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Asian J Endosc Surg ISSN 1758-5902
C A S E R E P O RT
Thymic metastasis of breast cancer 22 years after surgery: A case report Shinji Fujioka,1 Hiroshige Nakamura,1 Ken Miwa,1 Yuzo Takagi,1 Yohei Yurugi,1 Yuji Taniguchi1 & Kiyosuke Ishiguro2 1 Division of General Thoracic Surgery, Tottori University Hospital, Yonago, Japan 2 Division of Breast Surgery, Tottori University Hospital, Yonago, Japan
Keywords Breast cancer; thoracoscopic surgery; thymic metastasis Correspondence Hiroshige Nakamura, Division of General Thoracic Surgery, Tottori University Hospital, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan. Tel: +81 859 38 6737 Fax: +81 859 38 6730 Email: [email protected] Received: 23 May 2013; revised 23 July 2013; accepted 24 July 2013 DOI:10.1111/ases.12060
Abstract We report a rare case of thymic metastasis of breast cancer. A 68-year-old woman, who had undergone surgery for cancer in her right breast and had been free of recurrence for 22 years, was noted to have an abnormal shadow on a chest X-ray at a regular medical checkup. Further workup, including chest CT, revealed a 22 × 18-mm mass in the anterior mediastinum. Fluorine-18fluorodeoxyglucose-PET showed increased fluorine-18-fluorodeoxyglucose uptake that was highly suggestive of thymoma. Thoracoscopic thymothymectomy was performed. The tumor had invaded the pericardium, which was also resected. A small nodule was found in the right lung, and it was also resected. The intraoperative frozen-section diagnosis was breast cancer metastasis to the thymus and lung. The pathological diagnosis was luminal A solid tubular carcinoma (strongly estrogen receptor and progesterone receptor positive, HER2 negative) with an MIB-1 index of less than 5%. After surgery, the patient was treated with an aromatase inhibitor. As of August 2013, she has been free of recurrence for more than 36 months. It is extremely rare for breast cancer to metastasize to the thymus more than 20 years after surgery.
Introduction Breast cancer metastasis to the thymus is extremely rare, and few patients experience recurrence more than 20 years after surgery. We report a patient who was suspected of having thymoma before surgery, underwent thoracoscopic thymothymectomy, and was diagnosed with breast cancer metastasis to the thymus. A review of the literature is included.
Case Presentation A 68-year-old woman was noted to have an abnormal shadow on a chest X-ray at a regular medical checkup in a neighborhood hospital. She subsequently visited our hospital where chest CT revealed no lesion at the site, but a tumor mass in the anterior mediastinum was found. There were no subjective symptoms. The patient had undergone mastectomy and lymph node dissection for cancer in her right breast 22 years ago. The cancer was
330
staged as pT1N0M0. She took tamoxifen for 3 years after surgery and experienced no recurrence thereafter. Chest CT showed a 22 × 18-mm, contrast-enhanced, anterior mediastinal tumor that was partially demarcated from the pericardium (Figure 1a). MRI revealed an isointense, solid tumor on T1- and T2-weighted images. Fluorine-18fluorodeoxyglucose (FDG)-PET showed high FDG uptake with a maximum standard uptake value of 5.2 in the tumor, but no FDG uptake in the hilar area, mediastinal, parasternal, or supraclavicular lymph nodes, or other organs (Figure 1b).The tumor marker carcinoembryonic antigen was slightly high, at 5.2 ng/mL, and CA15-3 and National Cancer Center-Stomach 439 (NCC-ST439) were within normal limits. With a preoperative diagnosis of suspected thymoma, surgery was performed. During the procedure, the patient was placed in a supine position. Thoracoscopic thymothymectomy was performed using the anterior chest wall-lifting method and one-lung ventilation. Four chest ports were placed on the right side of the patient’s chest. Because the tumor
Asian J Endosc Surg 6 (2013) 330–332 © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd
Thymic metastasis of breast cancer
S Fujioka et al.
