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Anterior Segment Metastases from an Ovarian Choriocarcinoma
ANTERIOR S E G M E N T METASTASES FROM AN OVARIAN CHORIOCARCINOMA KARNI W. FRANK, M.D.,
H. S A U L SUGAR, M.D.,
H U G H BECKMAN, M.D., Detroit,
Most tumor metastases to the eye occur in the posterior uvea. Data accumulated from several series 1 - 3 indicate that only about 10% of ocular metastases occur in the anterior segment. The most common sites of the primary lesions are the breast and the lung. Choriocarcinoma is a rare malignant trophoblastic tumor that originates in the female uterus and ovary and in the male testis. Rarely, extragenital primary chori ocarcinomas have been described. 4 , 5 Ges tational and nongestational types of cho riocarcinoma are recognized, but gesta tional choriocarcinomas are associated with pregnancy, particularly pregnancy in which a hydatidiform mole occurs. Non gestational choriocarcinomas derive from germ cells of the testis or ovary. 6 Before the advent of chemotherapy choriocarci noma was fatal in over 85% of cases. With the introduction in 1955 of methotrexate therapy for this tumor the outlook changed dramatically. 7 Currently, a num ber of therapeutic agents, used singly or, more frequently, in combination, have produced clinical cures in as many as 98% of female patients whose cases are diagnosed early and treated vigorously, even in the presence of metastases. 8 Sixteen cases of choriocarcinoma metastatic to the eye have been reported. 5,9 ~ 23 We report herein an unusual case that From the Kresge Eye Institute, and the Depart ment of Pathology, Wayne State University School of Medicine (Dr. Frank), the Departments of Oph thalmology (Drs. Sugar, Beckman, and Thoms), and Obstetrics and Gynecology (Dr. Sherman), Sinai Hospital of Detroit, Detroit, Michigan. Reprint requests to Karni W. Frank, M.D., Oph thalmic Pathology Laboratory, Kresge Eye Institute, 3994 John R St., Detroit, MI 48201. 778
A L F R E D I. S H E R M A N ,
AND SUSAN T H O M S ,
M.D.,
M.D.
Michigan
documents metastatic choriocarcinoma solely to the anterior segment of the eye. We were able to make a tissue diagnosis of the ocular lesion early in its course, and were able to document the effect of thera py through clinical follow up and eventu al histopathologic examination of the globe. CASE REPORT A 28-year-old woman (gravida 2, para 2) was admitted to the hospital for the first time in January 1975 at age 25 years with a pelvic mass and marked ly increased human chorionic gonadotrophin titers of 5000 mlU/ml of serum determined by radioimmunoassay (normal by this method, < 1 mlU/ml). Her last menstrual period had been in August 1974. Her previous pregnancies had been unremarkable and she had never had a spontaneous abortion. A laparotomy was performed for diagnosis and the ovarian mass was resected. The tissue diagnosis was choriocarcinoma. No evidence of ectopic pregnancy was found, and teratomatous elements were not present within the tumor. Chemotherapy with methotrexate and dactinomycin (Actinomycin D) was initiated and the human chorionic gonadotrophin levels decreased to < 5 mlU/ml, but still were slight ly higher than the normal range. After four months they precipitously rose again to 300 mlU/ml. A chest x-ray revealed a mass in the lower lobe of the right lung. Cyclophosphamide was added to the thera peutic regimen. The pulmonary mass decreased in size radiographically and the human chorionic go nadotrophin levels fell transiently to within the normal range, but then began to rise again. In November 1975, the patient underwent a right lower lobectomy. Histopathologic examination revealed necrotic tumor. Subsequently, she developed central nervous system symptoms. Diagnostic evaluation indicated a mass in the right frontal lobe. A craniotomy was performed and the tumor was resected. Over the next few months human chorionic gonadotro phin levels decreased to the normal range where they remained for nearly five months. In late 1976, the patient developed an anterior uveitis in the left eye that was initially treated with topical corticosteroids and atropine. Initially, no metastatic lesions were visible in the eye although it was suspected that these were responsible for the uveitis when no response to corticosteroids was observed and the human chorionic gonadotrophin levels rose to
AMERICAN JOURNAL O F OPHTHALMOLOGY 87:778-782, 1979
VOL. 87, NO. 6
OVARIAN
CHORIOCARCINOMA
779
