Japanese Journal of Clinical Oncology 2004 34(10):630-633; doi:10.1093/jjco/hyh105
© 2004 Foundation for Promotion of Cancer Research
Pulmonary Metastasis 12 Years After Resection of Thymoma with Microscopic Capsule Invasion
Hiroaki Nomori1,
Kenichi Watanabe1,
Takashi Ohtsuka1,
Tsuguo Naruke1,
Keiichi Suemasu1,
Hideki Orikasa2 and
Kazuto Yamazaki2
1 Department of Thoracic Surgery and 2 Department of Pathology, Saiseikai Central Hospital, Tokyo, Japan
For reprints and all correspondence: Hiroaki Nomori, Department of Thoracic Surgery, Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo 108-0073, Japan. E-mail: hnomori{at}qk9.so-net.ne.jp
Received April 12, 2004;
accepted July 3, 2004
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Abstract
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We report on a 50-year-old female who developed pulmonary metastasis
12 years following the resection of a thymoma with microscopic
capsular invasion. The patient was found to have a mediastinal
mass at the age of 18 years; however, she refused to undergo
surgery. At the age of 38 years, the patient underwent surgery
for resection of the tumor; it was diagnosed as a macroscopically
encapsulated thymoma with microscopic capsular invasion. Multiple
pulmonary metastases occurred 12 years following the resection
of the tumor; all the metastatic masses were resected. Although
the patient suffered from myasthenia gravis 4 months following
the resection of pulmonary metastases, she remains free of myasthenia
gravis with no recurrence of tumor at 2 years post-surgery.
Long-term follow-up is essential for the detection of recurrence
after resection of a thymoma with microscopic capsular invasion,
and surgery could be the best treatment for distant metastasis
in case of resectable lesions.
Key Words: thymoma • pulmonary metastasis • prognosis • post-thymectomy myasthenia gravis
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INTRODUCTION
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Thymoma is usually a slow-growing tumor; however, it displays
unpredictable behavior on rare occasions (
1,
2). Although intrathoracic
recurrence occurs sometimes in patients with invasive thymoma,
few cases of distant metastasis following resection of a non-invasive
thymoma have been reported. We report a patient who developed
pulmonary metastasis 12 years following the resection of a macroscopically
encapsulated thymoma with microscopic capsular invasion.
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CASE REPORT
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The patient was a 50-year-old female. At the age of 18 years,
a mediastinal mass, approximately 3 cm in diameter, was noticed
on a routine chest X-ray (
Fig. 1). The mass gradually increased
in size; however, the patient refused to undergo surgery. At
the age of 38 years, the patient was admitted to our hospital
for resection of the mediastinal tumor, which had increased
to 10
x 6.5 cm in size (
Figs 2 and
3). The serum level of anti-acetylcholine
receptor (AchR) antibody (Ab) was found to be elevated to 5
nmol/l (normal range, <0.2 nmol/l); however, the patient
did not experience any symptoms of myasthenia gravis (MG). A
thymoma was diagnosed following percutaneous needle aspiration
biopsy. Therefore, a thymo-thymectomy was performed via a median
sternotomy. During surgery, the tumor was found to be significantly
compressing the adjacent organs; however, no invasion was observed.
Although the tumor was macroscopically encapsulated (
Fig. 4),
microscopic examination revealed capsular invasion that was
confined within the thymic tissue (
Fig. 5). On histology, the
thymoma was found to be of a mixed lymphocytic and epithelial
type. The epithelial cells were mixed with polygonal and spindle
cells. Following the resection of the primary tumor, the patient
was followed-up by CT scanning annually, without adjuvant chemotherapy
or radiation therapy. Twelve years following the resection (patient
age, 50 years), a chest CT scan showed bilateral pulmonary nodules.
One nodule (10 mm in diameter) was observed in the right lung,
and two nodules (3 and 10 mm in diameter, respectively) were
observed in the left lung (
Fig. 6). These tumors were resected
by bilateral thoracotomy. Microscopic examination of the resected
tumors showed findings that were similar to those of the primary
thymic tumor. Four months following the resection of the pulmonary
metastases, the patient complained of diplopia and ptosis, and
the serum level of anti-AchR Ab was found to be elevated to
14 nmol/l. The edrophonium chloride (antirex) test was found
to be positive. Therefore, postoperative MG was diagnosed, and
the patient was treated with an anti-cholinergic drug (pyridostigmine
bromide) for 12 months. She is doing well 24 months following
the resection of the pulmonary metastasis with no evidence of
recurrence of thymoma or MG symptoms; however, the serum level
of anti-AchR Ab remains elevated (12 nmol/l).