Figure 1 FDG-PET/CT. (a) Chest CT revealed a 22 × 18-mm contrast-enhanced, anterior mediastinal tumor that was partially demarcated from the pericardium (arrow). (b) FDG-PET showed high FDG uptake with an SUVmax of 5.2 in the mediastinal tumor, but no FDG uptake in the hilar area, mediastinal, parasternal, or supraclavicular lymph nodes, or other organs. FDG, fluorine-18-fluorodeoxyglucose; SUVmax, maximum standard uptake value.
had invaded through the thymic capsule into the pericardium, it was resected with the pericardium. The resulting pericardial defect (45 × 40 mm) was repaired with a Gore-Tex patch (W.L. Gore & Associates, Newark, USA). To repair the pericardial defect, we extended the only skin incision to 3 cm to facilitate better handling. The tumor measured 22 × 18 mm in diameter, and the intraoperative frozen-section diagnosis was breast cancer with metastasis to the thymus. An inspection of the right thoracic cavity revealed a 7-mm white nodule in the lower lobe of the right lung. After wedge resection, this nodule was also diagnosed as a metastatic breast cancer. Total blood loss was 10 mL, and operation time was 200 min. There was no complication. The final pathological diagnosis was luminal A solid tubular carcinoma (strongly estrogen receptor and progesterone receptor positive, HER2 negative) with an MIB-1 index of less than 5%, and the tumor cells extended irregularly through the thymic tissue and invaded the pericardium (Figure 2). No metastases were observed in other thymic tissue or distant lymph nodes. After surgery, the patient took an aromatase inhibitor. She has been free of intrathoracic or distant recurrence for more than 36 months, and her carcinoembryonic antigen has returned to a normal level of 3.7 ng/mL.
Discussion Breast cancer metastasis to the thymus is extremely rare. Middleton reported that thymic metastasis of breast cancer was found in 4 of 102 autopsied patients (about 4%) (1). However, a search of the literature revealed only two surgical cases of thymic metastasis of breast
Figure 2 Histological appearance (hematoxylin–eosin staining, ×200). Histological examination showed a solid tubular carcinoma sharply demarcated from the surrounding fibrous stroma.
cancer reported by Park et al. and Sakaguchi et al. (2,3). Clark reported that the blood–thymus barrier protects thymus tissue against the invasion of tumor cells and antigens, thereby making the possibility of thymic metastasis of cancer unlikely (4). The real thymic metastasis of the primary cancer is often a part of multiorgan metastasis. Indeed, no patients with thymic metastasis alone have been reported in the literature (1). As previously reported, the present patient also had a metastatic lesion in the right lung. Breast cancer usually recurs within 5 years after surgery, and the frequency of recurrence begins to decrease in the 10th postoperative year. Takeuchi et al. reported that 284 of 1116 patients with breast cancer experienced recurrence after surgery, and only 12 (4.4%)
Asian J Endosc Surg 6 (2013) 330–332 © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd
331
Thymic metastasis of breast cancer
S Fujioka et al.
of the 284 patients had recurrence more than 10 years after surgery (5). Recurrence occurs much less frequently 20 or more years after surgery, and Hasegawa et al. reported a recurrence rate of only 0.1% (6). Characteristically, late, ipsilateral, locoregional recurrence (such as metastasis to the ipsilateral chest wall, axillary lymph nodes, or supraclavicular lymph nodes) accounts for the majority (74%) of all recurrences, and distant metastasis accounts for a small proportion of all recurrences (6). Takeuchi et al. reported that lymph node metastases were found at the initial surgery in 10 of 12 patients with late recurrence (5), suggesting that lymph node metastasis at the initial presentation of breast cancer is closely associated with late recurrence. The two above-mentioned patients with thymic metastasis of breast cancer had axillary lymph node metastasis at the time of surgery, which recurred within 1 year after surgery (2,3). The present case is extremely rare in that the patient had breast cancer with no lymph node metastasis at the initial surgery; she developed late distant metastasis to the thymus 22 years after surgery, representing the first case in the literature. Using FDG-PET to detect metastatic breast cancer, Morris et al. found that the most frequent sites of metastasis were the bone, lung, liver, and lymphatic tissue. They also found that a correlation existed between FDG uptake and the prognosis of patients (7). In the present patient, preoperative FDG-PET showed increased FDG uptake in the thymus, but no FDG uptake in the hilar area, mediastinal, parasternal, or supraclavicular lymph nodes. Therefore, thymoma was suspected as the most likely preoperative diagnosis. Regarding the sensitivity of FDG-PET, it is said that small-diameter tumors tend to be negative for FDG uptake. Reinhardt et al. reported that the sensitivities of FDG-PET for malignant lesions 8–10 mm and 5–7 mm in diameter were 78% and 40%, respectively, indicating a particularly low sensitivity for tumors less than 7 mm in diameter (8). In the present case, the metastatic lesion in the right lung was 7 mm in diameter, presumably resulting in no significant FDG uptake (or false-negative FDG uptake). Therefore, it is safe to assume that metastases too small to be detected were present elsewhere in the body. Endocrine therapy is considered the mainstay of treatment for patients with
332
distant metastases in the absence of hepatic or other visceral metastases, and aromatase inhibitors are recommended for postmenopausal patients with luminal A or B breast cancer (9). The present patient had luminal A breast cancer and was treated with an aromatase inhibitor alone. As of August 2013, 36 months after surgery, she is free of locoregional or distant metastasis, with a normal carcinoembryonic antigen level.
