Solitary Fibrous Tumor of the Thymus with Local Invasiveness and Pleural Dissemination: Report of a Case
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1 Case Report Solitary Fibrous Tumor of the Thymus with Local Invasiveness and Pleural Dissemination: Report of a Case Takashi Iwata, MD 1, Noritoshi Nishiyama, MD, 1 Nobuhiro Izumi, MD, 1 Takuma Tsukioka, MD, 1 and Shigefumi Suehiro, MD 2 A 74-year-old asymptomatic female presented with an anterior mediastinal mass incidentally discovered on a routine chest X-ray. Systemic evaluation demonstrated no metastatic lesions. The patient underwent an extended thymectomy via median sternotomy on suspicion of a thymoma. The tumor had arisen from the left half of the thymus without a pedicle and had directly invaded into the left lung and pericardium. The tumor was resected with the entire thymic tissue, and the invaded lung and pericardium were resected en-bloc. The size of the tumor was cm. A disseminated lesion on the mediastinal pleura was also resected. Histopathologically, the lesion mainly consisted of non-atypical spindle-shaped tumor cells in a so-called patternless pattern with various densities of collagenous background. Pleomorphism and mitoses were not significant. Immunohistochemical analysis revealed mesenchymal positive markers such as vimentin and CD34. Epithelial markers such as CAM 5.2 and AE1/AE3 were negative. S-100 protein and desmin were not stained. Solitary fibrous tumor of the thymus was diagnosed histologically. Postoperative adjuvant chemotherapy or radiotherapy was not undertaken because the benefits were uncertain. She is well without recurrence 3 months after the operation. (Ann Thorac Cardiovasc Surg 2007; 13: ) Key words: adult, neoplasm, solitary fibrous tumor, thymoma, mediastinum Introduction Solitary fibrous tumor (SFT) is a mesenchymal tumor often arising from the pleura and usually showing a benign clinical course. We herein report a rare case that was considered to originate in the thymus and showed clinically malignant behavior such as pleural dissemination and direct invasion into the lung, although without histologically malignant features. Case A 74-year-old female presented with an abnormal medi- Departments of 1 Thoracic and 2 Cardiovascular Surgery, Osaka City University Hospital, Osaka, Japan Received October 6, 2006; accepted for publication October 26, 2006 Address reprint requests to Takashi Iwata, MD: Department of Thoracic Surgery, Osaka City University Hospital, Asahimachi, Abeno-ku, Osaka , Japan. astinal shadow in a routine follow-up chest X-ray after a pacemaker implantation 9 years previously (Fig. 1). She was asymptomatic and had no history of asbestos exposure. A chest computed tomography (CT) revealed a large round mass in the anterior mediastinum, just anterior to the heart (Fig. 2). All tumor markers were within the normal ranges. Systemic evaluation demonstrated no metastatic lesions. The patient underwent an extended thymectomy via median sternotomy on suspicion of thymoma. The tumor had arisen from the left half of the thymus without a pedicle, and had invaded directly into the lung (Fig. 3A). The part of the lung with the tumor was resected. The adjacent pericardium seemed to be invaded and was resected with the tumor. The size of the tumor was cm. One disseminated lesion, with a diameter of approximately 1.5 cm, was observed on the mediastinal pleura and was also resected. The cut surface revealed a yellowish-white solid tumor with partial cystic degenerations. (Fig. 3B). She complained of muscle weakness in the right upper limb 8 hours after the operation. 198 Ann Thorac Cardiovasc Surg Vol. 13, No. 3 (2007)
2 Solitary Fibrous Tumor of the Thymus Fig. 1. Chest X-ray demonstrates a smooth-surfaced, welldemarcated mass overlapping the heart (arrows). Fig. 3. A: Gross specimen. The tumor seemed to originate from the thymus. B: The cut surface of the specimen shows a yellowish-white, well-encapsulated solid tumor tissue with clear demarcation; approximately 5 cm in diameter. Cystic degeneration was observed. Necrotic or hemorrhagic portions were absent. Fig. 2. Computed tomography shows a large mass in the anterior mediastinum (black arrows). The tumor is poorly enhanced by contrast medium. A disseminated lesion was demonstrated (white arrow). The patient was diagnosed as having a transient ischemic attack and the symptoms disappeared within a day through conservative treatment. She was discharged on the 19th postoperative day without further disturbances. SFT of the thymus was diagnosed from the histologi- cal examination of the specimen and the results of immunohistochemical