Amyloidosis includes a spectrum of diseases associated with an abnormal extracellular deposition of amyloid.  Amyloid deposition can occur in association with inflammatory, hereditary, or neoplastic entities.

   Visit:   Non-Neoplastic Pulmonary Diseases

The respiratory system is involved in approximately 50% of patients with amyloidosis.

In the lung amyloid deposition may be localized or diffuse and may have a variety of appearances.

On average, affected patients are in the 6th decade of life. Nodular amyloidosis is usually asymptomatic and thus found incidentally.

Atelectasis and secondary bronchiectasis due to obstruction of a bronchus have been reported .

Three forms of Primary pulmonary amyloidosis: 

 i) Tracheobronchial ii) Nodular parenchymal, and iii) Alveolar septal.

Tracheobronchial amyloidosis is the most frequent manifestation of pulmonary amyloidosis.

Nodular pulmonary amyloidosis is a limited form of amyloidosis. It is characterized by  single or multiple intrapulmonary nodules or masses and is also known as amyloidoma.

Amyloidoma usually occur  in the lower lobes. These may be mistaken as a tumour. The lesion may calcify or undergo osseous metaplasia.

Resection of these nodules is both diagnostic and curative.

Nodular pulmonary "amyloidomas"  are characterized by a benign course and are not associated with systemic amyloidosis. Despite its localized nature, tracheobronchial amyloid deposition may be asymptomatic or may result in significant morbidity due to obstructive phenomena. Pulmonary amyloidosis associated with primary systemic amyloidosis generally presents as a diffuse interstitial pattern with or without pleural effusion.

Imaging Features:  Imaging of nodular amyloidosis shows solitary or multiple nodules with a smooth or lobular contour. Nodules are often seen in a subpleural or peripheral location . Calcification may occur in up to 50% of nodules seen at CT scan.

Pathologic features:  Image Link

Gross examination:  Amyloid nodules are either yellow, gray, or pale tan. The nodules range in size from 0.6 to 15 cm. Larger lesions may cavitate or exhibit hemorrhage, necrosis, fibrosis, or calcification.

Microscopic features: 

Amyloid appears as an amorphous sheet of eosinophilic extracellular material that surrounds vessels.

The protein takes up Congo red stain and exhibits apple-green birefringence at polarized microscopic analysis.    Image Link

Differential diagnosis -  Primary or metastatic neoplasms.  Amyloid-like nodules should be distinguished from nodular amyloidosis and, in some patients, might represent a localized form of light-chain deposition.

A review of routine histopathological samples and autopsies examined at the Department of Pathology, University of Malaya revealed 15 cases of amyloidosis of the lung. Two were localized depositions limited to the lung while in the remainder, lung involvement was part of the picture of systemic amyloidosis. Both cases of localized amyloidosis presented with symptomatic lung/bronchial masses and a clinical diagnosis of tumour. Histology revealed "amyloidomas" associated with heavy plasma cell and lymphocytic infiltration and the presence of multinucleated giant cells. In both cases, the amyloid deposits were immunopositive for lambda light chains and negative for kappa chains and AA protein. One was a known systemic lupus erythematosus patient with polyclonal hypergammaglobulinaemia. The other patient was found to have plasma cell dyscrasia with monoclonal IgG lambda gammopathy. Both patients did not develop systemic amyloidosis. In contrast, lung involvement in systemic AA amyloidosis was not obvious clinically or macroscopically but was histologically evident in 75% of cases subjected to autopsy. Amyloid was detected mainly in the walls of arterioles and small vessels, and along the alveolar septa. It was less frequently detected in the pleura, along the basement membrane of the bronchial epithelium and around bronchial glands. In one case of systemic AL amyloidosis associated with multiple myeloma, an "amyloidoma" occurred in the subpleural region reminiscent of localized amyloidosis. These cases pose questions on (1) whether localized "tumour-like" amyloidosis is a forme fruste of systemic AL amyloidosis and (2) the differing pattern of tissue deposition of different chemical types of amyloid fibrils, with the suggestion that light chain amyloid has a greater tendency to nodular deposition than AA amyloid.

Nodular pulmonary amyloidosis. Diagnosis by transbronchial biopsy.Mod Pathol. 2000 Sep;13(9):934-40.

