From Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Sander R. Dubovy, MD, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Florida Lions Eye Bank–Ocular Pathology Laboratory, 900 NW 17th Street, Miami, FL 33136. E-mail: firstname.lastname@example.org
Pseudohypopyon secondary to metastatic neoplastic processes is rarely seen. The choroid is the most common site for uveal metastasis, whereas involvement of the iris and anterior segment accounts for less than 10% of metastases.1 Metastases of lung primary rarely present in the iris or anterior chamber. Pseudohypopyon has only been reported in association with esophageal carcinoma.2 We report the first case of pseudohypopyon secondary to a non–small-cell carcinoma of the lung.
A 74-year-old man presented with a choroidal and vitreous infiltrate and a history of primary central nervous system and splenic lymphoma, as well as lung (Fig. 1A), bladder, and prostate carcinoma. The patient had been diagnosed 2 years prior to presentation as having non–small-cell carcinoma of the lung and had received chemotherapy (carboplatin and paclitaxel 45 mg/m2) and 7,000 cGy radiation (35 treatments) to the left lower pleural base for 2 months.
Figure 1. Ocular presentation of metastasis, digitally processed images. (A) Axial computed tomography of lung showing a left pleural-based upper lobe mass. (B) Montage photograph of the left eye displays a feathery, fluffy amelanotic white choroidal infiltrate with dense vitreous seeding nasal to the optic nerve head. Dense vitreous seeding is present along the borders of the lesion and temporal to the fovea, with dense vitreous opacities inferiorly. (C) Diagnostic B-scan ultrasound exhibits dense vitreous and subvitreal opacities and irregular thickening of the nasal fundus measuring 1.5 mm in height. (D) Spectral-domain optical coherence tomography (Heidelberg Engineering, Carlsbad, CA) displays a layer of cellular material overlying the anterior surface of the macula.
At initial presentation, visual acuity was 20/30 in the right eye and 20/200 in the left eye. Pupils were unremarkable without an afferent pupillary defect. Visual field, Amsler grid testing, and intraocular pressures were unremarkable. External and slit-lamp examinations were unremarkable except for 2+ nuclear sclerosis of the crystalline lenses. The dilated fundus of the right eye was unremarkable; the left eye displayed a feathery amelanotic choroidal infiltrate (Fig. 1B) with dense vitreous opacities and irregular thickening of the nasal fundus measuring 1.5 mm in height (Fig. 1C) with medium to high reflectivity was identified on A-scan from the 7- to 11-o’clock positions. In addition, Heidelberg spectral-domain optical coherence tomography (SD-OCT) displayed a layer of material present along the anterior surface of the macula (Fig. 1D).
Given multiple potential etiologies, a diagnostic vitrectomy of the involved eye was performed. Flow cytometry and gene rearrangement studies were unremarkable for a monoclonal hematopoietic cell population (lymphoma) and light microscopy demonstrated atypical cells with prominent nucleoli that stained positively for cytokeratin (DAKO Inc., Carpinteria, CA) and thyroid transcription factor-1 (TTF-1) (DAKO Inc.), consistent with a diagnosis of metastatic non–small-cell carcinoma of the lung.
The patient underwent consolidating external beam brain radiotherapy (Tomotherapy Inc., Madison, WI), 3,750 cGy (15 treatments) over a 3-week period, with target dose coverage to the choroid and posterior chamber of the left eye. Three months postoperatively, visual acuity had decreased to 1/200 in the left eye. Anterior segment examination of the left eye disclosed a gray-white cellular collection, layered inferiorly, that measured 3 mm in height (Fig. 2A) and a flat iris without any mass. Fundus examination revealed an exudative retinal detachment with vitreous tumor involvement and pre-retinal traction. A pars plana vitrectomy, membrane peel, laser treatment, silicone oil tamponade, and intravitreal bevacizumab injection (1.25 mg/0.05 mL) were performed. Anterior chamber biopsy was performed and identified a carcinoma (Fig. 2B) that stained positively for TTF-1 (Fig. 2C) and cytokeratin with morphological features consistent with non–small-cell carcinoma of lung primary (Fig. 2D).
