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Langerhans cell histiocytosis is an uncommon, multisystem disease with
a clinical spectrum that includes benign unifocal disease (eosinophilic granuloma),
chronic multifocal disease (Hand-Schüller-Christian disease), and acute
or subacute fatal disseminated disease (Letterer-Siwe disease).1
It accounts for 1% to 7% of biopsied orbital tumors.2
Eosinophilic granuloma is the most common variant of Langerhans cell histiocytosis,
with approximately 20% of cases affecting the orbital area.2
When it occurs in the orbit, it is usually unilateral and localized. We are
unaware of a previously reported case of eosinophilic granuloma with bilateral
orbital involvement, and a computerized literature search using Medline disclosed
no other examples. We herein report a case of eosinophilic granuloma that
exhibited sequential bilateral orbital involvement.
In November 1988, a 5-year-old otherwise healthy boy was referred to
us for evaluation of left eyelid swelling and proptosis that had developed
over 1 month (Figure 1A). He had
been diagnosed elsewhere as having allergic eyelid edema, and he had been
treated with topical corticosteroids with no response. There was a history
of head trauma 3 months earlier that caused bilateral eyelid ecchymoses, and
spontaneous healing occurred.
A, A 5-year-old boy developed
eyelid swelling and proptosis of the left eye. B, Axial computed tomography
reveals a left orbital mass eroding the frontal bone with extension into the
temporal fossa. C, Histopathologic examination showed admixture of histiocytes
with nuclear folds, eosinophils, and multinucleated giant cells (hematoxylin-eosin,
original magnification ×250).
Ocular examination disclosed visual acuity of 20/20 OU. There was 5
mm of left axial proptosis without palpable mass. Computed tomography (CT)
showed an orbital mass with a heterogeneous internal structure in the lateral
wall of the left orbit and temporal fossa, with erosion of the frontal and
zygomatic bones (Figure 1B). Incisional
biopsy findings revealed a dark brown mass consistent with degenerated blood.
Histopathologic examination showed clotted blood that contained eosinophils,
histiocytes, and small multinucleated giant cells (Figure 1C). These findings suggested the diagnosis of either giant
cell reparative granuloma or Langerhans cell histiocytosis. The bone defect
closed spontaneously without treatment in 8 months.
In June 1990, 18 months after initial examination, the boy developed
painful, nonerythematous swelling of his right upper eyelid. The CT findings
disclosed a similar lesion in the superolateral aspect of the right orbit
with destruction of frontal bone and extension into the brain and temporal
fossa. The mass contained densities consistent with fragments of bone. The
previously affected left orbit appeared normal (Figure 2). Incisional biopsy of the right orbital mass was performed,
and dark black tissue consistent with degenerated blood was observed intraoperatively.
Histopathologic examination showed hemorrhagic tissue with small multinucleated
giant cells, large histiocytes with folded nuclei, eosinophils, and fibrosis.
The histiocytic cells showed intense positive immunoreactivity for S-100 protein,
supporting the diagnosis of eosinophilic granuloma in the right orbit. After
6 months' follow-up, the second lesion healed spontaneously without further
therapy. At 93 months' follow-up, the patient remains healthy without systemic
Axial computed tomography demonstrated
a similar mass in the superolateral aspect of the right orbit with destruction
of the frontal bone into the brain and temporal fossa. The left orbit showed
a healed lesion and bone defect.
Eosinophilic granuloma is a rare disease that is classified as a variant
of Langerhans cell histiocytosis. It is generally diagnosed in children or
young adults and shows a predilection for males.1
In the orbit, it typically manifests as a painful, tender, erythematous swelling
near the superolateral part of the orbit anteriorly. In more posteriorly located
tumors, eyelid swelling or proptosis can be the first sign. Computed tomography
is the most helpful diagnostic test and shows an irregular, serrated osteolytic
lesion with sclerotic margins. Histopathologic evaluation displays a proliferation
of large histiocytic cells with folded nuclei consistent with Langerhans cells
with interspersed eosinophils and small multinucleated giant cells. The histiocytic
cells show a positive immunoreactivity for S-100 protein, CD1 (OKT6) antigen,
and α-1 antichymotrypsin. Electron microscopy demonstrates intracytoplasmic
Birbeck granules corroborating the diagnosis of Langerhans cell histiocytosis.1 In the orbit, the differential diagnosis in children
includes dermoid cyst, lacrimal gland tumor, primary bone tumors such as osteosarcoma,
aneurysmal bone cyst, ossifying fibroma, fibrous dysplasia, and metastatic
tumors, such as neuroblastoma and Ewing sarcoma.
