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
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.
Ophthalmoscopic appearance of
the left eye showing an elevated macular lesion with pigmentary changes.
An ultrasonographic B-scan of
the left eye (longitudinal scan through the macular area) showing an elevated
subretinal mass (arrowhead).
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.
A, Axial T1-weighted postcontrast
magnetic resonance imaging scan with fat saturation shows a thickened macula
in the left eye (arrowhead). Expansive masses are present bilaterally in the
sphenoid wings (arrows), both of which project into the middle cranial fossa
as epidural masses. The mass on the left projects into the orbit, displacing
the lateral rectus medially. B, Coronal T1-weighted postcontrast magnetic
resonance imaging scan with fat saturation shows complete replacement of the
sphenoid bone, with extension into the middle cranial fossa (arrows).
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.
Trephine bone marrow biopsy specimen
demonstrating diffuse involvement of the marrow space with mast cells (original
magnification ×100, hematoxylin-eosin). Inset shows high-power view
(original magnification ×400).
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: firstname.lastname@example.org).
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