CASE REPORT
The Clinical Respiratory Journal
A rare case of multinodular pulmonary amyloidosis Jizhen Feng1, Jiamei Li2, Chunxiang Ling1 and Qingwei Liu1 1 Department of Radiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China 2 Department of Pathology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China
Abstract Background and Aims: Pulmonary amyloidosis is usually associated with systemic amyloidosis. Localized pulmonary amyloidosis without systemic amyloidosis is even rare. We reported a rare case of multinodular pulmonary amyloidosis to improve the understanding of the disease. Methods: Report of a case. Results: We present an unusual case of primary pulmonary multinodular amyloidosis in a middle-aged woman. She presented our hospital with cough and chest distress only. Results of computed tomography (CT) showed multiple nodules with diffused calcification and thick-walled cavity in bilateral lung parenchyma. And the diagnosis of nodular amyloidosis was established by a CT-guided core needle biopsy. Conclusions: The case clearly shows it is difficult to distinguish parenchymal nodular amyloidosis from malignant primary lung neoplasm in radiology because of their similar images. Thus, the role of CT-guided core needle biopsy in diagnosis of pulmonary mutinodular amyloidosis is very important. Please Q. AA rare rare case case of of multinodular multinodular Please cite cite this this paper paper as: as: Feng J,J, Li J, Ling C and Liu Q. pulmonary DOI:10.1111/crj.12220. pulmonary amyloidosis. amyloidosis.Clin ClinRespir RespirJ 2016; J 2014;10:••:389–392. ••–••. DOI:10.1111/crj.12220.
Ethics Approval of the concerned ethics committee was given and written informed consent was given by the studied patient.
Correspondence Qingwei Liu, MD, Department of Radiology, Shandong Provincial Hospital affiliated to Shandong University, Jingwu Road 324, 250021 Jinan, China. Tel: +86 053168776150 Fax: +86 053168773665 email: [email protected] Received: 14 April 2014 Revision requested: 31 August 2014 Accepted: 29 September 2014 DOI:10.1111/crj.12220 Authorship and contributorship Jizhen Feng and Qingwei Liu are responsible for initiating and performing the study. Jiamei Li and Chunxiang Ling have made substantial contribution in developing the case record form and interpreting the data.
Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
Introduction Amyloidosis is not a common disease, characterized by extracellular deposition of insoluble fibrillar proteins. It could be present either localized or systemic. Primary pulmonary nodular amyloidosis that is not associated with primary systemic amyloidosis is even rare (1). Here, we reported a case of multinodular pulmonary amyloidosis without systemic involvement.
Case report A 48-year-old woman presented with cough and chest distress only more than 2 weeks without the other
The Clinical Respiratory Journal (2016) (2014) • ISSN 1752-6981 C 2014 V © 2014 John John Wiley Wiley && Sons Sons Ltd Ltd
Key words computed tomography – CT-guided core needle biopsy – mutinodular – pulmonary amyloidosis
symptoms, such as chest pain, breathlessness, fever, hemoptysis, nausea or vomiting. She denied a history of smoking, lung disease, malignancy or connective tissue disorders. A review of her systems was noncontributory. The results showed that the data of a peripheral blood count, tumor biomarker tests, a purified protein derivative test for tuberculosis, baseline serum chemistry screening and urinalysis were all normal, as so were electrocardiogram and heart ultrasound. A computed tomography (CT) of the chest was performed, which showed multiple nodules with diffused calcification and thick-walled cavity in bilateral lung parenchyma. The nodules were diffused in both lungs and varied in shape and size (range, 0.5∼4.5 cm,
1 389
Multinodular pulmonary amyloidosis
Feng et al.
