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Treatment outcomes in patients with extranodal marginal zone B-cell lymphoma of the lung

Open ArchivePublished:March 21, 2017DOI:https://doi.org/10.1016/j.jtcvs.2017.03.043

      Abstract

      Objectives

      To evaluate clinical presentations, treatment modalities, and outcomes of pulmonary mucosa–associated lymphoid tissue (MALT) lymphoma by stage strata.

      Methods

      We retrospectively reviewed 51 patients diagnosed with pulmonary MALT lymphoma between January 2003 and December 2015. To compare treatment modalities and outcomes, we stratified the patients into low-stage (IE/IIE) and high-stage (IIIE/IVE) groups using modified Ann Arbor staging. Progression-free survival was estimated using Kaplan-Meier curves, and differences were compared using the log-rank test. A hazard ratio of progression by stage strata, adjusted for other clinical variables, was determined using a Cox adjusted proportional hazards model.

      Results

      The majority of patients had stage IE disease (76.5%; 39 of 51). With advancing stage, patients were more likely to have respiratory and B symptoms and higher International Prognostic Index scores. The most common treatment modality was surgical resection in low-stage patients (33 of 43) and chemotherapy in high-stage patients (7 of 8). At a median follow-up of 40.7 months, progression-free survival was longer for low-stage patients (median, 40.7 months vs 24.9 months; P < .001), and high-stage patients were 9.2 times more likely to progress (hazard ratio, 9.24; 95% confidence interval, 1.93-44.36). Among 30 patients with surgically resected stage IE disease, 8 with central lesions were treated via lobectomy and 22 with peripheral lesions were treated via lobectomy (n = 8) or limited resection (n = 14). One of these patients, with a central lesion, experienced disease recurrence.

      Conclusions

      Our findings suggest that the clinical course of low-stage pulmonary MALT lymphoma, for which the mainstay of treatment is surgical resection, might be indolent.

      Key Words

      Abbreviations and Acronyms:

