Asian Cardiovasc Thorac Ann 2007;15:69-71
© 2007 Asia Publishing EXchange Ltd
Primary Pulmonary Amyloidosis Due to Low-Grade B Cell Lymphoma
Georgios P Georghiou, MD,
Olga Boikov, MD1,
Bernardo A Vidne, MD,
Milton Saute, MD
Department of Cardiothoracic Surgery
1 Institute of Pathology, Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel
For reprint information contact: Georgios P Georghiou, MD, Tel: 357 22 819 666, Fax: 357 22 819 667, Email: georgios{at}ahi.com.cy, Department of Cardiothoracic Surgery, American Heart Institute, 20 Lefkotheou Avenue, Nicosia 2054, Cyprus.
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ABSTRACT
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Pulmonary involvement is not an infrequent complication of systemic amyloidosis, although affected patients rarely have significant pulmonary symptoms. In contrast, localized (primary) pulmonary amyloidosis is rare. We report a case of pulmonary low-grade B cell lymphoma with amyloid production, causing localized pulmonary amyloidosis.
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INTRODUCTION
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Pulmonary amyloidosis is characterized by the deposition of insoluble monoclonal immunoglobulin light-chain fragments in lung tissue. Amyloid deposits in the respiratory tract are common in both primary systemic amyloidosis and amyloidosis secondary to systemic disease processes, such as chronic renal failure, chronic infections, rheumatoid arthritis, tuberculosis, syphilis, osteomyelitis, and inflammatory bowel disease. Localized amyloid deposition in lung tissue is a well-described, but less frequently observed form, occurring in tracheobronchial, nodular parenchymal, or diffuse interstitial patterns. The findings are not associated with systemic amyloid involvement.1,2 We describe a patient with localized pulmonary amyloidosis in whom histologic and immunohistochemical studies revealed lymphoplasmacytic features with heavy amyloid deposition.
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CASE REPORT
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A 69-year-old man presented with a history of chronic episodic cough, recurrent pneumonia, and recent onset of night sweats. He also complained of joint pain, myalgia, and dyspnea on exertion. On physical examination, inspiratory and expiratory wheezes were noted over the left lung, with mild diminution of breath sounds. Chest radiography demonstrated an infiltrating mass on the left upper lobe (Figure 1A
), and magnetic resonance imaging showed a left hilar mass obstructing the left upper lobe pulmonary artery and invading the mediastinum (Figure 1B). The lingular bronchus lumen was occluded with postobstructive atelectasis. Positron emission tomography was positive, raising the possibility of malignancy. A bronchoscopic biopsy was performed and the results were conclusive for amyloid deposition. There was no evidence of extrapulmonary organ involvement with amyloidosis. Moreover, findings on blood and urine chemical analyses, including serum immunoelectrophoresis for light chains, were negative, consistent with the diagnosis of primary (localized) pulmonary amyloidosis. The patient was referred for surgery. A thoracic epidural infusion catheter was inserted, and general anesthesia was induced with placement of a double-lumen endotracheal tube. A standard left posterolateral thoracotomy was performed through the 5th intercostal space, followed by a left upper lobectomy. Macroscopically, a poorly defined tumor-like gray tissue occupied the whole lobe. Only a thin rim of normal lung parenchyma was found. The postoperative course was uneventful. At the 1-year follow-up, the patient was doing well and had no respiratory complaints.
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Figure 1. (A) Plain radiograph showing a left upper lobe mass; (B) Magnetic resonance image showing a giant soft tissue mass at the left upper lobe, invading the mediastinum.
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Histologic examination revealed extensive infiltration of the lung tissue by low-grade B-cell lymphoma, accompanied by heavy deposition of amorphous proteinaceous eosinophilic material. Immunohistochemically, the neoplastic cells were identified as small lymphocytes and plasmacytoid lymphocytes, monoclonal for immunoglobulin G and lambda light chains (Figure 2A). The proteinaceous substance stained positive with Congo red, and an apple-green birefringence was observed by polarizing microscopy. The findings were consistent with monoclonal immunoglobulin lambda lymphoplasmacytic lymphoma with accompanying heavy amyloid deposition (Figure 2B).
