 |
|
Sclerosing Inflammatory Pseudotumor of the Eye
Harvey S. Uy, MD;
Quan Dong Nguyen, MD, MSc;
Jean Arbour, MD;
Michel Gravel, MD;
Donald J. D'Amico, MD;
Frederick A. Jakobiec, MD;
C. Stephen Foster, MD
Arch Ophthalmol. 2001;119:603-607.
ABSTRACT
We report the clinical course and pathologic findings in a case of intraocular
sclerosing inflammatory pseudotumor in a 21-year-old man. The patient initially
had a unilateral right interstitial keratitis, scleritis, uveitis, ciliary
body mass, and retinal detachment. Scleral and vitreous biopsy specimens revealed
an inflammatory process. The eye was eventually enucleated despite therapy
with high doses of prednisone and ciprofloxacin hydrochloride. Histologic
examination of the globe showed nongranulomatous, acute (neutrophils) and
chronic (lymphocytes and histiocytes) inflammation with proliferation of fibrous
tissue within the vitreous cavity, uvea, sclera, and contiguous orbital fibroadipose
tissue. The contralateral eye later developed a similar mass that resolved
following aggressive and prolonged immunosuppressive therapy with retention
of 20/16 visual acuity.
INTRODUCTION
Inflammatory pseudotumors compose a group of rare, poorly understood,
idiopathic, inflammatory mass lesions. They may be classified as sclerosing
or nonsclerosing according to the presence or absence of a dense fibrotic
stroma. The nonsclerosing type is more common and has been reported to occur
in almost every part of the body, including orbital tissues and the uveal
tract.1-3 Sclerosing
inflammatory pseudotumors have been described in the orbit4-6
and lacrimal glands.7 We report herein a case
of bilateral intraocular sclerosing inflammatory pseudotumor with eventual
extraocular extension, presenting as a ciliochoroidal and vitreous mass with
scleritis, keratitis, uveitis, and retinal detachment in one eye. To the best
of our knowledge, this is the first such case reported in the literature with
successful treatment and preservation of vision in one eye.
REPORT OF A CASE
A 21-year-old healthy white man noted inferior redness of his right
eye associated with mild eye pain that began in May 1997. This was diagnosed
as conjunctivitis and treated with topical steroids for a month without resolution.
The patient noticed diminished vision, floaters, and worsening of the eye
pain in July 1997. Posterior segment examination revealed 3+ vitreous haze
and peripheral snowballs. A diagnostic vitrectomy and conjunctival biopsy
were performed. The latter revealed macrophages, lymphocytes, and neutrophils;
no microorganisms or malignant cells were seen. The patient was treated with
subconjunctival triamcinolone acetonide injections and oral prednisone for
1 month. Despite treatment, the patient's eye pain continued to worsen and
he required 24-hour narcotic analgesia. He was subsequently referred to the
Ocular Immunology and Oncology Services of the Massachusetts Eye and Ear Infirmary,
Boston, in August.
When we saw him, the patient's visual acuities were counting fingers
OD and 20/20 OS. The pupillary responses were intact. Extraocular muscle movements
were full. Intraocular pressures were 10 mm Hg OD and 12 mm Hg OS. External
examination of the right eye revealed a swollen, tender, erythematous sclera
with overlying episcleral and conjunctival injection located in the inferior
half of the globe extending from the perilimbal area to the fornix (Figure 1). An arcuate zone of interstitial
keratitis was observed that involved the peripheral cornea manifesting as
epithelial bullae and stromal haziness. The anterior chamber and vitreous
cavity contained 3+ inflammatory cells and 2+ flare. Fundus examination disclosed
a large, white-yellow mass in the ciliary body extending from the 3- to 9-o'clock
position with posterior extension but without macular involvement (Figure 2 and Figure 3). A few scattered hemorrhages and a shallow serous retinal
detachment were seen on the surface of this mass. The optic disc was hyperemic
but had distinct borders. The left eye was completely normal at the time of
initial presentation. B-scan ultrasonography revealed a low to medium reflectivity
with irregular internal structure (Figure
4). Magnetic resonance imaging demonstrated no extraocular extension.
|
|
|
|
Figure 1. Clinical appearance of the right
interstitial keratitis and inferior scleritis associated with intraocular
sclerosing inflammatory pseudotumor.
|
|
|
|
|
|
|
Figure 2. Fundus photograph of the inferiorly
located right ciliochoroidal mass visible through an intense vitreous inflammatory
reaction.