      CT (computed tomography), IQR (interquartile range), MALT (mucosa-associated lymphoid tissue), PFS (progression-free survival)
      Figure thumbnail fx1
      Progression-free survival of pulmonary MALT lymphoma by stage.
      The clinical course of low-stage (IE/IIE) pulmonary mucosa-associated lymphoid tissue lymphoma, for which the mainstay of treatment is surgical resection, is indolent.
      In this study, the mainstays of treatment for low-stage (IE/IIE) and high-stage (IIIE/IVE) pulmonary mucosa-associated lymphoid (MALT) lymphoma were surgical resection and chemotherapy, respectively. Low-stage lymphoma was associated with longer progression-free survival, suggesting that complete surgical resection may afford favorable treatment outcomes for low-stage pulmonary MALT lymphomas.
      See Editorial Commentary page 350.
      Primary non-Hodgkin lymphomas of the lung are very rare, composing only 0.5% to 1.0% of all lung malignancies
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      Pulmonary mucosa-associated lymphoid tissue lymphoma revisited.
      • Ferraro P.
      • Trastek V.F.
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      • Allen M.S.
      • Pairolero P.C.
      Primary non-Hodgkin's lymphoma of the lung.
      • Borie R.
      • Wislez M.
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      • Antoine M.
      • Rabbat A.
      • Couderc L.J.
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      Clinical characteristics and prognostic factors of pulmonary MALT lymphoma.
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      • Montoro J.
      • Steffanoni S.
      • Nowakowski G.S.
      • et al.
      A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG).
      • Stefanovic A.
      • Morgensztern D.
      • Fong T.
      • Lossos I.S.
      Pulmonary marginal zone lymphoma: a single centre experience and review of the SEER database.
      • Cadranel J.
      • Wislez M.
      • Antoine M.
      Primary pulmonary lymphoma.
      • Ahmed S.
      • Kussick S.J.
      • Siddiqui A.K.
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      • Sarewitz S.
      • et al.
      Bronchial-associated lymphoid tissue lymphoma: a clinical study of a rare disease.
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      • Reynaud-Gaubert M.
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      Primary pulmonary lymphomas. A clinical study of 70 cases in nonimmunocompromised patients.
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      • Leroy-Ladurie F.
      • et al.
      Low-dose radiation treatment in pulmonary mucosa-associated lymphoid tissue lymphoma: a plausible approach? A single-institution experience in 10 patients.
      • Wang L.
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      Radical surgery may be not an optimal treatment approach for pulmonary MALT lymphoma.
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      • Kawashima O.
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      • Sato K.
      • et al.
      Clinicopathological features of patients with bronchial-associated lymphoid tissue lymphoma.
      • Troch M.
      • Streubel B.
      • Petkov V.
      • Turetschek K.
      • Chott A.
      • Raderer M.
      Does MALT lymphoma of the lung require immediate treatment? An analysis of 11 untreated cases with long-term follow-up.
      • Oh S.Y.
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      Pulmonary marginal zone B-cell lymphoma of MALT type–what is a prognostic factor and which is the optimal treatment, operation, or chemotherapy?: Consortium for Improving Survival of Lymphoma (CISL) study.
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      • Casadei B.
      • Derenzini E.
      • Broccoli A.
      • et al.
      Extranodal marginal zone B-cell lymphoma of the lung: experience with fludarabine and mitoxantrone-containing regimens.
      • Kennedy J.L.
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      • Wislez M.
      • Antoine M.
      • Copie-Bergman C.
      • Thieblemont C.
      • Cadranel J.
      Pulmonary mucosa-associated lymphoid tissue lymphoma revisited.
      • Ferraro P.
      • Trastek V.F.
      • Adlakha H.
      • Deschamps C.
      • Allen M.S.
      • Pairolero P.C.
      Primary non-Hodgkin's lymphoma of the lung.
      • Borie R.
      • Wislez M.
      • Thabut G.
      • Antoine M.
      • Rabbat A.
      • Couderc L.J.
      • et al.
      Clinical characteristics and prognostic factors of pulmonary MALT lymphoma.
      • Sammassimo S.
      • Pruneri G.
      • Andreola G.
      • Montoro J.
      • Steffanoni S.
      • Nowakowski G.S.
      • et al.
      A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG).
      • Stefanovic A.
      • Morgensztern D.
      • Fong T.
      • Lossos I.S.
      Pulmonary marginal zone lymphoma: a single centre experience and review of the SEER database.
      • Cadranel J.
      • Wislez M.
      • Antoine M.
      Primary pulmonary lymphoma.
      • Ahmed S.
      • Kussick S.J.
      • Siddiqui A.K.
      • Bhuiya T.A.
      • Khan A.
      • Sarewitz S.
      • et al.
      Bronchial-associated lymphoid tissue lymphoma: a clinical study of a rare disease.
      • Cordier J.F.
      • Chailleux E.
      • Lauque D.
      • Reynaud-Gaubert M.
      • Dietemann-Molard A.
      • Dalphin J.C.
      • et al.
      Primary pulmonary lymphomas. A clinical study of 70 cases in nonimmunocompromised patients.
      • Girinsky T.
      • Paumier A.
      • Ferme C.
      • Hanna C.
      • Ribrag V.
      • Leroy-Ladurie F.
      • et al.
      Low-dose radiation treatment in pulmonary mucosa-associated lymphoid tissue lymphoma: a plausible approach? A single-institution experience in 10 patients.
      • Wang L.
      • Xia Z.J.
      • Zhang Y.J.
      • Huang H.Q.
      • Lin T.Y.
      • Lu Y.
      Radical surgery may be not an optimal treatment approach for pulmonary MALT lymphoma.
      • Imai H.
      • Sunaga N.
      • Kaira K.
      • Kawashima O.
      • Yanagitani N.
      • Sato K.
      • et al.
      Clinicopathological features of patients with bronchial-associated lymphoid tissue lymphoma.
      • Troch M.
      • Streubel B.
      • Petkov V.
      • Turetschek K.
      • Chott A.
      • Raderer M.
      Does MALT lymphoma of the lung require immediate treatment? An analysis of 11 untreated cases with long-term follow-up.
      • Oh S.Y.
      • Kim W.S.
      • Kim J.S.
      • Kim S.J.
      • Kwon H.C.
      • Lee D.H.
      • et al.
      Pulmonary marginal zone B-cell lymphoma of MALT type–what is a prognostic factor and which is the optimal treatment, operation, or chemotherapy?: Consortium for Improving Survival of Lymphoma (CISL) study.
      • Kim J.H.
      • Lee S.H.
      • Park J.
      • Kim H.Y.
      • Lee S.I.
      • Park J.O.
      • et al.
      Primary pulmonary non-Hodgkin's lymphoma.
      • Zinzani P.L.
      • Pellegrini C.
      • Gandolfi L.
      • Casadei B.
      • Derenzini E.
      • Broccoli A.
      • et al.
      Extranodal marginal zone B-cell lymphoma of the lung: experience with fludarabine and mitoxantrone-containing regimens.
      • Kennedy J.L.
      • Nathwani B.N.
      • Burke J.S.
      • Hill L.R.
      • Rappaport H.
      Pulmonary lymphomas and other pulmonary lymphoid lesions. A clinicopathologic and immunologic study of 64 patients.
      Unfortunately, the low prevalence and indolent clinical course of pulmonary MALT lymphoma makes it difficult to perform a randomized controlled trial comparing treatment modalities. Nevertheless, surgical resection is considered a useful initial treatment option when the lesion is localized; previous studies have reported favorable outcomes (with a high complete resection rate without subsequent disease recurrence) following surgical resection in patients with pulmonary MALT lymphoma.
      • Borie R.
      • Wislez M.
      • Antoine M.
      • Copie-Bergman C.
      • Thieblemont C.
      • Cadranel J.
      Pulmonary mucosa-associated lymphoid tissue lymphoma revisited.
      • Ferraro P.
      • Trastek V.F.
      • Adlakha H.
      • Deschamps C.
      • Allen M.S.
      • Pairolero P.C.
      Primary non-Hodgkin's lymphoma of the lung.
      • Borie R.
      • Wislez M.
      • Thabut G.
      • Antoine M.
      • Rabbat A.
      • Couderc L.J.
      • et al.
      Clinical characteristics and prognostic factors of pulmonary MALT lymphoma.
      • Sammassimo S.
      • Pruneri G.
      • Andreola G.
      • Montoro J.
      • Steffanoni S.
      • Nowakowski G.S.
      • et al.
      A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG).
      • Stefanovic A.
      • Morgensztern D.
      • Fong T.
      • Lossos I.S.
      Pulmonary marginal zone lymphoma: a single centre experience and review of the SEER database.
      • Cadranel J.
      • Wislez M.
      • Antoine M.
      Primary pulmonary lymphoma.
      • Ahmed S.
      • Kussick S.J.
      • Siddiqui A.K.
      • Bhuiya T.A.
      • Khan A.
      • Sarewitz S.
      • et al.
      Bronchial-associated lymphoid tissue lymphoma: a clinical study of a rare disease.
      Because most patients (up to approximately 85%) are diagnosed at an early disease stage (stage IE or IIE), studies seeking optimal treatment modalities for these patients are needed.
      It was recently suggested that limited resection of the lung might be a useful alternative to lobectomy when managing patients with small, early-stage non–small cell lung cancers.
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      Considering the indolent characteristics of pulmonary MALT lymphoma and the advantages of limited resection compared with lobectomy in preserving lung function and reducing postsurgical pulmonary complications, a similar strategy could be adopted to treat peripherally localized stage IE pulmonary MALT lymphomas. However, no study has yet evaluated treatment outcomes after limited resection of pulmonary MALT lymphomas in patients with peripherally localized lesions.
      In the present study, we evaluated the clinical characteristics of, treatment modalities prescribed for, and treatment outcomes of patients with pulmonary MALT lymphoma by stage strata. We also evaluated the outcomes after limited resection of peripherally localized stage IE pulmonary MALT lymphoma.

      Methods

      Patients

      The medical records of 51 patients diagnosed with pulmonary MALT lymphoma in Samsung Medical Center (a 1979-bed referral hospital in Seoul, Korea) between January 2003 and December 2015 were reviewed retrospectively. All patients were pathologically diagnosed with pulmonary MALT lymphoma; biopsy specimens were obtained via video-assisted thoracoscopic surgery (VATS) wedge resection (n = 38; 74.5%), transbronchial lung biopsy (n = 6; 11.8%), core needle biopsy (n = 6; 11.8%), and percutaneous needle aspiration (n = 1; 1.9%). The study was approved by the Institutional Review Board of Samsung Medical Center. Because of the study's retrospective nature, the need for written patient consent was waived (IRB no. 2016-04-111).