Figure 1. (A) Pulmonary window and (B) mediastinal window computed tomography (CT) images showed multiple nodules with diffused calcification and multiple thick-walled cavities in bilateral lung parenchyma. The nodules were diffused in lungs and varied in shape and size.
with an average of 1.8 cm; Fig. 1). Then a CT scan of her abdomen, magnetic resonance scan of brain and a bone scan were performed; all the images showed normal. At last, the patient received a CT-guided core needle biopsy of one of the pulmonary nodules, and a diagnosis of nodular amyloidosis was established. The biopsy had revealed amorphous acidophilic homogeneous material with a few lymphocytes, plasmocytes,
scattered histocytes and fibroblasts. The amorphous acidophilic homogeneous material was processed by potassium permanganate, and then confirmed as amyloid by Congo red staining (Fig. 2). Tracheobronchial infiltration was excluded by bronchial endoscopy. The patient was treated by chemotherapy with lowdose oral melphalan and prednisone. Three months after the treatment, the discomfort caused by cough
Figure 2. Histology of pulmonary nodular amyloidosis (A) showed amorphous acidophilic homogeneous material. Panel B showed the positive result of Congo red staining. Original magnification: A, 20×; B, 40×.
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The The Clinical Clinical Respiratory Respiratory Journal (2014) (2016) • ISSN 1752-6981 C 2014 V © 2014 John John Wiley & Sons Ltd
Feng et al.
and chest distress disappeared. However, the nodules have no changes and confirmed by a reviewed CT scan.
Discussion Localized pulmonary amyloidosis without systemic deposition is a rare disease, and the diagnostic standard is the birefringence at Congo red staining. Clinically, according to commonly encountered symptoms, radiographic findings, and treatment modalities, there are five classifications of localized pulmonary involved: nodular, tracheobronchial, diffuse alveolar, adenopathy and plural effusion (2). According to immunohistochemistry, there are four major categories of amyloidosis: (i) primary or immunoglobulin light chain (AL) disease; (ii) secondary or amyloid protein A disease; (iii) hereditary or mutant transthyretin disease; and (iv) dialysis-associated or β2-microglobulin disease. The AL fibril is a common type of amyloid deposit in the lung, usually the deposit is systemic (3, 4). However as in our case, the AL type was confirmed without systemic deposit. There are no special literatures that referred the different races of the incidence rate of pulmonary amyloisosis. In the past, Afro-Americans are more susceptible to pulmonary amyloidosis; however, more and more cases were diagnosed along with increasing cases reported, especially in Asian countries. In our opinion, the epidemiology of amyloidosis is difficult to define precisely. Firstly, the disease is often undiagnosed or misdiagnosed especially in Asian countries in the past because doctors had insufficient understanding of pulmonary amyloidosis. Secondly, selection bias potentially makes data from tertiary referral centers unrepresentative (3–8). Based on a literature review, nodular pulmonary amyloidosis is usually found incidentally on chest radiographs or at autopsy. Amyloid nodules have no distinctive radiographic characteristics and can be single or multiple, usually peripheral lesions. Calcification or ossification is seen in up to 50% of cases and can help indicate the diagnosis (1, 9–11). As in our case, the nodules diffused in bilateral lungs and varied in shape and size. Calcification was seen in almost every lesion. Nodular amyloidosis depositions may be associated with cyst. The proposed mechanisms include air trapping fragility and disruption of alveolar walls caused by amyloid depositions, while the alveolar wall destruction is due to ischemia (2). Nodular amyloidosis associated with thin-wall cyst is most common in patients with Sjogren syndrome (12–14). However, this patient was not associated with any connective tissue diseases.
The Clinical Respiratory Journal (2016) (2014) • ISSN 1752-6981 1752-6981 C 2014 V © 2014 John John Wiley Wiley && Sons Sons Ltd Ltd
Multinodular pulmonary amyloidosis
Because of the variability of amyloid involvement in the pulmonary system, management decisions are mostly based on an individual basis. Systemic amyloidosis can be treated with chemotherapy while localized forms are typically treated with local interventions (2). As in our case, we chose chemotherapy with oral melphalan and prednisone. Three months after treatment, the discomfort caused by cough and chest distress disappeared, but these nodules showed no changes. The differential diagnosis of nodular amyloidosis includes both malignant and benign primary lung neoplasm. It is difficult to diagnose these lesions, owing to their diverse clinical presentations and lack of definitive imaging properties. The golden standard is histopathologic confirmation, marked by Congo red staining. A positron emission tomography may provide additional diagnostic value in the diagnosis of malignant lung tumor and pulmonary nodular amyloidosis (15). However, this method also has its limitation; when the standardized uptake value ranged from 1.8 to 6.81, it is difficult to distinguish the lung tumor and amyloidosis (16). For this patient, metastatic tumor and tubercular granulomas were considered before biopsy because of calcification and cavity. In conclusion, it is difficult to distinguish parenchymal nodular amyloidosis from malignant primary lung neoplasm in radiology because of their image similarity. However, making a right diagnosis of nodular pulmonary amyloidosis is necessary, which decide the further treatment and prognosis. Thus, a CT-guided core needle biopsy is indispensable and can confirm the diagnosis of amyloidosis.
