Seminal vesicle metastasis after partial hepatectomy for hepatocellular carcinoma

Background Metastasis to the seminal vesicle is extremely rare for hepatocellular carcinoma (HCC). To our knowledge, it has been not reported in literature. The purpose of the present paper was to report a case of metastasis to the seminal vesicle after HCC resection, along with its histological features and immunohistochemical characteristics. Case Presentation A 46-year-old Chinese man was admitted to our hospital due to abdominal distension. He had a history of HCC related to hepatitis B virus infection. Moreover, left partial hepatectomy was performed in another hospital 28 months ago, and right partial hepatectomy for HCC recurrence in our hospital 4 months ago. After resection, radiofrequency ablation therapy had been performed. About 27 months after the initial operation, contrast-enhanced computed tomography (CT) of the pelvic cavity revealed a mass with homogeneous enhancement in the seminal vesicle. Transrectal needle biopsy revealed a poorly differentiated adenocarcinoma. Therefore, seminal vesiculectomy was resected. The histological diagnosis of the removed tumor was compatible with the original HCC. Immunohistochemical examination demonstrated that the tumor cells were positive for glypican-3 (GPC3), alpha-fetoprotein (AFP), hepatocyte paraffin-1 (Hep Par 1), cytokeratin 18 (CK 18), and hepatocyte antigen, which confirmed that the seminal vesicle tumor was a metastatic tumor of HCC. However, CT subsequently revealed multiple metastatic foci in the abdominal and pelvic cavities in May 2009 and August 2009, respectively. Conclusion The seminal vesicle is an extremely rare metastatic site for HCC, and the prognosis is very poor. A combination of clinical and pathological features is necessary for a correct diagnosis, and primary tumor should be excluded before diagnosing metastatic foci.


Background
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, accounting for nearly one million new cases each year [1]. The long-term prognosis for HCC remains poor, with a 5-year survival rate of < 5% [2], and intrahepatic and extrahepatic metastasis are the most important factors. The liver is the most common site of HCC metastasis, accounting for approximately 85% to 90% of all cases [3]. Extrahepatic metastases have been reported to occur in 13.5% to 42% of HCC patients [4][5][6]. The most frequent sites of extrahepatic metastases are lung, abdominal lymph node, and bone [4,7,8]. To our knowledge, it has not been reported in literature that HCC metastasize to the seminal vesicle. Here we report the case of a 46-year-old man with metastatic HCC to the seminal vesicle after a liver resection for HCC and recurrence, and observed its histological and immunohistochemical characteristics.

