Juvenile xanthogranuloma (JXG) is a benign cutaneous disorder that most commonly affects infants during the first year of life.1 This condition generally manifests with small, yellow-red, waxy papulonodular skin lesions. Without treatment, the lesions follow a benign course and generally regress during a few months.2 Extracutaneous JXG can affect the eye, brain, lungs, liver, spleen, and other organs.3 In a survey of 2,371 cases with JXG, Chang et al. reported eye involvement in approximately 0.3% of cases.4 Ocular involvement has been documented most often in the iris and less commonly in the eyelid, orbit, and choroid.5
Iris JXG commonly manifests with a nodular thickening in the iris, visible by slit-lamp biomicroscopy. Less commonly, the tumor is diffuse with flat infiltration of the iris, with no visible nodular mass. Both nodular and diffuse JXG can lead to spontaneous hyphema. In this study we describe an infant with multiple hyphemas but with no visible iris mass. After referral, using multimodal imaging, we detected iris thickening from diffuse JXG, confirmed on needle biopsy.
A 6-month-old female infant was referred to the Ocular Oncology Service at Wills Eye Hospital after developing three episodes of spontaneous hyphema in the left eye for a period of 2 months. She had no history of trauma and no systemic disorders. There were no cutaneous lesions. She was observed to have mild heterochromia with a blue iris in the right eye and a blue-green iris in the left eye (Figure 1A). Visual acuity at presentation was fix-and-follow in both eyes. At examination under anesthesia, the intraocular pressures were 21 mm Hg in both eyes and the anterior segment of the right eye was normal (Figure 1B). Funduscopic examination was normal in both eyes.
A 6-month-old female infant with recurrent hyphema and no visible mass. (A) Heterochromia iridis showing blue iris in the right eye and blue-green iris in the left eye. (B) The right iris is normal. (C) The left iris showing ochre-colored stringy blood in the anterior chamber and no iris tumor. (D) Late phase fluorescein angiography of the right iris showing normal radial vessels. (E) Late phase fluorescein angiography of the left iris showing diffuse hyperfluorescence with staining and leakage.
The findings were limited to the anterior segment in the left eye where ochre-colored stringy blood in the anterior chamber was noted without evident iris mass or structural abnormality (Figure 1C). Intravenous fluorescein angiography of the iris revealed normal iris vasculature in the right eye (Figure 1D), whereas the iris in the left eye demonstrated marked diffuse hyperfluorescence with staining and leakage (Figure 1E). Anterior segment optical coherence tomography (AS-OCT) of the iris in the right eye was normal with the presence of well-defined iris crypts (Figure 2A), whereas the left eye demonstrated a flat epiiridic membrane of 142 µm thickness and uniformly layered on the iris surface, obliterating iris crypts (Figure 2B). Ultrasound biomicroscopy (UBM) of the left eye confirmed slight iris thickening (Figures 2C–2D). Based on multimodal imaging, suspicion for diffuse iris JXG was raised.
(A) Anterior segment optical coherence tomography (AS-OCT) of the right eye showing normal iris (arrows) with intact crypts. (B) AS-OCT of the involved left iris showing flat surface without crypts and covered with an epiiridic membrane (arrows). (C) Ultrasound biomicroscopy of the left eye showing minimal iris thickening and (D) the anterior chamber blood is visible (arrow).
Fine-needle aspiration biopsy of the iris was performed through a clear corneal approach using a 27-gauge needle and submitted in Surepath preservative fluid (BD Diagnostics-Tripath, Burlington, NC). Cytopathology revealed a proliferation of lymphocytes and Touton giant cells (Figure 3A). Immunocytochemistry was positive for the histiocyte marker CD68 (Figure 3B). These findings were consistent with the diagnosis of JXG. The left eye was treated with a sub-Tenon injection of triamcinolone 10 mg. On follow-up examination, intraocular pressure was 14 mm Hg in the left eye, visual acuity was intact, and the hyphema had resolved by 2 months.
(A) Cytopathology showing lymphocytes and a giant cell (arrow). (B) Immunocytochemical stain for CD68, a histiocyte marker, was positive, consistent with iris juvenile xanthogranuloma (original magnification ×100).
Iris JXG can present as a clinically visible nodular mass or as a nearly invisible diffuse iris thickening. The nodular subtype is clinically visible, often of yellow-orange or tan-brown color and with slightly ill-defined margins from the discohesive inflammatory mass.1 The diffuse variant can be overlooked unless there is spontaneous hyphema or heterochromia. The diffuse variant is often transparent or translucent, lining the surface of the iris and best visualized with multimodal imaging.6
Recent advances in ocular imaging techniques have allowed subclinical detection of diseases, particularly retinal disease where the condition might be submillimeter in dimension, but visually symptomatic. With regard to anterior segment conditions, imaging with fluorescein angiography, UBM, and AS-OCT can assist in delineating the type and extent of disease. Brancato et al. described fluorescein angiography as a method for differentiating benign from malignant iris tumors because malignant tumors more often showed early fluorescence and late dye leakage.7 Regarding iris JXG, diffuse leakage in the entire iris has been documented.8 AS-OCT and UBM can be used to structurally image the anterior segment. AS-OCT provides higher resolution of approximately 5 µm compared to 25 µm with UBM. However, pigmented tissue causes dense shadowing with AS-OCT and not UBM. Therefore, AS-OCT is generally preferred for imaging iris stromal tumors, whereas UBM for densely pigmented tumors.9 With regard to iris JXG, Manjandavida et al.6 described a diffuse iris JXG on AS-OCT as a thin, uniform epiiridic layer, lining the entire surface of the iris and obliterating iris crypts, similar to our study. UBM showed iris thickening but with less resolution than AS-OCT, as in our study.6
In our study, needle aspiration biopsy was performed for tissue confirmation because the child had no cutaneous lesions. Sub-Tenon triamcinolone in addition to topical prednisolone acetate was delivered because this child had repetitive hyphemas, and the condition resolved following therapy.
Based on this case, multimodal ophthalmic imaging can be useful to recognize iris JXG, especially when the condition is not visible clinically. Our observations in combination with those of Manjandavida et al. suggest that there is a variant of iris JXG that is diffuse and nearly transparent, but with capability of producing hyphema and heterochromia.
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- Danzig CJ, Shields CL, Mashayekhi A, Ehya H, Manquez ME, Shields JA. Fluorescein angiography of iris juvenile xanthogranuloma. J Pediatr Ophthalmol Strabismus. 2008;45:110–112. doi:10.3928/01913913-20080301-03 [CrossRef]
- Bianciotto C, Shields CL, Guzman JM, et al. Assessment of anterior segment tumors with ultrasound biomicroscopy versus anterior segment optical coherence tomography in 200 cases. Ophthalmology. 2011;118:1297–1302.