CASE REPORT
The Clinical Respiratory Journal
Primary localized tracheobronchial amyloidosis presenting with massive hemoptysis: a case report and literature review Li-qin Zhang, Yi-chao Zhao, Xiao-wei Wang, Jian Yang, Zhi-wei Lu and Yu-sheng Cheng The Department of Respiratory Medicine, Yijishan Hospital, Wannan Medical College, Wuhu, China
Abstract Primary localized tracheobronchial amyloidosis (TBA) is a rare respiratory tract dysfunction, which is a heterogeneous group of diseases involving abnormal extracellular deposition of amyloid and autologous fibrillar protein material in β-pleated sheets. A 64-year-old man was referred to our hospital because of hemoptysis. Physical examination showed decreased breath sounds in the right lung on auscultation. Chest computed tomography scan displayed multiple nodules with varied size in main bronchia around bilateral hilus of the lung. After admission, bronchoscopy was performed for this patient, and roughness of mucosa in trachea and multiple nodules in respiratory tract were observed. Through further tissue biopsy, the diagnosis of primary TBA was confirmed. Please cite this paper as: Zhang L-q, Zhao Y-c, Wang X-w, Yang J, Lu Z-w and Cheng Y-s. Primary localized tracheobronchial amyloidosis presenting with massive hemoptysis: a case report and literature review. Clin Respir J 2015; ••: ••–••. DOI:10.1111/crj.12301.
Key words biopsy – bronchoscopy – hemoptysis – tracheobronchial amyloidosis Correspondence Yu-sheng Cheng, MD, The Department of Respiratory Medicine, Yijishan Hospital, Wannan Medical College, Jinghu District, 241001 Wuhu, China. Tel: (+86) 553 5739006 Fax: (+86) 553 5739006 email: [email protected] Received: 09 November 2014 Revision requested 02 February 2015 Accepted: 23 March 2015 DOI:10.1111/crj.12301 Authorship and contributorship Li-qin Zhang and Yi-chao Zhao are responsible for writing the article. Xiao-wei Wang and Jian Yang contributed in the follow-up and treatment of patients. Zhi-wei Lu contributed to writing the features of pathology and imaging in this case. Yu-sheng Cheng is responsible for designing, writing and correcting the article. Ethics This case report was approved by the institutional ethics committees of Yijishan Hospital of Wannan Medical College. Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
Introduction Primary localized tracheobronchial amyloidosis (TBA) is a rare respiratory tract dysfunction, which is a heterogeneous group of diseases involving abnormal extracellular deposition of amyloid and autologous fibrillar protein material in β-pleated sheets (1). Hemoptysis is an uncommon clinical symptom in
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
patients with TBA, although progressive dyspnea, productive cough and breathlessness are the most common symptoms of TBA (2).
Case presentation A 64-year-old man with repeated hemoptysis, the expectorated volume of which was over 100 mL in
1
Amyloidosis presenting with hemoptysis
24 h, was referred to our hospital. There was no associated history of fever, dyspnea and productive cough. He went to a local hospital where hemostatics (specific type unknown) were administered, but his symptom of hemoptysis was not relieved. On chest computed tomography (CT) scan, there were multiple nodules with varied size in main bronchia around bilateral hilus of the lung, but pulmonary parenchyma were normal (Fig. 1A–B). This patient had no history of smoking and other medical history. After the patient’s admission to our hospital, physical test showed decreased breath sounds in the right lung on auscultation; no other abnormal signs were found. The laboratory results were as follows: white blood cell, C-reactive protein level and erythrocyte sedimentation rate level stood in normal limits. Tests for serum tumor markers and antinuclear antibody were negative. Tests for liver function, renal function and coagulation profile were normal. Tests for acid-fast bacilli and fungi in three sputum samples were negative. There was no dysfunction in other organs, such as heart, digestive system and kidney. Hemoptysis in the patient was ceased after 6 h with the continuous administration of pituitrin. When this patient’s condition was stable for 1 week, he received a bronchoscopy, which revealed roughness of mucosa in trachea and multiple nodules in airway lumen (Fig. 1C). The diagnosis of primary TBA was confirmed by tissue biopsy, which showed Congo red dye staining of lesion was positive (Fig. 1D). Recurrence of
Zhang et al.
hemoptysis was not observed although the patient carried chest tightness sometimes during the follow-up of 6 months after his discharge.