Case presentation
A 46-year-old Chinese man was admitted to our hospital due to abdominal distension in January 2009. It was the second time that he was as an inpatient of our After leaving the hospital, the patient received thymic peptide injections twice a week, but the dosage was not provided. About half a year after the initial operation, abdominal ultrasound examination revealed a mass in the right lobe of the liver, which was determined to be recurrent HCC ( Figure 1). Thus, regular (one time/three months) radiofrequency ablation therapy (60W, 2 min/ time; the total 3 times) and transarterial interventions (embolization or chemoembolization) were performed until September 2008. During therapy, the serum level of AFP was elevated (21.51-4689 ng/ml) (the details could be seen in table 1). However, abdominal ultrasound examination also revealed multiple solid occupation in the liver (Figure 2 and 3). Thus, the patient underwent partial resection of the right anterior segment for HCC recurrence in our hospital on September 20, 2008. After operation, the patient was not received any antitumoral therapy due to his weakness. On   Figure 7). Of course, the Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Discussion
Metastasis from the liver to extrahepatic tissues is not common for HCC (13.5%-42% of cases) and has a poor prognosis [4][5][6]. For unknown reasons, the seminal vesicle is an extremely rare site of metastasis for HCC; therefore, clinical data is limited. Tumors of the seminal vesicles may be primary tumors or secondary tumors originating from adjacent organs such as the bladder, prostate, or rectum. Primary seminal vesicle tumors are rare and may be benign (papillary adenoma, cystadenoma, hydatid cyst, and amyloid deposition) or malignant (adenocarcinoma, sarcoma, cystosarcoma phyllodes, primary seminoma, and carcinoid). Adenocarcinoma is the most frequent malignant tumor. Therefore, we first excluded it before diagnosing the mass as metastasis from HCC. In 1956, Dalgaard and Giertson [9] established the following criteria for the diagnosis of primary seminal vesicle adenocarcinoma: 1) the tumor should be a microscopically verified carcinoma, localized exclusively or mainly to the seminal vesicle; 2) the presence of other simultaneous primary carcinoma should be excluded; and 3) the tumor should preferably resemble the architecture of the non-neoplastic seminal vesicle.    In the present case, the patient had a history of HCC. Moreover, according to the surgical doctor's introduction, the mass was only found in seminal vesicle during the operation. In addition, the histopathological characteristics of the mass from seminal vesicle were similar to that of primary HCC, although it had a poorly differentiated appearance. Immunohistochemically, the tumor cells were positive for GPC3, AFP, hepatocyte antigen, HepPar1, and CK18, but negative for CK7, CK20, PLAP, PSA, CA125, EMA, CD117, and CEA. Primary seminal vesicle adenocarcinoma expresses these markers as well as CK7, CA125 and CEA but not AFP, GPC3 and hepatocyte antigen [10]. It is known to all, AFP is a relatively specific but rather insensitive marker for hepatocellular differentiation and is present in only one quarter of the cases. Recently, GPC3 has been reported as novel serum and histochemical marker for HCC, with positive staining in 72% to 100% of cases [11][12][13][14][15][16]. Thus, based on the tumor cells positive reactivity for GPC3, AFP, hepatocyte antigen, Hep Par 1, and CK18, we thought that the seminal vesicle mass should firstly be considered as a metastatic HCC lesion. Of course, AFP, HepPar1 and GPC3 were not only positive in HCC. Many malignant tumors with AFP producing and hepatoid features resembling HCC, such as hepatoid adenocarcinoma of the stomach and primary hepatoid yolk sac tumor (H-YST) of ovary and testis, especially the latter, express AFP, Hep Par 1 and GPC3 [17,18]. Namely, AFP, Hep Par 1 and GPC3 are useful markers for HCC, but not entirely specific. However, the YST usually occurs in younger patients, and most of them occur in the ovaries and testis. About 20% arise in extraovarian sites, including the mediastinum, sacrococcygeal region, cervix, vulva, pelvis, and retroperitoneum [19][20][21][22][23][24]. We do not believe primary H-YST of the seminal vesicle has been reported in the literature. Moreover, gonadal dysgenesis and the presence of a residual component of typical yolk sac tumor or a polyvesicular vitelline pattern, or glandular-like structure some with mucin production, is helpful for differential diagnosis. In addition, immunohistochemically, the tumor cells of H-YSTs are positive for CK besides AFP and HepPar1, and negative for hepatocyte antigen, CK20, CEA and EMA. Thus, we finally considered it was a metastatic HCC lesion based on its clinical and pathological features.
No sufficient data is currently available regarding treatment for HCC with metastasis to the seminal vesicle. However, the prognosis appears to be poor. In our case, the patient had undergone regular radiofrequency ablation since the diagnosis of HCC, but intrahepatic and seminal vesicle metastatic lesions were found after half a year and 27 months, respectively. It was worse that CT revealed multiple metastatic foci in the abdominal and pelvic cavities after 32 months and 3 years, respectively.
In conclusion, the seminal vesicle is an extremely rare metastatic site for HCC, and the prognosis is very poor. Although AFP, Hep Par 1, hepatocyte antigen and GPC3 are useful markers for HCC. They are not, however, entirely specific, showing different extent staining in hepatoid adenocarcinoma and H-YST. Thus, a combination of clinical and pathological features is necessary for a correct diagnosis, and primary tumor should be excluded before diagnosing metastatic foci,