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ISSN 2278-1900
SJHS
A Taif University Peer-reviewed Journal Devoted for the Advancement of Basic and Applied Health Sciences
Volume 6 / Issue 2 / May-August 2017
Online full text at www.saudijhealthsci.org
Saudi Journal for Health Sciences • Volume 6 • Issue 2 • May-August 2017 • Pages 71-???
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© 2017 Saudi Journal for Health Sciences | Published by Wolters Kluwer - Medknow 119
INTRODUCTION
Langerhans cell histiocytosis (LCH), formerly known as
histiocytosis X, is a rare group of idiopathic disease that
has always caused diagnostic dilemma.[1] The disease has
a spectrum of a milder form on one end, eosinophilic
granuloma and an aggressive form on the other, Letterer–
Siwe disease with an intermediate form in between, Hand–
Schuller–Christian disease, so the patients could present
with all kinds of clinical presentation.[2] Even the etiology is
debatable: some argue that it is an inflammatory disorder
while others advocate neoplastic origin while yet others
describe immune disorder as the basis of the disease.
[2‑4]Histopathologyischaracterizedbythepresenceof
multinucleated giant cells (MNGCs) with a lot of osteoclastic
activity.[5] Otolaryngologists and family physicians usually see
these patients presenting to them with ear‑related problems
often as indolent as mimicking otitis media and sometimes as
severe as mastoiditis, ear polyps, and granulations.[2,6,7] Hence,
the diagnosis always got delayed as they do not improve or
presented with recurrent symptoms.
The purpose of this case report is to demonstrate how this
disease mimics common acute and chronic ear, nose, and
throat (ENT) diseases so that we can suspect this disease if
such diseases are refractory to usual treatment. This will avoid
unnecessary delay in diagnosis, and appropriate measures
for referral and treatment could be taken timely to improve
the quality of life of these patients.
CASE REPORT
A 22‑month‑old Saudi boy presented to emergency
department of our hospital with a chronic discharging ulcer
of the left mastoid [Figure 1]. He was diagnosed elsewhere
as a case of mastoiditis where he was treated with incision/
drainage and systemic antibiotics. Seven months before his
presentation, there was a history of left mastoid swelling
and adjoining area of temporal bone; it was not associated
with otorrhea. Clinically, the child was afebrile, there was
a 15 mm × 15 mm ulcer in the left postauricular area with
granulation tissue, and tympanic membrane was slightly dull.
A provisional diagnosis of complicated mastoiditis was
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DOI:
10.4103/sjhs.sjhs_6_17
Langerhans cell histiocytosis mimicking a
complicated mastoiditis: A review and case
report
Mohiyuddin A. Q. Ali, Sami A. Al‑Kindy1
Department of ENT, Ain Al-Khaleej Hospital, Al-Ain, UAE, 1Department of Surgery, Taif University, Saudi Arabia
Address for correspondence:
Dr. Mohiyuddin A. Q. Ali,
Department of ENT, Ain Al-Khaleej
Hospital, P. O. Box 88206, Al-Ain, UAE.
E‑mail: drmohiyuddinali@yahoo.com
Langerhans cell histiocytosis (LCH) is a rare entity of an unknown etiology, usually reported
in children. It commonly involves cranial bones mimicking an otological disease. We report
a case of a 22-month-old Saudi boy who was referred to our Otolaryngology Department,
in the North West Armed Forces Hospital, Tabuk, Saudi Arabia, as a case of complicated
mastoiditis with a stula that was resistant to conventional treatment. The patient underwent
surgical exploration, and a biopsy conrmed the diagnosis of LCH X. The case was treated
accordingly. LCH of temporal bone can be misdiagnosed and mismanaged. This, however,
can be minimized by a high index of suspicion, appropriate radiological and histopathological
examination.