References 1. Kitamura H, Kobayashi T, Kaneko M, et al. Pulmonary amyloidosis diagnosed by CT-guided transbronchial biopsy: a case report. Jpn J Clin Oncol. 2001;31: 209–11. 2. Lund ME, Bakaya P, Hoag JB. Pulmonary manifestations of amyloidosis. In: Güvenç PA, editor. Amyloidosis-An Insight to Disease of System and Novel Therapies. Rijeka, Janeza Trdine, 2011: 63–76. 3. Berk JL, O’Regan A, Skinner M. Pulmonary and tracheobronchial amyloidosis. Semin Respir Crit Care Med. 2002;23: 155–65. 4. Hecser L, Dacian B, Delia G, et al. Primary pulmonary systemic amyloidosis-case report. Rom J Leg Med. 2009;17: 265–70. 5. Pinney JH, Smith CJ, Taube JB, et al. Systemic amyloidosis in England: an epidemiological study. Br J Haematol. 2013;161: 525–32. 6. Panizo N, Rivera F. Decreasing incidence of AA amyloidosis in Spain. Eur J Clin Invest. 2013;43: 767–73.
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Multinodular pulmonary amyloidosis
7. Chu H, Zhao L, Zhang Z, et al. Clinical characteristic of amyloidosis with isolated respiratory system involvement: a review of 13 cases. Ann Thorac Med. 2012;7: 243–9. 8. Liu M, Wei S, Li X, et al. Pulmonary nodular amyloidosis in a patient undergoing lobectomy: a case report. J Med Case Rep. 2013;7: 248. 9. Lee AY, Godwin JD, Pipavath SN. Case: 182: pulmonary amyloidosis. Radiology. 2012;263: 929–32. 10. Utz JP, Swensen SJ, Gertz MA. Pulmonary amyloidosis. The Mayo Clinic experience from 1980 to 1993. Ann Intern Med. 1996;124: 407–13. 11. Bhavsar T, Huang Y, GauSghan C, et al. Bilateral pulmonary nodular amyloidosis: a case report and review of the literature. World J Respirol. 2012;2: 6–8. 12. Aylwin AC, Gishen P, Copley SJ. Imaging appearance of thoracic amyloidosis. J Thorac Imaging. 2005;20: 41–6.
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Feng et al.
13. Kim HY, Im JC, Song KS, et al. Localized amyloidosis of the respiratory system: CT features. J Comput Assist Tomogr. 1999;23: 627–31. 14. Desai SR, Nicholson AG, Stewart S, et al. Benign pulmonary lymphocytic infiltration and amyloidosis: computed tomographic and pathologic features in three cases. J Thorac Imaging. 1997;12: 215–20. 15. Noordzij W, Glaudemans AW, van Rheenen RW, et al. Additional diagnostic value of SPECT/CT to planar Iodine-123 labeled serum amyloid P component scintigraphy in a patient with pulmonary nodular amyloidosis. Amyloid. 2014;21: 131–3. 16. Miyazaki D, Yazaki M, Ishii W, et al. A rare lung nodule consisting of adenocarcinoma and amyloid deposition in a patient with primary systemic AL amyloidosis. Intern Med. 2011;50: 243–6.
