CLINICOPATHOLOGIC REPORT

SECTION EDITOR: W. RICHARD GREEN, MD Presumed Adenocarcinoma of the Retinal Pigment Epithelium in a Blind With a Staphyloma

Chaim Edelstein, MD, FRCSC; Carol L. Shields, MD; Jerry A. Shields, MD; Ralph C. Eagle, Jr, MD

he retinal pigment epithelium (RPE) can undergo reactive hyperplasia and metaplasia following a variety of ocular insults. However, true neoplasms of the RPE are rare. We report a case of a papillary adenocarcinoma of the RPE arising in the blind staphylo- matous right eye of a 79-year-old woman with a long history of bilateral posterior staphy- Tlomas who was seen with increasing pain and of the right eye. Findings from ul- trasonography and computed tomography demonstrated linear calcification consistent with osseous metaplasia of the RPE. Progression of the exophthalmos and worsening exposure keratitis led to enucleation of the eye. Gross pathology showed a 79-mm-long . Histopathologic findings re- vealed a largely amelanotic papillary adenocarcinoma arising from the RPE. Positive immunore- activity for cytokeratin supported the epithelial origin of the tumor. Adenocarcinoma of the RPE is rare but may develop in a blind eye. Arch Ophthalmol. 1998;116:525-528

True malignancies of the retinal pigment Findings on examination revealed epithelium (RPE) are extremely rare.1-3 The that the right eye could not perceive light RPE, however, can be involved in a re- and was 9-mm proptotic by Hertel exoph- markable variety of pathologic processes thalmometry. The was com- including reactive hyperplasia, congeni- pletely opaque, precluding a view of the tal hypertrophy, combined hamartoma, fundus, and the episcleral and conjuncti- and, less commonly, adenoma.1 We re- val vessels were diffusely vasodilated port herein a case of an adenocarcinoma (Figure 1). There was marked limita- of the RPE found in a blind eye with a large tion of extraocular movement in all direc- posterior staphyloma. tions of gaze. The intraocular pressure OD was 55 mm Hg. The visual acuity was light perception in the aphakic left eye with an REPORT OF A CASE intraocular pressure of 15 mm Hg. Find- ings on fundus examination showed a large A 79-year-old white woman was seen with posterior pole staphyloma and extensive increasing pain and exophthalmos of the myopic degeneration. right eye. The vision in the right eye had Orbital computed tomographic find- been poor since childhood following an al- ings revealed anterior displacement of the kali burn. Ten years prior to our seeing her, right eye by a massive staphyloma and lin- the vision in that eye had been noted to be ear calcification along the eye wall. The no light perception. was solid, well-circumscribed staphyloma was performed on the left eye, but her vision heterogeneous in density and was con- remained hand motions because of exten- tinuous with the posterior pole of the globe sive myopic degeneration and posterior (Figure 2). The left eye showed a pos- staphyloma. Beginning 3 months prior to terior staphyloma. Magnetic resonance im- our seeing her, her right eye had become aging findings showed a heterogeneous sig- increasingly prominent and painful. nal in the right eye slightly higher than that From the Ocular Oncology Service (Drs Edelstein, J. A. Shields, and C. L. Shields), and of the left eye (Figure 3). Linear signal the Department of Pathology (Dr Eagle), Wills Eye Hospital, Thomas Jefferson voids on both spin-echo sequences were University, Philadelphia, Pa. related to intraocular calcification. The

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 Figure 1. External photograph of the right eye showing pannus and complete Figure 2. Axial computed tomographic scan demonstrating exophthalmos of opacification of the cornea (November 1995). the right globe and linear calcification along the eye wall. Massive lesion filling the is contiguous with the posterior aspect of globe.