Acknowledgment The authors have no conflict of interest to report.
References 1. Middleton G. Involvement of the thymus by metastatic neoplasms. Br J Cancer 1966; 20: 41–46. 2. Park SB, Kim HH, Shin HJ et al. Thymic metastasis in breast cancer: A case report. Korean J Radiol 2007; 8: 360–363. 3. Sakaguchi M, Kido T, Tamura M et al. A case of breast metastasis to the intra-thymic lymph node diagnosed by partial resection of the thymus using video-assisted thoracoscopic surgery. Nihon Kokyuki Geka Gakkai Zasshi (Jpn J Chest Surg) 2006; 20: 56–59. (In Japanese) 4. Clark SL. The reticulum of lymph nodes in mice studied with the electron microscope. Am J Anat 1962; 110: 217–257. 5. Takeuchi H, Muto Y, Tashiro H. Clinicopathological characteristics of recurrence more than 10 years after surgery in patients with breast carcinoma. Anticancer Res 2009; 29: 3445– 3448. 6. Hasegawa S, Chishima T, Higuchi A et al. A case of local recurrence of breast cancer developed 34 years after radical mastectomy. Nihon Rinsho Geka Gakkai Zasshi (J Jpn Surg Assoc) 2008; 69: 2804–2808. (In Japanese) 7. Morris PG, Ulaner GA, Eaton A et al. Standardized uptake value by positron emission tomography/ computed tomography as a prognostic variable in metastatic breast cancer. Cancer 2012; 118: 5454–5462. 8. Reinhardt MJ, Wiethoelter N, Matthies A et al. PET recognition of pulmonary metastases on PET/CT imaging: Impact of attenuation-corrected and non-attenuation-corrected PET images. Eur J Nucl Med Mol Imaging 2006; 33: 134–139. 9. Buzdar A, Douma J, Davidson N et al. Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol 2001; 19: 3357–3366.
Asian J Endosc Surg 6 (2013) 330–332 © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd
Asian J Endosc Surg ISSN 1758-5902
C A S E R E P O RT
Thymic metastasis of breast cancer 22 years after surgery: A case report Shinji Fujioka,1 Hiroshige Nakamura,1 Ken Miwa,1 Yuzo Takagi,1 Yohei Yurugi,1 Yuji Taniguchi1 & Kiyosuke Ishiguro2 1 Division of General Thoracic Surgery, Tottori University Hospital, Yonago, Japan 2 Division of Breast Surgery, Tottori University Hospital, Yonago, Japan
Keywords Breast cancer; thoracoscopic surgery; thymic metastasis Correspondence Hiroshige Nakamura, Division of General Thoracic Surgery, Tottori University Hospital, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan. Tel: +81 859 38 6737 Fax: +81 859 38 6730 Email: [email protected] Received: 23 May 2013; revised 23 July 2013; accepted 24 July 2013 DOI:10.1111/ases.12060
Abstract We report a rare case of thymic metastasis of breast cancer. A 68-year-old woman, who had undergone surgery for cancer in her right breast and had been free of recurrence for 22 years, was noted to have an abnormal shadow on a chest X-ray at a regular medical checkup. Further workup, including chest CT, revealed a 22 × 18-mm mass in the anterior mediastinum. Fluorine-18fluorodeoxyglucose-PET showed increased fluorine-18-fluorodeoxyglucose uptake that was highly suggestive of thymoma. Thoracoscopic thymothymectomy was performed. The tumor had invaded the pericardium, which was also resected. A small nodule was found in the right lung, and it was also resected. The intraoperative frozen-section diagnosis was breast cancer metastasis to the thymus and lung. The pathological diagnosis was luminal A solid tubular carcinoma (strongly estrogen receptor and progesterone receptor positive, HER2 negative) with an MIB-1 index of less than 5%. After surgery, the patient was treated with an aromatase inhibitor. As of August 2013, she has been free of recurrence for more than 36 months. It is extremely rare for breast cancer to metastasize to the thymus more than 20 years after surgery.
Introduction Breast cancer metastasis to the thymus is extremely rare, and few patients experience recurrence more than 20 years after surgery. We report a patient who was suspected of having thymoma before surgery, underwent thoracoscopic thymothymectomy, and was diagnosed with breast cancer metastasis to the thymus. A review of the literature is included.
