Presumed Choroidal and Orbital Mastocytosis

Mastocytosis is a condition characterized by the presence of excessive numbers of tissue mast cells in distinctive distributions, which produce symptoms related to mast cell mediator release and the disruption of normal tissue function. To the best of our knowledge, mastocytosis with ocular and orbital involvement has not been previously documented. We describe a 42-year-old white man with biopsy-proven mastocytosis and multiple disseminated lesions who developed a reduction in visual acuity to counting fingers OS, an elevated choroidal mass in the macula, and bilateral orbital tumors.

A 42-year-old non-Hispanic white man was diagnosed as having mastocytosis in 1996 after a bone marrow biopsy. He had a 1-year history of recurrent episodes of flushing, chest tightness, headache, and fever and on examination was noted to have lymphadenopathy and hepatosplenomegaly. No dermatologic lesions were present.

He subsequently developed an extramedullary mass lesion in thoracic vertebrae 2 through 8, which was compressing the spinal cord and was treated with excision and radiation therapy. A pathologic examination confirmed the lesion to consist of confluent mast cells. Six months later the patient developed urinary retention, and magnetic resonance imaging demonstrated a new mass lesion at sacral vertebrae 1 and 2. The second lesion was nonresectable and responded minimally to radiation therapy.

In May 1999, the patient went to an outside ophthalmologist complaining of a 4-week history of vision loss in the left eye. According to the patient's medical records, the examination results were remarkable for visual acuities of 20/20 OD, 20/40 OS, and a small serous retinal detachment involving the macula of the left eye. His visual acuity decreased further from 20/60 OS in August 1999 to 20/400 OS in January 2000, and the serous detachment had enlarged with extension beyond the vascular arcades.

The patient first came to the National Eye Institute (Bethesda, Md) in April 2000. At that time, his visual acuities were 20/16 OD and counting fingers OS, with intraocular pressure readings of 15 mm Hg OD and 13 mm Hg OS. There was no proptosis according to Hertel exophthalmometry. Extraocular movements were normal, and slitlamp examination results were normal in both eyes. A dilated retinal examination showed an approximately 200-µm pigment defect superior to the right fovea, an elevated macular lesion with pigmentary changes, and an inferior exudative retinal detachment in the left eye (Figure 1). The visual field was normal in the right eye but showed a dense central scotoma in the left (Humphrey Visual Field Analyzer; Zeiss Humphrey Systems, Dublin, Calif). An ultrasonographic B-scan showed an elevated subretinal mass in the macular area (Figure 2) and a shallow serous retinal detachment inferior to this lesion. The mass was well outlined, was located in the choroid or subretinal space, and had a diameter of 9.6 mm and an elevation of 3.5 mm. A standardized ultrasonographic A-scan indicated that the lesion had moderately low acoustic reflectivity, which suggested that the mass had a homogeneous internal structure and was not calcified.

An orbital T1-weighted postcontrast magnetic resonance imaging scan with fat saturation showed a thickened, enhanced posterior pole in the left eye corresponding to the sonographic lesion. An extraconal mass was centered on the greater wing of the sphenoid bone and projected into the orbit, medially displacing the lateral rectus. It also projected into the middle cranial fossa as an epidural mass. The marrow of the sphenoid bone was replaced throughout (Figure 3). A computed tomographic scan of the chest, abdomen, and pelvis revealed multiple pleural-based densities, a 1-cm low-density lesion in the right lobe of the liver, splenomegaly, and retroperitoneal adenopathy. A skeletal survey using plain film showed diffuse mottling of bony structures including the ribs, pelvis, and spine. Results of an upper gastrointestinal endoscopy and colonoscopy were negative.

Laboratory studies were notable for mild pancytopenia, but no circulating mast cells were seen. A trephine biopsy at the iliac crest revealed diffuse involvement of the marrow with sheets of fusiform mast cells (Figure 4). Results of immunohistochemical staining for the mast cell markers tryptase and surface CD117 (kit) were positive. Findings from immunohistochemical staining for other hematologic neoplasms were negative. Results of a sternal marrow aspirate were abnormal, with 16% intact mast cells. Immunohistochemical staining of the resected paraspinal lesions was similarly consistent with mast cell tumor. Plasma tryptase concentrations greater than 20 ng/mL are associated with mastocytosis; the level in this patient was 293 ng/mL, suggesting an extremely high mast cell burden. The erythrocyte sedimentation rate was 35 mm/h. Results of serologies for human immunodeficiency virus, syphilis, and cytomegalovirus were negative.

