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Show Cancer-Associated Retinopathy in Neuroendocrine Carcinoma of the Fallopian Tube Anitha Raghunath, MD, Grazyna Adamus, PhD, Diane C. Bodurka, MD, Jinsong Liu, MD, PhD, Jade S. Schiffman, MD Abstract: A 70-year-old woman developed progressive visual loss with compromised visual acuity and visual fields, cells in the anterior chamber and vitreous, atten-uated retinal arterioles, and macular edema. She had undergone right oophorectomy and partial salpingectomy nearly 50 years earlier. Full-field and multifocal electro-retinography showed waveforms of markedly attenuated amplitudes, findings consistent with cancer-associated retinopathy (CAR). Positron emission tomography revealed a nodule in the anterior wall of a right hydro-salpinx. Total laparoscopic hysterectomy yielded a neu-roendocrine fallopian tube malignancy. She underwent partial treatment with paclitaxel and carboplatin that was aborted because of the development of herpes zoster infection. At 15 months following diagnosis, her oph-thalmic status was stable. This is the first report of CAR in neuroendocrine carcinoma of the fallopian tube. Journal of Neuro-Ophthalmology 2010;30:252-254 doi: 10.1097/WNO.0b013e3181e22ef0 2010 by North American Neuro-Ophthalmology Society Although paraneoplastic syndromes affecting vision, including cancer-associated retinopathy (CAR), are well documented in patients with small cell carcinomas, fallopian tube neuroendocrine carcinoma causing CAR has not been reported. We report such a case. CASE REPORT A 70-year-old woman reported progressive worsening of vision in both eyes (left eye more than right eye) for approximately 18 months. The patient had undergone bilateral cataract surgery 18 months earlier with a temporary improvement in vision. She described intermittent diarrhea for 2 years for which evaluation had been unrevealing. Nearly 50 years earlier, she had been diagnosed with an ovarian cyst and had undergone right oophorectomy and partial salpingectomy in conjunction with an incidental appendectomy. Although the cyst was benign, it had been necessary to remove part of the adjoining fallopian tube for complete excision of the ovarian cyst. She also had a history of hypothyroidism and excision of basal cell carcinoma of the nose. Three months before she presented to us, she had been evaluated by a neuro-ophthalmologist who had recorded visual acuities of 20/20 in the right eye and 20/25 in the left eye. Color vision had been severely impaired, but no afferent pupillary defect had been found. Posterior segment examination had revealed vitreous cells, mild retinal arte-riolar attenuation, and normal optic discs. Intraocular pressures had been 32 mmHg in the right eye and 19 mmHg in the left eye. Brain MRI had disclosed mild white matter signal abnormalities. Full-field electroretinography had shown extinguished or attenuated responses in nearly all photopic and scotopic conditions (Fig. 1). Negative tests had in-cluded serology for paraneoplastic neuronal and antiretinal antibodies, fluorescent treponemal antibody absorption test, rapid plasma reagin, angiotensin-converting enzyme, anti-neutrophil cytoplasmic antibody, Borrelia burgdorferi anti-body, and spinal fluid examination. The patient had been treated with bimatoprost eyedrops to lower intraocular pressure but was distressed by deteriorating vision and glare. Two months before consulting us, a second neuro-ophthalmologist recorded that visual acuities had deteriorated to 20/40 in the right eye and 20/50 in the left eye. Color vision was reduced in both eyes, and vitreous cells and slight pallor of both optic nerves were observed. Visual field examination showed enlargement of the blind spots with constricted isopters along the Departments of Ophthalmology (AR, JSS), Gynecologic Oncology (DCB), and Pathology (JL), The University of Texas M. D. Anderson Cancer Center, Houston, Texas; Department of Ophthalmology and Visual Sciences (AR), University of Texas Medical Branch, Galves-ton, Texas; and Ocular Immunology Laboratory, Department of Ophthalmology (GA), Casey Eye Institute, Oregon Health & Science University, Portland, Oregon. Address correspondence to Jade S. Schiffman, MD, Department of Ophthalmology, Unit 1445, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030; E-mail: jschiffm@mdanderson.org. 252 Raghunath et al: J Neuro-Ophthalmol 2010; 30: 252-254 Original Contribution Copyright © North American Neuro-ophthalmology Society.Unauthorized reproduction of this article is prohibited. horizontal meridian. A retinal fluorescein angiogram was sug-gestive of vasculitis. Optical coherence tomography showed subfoveal fluid bilaterally.Multifocal electroretinography showed bilateral near flattening of the waveforms. The patient was di-agnosed with bilateral chronic posterior uveitis, retinal vasculitis, and macular edema. No treatment was instituted. On our examination, best-corrected visual acuities were 20/25 in the right eye and 20/60 in the left eye. She was able to identify 4/14 Ishihara color plates with the right eye and 0/14 with the left eye. There was a left afferent pupillary defect of 0.6-0.9 log units. There were 2+ cells in the anterior chamber and 3+ cells in the vitreous in both eyes. Optic discs appeared normal, but macular edema was seen in the left eye. Amsler grid testing showed a dense ring scotoma with minimal central preservation in both eyes. With automated visual fields (Fig. 2), a dense ring scotoma