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Figure 1. Chest X-ray at the age of 18 years shows the mass shadow in the right, upper mediastinum (indicated by an arrow).
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Figure 2. Chest X-ray at the age of 38 years shows that the mass has increased in size to 10 cm x 6.5 cm.
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Figure 3. Chest CT scan shows the tumor in the middle compartment of the mediastinum compressing the lung, superior vena cava and trachea.
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Figure 4. Macroscopic finding of the primary tumor. The cut surface shows a completely encapsulated mass.
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Figure 5. Microscopic picture shows that the tumor invades the capsule but remains confined within the thymic tissue.
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Figure 6. Chest CT scan showing one of the metastatic lesions in the left lung (indicated by an arrow).
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DISCUSSION
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The postoperative recurrence rate for invasive and non-invasive
thymoma has been reported to be 11–36% and 0–7%,
respectively (
3,
4). The majority of recurrences are local, and
distant metastasis is rare, particularly following the resection
of non-invasive or microscopically invasive thymoma. To our
knowledge, only six cases of distant metastasis following the
resection of a non-invasive thymoma have been reported (
Table 1)
(
5–
8). The clinical characteristics of the six patients
were as follows: (i) ages between 20 and 51 years (mean 44 ±
12 years); (ii) five females and one male; (iii) the interval
between primary tumor resection and recurrence ranged from 4
to 14 years (mean 7 ± 5 years); (iv) one patient suffered
from MG; and (v) the sites of metastasis were the lungs in three
patients, liver in two patients and pleura, pectoralis muscle,
brain, bone, thyroid and spleen in one patient each. Five of
the six patients underwent a total excision of the metastases;
three patients survived for 1–4 years following the excision.
Microscopic capsular invasion was detected in the thymoma of
the present patient; however, it was confined within the tissue
of the thymus gland (Masaoka's stage II) (
3). Furthermore, it
showed slow progression, i.e. the interval between initial detection
and primary tumor resection was 20 years and that between the
primary tumor resection and treatment of the lung metastases
was 12 years (a total of 32 years). Although the present tumor
displayed very slow growth, it had invaded the capsule and was
potentially malignant; this resulted in distant metastasis.
Therefore, a long-term follow-up is essential in order to detect
recurrence even after the resection of a macroscopically non-invasive
but microscopically invasive thymoma.
The treatment of recurrent thymoma remains controversial due
to the unpredictable natural history of this tumor. Ruffini
et al. reported the outcome in 30 patients with recurrent thymoma
and drew the following conclusions: (i) total resection of a
locally recurrent thymoma resulted in a better prognosis than
that observed with radiation therapy; and (ii) the 5-year survival
rate was 100% following resection of local recurrence; this
was significantly better as compared to the 30% 5-year survival
rate following resection of distant metastasis (
9). Although
these data did not suggest that the resection of distant metastasis
from a thymoma resulted in prognostic benefit,
Table 1 shows
the possibility of long-term survival following the resection
of distant metastases from an encapsulated thymoma. We believe
that surgical treatment may result in a good prognosis for patients
with distant metastases from an encapsulated or microinvasive
thymoma due to its slow-growing characteristic.
The present patient suffered from MG, 4 months following the resection of pulmonary metastases. The occurrence of post-thymectomy MG has been reported in 4.6% of patients without symptoms of MG prior to surgery (10,11). Early as well as late onset of post-thymectomy MG has been reported; the former could be caused by subclinical MG that existed prior to surgery, and some cases of the latter could be caused by the recurrence of tumors (10). To our knowledge, the present patient is the first case who suffered from MG following the resection of metastatic thymoma. The patient had elevated serum level of anti-AchR Ab prior to the resection of primary tumor and did not have any clearly demonstrable remnant thymus or recurrent thymoma at the time of the occurrence of MG. Therefore, it is considered that a surgical stress caused by the excision of the lung metastases could have manifested the subclinical MG.
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References
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Abstract
INTRODUCTION