Ophthalmic Surgery, Lasers and Imaging Retina

Case Report 

Retinal Metastasis Simulating Cytomegalovirus Retinitis

John F. Payne, MD; Hassan T. Rahman, MD; Hans E. Grossniklaus, MD; Chris S. Bergstrom, MD, OD

Abstract

A 62-year-old man with lung cancer presented with a 2-week history of decreased vision and clinical features of cytomegalovirus retinitis. The patient was empirically treated for viral retinitis, but microbiological testing of the vitreous fluid was negative. Based on the suspicion for retinal metastasis, the patient underwent pars plana vitrectomy with retinal biopsy. Surgical techniques included the use of a chandelier illumination to enable bimanual manipulation of the retinal tissue, creation a focal retinal detachment with a 41-gauge subretinal cannula, diathermy demarcation of the biopsy site, localized retinectomy with vertical scissors, endolaser, and long-acting gas tamponade. Histopathologic examination revealed sheets of tumor cells with pleomorphic nuclei and positive staining for cytokeratins consistent with metastatic adenocarcinoma. The patient subsequently underwent external beam radiation and was alive 10 months after presentation. This surgical technique may be valuable in select patients with retinal metastasis for diagnostic, therapeutic, and counseling purposes.

From the Department of Ophthalmology, Emory Eye Center, Atlanta, Georgia.

Supported in part by a grant to Emory Eye Center from Research to Prevent Blindness, Inc., New York, New York.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Chris S. Bergstrom, MD, Emory Eye Center, 1365 B Clifton Road, Room B2400, Atlanta, GA 30322. E-mail: cbergs2@emory.edu

Received: January 07, 2012
Accepted: July 24, 2012
Posted Online: August 30, 2012

Abstract

A 62-year-old man with lung cancer presented with a 2-week history of decreased vision and clinical features of cytomegalovirus retinitis. The patient was empirically treated for viral retinitis, but microbiological testing of the vitreous fluid was negative. Based on the suspicion for retinal metastasis, the patient underwent pars plana vitrectomy with retinal biopsy. Surgical techniques included the use of a chandelier illumination to enable bimanual manipulation of the retinal tissue, creation a focal retinal detachment with a 41-gauge subretinal cannula, diathermy demarcation of the biopsy site, localized retinectomy with vertical scissors, endolaser, and long-acting gas tamponade. Histopathologic examination revealed sheets of tumor cells with pleomorphic nuclei and positive staining for cytokeratins consistent with metastatic adenocarcinoma. The patient subsequently underwent external beam radiation and was alive 10 months after presentation. This surgical technique may be valuable in select patients with retinal metastasis for diagnostic, therapeutic, and counseling purposes.

From the Department of Ophthalmology, Emory Eye Center, Atlanta, Georgia.

Supported in part by a grant to Emory Eye Center from Research to Prevent Blindness, Inc., New York, New York.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Chris S. Bergstrom, MD, Emory Eye Center, 1365 B Clifton Road, Room B2400, Atlanta, GA 30322. E-mail: cbergs2@emory.edu

Received: January 07, 2012
Accepted: July 24, 2012
Posted Online: August 30, 2012

Retinal Metastasis Simulating Cytomegalovirus Retinitis

Introduction

Cytomegalovirus retinitis is the most frequent ocular opportunistic infection among patients with acquired immunodeficiency syndrome and is relatively common in other immunocompromised hosts.1,2 In contrast to choroidal metastasis, the most common intraocular malignancy in adults, metastatic disease of the retina is exceedingly rare.3,4 Patients often present with white or yellow-white retinal patches, intraretinal hemorrhages, and perivascular infiltrates.3 Although these entities can be distinguished by their histopathologic characteristics, obtaining adequate tissue for diagnostic purposes prior to enucleation can be challenging. In this report, we describe the surgical technique of pars plana vitrectomy and excisional biopsy in a patient with intraretinal metastatic adenocarcinoma that simulated cytomegalovirus retinitis.