|
|
|
|
|
|
|
Figure 3. Fundus photograph of the enlargement
of the inflammatory mass with extension to the posterior pole causing overlying
hemorrhages and serous retinal detachment.
|
|
|
|
|
|
|
Figure 4. Preoperative B-scan ultrasonogram
showing the anteriorly located right intraocular mass.
|
|
|
A review of symptoms was unremarkable except for a history of an ordinary
childhood case of chickenpox. The differential diagnoses of sclerouveitis
with associated ciliochoroidal mass includes granulomatous inflammatory conditions
(sarcoidosis, Wegener granulomatosis, and foreign body reaction), infectious
causes (bacteria, herpesviruses, and fungi), and neoplastic masquerade syndrome
(leukemia, lymphoma, melanoma, metastatic carcinoma). Findings from an extensive
diagnostic evaluation were negative except for an elevated varicella zoster
virus (VZV) IgG titer that was elevated to 156 enzyme immunoassay units (reference
range, 0-15 enzyme immunoassay units).
Specimens obtained from vitreous and scleral biopsies performed on September
1, 1997, revealed acute (neutrophils) and chronic (lymphocytes and histiocytes)
nongranulomatous inflammation. Microbial cultures were negative for bacteria,
fungi, and acanthamoeba. Neither malignant cells nor microorganisms were observed
on pathologic examination. Immunoperoxidase stains performed on the scleral
tissue and polymerase chain reaction analysis of vitreous samples failed to
detect gene sequences for acid-fast bacilli, herpesvirus 1 and 2, cytomegalovirus,
VZV, Borrelia burgdorferi, and
Toxoplasma.
The working diagnosis at this time was idiopathic sclerouveitis. The
patient was already taking famcyclovir, 500 mg orally 3 times a day, and oral
prednisone, 60 mg daily, and was reluctant to alter these medications. We
prescribed intravenous cyclophosphamide infusions at a dose of 1 g every 3
to 4 weeks and hourly 1% prednisolone acetate eyedrops, in the belief that
the problem was primarily immunologic/inflammatory in nature. Postoperatively,
the visual acuity improved to 20/400 OD with marked reduction of pain and
eye redness.
One month later, however, the patient returned with an increase in the
size of the ciliochoroidal mass, progression of retinal detachment up to the
macula, and visual acuity reduced to hand motions. Findings from B-scan ultrasonography
were suggestive of extrascleral extension of the process. On October 8, the
patient underwent repeated vitrectomy, 3 retinal biopsies, 1 large debulking
choroidal biopsy, and successful retinal detachment repair using silicone
oil. The biopsy specimens revealed an intact retina and nongranulomatous inflammation
with abundant plasma cells and neutrophils associated with increased collagen
and vascularity of the choroid. Malignant cells were not found in the vitreous.
Immunohistochemical staining of the ciliary body disclosed a large number
of cells bearing IgA, IgG, IgM, IgE, IgD, and C4. The retina was uninvolved
histologically. Malignant cells were not found in the vitreous. Flow cytometry
of vitreous cells disclosed CD4+ and CD8+ T lymphocytes, as well as polyclonal 
and  immunoglobulin light chain–positive B lymphocytes. The
patient's immunosuppressive regimen was continued postoperatively, with the
addition of diflunisal, 1000 mg by mouth daily. The patient's eye pain decreased
and his visual acuity improved to 20/200 OD on November 4, 1997.
Six weeks postoperatively, the cultures from the vitreous samples yielded
growth of coral pink negative rods interpreted as Methylobacterium
extorquens, sensitive to ciprofloxacin and amikacin. The subretinal
mass had continued to enlarge, prompting cessation of intravenous cyclophosphamide
treatment and reduction in the prednisone dosage since the concern now was
that of infection. Treatment with intravenous ciprofloxacin hydrochloride
was begun. Despite these measures, the patient returned 2 weeks later with
further enlargement of the mass that now involved the entire macula. Visual
acuity was reduced to light perception and the patient's eye pain had recurred.
Computed tomography revealed a soft tissue density along the inferior and
lateral aspect of the right globe similar to that seen on magnetic resonance
imaging. The left globe was normal. A transscleral biopsy was performed, the
results of which revealed acute and chronic inflammation only. Because of
the lack of response to antimicrobial treatment and the opinion of the infectious
disease consultant that the finding of M extorquens
in the culture yield was most likely a contaminant, the concern about an infectious
origin was abandoned. The prednisone regimen was increased to 50 mg daily.
