Interact CardioVasc Thorac Surg 2009;9:903-905. doi:10.1510/icvts.2009.210229
© 2009 European Association of Cardio-Thoracic Surgery
Case report - Thoracic oncologic |
Thymic neuroblastoma with the syndrome of inappropriate secretion of antidiuretic hormone
Fumihiro Ogawa,
Hideki Amano,
Akira Iyoda and
Yukitoshi Satoh*
Department of Thoracic Surgery, Kitasato University School of Medicine, 1-15-1, Kitasato, Sagamihara, Kanagawa 228-8555, Japan
Received 24 April 2009;
received in revised form 17 July 2009;
accepted 20 July 2009
 A part of this study was supported by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (No. 20591676), as well as a grant from the Ministry of Health, Labour and Welfare, Japan (No. 19-12).
*Corresponding author. Tel.: +81-427-788111; fax: +81-427-789840.
E-mail address: ysatoh{at}med.kitasato-u.ac.jp (Y. Satoh).
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Abstract
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We describe a rare case of thymic neuroblastoma with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). A 60-year-old male patient was admitted to our hospital for further examination and treatment of anterior mediastinal tumor found at a regular health check-up. On examination there was hyponatremia, decrease in plasma osmolarity and elevation of plasma antidiuretic hormone (ADH) level. Thus, he underwent total thymectomy under the diagnosis of thymoma with SIADH. The tumor was located in the right lobe of the thymus and the final diagnosis was thymic neuroblastoma. To our knowledge, this is the first reported case of thymic neuroblastoma in which production of ADH by tumor cells is demonstrated immunohistochemically. This case highlights the need to consider functional activity of thymic neuroblastoma and complete resection of the tumor is warranted for treatment.
Key Words: Anterior mediastinal tumor; Neuroblastoma; Syndrome of inappropriate secretion of antidiuretic hormone
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1. Introduction
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The neuroblastoma is a tumor of the sympathetic nervous system. It most commonly occurs in the 2–4-year age group of children, and is extremely rare in adults [1, 2]. Although, many neuroblastomas occur in the posterior mediastinum only nine primary anterior mediastinal examples have been reported [3]. We here describe a very rare case of thymic neuroblastoma in an adult with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH).
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2. Case report
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A 60-year-old Japanese man was admitted to Kitasato University Hospital for further examination and treatment of a chest abnormal shadow found at a regular health check-up. Chest X-rays showed a solid mass with a clear border at the right hilum and a positive silhouette sign for the right first arch (Fig. 1a). Enhanced chest computed tomography (CT) revealed a 47-mm sized solid mass with a clear rim in the anterior mediastinum (Fig. 1b). Magnetic resonance imaging (MRI) using intravenous contrast showed iso-intensity and high-intensity of the mass on T1- and T2-weighted images, respectively. Based on chest CT and MRI there was no invasion to adjacent organs. Important laboratory findings were a serum sodium concentration of 119 mEq/l, a plasma osmolarity of 261 mEq/l and an elevated plasma antidiuretic hormone (ADH) level of 6.4/l.
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Fig. 1. Chest X-ray showing a solid mass with a clear border at the right hilum and a positive silhouette sign for the right first arch (a). Enhanced chest CT-scan revealing a 47-mm sized solid mass with a clear rim in the anterior mediastinum (b).
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Under the diagnosis of thymoma with the SIADH, he underwent total thymectomy. The tumor was located in the right lobe of the thymus without any invasion to adjacent organs such as aorta, superior vena cava, pericardium, bilateral phrenic nerve, bilateral parietal pleura, and right lung. Serum sodium levels and blood osmolarity quickly returned to normal after the tumor removal.
Macroscopically, the tumor surrounded by thymic fat tissue was 45 mm in diameter and elastic with a clear border. Its cut surface was yellowish-gray, lobulated and well-circumscribed with a thin fibrous capsule clearly separated from the tumor to the thymic tissue.
Microscopically, the tumor had lobular structure consisting of small uniform cells having round and hyperchromatic nuclei, indistinct cell borders, and abundant fibrillary eosinophilic matrix material. Scattered large cells with eosinophilic cytoplasm were considered to be cells featuring differentiation to gangliocytes (Fig. 2a). The tumor had a fibrous capsule without invasion to the surrounding atrophic thymic tissue.
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Fig. 2. The tumor cells feature round and hyperchromatic nuclei, indistinct cell borders, and abundant eosinophilic matrix material with a neuropil structure. Note scattered large cells with abundant eosinophilic cytoplasm (hematoxylin and eosin staining, x100; a). Immunohistochemically, the tumor cells proved positive for ADH staining (x400; b). In an electron micrograph, many neuroendocrine granules are evident in the cytoplasm (c).
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Immunohistochemically, the tumor cells were positive for neuroendocrine markers such as neuron specific enolase (NSE), synaptophysin and chromogranin A, and also ADH (Fig. 2b). Under the electron microscope, the cytoplasm of the tumor cells contained many neuroendocrine granules (Fig. 2c). Based on the above findings, the final diagnosis was thymic neuroblastoma.
Although the patient was provided with detailed information about the disease, he did not desire adjuvant therapy after the operation, and was therefore strictly followed-up as an outpatient.
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3. Discussion
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Primary neuroendocrine neoplasms occurring in the mediastinum are very rare and a review of literature disclosed only nine reported cases of primary anterior mediastinal neuroblastoma during the past forty years [3]. Among these cases only four were associated with SIADH. The exact origin of neuroblastomas in the thymus is still debated [3] and different theories have been proposed as follows: (1) genesis from autonomic ganglia located in the thymus with innervations from cervical sympathetic ganglia; (2) origin from neuroectodermal cells residing in the thymus; (3) genesis from progenitors of thymic epithelial cells with the potential to differentiate along neural lines; and (4) malignant transformation of mediastinal residual teratomas [3]. Since our case was completely separated from thymic tissue and phrenic nerve and had no teratoma components, it was considered probable that the tumor arose from autonomic ganglia or neuroectodermal cells residing in the thymus.
The mediastinal tumor most commonly associated with SIADH is the metastatic pulmonary small cell carcinoma; 15% of such tumors were associated with SIADH in one series [3]. The particular interest is that SIADH is closely associated with ectopic secretion of ADH by neoplastic cells [4, 5]. Immunohistochemical studies demonstrated inappropriate ADH production and secretion to be caused by neuroblastoma in our case. If the progenitor of ADH-producing thymic epithelial cells also can differentiate along neural lines, the association between thymic neuroblastoma and SIADH would be easier to explain. The present case also supports the possibility that this type of tumor in other regions could cause SIADH.
Since thymic neuroblastoma in adults is very rare, a standard therapy has yet to be established [6, 7]. However, from our findings we consider that complete resection of the tumor with careful follow-up is warranted.
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Acknowledgements
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The authors thank Drs Masaomi Kikuchi, Mitsugu Tokuyama, Tetuo Mikami, Jiang Shixu and Isao Okayasu, Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan, for the pathologic diagnosis and Dr Kenji Nezu, Department of Thoracic Surgery, Kitasato University School of Medicine, Kanagawa, Japan, for clinical support.
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Abstract
1. Introduction