Fig. 1 (Frank and associates). Left eye two weeks before biopsy of conjunctival nodule (May 1977), showing a hemorrhagic mass in the anterior cham ber and a subconjunctival nodule (arrow) apparently extending from it. 35 mlU/ml. By May 1977, a mass was visible in the inferonasal quadrant of the anterior chamber of the left eye and a second mass, which appeared to have extended from it, was visible subconjunctivally in the same quadrant (Fig. 1). Results of examination of the fundus, including indirect ophthalmoscopy with scleral depression were negative. Biopsy of the subconjunctival mass was done in June 1977 and histopathologic examination revealed a markedly vascular and hemorrhagic tumor (Fig. 2) composed of two cell types, consistent with the cytotrophoblastic and syncytiotrophoblastic elements of choriocarcinoma (Fig. 3). The cytotrophoblastic cells were large, polygonal cells, with pale-staining-to-clear cytoplasm, distinct cellular borders, and large, ve sicular nuclei with prominent nucleoli (C, Fig. 3). The syncytiotrophoblastic cells had deeply staining
Fig. 2 (Frank and associates). Left eye, section of biopsy specimen showing a highly vascularized and hemorrhagic mass in the substantia propria of the bulbar conjunctiva. The area enclosed by the white rectangle is enlarged in Figure 3 (hematoxylin and eosin, x95).
Fig. 3 (Frank and associates). Enlargement of the area within the rectangle in Figure 2 showing cyto trophoblastic cells (C), and syncytiotrophoblastic cells (S). (hematoxylin and eosin, x630). eosinophilic cytoplasm and hyperchromatic nuclei. Their cell borders were indistinct and at times the cells had a tendency to form a multinucleated syncytium (S, Fig. 3). After surgery, visual acuity was 6/6 (20/20) in the right eye and 6/30 (20/100) in the left eye with moderate flare, cells, and posterior synechiae pre sent. Gonioscopy revealed several apparent tumor nodules in the chamber angle, and ultrasonography showed a mass in the anterior segment but no abnormalities posteriorly. Ophthalmoscopic exami nation also continued to show no lesions in the posterior segment. Multiple photocoagulation treat ments with the argon laser were given using the slit-lamp delivery system and the Goldmann gonioscopic lens to ablate tumor nodules in the chamber angle. In August 1977, radiation treatment to bulky portions of tumor located in the ciliary body was begun. The treatment consisted of 25 fractionated doses of radioactive isotope of cobalt (60C) given over a period of 38 days; 200 rads per dose were
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given, bringing the total to 5000 rads. The patient continued to receive topical corticosteroids and atropine. There appeared to be some shrinkage of the tumor, and over the next three months, human chorionic gonadotrophin levels decreased to within the normal range. In October 1977, seizures developed and another cerebral metastasis was found. System ic chemotherapy with methotrexate, dactinomycin, cyclophosphamide, and doxorubicin HC1 (Adriamycin) was re-administered. Additionally, subconjunctival methotrexate was administered in Novem ber 1977 in an attempt to destroy residual ocular tumor. The uveitis persisted and the eye became painful and soft. Visual acuity decreased to 6/120 (20/400). Corneal epithelial defects and a vascular pannus were noted. Human chorionic gonadotrophin levels rose again to over 100 mlU/ml and the chemotherapeutic regimen was altered to include dactin omycin, vincristine, bleomycin sulfate, and cisplatinum. By March 1978, vision had decreased to light perception and the eye remained soft and painful. Enucleation was performed on April 19, 1978. Histopathologic examination revealed an irregular cor neal epithelium that was absent in many areas and hyperplastic in others. A degenerative pannus was present, and there was extensive stromal necrosis with vascularization and a dense infiltrate of inflam matory cells. The iris showed necrosis and atrophy of the stroma and almost total disappearance of the sphincter and dilator muscles. There were posterior synechiae. Rubeosis iridis, together with extensive peripheral anterior synechiae and hyphema, were noted. The only evidence of residual tumor cells was found in the inferior temporal quadrant where, within the longitudinal portion of the ciliary mus cle, there was a group of tumor cells (Fig. 4) with large, irregularly shaped hyperchromatic nuclei, prominent nucleoli, and a vacuolated cytoplasm
Fig. 4 (Frank and associates). Clumps of residual tumor cells in ciliary muscle after massive treatment by various modalities. The area enclosed by the white rectangle is enlarged in Figure 5 (hematoxylin and eosin, x 160).
