SURGERY TODAY C Springer 2008
Alpha-fetoprotein (AFP)-Producing Adrenocortical Carcinoma - Long Survival with Various Therapeutic Strategies Including a Lung Resection: Report of a Case
WAKAKO HAMANAKA1,3, SATOSHI YONEDA1, TAKAYUKI SHIRAKUSA3, HIROSHI SHIRAHAMA2, YUKIE TASHIRO2, AKINORI IWASAKI3, TAKESHI SHIRAISHI3, and HIROHUMI TSURU1
Departments of 1Thoracic Surgery and 2 Pathology, Imakiire General Hospital, 4-16 Shimotatsuo-cho, Kagoshima 892-0852, Japan 3 Department of Thoracic Surgery, School of Medicine, Fukuoka University, Fukuoka, Japan
Abstract
We experienced a very rare case of late pulmonary metastasis from ACC. The patient was a 40-year-old woman who had undergone a left adrenectomy 12 years earlier. Instead of a large metastatic lung tumor with hemothorax and the existence of metastases in other organs, combined therapy of repeated resections for metastases and adjuvant therapy allowed for almost a 36-month survival following the first recurrence and a good quality of life. In addition, a blood and pathologi- cal study revealed that the tumor in this case was an alpha-fetoprotein-producing ACC, which is, as far as we could ascertain, the first case of its kind.
Key words Metastatic lung tumor · Adrenocortical car- cinoma . AFP-producing tumor . Hemothorax . Long survival
Introduction
Adrenocortical carcinoma (ACC) is uncommon, accounting for only 0.23% of all cancer cases1. The typical delay in the diagnosis and the high frequency of metastasis tend to make its prognosis worse. Treatments for recurrence and metastatic disease with chemother- apy including mitotane, or with radiation only, have had limited success. In contrast, chemotherapy following a local resection has shown a better patient survival.2-9 Therefore, a complete surgical excision is essential for prolonged survival. On the other hand, pulmonary metastasis from ACC is very rare with regard to meta- static lung tumors. In more than 20 years in our unit, we have never experienced this type of metastasis.
We report a successful case of a large pulmonary metastasis, which occurred 12 years after the initial operation. Furthermore, this patient has been living with the disease for 36 months from the first recurrence until the last follow-up.
Case Report
A 40-year-old woman was admitted for sudden right chest pain and dyspnea in October 2003. The patient had a one-pack-per-day history of smoking for several years from the time she was 30 years old, but she was not a habitual drinker. Her past medical history included a left adrenalectomy at another institution in 1991 for a large adrenocortical tumor (14 × 11 × 10cm) without hormone production. Around that time she tested posi- tive for hepatitis B virus, and her hepatic function was also monitored thenceforth. Roentgenograms and com- puted tomography revealed a huge mass in the left upper lobe and left hemothorax (Fig. 1). The findings on admission revealed severe anemia and low blood pres- sure due to bleeding from the tumor. After intubation with a chest tube and blood transfusion, the patient’s state became stable, and she underwent surgical treat- ment on the fifth day following admission. Because the preoperative diagnosis was not complete, a typical left upper lobectomy including the huge tumor (6 x 5 x 4cm) was performed with a hilar and mediastinal lymph node dissection (Fig. 2). The histology showed the pres- ence of atypical epithelial cells forming an alveolar pattern separated by thin fibrovascular stroma. In addition, many anaplastic large cells, multinucleated cells, and several mitotic cells were recognized. These histological features were almost identical to the previ- ous specimen in 1991 (Fig. 3a, d). Furthermore, only one of the intrapulmonary lymph nodes showed any metas- tasis of carcinoma.
a
L
Immunohistochemistry (IHC) of the resected adrenal and lung tumors has revealed positive findings for Ad4BP/SF-1 (Fig. 3c, f), Cytokeratin (CK) AE1/ AE3, and alphainhibin (partially), while showing nega- tive findings for Hepatocyte Specific Antigen (HSA), CK7, Epithelial membrane antigen (EMA), and Surfac- tant Apoprotein A (SPA), thus suggesting the lung tumor to be a metastatic lesion from primary adreno- cortical carcinoma. The postoperative course was uneventful.