Figure 3. Axial T1-weighted magnetic resonance imaging scan showing orbital mass behind the right globe with a heterogeneous signal that shows Figure 4. Large, thin-walled posterior staphyloma filled with a mixture of high signal intensity. blood and tumor tissue protrudes from the posterior aspect of the eye. Light-colored necrotic tumor fills the vitreous cavity. C indicates the cornea; arrows, abrupt transition to staphyloma.

massive staphyloma involving the in their entirety and fixed in form- markedly atrophic remnants of the right eye showed a heterogeneous aldehyde. and ciliary body. A thick layer signal with hyperintense foci on T1- of dense collagen incorporating weighted images and hypointense/ large quantities of metaplastic bone PATHOLOGIC FINDINGS hyperintense foci on T2-weighted covered the inner surface of the images suggestive of blood prod- choroid. Retina was not identified. ucts (oxyhemoglobin/methemoglo- Macroscopically, a dark brown mass A papillary neoplasm composed of bin). The staphylomatous left eye with a smooth multinodular sur- polarized, cuboidal, and columnar demonstrated a normal low signal face protruded from the posterior epithelial cells with moderately intensity on T1-weighted images and surface of the firm right globe. The pleomorphic round to oval nuclei high signal intensity on T2-weighted anteroposterior length of the eye and and nucleoli filled the remaining images. posterior mass was 79 mm. The cor- interior of the globe and posterior The patient was followed up nea was scarred and opacified. The staphyloma. The tumor cells closely for 9 months and was found globe contained bone, necessitat- formed tubules, cords, and papillae to have increasing exophthalmos of ing decalcification prior to section- and rested on prominent connec- the right eye (13 mm) and worsen- ing. After sectioning, tan to brown tive tissue septa (Figure 5). ing exposure keratitis with corneal tumor tissue mixed with blood Although the tumor was largely epithelial breakdown. Because the was found to fill the interior of the amelanotic, a few strands of cells eye was blind and painful, with globe and posterior staphyloma contained melanin, suggesting ori- chronic corneal exposure and im- (Figure 4). gin from the RPE. Twenty-eight minent corneal ulceration, enucle- Microscopically, a thick layer mitotic figures were counted in 40 ation was recommended. Using a of dense fibrous tissue adhered to high-power fields. Focal necrosis modified enucleation approach with the posterior surface of the scarred and extensive intralesional hemor- lateral canthotomy, the globe and and ectatic cornea, obliterating the rhage were present. Parts of the massive staphyloma were removed anterior chamber and enveloping clotted blood were markedly

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 Figure 5. Top, Amelanotic epithelial cells composed of papillary Figure 6. Neoplastic epithelium composed of papillary tumor exhibits adenocarcinoma rest on prominent connective tissue septae. Cells show mild intense positive immunoreactivity for cytokeratin cell adhesion molecule nuclear pleomorphism (hematoxylin-eosin, original magnification ϫ100). marker CAM 5.2 (immunoperoxidase, original magnification ϫ50). Bottom, Arrows denote septa in this higher-magnification photomicrograph (hematoxylin-eosin, original magnification ϫ250).

