PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 23 no. 1 January – June 2008
CASE REPORTS
20 PhiliPPine Journal of otolaryngology-head and neck Surgery
ABSTRACT
Objective: To describe an unusual presentation of Langerhans cell histiocytosis in the
craniofacial skeleton in a patient previously diagnosed with Pott’s disease.
Methods:
Design: Case report.
Setting: Tertiary care center.
Patient: One (1)
Result: A 30-year-old male who previously underwent cervical spine surgery for Pott’s
disease, presenting with watery ear discharge and mandibular resorption was initially
diagnosed with tuberculosis. On MRI, a mildly contrast-enhancing soft tissue mass
involving the left infratemporal and middle cranial fossae consistent with residual
or recurrent tumor as well as an inflammatory process was seen. He underwent
transtemporal excision of the mass with external auditory canal blind sac closure and
obliteration. Final histopathology revealed Langerhans cell histiocytosis. A review of
slides of the specimen from the previous spine surgery was done and signed out as
Langerhans cell histiocytosis.
Conclusion: Langerhans cell histiocytosis occurs rarely, but has frequent head and neck
manifestations. It may also be confused with other diseases in the head and neck, such
as tuberculosis, in this case. Otorhinolaryngologists and head and neck surgeons should
be well aware that isolated lesions in the bony framework of the head and neck should
include Langerhans cell histiocytosis in the differential diagnosis. Early detection is the
key to preventing disease progression and instituting timely definitive management.
Key words: Langerhans cell histiocytosis, watery ear discharge, mandibular resorption
Langerhans Cell Histiocytosis:
An Unusual Presentation
Kathleen R. Fellizar, MD1
Charlotte M. Chiong, MD1,2
1 Department of Otorhinolaryngology
Philippine General Hospital
University of the Philippines Manila
2 Philippine National Ear Institute
National Institutes of Health
University of the Philippines Manila
Correspondence: Kathleen R. Fellizar, MD
Department of Otorhinolaryngology
Ward 10, Philippine General Hospital
Taft Avenue, Ermita, Manila 1000
Philippines
Phone: (632) 526 4360
Fax: (632) 525 5444
Email: orlpgh@yahoo.com
Reprints will not be available from the author
No funding support was received for this study. The authors
signed a disclosure that they have no proprietary or financial
interest with any organization that may have a direct
interest in the subject matter of this manuscript, or in any
product used or cited in this report
Presented at the Interesting Case Contest (1st Place)
Philippine Society of Otolaryngology Head and Neck Surgery
Midyear Convention, Legazpi City, Bicol, April 28, 2006 Philipp J Otolaryngol Head Neck Surg 2008; 23 (1): 20-24 c Philippine Society of Otolaryngology – Head and Neck Surgery, Inc.
PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 23 no. 1 January – June 2008
CASE REPORTS
PhiliPPine Journal of otolaryngology-head and neck Surgery 21
Langerhans cell histiocytosis (LCH) comprise a group
of idiopathic disorders characterized by the proliferation of
specialized bone marrow–derived Langerhans cells as well
as mature eosinophils. It is considered rare and the reported
prevalence is higher among whites than other races and greater
in males than females with a ratio of 2:1.
The head and neck are commonly involved especially
the temporal bone. Previous reports noted that 25-30% of
patients with various forms of this disease have temporal bone
destruction. One case series has found nearly 50% involvement
in the remainder of the head and neck. These consist mostly of
isolated lesions of the mandible and skull.1
The frequency of head and neck manifestations, as well as
possible confusion with other diseases in the head and neck make
an understanding of the disease and its peculiarities important
for the otolaryngologist. We report the rare case of a 30-year-
old male presenting with watery otorrhea and mandibular
resorption, the diagnostic examinations requested, the dilemma
that arose with the case, and the surgical treatment done.
CASE REPORT
A 30-year-old male from Lucena City underwent cervical
spine surgery in 2001 for Pott’s disease. Histopathologic results
were read as tuberculosis for which he took anti-tuberculosis
medications for two months. The present consult involved a
one- year history of recurrent, clear, watery nonfoul-smelling
left ear discharge, which was resistant to medical management,
associated with gradual decrease in the size of the mandible,
clear discharge coming from the lower tooth sockets and
loosening and eventual extrusion of the lower teeth. There was
also gradual hearing loss in the left ear.
Three months prior to admission, the patient consulted an
otolaryngologist who noted active milky-white discharge from
the left ear with a positive fistula test, milky-white discharge from
previous tooth extraction sites in the mandible and retrognathia.
This led to a diagnosis of tuberculous otitis, left and tuberculous
osteomyelitis of the mandible. A cranial CT scan was requested,
but the patient was lost to follow-up.
Two months later, the patient returned with the CT scan,
revealing a heterogenous soft tissue mass in the left masseter
space with extension into the left middle cranial fossa. A bony
defect involving the floor and lateral wall of the left middle cranial
fossa was noted. The cochlea, jugular bulb and sigmoid sinus
were absent in the left side (Figure 1). A soft tissue sarcoma was
Figure 1. Cranial CT scan with bone window algorithm showing a large bony
defect involving the floor and lateral wall of the left middle cranial fossa as well
as destruction of the cochlea and the posterior fossa plate (white arrows). C =
cochlea; J = jugular bulb; S = sigmoid sinus. Note the absence of the cochlea,
jugular bulb and sigmoid sinus plate in the left side.