      Initial Diagnosis and Staging of Pulmonary MALT Lymphoma

      Staging was performed using modified Ann Arbor staging; anatomic staging was used for patients undergoing curative surgical resection. Otherwise, patients were clinically staged (Figure 1).
      • Ferraro P.
      • Trastek V.F.
      • Adlakha H.
      • Deschamps C.
      • Allen M.S.
      • Pairolero P.C.
      Primary non-Hodgkin's lymphoma of the lung.
      Initial pulmonary MALT lymphoma staging featured the following evaluations: comprehensive medical history, physical examination, and radiologic imaging, including computed tomography (CT) scans of the chest and abdomen and positron emission tomography/CT. Radiologic findings were classified as one of the following patterns according to the pattern and distribution of lung lesions: (1) single nodular or consolidation pattern, (2) multiple nodular or consolidation pattern, (3) bronchiectasis and bronchiolitis pattern, or (4) diffuse interstitial lung disease pattern.
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      • et al.
      Marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue: imaging findings in 21 patients.
      Tumor locations in CT scans were defined as follows: tumors not involving the lobes or more proximal airway and surrounded by lung parenchyma were classified as peripheral, and all others were classified as central.
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      Brain magnetic resonance imaging or bone marrow biopsy was performed in selected patients at the attending physician's clinical discretion.

      Treatment and Response Criteria

      Patients with pulmonary MALT lymphoma were managed by a multidisciplinary team comprising several specialists, including a pulmonologist, thoracic surgeon, radiologist, and oncologist. In general, the patients were treated with respect to stage. Patients with stage IE pulmonary MALT lymphoma with unilateral pulmonary involvement were treated by surgical resection or simple follow-up (ie, without any treatment). In cases where the tumors were completely resected, no adjuvant treatment was provided. In contrast, patients with stage IE pulmonary MALT lymphoma with bilateral pulmonary involvement or multifocal lesions underwent surgical resection, received chemotherapy, or were followed-up without treatment. Patients with stage IIE pulmonary MALT lymphoma underwent surgical resection if the pulmonary lesions and mediastinal lymph nodes were completely resectable; if surgical resection was not possible, the patients received chemotherapy or were closely followed without treatment. Patients with stage IIIE or IVE disease were treated principally with chemotherapy.
      Following initial treatment, the patients were followed up with chest CT scans, abdominal CT scans (for patients with stage IIIE/IVE disease), and laboratory studies at 3-month intervals during the first year of follow-up and at 6-month intervals thereafter. The responses seen on CT scans were categorized based on the literature as complete response, partial response, stable disease, or progressive disease.
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      • et al.
      Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group.
      In patients undergoing curative surgical resection, response was categorized as complete response (ie, no evidence of recurrence) or progressive disease (ie, recurrence or new pulmonary and extrapulmonary lesions [nodes and extranodal sites other than lung]); otherwise, response was categorized as complete response (ie, disappearance of all lymphoma imaging on CT scans and all nodes ≤1.5 cm in longest diameter), partial response (ie, ≥50% reduction in the sum of the products of the perpendicular diameters of up to 6 dominant pulmonary and extrapulmonary lesions for multiple lesions, or ≥50% reduction in the product of the perpendicular diameter for a single lesion), stable disease (ie, <50% reduction from baseline in the sum of the products of the perpendicular diameters of pulmonary and extrapulmonary lesions, including nodes and extranodal sites, and no criteria met for progressive disease), or progressive disease (ie, ≥50% increase from baseline in the sum of the products of the perpendicular diameters of any previously identified abnormal pulmonary and extrapulmonary lesions, or the appearance of new lesions).
      Patients with disease progression were generally treated as follows. Surgical resection was performed for patients with completely resectable tumors, and second-line chemotherapy was provided to patients who progressed following initial chemotherapy. Progression-free survival (PFS) was defined as the time from the date of treatment initiation to the date of progression in patients who received treatment or as the time from the date of the decision to watch and wait to the date of progression in patients who received simple follow-up without any treatment.

      Statistical Analyses

      Continuous variables are described as median with interquartile range (IQR), and categorical variables are reported number and percentage. Continuous variables were compared using the Mann-Whitney U test, and categorical variables were compared using the χ2 test with Yates continuity correction. Clinical presentations were evaluated by stage strata (from IE to IVE). The Cochran–Armitage test was used to evaluate the associations between the proportions of patients with respiratory symptoms, B symptoms, and higher International Prognostic Index (IPI) scores (2-3) and an increase in stage. To compare treatment modalities and treatment outcomes, patients were further stratified by low-stage (IE/IIE) versus high-stage (IIIE/IVE). PFS was estimated by the Kaplan-Meier method, and the distribution of survival over time between low-stage and high-stage patients was compared using the log-rank test. A Cox proportional hazard model was used to determine whether a high stage was associated with reduced PFS. The initial clinical variables entered into the model included age, sex, performance status, and modified Ann Arbor stage. A stepwise backward selection method, with elimination of variables exhibiting a P value >.20 in univariable analyses, was used to identify clinical variables for inclusion in the final model. A 2-sided P value <.05 was considered to reflect statistical significance. All statistical analyses were performed using R version 3.2.3 (R Foundation for Statistical Computing, Vienna, Austria).

