Case report

The Neuroradiology Journal

0(00) 17

Head and neck inflammatory pseudotumor: ! The Author(s) 2016

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Case series and review of the literature DOI: 10.1177/1971400916665377
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Sagar Kansara1, Diana Bell2, Jason Johnson3 and Mark Zafereo4

Abstract
Inflammatory pseudotumor (IP) is an uncommon idiopathic lesion that often imitates malignancy clinically and radio-
logically. Inflammatory pseudotumors have been found to occur in various sites but rarely in the head and neck. The
histopathology, imaging, and treatment of three unique cases of head and neck inflammatory pseudotumors are described
in this case series. Patients in Cases 1 and 2 presented with right level II neck mass and left parotid tail mass, respectively.
The patient in Case 3 presented with otalgia, jaw pain and trismus, and a left parapharyngeal space mass. The tumors in
Cases 1 and 3 significantly decreased in size with tapered courses of oral corticosteroids. The tumor in Case 2 was surgically
excised without disease recurrence. Malignancy must be ruled out with incisional or excisional biopsy. Treatment includes
surgical excision, oral corticosteroids, or both. The literature shows that radiotherapy and small-molecule inhibitors may be
promising alternatives.

Keywords
Head and neck neoplasms, inflammatory pseudotumor, head and neck oncology, IgG4 disease

showing densely sclerotic tissue and multifocal dense

Introduction
First characterized by Brunn in 1939,1 inammatory
pseudotumor (IP) is an exceedingly rare benign condi-
tion that often presents as a locally invasive mass. IP is
named for its ability to mimic invasive malignancies on
clinical presentation, imaging, and histology. IP most
often occurs in the lungs and the orbit, with only 15%
occurring in the nonorbital head and neck region.2,3
Here we describe three unique cases of extraorbital
IPs in the head and neck, with discussion of diagnostic
and management considerations.
Case reports
Case 1
A 46-year-old woman with past medical history of dia-
betes mellitus presented with a progressively enlarging
and painful right neck mass. Computed tomography
(CT) imaging showed a 4 cm solid right level II
neck mass (Figure 1(a)) and an adjacent 2.5 cm
mass (Figure 1(b)). 18-Fluorodeoxyglucose positron-
emission tomography (FDG PET) imaging revealed
the dominant mass to be intensely FDG avid
(Figure 1(e)). Multiple ultrasound-guided ne-needle
and core biopsies of the mass revealed dense brous
tissue and skeletal muscle with chronic inammation,
with no evidence of malignant cells or lymphoma.
Incisional biopsy was performed with pathology
lymphoplasmocytic inltrate without evidence of malig-
nancy. Scattered intermixed eosinophils and histiocytes
with occasional multinucleated giant cells were present.
Immunohistochemical studies showed CD3 and
CD20 cells, indicating mixed T-cells and B-cells.
A subset of the cells were positive for immunoglobulin
(Ig)G4 (20% IgG4/IgG ratio) but not denitive for
IgG4-related sclerosing disease. The patient was started
on a tapered course of oral prednisone. Three months
later she reported an improvement in her neck pain and
swelling, and CT imaging showed a 50% decrease in the
size of the mass. Two additional courses of steroids were
administered, with progressively decreasing mass size
and eventual resolution of symptoms (Figure 2).
Case 2
A 41-year-old male with a six-week history of enlarging
3 cm left parotid tail mass presented with neck swelling
1
Department of Head and Neck Surgery, MD Anderson Cancer Center, The
University of Texas Medical School at Houston, USA
2
Department of Pathology, MD Anderson Cancer Center, USA
3
Department of Diagnostic Radiology, MD Anderson Cancer Center, USA
4
Department of Head and Neck Surgery, MD Anderson Cancer Center, USA
Corresponding author:
Mark Zafereo, University of Texas, MD Anderson Cancer Center, 1515
Holcombe Blvd, Houston, TX 77030, USA.
Email: MZafereo@mdanderson.org
2 The Neuroradiology Journal 0(00)