Figure 2. External photograph and photomicrographs. (A) Left eye demonstrates a clear cornea and a gray-white pseudohypopyon along the inferior portion of the chamber secondary to metastatic seeding from a lung primary. (B) Anterior chamber cytology exhibits atypical vacuolated epithelial cells that are variably multi-nucleated (hematoxylin–eosin, original magnification ×400). (C) Anterior chamber cytology, positive TTF-1 stain (thyroid transcription factor-1, original magnification ×200). (D) Lung biopsy, fine needle aspiration. Well-differentiated clusters of epithelial tumor cells exhibiting prominent eosinophilic intracytoplasmic globules along alveolar walls (hematoxylin–eosin, original magnification ×200). Inset: Touch preparation of lung biopsy. High magnification reveals the adjacent nuclei vary widely in size (hematoxylin–eosin, original magnification ×400).
Pseudohypopyon is a non-inflammatory cellular infiltrate associated with protean clinical presentations, as opposed to the more common neutrophilic or lymphocytic hypopyon exudate associated with endophthalmitis or uveitis. Pseudohypopyon has been reported with primary malignancies such as retinoblastoma3 and lymphoma,4 in addition to metastatic malignancies such as esophageal carcinoma,2 multiple myeloma,5 and acute myelogenous leukemia.6 In recent years, iatrogenic etiologies for pseudohypopyon have been reported, with the most common cause being after injection of triamcinolone acetonide.7
Symptomatic anterior segment metastases are much less common than diffuse uveal tract metastases. This case presents the rare metastatic involvement of both the anterior and posterior uveal tract and the anterior chamber. Metastases usually affect a single ocular tissue, and it is unusual for such widespread ocular involvement to be the first sign of systemic metastasis from a primary neoplasm. Having been treated with chemoradiotherapy for multiple previous malignancies, the presenting symptoms led to a wide differential diagnosis including primary intraocular lymphoma, metastatic carcinoma of lung, bladder, or prostate, or metastatic splenic lymphoma.
Patients with a history of malignancy presenting with a pseudohypopyon necessitate a comprehensive evaluation including diagnostic imaging (computed tomography of entire body and ultrasonography), flow cytometry, gene rearrangement, serological markers, and immunohistological staining of material obtained by anterior chamber paracentesis. This case demonstrates the importance of using multiple diagnostic modalities to ascertain the source of malignancy and implement appropriate therapy.
- Shields JA, Shields CL, Kiratli H, de Potter P. Metastatic tumors to the iris in 40 patients. Am J Ophthalmol. 1995;119:422–430.
- Kiuchi K, Kimoto T, Takahashi K, Shima C, Nishimura T, Matsumura M. Case with metastasis of a squamous esophageal cancer of the iris with resemblance to hypopyon [article in Japanese]. Nippon Ganka Gakkai Zasshi. 2007;111:735–740.
- Wang AG, Hsu WM, Hsia WW, Liu JH, Yen MY. Clinicopathologic factors related to metastasis in retinoblastoma. J Pediatr Ophthalmol Strabismus. 2001;38:166–171.
- Dorrepaal SJ, Margolin EA, Wang C. Bilateral pseudohypopyon as a presenting feature of recurrent diffuse large B-cell lymphoma. J Neur-oophthalmol. 2010;30:67–69. doi:10.1097/WNO.0b013e3181ce2c98 [CrossRef]
- Tranos PG, Andreou PS, Wickremasinghe SS, Brazier JD. Pseudohypopyon as a feature of multiple myeloma. Arch Ophthalmol. 2002;120:87–88.
- Ells A, Clarke WN, Noel LP. Pseudohypopyon in acute myelogeneous leukemia. J Pediatr Ophthalmol Strabismus. 1995;32:123–124.
- Moshfeghi AA, Scott IU, Flynn HW Jr, Puliafito CA. Pseudohypopyon after intravitreal triamcinolone acetonide injection for cystoid macular edema. Am J Ophthalmol. 2004;138:489–492. doi:10.1016/j.ajo.2004.03.025 [CrossRef]