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• W2085497441 abstract "A case of large cell neuroendocrine carcinoma of the thymus successfully treated with chemoradiation, followed by extended resection under cardiopulmonary bypass, is reported. A 44-year-old man diagnosed with thymic large cell neuroendocrine carcinoma received induction chemoradiation therapy (3 cycles of cisplatin/etoposide and 45 Gy of hyperfractionated radiation) because of invasion to the aortic arch and pulmonary trunk. After radiographic partial response was noted, a radical resection under cardiopulmonary bypass was performed. Pathologic examination revealed no viable cells in the tumor. The patient is alive 3 years later, without recurrence. Aggressive multimodality therapy could be an option for thymic large cell neuroendocrine carcinoma. A case of large cell neuroendocrine carcinoma of the thymus successfully treated with chemoradiation, followed by extended resection under cardiopulmonary bypass, is reported. A 44-year-old man diagnosed with thymic large cell neuroendocrine carcinoma received induction chemoradiation therapy (3 cycles of cisplatin/etoposide and 45 Gy of hyperfractionated radiation) because of invasion to the aortic arch and pulmonary trunk. After radiographic partial response was noted, a radical resection under cardiopulmonary bypass was performed. Pathologic examination revealed no viable cells in the tumor. The patient is alive 3 years later, without recurrence. Aggressive multimodality therapy could be an option for thymic large cell neuroendocrine carcinoma. Large cell neuroendocrine carcinoma (LCNEC) of the thymus is a rare type of neuroendocrine carcinoma that has an extremely poor prognosis, and no standard treatment has been established. A patient with thymic LCNEC successfully treated with induction chemoradiotherapy, followed by radical resection under cardiopulmonary bypass, is reported. A 44-year-old man presented with a cough, and a left lateral mediastinal mass was seen on chest roentgenogram. Chest computed tomography (CT) showed an anterior mediastinal tumor, 10.0 cm × 5.3 cm in size, with suspected invasion to the proximal aortic arch and pericardium (Fig 1A). 2-[18F] Fluoro-2-deoxyglucose (FDG) positron-emission tomography (FDG-PET) showed significant FDG uptake (Fig 1B). Histopathologic analysis of a CT-guided percutaneous core biopsy specimen resulted in the diagnosis of LCNEC of the thymus (grade 3). The tumor cells were large and showed an organoid nesting pattern immunoreactive for chromogranin A and neuron-specific enolase (Fig 2). A complete resection seemed to be impossible because of the direct invasion of the aorta, and induction chemoradiotherapy, consisting of 3 cycles of cisplatin (day 1, 80 mg/m2) and etoposide (days 1, 2, and 3, 90 mg/m2), with hyperfractionated radiation (45 Gy), was administered. The size of the tumor decreased to 4.5 cm × 2.8 cm on chest CT scan (Fig 3A), and FDG accumulation decreased to background levels (Fig 3B).Fig 2Histopathologic findings of the thymic tumor for the diagnosis of large cell neuroendocrine carcinoma. (A) Hematoxylin and eosin staining shows large neoplastic cells including anaplastic giant cells (original magnification ×400). Immunohistochemical staining is positive for (B) chromogranin A (original magnification ×400) and (C) neuron-specific enolase (original magnification ×400). More than 10 mitoses per 2 mm2 (10 high-power fields) are observed. (D) The Ki 67 labeling index is approximately 60% (original magnification ×400).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig 3Radiographic images after induction treatment with chemoradiation therapy. (A) The size of the tumor has decreased to 4.5 cm × 2.8 cm on the chest computed tomography scan. (B) Uptake of 2-[18F] fluoro-2-deoxyglucose has diminished to the background level on the positron emission tomography–computed tomography scan.View Large Image Figure ViewerDownload Hi-res image Download (PPT) About 2 months later, after induction therapy was completed, a radical resection was performed through a hemiclamshell incision. Cardiopulmonary bypass (CPB) was established through the right atrium and the right femoral artery because the proximal site of the aortic arch and pulmonary trunk were involved by the tumor. The tumor was excised from the aorta and pulmonary trunk with sharp dissection under CPB without cardiac arrest because of the severe adhesion. Intraoperative pathologic examination showed fibrous change without viable cancer cells, and graft replacement was not necessary. The left phrenic and vagus nerves, as well as the left upper lobe of the lung, were resected because of direct invasion. A complete resection was achieved. The preoperative radiotherapy did not cause any intraoperative adverse events. Operative time was 586 minutes, and blood loss was 5,500 mL. The patient was discharged on postoperative day 13 and has been free from relapse for 3 years after the operation. No viable cell with fibrous and hyalinized change was observed in the final pathologic report. LCNEC of the thymus is classified as a rare and poorly differentiated neuroendocrine tumor. Thymic neuroendocrine carcinomas account for approximately 2% to 5% of thymic epithelial tumors [1Marx A. Shimosato Y. Kuo T.T. Chan J.K.C. Travis W.D. Wick M.R. Thymic neuroendocrine tumours.in: Travis W.D. Brambilla E. Mueller-Hermelink H.K. Harris C.C. World Health Organization classification of tumors. Pathology & genetics. Tumours of the lung, pleura, thymus and heart. WHO Press, Geneva2004: 188-190Google Scholar]. Moran and colleagues [2Moran C.A. Suster S. Neuroendocrine carcinomas (carcinoid tumor) of the thymus. A clinicopathologic analysis of 80 cases.Am J Clin Pathol. 