degenerated and contained choles- reported by Garner,3 none of the me- In our case, the soft tissue defi- terol clefts and large amounts of tastases were confirmed histologi- nition of computed tomographic hematoidin and hemosiderin pig- cally. Loeffler et al7 reported a case studies was insufficient to differen- ment consistent with chronicity. of RPE malignancy with suspected tiate a solid neoplasm from a hem- The tumor cells showed intense extraocular extension. Some au- orrhagic process. The excellent soft (+4)positiveimmunoreactivityforcy- thors believe that an adenocarci- tissue contrast of magnetic reso- tokeratin cell adhesion molecule noma of the RPE with extraocular nance imaging studies was also un- marker CAM 5.2 (Figure 6) and extension is capable of metastasis to able to differentiate the hemorrhagic moderatelyintense(+2to+3)focalim- distant sites.8 from the neoplastic component munoreactivity for low-molecular Tumors of the RPE usually oc- within the lesion. Furthermore, the cytokeratin AE-1 and vimentin. cur in the peripheral retina but may relatively poor histopathological Staining for melanoma-specific occur close to the optic disc. Vitre- specificity of magnetic resonance im- antigen HMB-45, carcinoembry- ous seeding may occur if the tumor aging does not readily allow differ- onic antigen, S100 protein, and breaks through sensory retina. His- entiating primary from secondary high-molecular weight AE-3 was topathologically, tumors of the cili- uveal or retinal tumors.10 negative. ary pigment epithelium and RPE are This papillary malignancy was classified into vacuolated, tubular, and found coincidentally on histo- COMMENT mixed types. The more anterior tu- pathological sectioning of the mors tend to be vacuolated whereas globe. Following histopathological Although the RPE rarely gives rise the more posterior ones tend to be tu- diagnosis, it was decided not to to true neoplasms,1-3 it readily bular.1,2 Immunohistochemistry find- treat the patient with radiation undergoes reactive hyperplasia and ings may demonstrate immunoreac- and/or systemic chemotherapy due metaplasia following trauma, inflam- tivity for low molecular weight to her age, fragile health, and mation, or degenerative processes that cytokeratins, vimentin, and S100 because the mass was excised in its involve the choroid or retina. This protein, which is consistent with the entirety with no evidence of orbital may also occur without apparent neuroectodermal origin of the seeding. At 6 months following the cause. cells.7,9 enucleation, the patient continues Adenoma and adenocarci- Our case is interesting for sev- to do well with no evidence of noma of the RPE are both ex- eral reasons. This tumor was pres- metastatic disease or orbital recur- tremely rare. It is usually impos- ent in a staphylomatous globe that rence. It is known that reactive sible to distinguish between them was enucleated for other reasons. hyperplasia of the RPE may occur clinically.1-4 There are only a few The tumor was not diagnosed pre- secondary to trauma or inflamma- well-documented cases of adenocar- operatively as there was no view of tion. It has been suggested that cinoma of the RPE.4-6 These malig- the fundus clinically. In retrospect, hyperplasia of the RPE may rarely nancies tend to exhibit local inva- there may have been a suggestion of transform into a malignant tumor.4,7 siveness into the choroid and sensory a solid mass lesion on imaging stud- In the case reported here, there was retina. However, to the best of our ies, but the presence of an intraocu- a history of ocular trauma and knowledge, there are no histologi- lar tumor was not a serious consid- chronic inflammation. Although the cally proven cases of adenocarci- eration in the decision to perform the most frequent malignant intraocu- noma of the RPE that have metas- enucleation. This scenario is simi- lar tumor in phthisical is cho- tasized to other sites. Although 3 lar to the case of Loeffler and asso- roidal melanoma, other malignan- deaths from metastatic tumor were ciates.7 cies including adenocarcinoma of