Key words: Ear-nose-throat manifestation, histiocytosis X, Langerhans cell histiocytosis,
mastoid stula
ABSTRACT
Case Report
How to cite this article: Ali MA, Al-Kindy SA. Langerhans cell histiocytosis
mimicking a complicated mastoiditis: A review and case report. Saudi J Health
Sci 2017;6:119-22.
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Ali and Al‑Kindy: Langerhans cell histiocytosis mimicking complicated mastoiditis
120 Saudi Journal for Health Sciences - Volume 6, Issue 2, May-August 2017
made. The patient was admitted for further investigations.
Computed tomography (CT) examination showed a lytic lesion
of the temporal bone [Figure 2]. Exploration of the mastoid
was done where the cavity was full of friable and gelatinous
tissue; it was highly suspicious of Langerhans histiocytosis,
which was later confirmed by H and E histopathology and
immunohistochemistry studies (CD1a and S100).
The patient was later referred to pediatric oncology where
he was classified as multistage LCH Hand–Schuller–Christian
variant as he was also found to have pulmonary infiltrates
with effusions and cervical lymphadenopathy, following
screening by CT scan. However, bone marrow aspiration
biopsy was free from disease. Over the next 50 weeks,
he underwent 17 cycles of chemotherapy consisting of
vinblastine 3 mg, with prednisolone (6.6 mg–7 mg TID for
5 days) and 6‑mercaptopurine (25 mg PO OD 21 days). The
child is currently in clinical remission [Figure 3].
DISCUSSION
LCH, a rare group of idiopathic disorder (incidence of
0.5–5.0/million/year in USA), is a systemic disease that may
manifest and present as a primary otorhinolaryngology
disease, causing a diagnostic and management dilemma.
It was formerly known as “histiocytosis X” because the
cellular basis of these disorders was unknown. However,
with the advances, cells with morphology of Langerhans
cells are present in the stroma along with other cells such as
eosinophils, macrophages, and T‑cells.[1] Hence, the Histiocyte
Society in 1985 recommended using the term “Langerhan
cell histiocytosis” instead.
The Histiocyte Society classified histiocytic disorders into
three groups: dendritic cell histiocytosis, macrophage‑related
disorders, and malignant histiocytosis.[8] LCH is included
in the first group and denotes a spectrum of diseases that
includes the indolent eosinophilic granuloma on one end to
the fulminant and disseminated Letterer–Siwe disease on
the other end. In the middle of this clinical spectrum lies
Hand–Schuller–Christian disease.[2] This latter disease may
present itself as proptosis and lytic lesions of the skull bones
and may sometimes mimic ENT diseases such as otitis media
and mastoiditis.
The exact pathophysiology of this disease is unknown, but
there are all the possible theories. There is a group that
proposes inflammatory pathophysiology on the basis of the
fact that there are incidences of spontaneous remissions and
elaboration of cytokines by dendritic cells and T‑cells.[3,9,10]
Another group advocates the neoplastic origin as there
is infiltration of organs by aberrant monoclonal cells and
favorable response to treatment with anticancer drugs.[2‑4,11‑14]
Some suggest immune dysfunction as the possible
pathogenesis of LCH.[4] Histopathology of LCH shows,
among other cells, MNGCs. These show osteoclastic activity
and cause bone necrosis. Researchers have shown that
certain cytokines such as macrophage colony stimulating
factor and receptor activator of nuclear factor‑κB ligand
expressed by LCH cells cause fusion of normal dendritic
cells into MNGCs.[5,9] In some families, multiple incidences
of LCH have been documented raising the possibility of it
being a genetic disorder.[12] It is commonly seen in males in
the age group of 0–15 years; however, any age group can
Figure 1: The lesion as it appeared before our intervention
Figure 2: A coronal cut through the skull computed tomography
scan showing the typical lytic lesions of the vault bones
Figure 3: Posttreatment during follow-up showing healed lesion
Ali and Al‑Kindy: Langerhans cell histiocytosis mimicking complicated mastoiditis
Saudi Journal for Health Sciences - Volume 6, Issue 2, May-August 2017 121
be involved.[9] Almost 50%–70% of the children with LCH
present with multiple organ involvement.[8] In contrast,
most of the studies have shown that almost 70% of adults
present with single organ involvement, although some
recent series reported otherwise.[8] ENT manifestation
usually occurs in the Hand–Schuller–Christian disease.