Fig. 5 shown zation eosin,
JUNE, 1979
(Frank and associates). Same tumor cells as in Figure 4 (within rectangle). Note vacuoliof cytoplasm and nuclei, (hematoxylin and x630).
(Fig. 5). The lens was cataractous. Macrophages and acute inflammatory cells were present in the vitre ous. The retina revealed loss of ganglion cells. The choroid was normal. The optic disk showed cupping and posterior bowing of the lamina cribrosa. After enculeation the patient's condition contin ued to deteriorate. H u m a n chorionic gonadotrophin levels rose to 360 mlU/ml. Subsequent courses of chemotherapy were cautiously given because of the development of jaundice, thought to be caused by drug toxicity rather than by the development of hepatic metastases. The patient died in January 1979. Permission for autopsy was not obtained. DISCUSSION
It is unusual that ocular metastases occurred solely in the anterior segment. Choriocarcinomas metastasize via the bloodstream, and because there are no lymphatics in the eye, ocular metastases from this tumor should be located prefer entially in the posterior uvea because of the larger volume of blood flow to the choroid than to any other region of the eye. Histopathologic evidence showed that aggressive treatment by several modali ties caused regression of this patient's ocular tumor but did not totally destroy it, and contributed to the complications that led to loss of the eye. The tumor cells present in the enucleated eye showed typical treatment changes that can be caused either by radiation or by chemo therapy, but one cannot conclude from the histologic presence of such changes that these cells are no longer viable. The
VOL. 87, NO. 6
OVARIAN CHORIOCARCINOMA
corneal destruction represents complica tions of treatment, 2 4 - 2 7 whereas the ab normalities present in the iris and lens may be caused by the direct effects of treatment or by the persistent uveitis, which was perhaps exacerbated by the presence of material released by necrotic tumor cells. A good prognosis for effective treat ment of choriocarcinoma by chemothera py generally depends on several factors: a relatively short duration of the disease before initiation of therapy, a pretreatment human chorionic gonadotrophin level that is not markedly increased, the absence of cerebral or hepatic metastases at the outset of treatment, and the pres ence of a gestational, rather than a nongestational, type of neoplasm. 8,28 In our case, the patient's clinical disease, dated from her last menstrual period, could not have been more than five months in dura tion, and she initially had no detectable cerebral or hepatic metastases, but her human chorionic gonadotrophin levels were massively increased. It is difficult to determine whether her tumor was of the gestational or of the nongestational type. Gestational choriocarcinomas primary in the ovary are extremely rare; however, nongestational pure primary ovarian choriocarcinomas unaccompanied by teratomatous elements are also unusual. 2 8 No products of conception could be found in the specimen obtained at laparotomy, but it is possible that this tumor may have represented an ovarian metasta sis from a small and undetected uterine primary. SUMMARY
A 28-year-old woman with ovarian cho riocarcinoma developed a uveitis in her left eye. Subsequently, a mass was ob served in the anterior segment of that eye together with a subconjunctival mass that appeared to extend from it. Biopsy of the subconjunctival nodule showed two dif
781
ferent cell types consistent with the cytotrophoblastic and syncytiotrophoblastic elements typical of choriocarcinoma. No abnormalities of the posterior segment were found on careful examination. Treatment consisted of systemic chemo therapy with a variety of therapeutic agents, argon laser photocoagulation of tumor seedings in the anterior chamber angle, radiation to the eye, and finally, subconjunctival injections of methotrexate. The eye became blind and painful and was enucleated. Histopathologic ex amination revealed residual tumor cells in the anterior segment indicating treat ment changes, but there were no abnor malities posteriorly. Choriocarcinoma rnetastatic to the eye has been reported infrequently, and this is the first case in which anterior segment metastases have been observed and the effects of treatment thoroughly documented. REFERENCES 1. Ferry, A. P., and Font, R. L.: Carcinoma rneta static to the eye and orbit. 1. A clinicopathologic study of 277 cases. Arch. Ophthalmol. 92:276,1974. 2. Ferry, A. P., and Font, R. L.: Carcinoma rneta static to the eye and orbit. 2. A clinicopathologic study of 26 patients with carcinoma, rnetastatic to the anterior segment of the eye. Arch. Ophthalmol. 93:472, 1975. 3. Duke-Elder, S., and Perkins, E. S.: Diseases of the Uveal Tract. In Duke-Elder, S. (ed.): System of Ophthalmology, vol. 9. London, Henry Kimpton, 1966, p . 935. 4. Li, M. C : Trophoblastic disease. Natural his tory, diagnosis and treatment. Ann. Intern. Med. 74:107. 1971. 5. Lahav, M., Berkowitz, S., and Albert, D. M.: Primary mediastinal choriocarcinoma in a male rnet astatic to the choroid. Albrecht von Graefes Arch. Klin. Ophthalmol. 206:191, 1978. 6. Anderson, W. A. D., and Kissane, J. M.: Pa thology, vol. 2, 7th ed. St. Louis, C. V. Mosby Co., 1977, p . 174. 7. Hertz, R., Lewis, J. L., and Lipsett, M. B.: Five years experience with the chemotherapy of rnetastat ic choriocarcinoma and related trophoblastic tumors in women. Am. J. Obstet. Gynecol. 82:631, 1961. 8. Hammond, C. B., Borchert, L. G., Tyrey, L., Creasman, W. T., and Parker, R. T.: Treatment of rnetastatic trophoblastic disease. Good and poor prognosis. Am. J. Obstet. Gynecol. 115:451, 1973. 9. Riechling, W.: Ocular metastasis of chorionepithelioma. Arch. Ophthalmol. 19:156, 1938.
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10. Godfredsen, E.: Choroid metastasis in chorionepithelioma of the testicle. Acta Ophthalmol. (Kbh) 22:300, 1944. 11. Kambara, G.: Choroidal metastasis of a testicular chorionic epithelioma. Arch. Ophthalmol. 4 1 : 587. 1949. 12. MacDonald, A. E.: Choroidal chorioepitheli oma secondary to teratoma of the testicle. Arch. Ophthalmol. 16:672, 1936. 13. Mulock-Houwer, A. W.: Metastase eines malignen Chorioepithelioms im Auge. Klin. Monatsbl. Augenheilkd. 77:226, 1926. 14. Slavik, B.: Metastasis of malignant chorionepithelioma into choroid. Cas. Lek. Cesk. 72:756, 1933. 15. Simidu, S.: Metastasis of malignant chorioepi thelioma into the choroid. Acta Societatis Ophthalmologicae 39:2023, 1935. 16. Wagner, F., and Busonny-Caspari, W.: Zur Frage der Adernhautmetastasierung von Chorionepitheliomen. Klin. Monatsbl. Augenheilkd. 123:461, 1954. 17. Kulvin, M. M.: Chorionepithelioma of cho roid. Metastatic from tumor in testicle. Am. J. Oph thalmol. 34:217, 1951. 18. Chitwood, Jr., E. M.: Chorioepithelioma of testicle with bilateral choroidal metastasis. Arch. Ophthalmol. 50:363, 1953.
