Orbital unifocal Langerhans cell histiocytosis (eosinophilic granuloma)

Case Review
Orbital unifocal Langerhans cell histiocytosis
(eosinophilic granuloma)
Yahya Al-Muazen 1 , Mohamed El-Shawarby 2 , Saleh Al-Sowayan 2
Abstract: Langerhans cell histiocytosis (LCH) is a clinical entity characterized by abnormal proliferation of
Langerhans cells that probably results from an immunoregulatory defect which can be triggered by several different
factors. Orbital involvement by LCH most often represents unifocal disease (eosinophilic granuloma). The condition
is uncommon and descriptions of eosinophilic granuloma of the orbit generally have been limited to single case
reports or small case series. A case of orbital eosinophilic granuloma is reported, followed by a discussion
encompassing a literature review. (p66-69)
Introduction
Langerhans cell histiocytosis (LCH), previously termed
‘histiocytosis X’, is a clinical entity characterized by abnormal
proliferation of Langerhans cells, which exert a mass
effect. The disease primarily involves bones but can also
affect other organ systems. Langerhans cell histiocytosis is
actually a term that encompasses three related disease
subtypes: acute disseminated LCH (Letterer-Siwe disease),
multifocal LCH (Hand-Schuller-Christian syndrome) and
unifocal LCH (also known as eosinophilic granuloma,
which represents about 70% of cases of LCH). 1
movements. On examination, a soft, painless lump was
noted, measuring 2 × 2 cm. Ophthalmologic, neurological
and systemic examinations were within normal limits.
Haematology and biochemistry investigations were likewise,
within normal limits. Computed tomography (CT) scan of
the brain with orbital view showed right orbital tumour with
supraorbital bone erosion (Fig. 1). Magnetic resonance
imaging (MRI) of the brain showed soft tissue mass lesion
extending from the supraorbital to intraorbital cavity
compressing the eye globe (Fig. 2).
Orbital involvement by LCH most often represents unifocal
disease. The condition is uncommon, representing less than
1% of all orbital tumours and 23% of LCH, and
descriptions of eosinophilic granuloma of the orbit
generally have been limited to single case reports or small
case series. 2-4
Case Report
A 9-year-old girl presented with a left supraorbital lump of
one month duration, which was noticed by the parents after
a direct trauma. It subsequently developed into partial
eyelid drop without visual changes, nor limitations of eye
1 Department of Neurosurgery
2 Department of Pathology
King Fahad Hospital of the University
Al-Khobar
Saudi Arabia
Correspondence:
Dr. Yahya Al-Muazen
Department of Neurosurgery
King Fahad Hospital of the University
PO Box 40176
Al-Khobar 31952
Saudi Arabia
Email: ymmuazen@yahoo.com
Figure 1 - CT scan of the brain with orbital view. Bone window
shows the erosion of the supraorbital bone and compression
of the left eye globe. Figure 2 - MRI axial view of the brain
with orbital view showing soft tissue at the left orbital region
compressing the left eye globe.
Intraoperatively, there was a well circumscribed supraorbital
lesion composed of vascular soft tissue eroding
through supraorbital bone and extending into the orbital
cavity. The eye globe was completely intact with surrounding
periorbital fat and no evidence of infiltration by the
lesion, which was removed in toto.
Histologic examination revealed vascularized fibrofatty
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tissue with variable infiltration by an eosinophil rich
inflammatory cell infiltrate that also included mature
lymphocytes and aggregates of histiocytic cells with indented
nuclei and abundant cytoplasm, that showed strong
cytoplasmic and nuclear immunoreactivity for S-100
protein. There were also few scattered multinucleate giant
cells exhibiting the same nuclear and immunohistochemical
features. There was no nuclear pleomorphism and mitoses
could not be demonstrated (Figs. 3 - 7).
One year postoperatively, MRI was done and showed no
recurrence of lesion (Fig. 8).
Figure 3 - Eosinophilic granuloma: note numerous eosinophils, histiocytes and lymphocytes (HE × 200). Figure 4 - Eosinophilic
granuloma: note aggregates of histiocytes (HE × 100).
Figure 5 - Eosinophilic granuloma: note histiocytes with abundant cytoplasm and indented nuclei (consistent with Langerhans
cells). There is also a multinucleate giant cell and few eosinophils (HE × 400). Figure 6 - Eosinophilic granuloma: note positive
nuclear and cytoplasmic staining of histiocytes for S-100 protein. Immunohistochemistry × 200.
Figure 7 - Eosinophilic granuloma: note positive nuclear and cytoplasmic staining of histiocytes for S-100 protein. Immunohistochemistry
× 400. Figure 8 - Postoperative MRI axial view of the brain with orbital, after 1 year showing no evidence of
recurrence.
