A 2.5-year-old boy was noted to have heterochromia at birth. He was born at full term and was otherwise healthy and not taking any medications. The patient’s right eye was noted to be blue and the left eye was brown (Figure 1). On further examination, no red reflex was present in the left eye. An infiltrative hypervascular lesion of the iris with anterior chamber hemorrhage was also found in the left eye.
Patient as an infant with heterochromia. The left eye with juvenile xanthogranuloma has a dark brown iris while the right iris is blue.
He was referred to the ocular oncology service at Memorial Sloan Kettering Cancer Center, where examination under anesthesia by one surgeon (BM) resulted in a clinical diagnosis of ocular juvenile xanthogranuloma due to additional findings of a thickened iris by ultrasound and an iris lesion suggestive of juvenile xanthogranuloma. Vitreous hemorrhage was also noted, with a normal fundus. There were no lesions involving the skin at this time. Subsequently, the patient was treated with topical steroid drops in the left eye and monitored. On follow-up examination, the anterior chamber and anterior vitreous hemorrhage had cleared and the heterochromia had resolved (Figure 2). At 22 months of age, the patient was found to have anisometropic amblyopia with a cycloplegic refraction of +1.00 in the right eye and −2.00 in the left eye. He was also found to have a small anterior lens opacity in the left eye. He was given glasses and patched.
Patient at 22 months of age with resolved heterochromia.
At 2 years of age, he developed multiple cutaneous lesions on his chest that were small, red, and granulomatous. Darier’s sign was present. Given his previous diagnosis of ocular juvenile xanthogranuloma, these lesions were initially presumed to be juvenile xanthogranulomas, although the differential diagnosis of mastocytosis was entertained (Figure 3). A skin biopsy was done that confirmed the diagnosis of mastocytosis. No ocular manifestations of mastocytosis or skin lesions of juvenile xanthogranuloma have been found on his examinations to date.
Patient at 2 years of age with cutaneous lesions on the chest, which was biopsy-proven cutaneous mastocytosis.
Mastocytosis is a heterogenous group of diseases involving proliferation and abnormal infiltration of mast cells. Mastocytosis may just be limited to the skin, although patients may develop systemic disease. Systemic mastocytosis involves one or more extracutaneous organs with or without skin infiltration.1 Cutaneous mastocytosis is typically benign and limited to the skin.2 Cutaneous mastocytosis can be subdivided into three types that have been seen in children. These include diffuse cutaneous mastocytosis, solitary mastocytoma, and urticaria pigmentosa.
Urticaria pigmentosa is the most common type of cutaneous mastocytosis. It is typically diagnosed between birth and 2 years of age. The associated skin lesions are described as reddish brown macules or papules, most commonly involving the trunk and/or extremities. Stroking of the lesions produces Darier’s sign, an urticarial local reaction with edema and erythema due to the exuberant release of histamine from the mast cells.3
Ocular mastocystosis is rare, but has been reported to involve the conjunctiva, eyelid, and cornea, choroid, and orbit.3–7 Intraocular involvement of the anterior chamber includes one case report of iritis; however, iris tumors have not been reported in any cases of ocular mastocytosis.2
The skin lesions of mastocytosis and those of juvenile xanthogranuloma may have a similar clinical appearance. Juvenile xanthogranuloma is a cutaneous disease that commonly presents in infancy or before 1 year of age.8 It is a non-Langerhans cell histiocytosis presenting with red-brown or orange papulonodular skin lesions that are most commonly seen on the head, neck, and trunk. The condition is typically benign and self-limiting.9 Patients may have ocular involvement, with a solitary iris xanthogranuloma with hyphema as the most common ocular finding.10 Diagnosis of ocular juvenile xanthogranuloma is usually clinical because iris biopsy is associated with significant risks.
It is extremely rare for juvenile xanthogranuloma and mastocytosis to occur in the same patient. Co-occurrence of biopsy-proven cutaneous juvenile xanthogranuloma and urticaria pigmentosa has been described in four case reports in the literature.11–14 After a review of the literature, no cases of ocular juvenile xanthogranuloma and cutaneous lesions of mastocytosis have been described in the same patient prior to this case.