Figure 1. A 46-year-old woman with inflammatory pseudotumor of the right level II neck. (a) Axial CT scan of the neck with contrast
reveals a 4 cm mass (arrow) as well as adjacent (b) abnormal shaped 26 mm lymph node with increase peripheral enhancement (arrow).
Surgical changes are noted superficially to this abnormal lymph node overlying the sternocleidomastoid muscle. (c) Ultrasound imaging
of the right level II neck mass (arrow) reveals a well-defined hypoechoic lesion. (d) Color Doppler flow imaging overlaid on the gray-scale
ultrasound image of the right level II mass (arrow) reveals increased flow to the mass. (e) FDG PET CT imaging displays significant
hypermetabolism of the mass (arrow). CT: computed tomography; FDG PET: 18-fluorodeoxyglucose positron-emission tomography.

Figure 2. A 46-year-old woman with inflammatory pseudotumor of the right level II neck. (a) Axial CT scan of the neck with contrast three
weeks after presentation shows no appreciable interval change in the right level II neck mass (arrow). (b) Repeat axial CT scan of the neck
with contrast four months following presentation and following a course of oral tapered corticosteroids reveals modest improvement in
size of the lesion (arrow). (c). Reassessment CT scan of the neck with contrast eight months from presentation and after a total of three
courses of oral tapered corticosteroids shows resolution of the right level II neck mass. CT: computed tomography.

and minimal tenderness that did not improve with
two weeks of Amoxicillin/clavulanic acid followed by
an additional 10 days of clindamycin. CT scan showed
a left level 1B multilobulated neck mass between
the parotid tail and submandibular gland that
extended supercially to the platysma muscle
(Figure 3(a) and (b)). Fine-needle aspiration (FNA)
and core needle biopsy illustrated acute and chronic
inammation with histiocytes, granulation tissue, and
fragments of skeletal muscle, but malignant cells were
absent. Excisional biopsy showed spindle cell prolifer-
ation with chronic lymphoplasmacytic inltration and
acute inammation, favoring an infectious or inam-
matory myobroblastic process. Flow cytometry and
immunohistochemical stains showed a polytypic
plasma and B-cell population without evidence of
lymphoma or IgG4 disease. Tissue cultures were
positive for Aggregatibacter actinomycetemcomitans.
CT scan 10 months post-excision showed no evidence
of disease (Figure 4).
Case 3
A 32-year-old female with no signicant past medical
history presented with left otalgia, jaw pain, and tris-
mus. She received several courses of antibiotics for
treatment of left otitis media. CT and magnetic reson-
ance imaging (MRI) revealed a 3 cm left parapharyn-
geal space mass extending to the adjacent nasopharynx
and skull base with left neck level Ib lymphadenopathy
(Figures 5 and 6). CT-guided biopsy of the mass sug-
gested bromuscular connective tissue with no evidence
of malignancy. FNA and core needle biopsies of
enlarged left neck lymphadenopathy revealed poly-
morphous lymphoid population consistent with
reactive lymph nodes. Endoscopic biopsies of the
Kansara et al. 3

Figure 3. A 41-year-old male with inflammatory pseudotumor of the left submandibular space. (a) Axial and (b) coronal CT scan of the
neck with contrast shows a 3 cm left submandibular mass (arrow) adjacent to the parotid tail with inflammatory stranding of the
surrounding soft tissues and thickening of the overlying platysma muscle. (c) Gray-scale ultrasound imaging of the mass (arrow) reveals
a well-defined, largely hypoechoic mass with (d) mildly increased flow (arrow) on overlaid color Doppler imaging. CT: computed
tomography.

