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Pleomorphic Adenocarcinoma of the Ciliary Body
Pleomorphic Adenocarcinoma of the Ciliary Body Immunohistochemical and Electron Microscopic Features HANS E. GROSSNIKLAUS, MD,t,2 LORENZ E. ZIMMERMAN, MD,2 MARY LOU KACHMER, MD3
Abstract: An 80-year-old man was evaluated for an epibulbar tumor on a phthisical eye. The initial biopsy diagnosis of the epibulbar tumor was poorly differentiated neoplasm. Exenteration of the phthisical eye and orbital contents showed an extensive pleomorphic adenocarcinoma of the nonpigmented epithelium of the ciliary body with extraocular extension. There was evidence of hyaluronic acid secretion and immunohistochemical staining was strong for vimentin, focal for epithelial membrane antigen and 8-100 protein, and weak for neuron-specific-enolase. Electron microscopy demonstrated desmosomes between tumor celis, areas of thick, multilaminar basement membrane production surrounding individual tumor celis, and occasional intracytoplasmic intermediate filaments. Ophthalmology 1990; 97:763-768
Among the rarest of intraocular tumors are adenocarcinomas of the nonpigmented epithelium of the ciliary body.1-13 Large, poorly differentiated tumors of this type are most likely to be found in phthisical eyes with or without a past history of trauma or ocular inflammation. 6 - 13 There have been several reports of epibulbar extension of Originally received: October 16, 1989. Revision accepted: February 14, 1990. Departments of Ophthalmology and Pathology, Emory University School of Medicine, Atlanta. 2 Department of Ophthalmic Pathology, Armed Forces Institute of Pathol· ogy, Washington. 3 Division of Ophthalmology, Case Westem Reserve University School of Medicine, Cleveland.
adenocarcinomas of the ciliary epithelium,8-14 and in at least one instance, it simulated a primary epibulbar tumor.14 We present an additional case of a pleomorphic adenocarcinoma of the ciliary body with epibulbar extension arising in a phthisical eye. Immunohistochemical and ultrastructural features of the tumor, including previously unreported findings, are described and discussed.
CASE REPORT
1
Presented at the Annual Meeting of the Eastern Ophthalmic Pathology Society, Hilton Head, South Carolina, Oct 8, 1989. The opinions or assertions contained herein are the private views of the authors and should not be construed as being official or as representing the views of the Department of the Army or the Department of Defense. Reprint requests to Hans E. Grossniklaus, MD, L. F. Montgomery Eye Pathology Laboratory, Emory Eye Center, 1327 Clifton Rd, NE, Atlanta, GA 30322.
An 80-year-old man was first evaluated in 1985 during a routine ophthalmic examination. He was a poor historian and did not report any specific visual complaint, or history of trauma or ocular surgery. His visual acuity was no light perception in his right eye and 20/30 in his left. Results of examination of his right eye disclosed rubeosis iridis and a dense cataract that precluded funduscopic examination. Results of examination of his left eye showed no significant abnormalities. Computed tomography of the orbits and B-scan ultrasonography of the right eye disclosed a retinal detachment with an underlying mass with intraocular calcification in the right eye. No extraocular extension of the mass was noted at that time. Enucleation of the right eye was recommended; however, the patient declined. Because of a
763
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Fig 1. Computed tomography demonstrates the epibulbar (arrowhead) and intraocular (arrow) masses of the right globe. Intraocular calcifications are present. No orbital extension is evident.