Case Presentation A 68-year-old woman was noted to have an abnormal shadow on a chest X-ray at a regular medical checkup in a neighborhood hospital. She subsequently visited our hospital where chest CT revealed no lesion at the site, but a tumor mass in the anterior mediastinum was found. There were no subjective symptoms. The patient had undergone mastectomy and lymph node dissection for cancer in her right breast 22 years ago. The cancer was
330
staged as pT1N0M0. She took tamoxifen for 3 years after surgery and experienced no recurrence thereafter. Chest CT showed a 22 × 18-mm, contrast-enhanced, anterior mediastinal tumor that was partially demarcated from the pericardium (Figure 1a). MRI revealed an isointense, solid tumor on T1- and T2-weighted images. Fluorine-18fluorodeoxyglucose (FDG)-PET showed high FDG uptake with a maximum standard uptake value of 5.2 in the tumor, but no FDG uptake in the hilar area, mediastinal, parasternal, or supraclavicular lymph nodes, or other organs (Figure 1b).The tumor marker carcinoembryonic antigen was slightly high, at 5.2 ng/mL, and CA15-3 and National Cancer Center-Stomach 439 (NCC-ST439) were within normal limits. With a preoperative diagnosis of suspected thymoma, surgery was performed. During the procedure, the patient was placed in a supine position. Thoracoscopic thymothymectomy was performed using the anterior chest wall-lifting method and one-lung ventilation. Four chest ports were placed on the right side of the patient’s chest. Because the tumor
Asian J Endosc Surg 6 (2013) 330–332 © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd
Thymic metastasis of breast cancer
S Fujioka et al.
Figure 1 FDG-PET/CT. (a) Chest CT revealed a 22 × 18-mm contrast-enhanced, anterior mediastinal tumor that was partially demarcated from the pericardium (arrow). (b) FDG-PET showed high FDG uptake with an SUVmax of 5.2 in the mediastinal tumor, but no FDG uptake in the hilar area, mediastinal, parasternal, or supraclavicular lymph nodes, or other organs. FDG, fluorine-18-fluorodeoxyglucose; SUVmax, maximum standard uptake value.
had invaded through the thymic capsule into the pericardium, it was resected with the pericardium. The resulting pericardial defect (45 × 40 mm) was repaired with a Gore-Tex patch (W.L. Gore & Associates, Newark, USA). To repair the pericardial defect, we extended the only skin incision to 3 cm to facilitate better handling. The tumor measured 22 × 18 mm in diameter, and the intraoperative frozen-section diagnosis was breast cancer with metastasis to the thymus. An inspection of the right thoracic cavity revealed a 7-mm white nodule in the lower lobe of the right lung. After wedge resection, this nodule was also diagnosed as a metastatic breast cancer. Total blood loss was 10 mL, and operation time was 200 min. There was no complication. The final pathological diagnosis was luminal A solid tubular carcinoma (strongly estrogen receptor and progesterone receptor positive, HER2 negative) with an MIB-1 index of less than 5%, and the tumor cells extended irregularly through the thymic tissue and invaded the pericardium (Figure 2). No metastases were observed in other thymic tissue or distant lymph nodes. After surgery, the patient took an aromatase inhibitor. She has been free of intrathoracic or distant recurrence for more than 36 months, and her carcinoembryonic antigen has returned to a normal level of 3.7 ng/mL.
Discussion Breast cancer metastasis to the thymus is extremely rare. Middleton reported that thymic metastasis of breast cancer was found in 4 of 102 autopsied patients (about 4%) (1). However, a search of the literature revealed only two surgical cases of thymic metastasis of breast
Figure 2 Histological appearance (hematoxylin–eosin staining, ×200). Histological examination showed a solid tubular carcinoma sharply demarcated from the surrounding fibrous stroma.
cancer reported by Park et al. and Sakaguchi et al. (2,3). Clark reported that the blood–thymus barrier protects thymus tissue against the invasion of tumor cells and antigens, thereby making the possibility of thymic metastasis of cancer unlikely (4). The real thymic metastasis of the primary cancer is often a part of multiorgan metastasis. Indeed, no patients with thymic metastasis alone have been reported in the literature (1). As previously reported, the present patient also had a metastatic lesion in the right lung. Breast cancer usually recurs within 5 years after surgery, and the frequency of recurrence begins to decrease in the 10th postoperative year. Takeuchi et al. reported that 284 of 1116 patients with breast cancer experienced recurrence after surgery, and only 12 (4.4%)
Asian J Endosc Surg 6 (2013) 330–332 © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd
331
Thymic metastasis of breast cancer
S Fujioka et al.
of the 284 patients had recurrence more than 10 years after surgery (5). Recurrence occurs much less frequently 20 or more years after surgery, and Hasegawa et al. reported a recurrence rate of only 0.1% (6). Characteristically, late, ipsilateral, locoregional recurrence (such as metastasis to the ipsilateral chest wall, axillary lymph nodes, or supraclavicular lymph nodes) accounts for the majority (74%) of all recurrences, and distant metastasis accounts for a small proportion of all recurrences (6). Takeuchi et al. reported that lymph node metastases were found at the initial surgery in 10 of 12 patients with late recurrence (5), suggesting that lymph node metastasis at the initial presentation of breast cancer is closely associated with late recurrence. The two above-mentioned patients with thymic metastasis of breast cancer had axillary lymph node metastasis at the time of surgery, which recurred within 1 year after surgery (2,3). The present case is extremely rare in that the patient had breast cancer with no lymph node metastasis at the initial surgery; she developed late distant metastasis to the thymus 22 years after surgery, representing the first case in the literature. Using FDG-PET to detect metastatic breast cancer, Morris et al. found that the most frequent sites of metastasis were the bone, lung, liver, and lymphatic tissue. They also found that a correlation existed between FDG uptake and the prognosis of patients (7). In the present patient, preoperative FDG-PET showed increased FDG uptake in the thymus, but no FDG uptake in the hilar area, mediastinal, parasternal, or supraclavicular lymph nodes. Therefore, thymoma was suspected as the most likely preoperative diagnosis. Regarding the sensitivity of FDG-PET, it is said that small-diameter tumors tend to be negative for FDG uptake. Reinhardt et al. reported that the sensitivities of FDG-PET for malignant lesions 8–10 mm and 5–7 mm in diameter were 78% and 40%, respectively, indicating a particularly low sensitivity for tumors less than 7 mm in diameter (8). In the present case, the metastatic lesion in the right lung was 7 mm in diameter, presumably resulting in no significant FDG uptake (or false-negative FDG uptake). Therefore, it is safe to assume that metastases too small to be detected were present elsewhere in the body. Endocrine therapy is considered the mainstay of treatment for patients with
332
distant metastases in the absence of hepatic or other visceral metastases, and aromatase inhibitors are recommended for postmenopausal patients with luminal A or B breast cancer (9). The present patient had luminal A breast cancer and was treated with an aromatase inhibitor alone. As of August 2013, 36 months after surgery, she is free of locoregional or distant metastasis, with a normal carcinoembryonic antigen level.
Acknowledgment The authors have no conflict of interest to report.
References 1. Middleton G. Involvement of the thymus by metastatic neoplasms. Br J Cancer 1966; 20: 41–46. 2. Park SB, Kim HH, Shin HJ et al. Thymic metastasis in breast cancer: A case report. Korean J Radiol 2007; 8: 360–363. 3. Sakaguchi M, Kido T, Tamura M et al. A case of breast metastasis to the intra-thymic lymph node diagnosed by partial resection of the thymus using video-assisted thoracoscopic surgery. Nihon Kokyuki Geka Gakkai Zasshi (Jpn J Chest Surg) 2006; 20: 56–59. (In Japanese) 4. Clark SL. The reticulum of lymph nodes in mice studied with the electron microscope. Am J Anat 1962; 110: 217–257. 5. Takeuchi H, Muto Y, Tashiro H. Clinicopathological characteristics of recurrence more than 10 years after surgery in patients with breast carcinoma. Anticancer Res 2009; 29: 3445– 3448. 6. Hasegawa S, Chishima T, Higuchi A et al. A case of local recurrence of breast cancer developed 34 years after radical mastectomy. Nihon Rinsho Geka Gakkai Zasshi (J Jpn Surg Assoc) 2008; 69: 2804–2808. (In Japanese) 7. Morris PG, Ulaner GA, Eaton A et al. Standardized uptake value by positron emission tomography/ computed tomography as a prognostic variable in metastatic breast cancer. Cancer 2012; 118: 5454–5462. 8. Reinhardt MJ, Wiethoelter N, Matthies A et al. PET recognition of pulmonary metastases on PET/CT imaging: Impact of attenuation-corrected and non-attenuation-corrected PET images. Eur J Nucl Med Mol Imaging 2006; 33: 134–139. 9. Buzdar A, Douma J, Davidson N et al. Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol 2001; 19: 3357–3366.
Asian J Endosc Surg 6 (2013) 330–332 © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd
