respiratory investigation 52 (2014) 144 –146
Contents lists available at ScienceDirect
Respiratory Investigation journal homepage: www.elsevier.com/locate/resinv
Case report
Two tracheal BALT lymphoma patients successfully treated with chemotherapy including rituximab Yoshihisa Hiraishia,n, Motoyasu Iikurab, Yoshihito Kogurec, Junko Hirashimab, Shinyu Izumib, Haruhito Sugiyamab a Department of Respiratory Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan b Department of Respiratory Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan c Department of Respiratory Medicine, NHO Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya 460-0001, Japan
ar t ic l e in f o
abs tra ct
Article history:
Bronchus-associated lymphoid tissue (BALT) lymphoma of the trachea, an important
Received 6 March 2013
differential diagnosis for tracheal tumors, is a rare disease with characteristic broncho-
Received in revised form
scopic findings. In this study, we reviewed 2 cases of patients who were symptomatic at
12 July 2013
the time of diagnosis, with tumors in the trachea and left main bronchus, putting them at
Accepted 12 July 2013
high risk for asphyxia. Chemotherapies including rituximab were administered, and
Available online 30 August 2013
complete remission was confirmed in both cases. Because tracheal tumors often have a
Keywords:
pernicious course, it might be beneficial to initiate a chemotherapeutic treatment regimen
BALT
instead of adopting the “wait-and-see” approach in patients with symptomatic tracheal
Bronchoscopy
BALT lymphoma.
Lymphoma
& 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
Chemotherapy Rituximab
1.
Introduction
Accounting for less than 1% of all non-Hodgkin lymphomas, bronchus-associated lymphoid tissue (BALT) lymphoma is a rare disease that is the major type of primary pulmonary lymphoma [1]. Tracheal BALT lymphoma is also very rare [2,3]. Because tracheal tumors often follow a pernicious course, radiation or stent insertion is the usual form of treatment. In this study, we reviewed 2 cases of BALT lymphoma with multiple tracheal tumors in which good
clinical response was achieved with chemotherapy containing rituximab.
2.
Case reports
2.1.
Case 1
A 61-year-old man was referred for an abnormal shadow observed on chest computed tomography (CT) (Fig. 1a). Three
n
Corresponding author. Tel.: +81 3 3815 5411; fax: +81 3 3815 5954. E-mail address: [email protected] (Y. Hiraishi).
2212-5345/$ - see front matter & 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.resinv.2013.07.006
respiratory investigation 52 (2014) 144 –146
145
(Fig. 1c). The abnormal shadows observed on chest CT at the time of diagnosis gradually disappeared after several courses of chemotherapy, indicating that these abnormal lung shadows were also mucosa-associated lymphoid tissue (MALT) lymphomas.
2.2.
Case 2
An 82-year-old man, with a medical history including disturbance in swallowing and chronic cough for several months, was referred for nausea and abdominal pain. Gastroscopy revealed a duodenal ulcer, treatment with a proton pump inhibitor was initiated, and the patient developed aspiration pneumonia. Multiple tracheal tumors were observed by chest CT (Fig. 2a) and bronchoscopy (Fig. 2b), and a bronchial tissue biopsy revealed BALT lymphoma. Treatment with cyclophosphamide, prednisolone, and vincristine plus rituximab (R-COP) was initiated. After 8 courses of this regimen, the tracheal tumors had nearly resolved (Fig. 2c). Three months after completing R-COP therapy, the patient died of peritonitis secondary to the duodenal ulcer and abdominal perforation. No recurrence of BALT lymphoma was observed on autopsy.
Fig. 1 – Case 1. (a) A nodule of the left lower lobe of the lung on chest CT in patient 1. (b) BALT lymphoma of the trachea after 3 years without any treatment. (c) Bronchoscopic observation of the trachea after R-CP treatment.
years previously, small cell lung carcinoma (cT1aN1M0) was diagnosed, and the patient was treated with neoadjuvant chemotherapy, right upper lung lobectomy, adjuvant chemotherapy, and prophylactic cranial irradiation. Complete response (CR) was maintained for the next 2 years. On bronchoscopic examination at presentation, multiple tumors in the trachea and left main bronchus were observed, and biopsy revealed extranodal marginal cell, or BALT lymphoma. With bronchoscopic lung biopsy, we failed to obtain a specimen from the region of the abnormal shadow observed on chest CT, and the patient was kept under observation for a brief period because of the typically slow progression seen for this type of lymphoma. Bronchoscopic examinations were periodically performed, and gradual tumor progression was observed (Fig. 1b). The patient began to complain of chronic cough, and 2 courses of cyclophosphamide plus prednisolone (CP) and 4 courses of CP plus rituximab (R-CP) were administered. This treatment resulted in hematological toxicity with development of WHO grade II/III leukocytopenia. After completion of the therapeutic regimens, the tumors had nearly resolved
Fig. 2 – Case 2. (a) Chest CT findings of the trachea in patient 2. (b) Diagnostic bronchoscopy showing BALT lymphoma of the trachea. (c) Bronchoscopic observation of the trachea after RCOP treatment.
146
3.
respiratory investigation 52 (2014) 144 –146
Discussion
Accounting for less than 1% of all non-Hodgkin lymphomas, BALT lymphoma is a rare disease that is the major type of primary pulmonary lymphoma [1]. BALT lymphoma belongs to the group of extranodal marginal B-cell lymphomas, of which gastric MALT lymphoma is most common. MALT lymphoma may affect virtually any organ of the human body. Although the lung is one of the most frequent nongastrointestinal organs affected by MALT lymphomas [4], tracheal BALT lymphoma is uncommon. Both patients presented in this study had multiple tracheal tumors, which is a rare finding with BALT lymphoma. Gelder et al. reviewed 321 primary tracheal tumors from a 10year national survey in the United Kingdom and reported that only 4 out of the 321 patients (1.2%) had lymphoma [2]. In addition, Fidias et al. reviewed 6 patients with primary tracheal non-Hodgkin lymphoma and stated that 1 patient (17%) had MALT lymphoma [3]. Few reports of tracheal BALT lymphoma have been reported [5–7], suggesting that these cases are extremely rare. Bronchoscopic findings of BALT lymphoma might provide the characteristics for differential diagnosis of BALT lymphoma from other tracheal tumors. Although there are very few reviews of the bronchoscopic findings of BALT lymphoma, Fidias et al. described its appearance as “fleshy-polypoid” [3]. In our 2 cases, multiple tumors of a widely stalked, fleshy-polypoid nature with intact superficial mucosa were noted. This is in contrast to the major pathological type of tracheal tumors, squamous cell or adenoid cystic carcinoma, which usually presents as a solitary polyp [8,9]. The characteristic features of tracheal BALT lymphoma are multiple, widely stalked, fleshy polyps covered with smooth bronchial mucosa. In the first case, gastroscopy revealed Helicobacter pylori infection. Despite antibiotic and antacid therapy, the tracheal tumors progressed. The second patient did not have H. pylori infection. Several previous studies resulted in regression of gastric MALT lymphoma after combination therapy for H. pylori [10,11], but no association of H. pylori with BALT lymphoma was found [4]. Considering these results as well as our cases, H. pylori eradication may be an ineffective treatment of BALT lymphoma. Both patients presented here were successfully treated with chemotherapy plus rituximab. According to the NCCN guideline version 1.2013, observation, radiotherapy, or chemotherapy including rituximab is the standard therapy of non-gastric MALT lymphoma based on age or performance status. Raderer et al. retrospectively analyzed the outcomes of treatment with rituximab plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine, and prednisolone (R-CHOP/ R-CNOP) in 26 patients with relapsed MALT lymphoma [12]. Complete remission was seen in 20 of the 26 patients (77%) and 6 (23%) achieved partial remission. In the absence of any prospectively collected data concerning the long-term outcome for patients with BALT lymphoma, the optimal standard treatment with regard to the role of surgery, chemotherapy, and radiotherapy, alone or in combination, as well as therapeutic abstention, is not clearly defined [4].
In the cases presented here, both of the current patients had been symptomatic, and tumors had developed in the trachea and left main bronchus, putting them at high risk for asphyxia. Therefore, chemotherapy was administered because it was less invasive than surgical treatment. Ultimately, complete remission was confirmed clinically in case 1 and histopathologically in case 2. In this study, we reviewed 2 cases of BALT lymphoma that had good clinical responses to chemotherapy including rituximab. Because symptomatic tracheal tumors often have a pernicious course, it might be beneficial to initiate a chemotherapeutic treatment regimen instead of adopting the “wait-and-see” approach.
Conflicts of interest The authors have no conflicts of interest.
r e f e r e n c e s
[1] Koss MN, Hochholzer L, Nichols PW, et al. Primary nonHodgkin's lymphoma and pseudolymphoma of lung: a study of 161 patients. Hum Pathol 1983;14:1024–38. [2] Gelder CM, Hetzel MR. Primary tracheal tumours: a national survey. Thorax 1993;48:688–92. [3] Fidias P, Wright C, Harris NL, et al. Primary tracheal nonHodgkin's lymphoma. A case report and review of the literature. Cancer 1996;77:2332–8. [4] Ahmed S, Siddiqui AK, Rai KR. Low-grade B-cell bronchial associated lymphoid tissue (BALT) lymphoma. Cancer Invest 2002;20:1059–68. [5] Andratschke M, Stelter K, Ihrler S, et al. Subglottic tracheal stenosis as primary manifestation of a marginal zone B-cell lymphoma of the larynx. In vivo 2005;19:547–50. [6] Kaplan MA, Pettit CL, Zukerberg LR, et al. Primary lymphoma of the trachea with morphologic and immunophenotypic characteristics of low-grade B-cell lymphoma of mucosaassociated lymphoid tissue. Am J Surg Pathol 1992;16:71–5. [7] Okubo K, Miyamoto N, Komaki C. Primary mucosaassociated lymphoid tissue (MALT) lymphoma of the trachea: a case of surgical resection and long term survival. Thorax 2005;60:82–3. [8] Honings J, Gaissert HA, van der Heijden HF, et al. Clinical aspects and treatment of primary tracheal malignancies. Acta Otolaryngol 2010;130:763–72. [9] Webb BD, Walsh GL, Roberts DB, et al. Primary tracheal malignant neoplasms: the University of Texas MD Anderson Cancer Center experience. J Am Coll Surg 2006;202:237–46. [10] Pinotti G, Zucca E, Roggero E, et al. Clinical features, treatment and outcome in a series of 93 patients with lowgrade gastric MALT lymphoma. Leuk Lymphoma 1997;26:527–37. [11] Zucca E, Roggero E, Pileri S. B-cell lymphoma of MALT type: a review with special emphasis on diagnostic and management problems of low-grade gastric tumours. Br J Haematol 1998;100:3–14. [12] Raderer M, Wohrer S, Streubel B, et al. Activity of rituximab plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine and prednisone in patients with relapsed MALT lymphoma. Oncology 2006;70:411–7.
Contents lists available at ScienceDirect
Respiratory Investigation journal homepage: www.elsevier.com/locate/resinv
Case report
Two tracheal BALT lymphoma patients successfully treated with chemotherapy including rituximab Yoshihisa Hiraishia,n, Motoyasu Iikurab, Yoshihito Kogurec, Junko Hirashimab, Shinyu Izumib, Haruhito Sugiyamab a Department of Respiratory Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan b Department of Respiratory Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan c Department of Respiratory Medicine, NHO Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya 460-0001, Japan
ar t ic l e in f o
abs tra ct
Article history:
Bronchus-associated lymphoid tissue (BALT) lymphoma of the trachea, an important
Received 6 March 2013
differential diagnosis for tracheal tumors, is a rare disease with characteristic broncho-
Received in revised form
scopic findings. In this study, we reviewed 2 cases of patients who were symptomatic at
12 July 2013
the time of diagnosis, with tumors in the trachea and left main bronchus, putting them at
Accepted 12 July 2013
high risk for asphyxia. Chemotherapies including rituximab were administered, and
Available online 30 August 2013
complete remission was confirmed in both cases. Because tracheal tumors often have a
Keywords:
pernicious course, it might be beneficial to initiate a chemotherapeutic treatment regimen
BALT
instead of adopting the “wait-and-see” approach in patients with symptomatic tracheal
Bronchoscopy
BALT lymphoma.
Lymphoma
& 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
Chemotherapy Rituximab
1.
Introduction
Accounting for less than 1% of all non-Hodgkin lymphomas, bronchus-associated lymphoid tissue (BALT) lymphoma is a rare disease that is the major type of primary pulmonary lymphoma [1]. Tracheal BALT lymphoma is also very rare [2,3]. Because tracheal tumors often follow a pernicious course, radiation or stent insertion is the usual form of treatment. In this study, we reviewed 2 cases of BALT lymphoma with multiple tracheal tumors in which good
clinical response was achieved with chemotherapy containing rituximab.
2.
Case reports
2.1.
Case 1
A 61-year-old man was referred for an abnormal shadow observed on chest computed tomography (CT) (Fig. 1a). Three
n
Corresponding author. Tel.: +81 3 3815 5411; fax: +81 3 3815 5954. E-mail address: [email protected] (Y. Hiraishi).