Case Report

A 62-year-old man with a history of small-cell lung cancer presented with a 2-week history of acute, painless vision loss in the left eye. Nine months prior to symptom onset, he was diagnosed as having a high-grade, small-cell lung carcinoma that had metastatic spread to bone and supraclavicular lymph nodes. He subsequently completed chemotherapy with carboplatin and etoposide and prophylactic brain radiotherapy (30 Gy), which included the posterior one-third of the globes, approximately 2 months prior to symptom onset. Visual acuity at presentation was 20/20 in the right eye and 20/400 in the left eye. There was no relative afferent papillary defect, but a large nasal visual field defect. Examination of the left eye showed no anterior chamber cell, 1+ vitreous haze, and a large area of retinal whitening in the temporal macula and mid-periphery with associated preretinal hemorrhage (Figures 1A–1B). Optical coherence tomography revealed thickening and hyperreflectance of the inner retina, and ultrasound showed a 2.4-mm thick lesion with medium internal reflectivity (Figures 1C–1D). Based on suspicion for viral retinitis, he underwent a vitreous paracentesis and intravitreal injection of foscarnet 2.4 mg, and started oral valacyclovir 900 mg twice a day. Polymerase chain reaction testing of the vitreous fluid was negative for cytomegalovirus, varicella zoster virus, herpes simplex virus, and Toxoplasmosis gondii. Cytologic examination of the vitreous fluid showed proteinaceous material, but no neoplastic cells.

Clinical features at presentation. (A) Color fundus photograph shows mild to moderate vitreous haze and an area of retinal whitening with intraretinal hemorrhage temporal to the fovea. (B) Montage photograph shows the extent of retinal whitening and layering of blood and cellular aggregate on the posterior hyaloid inferiorly. (C) Spectral-domain optical coherence tomography image demonstrates thickening and hyperreflectance of the inner retina temporal to the fovea. (D) B-scan ultrasonography shows a 2.4 mm thick retinal lesion temporal to the macula.

Figure 1. Clinical features at presentation. (A) Color fundus photograph shows mild to moderate vitreous haze and an area of retinal whitening with intraretinal hemorrhage temporal to the fovea. (B) Montage photograph shows the extent of retinal whitening and layering of blood and cellular aggregate on the posterior hyaloid inferiorly. (C) Spectral-domain optical coherence tomography image demonstrates thickening and hyperreflectance of the inner retina temporal to the fovea. (D) B-scan ultrasonography shows a 2.4 mm thick retinal lesion temporal to the macula.

With no clinical improvement for 2 weeks, the patient underwent pars plana vitrectomy, retinal biopsy, endolaser, and C3F8 gas tamponade. Histopathologic examination revealed sheets of tumor cells with pleomorphic nuclei and positive immunohistochemical staining for AE1/3, consistent with metastatic adenocarcinoma (Figures 2A–2B). Examination by transmission electronmicroscopy showed sheets of cells with pleomorphic nuclei, prominent nucleoli, and chromatin margination (Figure 2C).

Pathologic examination. (A) Low power magnification shows sheets of tumor cells (arrowheads) with pleomorphic nuclei overlying the retina (arrows) (hematoxylin-eosin, original magnification ×100). (B) Immunohistochemical staining for cytokeratins AE 1/3 is positive in the tumor cells (arrows) on the inner retina (original magnification ×100). (C) Transmission electronmicrograph shows tumor cells with prominent nucleoli and chromatin margination overlying the internal limiting membrane (*) (original magnification ×1,900).

Figure 2. Pathologic examination. (A) Low power magnification shows sheets of tumor cells (arrowheads) with pleomorphic nuclei overlying the retina (arrows) (hematoxylin-eosin, original magnification ×100). (B) Immunohistochemical staining for cytokeratins AE 1/3 is positive in the tumor cells (arrows) on the inner retina (original magnification ×100). (C) Transmission electronmicrograph shows tumor cells with prominent nucleoli and chromatin margination overlying the internal limiting membrane (*) (original magnification ×1,900).

Repeat magnetic resonance imaging shortly after surgery failed to show brain metastasis. The patient subsequently underwent palliative external beam radiation (45 Gy over 25 fractions) to the left eye and orbit. Ten months after presentation the patient was alive. At final follow-up, the patient’s vision was counting fingers at 2 feet, and although the retina was fully attached, the vasculature was sclerotic and the metastatic retinal lesion appeared atrophic (Figure 3).