Two weeks later, the patient returned with a white mass in the superotemporal
ciliary body of the opposite eye at the 2-o'clock position with adjacent scleritis.
Repeated systemic evaluation was not contributive. Because of the poor prognosis
for recovery of the right eye and the probability for progression of the disease
in the left eye, diagnostic enucleation of the right eye was offered to the
patient; this was accomplished on January 27, 1998. Histopathologic examination
findings of the enucleated globe revealed an inferior vitreous mass, obliteration
of the uvea, and scleral thickening; the process extended through the sclera
to involve the inferior orbital fat (Figure
5 and Figure 6). Within
the mass were nonspecific acute (neutrophilic, Figure 7) and chronic inflammation characterized by mononuclear,
lymphocytic, and plasmacytic infiltration, together with proliferation of
collagenous tissue and absence of granulomatous inflammation (Figure 8). Specific stains for microorganisms (acid-fast, methenamine
silver, Brown-Hopps) and electron microscopic studies failed to disclose any
organisms. Several ocular and general pathologists reviewed the pathology
slides, and the consensus was that of a sclerosing inflammatory pseudotumor
of the eye with scleritis probably of autoimmune origin.
|
|
|
|
Figure 5. Gross view of enucleated right
globe showing an inferior vitreous mass and fibrous tissue adherent to the
inferior wall of the globe. The inferior sclera was replaced by a mass of
inflamed sclerotic tissue, which had destroyed the inferior choroid.
|
|
|
|
|
|
|
Figure 6. Fibrotic inflamed tissue replacing
inferior orbital fat (hematoxylin-eosin, original magnification x20).
|
|
|
|
|
|
|
Figure 7. A focus of acute inflammation
in the vitreous cavity (hematoxylin-eosin, original magnification x200)
|
|
|
|
|
|
|
Figure 8. Sclerosing tissue in the plane
of the choroid exhibits dense bands of collagenous tissue, abundant plasma
cells, and scattered surviving choroidal melanocytes (hematoxylin-eosin, original
magnification x 220).
|
|
|
The patient was started on therapy with intravenous cyclophosphamide
and high-dose oral prednisone once more in an effort to salvage his remaining
eye. Over the next 4 weeks, the mass in the left eye remained the same size
and the scleritis persisted. However, on the eighth week of immunosuppression,
there was reduction in mass size and by the 14th week, the mass had disappeared
and the scleritis resolved, leaving an anterior staphyloma. The prednisone
was slowly tapered over a period of 8 weeks without relapse. Pulse intravenous
cyclophosphamide therapy was maintained together with oral diflunisal, 1000
mg daily. The final visual acuity OS was 20/16, in October 1999, 10 months
after cessation of intravenous cyclophosphamide and prednisone therapy.
COMMENT
Intraocular sclerosing inflammatory pseudotumor is a rare condition
that can present as a ciliochoroidal mass, sclerouveitis, and interstitial
keratitis. This case appears to be clinically and histologically different
from the hypercellular and nonfibrotic reactive lymphoid hyperplasias described
by Ryan, Jakobiec, and others.8-10
Intraocular inflammatory pseudotumors appear to arise from uveal tissues and
are associated with uveitis.2, 11-12
This case is clinically distinguished from previous reports of intraocular
pseudotumors by the presence of scleritis with orbital extension and interstitial
keratitis, and it is histologically distinguished by the presence of dense
fibrotic stroma in the presence of an intense plasmacytic and neutrophilic
infiltrate. It is believed by some authors that the sclerosing variant may
represent a more aggressive or more recalcitrant form of the disease.5 However, other authors have found no differences in
duration of illness and response to corticosteroids between the sclerosing
and nonsclerosing variants.1, 7
The origin of intraocular pseudotumor is unknown but is widely believed
to be either infectious or autoimmune. The autoimmune theory is supported
by the observation of concomitant autoimmune disorders such as rheumatoid
arthritis, systemic lupus erythematosus, diabetes mellitus, and associated
drug therapy1, 11 and by the response
to corticosteroids and, in this case, to cyclophosphamide. The proposed pathogenesis
of sclerosing pseudotumor is exaggerated proliferation of fibroblasts and
deposition of extracellular matrix caused by the aberrant immune-mediated
production of fibrogenic cytokines (platelet-derived growth factor, transforming
growth factor  ).1, 7
Previous reports have described ciliary body masses, uveitis, iris infiltration,
narrow-angle glaucoma, and retinal detachment as manifestations of inflammatory
pseudotumor. This case adds scleritis, interstitial keratitis, and extraocular
orbital extension to that list. Our approach to management involved a thorough
review of systems and an initially noninvasive diagnostic search for systemic
diseases associated with inflammatory intraocular masses. Strong support for
the diagnosis of inflammatory pseudotumor is obtained by histopathologic means,
which must rule out neoplasm and infection. We recommend immediate institution
of immunosuppressive therapy once the disease is recognized. As this case
illustrates, treatment may require a combination of high-dose corticosteroids
and cyclophosphamide to effect resolution, although response to treatment
may be delayed by several weeks. It is difficult to assess the prognosis of
intraocular pseudotumors given the small number of reported cases in the literature.