Moreover, nodulo‑ulcerative cutaneous lesions can occur
in the mandible, scalp, and retroauricular areas. Multifocal
bony lytic lesions can cause recurrent otitis media and aural
polyps.[6] Occasionally, mastoiditis and destructive tumor in
mastoids have been reported.[2,7,15‑17,20] Hearing impairment
withorwithoutdizzinessbydestroyingthebonesofmiddle
ear and temporal bone has been reported, sometimes
even bilaterally.[9,18,19] Similar lesions in the orbit can cause
exophthalmos. Secondary acquired cholesteatoma has been
reported to develop from previously treated LCH as a result
of posterior canal wall defect.[10] This may cause a misleading
diagnosis of recurrence of LCH, but in fact, it is not and may
require mastoid exploration as any other cholesteatomatous
ear disease. It has been reported in maxillary sinus
also.[17] The diagnosis is usually clinicopathological.[8] From
the diagnostic point of view, when the history seems to
indicate a disease with systemic involvement and routine
plain films show lytic lesions of the skull, LCH should be
considered in the differential diagnosis. In such cases,
pediatricians are involved for skeletal screening with
plain films as well as CT scan and/or magnetic resonance
imaging.[19,20] Endocrine evaluation may reveal diabetes
insipidus. Diagnosis is usually established after biopsy that
is usually carried out on one of the cutaneous ulcers or
masses. Microscopic examination shows typical features of
a granulomatous lesion, however, the key to diagnosis is
to identify the pathologic Langerhans cell that resembles
a typical Langerhans cell but it is nondendritic.[13] Birbeck
granules, which are intracytoplasmic inclusions, are the
hallmark of a pathologic Langerhans cell. Special tests such
as transmission electron microscopy might be needed to
identify them.[8] Other special tests are immunohistochemical
tests such as CD1a, S‑100, and CD207 (langerin). Currently,
demonstration of CD1a and Birbeck granule is required
for the diagnosis. Moreover, CD207 has been found to be
associated with Birbeck granules with a 100% concordance,
and hence, immunohistochemical positivity of these two
markers (CD1a and CD207) defines the disease.[8,9]
LCH is staged by the Histiocyte Society into single‑system LCH
or multi‑system LCH depending on the number of systems
involved.[9]
The treatment depends on the stage and the severity of
the disease. It ranges from simple topical application of
corticosteroids or antineoplastic agents, intralesional
corticosteroid injections, and surgical curettage of skin
lesions to full‑blown course of systemic antineoplastic agents
lasting up to a year.[8,11]
The prognosis also depends on the stage and the severity
of the disease. Unifocal LCH has the best prognosis with
complete remission seen in cases of solitary lymph node
involvement or isolated skin lesions. The disseminated
disease (Letterer–Siwe disease) has the worst prognosis
among all the forms of LCH with mortality in excess of 50%.
The prognosis of the multifocal variant lies in‑between and is
bad in patients in extremes ages and those with pulmonary
involvement. The mortality rate is around 10%, and less than a
third of the patients could achieve complete remission.[15] The
bestprognosticindicator,afteranalyzingmanyclinicaltrials,
has been demonstrated to be the response of the patient to
chemotherapy during the 6‑week induction phase.[8]
CONCLUSION
LCH is a rare disease with a diversity of clinical presentations
that may involve any organ. Otorhinolaryngology
manifestations may cause diagnostic difficulties; a high index
of suspicious and its inclusion in the differential diagnosis
are suggested.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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