J U N E , 1979
19. Weisse, V.: Adernhautmetastase eines Chorionepithelimos. Klin. Monatsbl. Augenheilkd. 145: 740, 1964. 20. Keates, R.J., and Billig, S. L.: Metastatic uveal choriocarcinoma. Arch. Ophthalmol. 84:381, 1970. 21. LeRebeller, J., Chauvergne, J., and Meuge, C : A case of choroid metastasis of a choriocarcino ma. Bull. Soc. Ophtalmol. Fr. 75:735, 1975. 22. Dhir, S. P., Jain, I. S., Gangwar, D. N., and Jain, G. C : Chorioepithelioma of choroid. Indian J. Ophthalmol. 23:25, 1976. 23. Kiendler, W.: Solitary choroidal metastasis as the only clinical manifestation of a chorionic epithe lial uterine neoplasm. Klin. Monatsbl. Augenheilkd. 154:850, 1969. 24. Blodi, F. C : The late effects of x-radiation on the cornea. Trans. Am. Ophthalmol. Soc. 56:413, 1958. 25. Linnell, P. C , and Wolter, J. R.: Corneal ne crosis after x-ray treatment. Eye Ear Nose Throat Mon. 46:328, 1967. 26. Macfaul, P. A., and Bedford, M. A.: Ocular complications after therapeutic irradiations. Br. J. Ophthalmol. 54:237, 1970. 27. Jones, R. F.: Glaucoma following radiothera py. Br. J. Ophthalmol. 42:636, 1958. 28. Goldstein, D. P., and Welch, W. R.: Case re cords of the Massachusetts General Hospital. N. Engl. J. Med. 296:926, 1977.
H. S A U L SUGAR, M.D.,
H U G H BECKMAN, M.D., Detroit,
Most tumor metastases to the eye occur in the posterior uvea. Data accumulated from several series 1 - 3 indicate that only about 10% of ocular metastases occur in the anterior segment. The most common sites of the primary lesions are the breast and the lung. Choriocarcinoma is a rare malignant trophoblastic tumor that originates in the female uterus and ovary and in the male testis. Rarely, extragenital primary chori ocarcinomas have been described. 4 , 5 Ges tational and nongestational types of cho riocarcinoma are recognized, but gesta tional choriocarcinomas are associated with pregnancy, particularly pregnancy in which a hydatidiform mole occurs. Non gestational choriocarcinomas derive from germ cells of the testis or ovary. 6 Before the advent of chemotherapy choriocarci noma was fatal in over 85% of cases. With the introduction in 1955 of methotrexate therapy for this tumor the outlook changed dramatically. 7 Currently, a num ber of therapeutic agents, used singly or, more frequently, in combination, have produced clinical cures in as many as 98% of female patients whose cases are diagnosed early and treated vigorously, even in the presence of metastases. 8 Sixteen cases of choriocarcinoma metastatic to the eye have been reported. 5,9 ~ 23 We report herein an unusual case that From the Kresge Eye Institute, and the Depart ment of Pathology, Wayne State University School of Medicine (Dr. Frank), the Departments of Oph thalmology (Drs. Sugar, Beckman, and Thoms), and Obstetrics and Gynecology (Dr. Sherman), Sinai Hospital of Detroit, Detroit, Michigan. Reprint requests to Karni W. Frank, M.D., Oph thalmic Pathology Laboratory, Kresge Eye Institute, 3994 John R St., Detroit, MI 48201. 778
A L F R E D I. S H E R M A N ,
AND SUSAN T H O M S ,
M.D.,
M.D.