Discussion Amyloidosis is a heterogeneous group of proteinfolding diseases characterized by extracellular deposition of a specific soluble precursor protein that aggregates in the form of insoluble fibrils, which is localized (restricted to one organ or site in the body) or systemic (in various organs and tissues throughout the body) (3). Typically, systemic immunoglobulin lightchain amyloidosis (AL) is the most common subtype of amyloidosis. Systemic light chain is a monoclonal light chain secreted by an underlying clonal plasma cell dyscrasia, which cause organ dysfunction and death through direct toxicity (3, 4). In comparison with systemic AL, localized AL amyloidosis is characterized by amyloid deposits at a single site without evidence of systemic involvement (5). Serum amyloid A amyloidosis is another major constituent of systemic amyloidosis and represents an evolutionarily conserved family of inflammatory acute-phase proteins (6). A large body of evidence shows that amyloidosis may contribute to dysfunction in multiple organs, such as heart, kidneys, liver, gastrointestinal tract, autonomic and so on. However, involvement of respiratory system is rare (5). Primary respiratory tract amyloidosis is
Figure 1. Computed tomography scan revealed multiple nodules with varied size in the right intermediate bronchus, but pulmonary parenchyma were normal (A, B). Bronchoscopy revealed roughness of mucosa in trachea and multiple nodular in airway lumen (C). Amyloidosis was confirmed by tissue biopsy, which showed Congo red dye staining of lesion was positive (D).
2
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
Zhang et al.
classified into four subtypes according to the site of the lesions: TBA, nodular amyloidosis, infiltrating interstitial amyloidosis and lymph node amyloidosis. Previous studies showed that TBA was the most common subtype, but only accounting for 0.5% of all symptomatic tracheobronchial lesions (7, 8). In 1877, Berraondo et al. first observed amyloid localized to the respiratory tract, the most subtype of which was AL amyloidosis (9). In this case report, no evidence of amyloidosis involving other organs was found, so this case was classified into localized primary TBA. However, there was a limitation in our study that we did not analyze the type of protein in amyloid lesion because of some technical restrictions. It is rather difficult to diagnose TBA early, and many cases are often misdiagnosed as lung cancer (7). Accumulated data show that the frequent clinical manifestations include dyspnea, chest tightness, cough and expectoration in TBA, but hemoptysis is rare (8). Furthermore, massive hemoptysis is one of the main causes of death in localized pulmonary amyloidosis (10). Distal atelectasis or recurrent pneumonia is caused by narrowing of the airways in TBA (9). Many pathogenetic factors, such as coagulation factor deficiencies, hyperfibrinolysis and platelet dysfunction, might contribute to hemoptysis in TBA. In addition, amyloid deposition leads to increased fragility of blood vessels, and impaired vasoconstriction is also a main cause of abnormal bleeding (11). Any patient with suspected TBA should undergo chest CT scan. High-resolution CT can distinguish the different patterns of pulmonary involvement (12). According to CT imaging, pulmonary amyloidosis appears in four patterns: parenchymal nodules, interstitial shadowing, tracheobronchial submucosal plaques or intraluminal nodules. Diagnosis of localized primary TBA requires investigations to exclude systemic amyloidosis (12). Moreover, bronchoscopy and tissue biopsy are essential for the diagnosis of TBA (7). Systemic AL amyloidosis carries a poor prognosis and necessitates conventional chemotherapy, including melphalan, thalidomide, bortezomib, lenalidomide and bendamustine in combination with dexamethasone (5). In a recent study, high-dose chemotherapy combined with autologous stem cell transplantation conferred better prognosis in systemic light chain AL-amyloidosis comparing with conventional chemotherapy (13). However, the management of localized TBA is largely dependent on symptoms (7). Treatment of TBA consists of laser or forceps resection, external radiation, systemic therapy or observation (14). Endo-
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
Amyloidosis presenting with hemoptysis
scopic therapies, such as stenting, carbon dioxide laser ablation and Nd:YAG laser therapy are crucial to alleviate the airway obstruction and control hemoptysis (7, 10, 15).