      Results

      Patients

      The baseline characteristics of 51 patients with pulmonary MALT lymphoma are summarized by stage strata in Table 1. Using the modified Ann Arbor staging system, patients were stratified into 2 groups: low-stage (stage IE/IIE; n = 43; 39 and 4, respectively) and high-stage (stage IIIE/IVE; n = 8; 3 and 5, respectively). There were no significant between-group differences in the clinical factors, including age, sex, smoking history, comorbidities, radiologic findings, or performance status across the stages. However, the proportion of patients with respiratory and B symptoms and a high IPI score (2-3) increased with advancing stage (Ptrend = .003 for cough, .023 for sputum, .031 for dyspnea, .032 for hemoptysis, <.001 for B symptoms, and <.001 for high IPI score).
      Table 1Clinical characteristics of patients with pulmonary MALT lymphoma by stage strata
      CharacteristicTotal (n = 51)Low-stageHigh-stageP value
      Stage IE (n = 39)Stage IIE (n = 4)Stage IIIE (n = 3)Stage IVE (n = 5)
      Age, y, median (IQR)54 (49-60)54 (50-61)55 (42-62)48 (41-52)58 (54-59).575
      Male sex, n (%)27 (52.9)21 (53.8)4 (100)1 (33.3)1 (20.0).102
      Never smoker, n (%)33 (64.7)24 (61.5)4 (100)2 (66.7)3 (60.0).492
      Comorbidities, n (%)
       Chronic pulmonary disease12 (23.5)8 (20.5)0 (0)2 (66.7)2 (40.0).152
       Hypertension10 (19.6)9 (23.1)0 (0)1 (33.3)0 (0).415
       Previous malignancy8 (15.7)7 (17.9)1 (25.0)0 (0)0 (0).593
       Autoimmune disease7 (13.7)4 (10.3)2 (50.0)1 (33.3)0 (0).085
       Diabetes mellitus3 (5.9)3 (7.7)0 (0)0 (0)0 (0).806
      Respiratory symptoms, n (%)
       Cough30 (58.8)18 (46.2)4 (100)3 (100)5 (100).003
      P value for trend test.
       Sputum19 (37.3)11 (28.2)2 (50.0)3 (100)3 (60.0).023
      P value for trend test.
       Dyspnea4 (7.8)1 (2.6)1 (25.0)1 (33.3)1 (20.0).031
      P value for trend test.
       Hemoptysis3 (5.9)1 (2.6)0 (0.0)1 (33.3)1 (20.0).032
      P value for trend test.
      B symptoms, n (%)9 (17.6)1 (2.6)1 (25.0)3 (100)4 (80.0)<.001
      P value for trend test.
      Performance status, n (%).533
       041 (80.4)32 (82.1)3 (75.0)3 (100)3 (60.0)
       110 (19.6)7 (17.9)1 (25.0)0 (0)2 (40.0)
      Radiologic findings, n (%).153
       Single nodular or consolidation28 (54.9)24 (61.5)2 (50.0)1 (33.3)1 (20.0)
       Multiple nodular or consolidation14 (27.5)9 (23.1)2 (50.0)2 (66.7)1 (20.0)
       Bronchiectasis and bronchiolitis5 (9.8)4 (10.3)0 (0)0 (0)1 (20.0)
       Diffuse interstitial lung disease4 (7.8)2 (5.1)0 (0)0 (0)2 (40.0)
      Diagnostic method, n (%).037
       Percutaneous needle aspiration/biopsy7 (13.7)3 (7.7)0 (0.0)1 (33.3)3 (60.0)
       Transbronchial lung biopsy6 (11.8)4 (10.2)1 (25.0)1 (33.3)0 (0)
       VATS wedge resection38 (74.5)32 (82.1)3 (75.0)1 (33.3)2 (40.0)
      IPI score, n (%)<.001
      P value for trend test.
       0-138 (74.5)34 (87.2)3 (75.0)1 (33.3)0 (0)
       2-313 (25.5)5 (12.8)1 (25.0)2 (66.7)5 (100)
      IQR, Interquartile range; VATS, video-assisted thoracoscopic surgery; IPI, International Prognostic Index.
      P value for trend test.
      Regarding diagnostic methods, more than 75% of low-stage patients underwent VATS wedge resection (82.1% for stage IE and 75% for stage IIE) for the diagnosis of pulmonary MALT lymphoma. For the high-stage patients, various diagnostic methods were used.

      Treatment Modalities and Treatment Responses in Patients With Pulmonary MALT Lymphoma

      As shown in Table 2, patients with low-stage disease were more likely to undergo surgical resection (76.7% [33 of 43] vs 0% [0 of 8]; P < .001), whereas patients with high-stage disease were more likely to receive systemic chemotherapy (87.5% [7 of 8] vs 14.0% [6 of 43]; P < .001). There was no significant difference in the median duration of follow-up between patients with low-stage and high-stage disease (40.7 months [IQR, 16.0-79.1 months] vs 35.9 months [IQR, 22.4-61.2 months]; P = .990). During the follow-up period, the proportion of patients remaining in complete response was higher in the low-stage disease group (81.4% [35 of 43] vs 25.0% [2 of 8]; P = .004), but the proportion of patients developing progressive disease was higher in the high-stage disease group (50% [4 of 8] vs 7.0% [3 of 43]; P = .007).
      Table 2Treatment modalities and treatment responses in patients with low-stage and high-stage pulmonary MALT lymphoma
      VariableLow-stage (IE/IIE) (n = 43)High-stage (IIIE/IVE) (n = 8)P value
      Treatment, n (%)< .001
       Surgical resection33 (76.7)0 (0)
       Systemic chemotherapy6 (14.0)7 (87.5)
       Watch-and-wait4 (9.3)1 (12.5)
      Treatment response, n (%)
       Complete response35 (81.4)2 (25.0).004
       Partial response or stable disease5 (11.6)2 (25.0).653
       Progressive disease3 (7.0)
      Among 3 patients with low-stage MALT lymphoma who had progressive disease, 1 died of sepsis during second-line chemotherapy for progressive disease.
      4 (50.0).007
       Death1 (2.3)
      Among 3 patients with low-stage MALT lymphoma who had progressive disease, 1 died of sepsis during second-line chemotherapy for progressive disease.
      0 (0)1.0
      Follow-up duration, mo, median (IQR)40.7 (16.0-79.1)35.9 (22.4-61.2).990
      Time to progression, mo, median (IQR)59.7 (38.2-81.2)12.6 (6.8-23.7).064
      IQR, Interquartile range.
      Among 3 patients with low-stage MALT lymphoma who had progressive disease, 1 died of sepsis during second-line chemotherapy for progressive disease.
      As shown in Figure 2, PFS was significantly longer in the low-stage disease group (median, 24.9 months [IQR, 12.6-45.6 months] vs 40.7 months [IQR, 16.0-75.2 months]; P < .001). Patients in the high-stage disease group were 9.2 times more likely to progress when adjusted for other clinical variables (hazard ratio, 9.24; 95% confidence interval, 1.93-44.36) (Table 3).
      Figure thumbnail gr2
      Figure 2Progression-free survival of patients with stage IE/IIE and stage IIIE/IVE pulmonary MALT lymphoma.
      Table 3Results of the univariable and multivariable Cox proportional hazard model of disease progression in patients with pulmonary MALT lymphoma
      VariableUnivariable analysisMultivariable analysis
      HRP valueAdjusted HR95% CI
      Age1.03.426
      Male sex5.98.0386.050.93-39.57
      Modified Ann Arbor stage
       Low-stage (stage IE/IIE)ReferenceReference
       High-stage (stage IIIE/IVE)7.66.0059.241.93-44.36
      Performance status
       0ReferenceReference
       12.84.1554.030.34-19.45
      A Cox proportional hazard model was used to determine whether advanced disease stage was associated with reduced progression-free survival. The initial clinical variables entered into the model included age, sex, performance status, and the modified Ann Arbor stage. A stepwise backward selection method, with elimination of variables exhibiting P values < .20 in univariable analyses, was used to identify clinical variables for inclusion in the final model. HR, Hazard ratio; CI, confidence interval.