Figure 2. MRI of the skull base showing a mildly contrast-enhancing soft tissue
mass involving the left middle cranial fossa (arrows).
Figure 3. Panoramic radiograph of the patient, mandible absence is noted.
PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 23 no. 1 January – June 2008
CASE REPORTS
22 PhiliPPine Journal of otolaryngology-head and neck Surgery
called Hand-Schüller-Christian disease.2
LCH is seen in different ages, but a clear predominance exists
for the pediatric age group.3 It is a rare condition in adults.4
Thus, a 30-year-old male presenting with otorrhea, mandibular
resorption and cervical spine erosion does not typify a patient
with Langerhans cell histiocytosis.
Destruction of the temporal and mastoid bones manifest
as mastoid swelling, middle ear polyps, and in this case, CSF
otorrhea, and erosion of the posterior bony external auditory
canal. Infiltration of the mandible will present with loose teeth
and eventual resorption as seen in this patient. Vertebral collapse
with spinal cord compression has occasionally been described,
which may have happened in the patient when he was initially
diagnosed with cervical Pott’s disease four years prior to the
onset of watery ear discharge.
There may be confusion with Langerhans cell histiocytosis and
other diseases in the head and neck, particularly granulomatous
inflammations, such as tuberculosis (TB). Many of the clinical
features of Langerhans cell histiocytosis mimic this highly
endemic disease in the Philippines.5 As seen in this case,
radiographs were not able to differentiate between TB and LCH.
Even the final histopathology of the cervical lesion was initially
read as tuberculosis.
Both Langerhans cell histiocytosis and tuberculosis may
present with multisystem involvement. Symptoms in this patient
presented in a sequential manner with cervical erosion, followed
by mandibular resorption, and finally otorrhea, which is more in
accordance with Langerhans cell histiocytosis.6 In the case of
tuberculosis, symptoms usually appear simultaneously although
progressive multi-organ involvement sequentially occurs in
many cases.
Histologically, a typical tuberculous granuloma would
normally be described as chronic granulomatous inflammation
with caseation necrosis and Langhans’ type giant cells mixed
with chronic inflammatory infiltrates consisting of lymphocytes.
(Figure 4a) In the patient’s cervical spine specimen, cells were
arranged in a granuloma-like pattern, and as such may have been
mistaken for a tuberculous granuloma. (Figure 4b) Both diseases
show aggregates of histiocytes. Histiocytes of tuberculosis are
epithelioid and spindle-shaped. (Figure 5a) On the other hand,
histiocytes seen in Langerhans cell histiocytosis are atypical,
in that they are large, ovoid, mononuclear cells. (Figure 5b)
Aside from this, LCH also presents with a large component of
eosinophils in contrast to lymphocytes seen in TB.7
considered, for which cytologic correlation was recommended.
The patient was referred to a neurosurgeon who requested an
MRI of the skull base. This showed a mildly contrast-enhancing
soft tissue mass in the left infratemporal and middle cranial
fossae (Figure 2). A biopsy was the next logical step but there
was a dilemma on how to approach the mass.
Another otolaryngologist saw the patient and noted watery,
clear, pulsatile non foul-smelling discharge from the left ear.
Retrognathia was noted, for which a panoramic radiograph was
done, showing total absence of the mandible (Figure 3). An
assessment of CSF otorrhea secondary to TB lytic destruction
with mandibular resorption was made.
In order to address both biopsy of the primary lesion and
treatment of the CSF otorrhea, transtemporal excision of
the mass with external auditory canal blind sac closure and
obliteration under general anesthesia was done at the Philippine
General Hospital. Intra-operative findings include the absence
of the posterior bony external auditory canal wall, and an “eaten-
out” temporal bone. A fleshy mass was seen in the area of the
mastoid cavity. Part of the mass was sent for frozen section
which was read as chronic inflammation with gliosis. Near total
gross excision of the mass was done. Blind sac closure of the
external auditory canal was followed by temporalis muscle flap
rotation and obliteration of the temporal bone defect to address
the CSF leak.
Final histopathologic diagnosis was Langerhans cell
histiocytosis. A review of slides of the specimen from the previous
spine surgery was requested, which likewise revealed Langerhans
cell histiocytosis. To strengthen the diagnosis, immunostaining
with S-100 protein was done. Both specimens were positive.
The post-operative course was uneventful except for
episodes of dizziness and vomiting. The patient was discharged
after 12 days, but was again lost to follow-up. Despite repeated
calls, the patient refused the recommendation to undergo
chemotherapy.
DISCUSSION
Langerhans cell histiocytosis (LCH), formerly known as
histiocytosis X, denotes a group of diseases characterized by
infiltration or proliferation of histiocytes in various body tissues.