Figure 4. A 41-year-old male with inflammatory pseudotumor of the left submandibular space. Baseline imaging (a) CT scan of the neck
with contrast reveals the left submandibular space mass and surrounding inflammatory changes (arrow). (b) Repeat CT scan of the neck
with contrast four months after surgical excision shows post-operative inflammatory changes with no evidence of residual tumor.
(c) Surveillance imaging approximately 22 months after presentation shows no evidence of disease. (d) Hematoxilin and eosin stain
showing dense fibrosis and inflammation adjacent to the salivary gland (e). Higher power illustrating germinal center formation.
CT: computed tomography.

nasopharynx, pterygoid musculature, pterygopalatine Immunohistochemical studies of these specimens

fossa, and left skull base revealed a broproliferative revealed negative CD20, CD3, CD30, CD68, lysozyme,
inammatory process with broblastic proliferation, k, and  stains, excluding the possibility of a hemato-
brous stroma, and scant lymphocytic inltrate. lymphoid neoplasm. The patient was prescribed
4 The Neuroradiology Journal 0(00)

Figure 5. A 32-year-old female with inflammatory pseudotumor of the left masticator space. Axial image (a) and coronal reformat (b) of
a CT scan of the neck with contrast displays a non-enhancing infiltrative mass (arrow) centered in the left masticator space with extension
along the Eustachian tube, ipsilateral longus coli muscle and skull base. ((c)(f)) Hematoxilin and eosin stain showing dense fibrotic
stroma with interspersed inflammatory infiltrate. CT: computed tomography.
Kansara et al. 5

Figure 6. A 32-year-old female with inflammatory pseudotumor of the left masticator space. Axial T1WI (a) and T2WI (b) of the left
masticator space at the level of the condyle of the mandible better delineates the abnormality seen in Figure 5 with isointense (T1) and
hypointense (T2) abnormality extending throughout the muscles of the masticator space (black arrows), along the Eustachian tube and
the left petrous bone and carotid space (white arrows). Axial (c) T1WI and (d) T2WI of the left skull base at the level of the internal auditory
canal shows the abnormality extends along the left sphenoid bone (black arrows) and the carotid space at the petrous apex (white arrow).
T1WI: T1-weighted imaging; T2WI: T2-weighted imaging.