      Treatment Responses in Patients Who Underwent Surgical Resection and Those Who Did Not Undergo Surgical Resection Among Patients With Low-Stage Pulmonary MALT Lymphoma

      Of the 43 patients with low-stage pulmonary MALT lymphoma, 33 underwent complete surgical resection, and the other 10 did not undergo surgery (systemic chemotherapy, n = 6; watch and wait, n = 4). Among the 33 patients who underwent surgical resection, 32 (97%) remained in complete remission and 1 (3%) developed progressive disease. In comparison, among the 10 patients who did not undergo surgical resection, 3 remained in complete remission, 3 remained in stable disease, 2 had partial response, and 2 developed progressive disease (1 of whom died of sepsis during second-line chemotherapy for progressive disease). Although the proportion of patients who remained in complete remission was significantly higher in patients who underwent surgical resection compared with those who did not (97.0% [32 of 33] vs 30.0% [3 of 10]; P < .001), there was no significant difference between the 2 groups in the proportion of patients who developed progressive disease (3.0% [1 of 33] vs 20.0% [2 of 10]; P = .256). In survival analysis, there was also no significant difference in PFS between the patients who underwent surgical resection and those who did not (P = .319).

      Surgical Treatments and Treatment Responses in Patients With Stage IE Pulmonary MALT Lymphoma

      Figure thumbnail fx2
      Video 1VATS wedge resection for the treatment of localized pulmonary MALT lymphoma. Video available at: http://www.jtcvsonline.org/article/S0022-5223(17)30547-0/addons.
      Table 4Clinical characteristics and treatment outcomes in patients with stage IE pulmonary MALT lymphoma who underwent surgical resection
      VariableCentral tumor (n = 8)Peripheral tumor (n = 22)P value
      Age, y, median (IQR)58 (53-61)52 (47-58).279
      Female sex, n (%)4 (50.0)12 (54.5)1.0
      Radiologic findings
       Longest diameter, cm, median (IQR)28.0 (20.5-34.5)21.0 (16.0-28.0).204
       Classification, n (%).281
      Single nodular or consolidation7 (87.5)16 (72.7)
      Multiple nodular or consolidation0 (0)5 (22.7)
      Bronchiectasis and bronchiolitis1 (12.5)1 (4.5)
      Diagnostic methods, n (%)<.001
       Percutaneous needle biopsy2 (25.0)0 (0)
       Transbronchial biopsy3 (37.5)0 (0)
       VATS wedge resection3 (37.5)22 (100)
      Treatment characteristics, n (%)
       Surgical treatment.007
      VATS, lobectomy8 (100)
      Prolonged pneumothorax attributable to an air leak.
      8 (36.4)
      Chylothorax.
      VATS, limited resection0 (0)14 (63.6)
       Complications1 (12.5)
      Prolonged pneumothorax attributable to an air leak.
      1 (4.5)
      Chylothorax.
      1.0
      Treatment outcome
       Progressive disease, n (%)1 (12.5)0 (0).591
      Follow-up duration, mo, median (IQR)62.2 (39.5-81.4)22.1 (9.9-69.2).039
      IQR, Interquartile range; VATS, video-assisted thoracoscopic surgery.
      Prolonged pneumothorax attributable to an air leak.
      Chylothorax.
      Regarding postoperative complications, no complications developed after surgery in patients who underwent limited resection, whereas postoperative complications occurred in 2 patients who underwent lobectomy (chylothorax in one with a peripheral tumor and prolonged pneumothorax attributable to an air leak in the other with a central tumor).