2000; 114: 100-110Crossref PubMed Scopus (242) Google Scholar] reported that the 5-year survival rates of patients with thymic neuroendocrine carcinomas were 50%, 20%, and 0% for low-grade, intermediate-grade, and high-grade tumors, respectively. Tumor grade was determined according to histopathologic features, including growth pattern, cytologic atypia, and mitotic activity [2Moran C.A. Suster S. Neuroendocrine carcinomas (carcinoid tumor) of the thymus. A clinicopathologic analysis of 80 cases.Am J Clin Pathol. 2000; 114: 100-110Crossref PubMed Scopus (242) Google Scholar]. LCNEC of the thymus has a poorer prognosis than other neuroendocrine tumors because of the frequent distant and lymph node metastases [3Cardillo G. Rea F. Lucchi M. et al.Primary neuroendocrine tumors of the thymus: a multicenter experience of 35 patients.Ann Thorac Surg. 2012; 94: 241-245Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar]. A complete resection might contribute to long-term survival [4Economopoulos G.C. Lewis Jr., J.W. Lee M.W. Silverman N.A. Carcinoid tumors of thymus.Ann Thorac Surg. 1990; 50: 58-61Abstract Full Text PDF PubMed Scopus (92) Google Scholar], whereas adjuvant therapy including radiotherapy or chemotherapy using cisplatin and etoposide is applied according to the regimens used to treat LCNEC of the lung [5Sun J.M. Ahn M.J. Ahn J.S. et al.Chemotherapy for pulmonary large cell neuroendocrine carcinoma: similar to that for small cell lung cancer or non-small cell lung cancer?.Lung Cancer. 2012; 77: 365-370Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar, 6Tiffet O. Nicholson A.G. Ladas G. Sheppard M.N. Goldstraw P. A clinicopathologic study of 12 neuroendocrine tumors arising in the thymus.Chest. 2003; 124: 141-146Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar]. So far, 24 patients with thymic LCNEC have been reported in the Japanese literature. Among these, surgical resection was performed in 21 patients, of whom 3 and 9 underwent induction chemotherapy and adjuvant therapy, respectively. The prognosis was recorded in 13 patients, and of these, 5 patients classified as Masaoka stage IVb relapsed within 1 year after the operation. Among 4 relapse-free patients, 1 patient with stage I and 2 patients with stage III received adjuvant therapy. Cardillo and colleagues [7Cardillo G. Treggiari S. Paul M.A. et al.Primary neuroendocrine tumours of the thymus: a clinicopathologic and prognostic study in 19 patients.Eur J Cardiothorac Surg. 2010; 37: 814-818Crossref PubMed Scopus (31) Google Scholar] reported 3 relapse-free patients who underwent radiotherapy after surgical resection, all of whom had Masaoka stage III disease. This indicates that complete resection and adjuvant therapy might contribute to long-term survival if the tumor is localized in the mediastinum without lymphatic spread. Complete resection has been reported to contribute to good prognosis in patients with thymic cancer [8Lee C.Y. Bae M.K. Park I.K. Kim D.J. Lee J.G. Chung K.Y. Early Masaoka stage and complete resection is important for prognosis of thymic carcinoma: a 20-year experience at a single institution.Eur J Cardiothorac Surg. 2009; 36: 159-162Crossref PubMed Scopus (39) Google Scholar]. Therefore, a radical complete resection was performed under CPB without graft replacement of the aortic arch because there were, fortunately, no viable cancer cells at the site of direct invasion. However, CPB was necessary for sharp dissection of the aorta and pulmonary trunk from the tumor to avoid the fatal complication of uncontrollable intraoperative hemorrhage. Only a few reports have described the use of induction therapy for thymic LCNEC. Two previous reports in the Japanese literature described the use of cisplatin plus etoposide for the treatment of thymomas. The present report is the first describing the use of induction chemotherapy for thymic LCNEC using a regimen described for pulmonary neuroendocrine carcinoma. Histopathologic results after resection indicate that the regimen used to treat small cell lung carcinoma might also be effective for LCNEC of the thymus. Thus, histopathologic diagnosis of a percutaneous core biopsy specimen should be considered when choosing the treatment strategy in patients with invasive mediastinal tumor when a complete resection is initially impossible." @default.
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• W2085497441 date "2013-10-01" @default.
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• W2085497441 title "Multimodality Therapy for Large Cell Neuroendocrine Carcinoma of the Thymus" @default.
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