Nodular amyloidomas (NA) of the lung are non-neoplastic inflammatory nodules containing eosinophilic amyloid deposits and a lymphoplasmacytic infiltrate. In some instances, the extensive amyloid deposits may obscure an underlying lymphoproliferative disorder. The histologic and immunohistologic features that discriminate these two differential diagnostic possibilities were studied in this series of six cases of NA and five cases of primary low-grade malignant lymphomas of lung with secondary amyloid deposits (ML). Two of lymphoma cases showed histopathologic and immunophenotypic features of B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-cell CLL/SLL), and three cases were low-grade B-cell lymphoma derived from mucosa associated lymphoid tissue (MALT lymphoma). Key discriminating morphologic features between NA and ML included lymphatic tracking of the cellular infiltrate (3/5 ML; 1/6 NA), pleural infiltration (3/5 ML; 0/6 NA), sheet-like masses of plasma cells (5/5 ML; 0/6 NA) and reactive follicles (4/5 ML; 1/6 NA). Lesional circumscription, vascular and bronchial destruction, lymphoepithelial lesions, and granulomas were not helpful discriminators. Immunohistochemical features indicating a dominant CD20+, CD79a+ B-cell population (5/5 ML; 0/6 NA), light chain restriction (4/5 ML; 0/6 NA), and aberrant antigen expression of CD20/CD43 (2/5 ML; 0/6 NA) were helpful. Amyloid tumors with a reactive lymphoplasmacytic infiltrate can be separated from low-grade malignant lymphomas utilizing both histologic and immunohistochemical features.

Nodular pulmonary amyloidosis in a patient with rheumatoid arthritis.Clin Rheumatol. 2007 Mar 2;

We describe a 67-year-old white woman with a long-standing active rheumatoid arthritis who refused treatment. Chest roentgenograms performed in 2000 revealed a pulmonary nodule in the mid-left lung. Progression of the nodule was followed annually by computerized tomography (CT). In the last CT in 2002, we observed multiple nodules in both lungs in the absence of lymph gland involvement. The patient was operated by videothoracoscopy to resect one of the pulmonary nodules. Pathological examination of the excised tissue revealed amyloid A-type (AA) amyloidosis. Although pulmonary amyloidosis is rare in patients with systemic AA amyloidosis, we recommend that this possibility be considered when confronted with a patient with these characteristics.

Pulmonary nodular amyloidosis.Cir Esp. 2007 Jan;81(1):43-5.

Amyloidosis is a systemic disease caused by extracellular accumulation of amyloid in different parts of the body. Pulmonary involvement is infrequent and nodular amyloidosis is extremely rare. We present the case of a 72-year-old man with chronic obstructive pulmonary disease in whom a 3-cm pulmonary nodule was discovered during routine radiological follow-up. After various complementary investigations failed to identify the etiology of the nodule, surgical excision was performed. Subsequent histopathological study revealed the presence of amyloid deposits with characteristic apple-green birefringence when stained with Congo-red under polarized light microscopy.

A case of multiple nodular pulmonary amyloidosis complicated with primary Sjogren syndrome.Nihon Kokyuki Gakkai Zasshi. 2007 Apr;45(4):356-60.

A 79-year-old woman was admitted to the Department of Orthopedics Surgery for treatment of osteoarthritis in her knee. Multiple pulmonary nodular lesions were found on preoperative chest x-ray film screening. Metastatic lung tumor was suspected, but no tumorous lesions were detected in other organs. CT guided lung biopsy was performed. Histopathological examination revealed amyloid consisting of homogenous eosinophilic materials. No amyloid deposits were detected in other organs, so we diagnosed localized nodular pulmonary amyloidosis. She was subsequently given a diagnosis of primary Sjögren syndrome. We believe that such a case of multiple nodular pulmonary amyloidosis with Sjögren syndrome is rare, and the case showed interesting radiological findings, such as mimicking metastatic lung tumor.

Nodular pulmonary amyloidosis. Jpn J Thorac Cardiovasc Surg. 2006 Sep;54(9):399-401.

A 72-year-old woman with a diagnosis of suspected rheumatoid arthritis was admitted with multiple pulmonary nodules in the bilateral lung field. To obtain a diagnosis, a nodule was resected using video-assisted thoracic surgery. Microscopically, amorphous eosinophilic acellular substances were surrounded by inflammatory infiltrates, which were confirmed to be amyloid deposits by congo red staining. Thus, a diagnosis of pulmonary amyloidosis was obtained. The clinical features and diagnostic process are discussed.

Primary pulmonary nodular amyloidosis.Monaldi Arch Chest Dis. 2005 Sep;63(3):173-5.

