Recurrent pleural effusions occurring in association with immunoglobulin light chain amyloidosis and not associated with amyloid cardiomyopathy are rare. These portend an overall poor prognosis with mean survival time of approximately 1.8 months. We hereby report a case of a 59-year-old Caucasian female with recurrent pleural effusions and an ultimate diagnosis of pulmonary amyloidosis in association with plasma cell myeloma. The optimal treatment for recurrent pleural effusions in amyloidosis has not been determined; however, our patient responded to therapy with Cyclophosphamide-Bortezomib- (Velcade-) Dexamethasone (CyBorD) and had no repeat hospitalizations or recurrence of pleural effusion at four-month follow-up after initiation of therapy.
Amyloidosis is a rare disorder of protein misfolding and deposition in various organs and tissues [
We hereby present a case report of a 59-year-old female with persistent pleural effusions and diagnosis of primary pulmonary amyloidosis in association with plasma cell myeloma.
A 59-year-old Caucasian female with history of recurrent bilateral pleural effusions was admitted with worsening dyspnea and a nonproductive cough present over the course of one week. She had undergone outpatient right-sided thoracentesis on the day prior to admission, with drainage of 1500 mL of pleural fluid.
The recurrent pleural effusions had been occurring for three months prior to this presentation, and she had undergone thoracentesis twice for the right-sided pleural effusion and six times for the left-sided pleural effusion without any conclusive diagnosis. Results from all of thoracentesis procedures were suggestive of transudative effusions and cultures were negative.
On physical exam, this patient was mildly dyspneic but without retractions or accessory muscle use. There were decreased breath sounds at both lung bases. Temperature was 98.5°F, heart rate was 94/min, respiratory rate was 18/min, blood pressure was 97/55 mm Hg, and oxygen saturations were 99% on room air. Complete blood count and basic metabolic panel showed WBC 8.6 thou/
CT scan of the chest showing bilateral pleural effusions.
Thickened intrapulmonary vessel with adjacent interstitial eosinophilic amorphous material confirmed to be amyloid on Congo Red. (H&E, 100x).
Intrapulmonary interstitial deposits of eosinophilic amorphous material that showed apple-green birefringence under polarized light on Congo Red stains (H&E, 400x).
Pulmonary endothelial lined small vascular structure surrounded by amyloid deposits and marginated by a rim of reactive Type II pneumocytes (H&E, 400x).
The patient underwent hematology/oncology evaluation. Echocardiogram showed left concentric ventricular hypertrophy. Rheumatoid factor and thyroid stimulating hormone levels were normal. Follow-up immunoglobulin and electron microscopy as well as bone marrow biopsy were performed and favored plasma cell myeloma over primary amyloidosis. There were 6% plasma cells on aspirate smears and 15–20% on CD138 immunohistochemical staining of biopsy and clot sections. Flow cytometry showed 1.4% of monoclonal plasma cells typical of a plasma cell dyscrasia.
The patient was started on Cyclophosphamide, Dexamethasone, and Bortezomib (Velcade) therapy and was discharged in stable condition with outpatient follow-up. She had no recurrent pleural effusions at four-month follow-up.
Amyloidosis is a rare disorder that involves the formation of abnormal protein fibrils and deposition of these fibrils within various organs and tissues throughout the body. Amyloid fibrils are composed of low molecular weight protein subunits, which are normally soluble in the plasma [
Amyloidosis can be primary or secondary, systemic or localized, and inherited or acquired. AL amyloidosis is caused by immunoglobulin light chain fibril formation and deposition and is typically thought of as primary amyloidosis. It may occur alone or in association with a plasma cell dyscrasia. AA amyloidosis is caused by fibril formation by the acute phase reactant, amyloid A. This is typically seen in association with chronic diseases of inflammation and is therefore generally thought of as a secondary amyloidosis. Heritable forms of amyloidosis also occur and are generally referred to as AF amyloidosis, or familial amyloidosis. As the name implies, these disorders tend to be familial and associated with consistent patterns of clinical manifestation within families. The incidence of AL amyloidosis is unknown, but has been reported to be about 6 to 10 cases per million person-years [
AL amyloidosis is a systemic disorder that presents with a variety of clinical manifestations depending on the predominantly affected organ system. Commonly involved organ systems include renal, cardiac, gastrointestinal, neurologic, musculoskeletal, hematologic, and dermatologic. Pulmonary involvement has rarely been reported, and published literature has suggested that only 1-2% of patients with systemic amyloidosis develop persistent pleural effusions. We have presented a patient with primary pulmonary AL amyloidosis whose initial presentation was for recurrent bilateral pleural effusions in order to contribute to the current literature for such patients. Our patient was also female and therefore provides information which may later serve as a reference for those who are in the minority of individuals affected by this disease.
Diagnostic criteria have been established by the Mayo Clinic and International Myeloma Working Group and require four criteria to be met for the diagnosis of AL amyloidosis. These include (1) amyloid deposition with distinct organ system involvement, (2) documentation of the presence of amyloid deposition by Congo Red staining, (3) evidence that the amyloid itself is formed by immunoglobulin light-chains, and (4) evidence of a monoclonal plasma cell proliferative disorder. This may be observed with serum or urine M protein, an abnormal serum free light chain ratio, or clonal plasma cells noted within the bone marrow [
In one retrospective analysis, medical records were examined for AL amyloidosis patients that had isolated respiratory system involvement between 1990 and 2011 [
Another published study compared persistent pleural effusions occurring in AL amyloidosis patients with cardiac involvement and those occurring in AL amyloidosis without cardiac involvement. Pleural involvement in this study indicated limited survival where the untreated persistent pleural effusions that occurred alone conferred a median survival of 1.8 months and where untreated persistent pleural effusions that occurred in association with cardiac involvement resulted in a mean survival of 6 months. These findings were found to be statistically significant with a
Various case reports have been published for pleural effusions presenting in cases of AL amyloidosis, and the presentations have been just as varied as amyloidosis has proven to be as a disease overall. There have been case reports of transudative as well as exudative pleural effusions (which appear to occur in about the same frequency) [
It should be noted that pleural effusions might occur in AL amyloidosis as well as AA amyloidosis and Senile Systemic Amyloidosis [
Current treatment guidelines for AL amyloidosis involve the use of chemotherapy and autologous stem cell transplantation [
In another published report, a patient that had diffuse parenchymal pulmonary amyloidosis was treated with melphalan, prednisolone, and Bortezomib chemotherapy [
Pleural effusions occur rarely in cases of systemic amyloidosis and have variable pleural fluid compositions. Because they portend a poor prognosis with a mean survival of 1.8 months when they occur in patients with AL amyloidosis, prompt diagnosis is critical in order to initiate treatment, which may improve pulmonary function and oxygenation and ultimately improve survival. This case provides an additional report of pleural effusions as they presented in a patient with AL amyloidosis and documents a current case being treated with CyBorD therapy.
The authors of this paper declare that there is no conflict of interests.