Acknowledgments Natural Science Foundation of Wannan Medical College for Middle-Aged and Young Scientific Researchers supports the collection and interpretation of patient information. Ren-guang Pei (Department of Interventional Therapy, Yi-ji Shan Hospital of Wannan Medical College) provides valuable work to revise this manuscript.
References 1. Sommer P, Kumar G, Lipchik RJ, Patel JJ. Tracheobronchial amyloidosis managed with multimodality therapies. Ther Adv Respir Dis. 2014;8: 48–52. 2. Ding L, Li W, Wang K, et al. Primary tracheobronchial amyloidosis in China: analysis of 64 cases and a review of literature. J Huazhong Univ Sci Technolog Med Sci. 2010;30: 599–603. 3. Hazenberg BP. Amyloidosis: a clinical overview. Rheum Dis Clin North Am. 2013;39: 323–45. 4. Chaulagain CP, Comenzo RL. New insights and modern treatment of AL amyloidosis. Curr Hematol Malig Rep. 2013;8: 291–8. 5. Mahmood S, Palladini G, Sanchorawala V, Wechalekar A. Update on treatment of light chain amyloidosis. Haematologica. 2014;99: 209–21. 6. Lu J, Yu Y, Zhu I, Cheng Y, Sun PD. Structural mechanism of serum amyloid A-mediated inflammatory amyloidosis. Proc Natl Acad Sci U S A. 2014;111: 5189–94. 7. Xu L, Cai BQ, Zhong X, Zhu YJ. Respiratory manifestations in amyloidosis. Chin Med J (Engl). 2005;118: 2027–33. 8. Chu H, Zhao L, Zhang Z, Gui T, Yi X, Sun X. Clinical characteristics of amyloidosis with isolated respiratory system involvement: a review of 13 cases. Ann Thorac Med. 2012;7: 243–9. 9. Berraondo J, Novella L, Sanz F, Lluch R, de Casimiro E, Lloret T. Management of tracheobronchial amyloidosis with therapeutic bronchoscopic techniques. Arch Bronconeumol. 2013;49: 207–9. 10. Gillmore JD, Hawkins PN. Amyloidosis and the respiratory tract. Thorax. 1999;54: 444–51. 11. Sucker C, Hetzel GR, Grabensee B, Stockschlaeder M, Scharf RE. Amyloidosis and bleeding: pathophysiology, diagnosis, and therapy. Am J Kidney Dis. 2006;47: 947–55. 12. Zalewska KI, Brown A, McKeon DJ. An unusual cause of haemoptysis: isolated tracheobronchial amyloidosis. BMJ Case Rep. 2014; doi:10.1136/bcr-2014-205118.
3
Amyloidosis presenting with hemoptysis
13. Raschle J, Banz Y, Suter T, Pabst T. A single-centre cohort of patients with systemic light chain AL-amyloidosis treated with conventional chemotherapy or with high-dose chemotherapy and autologous stem cell transplantation. Swiss Med Wkly. 2014;144: w13922.
4
Zhang et al.
