Mastoiditis and facial paralysis as initial manifestations of temporal bone systemic diseases – the significance of the histopathological examination ALMA AURELIA MANIU1), OANA HARABAGIU1), LAURA OTILIA DAMIAN2), EUGEN HORAŢIU ŞTEFĂNESCU3), BOGDAN MARIUS FĂNUŢĂ4), ANDREEA CĂTANĂ5), CARMEN AURELIA MOGOANTĂ6)

Abstract

Several systemic diseases, including granulomatous and infectious processes, tumors, bone disorders, collagen–vascular and other autoimmune diseases may involve the middle ear and temporal bone. These diseases are difficult to diagnose when symptoms mimic acute otomastoiditis. Case reports: The present report describes our experience with three such cases initially misdiagnosed. Their predominating symptoms were otological with mastoiditis, hearing loss, and subsequently facial nerve palsy. The cases were considered an emergency and the patients underwent tympanomastoidectomy, under the suspicion of otitis media with cholesteatoma, in order to remove a possible abscess and to decompress the facial nerve. The common features were the presence of severe granulation tissue filling the mastoid cavity and middle ear during surgery, without cholesteatoma. The definitive diagnoses was made by means of biopsy of the granulation tissue from the middle ear, revealing granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) in one case, middle ear tuberculosis and diffuse large B-cell lymphoma respectively. After specific associated therapy facial nerve functions improved, and atypical inflammatory states of the ear resolved. Conclusions: As a group, systemic diseases of the middle ear and temporal bone are uncommon, but aggressive lesions. After analyzing these cases and reviewing the literature, we would like to stress upon the importance of microscopic examination of the affected tissue, required for an accurate diagnosis and effective treatment.

Full text

Rom J Morphol Embryol
2016, 57(1):243–248
ISSN (print) 1220–0522 ISSN (online) 2066–8279
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Mastoiditis and facial paralysis as initial manifestations of
temporal bone systemic diseases – the significance of the
histopathological examination
ALMA AURELIA MANIU1), OANA HARABAGIU1), LAURA OTILIA DAMIAN2), EUGEN HORAŢIU ŞTEFĂNESCU3),
BOGDAN MARIUS FĂNUŢĂ4), ANDREEA CĂTANĂ5), CARMEN AURELIA MOGOANTĂ6)
1)
Department of Otorhinolaryngology, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
2)
Department of Rheumatology, Emergency County Hospital, Cluj-Napoca, Romania
3)
Department of Otorhinolaryngology, “Victor Babeş” University of Medicine and Pharmacy, Timisoara, Romania
4)
Department of Otorhinolaryngology, Emergency County Hospital, Craiova, Romania
5)
Department of Molecular Sciences, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
6)
Department of Otorhinolaryngology, University of Medicine and Pharmacy of Craiova, Romania
Abstract
Several systemic diseases, including granulomatous and infectious processes, tumors, bone disorders, collagen–vascular and other
autoimmune diseases may involve the middle ear and temporal bone. These diseases are difficult to diagnose when symptoms mimic acute
otomastoiditis. Case reports: The present report describes our experience with three such cases initially misdiagnosed. Their predominating
symptoms were otological with mastoiditis, hearing loss, and subsequently facial nerve palsy. The cases were considered an emergency
and the patients underwent tympanomastoidectomy, under the suspicion of otitis media with cholesteatoma, in order to remove a possible
abscess and to decompress the facial nerve. The common features were the presence of severe granulation tissue filling the mastoid cavity
and middle ear during surgery, without cholesteatoma. The definitive diagnoses was made by means of biopsy of the granulation tissue
from the middle ear, revealing granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis) in one case, middle ear
tuberculosis and diffuse large B-cell lymphoma respectively. After specific associated therapy facial nerve functions improved, and atypical
inflammatory states of the ear resolved. Conclusions: As a group, systemic diseases of the middle ear and temporal bone are uncommon,
but aggressive lesions. After analyzing these cases and reviewing the literature, we would like to stress upon the importance of microscopic
examination of the affected tissue, required for an accurate diagnosis and effective treatment.