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Fig 3. Horizontal anterior-posterior section of the exenteration specimen exhibits a variably colored epibulbar mass (white arrowhead), and an intraocular mass invading the lens (between black arrowheads), displacing it anteriorly.
was learned that the patient had been treated for adenocarcinoma of the prostate and that a pulmonary nodule of unknown nature had been discovered 1 year after initial ophthalmic examination. The pulmonary nodule remained unchanged in size during the ensuing 2 years and results of a metastatic workup were negative. The patient suffered a stroke 1 month after exenteration and computed tomography of the head showed cerebral lacunar infarcts without evidence of metastases. The patient recovered from the stroke with minimal paralysis in one leg and was discharged from the hospital. PATHOLOGIC FINDINGS
Fig 2. The epibulbar mass is composed of sheets and cords of poorly differentiated cells with numerous mitotic figures (arrows). Some tumor cells line up, suggesting an epithelial arrangement (periodic acid-Schiff; original magnification, X 150).
bleeding epibulbar mass on his right eye, he was again evaluated 21h years after initial examination. Results of examination disclosed a hemorrhagic epibulbar mass of his right eye that measured 2 X 2 X 1.5 cm. The mass covered the anterior surface of the right globe and precluded internal examination. Computed tomography showed an intraocular mass as previously described with associated calcification but with extraocular extension (Fig 1). Results of examination of the left eye showed no abnormalities. Results of frozen-section examination of a biopsy of the epibulbar mass was performed (see Pathologic Findings section) and the mass was classified as a poorly differentiated malignant neoplasm. Exenteration of the right globe and orbital contents was performed immediately after biopsy (see Pathologic Findings section) since the tumor appeared to invade the anterior orbit and the patient was relatively healthy. On this admission, it also
764
Results of examination of the intraoperative frozen section of the epibulbar mass showed sheets and cords of loosely cohesive, poorly differentiated, nonpigmented neoplastic cells with eosinophilic cytoplasm, large nuclei, prominent nucleoli, and numerous bizarre mitotic figures (Fig 2). Some tumor cells appeared to be lined up in single file, suggesting an epithelial neoplasm. Results of examination of the exenteration specimen showed a right eye and periocular soft tissue that measured 45 X 45 X 40 mm. The anterior surface of the eye was covered with a multinodular firm variably colored mass. The specimen was opened horizontally with first removal of the superior calotte. In the opened eye was a mass of similar color and consistency to the epibulbar mass that fully occupied the globe; it displaced the partially calcified lens anteriorly (Figs 3, 4). Results of microscopic examination showed an ulcerated, hemorrhagic epibulbar tumor that appeared to be either a poorly differentiated carcinoma or an am elan otic melanoma. The central corneal epithelium was intact and a subepithelial fibrous pannus was present. The corneal endothelium was absent and proteinaceous fluid, necrotic material, inflammatory cells, and occasional tumor cells occupied the anterior chamber. Necrotic iris leaflets and
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Fig 4. Histologic section corresponding to Figure 3 discloses an epibulbar mass and an intraocular mass with glandular features invading the lens (between arrowheads) (hematoxylin-eoxin; original magnification, X4).
Fig 6. Immunohistochemical stain for epithelial membrane antigen (A) and S-IOO protein (B) are focally positive (arrowheads). Immunohistochemical stains for vimentin (C) are diffusely positive (peroxidase antiperoxidase; original magnification, X300).
Fig 5. The intraocular mass is composed of tumor with gland-like formations surrounding hyalinized stroma (H). In areas, a thick periodic acid-Schiff-positive basement membrane is present (arrowhead) (periodic acid-Schiff; original magnification, X7S).
a partially calcified, cataractous lens were displaced forward by a tumor that occupied the posterior compartment and invaded the lens. The tumor appeared to arise from the nonpigmented epithelium of the ciliary body and was composed of tubules and gland-like formations of pleomorphic epithelial cells that surrounded cores of variably hyalinized stroma (Fig 5). Portions of tumor were necrotic but periodic acid-Schiff-positive basement membranes were particularly obvious in the areas of necrosis. Osseous metaplasia was present near necrotic tumor. The tumor had invaded the uveal tract in which there were islands of tumor similar in histologic appearance to the epibulbar mass. Extraocular extension via emissary canals and optic nerve invasion by the tumor were present.
Special stains demonstrated intraluminal hyaluronidase-sensitive mucopolysaccharide within the tumor. Fontana and Warthin-Starry stains for melanin were negative. Immunohistochemical stains were strongly positive for vimentin (Biogenics, 1:400 dilution) in 80 to 90% of tumor cells, positive for epithelial membrane antigen (Dako, 1:400 dilution) and S-100 protein (Dako, 1: 1000 dilution) in approximately 5% of tumor cells, weakly positive for neuron-specific enolase (Biogenics, 1:800 dilution), and negative for keratin, GFAP, prostatic specific antigen, and prostatic acid phosphatase (Fig 6). Electron microscopy showed areas of well-formed desmosomes between tumor cells (Fig 7) and areas of thick, multilaminated basement membrane surrounding individual tumor cells (Fig 8). Occasional tumor cells contained intracytoplasmic intermediate filaments. Some tumor cells formed lumina with the cell membranes lining the lumina containing microvillous processes.
DISCUSSION We have reviewed reports of20 previously documented cases of adenocarcinoma probably arising in the nonpig765
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Fig 7. Electron micrograph demonstrates tumor cells forming desmosomes (arrow and inset) and adjacent basement membrane-like material (BM) (original magnification, X3000; inset, original magnification X 12,000).
mented epithelium of the ciliary body (Table 1)}-13 It is difficult to determine in some cases if the pigment epithelium of the ciliary body also was neoplastic or hyperplastic. It may be possible that primitive tumor cells derived from the ciliary epithelium differentiate into both nonpigmented and pigmented cells. Additionally, previous authors have probably classified some adenocarcinomas of the ciliary body as "adult-type medulloepitheliomas," therefore making the precise number of reported adenocarcinomas of the nonpigmented ciliary epithelium difficult to ascertain. Adenocarcinomas of the ciliary body have been described as having one of four basic patterns: glandular or papillary, pleomorphic of low grade, pleomorphic with hyaline stroma, or anaplastic. 14 In our case, the tumor could be classified as pleomorphic with hyaline stroma. These tumors may arise in phthisical eyes with or without
766
history of previous trauma or inflammation. 6 ,8 It is possible that reactive hyperplasia of the nonpigmented epithelium of the ciliary body first develops and later malignant transformation takes place. Previously traumatized or inflamed eyes contain more poorly differentiated adenocarcinomas of the ciliary body than uninflamed or uninjured eyes. 6,14 Althou~h our patient was a poor historian, histologic evidence of intraocular osseous metaplasia indicates that the patient had a long-standing ophthalmic process, and the eye was already blind when examined 21/2 years before exenteration. Epibulbar extension of adenocarcinomas of the ciliary body, as was present in our case, has been observed previously.8,14 The manifestation that prompted our patient to seek medical attention was a bleeding epibulbar mass. Results of histologic study of the epibulbar mass demonstrated a poorly differentiated malignant neoplasm;
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Fig 8. Occasional tumor cells are completely surrounded by thick, multilaminated basement membrane (BM) (top inset). Some tumor cells contain intracytoplasmic intermediate filaments (bottom inset) (original magnification, X4400; insets, original magnification X 12,000).
however, the possibility of an adenocarcinoma of the nonpigmented epithelium of the ciliary body was not suspected until the intraocular portion of the tumor was examined. Similar cases have been described. 8,13,14 Harris and co-workers8 reported the case of a 74-year-old man with an epibulbar mass overlying his blind left eye. A wedge biopsy of the mass disclosed a poorly differentiated pleomorphic neoplasm. Enucleation was recommended and results of examination of the eye showed that the epibulbar tumor had arisen from the nonpigmented ciliary epithelium. Rodrigues and co-workers 14 described a 72year-old woman with epibulbar nodules overlying a blind, painful eye. The nodules were excised and initially interpreted to be anaplastic squamous cell carcinoma of the conjunctiva. Only after examination of the enucleation specimen was it determined that the epibulbar nodules were extensions from an adenocarcinoma of the ciliary body.
Table 1. Age and Ocular History of Patients with Adenocarcinoma of the Nonpigmented Ciliary Epithelium Reference
Patient Age (yrs)
Previous Trauma or Inflammation
Fuchs, 19081 Barrow and Stallard, 193t Wadsworth, 19494 Walter and James 19585 Andersen, 19626 Timm and Fritsch, 19647 Harris et ai, 19688 Horie et aI, 19729 Vogel, 197410 Kuchynka, 197911 Dryja et ai, 1981 12 Current case
? 61 56* 39 87 56 74 63 60 57 41 80
+
? 4 of 9
+ + ?
+ ?
?
? ? ?
* Average age of nine patients.
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Previous eyes with adenocarcinomas of the nonpigmented epithelium of the ciliary body also have had cataractous changes with ruptured capsules. I 1-13 Histologic evidence of tumor invasion into the lens was present in our case (Fig 5). Our case also exhibited features of intraocular osseous metaplasia and tumor invasion into the optic nerve as described in previous reports. 8 •14 Histochemical stains demonstrated intraluminal- but not intracytoplasmic hyaluronidase-sensitive mucopolysaccharide. This feature helps distinguish a primary adenocarcinoma of the ciliary body from a metastatic adenocarcinoma l5 and was of practical importance in our case since the patient had a history of adenocarcinoma of the prostate. The diagnosis of prostatic adenocarcinoma was made after the initial ophthalmic examination, but the histologic appearance, staining pattern for mucopolysaccharide, and lack of staining of the intraocular tumor for prostate specific antigen or prostatic acid phosphatase ruled out metastatic prostatic adenocarcinoma to the eye. 16 Immunohistochemical stains were positive for vimentin, epithelial membrane antigen, S-IOO protein, weakly positive for neuron-specific enolase, and negative for keratin in tumor cells. This is the first study to report these immunohistochemical findings in this tumor. Previous reports have mentioned negative staining for cytokeratin in an adenocarcinoma of the ciliary bodyl4 and positive staining for S-1 00 protein, vimentin, and neuron-specific enolase in neuroepithelial cells in a medulloepithelioma of the ciliary body. I? Those findings were similar to ours. Transmission electron microscopy demonstrated multilaminated basement membrane, desmosomes, and occasional intracytoplasmic intermediate filaments in the tumor as described in previous reports. 10.14 It appears that this tumor is a slow-growing malignancy in individuals of advanced age. Recommended treatment is enucleation or possible local excision. 6.12 However, the prognosis of patients with this tumor is uncertain, in part because of the paucity of well-documented cases. Five of 16 patients in whom adequate follow-up data were available are reported to have died of tumor extension or metastatic disease. 13 Poor prognosis may be related to tumor present at the surgical margin of resection. It is therefore
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conceivable that more aggressive surgery, such as exenteration, is indicated in otherwise healthy individuals with orbital or optic nerve invasion.
REFERENCES 1. Fuchs E. Wucherungen und geschwUlste des ciliarepithels. Albrecht von Graefes Arch Ophthalmol1908; 68:534-87. 2. Barrow RHB, Stallard HB. A case of primary melano-carcinoma of the ciliary body. Br J Ophthalmol 1932; 16:98-102. 3. Nordmann J. Les tumeurs de la retine ciliare. Ophthalmologica 1941; 102:257-74. 4. Wadsworth JAC. Epithelial tumors of the ciliary body. Am J Ophthalmol 1949; 32:1487-1501. 5. Wolter JR, James BA. Adult type of medullo-epithelioma of the ciliary body. Am J Ophthalmol1958; 46:19-26. 6. Andersen SA. Medulloepithelioma of the retina. Int Ophthalmol Clin 1962; 2(2):483-506. 7. Timm G, Fritsch S. Uber epitheliale Tumoren des Ciliarktirpers. Frankfurt Z Path 1964; 73:401-17. 8. Harris JL, Gumucio CC, Ohanion MB. Adenocarcinoma of the ciliary epithelium. Arch Ophthalmol1968; 80:217-9. 9. Horie A, Iwata Y, Tanaka K, Hayaski F. Electron microscopic study on the so-called malignant medula-epithelioma (ciliary epithelial carcinoma). Virchows Arch [Pathol Anat] 1972; 355:284-9. 10. Vogel MH. Tumoren des Ziliarktirperepithels. Klin Monatsbl Augenheilkd 1974; 165:458-69. 11. Kuchynka P. Malignant epithelioma of the ciliary body. Ophthalmologica 1979; 178:190-3. 12. Oryja TP, Albert OM, Homs O. Adenocarcinoma arising from the epithelium of the ciliary body. Ophthalmology 1981; 88: 1290-2. 13. Green WR. Retina. In: Spencer WH, Ophthalmic Pathology. An Atlas and Textbook. Philadelphia: WB Saunders, 1985; vol. 2, 589-1291. 14. Rodrigues M, Hidayat A, Karesh J. Pleomorphic adenocarcinoma of ciliary epithelium simulating an epibulbar tumor. Am J Ophthalmol 1988; 106:595-600. 15. Jakobiec FA, Zimmerman LE, Spencer WH, et al. Metastatic colloid carcinoma versus primary carcinoma of the ciliary epithelium. Ophthalmology 1987; 94:1469-80. 16. Reifler OM, Kini SR, Liu 0, Littleton RH. Orbital metastasis from prostatic carcinoma: identification by immunocytology. Arch Ophthalmol 1984; 102:292-5. 17. Kivela T, Tarkkanen A. Recurrent medulloepithelioma of the ciliary body: immunohistochemical characteristics. Ophthalmology 1988; 95: 1565-75.
Abstract: An 80-year-old man was evaluated for an epibulbar tumor on a phthisical eye. The initial biopsy diagnosis of the epibulbar tumor was poorly differentiated neoplasm. Exenteration of the phthisical eye and orbital contents showed an extensive pleomorphic adenocarcinoma of the nonpigmented epithelium of the ciliary body with extraocular extension. There was evidence of hyaluronic acid secretion and immunohistochemical staining was strong for vimentin, focal for epithelial membrane antigen and 8-100 protein, and weak for neuron-specific-enolase. Electron microscopy demonstrated desmosomes between tumor celis, areas of thick, multilaminar basement membrane production surrounding individual tumor celis, and occasional intracytoplasmic intermediate filaments. Ophthalmology 1990; 97:763-768
Among the rarest of intraocular tumors are adenocarcinomas of the nonpigmented epithelium of the ciliary body.1-13 Large, poorly differentiated tumors of this type are most likely to be found in phthisical eyes with or without a past history of trauma or ocular inflammation. 6 - 13 There have been several reports of epibulbar extension of Originally received: October 16, 1989. Revision accepted: February 14, 1990. Departments of Ophthalmology and Pathology, Emory University School of Medicine, Atlanta. 2 Department of Ophthalmic Pathology, Armed Forces Institute of Pathol· ogy, Washington. 3 Division of Ophthalmology, Case Westem Reserve University School of Medicine, Cleveland.
adenocarcinomas of the ciliary epithelium,8-14 and in at least one instance, it simulated a primary epibulbar tumor.14 We present an additional case of a pleomorphic adenocarcinoma of the ciliary body with epibulbar extension arising in a phthisical eye. Immunohistochemical and ultrastructural features of the tumor, including previously unreported findings, are described and discussed.
CASE REPORT
1
Presented at the Annual Meeting of the Eastern Ophthalmic Pathology Society, Hilton Head, South Carolina, Oct 8, 1989. The opinions or assertions contained herein are the private views of the authors and should not be construed as being official or as representing the views of the Department of the Army or the Department of Defense. Reprint requests to Hans E. Grossniklaus, MD, L. F. Montgomery Eye Pathology Laboratory, Emory Eye Center, 1327 Clifton Rd, NE, Atlanta, GA 30322.
An 80-year-old man was first evaluated in 1985 during a routine ophthalmic examination. He was a poor historian and did not report any specific visual complaint, or history of trauma or ocular surgery. His visual acuity was no light perception in his right eye and 20/30 in his left. Results of examination of his right eye disclosed rubeosis iridis and a dense cataract that precluded funduscopic examination. Results of examination of his left eye showed no significant abnormalities. Computed tomography of the orbits and B-scan ultrasonography of the right eye disclosed a retinal detachment with an underlying mass with intraocular calcification in the right eye. No extraocular extension of the mass was noted at that time. Enucleation of the right eye was recommended; however, the patient declined. Because of a
763
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Fig 1. Computed tomography demonstrates the epibulbar (arrowhead) and intraocular (arrow) masses of the right globe. Intraocular calcifications are present. No orbital extension is evident.
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Fig 3. Horizontal anterior-posterior section of the exenteration specimen exhibits a variably colored epibulbar mass (white arrowhead), and an intraocular mass invading the lens (between black arrowheads), displacing it anteriorly.
was learned that the patient had been treated for adenocarcinoma of the prostate and that a pulmonary nodule of unknown nature had been discovered 1 year after initial ophthalmic examination. The pulmonary nodule remained unchanged in size during the ensuing 2 years and results of a metastatic workup were negative. The patient suffered a stroke 1 month after exenteration and computed tomography of the head showed cerebral lacunar infarcts without evidence of metastases. The patient recovered from the stroke with minimal paralysis in one leg and was discharged from the hospital. PATHOLOGIC FINDINGS
Fig 2. The epibulbar mass is composed of sheets and cords of poorly differentiated cells with numerous mitotic figures (arrows). Some tumor cells line up, suggesting an epithelial arrangement (periodic acid-Schiff; original magnification, X 150).
bleeding epibulbar mass on his right eye, he was again evaluated 21h years after initial examination. Results of examination disclosed a hemorrhagic epibulbar mass of his right eye that measured 2 X 2 X 1.5 cm. The mass covered the anterior surface of the right globe and precluded internal examination. Computed tomography showed an intraocular mass as previously described with associated calcification but with extraocular extension (Fig 1). Results of examination of the left eye showed no abnormalities. Results of frozen-section examination of a biopsy of the epibulbar mass was performed (see Pathologic Findings section) and the mass was classified as a poorly differentiated malignant neoplasm. Exenteration of the right globe and orbital contents was performed immediately after biopsy (see Pathologic Findings section) since the tumor appeared to invade the anterior orbit and the patient was relatively healthy. On this admission, it also
764
Results of examination of the intraoperative frozen section of the epibulbar mass showed sheets and cords of loosely cohesive, poorly differentiated, nonpigmented neoplastic cells with eosinophilic cytoplasm, large nuclei, prominent nucleoli, and numerous bizarre mitotic figures (Fig 2). Some tumor cells appeared to be lined up in single file, suggesting an epithelial neoplasm. Results of examination of the exenteration specimen showed a right eye and periocular soft tissue that measured 45 X 45 X 40 mm. The anterior surface of the eye was covered with a multinodular firm variably colored mass. The specimen was opened horizontally with first removal of the superior calotte. In the opened eye was a mass of similar color and consistency to the epibulbar mass that fully occupied the globe; it displaced the partially calcified lens anteriorly (Figs 3, 4). Results of microscopic examination showed an ulcerated, hemorrhagic epibulbar tumor that appeared to be either a poorly differentiated carcinoma or an am elan otic melanoma. The central corneal epithelium was intact and a subepithelial fibrous pannus was present. The corneal endothelium was absent and proteinaceous fluid, necrotic material, inflammatory cells, and occasional tumor cells occupied the anterior chamber. Necrotic iris leaflets and
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Fig 4. Histologic section corresponding to Figure 3 discloses an epibulbar mass and an intraocular mass with glandular features invading the lens (between arrowheads) (hematoxylin-eoxin; original magnification, X4).
Fig 6. Immunohistochemical stain for epithelial membrane antigen (A) and S-IOO protein (B) are focally positive (arrowheads). Immunohistochemical stains for vimentin (C) are diffusely positive (peroxidase antiperoxidase; original magnification, X300).
Fig 5. The intraocular mass is composed of tumor with gland-like formations surrounding hyalinized stroma (H). In areas, a thick periodic acid-Schiff-positive basement membrane is present (arrowhead) (periodic acid-Schiff; original magnification, X7S).
a partially calcified, cataractous lens were displaced forward by a tumor that occupied the posterior compartment and invaded the lens. The tumor appeared to arise from the nonpigmented epithelium of the ciliary body and was composed of tubules and gland-like formations of pleomorphic epithelial cells that surrounded cores of variably hyalinized stroma (Fig 5). Portions of tumor were necrotic but periodic acid-Schiff-positive basement membranes were particularly obvious in the areas of necrosis. Osseous metaplasia was present near necrotic tumor. The tumor had invaded the uveal tract in which there were islands of tumor similar in histologic appearance to the epibulbar mass. Extraocular extension via emissary canals and optic nerve invasion by the tumor were present.
Special stains demonstrated intraluminal hyaluronidase-sensitive mucopolysaccharide within the tumor. Fontana and Warthin-Starry stains for melanin were negative. Immunohistochemical stains were strongly positive for vimentin (Biogenics, 1:400 dilution) in 80 to 90% of tumor cells, positive for epithelial membrane antigen (Dako, 1:400 dilution) and S-100 protein (Dako, 1: 1000 dilution) in approximately 5% of tumor cells, weakly positive for neuron-specific enolase (Biogenics, 1:800 dilution), and negative for keratin, GFAP, prostatic specific antigen, and prostatic acid phosphatase (Fig 6). Electron microscopy showed areas of well-formed desmosomes between tumor cells (Fig 7) and areas of thick, multilaminated basement membrane surrounding individual tumor cells (Fig 8). Occasional tumor cells contained intracytoplasmic intermediate filaments. Some tumor cells formed lumina with the cell membranes lining the lumina containing microvillous processes.
DISCUSSION We have reviewed reports of20 previously documented cases of adenocarcinoma probably arising in the nonpig765
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Fig 7. Electron micrograph demonstrates tumor cells forming desmosomes (arrow and inset) and adjacent basement membrane-like material (BM) (original magnification, X3000; inset, original magnification X 12,000).
mented epithelium of the ciliary body (Table 1)}-13 It is difficult to determine in some cases if the pigment epithelium of the ciliary body also was neoplastic or hyperplastic. It may be possible that primitive tumor cells derived from the ciliary epithelium differentiate into both nonpigmented and pigmented cells. Additionally, previous authors have probably classified some adenocarcinomas of the ciliary body as "adult-type medulloepitheliomas," therefore making the precise number of reported adenocarcinomas of the nonpigmented ciliary epithelium difficult to ascertain. Adenocarcinomas of the ciliary body have been described as having one of four basic patterns: glandular or papillary, pleomorphic of low grade, pleomorphic with hyaline stroma, or anaplastic. 14 In our case, the tumor could be classified as pleomorphic with hyaline stroma. These tumors may arise in phthisical eyes with or without
766
history of previous trauma or inflammation. 6 ,8 It is possible that reactive hyperplasia of the nonpigmented epithelium of the ciliary body first develops and later malignant transformation takes place. Previously traumatized or inflamed eyes contain more poorly differentiated adenocarcinomas of the ciliary body than uninflamed or uninjured eyes. 6,14 Althou~h our patient was a poor historian, histologic evidence of intraocular osseous metaplasia indicates that the patient had a long-standing ophthalmic process, and the eye was already blind when examined 21/2 years before exenteration. Epibulbar extension of adenocarcinomas of the ciliary body, as was present in our case, has been observed previously.8,14 The manifestation that prompted our patient to seek medical attention was a bleeding epibulbar mass. Results of histologic study of the epibulbar mass demonstrated a poorly differentiated malignant neoplasm;
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Fig 8. Occasional tumor cells are completely surrounded by thick, multilaminated basement membrane (BM) (top inset). Some tumor cells contain intracytoplasmic intermediate filaments (bottom inset) (original magnification, X4400; insets, original magnification X 12,000).
however, the possibility of an adenocarcinoma of the nonpigmented epithelium of the ciliary body was not suspected until the intraocular portion of the tumor was examined. Similar cases have been described. 8,13,14 Harris and co-workers8 reported the case of a 74-year-old man with an epibulbar mass overlying his blind left eye. A wedge biopsy of the mass disclosed a poorly differentiated pleomorphic neoplasm. Enucleation was recommended and results of examination of the eye showed that the epibulbar tumor had arisen from the nonpigmented ciliary epithelium. Rodrigues and co-workers 14 described a 72year-old woman with epibulbar nodules overlying a blind, painful eye. The nodules were excised and initially interpreted to be anaplastic squamous cell carcinoma of the conjunctiva. Only after examination of the enucleation specimen was it determined that the epibulbar nodules were extensions from an adenocarcinoma of the ciliary body.
Table 1. Age and Ocular History of Patients with Adenocarcinoma of the Nonpigmented Ciliary Epithelium Reference
Patient Age (yrs)
Previous Trauma or Inflammation
Fuchs, 19081 Barrow and Stallard, 193t Wadsworth, 19494 Walter and James 19585 Andersen, 19626 Timm and Fritsch, 19647 Harris et ai, 19688 Horie et aI, 19729 Vogel, 197410 Kuchynka, 197911 Dryja et ai, 1981 12 Current case
? 61 56* 39 87 56 74 63 60 57 41 80
+
? 4 of 9
+ + ?
+ ?
?
? ? ?
* Average age of nine patients.
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Previous eyes with adenocarcinomas of the nonpigmented epithelium of the ciliary body also have had cataractous changes with ruptured capsules. I 1-13 Histologic evidence of tumor invasion into the lens was present in our case (Fig 5). Our case also exhibited features of intraocular osseous metaplasia and tumor invasion into the optic nerve as described in previous reports. 8 •14 Histochemical stains demonstrated intraluminal- but not intracytoplasmic hyaluronidase-sensitive mucopolysaccharide. This feature helps distinguish a primary adenocarcinoma of the ciliary body from a metastatic adenocarcinoma l5 and was of practical importance in our case since the patient had a history of adenocarcinoma of the prostate. The diagnosis of prostatic adenocarcinoma was made after the initial ophthalmic examination, but the histologic appearance, staining pattern for mucopolysaccharide, and lack of staining of the intraocular tumor for prostate specific antigen or prostatic acid phosphatase ruled out metastatic prostatic adenocarcinoma to the eye. 16 Immunohistochemical stains were positive for vimentin, epithelial membrane antigen, S-IOO protein, weakly positive for neuron-specific enolase, and negative for keratin in tumor cells. This is the first study to report these immunohistochemical findings in this tumor. Previous reports have mentioned negative staining for cytokeratin in an adenocarcinoma of the ciliary bodyl4 and positive staining for S-1 00 protein, vimentin, and neuron-specific enolase in neuroepithelial cells in a medulloepithelioma of the ciliary body. I? Those findings were similar to ours. Transmission electron microscopy demonstrated multilaminated basement membrane, desmosomes, and occasional intracytoplasmic intermediate filaments in the tumor as described in previous reports. 10.14 It appears that this tumor is a slow-growing malignancy in individuals of advanced age. Recommended treatment is enucleation or possible local excision. 6.12 However, the prognosis of patients with this tumor is uncertain, in part because of the paucity of well-documented cases. Five of 16 patients in whom adequate follow-up data were available are reported to have died of tumor extension or metastatic disease. 13 Poor prognosis may be related to tumor present at the surgical margin of resection. It is therefore
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NUMBER 6
conceivable that more aggressive surgery, such as exenteration, is indicated in otherwise healthy individuals with orbital or optic nerve invasion.
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