The clinical spectrum includes the acute fulminant, disseminated
Letterer-Siwe disease, solitary or few, indolent and chronic,
lesions of bone or other organs called eosinophilic granulomas,
(under which the patient may fall) and the intermediate form
PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 23 no. 1 January – June 2008
CASE REPORTS
PhiliPPine Journal of otolaryngology-head and neck Surgery 23
Figure 4. H&E photomicrographs. (a) Typical tuberculous granuloma versus (b) granuloma seen in the cervical spine specimen of the patient.
Figure 5. H&E photomicrographs of tuberculosis specimen and LCH specimen of the patient. Histiocytes (arrows) of tuberculosis (a) versus histiocytes (arrows) of Langerhans cell histiocytosis in the specimen of
the patient (b).
Table 1. Similarities and differences between Langerhans cell histiocytosis and
tuberculosis noted in the case
Langerhans cell histiocytosis Tuberculosis
Multisystem involvement
Appearance of symptoms
Histologic arrangement
of cells
Appearance of histiocytes
Inflammatory infiltrates
S-100 reactivity
Present
Sequential
Granuloma-like pattern
Atypical; large, ovoid
mononuclear cells
Eosinophils
Positive
Present
Often simultaneous , may
be sequential over time
Chronic granulomatous
inflammation with casea-
tion necrosis and Langhans’
type giant cells
Epitheliod, spindle-shaped
Lymphocytes
Negative
S-100 staining strengthened the diagnosis of LCH in this case.
Both normal and diseased Langerhans cells will stain positive for
S-100. Tuberculosis cells do not.
The similarities and differences between Langerhans cell
histiocytosis and tuberculosis noted in this case are summarized
in Table 1.
The initial misleading histopathologic diagnosis of
tuberculosis of the cervical spine specimen allowed progression
of the disease to involve the mandible and then the temporal
bone. The patient’s poor follow-up record compounded this
progression, adding to delays in diagnosis and treatment.
Transtemporal excision of the mass with blind sac closure
of the external auditory canal was considered for the definitive
PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 23 no. 1 January – June 2008
CASE REPORTS
24 PhiliPPine Journal of otolaryngology-head and neck Surgery
ACKNOWLEDGEMENT
The authors wish to thank the following individuals from the University of the Philippines
College of Medicine - Philippine General Hospital without whose help this paper would not have been
possible: Dr. Jose Maria Avila, Chairman, Department of Pathology who was our resource person for
pathology; Drs. Joselito Jamir and Romeo Villarta Jr. former chairman and consultant, respectively
of the Department of Otorhinolaryngology, who were our scientific advisors; Dr. Gerardo Legaspi,
consultant, Department of Neurosciences Section of Neurosurgery who was the co-managing
neurosurgeon; and Dr. Sherjan Kalim, resident of the Department of Pathology for assisting with the
photomicrographs.
REFERENCES
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2. Smith RJ, Evans JN. Head and neck manifestations of histiocytosis X. Laryngoscope, 1984;94:395-
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3. Kilpatrick SE, Wenger DE, Gilchrist GS, Shives TC, Wollan PC, Unni KK. Langerhans’ cell
histiocytosis (histiocytosis X) of bone: A clinicopathologic analysis of 263 pediatric and adult
cases. Cancer. 1995;76(12):2471-2484.
4. Malpas JS. Langerhans cell histiocytosis in adults. Hematol Oncol Clin North Am. 1998;12(2):
159-165.
5. Lorenzo PR, Martinez NV. Histiocytosis X: A pathologist’s challenge. Philipp J Otolaryngol Head
Neck Surg. 1992:140-145.
6. Bertram C, Madert J, Eggers C. Eosinophilic granuloma of the cervical spine. Spine.
2002;1:27(13):1408-13.
7. Avila JM. Professor of Pathology, University of the Philippines College of Medicine. (personal
communication, March 2006).
8. Davis SE, Rice DH. Langerhans cell histiocytosis: current trends and the role of the head and
neck surgeon. Ear Nose Throat J. 2004 May:83(5):340-350.
management of CSF otorrhea in this case while, at the same time,
obtaining a good specimen for biopsy.
In retrospect, had a correct diagnosis been made at the
time of cervical spine surgery, the resultant CSF otorrhea could
have been prevented. Though initially managed by topical
drops, the diagnosis of CSF otorrhea and definite management
with external ear canal blind sac closure was very important.
The latter is most relevant in preventing the possible life-
threatening condition of meningitis. However, the contralateral
temporal bone is likewise at risk. Definitive treatment, in the
form of chemotherapy consisting of low to moderate doses of
methotrexate, prednisone, and vinblastine hopefully can save
this patient from further lytic destruction of other bony sites.8 This
option has been presented to the patient, as well as the possible
side effects of chemotherapy, including hair loss and vomiting.
The patient was not open to these particular side effects, thus
refusing this therapeutic option.
Otorhinolaryngologists and head and neck surgeons should
be well aware that isolated lesions in the bony framework of the
head and neck should include Langerhans cell histiocytosis in
the differential diagnosis because, as in the case of the different
diseases that have plagued mankind throughout the centuries,
early detection is still the key to preventing disease progression
with timely definitive management.