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 the RPE must still be considered. We Wills Eye Hospital, 900 Walnut St, 6. Ramahefasolo S, Coscas G, Regenbogen L, speculate that this malignant neo- Philadelphia, PA, 19107. Godel V. Adenocarcinoma of the retinal pig- ment epithelium. Br J Ophthalmol. 1987;71: plasm may have arisen from RPE hy- 516-520. perplasia secondary to chronic in- REFERENCES 7. Loeffler KU, Kivela T, Borgmann H, Witschel H. flammation, similar to previous Malignant tumor of the retinal pigment epithe- published cases.4,7 In any eye with lium with extraocular extension in a phthisical eye. opaque media and a history of 1. Shields JA, Shields CL. Intraocular Tumors: A Text Graefes Arch Clin Exp Ophthalmol. 1996;234:70- and Atlas. Philadelphia, Pa: WB Saunders Co; 75. trauma, an underlying neoplasm 1992:437-460. 8. Finger PT, McCormick SA, Davidian M, Walsh JB. should be considered. 2. Green WR. Retina. In: Spencer WH, Bilyk JR, Eagle Adenocarcinoma of the retinal pigment epithe- RC Jr, et al, eds.Ophthalmic Pathology: An Atlas lium: a diagnostic and therapeutic challenge. Accepted for publication December 19, and Textbook. Vol 2. Phildelphia, Pa: WB Saun- Graefes Arch Clin Exp Ophthalmol. 1996;234:22- 1997. ders Co; 1996:1312-1316. 27. 3. Garner A. Tumors of the retinal pigment epithe- 9. Lieb WE, Shields JA, Eagle RC Jr, Kwa D, Shields Supported by the Eye Tumor lium. Br J Ophthalmol. 1970;54:715-723. CL. Cystic adenoma of the pigmented ciliary epi- Research Foundation, Philadelphia, 4. Shields JA, Eagle RC, Barr CC, Shields CL, Jones thelium: clinical, pathologic, and immunohisto- Pa. Dr Edelstein is the recipient DE. Adenocarcinoma of the retinal pigment epithe- pathologic findings. Ophthalmology. 1990;97: of the McLaughlin Foundation Fel- lium arising from a juxtapapillary histoplasmosis 1489-1493. scar. Arch Ophthalmol. 1994;112:650-653. 10. De Potter P, Shields JA, Shields CL. Tumors of lowship. 5. Minckler D, Allen AW. Adenocarcinoma of the reti- the uvea. In: De Potter P, Shields JA, Shields CL, Reprints: Jerry A. Shields, MD, nal pigment epithelium. Arch Ophthalmol. 1978; eds. MRI of the Eye and Orbit. Philadelphia, Pa: Director, Ocular Oncology Service, 96:2252-2254. JB Lippincott Co; 1995:55-92.

IN OTHER AMA JOURNALS

ARCHIVES OF OTOLARYNGOLOGY—HEAD & NECK SURGERY The Effect of on Eyebrow Position Andrew S. Frankel, MD; Frank M. Kamer, MD Objective: To determine if upper blepharoplasty causes eyebrow position to drop in a cosmetic surgery population. Design: Retrospective, observational study. A treatment group that underwent upper eyelid blepharoplasty was compared with a matched control group that did not undergo the surgery. Setting: Private facial plastic surgery practice. All surgery was performed at an ambulatory surgical facility on an outpatient basis. Patients: A total of 82 patients (164 eyes) were included in this study: 54 (8 men and 46 women; average age, 46.8 years) in the treatment group and 28 (6 men and 22 women; average age, 43.8 years) in the control group. The treatment group was chosen in a retrospective fashion to include only those patients (1) for whom preop- erative and postoperative photographs were available and (2) who had undergone upper eyelid blepharoplasty by the senior author (F.M.K.). These patients underwent no other procedures, either before or during the time span between the photographs, that could affect eyebrow position. The control group consisted of patients who had an available set of matching photographs taken over time. These patients did not undergo blepharoplasty or any other procedure that could alter eyebrow position between their initial and final photographs. Intervention: Upper eyelid blepharoplasty performed by the senior surgeon (F.M.K.). The surgical technique was identical in all cases. Outcome Measure: The change in eyebrow height reflected as a percentage of the pretreatment height. Re- sults are based on measurements taken from standardized photographs. Results: Original treatment and control groups of 108 and 56 eyes, respectively, were restricted to a smaller number to create similar populations for comparison. Therefore, 40 eyes in the treatment group were matched with 28 eyes in the control group to control for the duration between measurements. A t test found no signifi- cant difference (P=.94) in eyebrow height between patients who had a blepharoplasty and those who had not. Conclusion: In a cosmetic surgery population, upper eyelid blepharoplasty does not cause a lowering of the eyebrow. Arch Otolaryngol Head Neck Surg. 1997; 123:393-396

Reprints: Andrew S. Frankel, MD, 201 S Lasky Dr, Beverly Hills, CA 90212.

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