Isolated eyeball metastasis of non-seminomatous germ cell testicular tumor

Introduction. Testicular tumors most frequently metastasize to regional lymph nodes. Non-seminomatous tumor metastasis of testicle (NSGCTT) to the eyeball is rare. Case report. We presented a 24-year old man, referred to the ophthalmologist due to acute pain and abrupt loss of sight in the left eye accompanied by its enlargement. Orbital and endocranial computerized tomography (CT) was carried out, indicating the tumor in the left eye. His previous medical history provided the information that the right testicle was painlessly enlarged for 8 months. Ultrasonography showed a completely tumorously altered testis. Abdominal and chest CT failed to reveal any secondary deposits in visceral organs and lymph glands. Tumor markers (AFP – alpha-fetoproteins, beta hCG – human choronic gonadotropin beta) were elevated. Right radical orchiactomy was performed (showed NSGCTT), followed by polychemotherapy with cisplatinum 100 mg/m2, etoposide 120 mg/m2, bleomycin 15 mg/m2 (PEB  4), resulting in normalization of tumor marker values and significant regression of the left eyeball. Next, the left eye enucleation and ocular prosthesis implantation was carried out. Pathohistological evaluation indicated fibrosis and necrosis only. In a 5-year follow-up period, the patient was free of recurrence. Conclusion. Isolated hematogenous metastasis of the NSGCTT to the eye is rare. In our case, the left eye was the only metastatic localization. After chemotherapy and eye enucleation the patient was in a 4year follow-up period free of the recurrence.


Introduction
Testicular tumors most frequently metastasize to regional lymph nodes. However, if histopathological examina-tion of testicular tumor confirms choriocarcinoma, hematogenous metastases might be expected. Most commonly metastatic sites can be present in pulmonary parenchyma, but rarely may be found in organs not otherwise expected. The brought to you by CORE View metadata, citation and similar papers at core.ac.uk very fact of the presence of nonpulmonary metastases represents poor prognostic factor. Unfortunately, the outcome of these patients is usually fatal in spite of chemotherapy and other therapeutic options [1][2][3][4] .
Isolated hematogenous metastases to distant organs (brain, kidney, liver, bones, eye) are rare. Secondary deposits in the eye are extremly rare, and such cases have been disscused in published articles.

Case report
A 24-year-old man with sudden pain and loss of sight in the left eye associated with its enlargement referred to the ophthalmologist. He reported that he had experienced the problems with sight about two weeks earlier manifested in blurred vision as if a "curtain" was pulled over his eye. Computerized tomography of the orbit and endocrainum ( Figure 1) revealed a 12 mm soft tissue mass in the eye, located in the left bulbus behind the lens, which was not stained after iv contrast injection. The left lacrimal gland was enlarged and the left upper lid was edematous.
The patient's medical history provided the information on painless enlargement of the right testicle some 8 months ago. A complete urological evaluation was carried out. A painless hard enlargement, 6  6 cm in size, of the right testicle was found. Ultrasonography examination showed the enlarged, nonhomogenous, completely tumorously altered testicle with intact tunica albuginea. Tumor marker levels were elevated: alpha-fetoproteins (AFP) 4977 ng/mL, and beta humane chorionic gonadotrophin (hCG) 3557 mIU/mL. Computerized tomography of the abdomen failed to show any secondary deposits in the parenchymatous organs or any enlargement of retroperitoneal lymphnodes. Radiography of the lungs was normal.
In a postoperative period, the values of tumor markers declined. Due to NSGCTT with the increased values of tumor markers and distant metastases, polychemotherapy by PEB protocol (cisplatinum 100 mg/m 2 , etoposide 120 mg/m 2 , bleomycin 15 mg/m 2 ) was introduced. A total of 4 cycles of the therapy were administered, which was well tolerated; consequently, the tumor marker values restored to normal (AFP 4.3 ng/mL, beta hCG 1.4 mlU/mL) with a considerable reduction of the formerly enlarged left eye, that was verified by CT scan of the orbit and endocranium (soft-tissue mass in the left bulbus was not imbibed by contrast) (Figure 2). Due to such outcome the left eye enucleation with ocular prosthesis implantation was carried out. Pathohistologicel examination proved the presence of fibrosis and necrosis only, without elements of vital cancer. The patent was controlled on regular basis and within a 4-year follow-up period the patient was free of recurrence of the underlying disease.

Discussion
Testicular tumors are completely curable diseases even when they present with distant metastases. They primarily metastasize via lymphatic pathway to regional lymphatics and along the major blood vessels. The most common visceral hematogenous metastases of testicular tumors are to the lungs, liver, brain and bones. For easier evaluation of prognosis of testicular tumors, prognostic factors have been introduced, ie high values of tumor markers, mediastinum-origin tumor and the presence of non-pulmonary visceral metastases.
Due to a new more efficacious therapeutical protocol and, thus, longer survival of patients with malignant tumors of different primary localizations, patients with orbital metastases are seen more often. However in case of patients with testicular tumors, orbital metastases are still exceptional. Only a few cases have been reported in the available literature. Nevertheless, in all of these cases, metastatic changes of the eye were associated with other organs metastases (lungs, retroperitoneum, brain, etc).
It is well-kown that choriocarcinoma metastasizes by hematogenous way and is followed by high hCG values, what accounts for multiple localizations of primary metastases. Literature review suggests that the very choriocarcinoma is the most frequent histological form found in intraocular metastases [5][6][7] . According to Kavanagh et al. 4 , metastases of testicular choriocarcinoma to the eye are rare, and a reader may find about dozen references in the literature, with that all the authors reported an association with other metastases. As the sequelae of secondary deposits in several organs and choriocarcinoma are unfavorable histological variation, the survival of these patients was very poor. Only Nakajima et al. 1 described a successful outcome of patients with multiple secondary deposits in the eye, brain and lungs.
Isolated orbital metastases are very rare. Rush et al. 2 published the article on metastasis of testicular seminoma to the eye which was successfully treated by radiotherapy. Lodato et al. 6 described metastasis of the embryonal cancer to the eye and, reviewing the primary and secondary eye tumors, they stressed the need for systemic examination in case of young people with ocular tumors. Kiymaz et al. 8 reported a case with embryonal testicular cancer with metastases to brain and eye with, unfortunately, fatal outcome, while the embryonal cancer tissue was found in the eye on postmortem examination.

Conclusion
In our case, the left eye was the only metastatic localization and isolated metastasis of non-seminomatous testicular tumor. During chemotherapy, the values of serum tumor markers were restored to the normal ones and the eye tumor volume was reduced. Eye enucleation, where residua of secondary deposits remained after chemotherapy, was necessary because it could not be definitely established if eye tumor had been completely eliminated by the therapy. Final histological examination of the eye specimen falied to show any vital cancer, with only fibrosis and necrosis found, as the result of chemotherapy with a complete response.