Amyloidosis is a clinical disorder caused by extracellular deposition of insoluble abnormal fibrils in various organs and is derived from the aggregation of misfolded, normally soluble, proteins (1). Primary pulmonary amyloidosis is a relatively rare pattern of amyloidosis that is confined to the lungs and associated structures without any other organ involvement. It occurs in 3 patterns: tracheobronchial, diffuse interstitial and nodular parenchymal (2). Radiographically, the lesions of primary nodular parenchymal pulmonary amyloidosis may be single or multiple, and are able to calcify or cavitate. It is usually considered in the differential diagnosis of pulmonary primary or metastatic neoplasms. In the present study, we report a case of primary nodular parenchymal pulmonary amyloidosis and review the literature for related cases in Medline (1970-October 2011) and Embase (1989-October 2011).

We identified 19 articles (3–21) describing primary nodular parenchymal pulmonary amyloidosis in Medline and Embase. Data on clinical presentation, radiographic pattern, biopsy and survival of 58 patients (including our case) are summarized in Table I. Ages ranged from 44 to 89 years and, consistent with previous findings, the average age of the patients was in the sixth decade (9,12,16). There were 8 male and 12 female cases, while the gender was not indicated in 38 cases. The patients were usually asymptomatic, and the amyloidosis was discovered accidentally on routine chest radiography. Few of these cases were associated with cough or hemoptysis. Radiologically, the nodular parenchymal pattern appeared as solitary or multinodular infiltrates in any lobe, usually mimicking neoplastic growth. Nodules ranged in diameter from 1 to 4 cm, with 15 cm being the largest nodule reported in the literature (22). Biopsy data were available for 22 patients. Of these 22 patients, nodule resection was conducted in 9, lobectomy was conducted in 8, and percutaneous FNA biopsy was conducted in 5. Patients with a nodular parenchymal pattern were all in good condition during follow-up.

Amyloidosis is a disease caused by extracellular amyloid deposits (23). Amyloid fibres are formed by the folding of various fibril precursor proteins into an alternative conformation rich in β-sheet structures. This characteristic structure results in specific staining with Congo red dye that yields an apple-green birefringence under polarized light microscopy. The genetic and/or environmental factors in individual susceptibility to amyloid deposition have not been elucidated (22). Primary pulmonary amyloidosis is characterized by amyloid deposition in the lungs and other associated structures. Radiologically, the primary nodular parenchymal pulmonary amyloidosis appear as single or multiple nodules in any lobe, and should be considered in the differential diagnosis of pulmonary primary or metastatic neoplasms. In our study, there is no specific examination for the preoperative diagnosis of primary nodular parenchymal pulmonary amyloidosis without the presence of classic clinical findings, laboratory tests and radiological results. The final diagnosis usually requires histological confirmation.

The optimal technique for biopsy is uncertain. In our study, open lung biopsy was the most commonly used method for obtaining biopsy material, but it was more invasive than CT-guided percutaneous FNA biopsy. It is worth noting that CT-guided percutaneous FNA biopsy has also been used when a less invasive approach is necessary and 5 cases of our study were diagnosed solely on the basis of material obtained by percutaneous FNA biopsy, avoiding unnecessary invasive surgical resection. Once the diagnosis is clear, nodular parenchymal amyloidosis rarely requires treatment, which may involve surgical resection if a large nodule causes a space-occupying effect. Additionally, the majority of patients with a nodular parenchymal pattern were in good condition during follow-up.

¹⁸F-FDG PET/CT is most widely used for cancer detection by revealing which tissues have a high metabolic rate and take up greater amounts of glucose in comparison to the surrounding tissues. To a certain extent, the high metabolic rate usually correlates with more aggressive tumors and a greater number of viable tumor cells (24). The use of ¹⁸F-FDG PET/CT for the diagnostic workup of pulmonary nodules to reduce inappropriate invasive diagnostic investigation and subsequent complications is emerging. Duhaylongsod et al (25) reported that the SUV of ¹⁸F-FDG uptake in malignant nodules (SUV≥2.5) was greater than benign pulmonary nodules; the sensitivity, specificity and accuracy were 97, 82 and 92%, respectively. However, ¹⁸F-FDG is known to have little uptake in malignancies with low metabolic activity, including bronchoalveolar cancer, carcinoid tumor and mucinous adenocarcinoma. Furthermore, certain noncancerous conditions may also demonstrate high metabolic rates (26). Increased ¹⁸F-FDG activity has been demonstrated in cases of tuberculosis, sarcoidosis, fungal disease, interstitial lung disease, osteoarthritis, vascular thromboses, osteoporosis and rheumatoid nodules (27–29). The reason that noncancerous conditions uptake ¹⁸F-FDG may be due to lesions with a high concentration of inflammatory cells, including neutrophils and activated macrophages, which increase glucose uptake (30,31). Our case and the case reported by Seo et al (21) exhibited multiple lung nodules of pulmonary amyloidosis with moderate ¹⁸F-FDG uptake, and an SUVmax of 1.19 and 1.8, respectively. Our results suggest that positive results of ¹⁸F-FDG PET/CT on pulmonary nodules should be interpreted with caution in differentiating pulmonary nodular amyloidosis from malignant lesions.

In conclusion, primary nodular parenchymal pulmonary amyloidosis is a relatively rare condition without classic clinical findings, laboratory tests and radiological results. Despite its rarity, primary nodular parenchymal pulmonary amyloidosis with a pattern of multiple nodules should be cautioned with the differential diagnosis of pulmonary metastases with high ¹⁸F-FDG uptake on PET/CT.