Michigan
documents metastatic choriocarcinoma solely to the anterior segment of the eye. We were able to make a tissue diagnosis of the ocular lesion early in its course, and were able to document the effect of thera py through clinical follow up and eventu al histopathologic examination of the globe. CASE REPORT A 28-year-old woman (gravida 2, para 2) was admitted to the hospital for the first time in January 1975 at age 25 years with a pelvic mass and marked ly increased human chorionic gonadotrophin titers of 5000 mlU/ml of serum determined by radioimmunoassay (normal by this method, < 1 mlU/ml). Her last menstrual period had been in August 1974. Her previous pregnancies had been unremarkable and she had never had a spontaneous abortion. A laparotomy was performed for diagnosis and the ovarian mass was resected. The tissue diagnosis was choriocarcinoma. No evidence of ectopic pregnancy was found, and teratomatous elements were not present within the tumor. Chemotherapy with methotrexate and dactinomycin (Actinomycin D) was initiated and the human chorionic gonadotrophin levels decreased to < 5 mlU/ml, but still were slight ly higher than the normal range. After four months they precipitously rose again to 300 mlU/ml. A chest x-ray revealed a mass in the lower lobe of the right lung. Cyclophosphamide was added to the thera peutic regimen. The pulmonary mass decreased in size radiographically and the human chorionic go nadotrophin levels fell transiently to within the normal range, but then began to rise again. In November 1975, the patient underwent a right lower lobectomy. Histopathologic examination revealed necrotic tumor. Subsequently, she developed central nervous system symptoms. Diagnostic evaluation indicated a mass in the right frontal lobe. A craniotomy was performed and the tumor was resected. Over the next few months human chorionic gonadotro phin levels decreased to the normal range where they remained for nearly five months. In late 1976, the patient developed an anterior uveitis in the left eye that was initially treated with topical corticosteroids and atropine. Initially, no metastatic lesions were visible in the eye although it was suspected that these were responsible for the uveitis when no response to corticosteroids was observed and the human chorionic gonadotrophin levels rose to
AMERICAN JOURNAL O F OPHTHALMOLOGY 87:778-782, 1979
VOL. 87, NO. 6
OVARIAN
CHORIOCARCINOMA
779
Fig. 1 (Frank and associates). Left eye two weeks before biopsy of conjunctival nodule (May 1977), showing a hemorrhagic mass in the anterior cham ber and a subconjunctival nodule (arrow) apparently extending from it. 35 mlU/ml. By May 1977, a mass was visible in the inferonasal quadrant of the anterior chamber of the left eye and a second mass, which appeared to have extended from it, was visible subconjunctivally in the same quadrant (Fig. 1). Results of examination of the fundus, including indirect ophthalmoscopy with scleral depression were negative. Biopsy of the subconjunctival mass was done in June 1977 and histopathologic examination revealed a markedly vascular and hemorrhagic tumor (Fig. 2) composed of two cell types, consistent with the cytotrophoblastic and syncytiotrophoblastic elements of choriocarcinoma (Fig. 3). The cytotrophoblastic cells were large, polygonal cells, with pale-staining-to-clear cytoplasm, distinct cellular borders, and large, ve sicular nuclei with prominent nucleoli (C, Fig. 3). The syncytiotrophoblastic cells had deeply staining
Fig. 2 (Frank and associates). Left eye, section of biopsy specimen showing a highly vascularized and hemorrhagic mass in the substantia propria of the bulbar conjunctiva. The area enclosed by the white rectangle is enlarged in Figure 3 (hematoxylin and eosin, x95).
