Sclerosing thymoma-like thymic amyloidoma with nephrotic syndrome: a case report

This case report presented a patient with sclerosing thymoma-like thymic amyloidoma that showed marked reduction in tumor size when steroids were administered for paraneoplastic nephrotic syndrome. Our patient was receiving palliative treatment because she could not undergo resection due to her age and pericardial dissemination.

The most common types of amyloidosis are light chain amyloidosis (AL amyloidosis) and AA amyloidosis. AL amyloidosis is associated with an underlying monoclonal plasma cell disorder. AA amyloidosis is associated with chronic inflammatory conditions, such as autoimmune diseases. In our case, our patient did not have any history of autoimmune diseases, multiple myeloma, or dialysis treatment. Nobody in her family had a history of amyloidosis. Immunohistochemical studies were negative both for kappa and lambda light chains and for AA amyloidosis. M protein was negative, and there was no evidence of systemic amyloidosis in clinical investigations.

Amyloidomas in the mediastinum are extremely rare, especially in the thymus. Only five cases of thymic amyloidosis have been reported to date [2‐6] (Table 2). The average age of the five cases of thymic amyloidosis reported so far was 53 years (33 to 85 years). One of the cases was male and the other four were female. There may be no clinical symptoms in some cases. Tumor diameter was 6.3 cm on average, and total thymectomy was performed in all cases. Four cases were positive for AL amyloidosis or AA amyloidosis; however, there was a case (Case number 5) that was negative both for AL amyloidosis and AA amyloidosis. Two cases were complicated with myasthenia gravis, and they had steroid therapy before surgery. Our case showed a marked reduction in tumor size after steroid therapy, but information was not available on whether the reported two cases showed a reduction in tumor size after steroid therapy.

Sclerosing thymoma is a rare thymoma subtype, which was first reported in 1994 by Kuo [7]; 14 cases have been reported to date. The clinical characteristics and causes remain unclear, and even its existence is not well known. On histological examination, it is characterized by a lesion that has extensive hyalinization of fibrous tissue [8]. The differential diagnosis for an anterior mediastinal mass with extensive fibrosis includes: solitary fibrous tumor, Hodgkin’s lymphoma (nodular sclerosing type), mediastinal diffuse large cell lymphoma with sclerosis, and amyloidoma. The different type of fibrosis for each of the tumors becomes important for differential diagnosis. A solitary fibrous tumor is characterized by proliferation of keloid-like collagen fibers around cluster of differentiation (CD) 34-positive cells. Hodgkin’s lymphoma (nodular sclerosing type) is characterized by multinodular arrangements of birefringent collagen fibers around the lesions, and the presence of lacunar cells. Mediastinal diffuse large cell lymphoma has a characteristic histology known as compartmentalization, where each tumor cell is surrounded by hyalinized fibrous components. Thymoma itself may at times show strong fibrosis; however, strongly convoluted hyalinized fibrosis is a characteristic of sclerosing thymoma [9]. In the present case, sclerosing thymoma is one of the differential diagnoses because the tumor consisted of strongly convoluted hyalinized fibrosis and epithelial cells possibly derived from the thymus. The 14 cases of sclerosing thymoma reported so far had an average age of 49 years (23 to 73 years); our case was the eldest. There were seven males and seven females. There may be no clinical symptoms in some cases. Chest pain and dyspnea may occur, and patients with myasthenia gravis may have muscle weakness. Three cases were complicated with myasthenia gravis. Tumor diameter was 5.6 cm on average, and total thymectomy was performed in all cases (Table 3). Tumor cell nests are not evident in the small specimens from needle biopsies because sclerosing thymoma consists of extensive hyalinization of fibrous tissue [8]. It is difficult to obtain a definitive diagnosis. The present case was diagnosed by thoracoscopic needle biopsy. The intraoperative findings showed firm adhesion of the left S1+2 and the mediastinal side. However, as induration was felt at the same location, four needle biopsies were performed using 20-gauge single-use tissue biopsy needle. When hyalinized fibrous tissue is collected from a biopsy of an anterior mediastinal mass, sclerosing thymoma should be considered one of the possibilities in the differential diagnosis. Special attention must be given to tumors found in the thymus gland that are composed primarily of fibrous tissue by, for example, preparing serial sections of the entire tumor, to ensure that minute thymomas are not overlooked. Relating to needle biopsy, fine needle aspiration techniques usually suffice for carcinomatous lesions but a cutting needle biopsy should be performed whenever possible. It is important to obtain larger specimens for a more accurate histological diagnosis [10]. Using 18 to 20-gauge biopsy needle, the diagnostic sensitivity and specificity of CT-guided percutaneous cutting needle biopsy for thymic tumors were 93.3 and 100% [11]. Therefore, our diagnosis is considered to be quite accurate.

While thymomas are the most common anterior mediastinal tumors, they are relatively rare, with an incidence of 1.5 cases per million people [12, 13]. The etiology is unknown. Approximately 30 to 50% of patients with thymoma develop comorbid myasthenia gravis [14]. Our case was not complicated with myasthenia gravis. The Masaoka staging system (modified) is most commonly used for the management of thymomas and prognosis prediction. This case was diagnosed as Masaoka stage IVa with pericardial dissemination because pericardial invasion was observed. The 5-year survival rate of patients with stage I to III thymoma is approximately 85%, and that of patients with stage IV is around 65% [15‐17]. In approximately 50% of patients, thymoma is not related to the cause of death [18]. On the other hand, myasthenia gravis is related to the cause of death in approximately 20% of patients. Surgery is recommended for all surgically resectable thymoma cases (complete resection of the thymus gland and the tumor). Completeness of resection is the most important factor for prognosis. Even for stage IV thymomas, multimodality treatment with possibly complete resection is recommended [19‐21]. The prognosis of sclerosing thymoma is unknown. Some cases are lost to follow-up, but some cases died of heart failure or pulmonary edema even in young patients. Since our case was diagnosed as having sclerosing thymoma (stage IVa)-like thymic amyloidoma, total thymectomy should be recommended, but she could not undergo resection due to her age and pericardial dissemination.

There are many reported cases of nephrotic syndrome as a secondary complication of malignant tumors and connective tissue disease; however, nephrotic syndrome as a complication in patients with thymoma is rare. In nephrotic syndrome associated with thymoma, many patients develop: (1) membranous nephropathy when the onset of nephrotic syndrome occurs concurrently with the thymoma; and (2) MCNS when the onset occurs after thymus resection [22]. In the present case, a definitive diagnosis of MCNS was not established since a kidney biopsy was not performed; however, based on the selectivity index, its selectivity of urinary protein was high. Therefore, MCNS was clinically diagnosed and steroid administration was started as treatment for nephrotic syndrome, which resulted in a marked reduction in tumor size. Steroid treatment has been shown to be effective in not only improving nephrotic syndrome and renal failure, but also in the regression of thymoma [23, 24]. Steroid treatment has provided successful results in thymoma, even when nephrotic syndrome is not a secondary complication. Glucocorticoid reactions that induced apoptosis of thymoma cells are thought to be triggered when steroids bind to glucocorticoid receptors in thymoma cells, resulting in the regression of thymomas [22]. There are only 14 reported cases of sclerosing thymoma in the world, and the treatment method has not yet been established.