Keywords: mastoiditis, facial nerve palsy, systemic disease, infectious processes.
 Introduction
Several systemic diseases, including granulomatous
and infectious processes, tumors, bone disorders, storage
diseases, collagen–vascular and other autoimmune diseases,
may involve the middle ear and temporal bone. In some,
the initial clinical symptoms may occur in the temporal
bone and can be confused with other diseases limited to
the middle ear and mastoid, such as chronic otitis media
[1]. The common presentation of a draining ear is nearly
indistinguishable from that of common otitis media. A
high index of suspicion and knowledge about possible
causes are required for accurate diagnosis and effective
treatment [2]. Granulomatosis with polyangiitis (GPA),
historically known as Wegener’s granulomatosis, is a
systemic vasculitis that affects small and medium vessels
predominately in the kidneys, lungs, and the mucosa of
the upper respiratory tract [3]. The majorities (73–93%)
of patients with GPA have otorhinolaryngological (ENT)
involvement at presentation and many of these patients
see an ENT surgeon in their first visit to the hospital [4].
Otological manifestations appear in between 6% and
56% of patients suffering from GPA. The most frequent
of middle ear lesions is serous otitis. Acute otitis media
or chronic otitis media, which develop because of the
presence of granulation tissue affecting the Eustachian
tube, middle ear or nasopharynx, are less frequent [5].
Facial paralysis, including bilateral cases, can also appear
associated with the presence of otomastoiditis [6]. The
diagnosis is achieved through clinical assessment, sero-
logical tests for ANCA (antineutrophil cytoplasmic anti-
bodies) and histological analysis [7].
Tuberculosis of the middle ear is a rare disease and
accounts for between 0.04–0.9% of all cases of chronic
suppurative otitis media. It is difficult to diagnose because
the disease presents like other chronic suppurative otitis
media. The significant features of aural tuberculosis are
abundant granulation tissue in mastoids with good pneu-
matization, cervical lymphadenopathy, profound hearing
loss, facial palsy, and foci of tuberculosis elsewhere [8].
The diagnosis of middle ear tuberculosis may be delayed
because of its similarity to other forms of otitis media in
the early stages.
Lymphomas represent the second most frequent
malignant tumor (incidence 2.5%) in the head and neck
region [9]. Non-Hodgkin’s lymphomas (NHLs) present
with cervical lymph node involvement, but in 40% extra-
nodal site could be primary involved: nasopharynx, the
lachrymal sac, the temporal bone, or the other areas [10].
NHLs of the ear are rarely reported. These temporal bone
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tumors are typically associated with facial nerve paralysis
and hearing loss, and few cases have granulation tissue
in the external auditory canal as well [11].
In this report, we present three such patients seen and
treated within our institution. All patients had the same
clinical features mimicking otomastoiditis with facial palsy
as initial symptoms that proved to be later a systemic
disease involving the temporal bone.
 Case presentations
Case No. 1
A 26-year-old male presented with left-side facial
nerve palsy, intense otalgia and fullness in the right ear.
He had been previously diagnosed with bilateral serous
otitis media and treated accordingly. After one month
of conservative treatment, the symptoms worsened. The
left tympanic membrane appeared to be perforated with
granulating tissue and purulent effusion and the right
tympanic membrane was inflamed. Audiometry tests
showed moderate to severe mixed hearing loss in the left
ear and conductive ear loss on the right side. Temporal bone
computed tomography (CT) scans revealed opacification
involving the left middle ear and mastoid cells without
signs of osteolytic injury (Figure 1). A tympanomastoid-
ectomy canal wall up procedure was performed under the
suspicions of chronic otitis media with cholesteatoma.