study. The lesion mainly consisted of non-atypical spindle-shaped tumor cells in a so-called patternless pattern with various densities of collagenous background (Fig. 4). Pleomorphism and mitoses were not significant. There were no necrotic or hemorrhagic lesions in the tumor tissue, and lymphocytic infiltration was not obvious. Direct invasion into the lung was histologically confirmed. However, invasion into the pericardium was not demonstrated. Immunohistochemical analysis revealed mesenchymal positive markers such as vimentin and CD34 (Fig. 5A). Epithelial markers such as CAM 5.2, AE1/AE3 were negative. Ki-67 (MIB-1) was positive in approximately 15% of the tumor cells (Fig. 5B). S-100 protein and desmin were not stained. Blood cell markers such as leukocyte common antigen (LCA; CD45), and Leu7 (CD57) were Ann Thorac Cardiovasc Surg Vol. 13, No. 3 (2007) 199
3 Iwata et al. Fig. 4. Histopathological examination (original magnification 200, hematoxylin-eosin stain) reveals the characteristic patternless pattern with non-atypical spindle or round tumor cells in the collagenous background. Fig. 5. Results of immunohistochemical staining (original magnification 200). A: CD34 is positive. B: Ki-67 is expressed in approximately 15% of the tumor cells. C: MIC2 protein is positive. D: Bcl-2 oncoprotein is expressed. Adding to these results, with a lack of S-100 protein and keratin, solitary fibrous tumor was diagnosed. 200 Ann Thorac Cardiovasc Surg Vol. 13, No. 3 (2007)
4 Solitary Fibrous Tumor of the Thymus negative. C-kit protein was not detected. Expression of both MIC2 protein (CD99) and bcl-2 oncoprotein was demonstrated (Fig. 5, C and D). From these immunohistochemical results, SFT was diagnosed histologically. The resected disseminated lesion was also histopathologically and immunohistochemically confirmed to be the same SFT. Postoperative adjuvant chemotherapy or radiotherapy was not undertaken because the benefit of this was uncertain. The patient is well without recurrence 3 months after operation. Discussion SFT was formerly called localized (or solitary) fibrous mesothelioma, or benign (fibrous) mesothelioma, and had been considered to be a subgroup of mesothelioma. After revision of pleural tumor classification by the World Health Organization in 1999, SFT was classified as an independent entity and was excluded from the mesothelioma subgroups. 1) SFT is an uncommon soft tissue neoplasm that mainly arises from the submesothelial layer of the pleura. In twothirds of cases, SFT arises from the submesothelial connective tissue of the pleura, however, occurrences arising from various anatomical sites as well as the pleura have been recently reported, such as the meninges, orbit, upper and lower respiratory tract, salivary glands, thyroid, breast, heart, liver, kidney, retroperitoneum, soft tissue, and urogenital organs. SFT originating in the mediastinum has been rarely reported. 2 5) In our case, because the majority of the tumor was in the anterior mediastinum, traced to the thymus and encapsulated with macroscopically intact pleura, we diagnosed that the tumor had originated in the thymic mesenchymal tissue, by gross specimen and histological examination. SFT of pleural origin usually has a pedicle, however, in our case it was absent. 4) Because the tumor was large and partially invading into the lung tissue, the exact origin could not be determined and the possibility of a pleural origin could not be excluded. Mediastinal SFT without actual connection to the pleura has been documented. 6) SFT is usually a slow-growing tumor with a favorable prognosis. The patient is usually asymptomatic until the tumor grows large enough to compress neighboring organs. Although the tumor is usually endocrinologically inactive, secretion of insulin-like growth factor II is documented, causing recurrent hypoglycemia. 7,8) The clinical behavior is usually benign, however, aggressive cases with local extension and/or recurrence have been reported in the literature. 2,9) Pleural dissemination has also been documented. 10,11) Complete surgical removal is the best treatment for SFT. Histopathologically, the patternless pattern with nonatypical spindle-shaped tumor cells in the collagenous background is the most characteristic, but not unique, finding in SFT. 12) Other spindle cell tumors, such as mesothelioma, hemangiopericytoma, synovial sarcoma, fibrosarcoma, sarcomatoid carcinoma, and malignant peripheral nerve sheath tumor are considerations for differential diagnosis. In particular, hemangiopericytoma is known to have a histopathological and immunohistochemical overlap and it is questionable that it can be separated clearly from SFT. 13) In cases with necrosis, hypercellularity, significant mitoses, atypia, and/or pleomorphism the SFT would be considered to have malignant features. However, in such cases, these histological findings do not always correlate with the clinical course. 