CASE REPORT

Thymic metastasis of breast cancer 22 years after surgery: Acase reportShinji 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

KeywordsBreast cancer; thoracoscopic surgery;

thymic metastasis

CorrespondenceHiroshige 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: hnaka@med.tottori-u.ac.jp

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-oldwoman, who had undergone surgery for cancer in her right breast and hadbeen free of recurrence for 22 years, was noted to have an abnormal shadowon a chest X-ray at a regular medical checkup. Further workup, including chestCT, revealed a 22 × 18-mm mass in the anterior mediastinum. Fluorine-18-fluorodeoxyglucose-PET showed increased fluorine-18-fluorodeoxyglucoseuptake that was highly suggestive of thymoma. Thoracoscopic thymo-thymectomy was performed. The tumor had invaded the pericardium, whichwas also resected. A small nodule was found in the right lung, and it was alsoresected. The intraoperative frozen-section diagnosis was breast cancer metas-tasis to the thymus and lung. The pathological diagnosis was luminal A solidtubular carcinoma (strongly estrogen receptor and progesterone receptor posi-tive, HER2 negative) with an MIB-1 index of less than 5%. After surgery, thepatient was treated with an aromatase inhibitor. As of August 2013, she hasbeen free of recurrence for more than 36 months. It is extremely rare for breastcancer 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 20years after surgery. We report a patient who was sus-pected of having thymoma before surgery, underwentthoracoscopic thymothymectomy, and was diagnosedwith breast cancer metastasis to the thymus. A review ofthe literature is included.

Case Presentation

A 68-year-old woman was noted to have an abnormalshadow on a chest X-ray at a regular medical checkup ina neighborhood hospital. She subsequently visited ourhospital where chest CT revealed no lesion at the site, buta tumor mass in the anterior mediastinum was found.There were no subjective symptoms. The patient hadundergone mastectomy and lymph node dissection forcancer in her right breast 22 years ago. The cancer was

staged as pT1N0M0. She took tamoxifen for 3 years aftersurgery and experienced no recurrence thereafter. ChestCT showed a 22 × 18-mm, contrast-enhanced, anteriormediastinal tumor that was partially demarcated fromthe pericardium (Figure 1a). MRI revealed an isointense,solid tumor on T1- and T2-weighted images. Fluorine-18-fluorodeoxyglucose (FDG)-PET showed high FDG uptakewith a maximum standard uptake value of 5.2 in thetumor, but no FDG uptake in the hilar area, mediastinal,parasternal, or supraclavicular lymph nodes, or otherorgans (Figure 1b).The tumor marker carcinoembryonicantigen was slightly high, at 5.2 ng/mL, and CA15-3 andNational Cancer Center-Stomach 439 (NCC-ST439) werewithin normal limits. With a preoperative diagnosis ofsuspected thymoma, surgery was performed.

During the procedure, the patient was placed in asupine position. Thoracoscopic thymothymectomy wasperformed using the anterior chest wall-lifting methodand one-lung ventilation. Four chest ports were placedon the right side of the patient’s chest. Because the tumor

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had invaded through the thymic capsule into thepericardium, it was resected with the pericardium. Theresulting pericardial defect (45 × 40 mm) was repairedwith a Gore-Tex patch (W.L. Gore & Associates, Newark,USA). To repair the pericardial defect, we extended theonly skin incision to 3 cm to facilitate better handling.

The tumor measured 22 × 18 mm in diameter, and theintraoperative frozen-section diagnosis was breast cancerwith metastasis to the thymus. An inspection of the rightthoracic cavity revealed a 7-mm white nodule in thelower lobe of the right lung. After wedge resection, thisnodule was also diagnosed as a metastatic breast cancer.Total blood loss was 10 mL, and operation time was200 min. There was no complication. The final pathologi-cal diagnosis was luminal A solid tubular carcinoma(strongly estrogen receptor and progesterone receptorpositive, HER2 negative) with an MIB-1 index of lessthan 5%, and the tumor cells extended irregularlythrough the thymic tissue and invaded the pericardium(Figure 2). No metastases were observed in other thymictissue or distant lymph nodes. After surgery, the patienttook an aromatase inhibitor. She has been free ofintrathoracic or distant recurrence for more than 36months, and her carcinoembryonic antigen has returnedto a normal level of 3.7 ng/mL.

