Ann Thorac Surg 2005;80:344-347
© 2005 The Society of Thoracic Surgeons
Case report
Clonal Light Chain Restricted Primary Intrapulmonary Nodular Amyloidosis
Patrick Ross, Jr, MD, PhDa,*,
Cynthia M. Magro, MDb
a Division of Cardiothoracic Surgery, The Ohio State University, Columbus, Ohio
b Department of Pathology, The Ohio State University, Columbus, Ohio
Accepted for publication January 14, 2004.
* Address reprint requests to Dr Ross Jr, Division of Cardiothoracic Surgery, The Ohio State University, N839 Doan Hall, 410 W 10th Ave, Columbus, OH43210 (Email: ross-3{at}medctr.osu.edu).
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Abstract
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Primary intrapulmonary nodular amyloidosis is a rare form of immunoglobulin associated amyloidosis, also falling under the alternative appellation of amyloidoma. Although amyloidomas in other organ sites may be reflective of a localized or more generalized plasma cell dyscrasia, in the context of its presentation in the lung the presumptive basis has long been held to be one of chronic inflammation. We encountered 2 patients with nodular amyloidosis in whom the pathologic examination disclosed the basis to be one of a light chain restricted clonal lymphocytic plasma cell infiltrate, although without morphologic features of coexisting pulmonary lymphoma. These 2 patients serve to underscore the potential categorization of some cases of pulmonary nodular amyloidosis as a form of low grade B cell lymphoproliferative disease.
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Introduction
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Amyloidosis represents the deposition of a protein matrix. Although heterogeneous in derivation, its morphologic expression is similar light microscopically and ultrastructurally. The commonest forms of amyloidosis are (1) light chain immunoglobulin derived from plasma cells, and (2) a nonimmunoglobulin protein synthesized by the liver-designated amyloid associated protein. Both forms may be associated with multiorgan involvement, defining systemic amyloidosis. The lung parenchyma and tracheobronchial tree may comprise two critical sites of amyloid deposition in this setting. However, it is also apparent that amyloid deposition may occur in the lung in the absence of extrapulmonary involvement, defining localized amyloidosis. Localized pulmonary amyloidosis is held to represent a form of light chain associated amyloidosis [1].
In contrast to the North American experience, which emphasizes its origin from reactive polyclonal plasmacellular infiltrates [1], authors from Japan and Germany have described primary nodular amyloidosis associated with monoclonal plasma cell infiltrates, therefore reflective of low grade B cell lymphoproliferative disease [2–9]. We report the first two North American cases of primary intrapulmonary nodular amyloidosis associated with a clonal light chain restricted plasmacellular infiltrate.
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Case Reports
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Patient 1
This 60-year-old woman presented in the summer of 2003 with a pneumothorax. Radiographic studies at that point in time revealed a right lung mass. Specifically, computed tomography of the chest revealed a 2.3 x 2.7 cm mass involving the lateral segment of the middle lobe as well as two smaller subpleural nodules, more anteriorly in the middle lobe measuring roughly 7 mm in size and 1.1 cm, respectively (Figs 1–3). A fine needle aspiration was interpreted as representing nonsmall cell carcinoma. The patient was referred for surgical staging and possible resection.
At right thoracotomy and bronchoscopy discrete nodules were found within all lobes. The patient underwent a wedge resection of a 1.5 x 2 cm lower lobe mass and two nodules of the upper lobe were performed; the lesions were benign on frozen section. Therefore, the dominant mass was then resected in its entirety by performing a middle lobectomy. Final pathology demonstrated amyloidosis. Subsequent investigations, including bone marrow evaluation, failed to disclose any evidence of lymphoma and or amyloidosis elsewhere and as well there was no serum or urine detection of a monoclonal paraprotein.
Patient 2
This 73-year-old woman presented with asymptomatic nodules involving the left upper lobe discovered on routine radiographic assessment. At left thoracotomy was performed revealing multiple white nodules involving the upper and lower lobes. Resection of the nodules was undertaken.
Her postoperative course was uneventful. She is currently alive and well without evidence of lymphoma, recurrent amyloidosis and/or features suggestive of extrapulmonary amyloidosis.
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Comment
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We have presented two cases of localized intrapulmonary nodular amyloidosis, whereby the pathologic evidence of their categorization was low grade B cell lymphoproliferative disease and more specifically, localized forms of plasma cell dyscrasia. First, light chain restricted plasmacellular infiltrates were observed in both cases, one with cardinal features of B cell neoplasia. Second, both cases had an accompanying small lymphocytic infiltrate composed almost exclusively of B cells in contrast to reactive intrapulmonary lymphocytic infiltrates that are usually composed of T cell lineage. Finally, the microdissected lymphocytic and plasmacellular infiltration in the cases revealed a clonal pattern and an oligoclonal pattern of heavy chain immunoglobulin rearrangement in patients 1 and 2, respectively. This finding indicates the emergence of a single clone (clonal) or few clones (oligoclonal) of B cells, molecular findings characteristic of B cell lymphoproliferative disease.
Nine cases of primary pulmonary nodular amyloidosis associated with a light restricted plasma cell infiltrate have been reported [2–9]. The mean age of presentation was 60 years with an equal gender distribution. Asymptomatic nodules apparent on imaging studies, pleural effusions, and pneumothorax were among the clinical presentations. A serum monoclonal gammopathy was uncovered in 2 patients. In one patient, the lung nodules presaged amyloid deposition in the kidney by 10 years. Another patient presented initially with an eyelid marginal zone lymphoma. Two patients had Sjögren’s syndrome.
The differential diagnosis for our cases includes pulmonary marginal zone lymphoma with secondary light chain restricted amyloidosis. Indeed pulmonary marginal zone lymphoma coexisting with parenchymal deposits of amyloid has been described [1, 10]. Marginal zone lymphoma of the lung is a low grade B cell lymphoma typically accompanied by a monoclonal plasmacytic infiltrate [11]. We would not use the designation of marginal zone lymphoma in either case as the dominant morphology was one of amyloid deposition with only small perivascular and peribronchial collections of B lymphocytes. In contrast, malignant lymphoma with or without amyloid deposition is characterized by extensive B cell infiltration, typically associated with architectural effacement of the lung parenchyma [1, 10].
In summary, we recommend careful pathologic evaluation of cases of nodular pulmonary amyloidosis to explore underlying low grade B cell lymphoproliferative disease. Hematologic dyscrasia is not typically considered a surgical disease. However the one exception is localized low grade extranodal B cell lymphoproliferative disease comprising extramedullary plasmacytomas, marginal zone lymphoma, follicular lymphoma, and light chain restricted amyloidomas. Low grade B cell lymphoma of the lung treated with lobectomy with or without adjuvant radiation therapy is associated with almost 100% 5-year survival [11]. Patients treated exclusively with surgery have rarely experienced relapses. In the Lim and colleagues’ [10] series, patients with amyloidosis coexisting with marginal zone lymphoma had local resection with 5 of 6 patients without evidence of disease. In five cases of pulmonary plasmacytoma, all underwent primary resection of their tumors with long-term survival in 2 patients [12]. Likely the best treatment option for light chain restricted intrapulmonary nodular amyloidosis would be definitive surgical resection with careful assessment for evidence of extrapulmonary disease.
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Fig 3. There is a predominance of kappa staining plasma cells, whereas PCR studies from DNA microdissected from this area (A) show a single band in samples 2 and 3 from patient 2 of this study, (B) revealing a dominant band compatible with clonal patterns.
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References
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Abstract
Introduction
