [26%] patients vs. 7/77 [9%]; p 0.004). We found that five patients (3%) had both pulmonary and gastric involvement, four of whom had a primary pulmonary lesion. Four of 23 patients with primary pulmonary involvement (17%) had an additional gastric lesion. de Boer et al. and Raderer et al. reported that seven of 13 patients with primary pulmonary and four of 11 patients with primary pulmonary lesions had gastric involvement, respectively [8,9]. Based on these findings, GI fiberscopic examination is essential, especially in cases with lung involvement at presentation. One of three patients (33%) whose primary site was the salivary gland had bilateral lesions, similar to the data of Troch et al. [12]. Interestingly, male patients tended to present with advancedstage disease at diagnosis. Twenty-seven of 83 male patients had advanced-stage disease, whereas only 17 of 101 female patients presented with advanced-stage disease. Four-year OS rates were similar between gastric and extragastric lymphoma. Moreover, 4-year OS rates were not different according to primary site, similar to the data of Wöhrer et al. [13]. High serum LDH level, Ann arbor stage IV or III–IV, nodal involvement, IPI high/high-intermediate risk, age 60, bone marrow involvement and 1 extranodal site have been shown to have an adverse impact on OS in extragastric lymphoma [3,14]. In our study, bone marrow involvement and 1 extranodal site were associated with a poorer prognosis through univariate analysis, in accordance with the study by Papaxoinis et al. [15]. However, the patients with MALT lymphoma in our study were not uniformly treated, and this may have obscured the influence on disease progression. In our study, bone marrow involvement was detected in six patients (3%) and was an unfavorable factor for OS. Zucca et al. reported that bone marrow involvement was not associated with a poor prognosis, but 25 of 180 patients (14%) had bone marrow involvement [3]. The influence of bone marrow involvement on prognosis in patients with MALT lymphoma is obscure; bone marrow examination may be necessary to comprehend disease dissemination in order to plan the strategy. MALT lymphoma is known to be an indolent disease; however, in our study, of the 184 patients, 35 patients had multiorgan involvement. The importance of full staging is suggested.
1 1
1
1 4 1
1 1
1
1
1
1
Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.
References [1] Issacson P, Wright DH. Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma. Cancer 1983;52:1410–1416. [2] Swerdlow SH, Campo E, Harris NL, editors. World Health Organization classification of tumors of haematopoietic and lymphoid tissues. Lyon: IARC; 2008. [3] Zucca E, Conconi A, Pedrinis E, et al. International Extranodal Lymphoma Study Group. Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Blood 2003;101:2489–2495. [4] Stathis A, Chini C, Bertoni F, et al. Long-term outcome following Helicobacter pylori eradication in a retrospective study of 105 patients with localized gastric marginal zone B-cell lymphoma of MALT type. Ann Oncol 2009;20:1086–1093. [5] Thieblemont C, Berger F, Dumontet C, et al. Mucosa-associated lymphoid tissue lymphoma is a disseminated disease in one third of 158 patients analyzed. Blood 2000;95:802–806. [6] Tsang RW, Gospodarowicz MK, Pintilie M, et al. Localized mucosaassociated lymphoid tissue lymphoma treated with radiation therapy has excellent clinical outcome. J Clin Oncol 2003;21:4157–4164. [7] Thieblemont C, Bastion Y, Berger F, et al. Mucosa-associated lymphoid tissue gastrointestinal and nongastrointestinal lymphoid behavior: analysis of 108 patients. J Clin Oncol 1997;15:1624–1630. [8] de Boer JP, Hiddink RF, Raderer M, et al. Dissemination patterns in non-gastric MALT lymphoma. Haematologica 2008;93:201–206. [9] Raderer M, Wöhrer S, Streubel B, et al. Assessment of disease dissemination in gastric compared with extragastric mucosa-associated lymphoid tissue lymphoma using extensive staging: a single-center experience. J Clin Oncol 2006;24:3136–3141. [10] Ishii Y, Tomita N, Takasaki H, et al. Clinical features of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Hematol Oncol 2012;30:186–189. [11] Carbone PP, Kaplan HS, Musshoff K, et al. Report of the committee on Hodgkin’s disease staging classification. Cancer Res 1971;31:1860–1861. [12] Troch M, Formanek M, Streubel B, et al. Clinicopathological aspects of mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland: a retrospective single-center analysis of 28 cases. Head Neck 2011;33:763–737. [13] Wöhrer S, Kiesewetter B, Fischbach J, et al. Retrospective comparison of the effectiveness of various treatment modalities of extragastric MALT lymphoma: a single-center analysis. Ann Hematol 2014;93:1287–1295. [14] Sretenovic M1, Colovic M, Jankovic G, et al. More than a third of non-gastric malt lymphomas are disseminated at diagnosis: a single center survey. Eur J Haematol 2009;82:373–380. [15] Papaxoinis G, Fountzilas G, Rontogianni D, et al. Low-grade mucosa-associated lymphoid tissue lymphoma: a retrospective analysis of 97 patients by the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol 2008;19:780–786.
ISSN: 1042-8194 (Print) 1029-2403 (Online) Journal homepage: http://www.tandfonline.com/loi/ilal20
Dissemination pattern of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue Yoshimi Ishii, Naoto Tomita, Taisei Suzuki, Yasufumi Ishiyama, Kumiko Kishimoto, Eri Yamamoto, Satoshi Koyama, Yukako Hattori, Yuki Nakajima, Kenji Motohashi, Hirotaka Takasaki, Rika Kawasaki, Chizuko Hashimoto, Sachiya Takemura, Katsumichi Fujimaki, Hiroyuki Fujita, Rika Sakai, Shin Fujisawa, Shigeki Motomura & Yoshiaki Ishigatsubo To cite this article: Yoshimi Ishii, Naoto Tomita, Taisei Suzuki, Yasufumi Ishiyama, Kumiko Kishimoto, Eri Yamamoto, Satoshi Koyama, Yukako Hattori, Yuki Nakajima, Kenji Motohashi, Hirotaka Takasaki, Rika Kawasaki, Chizuko Hashimoto, Sachiya Takemura, Katsumichi Fujimaki, Hiroyuki Fujita, Rika Sakai, Shin Fujisawa, Shigeki Motomura & Yoshiaki Ishigatsubo (2015) Dissemination pattern of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, Leukemia & Lymphoma, 56:9, 2750-2752, DOI: 10.3109/10428194.2015.1010161 To link to this article: http://dx.doi.org/10.3109/10428194.2015.1010161
View supplementary material
Accepted author version posted online: 03 Feb 2015. Published online: 06 Mar 2015.
Submit your article to this journal
Article views: 40
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ilal20 Download by: [University of Cambridge]
Date: 05 November 2015, At: 22:01
Leukemia & Lymphoma, September 2015; 56(9): 2750–2752 © 2015 Informa UK, Ltd. ISSN: 1042-8194 print / 1029-2403 online DOI: 10.3109/10428194.2015.1010161
Letter to the Editor
Dissemination pattern of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue Yoshimi Ishii1,2, Naoto Tomita1, Taisei Suzuki3, Yasufumi Ishiyama4, Kumiko Kishimoto2, Eri Yamamoto1, Satoshi Koyama1, Yukako Hattori5, Yuki Nakajima1, Kenji Motohashi2, Hirotaka Takasaki5, Rika Kawasaki6, Chizuko Hashimoto7, Sachiya Takemura8, Katsumichi Fujimaki6, Hiroyuki Fujita9, Rika Sakai5, Shin Fujisawa2, Shigeki Motomura5 & Yoshiaki Ishigatsubo1
Downloaded by [University of Cambridge] at 22:01 05 November 2015
1Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine,
Yokohama, Japan, 2Department of Hematology, Yokohama City University Medical Center, Yokohama, Japan, 3Department of Hematology, Shizuoka Red Cross Hospital, Shizuoka, Japan, 4Department of Hematology, Yokosuka City Hospital, Yokosuka, Japan, 5Department of Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan, and 6Department of Hematology/ Immunology, Fujisawa City Hospital, Fujisawa, Japan, 7Department of Hematology/Oncology, Yamato Municipal Hospital, Yamato, Japan, 8Department of Internal Medicine, Yokohama Ekisaikai Hospital, Yokohama, Japan and 9Department of Hematology, Saiseikai Yokohama Nanbu Hospital, Yokohama, Japan
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) was first described by Isaacson and Wright in 1983 [1]. MALT lymphoma, an extranodal lymphoma composed of morphologically heterogeneous small B cells, is a common subtype of non-Hodgkin lymphoma, constituting 7–8% of all B cell lymphomas and up to 50% of primary gastric lymphomas [2]. In addition to the stomach, MALT lymphomas can arise in various nongastrointestinal (GI) sites, including the salivary gland, conjunctiva, thyroid, orbit, lung, larynx, breast, liver, skin and dura mater. Patients with MALT lymphoma usually have an indolent course with a long disease-free and overall survival, associated with a slow dissemination rate of the disease [3–6]. There is no consensus on the best approach to manage this disease, and treatment decisions are often made on a caseby-case basis according to the disease dissemination pattern. Approximately 30–40% of patients present with advancedstage disease at diagnosis [3,5,7,8], and extensive staging is generally recommended to determine the best treatment in such patients [9]. We also previously reported the importance of full staging in patients with MALT lymphoma with advanced disease, given the significant proportion (5/16 [31%]) of patients with primary pulmonary MALT lymphoma with gastric involvement [10]. The dissemination pattern in patients with MALT lymphoma still remains unknown. Here, we present an analysis of the dissemination pattern in 184 cases of newly diagnosed MALT lymphoma. Between May 1998 and September 2013, 184 patients were newly diagnosed with MALT lymphoma and were treated in
Yokohama City University Hematology Group. The diagnosis was determined by institutional pathologists according to the World Health Organization classification criteria [2]. A central pathological review was not performed. Before the initiation of therapy, all 184 patients underwent a full staging, briefly consisting of physical examination, hematological and biochemical tests, chest radiography, computed tomography (CT) or positron emission tomography (PET)/CT from the cervix to the pelvis, and bone marrow aspiration and biopsy. Staging was performed according to the Ann Arbor classification [11]. Patient management varied and consisted of chemotherapy, radiotherapy, chemoradiotherapy, surgery, Helicobacter pylori eradication and watch-and-wait. Management decisions were made on a case-by-case basis according to clinical stage. Patients underwent follow-up CT or PET/CT every 6 months for at least 5 years. The median follow-up time was 50 months for surviving patients (range, 2–155 months). Overall survival (OS) was calculated from the date of diagnosis to the date of death or last follow-up assessment, whichever occurred first. Fisher’s exact test was used to calculate the differences between the two groups. Survival curves were constructed using the Kaplan–Meier method and compared using the log-rank test. A p-value 0.05 was considered statistically significant. All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University), which is a graphical user interface for R software (R Foundation for Statistical Computing). This study was approved by the institutional review board of Yokohama City University Hospital.
Correspondence: Dr. Naoto Tomita, Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa, Yokohama 236-0004, Japan. Tel: 81-45-787-2800. Fax: 81-45-786-3444. E-mail: [email protected] Received 20 September 2014; revised 13 January 2015; accepted 17 January 2015
2750
Downloaded by [University of Cambridge] at 22:01 05 November 2015
Letter to the editor 2751
Human immunodeficiency virus infection was not observed in any of the 184 patients. The median age was 69 years (range, 25–94 years). Eighty-three patients (45%) were male and 101 patients (55%) were female (male/female ratio, 0.82). The stage distribution was as follows: stage I, 112 patients (61%); stage II, 28 patients (15%); stage III, two patients (1%); and stage IV, 42 patients (23%). Thirty-three patients (18%) presented with 1 extranodal site, whereas 151 patients (82%) had only one extranodal site. According to International Prognostic Index (IPI) criteria, 67%, 22%, 10% and 1% of patients were in the low-, low-intermediate, high-intermediate and high-risk groups, respectively. Thirty-seven patients (20%) had nodal involvement. The serum lactate dehydrogenase (LDH) level was elevated in 28 patients (15%). Six patients (3%) had bone marrow involvement. Five patients (3%) had B symptoms. Two patients (1%) had Eastern Cooperative Oncology Group performance status 2–4. Soluble interleukin-2 receptor (sIL-2R) level was 1000 U/mL in 13 patients (7%). Male patients were diagnosed at a more advanced clinical stage compared with female patients (p 0.015). Advanced clinical stage was correlated with sIL-2R 1000 U/mL (p 0.003). In the 184 patients, a total of 259 lesions (including nodal and extranodal sites) were detected. The lesion sites are summarized in Figure 1. This figure shows the organ that MALT lymphoma tended to involve. Most patients (149/184 [81%]) presented with single-organ involvement. Thirty-five patients (19%) had multiorgan involvement. Of these patients, four (2%) had GI involvement and 31 (17%) had multiorgan involvement outside the GI tract. Twelve patients (7%) had both GI tract and non-GI tract involvement. Five patients (3%) had both lung and gastric involvement. The number of patients with multiorgan involvement was higher in patients with extragastric lymphoma than in patients with gastric lymphoma (28/107 [26%] patients vs. 7/77 [9%]; p 0.004).
Additional lymphoma localization at diagnosis and rate of stage according to initial presentation are summarized in Table I. Two patients had bilateral orbital lesions, and one patient had bilateral salivary gland lesions. Four of 23 (17%) with primary pulmonary involvement had additional gastric lesions. Two patients with orbital lymphoma had bone marrow involvement and one had a pulmonary lesion. Nine patients died. Death was related to lymphoma progression in three patients (33%), whereas the other six patients died of various causes including secondary acute myeloid leukemia (one patient), colon cancer (one patient), breast cancer (one patient), hepatitis (one patient), progressive multifocal leukoencephalopathy (one patient) and unknown reason (one patient). The 4-year OS rate was 96.2%. Four-year OS rates were similar between patients with disseminated and localized disease (96.1% vs. 95.5%; p 0.77). The 4-year OS rate was not significantly different between patients with gastric lymphoma and patients with extragastric lymphoma (95.5% vs. 96.7%; p 0.207). Fouryear OS rates were not different according to primary MALT site. In univariate analysis, elevated LDH, IPI, B symptoms, advanced stage, performance status 3–4, nodal involvement, age 65 and primary site did not influence the OS rate. Bone marrow involvement and 1 extranodal site were unfavorable prognostic factors, but not unfavorable factors through multivariate analysis. In our study, we evaluated 184 patients with newly diagnosed MALT lymphoma. Seventy-seven patients (42%) had primary gastric lymphoma and 104 patients (58%) had primary extragastric lymphoma, similar to other published data [9]. Raderer et al. reported that 15 (25%) of 61 patients with gastric MALT lymphoma had multifocal involvement and 37 (47%) of 79 patients with extragastric lymphoma had multiorgan involvement [9]. We also found that multiorgan involvement occurred more frequently in patients with primary
Figure 1. Lesion sites in 184 patients with MALT lymphoma. A total of 259 lesions were detected.
2752
Y. ishii et al.
Table I. Additional lymphoma localization at diagnosis and rate of stage according to primary site. Primary lesion (n) (stage at diagnosis; n)
Downloaded by [University of Cambridge] at 22:01 05 November 2015
Orbita (30) (I; 21, II; 4, III; 1, IV; 4) Salivary gland (3) (I; 1, II; 1, IV; 1) Waldeyer’s ring (4) (I; 3, II; 1) Thyroid (12) (I; 6, II; 5, IV; 1) Lung (23) (IV; 23) Stomach (77) (I; 59, II; 11, III; 1, IV; 6) Intestinal (17) (I; 14, II; 1, IV; 2)
Lymph Bone node marrow Orbita 5
2
1
1
1
Salivary Waldeyer’s gland ring Lung Stomach Liver Spleen Adrenal Intestinal Soft tissue
2
1
1
1
1 1
1
5
1
5 15
2
3
1
extragastric lymphoma than in patients with primary gastric lymphoma (28/107 [26%] patients vs. 7/77 [9%]; p 0.004). We found that five patients (3%) had both pulmonary and gastric involvement, four of whom had a primary pulmonary lesion. Four of 23 patients with primary pulmonary involvement (17%) had an additional gastric lesion. de Boer et al. and Raderer et al. reported that seven of 13 patients with primary pulmonary and four of 11 patients with primary pulmonary lesions had gastric involvement, respectively [8,9]. Based on these findings, GI fiberscopic examination is essential, especially in cases with lung involvement at presentation. One of three patients (33%) whose primary site was the salivary gland had bilateral lesions, similar to the data of Troch et al. [12]. Interestingly, male patients tended to present with advancedstage disease at diagnosis. Twenty-seven of 83 male patients had advanced-stage disease, whereas only 17 of 101 female patients presented with advanced-stage disease. Four-year OS rates were similar between gastric and extragastric lymphoma. Moreover, 4-year OS rates were not different according to primary site, similar to the data of Wöhrer et al. [13]. High serum LDH level, Ann arbor stage IV or III–IV, nodal involvement, IPI high/high-intermediate risk, age 