Discussion

Breast cancer metastasis to the thymus is extremely rare.Middleton reported that thymic metastasis of breastcancer was found in 4 of 102 autopsied patients (about4%) (1). However, a search of the literature revealedonly two surgical cases of thymic metastasis of breast

cancer reported by Park et al. and Sakaguchi et al. (2,3).Clark reported that the blood–thymus barrier protectsthymus tissue against the invasion of tumor cells andantigens, thereby making the possibility of thymic metas-tasis of cancer unlikely (4). The real thymic metastasis ofthe primary cancer is often a part of multiorgan metas-tasis. Indeed, no patients with thymic metastasis alonehave been reported in the literature (1). As previouslyreported, the present patient also had a metastatic lesionin the right lung.

Breast cancer usually recurs within 5 years aftersurgery, and the frequency of recurrence begins todecrease in the 10th postoperative year. Takeuchi et al.reported that 284 of 1116 patients with breast cancerexperienced recurrence after surgery, and only 12 (4.4%)

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.

Figure 2 Histological appearance (hematoxylin–eosin staining, ×200).

Histological examination showed a solid tubular carcinoma sharply

demarcated from the surrounding fibrous stroma.

S Fujioka et al. Thymic metastasis of breast cancer

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

of the 284 patients had recurrence more than 10 yearsafter surgery (5). Recurrence occurs much less frequently20 or more years after surgery, and Hasegawa et al.reported a recurrence rate of only 0.1% (6). Character-istically, late, ipsilateral, locoregional recurrence (such asmetastasis to the ipsilateral chest wall, axillary lymphnodes, or supraclavicular lymph nodes) accounts for themajority (74%) of all recurrences, and distant metastasisaccounts for a small proportion of all recurrences (6).Takeuchi et al. reported that lymph node metastases werefound at the initial surgery in 10 of 12 patients with laterecurrence (5), suggesting that lymph node metastasis atthe initial presentation of breast cancer is closely associ-ated with late recurrence. The two above-mentionedpatients with thymic metastasis of breast cancer hadaxillary lymph node metastasis at the time of surgery,which recurred within 1 year after surgery (2,3). Thepresent case is extremely rare in that the patient hadbreast cancer with no lymph node metastasis at the initialsurgery; she developed late distant metastasis to thethymus 22 years after surgery, representing the first casein the literature.

Using FDG-PET to detect metastatic breast cancer,Morris et al. found that the most frequent sites of metas-tasis were the bone, lung, liver, and lymphatic tissue.They also found that a correlation existed between FDGuptake and the prognosis of patients (7). In the presentpatient, preoperative FDG-PET showed increased FDGuptake in the thymus, but no FDG uptake in the hilararea, mediastinal, parasternal, or supraclavicular lymphnodes. Therefore, thymoma was suspected as the mostlikely preoperative diagnosis. Regarding the sensitivity ofFDG-PET, it is said that small-diameter tumors tend to benegative for FDG uptake. Reinhardt et al. reported thatthe sensitivities of FDG-PET for malignant lesions8–10 mm and 5–7 mm in diameter were 78% and 40%,respectively, indicating a particularly low sensitivity fortumors less than 7 mm in diameter (8). In the presentcase, the metastatic lesion in the right lung was 7 mm indiameter, presumably resulting in no significant FDGuptake (or false-negative FDG uptake). Therefore, it issafe to assume that metastases too small to be detectedwere present elsewhere in the body. Endocrine therapy isconsidered the mainstay of treatment for patients with

distant metastases in the absence of hepatic or othervisceral metastases, and aromatase inhibitors are recom-mended for postmenopausal patients with luminal A or Bbreast cancer (9). The present patient had luminal Abreast cancer and was treated with an aromatase inhibi-tor alone. As of August 2013, 36 months after surgery,she is free of locoregional or distant metastasis, with anormal carcinoembryonic antigen level.

Acknowledgment

The authors have no conflict of interest to report.

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