14. Capizzi SA, Betancourt E, Prakash UB. Tracheobronchial amyloidosis. Mayo Clin Proc. 2000;75: 1148–52. 15. Inaty H, Folch E, Stephen C, Majid A. Tracheobronchial amyloidosis in a patient with Sjogren syndrome. J Bronchology Interv Pulmonol. 2013;20: 261–5.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
The Clinical Respiratory Journal
Primary localized tracheobronchial amyloidosis presenting with massive hemoptysis: a case report and literature review Li-qin Zhang, Yi-chao Zhao, Xiao-wei Wang, Jian Yang, Zhi-wei Lu and Yu-sheng Cheng The Department of Respiratory Medicine, Yijishan Hospital, Wannan Medical College, Wuhu, China
Abstract Primary localized tracheobronchial amyloidosis (TBA) is a rare respiratory tract dysfunction, which is a heterogeneous group of diseases involving abnormal extracellular deposition of amyloid and autologous fibrillar protein material in β-pleated sheets. A 64-year-old man was referred to our hospital because of hemoptysis. Physical examination showed decreased breath sounds in the right lung on auscultation. Chest computed tomography scan displayed multiple nodules with varied size in main bronchia around bilateral hilus of the lung. After admission, bronchoscopy was performed for this patient, and roughness of mucosa in trachea and multiple nodules in respiratory tract were observed. Through further tissue biopsy, the diagnosis of primary TBA was confirmed. Please cite this paper as: Zhang L-q, Zhao Y-c, Wang X-w, Yang J, Lu Z-w and Cheng Y-s. Primary localized tracheobronchial amyloidosis presenting with massive hemoptysis: a case report and literature review. Clin Respir J 2015; ••: ••–••. DOI:10.1111/crj.12301.
Key words biopsy – bronchoscopy – hemoptysis – tracheobronchial amyloidosis Correspondence Yu-sheng Cheng, MD, The Department of Respiratory Medicine, Yijishan Hospital, Wannan Medical College, Jinghu District, 241001 Wuhu, China. Tel: (+86) 553 5739006 Fax: (+86) 553 5739006 email: [email protected] Received: 09 November 2014 Revision requested 02 February 2015 Accepted: 23 March 2015 DOI:10.1111/crj.12301 Authorship and contributorship Li-qin Zhang and Yi-chao Zhao are responsible for writing the article. Xiao-wei Wang and Jian Yang contributed in the follow-up and treatment of patients. Zhi-wei Lu contributed to writing the features of pathology and imaging in this case. Yu-sheng Cheng is responsible for designing, writing and correcting the article. Ethics This case report was approved by the institutional ethics committees of Yijishan Hospital of Wannan Medical College. Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
Introduction Primary localized tracheobronchial amyloidosis (TBA) is a rare respiratory tract dysfunction, which is a heterogeneous group of diseases involving abnormal extracellular deposition of amyloid and autologous fibrillar protein material in β-pleated sheets (1). Hemoptysis is an uncommon clinical symptom in
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
patients with TBA, although progressive dyspnea, productive cough and breathlessness are the most common symptoms of TBA (2).
Case presentation A 64-year-old man with repeated hemoptysis, the expectorated volume of which was over 100 mL in
1
Amyloidosis presenting with hemoptysis
24 h, was referred to our hospital. There was no associated history of fever, dyspnea and productive cough. He went to a local hospital where hemostatics (specific type unknown) were administered, but his symptom of hemoptysis was not relieved. On chest computed tomography (CT) scan, there were multiple nodules with varied size in main bronchia around bilateral hilus of the lung, but pulmonary parenchyma were normal (Fig. 1A–B). This patient had no history of smoking and other medical history. After the patient’s admission to our hospital, physical test showed decreased breath sounds in the right lung on auscultation; no other abnormal signs were found. The laboratory results were as follows: white blood cell, C-reactive protein level and erythrocyte sedimentation rate level stood in normal limits. Tests for serum tumor markers and antinuclear antibody were negative. Tests for liver function, renal function and coagulation profile were normal. Tests for acid-fast bacilli and fungi in three sputum samples were negative. There was no dysfunction in other organs, such as heart, digestive system and kidney. Hemoptysis in the patient was ceased after 6 h with the continuous administration of pituitrin. When this patient’s condition was stable for 1 week, he received a bronchoscopy, which revealed roughness of mucosa in trachea and multiple nodules in airway lumen (Fig. 1C). The diagnosis of primary TBA was confirmed by tissue biopsy, which showed Congo red dye staining of lesion was positive (Fig. 1D). Recurrence of
Zhang et al.
hemoptysis was not observed although the patient carried chest tightness sometimes during the follow-up of 6 months after his discharge.