The patient was treated with histamine₁ (H₁) and histamine₂ (H₂) blockers, aspirin, and oral corticosteroids. He underwent a series of radiation treatments that resulted in resolution of the choroidal lesion and marked reduction in the bulk of the orbital lesions.

We describe a patient with a choroidal lesion, neurosensory retinal detachment, and orbital masses emanating from the sphenoid bone. The differential diagnoses for the choroidal lesion would include a metastatic lesion, choroidal osteoma, amelanotic melanoma, hemangioma, neurilemoma, leiomyoma, lymphoma, and retinal pigment epithelium hypertrophy or hyperplasia. The history of systemic mastocytosis with biopsy-proven mastocytomas from multiple sites and disseminated lesions involving bone and the reticuloendothelial system provided strong evidence that the intraocular and orbital masses were mastocytomas. Although fine-needle aspiration of the choroidal lesion or open biopsy of the orbital lesions might have been of additional value in confirming the diagnosis,¹ the patient instead opted for radiation therapy in light of the well-defined disseminated process and the increased risk of complications associated with submacular biopsy. A thorough systemic evaluation, including a computed tomographic scan and gastrointestinal endoscopy showed no evidence of a concurrent primary carcinoma or lymphoma.

Mastocytosis is generally an indolent disease² characterized by the presence of an excessive number of tissue mast cells. The current classification system divides the disease into 4 categories: category 1A, indolent cutaneous mastocytosis, is the most common type. Category 1B, indolent systemic mastocytosis, is defined by mast cell infiltration of at least 1 organ system other than the skin. Category 2 refers to mastocytosis associated with a hematologic disorder, namely, myelodysplastic and myeloproliferative disorders. Aggressive mastocytosis, category 3, is associated with lymphadenopathy, hepatosplenomegaly, and marked eosinophilia. Finally, category 4, mast cell leukemia, is marked by atypical mast cells in the marrow and peripheral blood.³ The course of disease in our patient may be best described as aggressive mastocytosis.

The pathogenesis of mastocytosis is believed to be related to kit, the mast cell receptor for stem cell factor. Dysregulated kit or an excess of its ligand could conceivably lead to abnormal mast cell proliferation and the episodic release of preformed mediators, accounting for the signs and symptoms of mastocytosis.⁴ Demonstration that most adult-onset mastocytosis is associated with activating c-kit mutations is consistent with this hypothesis.^5,6 However, an initial screen of the resected mastocytoma tissue in this patient failed to demonstrate the presence of an activating c-kit mutation.

Therapy for mastocytosis is focused on blocking the effects of mast cell mediators. H₁ and H₂ antagonists and cromolyn sodium are effective. Topical and systemic corticosteroids may be efficacious in selected advanced cases. Aspirin may be used to ameliorate the adverse effects of prostaglandin release, although extreme caution must be exercised given the risk of precipitating secretory granule release. Triggers such as insect bites and alcohol should be avoided; portable injectable epinephrine is a prudent safeguard to treat anaphylaxis.⁷ Currently there are no curative therapies for disseminated mastocytosis. Aggressive mastocytomas may be treated with excision and/or radiation. Therapies under investigation at the National Institutes of Health (Bethesda, Md) include agents that target the kit pathway as well as bone marrow transplantation.

The ophthalmic literature includes only 1 report of a mastocytoma, in which a 1-cm firm yellow nodule on the lower right lid that had been present since birth was excised from a 4-month-old boy. A histopathologic diagnosis revealed this nodule to be a mastocytoma, and there was no reported recurrence within 8 months of follow-up.⁸

Our case suggests that mastocytosis may involve the choroid and orbit. The patient had a particularly aggressive form of mastocytosis that diffusely involved both the bone marrow and reticuloendothelial system and formed solid extramedullary collections of mast cells. This may explain the involvement of the choroid, which normally contains resident mast cells and has characteristics similar to lymphoid tissue.⁹

Corresponding author: Michael R. Robinson, MD, National Eye Institute, National Institutes of Health, Bldg 10/Room 10N112, 10 Center Dr, Bethesda, MD 20892-1863 (e-mail: mrobin@box-m.nih.gov).