Fig. 3 (Frank and associates). Enlargement of the area within the rectangle in Figure 2 showing cyto trophoblastic cells (C), and syncytiotrophoblastic cells (S). (hematoxylin and eosin, x630). eosinophilic cytoplasm and hyperchromatic nuclei. Their cell borders were indistinct and at times the cells had a tendency to form a multinucleated syncytium (S, Fig. 3). After surgery, visual acuity was 6/6 (20/20) in the right eye and 6/30 (20/100) in the left eye with moderate flare, cells, and posterior synechiae pre sent. Gonioscopy revealed several apparent tumor nodules in the chamber angle, and ultrasonography showed a mass in the anterior segment but no abnormalities posteriorly. Ophthalmoscopic exami nation also continued to show no lesions in the posterior segment. Multiple photocoagulation treat ments with the argon laser were given using the slit-lamp delivery system and the Goldmann gonioscopic lens to ablate tumor nodules in the chamber angle. In August 1977, radiation treatment to bulky portions of tumor located in the ciliary body was begun. The treatment consisted of 25 fractionated doses of radioactive isotope of cobalt (60C) given over a period of 38 days; 200 rads per dose were
780
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given, bringing the total to 5000 rads. The patient continued to receive topical corticosteroids and atropine. There appeared to be some shrinkage of the tumor, and over the next three months, human chorionic gonadotrophin levels decreased to within the normal range. In October 1977, seizures developed and another cerebral metastasis was found. System ic chemotherapy with methotrexate, dactinomycin, cyclophosphamide, and doxorubicin HC1 (Adriamycin) was re-administered. Additionally, subconjunctival methotrexate was administered in Novem ber 1977 in an attempt to destroy residual ocular tumor. The uveitis persisted and the eye became painful and soft. Visual acuity decreased to 6/120 (20/400). Corneal epithelial defects and a vascular pannus were noted. Human chorionic gonadotrophin levels rose again to over 100 mlU/ml and the chemotherapeutic regimen was altered to include dactin omycin, vincristine, bleomycin sulfate, and cisplatinum. By March 1978, vision had decreased to light perception and the eye remained soft and painful. Enucleation was performed on April 19, 1978. Histopathologic examination revealed an irregular cor neal epithelium that was absent in many areas and hyperplastic in others. A degenerative pannus was present, and there was extensive stromal necrosis with vascularization and a dense infiltrate of inflam matory cells. The iris showed necrosis and atrophy of the stroma and almost total disappearance of the sphincter and dilator muscles. There were posterior synechiae. Rubeosis iridis, together with extensive peripheral anterior synechiae and hyphema, were noted. The only evidence of residual tumor cells was found in the inferior temporal quadrant where, within the longitudinal portion of the ciliary mus cle, there was a group of tumor cells (Fig. 4) with large, irregularly shaped hyperchromatic nuclei, prominent nucleoli, and a vacuolated cytoplasm
Fig. 4 (Frank and associates). Clumps of residual tumor cells in ciliary muscle after massive treatment by various modalities. The area enclosed by the white rectangle is enlarged in Figure 5 (hematoxylin and eosin, x 160).
Fig. 5 shown zation eosin,
JUNE, 1979
(Frank and associates). Same tumor cells as in Figure 4 (within rectangle). Note vacuoliof cytoplasm and nuclei, (hematoxylin and x630).
(Fig. 5). The lens was cataractous. Macrophages and acute inflammatory cells were present in the vitre ous. The retina revealed loss of ganglion cells. The choroid was normal. The optic disk showed cupping and posterior bowing of the lamina cribrosa. After enculeation the patient's condition contin ued to deteriorate. H u m a n chorionic gonadotrophin levels rose to 360 mlU/ml. Subsequent courses of chemotherapy were cautiously given because of the development of jaundice, thought to be caused by drug toxicity rather than by the development of hepatic metastases. The patient died in January 1979. Permission for autopsy was not obtained. DISCUSSION