60, bone marrow involvement and 1 extranodal site have been shown to have an adverse impact on OS in extragastric lymphoma [3,14]. In our study, bone marrow involvement and 1 extranodal site were associated with a poorer prognosis through univariate analysis, in accordance with the study by Papaxoinis et al. [15]. However, the patients with MALT lymphoma in our study were not uniformly treated, and this may have obscured the influence on disease progression. In our study, bone marrow involvement was detected in six patients (3%) and was an unfavorable factor for OS. Zucca et al. reported that bone marrow involvement was not associated with a poor prognosis, but 25 of 180 patients (14%) had bone marrow involvement [3]. The influence of bone marrow involvement on prognosis in patients with MALT lymphoma is obscure; bone marrow examination may be necessary to comprehend disease dissemination in order to plan the strategy. MALT lymphoma is known to be an indolent disease; however, in our study, of the 184 patients, 35 patients had multiorgan involvement. The importance of full staging is suggested.
1 1
1
1 4 1
1 1
1
1
1
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Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.
References [1] Issacson P, Wright DH. Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma. Cancer 1983;52:1410–1416. [2] Swerdlow SH, Campo E, Harris NL, editors. World Health Organization classification of tumors of haematopoietic and lymphoid tissues. Lyon: IARC; 2008. [3] Zucca E, Conconi A, Pedrinis E, et al. International Extranodal Lymphoma Study Group. Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Blood 2003;101:2489–2495. [4] Stathis A, Chini C, Bertoni F, et al. Long-term outcome following Helicobacter pylori eradication in a retrospective study of 105 patients with localized gastric marginal zone B-cell lymphoma of MALT type. Ann Oncol 2009;20:1086–1093. [5] Thieblemont C, Berger F, Dumontet C, et al. Mucosa-associated lymphoid tissue lymphoma is a disseminated disease in one third of 158 patients analyzed. Blood 2000;95:802–806. [6] Tsang RW, Gospodarowicz MK, Pintilie M, et al. Localized mucosaassociated lymphoid tissue lymphoma treated with radiation therapy has excellent clinical outcome. J Clin Oncol 2003;21:4157–4164. [7] Thieblemont C, Bastion Y, Berger F, et al. Mucosa-associated lymphoid tissue gastrointestinal and nongastrointestinal lymphoid behavior: analysis of 108 patients. J Clin Oncol 1997;15:1624–1630. [8] de Boer JP, Hiddink RF, Raderer M, et al. Dissemination patterns in non-gastric MALT lymphoma. Haematologica 2008;93:201–206. [9] Raderer M, Wöhrer S, Streubel B, et al. Assessment of disease dissemination in gastric compared with extragastric mucosa-associated lymphoid tissue lymphoma using extensive staging: a single-center experience. J Clin Oncol 2006;24:3136–3141. [10] Ishii Y, Tomita N, Takasaki H, et al. Clinical features of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Hematol Oncol 2012;30:186–189. [11] Carbone PP, Kaplan HS, Musshoff K, et al. Report of the committee on Hodgkin’s disease staging classification. Cancer Res 1971;31:1860–1861. [12] Troch M, Formanek M, Streubel B, et al. Clinicopathological aspects of mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland: a retrospective single-center analysis of 28 cases. Head Neck 2011;33:763–737. [13] Wöhrer S, Kiesewetter B, Fischbach J, et al. Retrospective comparison of the effectiveness of various treatment modalities of extragastric MALT lymphoma: a single-center analysis. Ann Hematol 2014;93:1287–1295. [14] Sretenovic M1, Colovic M, Jankovic G, et al. More than a third of non-gastric malt lymphomas are disseminated at diagnosis: a single center survey. Eur J Haematol 2009;82:373–380. [15] Papaxoinis G, Fountzilas G, Rontogianni D, et al. Low-grade mucosa-associated lymphoid tissue lymphoma: a retrospective analysis of 97 patients by the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol 2008;19:780–786.
