Anterior Mediastinal Amyloidosis Mimics Thymic Carcinoma

In October 2019, a 71-year-old woman was referred to our hospital for the investigation of a mediastinal tumor-like mass found in a routine chest radiograph and computed tomography (CT). The chest CT revealed an anterior mediastinal mass containing necrotic or cystic areas and calcification (Fig. 1A). The patient did not report any symptoms. The serum levels of alpha-fetoprotein, beta-human chorionic gonadotropin, lactate dehydrogenase, and soluble interleukin-2 receptor were not elevated. The test for anti-acetylcholine receptor antibody was negative. Positron emission tomography–CT (PET-CT) revealed high fluorodeoxyglucose F 18 (¹⁸F-FDG) accumulation at the site of the mass (maximum standardized uptake value of 5.9) (Fig. 1B). Based on these findings, we strongly suspected that the anterior mediastinal mass was a thymic carcinoma. CT and magnetic resonance imaging revealed that the adjacent organs were not invaded; thus, mass resection and total thymectomy were performed. Macroscopically, the resected mass was a solid, hard, and yellow nodule measuring 100 mm by 60 mm by 30 mm and resembled a dried mango (Fig. 2A). The cut section was extremely hard and calcified. Microscopically, the mass was composed of amorphous eosinophilic substances surrounding thymic tissues and contained calcification and ossification in the middle (Fig. 2B). The apple-green birefringence of the eosinophilic substances on polarized light microscopy after direct fast scarlet staining confirmed the diagnosis of amyloidosis. Immunohistochemical analysis revealed that the substances were positive for kappa light chains but negative for lambda light chains, serum amyloid A, and amyloid transthyretin (Fig. 2C). Moreover, laser microdissection–liquid chromatography–tandem mass spectrometry revealed the predominance of kappa light chains (86%). These findings were consistent with kappa-type light chain amyloidosis. When reviewing an initial CT, thin-walled cysts scattered predominantly in the bilateral lower lung fields were observed. Subsequently, a positive test for antibodies against Sjogren syndrome-related antigen A and also the presence of focal lymphocytic sialadenitis on labial salivary gland biopsy confirmed the diagnosis of Sjogren syndrome. On the basis of these results, this patient was diagnosed with localized nodular mediastinal amyloidosis associated with Sjogren syndrome.

Figure 1.

(A) Chest computed tomography revealed an anterior mediastinal mass containing necrotic or cystic areas and calcification. (B) Positron emission tomography–computed tomography revealed high fluorodeoxyglucose F-18 accumulation at the site of the mass (a maximum standardized uptake value of 5.9).

Figure 2.

(A) Macroscopically, the resected mass was a solid, hard, and yellow nodule resembling a dried mango. (B) The mass was composed of amorphous eosinophilic substances surrounding thymic tissues (Hematoxylin and eosin staining, ×400 magnification). Calcification and ossification were also noted in the middle. (C) Immunohistochemical analysis revealed that the substances were positive for kappa light chains (×400 magnification).

An anterior mediastinal mass is a rare presentation of amyloidosis,¹ but localized tumor-like deposits of amyloids may occur in any of the mediastinal components.² In this patient, we initially determined that there was a high probability of thymic carcinoma on the basis of the radiologic findings, which included necrotic or cystic changes and calcification noted in CT and ¹⁸F-FDG accumulation in PET-CT. However, the calcifications in CT were nonspecific and irrelevant for clinical and radiologic diagnosis of thymic carcinoma.³ PET-CT is often performed for an anterior mediastinal mass suspected of thymic tumor or other malignancy because PET-CT results are often negative in more well-differentiated thymomas but are highly positive in thymic carcinomas.⁴ However, ¹⁸F-FDG PET-CT imaging can be misleading because nonmalignant conditions such as teratoma and thymic cysts and even a normal thymus could occasionally be reported as having ¹⁸F-FDG accumulation.⁵ Oncologists and chest physicians should be aware that histopathologic diagnosis is still the only way to confirm the neoplastic nature of an anterior mediastinal mass.