It is unusual that ocular metastases occurred solely in the anterior segment. Choriocarcinomas metastasize via the bloodstream, and because there are no lymphatics in the eye, ocular metastases from this tumor should be located prefer entially in the posterior uvea because of the larger volume of blood flow to the choroid than to any other region of the eye. Histopathologic evidence showed that aggressive treatment by several modali ties caused regression of this patient's ocular tumor but did not totally destroy it, and contributed to the complications that led to loss of the eye. The tumor cells present in the enucleated eye showed typical treatment changes that can be caused either by radiation or by chemo therapy, but one cannot conclude from the histologic presence of such changes that these cells are no longer viable. The
VOL. 87, NO. 6
OVARIAN CHORIOCARCINOMA
corneal destruction represents complica tions of treatment, 2 4 - 2 7 whereas the ab normalities present in the iris and lens may be caused by the direct effects of treatment or by the persistent uveitis, which was perhaps exacerbated by the presence of material released by necrotic tumor cells. A good prognosis for effective treat ment of choriocarcinoma by chemothera py generally depends on several factors: a relatively short duration of the disease before initiation of therapy, a pretreatment human chorionic gonadotrophin level that is not markedly increased, the absence of cerebral or hepatic metastases at the outset of treatment, and the pres ence of a gestational, rather than a nongestational, type of neoplasm. 8,28 In our case, the patient's clinical disease, dated from her last menstrual period, could not have been more than five months in dura tion, and she initially had no detectable cerebral or hepatic metastases, but her human chorionic gonadotrophin levels were massively increased. It is difficult to determine whether her tumor was of the gestational or of the nongestational type. Gestational choriocarcinomas primary in the ovary are extremely rare; however, nongestational pure primary ovarian choriocarcinomas unaccompanied by teratomatous elements are also unusual. 2 8 No products of conception could be found in the specimen obtained at laparotomy, but it is possible that this tumor may have represented an ovarian metasta sis from a small and undetected uterine primary. SUMMARY
A 28-year-old woman with ovarian cho riocarcinoma developed a uveitis in her left eye. Subsequently, a mass was ob served in the anterior segment of that eye together with a subconjunctival mass that appeared to extend from it. Biopsy of the subconjunctival nodule showed two dif
781
ferent cell types consistent with the cytotrophoblastic and syncytiotrophoblastic elements typical of choriocarcinoma. No abnormalities of the posterior segment were found on careful examination. Treatment consisted of systemic chemo therapy with a variety of therapeutic agents, argon laser photocoagulation of tumor seedings in the anterior chamber angle, radiation to the eye, and finally, subconjunctival injections of methotrexate. The eye became blind and painful and was enucleated. Histopathologic ex amination revealed residual tumor cells in the anterior segment indicating treat ment changes, but there were no abnor malities posteriorly. Choriocarcinoma rnetastatic to the eye has been reported infrequently, and this is the first case in which anterior segment metastases have been observed and the effects of treatment thoroughly documented. REFERENCES 1. Ferry, A. P., and Font, R. L.: Carcinoma rneta static to the eye and orbit. 1. A clinicopathologic study of 277 cases. Arch. Ophthalmol. 92:276,1974. 2. Ferry, A. P., and Font, R. L.: Carcinoma rneta static to the eye and orbit. 2. A clinicopathologic study of 26 patients with carcinoma, rnetastatic to the anterior segment of the eye. Arch. Ophthalmol. 93:472, 1975. 3. Duke-Elder, S., and Perkins, E. S.: Diseases of the Uveal Tract. In Duke-Elder, S. (ed.): System of Ophthalmology, vol. 9. London, Henry Kimpton, 1966, p . 935. 4. Li, M. C : Trophoblastic disease. Natural his tory, diagnosis and treatment. Ann. Intern. Med. 74:107. 1971. 5. Lahav, M., Berkowitz, S., and Albert, D. M.: Primary mediastinal choriocarcinoma in a male rnet astatic to the choroid. Albrecht von Graefes Arch. Klin. Ophthalmol. 206:191, 1978. 6. Anderson, W. A. D., and Kissane, J. M.: Pa thology, vol. 2, 7th ed. St. Louis, C. V. Mosby Co., 1977, p . 174. 7. Hertz, R., Lewis, J. L., and Lipsett, M. B.: Five years experience with the chemotherapy of rnetastat ic choriocarcinoma and related trophoblastic tumors in women. Am. J. Obstet. Gynecol. 82:631, 1961. 8. Hammond, C. B., Borchert, L. G., Tyrey, L., Creasman, W. T., and Parker, R. T.: Treatment of rnetastatic trophoblastic disease. Good and poor prognosis. Am. J. Obstet. Gynecol. 115:451, 1973. 9. Riechling, W.: Ocular metastasis of chorionepithelioma. Arch. Ophthalmol. 19:156, 1938.
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