The The Clinical Clinical Respiratory Respiratory Journal (2014) (2016) • ISSN 1752-6981 C 2014 V © 2014 John John Wiley & Sons Ltd
The Clinical Respiratory Journal
A rare case of multinodular pulmonary amyloidosis Jizhen Feng1, Jiamei Li2, Chunxiang Ling1 and Qingwei Liu1 1 Department of Radiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China 2 Department of Pathology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China
Abstract Background and Aims: Pulmonary amyloidosis is usually associated with systemic amyloidosis. Localized pulmonary amyloidosis without systemic amyloidosis is even rare. We reported a rare case of multinodular pulmonary amyloidosis to improve the understanding of the disease. Methods: Report of a case. Results: We present an unusual case of primary pulmonary multinodular amyloidosis in a middle-aged woman. She presented our hospital with cough and chest distress only. Results of computed tomography (CT) showed multiple nodules with diffused calcification and thick-walled cavity in bilateral lung parenchyma. And the diagnosis of nodular amyloidosis was established by a CT-guided core needle biopsy. Conclusions: The case clearly shows it is difficult to distinguish parenchymal nodular amyloidosis from malignant primary lung neoplasm in radiology because of their similar images. Thus, the role of CT-guided core needle biopsy in diagnosis of pulmonary mutinodular amyloidosis is very important. Please Q. AA rare rare case case of of multinodular multinodular Please cite cite this this paper paper as: as: Feng J,J, Li J, Ling C and Liu Q. pulmonary DOI:10.1111/crj.12220. pulmonary amyloidosis. amyloidosis.Clin ClinRespir RespirJ 2016; J 2014;10:••:389–392. ••–••. DOI:10.1111/crj.12220.
Ethics Approval of the concerned ethics committee was given and written informed consent was given by the studied patient.
Correspondence Qingwei Liu, MD, Department of Radiology, Shandong Provincial Hospital affiliated to Shandong University, Jingwu Road 324, 250021 Jinan, China. Tel: +86 053168776150 Fax: +86 053168773665 email: [email protected] Received: 14 April 2014 Revision requested: 31 August 2014 Accepted: 29 September 2014 DOI:10.1111/crj.12220 Authorship and contributorship Jizhen Feng and Qingwei Liu are responsible for initiating and performing the study. Jiamei Li and Chunxiang Ling have made substantial contribution in developing the case record form and interpreting the data.
Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
Introduction Amyloidosis is not a common disease, characterized by extracellular deposition of insoluble fibrillar proteins. It could be present either localized or systemic. Primary pulmonary nodular amyloidosis that is not associated with primary systemic amyloidosis is even rare (1). Here, we reported a case of multinodular pulmonary amyloidosis without systemic involvement.
Case report A 48-year-old woman presented with cough and chest distress only more than 2 weeks without the other
The Clinical Respiratory Journal (2016) (2014) • ISSN 1752-6981 C 2014 V © 2014 John John Wiley Wiley && Sons Sons Ltd Ltd
Key words computed tomography – CT-guided core needle biopsy – mutinodular – pulmonary amyloidosis
symptoms, such as chest pain, breathlessness, fever, hemoptysis, nausea or vomiting. She denied a history of smoking, lung disease, malignancy or connective tissue disorders. A review of her systems was noncontributory. The results showed that the data of a peripheral blood count, tumor biomarker tests, a purified protein derivative test for tuberculosis, baseline serum chemistry screening and urinalysis were all normal, as so were electrocardiogram and heart ultrasound. A computed tomography (CT) of the chest was performed, which showed multiple nodules with diffused calcification and thick-walled cavity in bilateral lung parenchyma. The nodules were diffused in both lungs and varied in shape and size (range, 0.5∼4.5 cm,
1 389
Multinodular pulmonary amyloidosis
Feng et al.