Postoperative appearance. Color fundus montage of the left eye three months after surgery reveals a flat chorioretinal scar at the retinal biopsy site, as well as patches of retinal pigment epithelial atrophy. The retinal vessels near the macula appear particularly sclerotic.

Figure 3. Postoperative appearance. Color fundus montage of the left eye three months after surgery reveals a flat chorioretinal scar at the retinal biopsy site, as well as patches of retinal pigment epithelial atrophy. The retinal vessels near the macula appear particularly sclerotic.

Discussion

Metastastic disease of the retina, which was first described in 1934,5 is rare and can be difficult to diagnose.3 In 2006, Pelzek and Schachat reviewed the 28 reported cases of retinal metastasis and found that patients often have known primary tumors at diagnosis, most commonly pulmonary or gastrointestinal adenocarcinomas or cutaneous melanomas.3 Conditions most likely to simulate retinal metastases include infectious retinitis and vaso-occulsive disorders.3,6–8 Patients with cytomegalovirus retinitis characteristically exhibit patches of yellow to white retinal necrosis and edema often with associated hemorrhage.9 The distribution of retinitis is often in a vascular pattern and when involving the macula can wrap circumferentially around the fovea.10 Furthermore, patients with cytomegalovirus retinitis typically present with symptoms of blurred central vision and loss of peripheral visual field. Our patient exhibited all of these clinical features and could be considered immunocompromised because of his recent chemotherapy and brain radiation. However, the amount of retinal thickening and medium internal reflectivity on ultrasonography was atypical for cytomegalovirus retinitis. Our patient also exhibited a layering of large white blood cells along the posterior hyaloid in a pseudohypopyon pattern (Figure 1B), which is uncharacteristic of cytomegalovirus retinitis.

Prior to 1979, most cases of retinal metastasis were diagnosed at the time of autopsy or enucleation.3 Since then, the clinical diagnosis has been verified in some cases by intraocular fluid cytology and in a few cases by chorioretinal biopsy.3 In 1988, Eagle reported a case of carcinomatous retinitis which had been diagnosed by vitreous aspirate and eye wall biopsy.6 In 1995, Balestrazzi et al. described local resection of a retinal metastatic lesion by a cutaneous melanoma,11 and later Spadea et al. described the technique for a chorioretinal biopsy using a transscleral approach.12 The surgical technique described in this report is advantageous because it yields an adequate sample for histopathologic examination and causes relatively little injury to the eye.

At the time of presentation, it was thought that his metastatic lung adenocarcinoma had been adequately treated with systemic chemotherapy and prophylactic brain radiotherapy, which included radiation to the posterior one-third of the globes. Because there were no other new metastatic brain foci at the time of presentation and because he had recently undergone eye/brain radiotherapy, there was a need to confirm the diagnosis with histopathologic examination. The implications of having recurrent metastatic disease of the central nervous system following chemotherapy and brain radiation were important factors in our recommendations for pars plana vitrectomy and retinal biopsy.

The biopsy site for this procedure was chosen at the edge of normal and abnormal retina to provide a “clean” margin for pathologic examination. Additionally, a peripheral location was chosen to minimize visual sequelae. By creating a localized retinal detachment with a subretinal cannula, the retina was able to be excised fairly easily without damaging the underlying choroid. The 2 × 2 mm sample obtained in this case was adequate for diagnosis and demonstrated sheets of tumor cells with pleomorphic nuclei in the inner retina.

Over the past 25 years, patients with retinal metastasis have most often been treated with palliative external beam radiation, as in this case, with enucleation being reserved for those with intractable pain.3 Systemic prognosis is guarded with an average survival of 10.5 months following diagnosis.3 Duration of survival reflects the aggressiveness of the primary cancer and the extent of metastasis.3 Our patient has tolerated his palliative external beam radiotherapy well and has shown regression of the intraocular metastatic disease at final follow-up.

We report the clinical features of a patient with intraretinal metastasis of a small-cell adenocarcinoma of the lung, which shared many similarities to cytomegalovirus retinitis. Additionally, we describe the surgical technique for performing a retinal biopsy using pars plana vitrectomy, subretinal fluid injection, endoresection, air–fluid exchange, laser and long-acting gas tamponade. This surgical procedure may potentially be beneficial for select patients with retinal metastatic disease for diagnostic and therapeutic purposes.

References

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