Systemic Amyloidosis Mimicking Lung Cancer

An 80-year-old woman presented to our multidisciplinary Lung Nodule Clinic with a remote 20-pack-year smoking history and an irregular, solid left upper lobe pulmonary nodule found on workup for a persistent cough of 2 years’ duration. The lesion was followed with serial computed tomography and showed growth from 8.7-mm maximal and 6-mm mean diameter to 12.4-mm maximal diameter and 11-mm mean diameter over 2 years, and demonstrated mild focal uptake on fluorodeoxyglucose–positron emission tomography (Figure 1). At an outside hospital, she received recommendations to undergo either resection or stereotactic body radiation therapy for presumed lung cancer. We recommended excision over stereotactic body radiotherapy because of the lesion’s proximity to the mediastinum.

Figure 1.

(A and B) Serial axial computed tomography images of the thorax in lung windows demonstrate the left upper lobe pulmonary nodule at baseline (arrow, A) and after 12 months (arrow, B). (C and D) Serial axial computed tomography images without (arrow, C) and with (arrow, D) fluorodeoxyglucose–positron emission tomography obtained 24 months after baseline demonstrate interval growth and mild focal uptake, respectively.

A thoracoscopic wedge resection was performed. Pathological examination revealed eosinophilic, anucleate material with both nodular and subtle diffuse interstitial involvement. No neoplastic cells were present. Congo Red staining confirmed amyloid deposition (Figure 2). Mass spectrometry revealed wild-type transthyretin amyloid, consistent with the diffuse interstitial amyloid pattern (1). Subsequently, the patient received a clinical diagnosis of systemic amyloidosis.

Figure 2.

(A and B) Histologic images of lung wedge resection, including hematoxylin and eosin–stained sections of the interface between the pulmonary nodule and normal lung (A, 5× magnification on whole slide imaging [WSI]; scale bar, 250 μm) and the anucleate eosinophilic amyloid material (B, 40× magnification on WSI; scale bar, 50 μm). (C and D) Congo Red–stained sections of interstitial amyloid under unpolarized (C, 200× magnification; scale bar, 100 μm) and polarized (D, 200× magnification; scale bar, 100 μm) light demonstrate the classical apple-green birefringence of the interstitial amyloid under polarized light. The images in A and B were acquired as a secondary capture from a 5× (2 μm/pixel) and 40× (0.25 μm/pixel) WSI system (Philips), respectively.

Solitary pulmonary amyloidomas are known mimickers of malignancy on computed tomography and positron emission tomography imaging (2). In contrast, systemic amyloidosis infrequently involves the lung in a clinically significant fashion, especially as the first site, and rarely presents as a solitary lung nodule (3–5). Through histological examination and mass spectrometry, this patient’s presumed lung malignancy was discovered to be undiagnosed systemic transthyretin amyloidosis with primary lung involvement.