Because skin lesions of juvenile xanthogranuloma and mastocytoma can appear clinically similar and can coexist, it is important for physicians treating patients with ocular lesions of juvenile xanthogranuloma to consider both disease processes in the differential diagnosis of the associated skin lesions and to consider subsequent histologic evaluation to confirm the diagnosis.
- Briley LD, Phillips CM. Cutaneous mastocytosis: a review focusing on the pediatric population. Clin Pediatr (Phila). 2008;47:757–761. doi:10.1177/0009922808318344 [CrossRef]
- Al-Mezaine H, Al-Obeidan S, Al-Hakeem M, Abu El-Asrar A. Refractory noninfectious anterior uveitis associated with systemic mastocytosis. J Pediatr Ophthalmol Strabismus. 2011;48:e1–e2.
- Scheck O, Horny HP, Ruck P, et al. Solitary mastocytoma of the eyelid: a case report with special reference to the immunocytology of human tissue mast cells, and a review of the literature. Virchows Arch A Pathol Anat Histopathol. 1987;412:31–36. doi:10.1007/BF00750728 [CrossRef]
- Mangone TM, Maric I, Hwang DG. Peripheral interstitial keratitis a novel manifestation of ocular mastocytosis. Cornea. 2006;3:364–367. doi:10.1097/01.ico.0000176604.95000.f3 [CrossRef]
- Mueller-Jensen K, Dehmel EM, Schumachers R. Mastocytomas of the conjunctiva in diffuse mastocytosis (urticaria pigmentosa) [article in German]. Klin Monatsbl Augenheilkd. 1967;151:170–175
- Jacoby BG, Wesley RE. Painful orbital inflammatory lesions and mastocytosis. Ann Ophthalmol. 1987;149:146–147.
- Fine HF, Akin C, Hematti P, et al. Presumed choroidal and orbital mastocytosis. Arch Ophthalmol. 2001;119:1716–1719.
- Pardanani A. Systemic mastocytosis: disease overview, pathogenesis, and treatment. Hematol Oncol Clin North Am. 2012;26:1117–1128. doi:10.1016/j.hoc.2012.08.001 [CrossRef]
- Naysan A, Kodsi SR, Kristal L. Solitary mastocytoma of the eyelid. J AAPOS. 2013;17:443–444. doi:10.1016/j.jaapos.2013.04.002 [CrossRef]
- Longmuir S, Dumitrescu A, Kwon Y, Boldt HC, Hong S. Juvenile xanthogranulomatosis with bilateral and multifocal ocular lesions of the iris, cornealscleral limbus, and choroid. J AAPOS. 2011;15:598–600. doi:10.1016/j.jaapos.2011.07.011 [CrossRef]
- Gruber R, Vassilaki I, Zelger B. Concomitant juvenile xanthogranuloma and cutaneous mastocytosis in a 3-year-old Swedish girl: case report and review of the literature. Int J Dermatol. 2011;50:611–614. doi:10.1111/j.1365-4632.2010.04553.x [CrossRef]
- De Villez RL, Limmer BL. Juvenile xanthogranuloma and urticaria pigmentosa. Arch Dermatol. 1975;111:365–366. doi:10.1001/archderm.1975.01630150085012 [CrossRef]
- Mann RE, Friedman KJ, Milgraum SS. Urticaria pigmentosa and juvenile xanthogranuloma: case report and brief review of the literature. Pediatr Dermatol. 1996;13:122–126. doi:10.1111/j.1525-1470.1996.tb01417.x [CrossRef]
- Tsutsui K, Asai Y, Kawashima Y. Urticaria pigmentosa occurring with juvenile xanthogranuloma. Br J Dermatol. 1999;140:990–991. doi:10.1046/j.1365-2133.1999.02842.x [CrossRef]