2212-5345/$ - see front matter & 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.resinv.2013.07.006
respiratory investigation 52 (2014) 144 –146
145
(Fig. 1c). The abnormal shadows observed on chest CT at the time of diagnosis gradually disappeared after several courses of chemotherapy, indicating that these abnormal lung shadows were also mucosa-associated lymphoid tissue (MALT) lymphomas.
2.2.
Case 2
An 82-year-old man, with a medical history including disturbance in swallowing and chronic cough for several months, was referred for nausea and abdominal pain. Gastroscopy revealed a duodenal ulcer, treatment with a proton pump inhibitor was initiated, and the patient developed aspiration pneumonia. Multiple tracheal tumors were observed by chest CT (Fig. 2a) and bronchoscopy (Fig. 2b), and a bronchial tissue biopsy revealed BALT lymphoma. Treatment with cyclophosphamide, prednisolone, and vincristine plus rituximab (R-COP) was initiated. After 8 courses of this regimen, the tracheal tumors had nearly resolved (Fig. 2c). Three months after completing R-COP therapy, the patient died of peritonitis secondary to the duodenal ulcer and abdominal perforation. No recurrence of BALT lymphoma was observed on autopsy.
Fig. 1 – Case 1. (a) A nodule of the left lower lobe of the lung on chest CT in patient 1. (b) BALT lymphoma of the trachea after 3 years without any treatment. (c) Bronchoscopic observation of the trachea after R-CP treatment.
years previously, small cell lung carcinoma (cT1aN1M0) was diagnosed, and the patient was treated with neoadjuvant chemotherapy, right upper lung lobectomy, adjuvant chemotherapy, and prophylactic cranial irradiation. Complete response (CR) was maintained for the next 2 years. On bronchoscopic examination at presentation, multiple tumors in the trachea and left main bronchus were observed, and biopsy revealed extranodal marginal cell, or BALT lymphoma. With bronchoscopic lung biopsy, we failed to obtain a specimen from the region of the abnormal shadow observed on chest CT, and the patient was kept under observation for a brief period because of the typically slow progression seen for this type of lymphoma. Bronchoscopic examinations were periodically performed, and gradual tumor progression was observed (Fig. 1b). The patient began to complain of chronic cough, and 2 courses of cyclophosphamide plus prednisolone (CP) and 4 courses of CP plus rituximab (R-CP) were administered. This treatment resulted in hematological toxicity with development of WHO grade II/III leukocytopenia. After completion of the therapeutic regimens, the tumors had nearly resolved
Fig. 2 – Case 2. (a) Chest CT findings of the trachea in patient 2. (b) Diagnostic bronchoscopy showing BALT lymphoma of the trachea. (c) Bronchoscopic observation of the trachea after RCOP treatment.
146
3.
respiratory investigation 52 (2014) 144 –146
Discussion
Accounting for less than 1% of all non-Hodgkin lymphomas, BALT lymphoma is a rare disease that is the major type of primary pulmonary lymphoma [1]. BALT lymphoma belongs to the group of extranodal marginal B-cell lymphomas, of which gastric MALT lymphoma is most common. MALT lymphoma may affect virtually any organ of the human body. Although the lung is one of the most frequent nongastrointestinal organs affected by MALT lymphomas [4], tracheal BALT lymphoma is uncommon. Both patients presented in this study had multiple tracheal tumors, which is a rare finding with BALT lymphoma. Gelder et al. reviewed 321 primary tracheal tumors from a 10year national survey in the United Kingdom and reported that only 4 out of the 321 patients (1.2%) had lymphoma [2]. In addition, Fidias et al. reviewed 6 patients with primary tracheal non-Hodgkin lymphoma and stated that 1 patient (17%) had MALT lymphoma [3]. Few reports of tracheal BALT lymphoma have been reported [5–7], suggesting that these cases are extremely rare. Bronchoscopic findings of BALT lymphoma might provide the characteristics for differential diagnosis of BALT lymphoma from other tracheal tumors. Although there are very few reviews of the bronchoscopic findings of BALT lymphoma, Fidias et al. described its appearance as “fleshy-polypoid” [3]. In our 2 cases, multiple tumors of a widely stalked, fleshy-polypoid nature with intact superficial mucosa were noted. This is in contrast to the major pathological type of tracheal tumors, squamous cell or adenoid