      Discussion

      Our evaluation of the clinical presentations, treatment outcomes, and prognoses of 51 patients with pulmonary MALT lymphoma shows that pulmonary MALT lymphoma is indolent and associated with favorable outcomes, but disease progression increases significantly as with advancing disease stage. Moreover, limited resection may be an effective treatment modality for the management of peripherally localized stage IE pulmonary MALT lymphoma. To the best of our knowledge, this is the first study to describe the treatment outcomes of limited surgical resection for peripherally localized pulmonary MALT lymphoma.
      In agreement with the results of previous studies,
      • Borie R.
      • Wislez M.
      • Antoine M.
      • Copie-Bergman C.
      • Thieblemont C.
      • Cadranel J.
      Pulmonary mucosa-associated lymphoid tissue lymphoma revisited.
      • Ferraro P.
      • Trastek V.F.
      • Adlakha H.
      • Deschamps C.
      • Allen M.S.
      • Pairolero P.C.
      Primary non-Hodgkin's lymphoma of the lung.
      • Borie R.
      • Wislez M.
      • Thabut G.
      • Antoine M.
      • Rabbat A.
      • Couderc L.J.
      • et al.
      Clinical characteristics and prognostic factors of pulmonary MALT lymphoma.
      • Sammassimo S.
      • Pruneri G.
      • Andreola G.
      • Montoro J.
      • Steffanoni S.
      • Nowakowski G.S.
      • et al.
      A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG).
      • Stefanovic A.
      • Morgensztern D.
      • Fong T.
      • Lossos I.S.
      Pulmonary marginal zone lymphoma: a single centre experience and review of the SEER database.
      • Cadranel J.
      • Wislez M.
      • Antoine M.
      Primary pulmonary lymphoma.
      • Ahmed S.
      • Kussick S.J.
      • Siddiqui A.K.
      • Bhuiya T.A.
      • Khan A.
      • Sarewitz S.
      • et al.
      Bronchial-associated lymphoid tissue lymphoma: a clinical study of a rare disease.
      • Cordier J.F.
      • Chailleux E.
      • Lauque D.
      • Reynaud-Gaubert M.
      • Dietemann-Molard A.
      • Dalphin J.C.
      • et al.
      Primary pulmonary lymphomas. A clinical study of 70 cases in nonimmunocompromised patients.
      • Girinsky T.
      • Paumier A.
      • Ferme C.
      • Hanna C.
      • Ribrag V.
      • Leroy-Ladurie F.
      • et al.
      Low-dose radiation treatment in pulmonary mucosa-associated lymphoid tissue lymphoma: a plausible approach? A single-institution experience in 10 patients.
      • Wang L.
      • Xia Z.J.
      • Zhang Y.J.
      • Huang H.Q.
      • Lin T.Y.
      • Lu Y.
      Radical surgery may be not an optimal treatment approach for pulmonary MALT lymphoma.
      • Imai H.
      • Sunaga N.
      • Kaira K.
      • Kawashima O.
      • Yanagitani N.
      • Sato K.
      • et al.
      Clinicopathological features of patients with bronchial-associated lymphoid tissue lymphoma.
      • Troch M.
      • Streubel B.
      • Petkov V.
      • Turetschek K.
      • Chott A.
      • Raderer M.
      Does MALT lymphoma of the lung require immediate treatment? An analysis of 11 untreated cases with long-term follow-up.
      • Oh S.Y.
      • Kim W.S.
      • Kim J.S.
      • Kim S.J.
      • Kwon H.C.
      • Lee D.H.
      • et al.
      Pulmonary marginal zone B-cell lymphoma of MALT type–what is a prognostic factor and which is the optimal treatment, operation, or chemotherapy?: Consortium for Improving Survival of Lymphoma (CISL) study.
      • Kim J.H.
      • Lee S.H.
      • Park J.
      • Kim H.Y.
      • Lee S.I.
      • Park J.O.
      • et al.
      Primary pulmonary non-Hodgkin's lymphoma.
      • Zinzani P.L.
      • Pellegrini C.
      • Gandolfi L.
      • Casadei B.
      • Derenzini E.
      • Broccoli A.
      • et al.
      Extranodal marginal zone B-cell lymphoma of the lung: experience with fludarabine and mitoxantrone-containing regimens.
      the presentation and clinical course of pulmonary MALT lymphoma was indolent. In terms of staging, most patients (86%) were diagnosed with early-stage disease (ie, stage IE/IIE). A previous study found that 86% of patients with pulmonary MALT lymphoma were in stage I/II at the time of diagnosis.
      • Sammassimo S.
      • Pruneri G.
      • Andreola G.
      • Montoro J.
      • Steffanoni S.
      • Nowakowski G.S.
      • et al.
      A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG).
      Another study found that approximately 50% of patients were in stage I at the time of initial diagnosis.
      • Stefanovic A.
      • Morgensztern D.
      • Fong T.
      • Lossos I.S.
      Pulmonary marginal zone lymphoma: a single centre experience and review of the SEER database.
      Because most patients are diagnosed early, the proportion of patients with symptoms is relatively low. In the present study, approximately two-thirds of patients had a cough, and one-third had sputum production. In previous studies, approximately one-half to two-thirds of patients had respiratory symptoms.
      • Borie R.
      • Wislez M.
      • Thabut G.
      • Antoine M.
      • Rabbat A.
      • Couderc L.J.
      • et al.
      Clinical characteristics and prognostic factors of pulmonary MALT lymphoma.
      • Sammassimo S.
      • Pruneri G.
      • Andreola G.
      • Montoro J.
      • Steffanoni S.
      • Nowakowski G.S.
      • et al.
      A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG).
      • Stefanovic A.
      • Morgensztern D.
      • Fong T.
      • Lossos I.S.
      Pulmonary marginal zone lymphoma: a single centre experience and review of the SEER database.
      • Oh S.Y.
      • Kim W.S.
      • Kim J.S.
      • Kim S.J.
      • Kwon H.C.
      • Lee D.H.
      • et al.
      Pulmonary marginal zone B-cell lymphoma of MALT type–what is a prognostic factor and which is the optimal treatment, operation, or chemotherapy?: Consortium for Improving Survival of Lymphoma (CISL) study.
      Constitutional symptoms were even less common.
      • Borie R.
      • Wislez M.
      • Thabut G.
      • Antoine M.
      • Rabbat A.
      • Couderc L.J.
      • et al.
      Clinical characteristics and prognostic factors of pulmonary MALT lymphoma.
      • Sammassimo S.
      • Pruneri G.
      • Andreola G.
      • Montoro J.
      • Steffanoni S.
      • Nowakowski G.S.
      • et al.
      A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG).
      • Stefanovic A.
      • Morgensztern D.
      • Fong T.
      • Lossos I.S.
      Pulmonary marginal zone lymphoma: a single centre experience and review of the SEER database.
      Only 18% of patients in the present study had B symptoms, and previous studies have reported constitutional symptoms in 15% to 43% of patients
      • Sammassimo S.
      • Pruneri G.
      • Andreola G.
      • Montoro J.
      • Steffanoni S.
      • Nowakowski G.S.
      • et al.
      A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG).
      • Stefanovic A.
      • Morgensztern D.
      • Fong T.
      • Lossos I.S.