During surgery granulating friable soft tissue, somewhat
hemorrhagic, was removed and submitted for histological
review (Figure 2). Additional medical therapy with anti-
biotics (Ceftriaxone) and intravenous steroids was asso-
ciated for 10 days. Hearing loss improved and facial nerve
palsy regressed almost entirely. The serology tests for
HIV (human immunodeficiency virus), hepatitis B and
C viruses, VDRL (venereal disease research laboratory),
rheumatoid factor, cytoplasmic (c)-ANCA, and perinuclear
(p)-ANCA came back negative. The patient was discharged
after spending 10 days in hospital and was sent home with
an antibiotic prescription. He returned after seven days
for the histopathology result, with a newly installed dry
cough. The histopathological exam from the ear revealed
granulomas with aggregates of activated macrophages,
multinucleated giant cells and a peripheral accumulation
of lymphocytes (Figure 3, a and b).
Taken into consideration the clinical features, histo-
logical pattern suggested a Wegener’s granulomatosis.
We repeated c-ANCA test, which this time came back
positive (1/20 titer). Chest CT scans revealed the presence
of lung parenchymal nodules. Therapy with Methyl-
prednisolone and Cyclophosphamide was initiated, and
the patient partially recovered his hearing thresholds, as
inflammation in the middle ear was controlled.
Figure 1 – (a) High-resolution CT scanning without contrast – coronal
planes–right ear – shows normal pneumatization of the mastoid cells; (b)
High-resolution CT scanning without contrast – coronal planes–left ear –
shows opacification of the mastoid cells without signs of septal osteolytic
injury.
Figure 2 – View during surgery of
the left ear revealing granulation
tissue and puss in the middle ear.
Figure 3 – (a) Biopsy specimen showing accumulation of lymphocytes and multinucleated giant cells; (b) Biopsy
specimen showing granuloma with aggregates of activated macrophages, multinucleated giant cells and a peripheral
accumulation of lymphocytes. HE staining: (a) ×200; (b) ×100.

Mastoiditis and facial paralysis as initial manifestations of temporal bone systemic diseases – the significance…
245
Case No. 2
A 5-year-old female child came into the Department
of Otorhinolaryngology with persistent painless otorrhoea
for two months, resistant to conventional treatment. One
week prior to admission, she associated a right-sided
lower motor neuron facial palsy. On examination there
was bulging of eardrum with granulation tissue presence.
Temporal bone high-resolution CT scans demonstrated
the entire tympanum and mastoid air cells were occupied
by soft tissue, bone destruction and sequestra. The patient
was taken to surgery. A cortical mastoidectomy was per-
formed and the florid granulation tissue was scraped out
(Figure 4). Histopathology examination revealed granu-
lation tissue with epithelioid cells and multinucleated giant
cells, areas of central necrosis, lymphocytic infiltration,
ulcerations and superficial resorption of the involved bone
(Figure 5, a and b). A diagnosis of the granulomatous
type tuberculous mastoiditis was made. The child was
referred to the Department of Pneumology for standard
systemic antituberculosis chemotherapy.
Figure 4 – View during surgery of the right ear
revealing granulation tissue in the mastoid.
Figure 5 – (a) Biopsy specimen showing granulomas with central area of necrosis, activated epithelioid macrophages,
Langhans giant cells, and a peripheral accumulation of lymphocyte; (b) Biopsy specimen under high-power view
showing granulomas with areas of caseating necrosis, activated epithelioid macrophages, Langhans giant cells (multi-
nucleated giant cells with abundant eosinophilic cytoplasm and nuclei forming an horseshoe arrangement), and a
peripheral accumulation of lymphocytes. This distinctive histological pattern suggests an inflammatory process specific
for tuberculosis. HE staining: (a) ×100; (b) ×400.
Case No. 3
A 4-year-old female child with left facial palsy and
retroauricular swelling presented to our institution after
being seen at another hospital for the facial palsy,
installed two weeks prior. She had been previously treated
for acute otitis media, but his symptoms were not improved
and retroauricular swelling developed on the same side
three days before he came to our attention (Figure 6). On
physical exam, the posterosuperior part of the external
auditory canal (EAC) showed marked bulging and the
tympanic membrane was not visible (Figure 7). Pure-
tone audiometry showed a left-side conductive hearing
loss of 35 dB. A CT scan of the temporal bone showed a
soft-tissue density filling the mastoid antrum and middle
ear. The soft tissue had eroded the mastoid cortex and
seemed to extend to the wall of the EAC.