cystic carcinoma, which usually presents as a solitary polyp [8,9]. The characteristic features of tracheal BALT lymphoma are multiple, widely stalked, fleshy polyps covered with smooth bronchial mucosa. In the first case, gastroscopy revealed Helicobacter pylori infection. Despite antibiotic and antacid therapy, the tracheal tumors progressed. The second patient did not have H. pylori infection. Several previous studies resulted in regression of gastric MALT lymphoma after combination therapy for H. pylori [10,11], but no association of H. pylori with BALT lymphoma was found [4]. Considering these results as well as our cases, H. pylori eradication may be an ineffective treatment of BALT lymphoma. Both patients presented here were successfully treated with chemotherapy plus rituximab. According to the NCCN guideline version 1.2013, observation, radiotherapy, or chemotherapy including rituximab is the standard therapy of non-gastric MALT lymphoma based on age or performance status. Raderer et al. retrospectively analyzed the outcomes of treatment with rituximab plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine, and prednisolone (R-CHOP/ R-CNOP) in 26 patients with relapsed MALT lymphoma [12]. Complete remission was seen in 20 of the 26 patients (77%) and 6 (23%) achieved partial remission. In the absence of any prospectively collected data concerning the long-term outcome for patients with BALT lymphoma, the optimal standard treatment with regard to the role of surgery, chemotherapy, and radiotherapy, alone or in combination, as well as therapeutic abstention, is not clearly defined [4].
In the cases presented here, both of the current patients had been symptomatic, and tumors had developed in the trachea and left main bronchus, putting them at high risk for asphyxia. Therefore, chemotherapy was administered because it was less invasive than surgical treatment. Ultimately, complete remission was confirmed clinically in case 1 and histopathologically in case 2. In this study, we reviewed 2 cases of BALT lymphoma that had good clinical responses to chemotherapy including rituximab. Because symptomatic tracheal tumors often have a pernicious course, it might be beneficial to initiate a chemotherapeutic treatment regimen instead of adopting the “wait-and-see” approach.
Conflicts of interest The authors have no conflicts of interest.
r e f e r e n c e s
[1] Koss MN, Hochholzer L, Nichols PW, et al. Primary nonHodgkin's lymphoma and pseudolymphoma of lung: a study of 161 patients. Hum Pathol 1983;14:1024–38. [2] Gelder CM, Hetzel MR. Primary tracheal tumours: a national survey. Thorax 1993;48:688–92. [3] Fidias P, Wright C, Harris NL, et al. Primary tracheal nonHodgkin's lymphoma. A case report and review of the literature. Cancer 1996;77:2332–8. [4] Ahmed S, Siddiqui AK, Rai KR. Low-grade B-cell bronchial associated lymphoid tissue (BALT) lymphoma. Cancer Invest 2002;20:1059–68. [5] Andratschke M, Stelter K, Ihrler S, et al. Subglottic tracheal stenosis as primary manifestation of a marginal zone B-cell lymphoma of the larynx. In vivo 2005;19:547–50. [6] Kaplan MA, Pettit CL, Zukerberg LR, et al. Primary lymphoma of the trachea with morphologic and immunophenotypic characteristics of low-grade B-cell lymphoma of mucosaassociated lymphoid tissue. Am J Surg Pathol 1992;16:71–5. [7] Okubo K, Miyamoto N, Komaki C. Primary mucosaassociated lymphoid tissue (MALT) lymphoma of the trachea: a case of surgical resection and long term survival. Thorax 2005;60:82–3. [8] Honings J, Gaissert HA, van der Heijden HF, et al. Clinical aspects and treatment of primary tracheal malignancies. Acta Otolaryngol 2010;130:763–72. [9] Webb BD, Walsh GL, Roberts DB, et al. Primary tracheal malignant neoplasms: the University of Texas MD Anderson Cancer Center experience. J Am Coll Surg 2006;202:237–46. [10] Pinotti G, Zucca E, Roggero E, et al. Clinical features, treatment and outcome in a series of 93 patients with lowgrade gastric MALT lymphoma. Leuk Lymphoma 1997;26:527–37. [11] Zucca E, Roggero E, Pileri S. B-cell lymphoma of MALT type: a review with special emphasis on diagnostic and management problems of low-grade gastric tumours. Br J Haematol 1998;100:3–14. [12] Raderer M, Wohrer S, Streubel B, et al. Activity of rituximab plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine and prednisone in patients with relapsed MALT lymphoma. Oncology 2006;70:411–7.