      Pulmonary marginal zone lymphoma: a single centre experience and review of the SEER database.
      • Wang L.
      • Xia Z.J.
      • Zhang Y.J.
      • Huang H.Q.
      • Lin T.Y.
      • Lu Y.
      Radical surgery may be not an optimal treatment approach for pulmonary MALT lymphoma.
      • Zinzani P.L.
      • Pellegrini C.
      • Gandolfi L.
      • Casadei B.
      • Derenzini E.
      • Broccoli A.
      • et al.
      Extranodal marginal zone B-cell lymphoma of the lung: experience with fludarabine and mitoxantrone-containing regimens.
      ; however, the proportion of patients with symptoms increased with advancing disease stage. Among patients with stage III/IV pulmonary MALT lymphoma, cough and sputum production were evident in 100% and 75%, respectively, and B symptoms were present in 88%. Given that previous studies did not compare clinical symptoms with respect to stage, our present work is informative in that it shows a close relationship between symptoms and stage. In line with previously reported findings,
      • Borie R.
      • Wislez M.
      • Antoine M.
      • Copie-Bergman C.
      • Thieblemont C.
      • Cadranel J.
      Pulmonary mucosa-associated lymphoid tissue lymphoma revisited.
      • Ferraro P.
      • Trastek V.F.
      • Adlakha H.
      • Deschamps C.
      • Allen M.S.
      • Pairolero P.C.
      Primary non-Hodgkin's lymphoma of the lung.
      • Borie R.
      • Wislez M.
      • Thabut G.
      • Antoine M.
      • Rabbat A.
      • Couderc L.J.
      • et al.
      Clinical characteristics and prognostic factors of pulmonary MALT lymphoma.
      • Sammassimo S.
      • Pruneri G.
      • Andreola G.
      • Montoro J.
      • Steffanoni S.
      • Nowakowski G.S.
      • et al.
      A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG).
      • Stefanovic A.
      • Morgensztern D.
      • Fong T.
      • Lossos I.S.
      Pulmonary marginal zone lymphoma: a single centre experience and review of the SEER database.
      • Cadranel J.
      • Wislez M.
      • Antoine M.
      Primary pulmonary lymphoma.
      • Ahmed S.
      • Kussick S.J.
      • Siddiqui A.K.
      • Bhuiya T.A.
      • Khan A.
      • Sarewitz S.
      • et al.
      Bronchial-associated lymphoid tissue lymphoma: a clinical study of a rare disease.
      • Cordier J.F.
      • Chailleux E.
      • Lauque D.
      • Reynaud-Gaubert M.
      • Dietemann-Molard A.
      • Dalphin J.C.
      • et al.
      Primary pulmonary lymphomas. A clinical study of 70 cases in nonimmunocompromised patients.
      • Girinsky T.
      • Paumier A.
      • Ferme C.
      • Hanna C.
      • Ribrag V.
      • Leroy-Ladurie F.
      • et al.
      Low-dose radiation treatment in pulmonary mucosa-associated lymphoid tissue lymphoma: a plausible approach? A single-institution experience in 10 patients.
      • Wang L.
      • Xia Z.J.
      • Zhang Y.J.
      • Huang H.Q.
      • Lin T.Y.
      • Lu Y.
      Radical surgery may be not an optimal treatment approach for pulmonary MALT lymphoma.
      • Imai H.
      • Sunaga N.
      • Kaira K.
      • Kawashima O.
      • Yanagitani N.
      • Sato K.
      • et al.
      Clinicopathological features of patients with bronchial-associated lymphoid tissue lymphoma.
      • Troch M.
      • Streubel B.
      • Petkov V.
      • Turetschek K.
      • Chott A.
      • Raderer M.
      Does MALT lymphoma of the lung require immediate treatment? An analysis of 11 untreated cases with long-term follow-up.
      • Oh S.Y.
      • Kim W.S.
      • Kim J.S.
      • Kim S.J.
      • Kwon H.C.
      • Lee D.H.
      • et al.
      Pulmonary marginal zone B-cell lymphoma of MALT type–what is a prognostic factor and which is the optimal treatment, operation, or chemotherapy?: Consortium for Improving Survival of Lymphoma (CISL) study.
      • Kim J.H.
      • Lee S.H.
      • Park J.
      • Kim H.Y.
      • Lee S.I.
      • Park J.O.
      • et al.
      Primary pulmonary non-Hodgkin's lymphoma.
      • Zinzani P.L.
      • Pellegrini C.
      • Gandolfi L.
      • Casadei B.
      • Derenzini E.
      • Broccoli A.
      • et al.
      Extranodal marginal zone B-cell lymphoma of the lung: experience with fludarabine and mitoxantrone-containing regimens.
      the prognosis of patients with pulmonary MALT lymphoma was relatively good. Over a median follow-up of 40.7 months, 7 patients (14%) developed progressive disease and 1 patient died of septic shock that developed during second-line chemotherapy to treat progressive disease. Following first-line chemotherapy to treat the pulmonary MALT lymphoma, the patient remained in stable disease for 68.2 months. Similar to the favorable treatment outcomes reported by previous studies,
      • Sammassimo S.
      • Pruneri G.
      • Andreola G.
      • Montoro J.
      • Steffanoni S.
      • Nowakowski G.S.
      • et al.
      A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG).
      • Stefanovic A.
      • Morgensztern D.
      • Fong T.
      • Lossos I.S.
      Pulmonary marginal zone lymphoma: a single centre experience and review of the SEER database.
      we found no significant difference in overall survival rate between patients with stage IE/IIE disease and those with stage IIIE/IVE disease. However, PFS was significantly longer in patients with stage IE/IIE disease, reflecting the slowly progressive nature of pulmonary MALT lymphoma.
      Two opposing opinions have been expressed in the context of surgical resection of pulmonary MALT lymphoma with localized lesions. Some experts have suggested that surgery (owing to its associated risks) should not be the first choice of treatment, the aim of which should be to preserve lung function.
      • Girinsky T.
      • Paumier A.
      • Ferme C.
      • Hanna C.
      • Ribrag V.
      • Leroy-Ladurie F.
      • et al.
      Low-dose radiation treatment in pulmonary mucosa-associated lymphoid tissue lymphoma: a plausible approach? A single-institution experience in 10 patients.
      • Wang L.
      • Xia Z.J.
      • Zhang Y.J.
      • Huang H.Q.
      • Lin T.Y.
      • Lu Y.
      Radical surgery may be not an optimal treatment approach for pulmonary MALT lymphoma.
      • Troch M.
      • Streubel B.
      • Petkov V.
      • Turetschek K.
      • Chott A.
      • Raderer M.
      Does MALT lymphoma of the lung require immediate treatment? An analysis of 11 untreated cases with long-term follow-up.
      • Oh S.Y.
      • Kim W.S.
      • Kim J.S.
      • Kim S.J.
      • Kwon H.C.
      • Lee D.H.
      • et al.
      Pulmonary marginal zone B-cell lymphoma of MALT type–what is a prognostic factor and which is the optimal treatment, operation, or chemotherapy?: Consortium for Improving Survival of Lymphoma (CISL) study.
      Oh et al
      • Oh S.Y.
      • Kim W.S.
      • Kim J.S.
      • Kim S.J.
      • Kwon H.C.
      • Lee D.H.
      • et al.
      Pulmonary marginal zone B-cell lymphoma of MALT type–what is a prognostic factor and which is the optimal treatment, operation, or chemotherapy?: Consortium for Improving Survival of Lymphoma (CISL) study.
      found no differences in overall survival between patients given chemotherapy and those who underwent surgery. In an evaluation of treatment outcomes in 17 patients with pulmonary MALT lymphoma (15 with stage IE and 2 with stage IV disease) treated with a fludarabine- and mitoxantrone-containing regimen, Zinzani et al
      • Zinzani P.L.
      • Pellegrini C.
      • Gandolfi L.
      • Casadei B.
      • Derenzini E.
      • Broccoli A.
      • et al.
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      found that 82% achieved complete response. More recently, Wang et al
      • Wang L.
      • Xia Z.J.
      • Zhang Y.J.
      • Huang H.Q.
      • Lin T.Y.
      • Lu Y.
      Radical surgery may be not an optimal treatment approach for pulmonary MALT lymphoma.
      reported that chemotherapy provided longer PFS compared with radical surgical resection, despite no differences in overall survival, in patients with early pulmonary MALT lymphoma.
      On the other hand, others consider surgical resection the treatment of choice, especially in young patients with pulmonary MALT lymphoma limited to one side of the lung.
      • Borie R.
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      • et al.
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      • Stefanovic A.
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      Pulmonary marginal zone lymphoma: a single centre experience and review of the SEER database.
      • Ahmed S.
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      • Bhuiya T.A.
      • Khan A.
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      • et al.
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      • Imai H.
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      • Sato K.
      • et al.
      Clinicopathological features of patients with bronchial-associated lymphoid tissue lymphoma.
      Numerous studies have shown that complete surgical resection is associated with prolonged complete response.
      • Ferraro P.
      • Trastek V.F.
      • Adlakha H.
      • Deschamps C.
      • Allen M.S.
      • Pairolero P.C.
      Primary non-Hodgkin's lymphoma of the lung.
      • Sammassimo S.
      • Pruneri G.
      • Andreola G.
      • Montoro J.
      • Steffanoni S.
      • Nowakowski G.S.
      • et al.
      A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG).
      • Stefanovic A.
      • Morgensztern D.
      • Fong T.
      • Lossos I.S.
      Pulmonary marginal zone lymphoma: a single centre experience and review of the SEER database.
      • Ahmed S.
      • Kussick S.J.
      • Siddiqui A.K.
      • Bhuiya T.A.
      • Khan A.
      • Sarewitz S.
      • et al.
      Bronchial-associated lymphoid tissue lymphoma: a clinical study of a rare disease.
      • Imai H.
      • Sunaga N.
      • Kaira K.
      • Kawashima O.
      • Yanagitani N.
      • Sato K.
      • et al.
      Clinicopathological features of patients with bronchial-associated lymphoid tissue lymphoma.
      • Kennedy J.L.
      • Nathwani B.N.
      • Burke J.S.
      • Hill L.R.
      • Rappaport H.
      Pulmonary lymphomas and other pulmonary lymphoid lesions. A clinicopathologic and immunologic study of 64 patients.
      In support of this latter position, we found that most patients who underwent surgical treatment did not develop progressive disease. Extending the findings of previous studies, we also found that limited resection for peripherally located tumors afforded favorable treatment outcomes. Moreover, no postoperative complication developed after limited resection, whereas 1 patient developed complication following lobectomy. Our results thus strongly suggest that peripherally localized stage IE pulmonary MALT lymphoma can be successfully managed by limited resection with maintenance of the advantage (complete response) afforded by lobectomy. To the best of our knowledge, this is the first study to evaluate the clinical implications and treatment outcomes of limited resection in patients with pulmonary MALT lymphoma.
      This study has several limitations. First, the study was retrospective in nature and confined to a single center. Second, the relatively small number of patients might have led to errors in the multivariable analyses. In addition, the lack of significance has a high likelihood of being a type II error in most of the subset analyses. Third, although we showed that limited resection may be a useful treatment in select patients with peripherally localized stage-IE pulmonary MALT lymphoma, we could not compare the treatment outcomes of limited resection versus lobectomy owing to the small number of patients. In addition, we also could not compare the treatment outcomes of surgical resection with those of such treatment modalities as watchful observation, immunotherapy, chemotherapy, and radiotherapy. Interestingly, Wang et al
      • Wang L.
      • Xia Z.J.
      • Zhang Y.J.
      • Huang H.Q.
      • Lin T.Y.
      • Lu Y.
      Radical surgery may be not an optimal treatment approach for pulmonary MALT lymphoma.
      also reported that radical surgical resection might not be the of treatment choice for early pulmonary MALT lymphoma. In that study, chemotherapy provided superior treatment outcomes compared with radical surgical resection. However, it should be emphasized that surgical resection is often necessary to confirm the diagnosis of pulmonary MALT lymphoma (especially for peripherally localized tumors) given the lack of definitive findings compatible with pulmonary MALT lymphoma, although single or multiple nodules or areas of consolidation that are indolent on serial CT scans are suggestive of the disease.
      • Bae Y.A.
      • Lee K.S.
      • Han J.
      • Ko Y.H.
      • Kim B.T.
      • Chung M.J.
      • et al.
      Marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue: imaging findings in 21 patients.
      Therefore, we suggest that surgical resection may be the treatment of choice for patients with localized lesions suspicious for pulmonary MALT lymphoma. In such cases, surgical resection allows for not only accurate diagnosis, but also successful management (thus with a high probability of complete response).
      In conclusion, our findings demonstrate pulmonary MALT lymphoma, for which the majority of low-stage patients are treated via surgical resection and high-stage patients are treated with chemotherapy, has indolent and favorable treatment outcomes. Low-stage pulmonary MALT lymphoma exhibited longer PFS, which suggests that complete surgical resection may afford favorable treatment outcomes. However, future studies with larger numbers of patients are needed to fully evaluate the role of surgical resection in the treatment of low-stage pulmonary MALT lymphoma.

      Conflict of Interest Statement

      Authors have nothing to disclose with regard to commercial support.

      Supplementary Data

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