In the orbit, in contrast to eosinophilic granuloma, dermoid cyst is
a round to ovoid lesion with a well-defined, enhancing thin wall and nonenhancing
contents on CT evaluation. Epithelial tumors of the lacrimal gland (except
adenoid cystic carcinoma) rarely affect young children and generally cause
bone fossa formation rather than a large bone defect that reflects an epicenter
of the lesion in the bone. Primary bone tumors do not exhibit the characteristic
lytic lesion with sclerotic margin of eosinophilic granuloma on CT scan. Metastatic
orbital tumors show the irregularly shaped bony defects, usually occurring
late in the course of neuroblastoma or Ewing sarcoma, and systemic evaluation
almost invariably reveals the primary tumor.
In a recent study, Lieberman et al3
suggested using the term Langerhans cell (eosinophilic) granuloma instead
of Langerhans cell histiocytosis and classified it further into unifocal and
multifocal eosinophilic granuloma. In a survey of 238 cases of eosinophilic
granuloma from the general pathology laboratory in a cancer center, multifocal
eosinophilic granuloma was found in 85 cases (36%) at the time of diagnosis.3 Of these cases, 63% involved only bones (n = 53),
24% involved both bone and soft tissue (n = 20), and 14% involved only soft
tissue (n = 12). The involved bone included skull (52%), femur (29%), and
rib (22%). Soft tissue involvement included skin (14%), lymph node (13%),
and lung (11%). Another review of 348 cases treated in multiple pediatric
hematology/oncology departments revealed that isolated bone lesions were mostly
unifocal or bifocal in 39% of cases and multifocal in 19% of cases.4 Different from unifocal eosinophilic granuloma,
multifocal eosinophilic granuloma usually has bimodal distribution and one
peak between the ages of 0 to 10 years and the other between the ages of 20
to 30 years. Bilateral sequential orbital involvement, as seen in our case,
is highly unusual, if not unique.
The treatment of eosinophilic granuloma may include surgical curettage,
low dose irradiation, administration of cytotoxic agents, systemic corticosteroids,
or intralesional corticosteroids.5 In some
cases, initial biopsy followed solely by observation is curative, leading
to spontaneous resolution of the inflammatory mass as occurred in our case.6 The systemic prognosis of patients with unifocal
eosinophilic granuloma and multifocal eosinophilic granuloma limited to bone
is excellent.3 In a review of 348 cases
treated in pediatric hematology/oncology departments, the survival rate was
96% to 100% at 7 years in patients with eosinophilic granuloma limited to
bone.4 However, in some cases, local recurrence
of the lesion is observed between 6 and 18 months.3
In our case, there has been no recurrence or progression to disseminated disease
after 8 years. The multivariate prognostic analysis in 348 cases showed that
organ involvement, age younger than 1 year, and failure responding to therapy
wereassociated with a bad prognosis.4 In
our case, none of these factors were present.
This study was supported in part by the Paul Kayser International Award
of Merit in Retina Research, Houston, Tex (Dr J. Shields), Macula Foundation,
New York, NY (Dr C. Shields), the Noel T. and Sara L. Simmonds Endowment for
Ophthalmic Pathology, Wills Eye Hospital (Dr Eagle), and the Eye Tumor Research
Foundation, Philadelphia, Pa (Dr C. Shields).
Corresponding author: Carol L. Shields, MD, Oncology Service, Wills
Eye Hospital, 900 Walnut St, Philadelphia, PA 19107.
Demirci H, Shields CL, Shields JA, Eagle RC. Bilateral Sequential Orbital Involvement by Eosinophilic Granuloma. Arch Ophthalmol. 2002;120(7):978-979. doi: