Occult primary carcinoma metastatic to the iris

A 61-year-old male underwent an uncomplicated trabeculectomy with Mitomycin-C for inflammatory glaucoma associated with debris in the right inferior angle, without histopathological examination of the trabeculectomy specimen. Two weeks later the subject developed vascularized, amelanotic nodules on his iris (Fig. 1) and was referred to the National Eye Institute for evaluation of unilateral anterior granulomatous uveitis. Thorough history and laboratory investigations were remarkable only for occasional gastrointestinal disturbances and an elevated erythrocyte sedimentation rate. Ultrasound biomicroscopy (system model 840; Humphrey Zeiss; San Leandro, California, USA) revealed a mass that extended from the ciliary body to the iris (Fig. 2). A fine needle aspiration biopsy of the lesion through the clear cornea using a 30-gauge needle revealed atypical mucin-producing cells with large nuclei, prominent nucleoli and abundant vacuolated cytoplasm. These cells were intermixed with macrophages, some of which contained melanin granules. Interestingly, those atypical mucin-producing cells could be stained with epithelial (cytokeratin) but not with melanocytic markers (HMB45), consistent with a metastatic carcinoma (Fig. 3). A systemic work-up for malignancy was negative. Clinical photograph of the right eye showing amelanotic vascularized masses, initially thought to represent granulomas, in the inferior angle. Ultrasonographic biomicroscopy of the lesion showing involvement of the peripheral iris, angle and ciliary body. (A) Photomicrograph of the cytology illustrating large atypical periodic acid-Shiff positive cells infiltrating the iris. Original magnification ×200. (B) Photomicrograph showing some atypical cells with melanin granules in the cytoplasm and others with cytoplasmic vacuoles. haematoxylin-eosin; original magnification ×600. (C) Photomicrograph of immunohistochemistry demonstrating positive labelling for cytokeratin, an epithelial marker. Avidin-biotin-complex immunoperoxidase; original magnification ×400. (D) Photomicrograph of immunohistochemistry demonstrating negative labelling for HBM45, a marker for melanocytes and neural crest-derived tumours, with blue-green background. Avidin-biotin-complex immunoperoxidase; original magnification ×400. In this particular case, cytology of the iris nodules, which had an unusual clinical appearance for granulomas, demonstrated malignant cells of possible gastrointestinal origin. In 25% of cases iris metastases may be the first manifestation of a malignancy. Breast (40%) and lung (28%) carcinomas are the most common causes of uveal metastases, whereas gastrointestinal carcinomas are less common. It is useful to consider masquerade syndrome in the differential diagnosis of uveitis and to exclude it when appropriate with a diagnostic procedure and appropriate pathological studies.