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ORBITAL UNIFOCAL LANGERHANS CELL HISTIOCYTOSIS • Muazen, et al
Discussion
Normal Langerhans cells begin as pleuripotential stem cells
in active bone marrow. 11,17 Under the influence of multiple
cytokines, those stem cells differentiate into two major
classes of histiocyte: antigen-processing macrophages and
antigen-presenting dendritic cells. Cytokines further induce
dendritic cells to diverge along multiple phenotypic paths,
with one leading to the Langerhans cell. The normal bone
marrow does not retain a large permanent population of
Langerhans cells 2 . Following migration to the epidermis,
oral mucosa, lungs and other sites, the cells participate in
immunosurveillance by engaging extrinsic antigens. 17
Langerhans cell-antigen complexes then travel via
lymphatics to regional lymph nodes, where the antigens are
presented to paracortical T-cells. The primary agent or
event that disrupts this orderly process and causes an
accumulation of pathologic Langerhans cells is unknown
but an immunoregulatory defect has been postulated that
can be triggered by several different factors, such as a viral
infection, a genetic defect, lymphoma or leukaemia. 21
Langerhans cell histiocytosis has a predilection for haemopoietically
active bone marrow (the residence of Langerhans
cell precursors) and skeletal lesions are present in the
majority of isolated and multisystem cases. 9,17
Orbital involvement by LCH most often represents unifocal
disease (i.e. an eosinophilic granuloma). Patients with
orbital eosinophilic granuloma tend to be males in their first
or second decade. Symptoms include swelling, upper
eyelid oedema and erythema, ptosis, rapidly progressive
proptosis, brow pain, and tenderness. 5,8,16,18 This patient, a
9-year-old female, presented with a supraorbital lump that
subsequently developed into partial eyelid drop. A destructive
bone lesion is commonly seen in the superior or
superotemporal orbit as was present in this patient. 4 A soft
tissue mass with irregular but clearly demarcated bone
destruction is thought to be a characteristic CT finding of
LCH involving the orbit. 20
The clinical differential diagnosis of LCH includes
metastatic tumours (e.g. Ewing’s sarcoma, neuroblastoma
and Wilms’ tumour), lacrimal gland neoplasms (e.g. mixed
tumour, adenoid cystic carcinoma and mucoepidermoid
carcinoma), primary bone tumours (e.g. giant cell reparative
granuloma, aneurysmal bone cyst and brown tumour of
hyperparathyroidism), lymphoma, haemangioma, cholesteatoma,
granulocytic sarcoma, inflammatory pseudotumour
and dacryoadenitis. 1,6,7,12 Considering the patient’s
age, the presence of bone destruction and the location of the
lesion, the initial clinical impression in our case was a
rhabdomyosarcoma.
Tissue biopsy is necessary for the diagnosis of LCH and to
rule out more aggressive lesions in the differential
diagnosis. Histologically, LCH lesions show sheets of large
histiocytes with grooved nuclei that exhibit immunoreactivity
for CD1a and S-100 protein (Langerhans cells),
interspersed with multinucleate giant cells, eosinophils,
lymphocytes and plasma cells. Electron microscopy
reveals characteristic intracytoplasmic inclusions known as
Birbeck granules in the Langerhans cells. 3,10 Although
electron microscopy was not performed in our case,
characteristic histologic findings and S-100 protein positivity,
supported by clinical features and the presence of
bone erosion on CT were considered adequate for the
diagnosis of LCH. In an appropriate clinicoradiologic
setting, a typical cytopathology can alone be used for
effective diagnosis. 13 Absence of multifocal and multiple
system involvement ruled out Hand-Schuller-Christian
syndrome and Lettere-Siwe disease, respectively.
The outcome for LCH patients without multisystem
involvement or organ dysfunction is usually very good. 5
There are no definitive recommendations on how to best
manage a case of orbital eosinophilic granuloma. No
modality has been proven to be more effective than the
other but lesions generally resolve after minimal intervention,
with a good prognosis. 1 Complete surgical removal of the
lesion is not even necessary. There are many reports of
complete resolution of an orbital eosinophilic granuloma
after biopsy and subtotal curettage alone. 14 Even lesions
with significant bone destruction and soft tissue involvement
respond to this minimal intervention. 5 In these cases,
it is unclear if the biopsy and curettage had a therapeutic
impact or if the lesions would have spontaneously resolved
without any intervention at all. The response to observation
alone is not clear however, since almost all patients are
diagnosed through tissue biopsy. 5 In the present case, an
MRI performed one year after surgical excision of the
lesion showed no evidence of recurrence.
Successful interventions have also been reported with the
use of low-dose radiation and intralesional corticosteroids.
Chemotherapy is considered for recurrent disease. 19
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