Primary nodular amyloidosis of the lung is an uncommon manifestation. The disease runs a benign course, but offers diagnostic problems due to non-specific radiological features entering the big field of the solitary nodule. We describe the case of a 60 year old man with multiple nodules on the left lung operated on diagnostic and therapeutic video-assisted thoracoscopy and discuss the possibilities, if any, of suspecting such a disease through radiologic characteristics along with findings from the patient's history, physical examination and laboratory tests.

Amyloid-like pulmonary nodules, including localized light-chain deposition: clinicopathologic analysis of three cases. Am J Clin Pathol. 2004 Feb;121(2):200-4.

Amyloid-like pulmonary nodules have been described in patients with systemic light-chain deposition disease, but their significance in other clinical contexts is unknown. We examined biopsy specimens of amyloid-like pulmonary nodules from 3 women without systemic light-chain deposition disease. Patient 1 (aged 62 years) had multiple pulmonary nodules and underwent 2 separate lung biopsies, the first showing nodules composed of kappa light-chain deposits accompanied by low-grade lymphoplasmacytic lymphoma limited to the lung and the second, obtained after chemotherapy 9 months later, showing only residual nodules without persistent lymphoma. Patients 2 (aged 65 years) and 3 (aged 69 years) had asymptomatic solitary pulmonary nodules. In all cases, electron microscopic examination showed dense granular extracellular deposits without the fibrillary characteristics of amyloid. Amyloid-like nodules should be distinguished from nodular amyloidosis and, in some patients, might represent a localized form of light-chain deposition.

Localized amyloidosis of the respiratory system: CT features.J Comput Assist Tomogr. 1999 Jul-Aug;23(4):627-31.

PURPOSE: Amyloidosis includes a spectrum of diseases associated with an abnormal extracellular deposition of amyloid. The respiratory system is involved in approximately 50% of patients with amyloidosis. The purpose of this review is to present the CT findings of localized amyloidosis of the respiratory system. METHODS: We reviewed the CT findings of localized amyloidosis of the respiratory system from the previous reports and our experiences. RESULTS: Three patterns of involvement in respiratory system are presented: tracheobronchial nodular and diffuse parenchymal. CT demonstrates nodules, plaques, or diffuse thickening of the airways with calcification. Postobstructive collapse is associated in case of diffuse airway involvement. Parenchymal nodules have sharp and lobulated margins with peripheral or subpleural locations. High-resolution CT shows reticular opacities, interlobular septal thickening, and small, well-defined nodules of 2 to 4-mm in diameter predominantly in the subpleural regions. CONCLUSION: Amyloidosis of respiratory system has variable findings and CT scans clearly depict extent and distribution of the disease, its postobstructive pulmonary complication, and other associated findings such as calcification and lymphadenopathy.

Nodular amyloidosis of the lung from intravenous drug abuse: an uncommon cause of multiple pulmonary nodules.South Med J. 1998 Apr;91(4):402-4.

Bilateral pulmonary nodules in an immunocompromised host may offer a diagnostic dilemma. We present a case of a human immunodeficiency virus positive patient with history of intravenous drug abuse (IVDA) who was incidentally found to have bilateral multiple pulmonary nodules. She was diagnosed as having nodular pulmonary amyloidosis, presumably serum amyloid A derived (AA) in origin but confirmed not to be of amyloid light chain derived origin (AL), histologically associated with focal birefringent material and foreign body giant cell reaction, probably due to IVDA. Asymptomatic multiple pulmonary nodules in amyloidosis are usually of AL origin; however, recently similar changes have been found in the AA form in patients with Sjogren's syndrome or Crohn's disease. It has not been previously described in association with IVDA. Thus, this case documents a unique cause of bilateral pulmonary nodules due to amyloidosis consequent to IVDA.

Nodular pulmonary amyloidosis associated with asbestos exposure.Pathol Int. 1996 Jan;46(1):66-70.

A 71 year old man was admitted for the purpose of diagnosis of a right solitary pulmonary nodule. The size of the nodule was 18 x 18 mm in diameter 2 years ago, but it has become large, 25 x 25 mm in diameter. The nodule was resected by thoracotomy. Microscopically, eosinophilic amorphous, acellular substances were surrounded by inflammatory infiltrates. It stained with Congo red stain and showed green birefringence with polarizing microscopy. Amyloid fibrils were observed electron microscopically. Asbestos bodies were observed in the lung parenchyma around the nodule. This case shows that a nodule in nodular pulmonary amyloidosis can grow gradually and suggests the possibility of asbestos fibers as one of the etiologic factors in nodular pulmonary amyloidosis.

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