Discussion Amyloidosis is a heterogeneous group of proteinfolding diseases characterized by extracellular deposition of a specific soluble precursor protein that aggregates in the form of insoluble fibrils, which is localized (restricted to one organ or site in the body) or systemic (in various organs and tissues throughout the body) (3). Typically, systemic immunoglobulin lightchain amyloidosis (AL) is the most common subtype of amyloidosis. Systemic light chain is a monoclonal light chain secreted by an underlying clonal plasma cell dyscrasia, which cause organ dysfunction and death through direct toxicity (3, 4). In comparison with systemic AL, localized AL amyloidosis is characterized by amyloid deposits at a single site without evidence of systemic involvement (5). Serum amyloid A amyloidosis is another major constituent of systemic amyloidosis and represents an evolutionarily conserved family of inflammatory acute-phase proteins (6). A large body of evidence shows that amyloidosis may contribute to dysfunction in multiple organs, such as heart, kidneys, liver, gastrointestinal tract, autonomic and so on. However, involvement of respiratory system is rare (5). Primary respiratory tract amyloidosis is
Figure 1. Computed tomography scan revealed multiple nodules with varied size in the right intermediate bronchus, but pulmonary parenchyma were normal (A, B). Bronchoscopy revealed roughness of mucosa in trachea and multiple nodular in airway lumen (C). Amyloidosis was confirmed by tissue biopsy, which showed Congo red dye staining of lesion was positive (D).
2
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
Zhang et al.
classified into four subtypes according to the site of the lesions: TBA, nodular amyloidosis, infiltrating interstitial amyloidosis and lymph node amyloidosis. Previous studies showed that TBA was the most common subtype, but only accounting for 0.5% of all symptomatic tracheobronchial lesions (7, 8). In 1877, Berraondo et al. first observed amyloid localized to the respiratory tract, the most subtype of which was AL amyloidosis (9). In this case report, no evidence of amyloidosis involving other organs was found, so this case was classified into localized primary TBA. However, there was a limitation in our study that we did not analyze the type of protein in amyloid lesion because of some technical restrictions. It is rather difficult to diagnose TBA early, and many cases are often misdiagnosed as lung cancer (7). Accumulated data show that the frequent clinical manifestations include dyspnea, chest tightness, cough and expectoration in TBA, but hemoptysis is rare (8). Furthermore, massive hemoptysis is one of the main causes of death in localized pulmonary amyloidosis (10). Distal atelectasis or recurrent pneumonia is caused by narrowing of the airways in TBA (9). Many pathogenetic factors, such as coagulation factor deficiencies, hyperfibrinolysis and platelet dysfunction, might contribute to hemoptysis in TBA. In addition, amyloid deposition leads to increased fragility of blood vessels, and impaired vasoconstriction is also a main cause of abnormal bleeding (11). Any patient with suspected TBA should undergo chest CT scan. High-resolution CT can distinguish the different patterns of pulmonary involvement (12). According to CT imaging, pulmonary amyloidosis appears in four patterns: parenchymal nodules, interstitial shadowing, tracheobronchial submucosal plaques or intraluminal nodules. Diagnosis of localized primary TBA requires investigations to exclude systemic amyloidosis (12). Moreover, bronchoscopy and tissue biopsy are essential for the diagnosis of TBA (7). Systemic AL amyloidosis carries a poor prognosis and necessitates conventional chemotherapy, including melphalan, thalidomide, bortezomib, lenalidomide and bendamustine in combination with dexamethasone (5). In a recent study, high-dose chemotherapy combined with autologous stem cell transplantation conferred better prognosis in systemic light chain AL-amyloidosis comparing with conventional chemotherapy (13). However, the management of localized TBA is largely dependent on symptoms (7). Treatment of TBA consists of laser or forceps resection, external radiation, systemic therapy or observation (14). Endo-
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
Amyloidosis presenting with hemoptysis
scopic therapies, such as stenting, carbon dioxide laser ablation and Nd:YAG laser therapy are crucial to alleviate the airway obstruction and control hemoptysis (7, 10, 15).