In our studied case, one eye was enucleated for diagnostic reasons once all
vision was lost, while the eventually affected contralateral eye retains 20/16
visual acuity.
AUTHOR INFORMATION
Accepted for publication August 22, 2000.
Corresponding author: C. Stephen Foster, MD, Department of Ophthalmology,
Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles St,
Boston, MA 02114 (e-mail: fosters{at}helix.mgh.harvard.edu).
From the Ocular Immunology and Uveitis Service, Massachusetts Eye and
Ear Infirmary, Harvard Medical School (Drs Uy, Nguyen, Baltatzis, and Foster),
Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School
(Drs Arbour and D'Amico), Boston; Hospital Sacre-Coeur, Montreal, Quebec (Dr
Gravel); Ocular Pathology Service, Massachusetts Eye and Ear Infirmary, (Dr
Jakobiec), and Schepens Retina Foundation, Schepens Eye Research Institute
(Dr Nguyen), Harvard Medical School.
REFERENCES
| |
1. Mombaerts I, Goldschmeding R, Schlingemann RO, Koornneef L. What is orbital pseudotumor? Surv Ophthalmol. 1996;41:66-78.
FULL TEXT
|
ISI
| PUBMED
2. Ryan SJ, Frank RN, Green WR. Bilateral inflammatory pseudotumors of the ciliary body. Am J Ophthalmol. 1971;72:586-591.
ISI
| PUBMED
3. Char DH, Miller T. Orbital pseudotumor: fine-needle aspiration biopsy and response to
therapy. Ophthalmology. 1993;100:1702-1710.
ISI
| PUBMED
4. Cervellini P, Volpin L, Curri D. Sclerosing orbital pseudotumor. Ophthalmologica. 1986;193:1-2, 39-44.
ISI
| PUBMED
5. Weissler MC, Miller E, Fortune MA. Sclerosing orbital pseudotumor: a unique clinicopathologic entity. Ann Otol Rhinol Laryngol. 1989;98:496-501.
ISI
| PUBMED
6. Levine MR, Kaye L, Mair S, Bates J. Multifocal fibrosclerosis: report of a case of bilateral sclerosing
pseudotumor and retroperitoneal fibrosis. Arch Ophthalmol. 1993;111:841-843.
ABSTRACT
7. Mombaerts I, Schlingemann RO, Goldschmeding R, et al. The surgical management of lacrimal gland pseudotumors. Ophthalmology. 1996;103:1619-1627.
ISI
| PUBMED
8. Ryan SJ, Zimmerman LE, King FM. Reactive lymphoid hyperplasia: an unusual form of intraocular pseudotumor. Trans Am Acad Ophthalmol Otolaryngol. 1972;76:652-671.
PUBMED
9. Jakobiec F, Sacks E, Kronish J, et al. Multifocal static creamy choroidal infiltrates: an early sign of lymphoid
neoplasia. Ophthalmology. 1987;94:397-406.
ISI
| PUBMED
10. Ciulla TA, Bains RA, Jakobiec FA, et al. Uveal lymphoid neoplasia: a clinical-pathologic correlation and review
of the early form. Surv Ophthalmol. 1997;41:467-476.
FULL TEXT
|
ISI
| PUBMED
11. Yeomans SM, Knox DL, Green WR, Murgatroyd GW. Ocular inflammatory pseudotumor associated with propranolol therapy. Ophthalmology. 1983;90:1422-1425.
ISI
| PUBMED
12. Gass JDM. Retinal detachment and narrow-angle glaucoma secondary to inflammatory
pseudotumor of the uveal tract. Am J Ophthalmol. 1967;64:Suppl:612-621.
SECTION EDITOR: W. RICHARD GREEN, MD
|