14) In our case, although there were no obvious malignant features revealed in the histopathological examination, the operative findings such as local invasion into the lung and pleural dissemination suggested that the tumor could have potential malignancy might have indicated a poorer prognosis, although the tumor has been resected completely. Immunohistochemically, the tumor expresses CD34 in % of the cases and bcl-2 in more than 80%, though it is negative for keratin and S-100 protein. 12,14,15) MIC2 (CD99) protein is also known to be expressed normally in the thymic cortex, but positive immunoreactivity for MIC2 in SFT has also been reported. 16) Cases with malignant transformation were reported to show diminished CD34 expression and positive p53 immunoreactivity. 17) In our case, Ki-67 was positive in approximately 15% of the cellular population. Ki-67 is considered to be an indicator of cell proliferation and was not significantly expressed in this case. In our case, although malignant features were absent histopathologically and CD34 expression was not diminished, because of the local invasiveness and dissemination, malignant behavior of the tumor is predicted. Careful scrutiny will be needed for long-term postoperative follow-up. Acknowledgments We thank Dr. Kenichi Wakasa, Department of Pathology, Osaka City University Hospital, for his kind assistance and Ann Thorac Cardiovasc Surg Vol. 13, No. 3 (2007) 201
5 Iwata et al. advice on histopathological diagnosis. We also thank Ms. Yukiko Wakita for help in preparing this manuscript. References 1. Travis WD, Colby TV, Corrin B. Histological Typing of Lung and Pleural Tumors. Third ed. Berlin: Springer Verlag; Shiraishi T, Hirayama S, Hiratsuka M, et al. Mediastinal solitary fibrous tumor: report of a case with direct invasion to the trachea. Thorac Cardiovasc Surg 2004; 52: Weidner N. Solitary fibrous tumor of the mediastinum. Ultrastruct Pathol 1991; 15: Witkin GB, Rosai J. Solitary fibrous tumor of the mediastinum: a report of 14 cases. Am J Surg Pathol 1989; 13: Goto Y, Sakurada T, Suzuki I, Nanjo H, Masuda H. A localized fibrous tumor (mesothelioma) in the mediastinum: report of a case. Surg Today 1997; 27: Balassiano M, Reichert N, Rosenman Y, Hertcheg E, Lieberman Y, Yellin A. Localized fibrous mesothelioma of the mediastinum devoid of pleural connections. Postgrad Med J 1989; 65: Tsuro K, Kojima H, Okamoto S, et al. Glucocorticoid therapy ameliorated hypoglycemia in insulin-like growth factor-ii-producing solitary fibrous tumor. Intern Med 2006; 45: Fukasawa Y, Takada A, Tateno M, et al. Solitary fibrous tumor of the pleura causing recurrent hypoglycemia by secretion of insulin-like growth factor ii. Pathol Int 1998; 48: Cassarino DS, Auerbach A, Rushing EJ. Widely invasive solitary fibrous tumor of the sphenoid sinus, cavernous sinus, and pituitary fossa. Ann Diagn Pathol 2003; 7: Miyashita K, Hayashi Y, Fujisawa H, Hasegawa M, Yamashita J. Recurrent intracranial solitary fibrous tumor with cerebrospinal fluid dissemination: case report. J Neurosurg 2004; 101: Zhang H, Lucas DR, Pass HI, Che M. Disseminated malignant solitary fibrous tumor of the pleura. Pathol Int 2004; 54: England DM, Hochholzer L, McCarthy MJ. Localized benign and malignant fibrous tumors of the pleura: a clinicopathologic review of 223 cases. Am J Surg Pathol 1989; 13: Goldsmith JD, van de Rijn M, Syed N. Orbital hemangiopericytoma and solitary fibrous tumor: a morphologic continuum. Int J Surg Pathol 2001; 9: Morimitsu Y, Nakajima M, Hisaoka M, Hashimoto H. Extrapleural solitary fibrous tumor: clinicopathologic study of 17 cases and molecular analysis of the p53 pathway. Apmis 2000; 108: Hasegawa T, Matsuno Y, Shimoda T, Hirohashi S, Hirose T, Sano T. Frequent expression of bcl-2 protein in solitary fibrous tumors. Jpn J Clin Oncol 1998; 28: Mentzel T, Bainbridge TC, Katenkamp D. Solitary fibrous tumour: Clinicopathological, immunohistochemical, and ultrastructural analysis of 12 cases arising in soft tissues, nasal cavity and nasopharynx, urinary bladder and prostate. Virchows Arch 1997; 430: Yokoi T, Tsuzuki T, Yatabe Y, et al. Solitary fibrous tumour: significance of p53 and cd34 immunoreactivity in its malignant transformation. Histopathology 1998; 32: Ann Thorac Cardiovasc Surg Vol. 13, No. 3 (2007)
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