Given these findings, the patient underwent a right
tympanomastoidectomy. The mastoid cavity contained
copious amounts of necrotic bone, mastoid cells filled
with some whitish amorphous material and granulating
tissue. Biopsies were taken.
Figure 6 – Right ear
(preoperative image):
it can be noted the
presence of a
retroauricular
abscess.
Figure 7 – Otoscopy of the
right ear. The postero-
superior part of the
external auditory canal
(EAC) showed marked
bulging and the tympanic
membrane was not visible.
Histological analysis showed a monomorphic infiltrate
of intermediate sized lymphoid cells. These cells stained
positively for CD20 and CD79a (a B-cell marker), and
stained negatively for T-cell markers CD3, cyclin D1
and CD23. The lymphoid cells had a stippled chromatin
pattern and a small rim of cytoplasm. Cell markers CD10
and TdT (terminal deoxynucleotidyl transferase) stained

Alma Aurelia Maniu et al.
246
positively. Mature cell markers were negative. Following
immunohistological staining and flow cytometry, a diag-
nosis of immature lymphoblastic non-Hodgkin’s B-cell
lymphoma was made (Figure 8, a and b). The child was
referred to the Department of Pediatric Oncology and
was started on a chemotherapeutic regimen.
Figure 8 – (a) Biopsy specimen: a fragment of keratinized, stratified squamous epithelium and subjacent tissue infiltrated
by a monotonous population of small lymphocyte-like cell (HE staining, ×200); (b) Biopsy specimen: the monotonous
population of small lymphocyte-like cells shows CD20 positivity (B-cell marker). Histological pattern and CD20 immuno-
staining positivity suggests a diffuse B-cell non-Hodgkin’s lymphoma, ×100.
 Discussion
Systemic diseases are not easily diagnosed when the
presenting symptoms mimic otomastoiditis, particularly
in patients who do not have associated symptoms at
disease onset. Granulomatosis with polyangiitis (GPA –
the former Wegener’s) is a relatively rare condition [5].
Current vasculitis assessment employs the Birmingham
Vasculitis Activity Score (BVAS). It is divided into nine
organ domains, and the ear, nose and throat (ENT) domain
encompasses five items [12]. Most patients with GPA with
ear involvement have chronic otitis media with effusion
caused by Eustachian tube disorders and sensorineural
hearing loss. Facial nerve palsy has been reported during
the course of the disease, but it is extremely rare as the
presenting feature [13]. Chronic otitis media occurs
consequently to the direct involvement of the middle ear
and the mastoid cavity by necrotizing granuloma, and
may develop accompanied by effusion, mastoiditis and
facial nerve palsy. Otomastoiditis associated with facial
nerve palsy is seen in 10% of the cases [14]. In our case,
the patient evolved this way, however without other
previous symptoms, as rarely reported in the literature.
The patient underwent urgent mastoidectomy with facial
nerve decompression. Previous studies recommend a
conservative approach to such complications in GPA [15],
as the nerve function does not recover after surgery.
However, in our case the histological examination was
the key-point to produce the diagnosis, as c-ANCA was
initially negative. However, a recent study confirmed that
mastoid surgery is performed in 5% of the patients before
the diagnosis of GPA is made [4]. Tuberculosis is a chronic
bacterial infection caused by Mycobacterium tuberculosis,
a slow-growing strict aerobic bacillus. It forms granulomas
with caseous necrosis due to the cell response of involved
tissues [16].
Tuberculosis is one of the major infectious diseases
with predominant involvement of lung and lymph nodes,
but tuberculosis of the middle ear is uncommon [17].