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Figure 2. (A) Low magnification of lung tissue showing involvement by lymphoplasmacytic lymphoma, accompanied by prominent amyloid deposition (hematoxylin and eosin stain, original magnification x 40); inset: high magnification showing a mixture of small lymphocytes, plasmacytoid cells, and plasma cells (hematoxylin and eosin stain, original magnification x 20); (B) Positive Congo red-stained section confirms the deposition of amyloid in the lung (Congo red stain, original magnification x 40).
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DISCUSSION
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Amyloidosis refers to a group of diseases characterized by extracellular deposition of the complex fibrillar protein, amyloid, in one or more organs of the body.3 Amyloidosis is generally classified according to either the anatomic site of involvement (localized or systemic) or the presence of co-existing diseases (primary or secondary).3,4 Systemic amyloidosis is associated with aging, myeloma, Hodgkin’s disease, chronic infections, or inflammatory disorders. Pulmonary involvement is not an infrequent complication of systemic amyloidoses, although affected patients rarely have significant pulmonary symptoms. By contrast, localized (primary) pulmonary amyloidosis is rare. Localized pulmonary amyloidosis is defined as amyloid deposition isolated to the respiratory tract, and does not include amyloidosis associated with systemic deposition (primary, secondary, or familial).2 Variants of localized pulmonary amyloidosis include the diffuse alveolar septal, nodular, and tracheobronchial types.
Primary amyloid light-chain (AL) amyloidosis usually has a systemic distribution. In our patient, monoclonal B cell proliferation caused the localized deposition of amyloid with a presumed chemically related precursor immunoglobulin lambda light-chain protein. Amyloid light-chain amyloidosis is the most heterogeneous form of the disease; as the fibril protein is unique in each patient, there is a distinct pattern of amyloid deposition in each patient. Virtually any organ system can be involved, and in almost any combination. The clonal B cell diseases that underlie AL amyloidosis also vary enormously: they can be benign or malignant, localized or generalized, and relatively chemosensitive or refractory to treatment. Localized AL amyloidosis is more often identified in the upper respiratory, urogenital, and gastrointestinal tract, in addition to the skin and orbit.5 In these cases, the amyloidogenic light chains are produced by a subtle clone of lymphoplasmacytes that is localized in proximity to the amyloid deposits.6 This type of amyloid is frequently nodular in character, but can occur diffusely throughout a particular tissue when it is associated with a more contiguous infiltrate of clonal cells.6 The biochemical features of localized amyloid can often be confirmed immunohistochemically or by sequencing the fibril protein, but it may not be possible to characterize the associated clonal cells because of their sparsity.
Interestingly, in the patient described here, it was the absence of systemic amyloidosis on rigorous clinical evaluation that corroborated the localized nature of the amyloidosis in association with pulmonary lymphoplasmacytoid lymphoma. In addition, we demonstrated that the amyloid was a light-chain type and that it matched the light-chain immunoglobulin expressed by the neoplastic lymphoma. Therefore, it is likely that the abnormal immunoglobulin was produced by the neoplastic cells and deposited locally in the tissues as light-chain amyloid. The positive result of positron emission tomography in our patient emphasizes the specificity of this imaging technique in characterizing pulmonary nodules, and the importance of confirming suspected malignancy with histology before potentially curative treatment is undertaken. True amyloid deposition may occur in lymphocytic interstitial pneumonitis, lymphoplasmacytic lymphomas, and localized plasma cell dyscrasias. In these disorders, however, the co-existent lymphoid or plasma cytoid proliferation is usually obvious.7 The co-existent pulmonary lymphoplasmacytic lymphoma and localized amyloidosis in our patient mandates further investigation into the pathogenetic mechanisms of pulmonary AL amyloidosis. The presence of amyloid deposits in the lung should raise suspicions of an underlying or concurrent lymphoma.
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REFERENCES
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ABSTRACT
INTRODUCTION