was present in the right eye and severe constriction in the left eye. Further investigations revealed a negative collapsing response-mediating protein 5 antibody but positive serum anti-retinal antibodies against carbonic anhydrase II, alpha-enolase, and a 97 kDa protein. Immunohistochemistry, performed at the Ocular Immunology Laboratory at Oregon Health and Science University, Portland, Oregon (G.A.), showed strong cytoplasmic staining of the outer nuclear layer and diffuse staining of the ganglion cell layer and neuronal fibers of human retina. The patient underwent investigations to exclude lym-phoma and other malignancies. Gastrointestinal system evaluation to exclude Whipple disease and neoplasia with FIG. 1. Full-field electroretinography performed 2 months before our first consultation shows attenuated or ex-tinguished responses in photopic single flash (A), phot-opic 30 Hz flicker (B), scotopic potential (C), photopic and scotopic potentials (D), and oscillatory potential (E). FIG. 2. Visual fields show bilateral ring-like scotomas with small areas of central preservation. Mean deviations were 221.5 dB in the left eye and 221.32 dB in the right eye. Original Contribution Raghunath et al: J Neuro-Ophthalmol 2010; 30: 252-254 253 Copyright © North American Neuro-ophthalmology Society.Unauthorized reproduction of this article is prohibited. endoscopy and colonoscopy showed only diverticular dis-ease. A whole-body fluorodeoxyglucose positron emission tomography (with noncontrast CT for attenuation correc-tion) showed a nodular area in the anterior wall of a right hydrosalpinx. This finding was confirmed by ultrasound, which also showed a thickened endometrial stripe suspi-cious for endometrial malignancy. CA-125 measurement was 12.9 U/mL (within normal limits). Over the next 4 months, the hydrosalpinx grew, so the patient underwent a total laparoscopic hysterectomy. After an intraoperative frozen section reported a fallopian tube malignancy, a bilateral salpingo-oophorectomy, pelvic lymph node dissection, and omentectomy were completed. Low-power histopathology showed extensive necrosis (Fig. 3A). High-power histopathology (Fig. 3B) showed hyper-chromatic nuclei and scanty indistinct cytoplasm, numerous mitoses, and great variation in tumor cell size with focally irregularly shaped nuclei. Immunohistochemical staining was positive for epithe-lial membrane antigen (Fig. 3C), cytokeratin, chromogra-nin, synaptophysin, and neurofilament and negative for leukocyte common antigen, placental alkaline phosphatase, and alpha-fetoprotein. The morphology and immunohis-tochemical profiles supported a diagnosis of high-grade neuroendocrine carcinoma with small cell features. No tumor was found in the ovaries, endometrium, lung, or gastrointestinal tract. The patient did not receive any immunosuppressive medication, but completed 2 of 6 planned cycles of paclitaxel and carboplatin. She failed to complete chemotherapy due to an outbreak of herpes zoster in the right lower back. She has no evidence ofmalignancy at 15months following surgical treatment. At the most recent ophthalmological evaluation, visual acuitieswere20/30in theright eye and20/40 in the left eye. Previous binocular vitrectomies had revealed no evidence of malignancy or infection. She continues to have mild panuveitis for which she has been receiving periocular corticosteroid injections. Secondary to the corticosteroid injections, she has developed uncontrolled glaucoma. DISCUSSION We believe this to be the first reported case of CAR in the context of a neuro-endocrine carcinoma of the fallopian tube. Such cancers account for only 1% of all gynecologic malignancies (1). Neuroendocrine carcinoma-which is more common in the lung, gastrointestinal tract, and genitourinary tract-is rare in the fallopian tube, where adenocarcinoma is much more likely (2). The first primary neuroendocrine tumor of the fallopian tube was reported in 2004 by Dursun et al (2). Neuroendocrine carcinomas of the gynecologic tract are associated with poor prognosis (3). However, the patient with fallopian tube neuroendocrine carcinoma reported by Dursun et al (2) was alive at 16 months with no evidence of disease. Our patient is also doing well at 15 months after treatment. REFERENCES 1. Rosenblatt KA, Weiss NS, Schwartz SM. Incidence of malignant fallopian tube tumors. Gynecol Oncol. 1989;35: 236-239. 2. Dursun P, Salman MC, Taskiran C, Usubutun A, Ayhan A. Primary neuroendocrine carcinoma of the fallopian tube: a case report. Am J Obstet Gynecol. 2004;190:568-571. 3. Bermudez A, Vighi S, Garcia A, Sardi J. Neuroendocrine cervical carcinoma: a diagnostic and therapeutic challenge. Gynecol Oncol. 2001;82:32-39. FIG. 3. Histopathology of the surgical specimen of the fallopian tube. A. Low-power view of tumor shows extensive necrosis (hematoxylin and eosin 3100). B. High-power view shows cells with hyperchromatic irregularly shaped nuclei and scant indistinct cytoplasm, numerous mitotic figures, and great variation in tumor cell size (hematoxylin and eosin 3400). C. Immunohistochemical staining of neoplastic cells is positive for epithelial membrane antigen. In addition, these neoplastic cells are also positive for cytokeratin, synaptophysin, and neurofilament and negative for leukocyte common antigen (not shown). Original Contribution 254 Raghunath et al: J Neuro-Ophthalmol 2010; 30: 252-254 Copyright © North American Neuro-ophthalmology Society.Unauthorized reproduction of this article is prohibited. |