Acknowledgments Natural Science Foundation of Wannan Medical College for Middle-Aged and Young Scientific Researchers supports the collection and interpretation of patient information. Ren-guang Pei (Department of Interventional Therapy, Yi-ji Shan Hospital of Wannan Medical College) provides valuable work to revise this manuscript.
References 1. Sommer P, Kumar G, Lipchik RJ, Patel JJ. Tracheobronchial amyloidosis managed with multimodality therapies. Ther Adv Respir Dis. 2014;8: 48–52. 2. Ding L, Li W, Wang K, et al. Primary tracheobronchial amyloidosis in China: analysis of 64 cases and a review of literature. J Huazhong Univ Sci Technolog Med Sci. 2010;30: 599–603. 3. Hazenberg BP. Amyloidosis: a clinical overview. Rheum Dis Clin North Am. 2013;39: 323–45. 4. Chaulagain CP, Comenzo RL. New insights and modern treatment of AL amyloidosis. Curr Hematol Malig Rep. 2013;8: 291–8. 5. Mahmood S, Palladini G, Sanchorawala V, Wechalekar A. Update on treatment of light chain amyloidosis. Haematologica. 2014;99: 209–21. 6. Lu J, Yu Y, Zhu I, Cheng Y, Sun PD. Structural mechanism of serum amyloid A-mediated inflammatory amyloidosis. Proc Natl Acad Sci U S A. 2014;111: 5189–94. 7. Xu L, Cai BQ, Zhong X, Zhu YJ. Respiratory manifestations in amyloidosis. Chin Med J (Engl). 2005;118: 2027–33. 8. Chu H, Zhao L, Zhang Z, Gui T, Yi X, Sun X. Clinical characteristics of amyloidosis with isolated respiratory system involvement: a review of 13 cases. Ann Thorac Med. 2012;7: 243–9. 9. Berraondo J, Novella L, Sanz F, Lluch R, de Casimiro E, Lloret T. Management of tracheobronchial amyloidosis with therapeutic bronchoscopic techniques. Arch Bronconeumol. 2013;49: 207–9. 10. Gillmore JD, Hawkins PN. Amyloidosis and the respiratory tract. Thorax. 1999;54: 444–51. 11. Sucker C, Hetzel GR, Grabensee B, Stockschlaeder M, Scharf RE. Amyloidosis and bleeding: pathophysiology, diagnosis, and therapy. Am J Kidney Dis. 2006;47: 947–55. 12. Zalewska KI, Brown A, McKeon DJ. An unusual cause of haemoptysis: isolated tracheobronchial amyloidosis. BMJ Case Rep. 2014; doi:10.1136/bcr-2014-205118.
3
Amyloidosis presenting with hemoptysis
13. Raschle J, Banz Y, Suter T, Pabst T. A single-centre cohort of patients with systemic light chain AL-amyloidosis treated with conventional chemotherapy or with high-dose chemotherapy and autologous stem cell transplantation. Swiss Med Wkly. 2014;144: w13922.
4
Zhang et al.
14. Capizzi SA, Betancourt E, Prakash UB. Tracheobronchial amyloidosis. Mayo Clin Proc. 2000;75: 1148–52. 15. Inaty H, Folch E, Stephen C, Majid A. Tracheobronchial amyloidosis in a patient with Sjogren syndrome. J Bronchology Interv Pulmonol. 2013;20: 261–5.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