Figure 1. (A) Pulmonary window and (B) mediastinal window computed tomography (CT) images showed multiple nodules with diffused calcification and multiple thick-walled cavities in bilateral lung parenchyma. The nodules were diffused in lungs and varied in shape and size.
with an average of 1.8 cm; Fig. 1). Then a CT scan of her abdomen, magnetic resonance scan of brain and a bone scan were performed; all the images showed normal. At last, the patient received a CT-guided core needle biopsy of one of the pulmonary nodules, and a diagnosis of nodular amyloidosis was established. The biopsy had revealed amorphous acidophilic homogeneous material with a few lymphocytes, plasmocytes,
scattered histocytes and fibroblasts. The amorphous acidophilic homogeneous material was processed by potassium permanganate, and then confirmed as amyloid by Congo red staining (Fig. 2). Tracheobronchial infiltration was excluded by bronchial endoscopy. The patient was treated by chemotherapy with lowdose oral melphalan and prednisone. Three months after the treatment, the discomfort caused by cough
Figure 2. Histology of pulmonary nodular amyloidosis (A) showed amorphous acidophilic homogeneous material. Panel B showed the positive result of Congo red staining. Original magnification: A, 20×; B, 40×.
2 390
The The Clinical Clinical Respiratory Respiratory Journal (2014) (2016) • ISSN 1752-6981 C 2014 V © 2014 John John Wiley & Sons Ltd
Feng et al.
and chest distress disappeared. However, the nodules have no changes and confirmed by a reviewed CT scan.
Discussion Localized pulmonary amyloidosis without systemic deposition is a rare disease, and the diagnostic standard is the birefringence at Congo red staining. Clinically, according to commonly encountered symptoms, radiographic findings, and treatment modalities, there are five classifications of localized pulmonary involved: nodular, tracheobronchial, diffuse alveolar, adenopathy and plural effusion (2). According to immunohistochemistry, there are four major categories of amyloidosis: (i) primary or immunoglobulin light chain (AL) disease; (ii) secondary or amyloid protein A disease; (iii) hereditary or mutant transthyretin disease; and (iv) dialysis-associated or β2-microglobulin disease. The AL fibril is a common type of amyloid deposit in the lung, usually the deposit is systemic (3, 4). However as in our case, the AL type was confirmed without systemic deposit. There are no special literatures that referred the different races of the incidence rate of pulmonary amyloisosis. In the past, Afro-Americans are more susceptible to pulmonary amyloidosis; however, more and more cases were diagnosed along with increasing cases reported, especially in Asian countries. In our opinion, the epidemiology of amyloidosis is difficult to define precisely. Firstly, the disease is often undiagnosed or misdiagnosed especially in Asian countries in the past because doctors had insufficient understanding of pulmonary amyloidosis. Secondly, selection bias potentially makes data from tertiary referral centers unrepresentative (3–8). Based on a literature review, nodular pulmonary amyloidosis is usually found incidentally on chest radiographs or at autopsy. Amyloid nodules have no distinctive radiographic characteristics and can be single or multiple, usually peripheral lesions. Calcification or ossification is seen in up to 50% of cases and can help indicate the diagnosis (1, 9–11). As in our case, the nodules diffused in bilateral lungs and varied in shape and size. Calcification was seen in almost every lesion. Nodular amyloidosis depositions may be associated with cyst. The proposed mechanisms include air trapping fragility and disruption of alveolar walls caused by amyloid depositions, while the alveolar wall destruction is due to ischemia (2). Nodular amyloidosis associated with thin-wall cyst is most common in patients with Sjogren syndrome (12–14). However, this patient was not associated with any connective tissue diseases.
The Clinical Respiratory Journal (2016) (2014) • ISSN 1752-6981 1752-6981 C 2014 V © 2014 John John Wiley Wiley && Sons Sons Ltd Ltd
Multinodular pulmonary amyloidosis
Because of the variability of amyloid involvement in the pulmonary system, management decisions are mostly based on an individual basis. Systemic amyloidosis can be treated with chemotherapy while localized forms are typically treated with local interventions (2). As in our case, we chose chemotherapy with oral melphalan and prednisone. Three months after treatment, the discomfort caused by cough and chest distress disappeared, but these nodules showed no changes. The differential diagnosis of nodular amyloidosis includes both malignant and benign primary lung neoplasm. It is difficult to diagnose these lesions, owing to their diverse clinical presentations and lack of definitive imaging properties. The golden standard is histopathologic confirmation, marked by Congo red staining. A positron emission tomography may provide additional diagnostic value in the diagnosis of malignant lung tumor and pulmonary nodular amyloidosis (15). However, this method also has its limitation; when the standardized uptake value ranged from 1.8 to 6.81, it is difficult to distinguish the lung tumor and amyloidosis (16). For this patient, metastatic tumor and tubercular granulomas were considered before biopsy because of calcification and cavity. In conclusion, it is difficult to distinguish parenchymal nodular amyloidosis from malignant primary lung neoplasm in radiology because of their image similarity. However, making a right diagnosis of nodular pulmonary amyloidosis is necessary, which decide the further treatment and prognosis. Thus, a CT-guided core needle biopsy is indispensable and can confirm the diagnosis of amyloidosis.
References 1. Kitamura H, Kobayashi T, Kaneko M, et al. Pulmonary amyloidosis diagnosed by CT-guided transbronchial biopsy: a case report. Jpn J Clin Oncol. 2001;31: 209–11. 2. Lund ME, Bakaya P, Hoag JB. Pulmonary manifestations of amyloidosis. In: Güvenç PA, editor. Amyloidosis-An Insight to Disease of System and Novel Therapies. Rijeka, Janeza Trdine, 2011: 63–76. 3. Berk JL, O’Regan A, Skinner M. Pulmonary and tracheobronchial amyloidosis. Semin Respir Crit Care Med. 2002;23: 155–65. 4. Hecser L, Dacian B, Delia G, et al. Primary pulmonary systemic amyloidosis-case report. Rom J Leg Med. 2009;17: 265–70. 5. Pinney JH, Smith CJ, Taube JB, et al. Systemic amyloidosis in England: an epidemiological study. Br J Haematol. 2013;161: 525–32. 6. Panizo N, Rivera F. Decreasing incidence of AA amyloidosis in Spain. Eur J Clin Invest. 2013;43: 767–73.
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Multinodular pulmonary amyloidosis
7. Chu H, Zhao L, Zhang Z, et al. Clinical characteristic of amyloidosis with isolated respiratory system involvement: a review of 13 cases. Ann Thorac Med. 2012;7: 243–9. 8. Liu M, Wei S, Li X, et al. Pulmonary nodular amyloidosis in a patient undergoing lobectomy: a case report. J Med Case Rep. 2013;7: 248. 9. Lee AY, Godwin JD, Pipavath SN. Case: 182: pulmonary amyloidosis. Radiology. 2012;263: 929–32. 10. Utz JP, Swensen SJ, Gertz MA. Pulmonary amyloidosis. The Mayo Clinic experience from 1980 to 1993. Ann Intern Med. 1996;124: 407–13. 11. Bhavsar T, Huang Y, GauSghan C, et al. Bilateral pulmonary nodular amyloidosis: a case report and review of the literature. World J Respirol. 2012;2: 6–8. 12. Aylwin AC, Gishen P, Copley SJ. Imaging appearance of thoracic amyloidosis. J Thorac Imaging. 2005;20: 41–6.
4 392
Feng et al.
13. Kim HY, Im JC, Song KS, et al. Localized amyloidosis of the respiratory system: CT features. J Comput Assist Tomogr. 1999;23: 627–31. 14. Desai SR, Nicholson AG, Stewart S, et al. Benign pulmonary lymphocytic infiltration and amyloidosis: computed tomographic and pathologic features in three cases. J Thorac Imaging. 1997;12: 215–20. 15. Noordzij W, Glaudemans AW, van Rheenen RW, et al. Additional diagnostic value of SPECT/CT to planar Iodine-123 labeled serum amyloid P component scintigraphy in a patient with pulmonary nodular amyloidosis. Amyloid. 2014;21: 131–3. 16. Miyazaki D, Yazaki M, Ishii W, et al. A rare lung nodule consisting of adenocarcinoma and amyloid deposition in a patient with primary systemic AL amyloidosis. Intern Med. 2011;50: 243–6.
The The Clinical Clinical Respiratory Respiratory Journal (2014) (2016) • ISSN 1752-6981 C 2014 V © 2014 John John Wiley & Sons Ltd