Very few cases of tuberculous otitis media (TOM) are
reported in the literature. Mills’ study mentioned that
the incidence of TOM has fallen dramatically since the
beginning of the last century [18]. The classic clinical
features of TOM were described by Wallmer in 1953 as
painless otorrhoea, multiple tympanic membrane perfo-
rations, pale granulation tissue, ipsilateral facial nerve
paralysis, and early severe hearing loss and bone necrosis
[19]. However, these classical features are rarely observed
today. Recently, a review of all TOM reports in the English
literature by Skolnik et al. refuted these findings. Their
research showed that facial palsy is present in only 16%
of cases and multiple tympanic perforations are equally
rare [20]. In the series described by Nishiike et al., none
of the patients had multiple perforations, facial nerve
palsy or bone erosion [21]. Therefore, in our case the
patient did not present with the classic symptoms of
middle ear tuberculosis. The classically described painless
otorrhoea was painful, due to granulation tissue in the
middle ear and possible bacterial super infection. Due to
the atypical clinical presentation a left mastoidectomy was
performed. The diagnosis was based on the histology
following middle ear exploration for acute mastoiditis.
TOM should be considered in the differential diagnosis
of chronic middle ear discharge that does not respond to
usual therapy. Delay in diagnosis can lead to complica-
tions. When surgery is combined with adequate chemo-
therapy, there is a fair chance of healing with a dry ear
and a good prognosis.
Lymphoblastic lymphomas (LBLs) are precursor
lymphoid neoplasms with less than 25% lymphoblasts
in the bone marrow [22]. More than 60% of patients
with LBLs are younger than the age of 18, and they
account for one fourth of all childhood non-Hodgkin’s
lymphomas in industrialized countries [23]. The majorities

Mastoiditis and facial paralysis as initial manifestations of temporal bone systemic diseases – the significance…
247
of LBLs are of T-lineage and frequently present with
a mass in the anterior mediastinum, whereas precursor
B-cell (pB)-LBLs constitute less than 10% of LBLs and
predominantly involve extranodal sites including the skin,
soft tissue, and bones. A pB-LBL of the ear is extremely
rare [24]. In our patient, the acute onset of conductive
hearing loss and retroauricular swelling accompanied by
facial palsy suggested an acute otomastoiditis and a
tympanomastoidectomy canal wall up procedure was
performed. Otitis media with effusion and cholesteatoma
are relatively common in children, even in the absence of
acute middle-ear inflammation. In contrast, less frequent
middle ear tumors can cause symptoms and signs that
are identical with those of otitis media [25]. In our case,
the histopatological examination was crucial to make
the diagnosis.
We would like to emphasize that systemic diseases
might be etiological factors in patients presenting with
otomastoiditis, facial nerve paralysis and unilateral hearing
loss. It is appropriate for an otorhinolaryngologist to
consider complete blood count, peripheral blood smear,
and temporal bone imaging and exclude any other systemic
diseases such as: granulomatosis with polyangiitis, middle
air tuberculosis, leukemia or temporal bone malignancy,
especially before steroid administration for facial nerve
paralysis treatment. Our cases showed how radiological
semiology and CT sometimes are not enough to diagnose
the nature of the disorder. Moreover, all patients were in
good general condition at the time of the examination;
they did not show history of previous immunodepression
or other risk factors. Biopsy of granulation tissue in the
middle ear rarely offers a diagnosis because of the limited
amount of sample taken for diagnosis, except for those
performed in the context of mastoidectomy [26]. In our
cases, surgical treatment was considered to be the best
opportunity for the patients, as long as they seemed to
be medical emergencies. Surgery also aimed to provide
the samples required for bacteriological and histological
examinations, allowing subsequently early diagnosis.
 Conclusions
In the case of facial palsy and acute otological
symptoms, the diagnosis of systemic diseases can be
challenging. Therefore, besides the usual clinical and
radiological examinations, the histopatological examination
is essential for accurate diagnosis.
Conflict of interests
The authors declare that they have no conflict of
interests.
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Corresponding author
Alma Aurelia Maniu, Lecturer, MD, PhD, Department of Otorhinolaryngology, “Iuliu Haţieganu” University of Medicine
and Pharmacy, 4–6 Clinicilor Street, 400006 Cluj-Napoca, Romania; Phone +40755–044 632, Fax +40264–590 226,
e-mail: almacjro@yahoo.com
Received: June 22, 2015
Accepted: March 15, 2016