Three months later, metastases were detected in the brain and left kidney. A tumorectomy and y-knife radia- tion were performed for the brain metastasis, in addi- tion to a left nephrectomy. After the nephrectomy, the patient received adjuvant therapy by mitotane. As of February 2007, the patient is still alive with the disease.
Discussion
Adrenocortical carcinoma is a rare disease with an annual incidence of 0.5-2 per million people.2,10-13 There is a bimodal occurrence by age, with peaks in the first and fourth to fifth decades.2,4 ACC can be broadly clas- sified by hormone production as either a functional type or a nonfunctional type. Tumors in adults are more commonly nonfunctional,4,10 and they occur much more often in men than in women.4 Whether the endocrine potential is a prognostic factor remains controver- sial.10,14-17 Even though many researchers and physicians have attempted to create a better prognosis, the overall 5-year survival rate remains between 10% and 35%.2,10 Icard et al.1º reported 253 cases in France in which the 5-year survival rates were 66% for stage I, 58% for stage II, 24% for stage III, and 0% for stage IV. In addition, more than 50% of the patients were stage III or IV at the time of diagnosis,10,11 and 85% of the patients had developed either local recurrence or metastasis after undergoing a curable resection.15 Pommier and Brennan,12 however, reported the mean survival time for patients with recurrence who were medically treated to be 19 months, as compared with 56 months for patients who underwent a reoperation. Surgical treatment is thus most important for both the primary disease and the recurrent or metastatic disease, and the completeness of a curable resection is considered to be essential for a good prognosis.18,19 In our case, the patient was stage II at the time of diagnosis, and she developed multifocal metastases 12 years after the first operation. A meta- static lung tumor was discovered because of symptoms of hemothorax, and a portion of the brain metastasis was treated by radiation therapy and mitotane only. Although this suggests that the risk of recurrence is high in this case, the patient has remained alive with the disease for 36 months without any new lesions since then. Stojadinovic and Brennan once reported20 that a disease-free interval beyond 24 months following the treatment of recurrence indicated a better survival rate.
a,b
c
d,e
f
Strictly speaking, our case is not valid for this result, but our case might be expected to have a prolonged survi- val with a careful follow-up and an early curable reop- eration when necessary. Generally, various metastatic tumors from intra-abdominal organs are frequently found, and the optimal therapeutic strategy for such cases might be a surgical resection according to Thom- ford’s Principle of Indications. Although the metastasis of ACC is very rare, the surgical option should also be considered if the number of metastases is not too large. This time the metastatic tumor was very large and it was associated with intrathoracic bleeding; therefore, a left upper lobectomy was necessary. However, a partial resection using video-assisted thoracoscopic procedures may be recommended for small metastatic lesions.
During the follow-up, we discovered an interesting relationship between the serum level of alpha-fetopro- tein (AFP) and the patient’s disease progress (Fig. 4). She underwent periodic examinations to evaluate her hepatic function because of chronic hepatitis. The serum level of AFP decreased to a normal level following the resection of the metastasis when compared with the markedly abnormal level before the operation. IHC revealed that many cells of the resected tumors are stained by both Ad4BP/SF-1 and AFP (Fig. 3b, c, e, f). This fact led us to conclude that the adrenal tumor in this case was an AFP-producing ACC. Yoshioka et al.21
ng/ml
300
250
*
200
៛
150
-AFP
100
50
0
01-Jun-03
10-Oct-03
05-Nov-03
29-Nov-03
03-Jan-04
31-Mar-04
02-Aug-04
22-Dec-04
17-Jun-05
date
reported the first patient in Japan with an adrenal hepa- toid carcinoma, which is an AFP-producing tumor, and this tumor was different from a hepatoid tumor with regard to its morphology. We retrospectively reviewed her documents, films, blood data, and other IHC, but there were no signs of primary tumors in other organs (data not shown). As far as could be ascertained, this is the first case of an AFP-producing ACC. We still cannot determine the precise cause, but the serum level of AFP was nevertheless considered to be a good predictor for recurrence in this case.
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