- © 2011 by American Society of Clinical Oncology
Seventeen-Year Survival of Small-Cell Lung Carcinoma Presenting As Carcinoma-Associated Retinopathy
Case Report
A 51-year-old man with bilateral rapid loss of vision and photopsia was referred. He smoked 20 cigarettes a day for 25 years and gave up smoking in 1989. His past medical and ophthalmologic histories were both unremarkable. Visual acuity was 20/50 in the right eye and 20/25 in the left eye. Pupillary reactions to light were normal. Eye movements were full in both eyes. Ishihara color plates were read fully in both eyes. Anterior segments and intraocular pressures were normal in both eyes. Funduscopy revealed retinal pigment epithelium changes in the macular region of both eyes and slight narrowing of retinal arteries. Goldman visual field testing was performed a few weeks later and disclosed generalized field loss with ring scotomas in the midperiphery (Fig 1, Goldman visual field of right eye [RE] and [LE] disclosing typical ring scotomas with preservation of islands of vision in the periphery in the right and left panels, respectively). Full-field (Ganzfeld) electroretinograms were abnormal, with a reduction in both rod and cone functions. Orbit and brain magnetic resonance imaging scans were also normal. The ophthalmic constellation of findings in this patient raised the suspicion of carcinoma-associated retinopathy (CAR). A computed tomographic scan of the chest demonstrated multiple hilar masses in the right hemithorax suggestive of a primary lung neoplasm. Both transbronchial fine-needle aspiration cytology and endobronchial biopsy confirmed a small-cell lung cancer (SCLC). A work-up for metastases yielded negative results. Blood marrow biopsy, computed tomography and ultrasound of the abdomen, CSF analysis, and bone scintigraphy were all negative. Lactate dehydrogenase levels were normal in the serum. The patient was therefore considered to have limited-stage SCLC. Combined radiation therapy up to 45 Gy and chemotherapy consisting of 36-day cycles of cisplatin and etoposide was started and maintained for a period of 6 months. In the mean time, the patient's serum was taken for immunoblotting and showed a 23-kDa protein, recoverin, consistent with the CAR autoantibody. The patient was offered 14 sessions of plasmapheresis during 2 months. One year later, without any further treatment the patient was still alive, but his vision had deteriorated to 20/200 in the RE and 20/25 in the LE. Funduscopy showed diffuse atrophy of the retina in the macula region of the RE (Fig 2, above: color pictures of the RE; six pictures show narrowing of arteries, RPE clumping in the peripheral retina, and diffuse REP atrophy. Below: color pictures of the LE; six pictures show narrowing of arteries, RPE clumping in the peripheral retina, and diffuse RPE atrophy.). Two years later the visual acuity in the LE dropped to 20/50 because of a cystoid macular edema that was successfully treated with a 6-week course of oral acetazolamide. Seventeen years later, the patient is still alive. His visual acuity is now 20/200 in the RE and 20/50 in the LE. Funduscopy remained unchanged.
Discussion
CAR was first described in 1987, and it is the most common paraneoplastic retinopathy syndrome.1 The prevalence is unknown and equal between men and women. CAR can be present before, during, or after the occurrence of the primary tumor. Initially, CAR patients have high titers of autoantibodies directed against a protein produced by their tumor that has homology to a specific 23-kDa retinal protein now identified as recoverin.2–4 Recoverin is a retinal photoreceptor calcium-binding protein involved in the regulation of rhodopsin phosphorylation. Recoverin was identified first in the tumor of a patient with small-cell carcinoma of the lung and later in gynecologic and breast cancers.5–10 Antirecoverin antibodies11 lead to apoptotic photoreceptor cell death equally affecting rods and cones. Cone dysfunction symptoms consist of photosensitivity, hemeralopia, reduced visual acuity, decreased color perception, and central scotomas. Rod dysfunction is characterized by nyctalopia, prolonged dark adaptation, and peripheral field loss. Typically, full-field Ganzfeld electroretinograms are markedly reduced. Fundal examination can appear normal initially and later show sheathing of the retinal vessels, narrowing of the arterioles, and clumping of the retinal pigment epithelium. CAR is a subacute, progressive autoimmune retinopathy in which the patient will ultimately lose vision in both eyes.12 In addition to recoverin, other antibodies reactive against retinal antigens with different molecular weights, such as antienolase antibodies13 at 46-kDa,14 a 45-kDa and a 60-kDa protein, heat-shock cognate protein 70, and tubby-like protein,13,15 have been found in patients with CAR. These antibodies are the products of several different tumors and react against different cell layers of the retina.13,14,16,17 Treatment of CAR has been found to be relatively ineffective. Corticosteroids provide some transient improvement,18,19 and a combination of corticosteroids and plasmapheresis was successful in one patient.20 Three reported patients have received intravenous immunoglobulins with variable results.21 Surgery, chemotherapy, and radiotherapy of the initial tumor have not resulted in an improvement in visual outcome.22
This patient outcome was exceptional in two ways. First, the patient survived 16 years after the diagnosis of CAR and SCLC; most patients suffering from SCLC die within 2 years.23 Patients with CAR are also expected to have a limited life span after diagnosis.24 Second, the patient maintained good vision in one eye compared with hitherto reported patients with CAR who characteristically have advanced visual loss within a few weeks of diagnosis despite any attempt at treatment.
One possible explanation for the long survival of this patient is the presence of antirecoverin antibodies interacting with exposed recoverin antigen in the SCLC cells leading to cell death. However, our patient did not show any detectable recoverin antibodies after his plasmapheresis treatment and still survived for many years.
The favorable predictive factors known for SCLC are limited-stage disease, good performance status, normal serum lactate dehydrogenase, and female sex.23
Our patient had a good performance status, normal lactate dehydrogenase, and limited-stage disease and was treated with radiotherapy and chemotherapy according to clinical guidelines.25 Another patient with recoverin-positive CAR associated with SCLC who survived 7 years has been reported.26 However, the authors did not provide information about his visual status at the end of the follow-up period. Another report described a patient with CAR syndrome surviving 15 years after resection of a lung adenocarcinoma.27 The patient's final vision was 20/200 in both eyes at the end of the 15-year period.
CAR should be considered in patients with unexplained visual loss with rod or cone dysfunction or with known or suspected malignancy.
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest.