a two-month course of tapered oral prednisone, where-
upon she had signicant improvement in pain and
trismus.
Discussion
IP is rare, and is often considered a diagnosis of exclu-
sion related to idiopathic inammation. Since patients
with IP generally present with clinical and radiological
features concerning for malignancy, the rst priority
is to establish a diagnosis. In Cases 1 and 3, incisional
biopsy was required for diagnostic purposes. Complete
excision would have resulted in signicant morbidity,
including resection of cranial nerves, major blood ves-
sels, and adjacent muscles. Diagnostic incisional biopsy
was followed by corticosteroids, which resulted in a
signicant clinical and radiographic response (Case 1).
In Case 2, the tumor was excised completely with min-
imal morbidity.
Within the spectrum of IP, there are a variety of
disease entities. IgG4 sclerosing disease is one such sub-
type that involves lymphocytes, IgG4-positive plasma
cells, and brosis. This has been reported in several sites
in the head and neck and has a favorable response to
corticosteroids if diagnosed early.4 Centers for Disease
Control (CDC) criteria for IgG4 disease requires: a
clinical exam showing localized swelling, blood studies
showing elevated serum IgG4, and histology showing
lymphocyte and plasmacyte inltration with IgG4 /
IgG cells > 40%.5 The patient in Case 1 displayed
localized tissue swelling and histopathologic exam
with lymphocytic inltrate, but an IgG4/IgG cell ratio
of only 20%. Although these ndings are not consistent
with the diagnosis of IgG4 disease, the patient did
respond to multiple courses of corticosteroids, which
is characteristic of IgG4 disease.
Other disease subtypes within the umbrella of IP
include benign tumors such as calcifying brous
tumors as well as inammatory myobroblastic tumor
(IMT). More aggressive and malignant tumors with
similar histopathologic features include IMT-like
de-dierentiated liposarcoma and EpsteinBarr virus
(EBV)-associated IP-like follicular dendritic cell
tumor. Numerous studies have attempted to character-
ize and prognosticate these IP subsets. Con et al.
showed that half of IMTs express cytoplasmic anaplas-
tic lymphoma kinase (ALK), a receptor tyrosine
kinase.6 All patients with metastatic IMTs were ALK
negative. Furthermore, nuclear expression of p53
occurred in 80% of IMTs, but only in 25% of the meta-
static subset. As a result, ALK and p53 expression may
predict a favorable prognosis. On the other hand, pres-
ence of ganglion-like cells, aneuploidy, and perinuclear
ALK expression portend a more aggressive course.7,8
Infection, trauma, and foreign bodies are among the
numerous etiologies that may be involved in the patho-
genesis of IP. Organisms such as mycobacteria,
Rhodococcus equi and Klebsiella rhinoscleromatis have
been shown to cause IPs.9,10 The tissue culture in Case 2
grew A. actinomycetemcomitans, an organism found in
periodontal disease. Case reports have demonstrated
this bacteria to occur in association with a mediastinal
mass imitating malignancy.11 Actinomyces, a closely
related species, has been implicated in submandibular
IP mimicking scrofula.12 These microbes incite inam-
mation, resulting in the characteristic pathology seen in
Case 2: spindle cell proliferation with chronic lympho-
cytoplasmic inltration along with atypical epithelioid
histiocytes (Figure 4(d) and (e)).
The most critical feature of IP on pathologic exam is
the presence of spindle cells, plasma cells, and lympho-
cytes.10 Fibroblasts, myobroblasts, histiocytes, and
inammatory inltrate may also be present.13 In a lit-
erature review of 84 cases of IPs, three basic patterns
were recognized: (a) myxoid, vascular, and inamma-
tory; (b) spindle cells with lymphocytes and plasma
cells; and (c) dense collagenous type resembling scar
tissue. However, as opposed to hematologic malig-
nancy, mitotic gures and necrosis are usually
absent.10 Pathology in Cases 1 and 3 showed densely
6 The Neuroradiology Journal 0(00)
sclerotic/brous tissue, whereas pathology in Case 2
showed the classic spindle cell proliferation with
chronic lymphoplasmacytic inltration and acute
inammation. Lymphocytic inltration, the seminal
feature of IP, was present in all of the cases.
Immunohistochemical exam of IP often reveals posi-
tive stains for cytokeratins, smooth muscle actin, ALK,
CD20, and an increased population of IgG4-positive
plasma cells.10 Immunostaining of Case 1 revealed
CD3, CD20, CD138, and IgG4, indicating cytes and plasma cells. In Case 1, the lymphoplasmocytic
mixed populations of polytypic B- and T-cells without
evidence for malignancy. Similar to Case 1, ow cyto-
metry and staining of tissue obtained in Case 2 revealed
a polytypic plasma and B-cell population without evi-
dence of lymphoma or increased plasmacytic dendritic
cells. Immunohistochemical studies of the mass in
Case 3 showed negative CD20, CD3, CD30, CD68,
lysozyme, k, and  stains, excluding hematological
neoplasm. The absence of CD3 and CD20 staining in
Case 3 underlines the scarcity of B- and T-cell popula-
tions within the mass, which was composed mostly of
brous stroma and collagenous material (Figure 5(c)
and (d)).
IP is nonspecic on imaging and presents as an inl-
trative soft tissue mass, which can be mistaken for a
variety of disease processes. Plain radiographs can dis-
play regional changes including hyperostosis or bony
erosion, suggesting a destructive process. The lesions
on ultrasound are variable and may display decreased
echogenicity (as in this case), or even increased echo-
genicity. Doppler ultrasound can display patterns of
hyper-vascularity (as seen in Figures 1(d) and 3(d)).10
CT ndings are nonspecic, and can be seen as homo-
geneous (Figure 3(a)) or heterogeneous (Figure 2(a)), as
well as variable densities compared to the surrounding
skeletal muscle. The lesions are typically seen as T1
and T2 hypointense on MR imaging (Figure 6).
T1-weighted imaging following gadolinium contrast
typically reveals marked enhancement.
Orbital IPs present with fat inltration, edema, and
bone remodeling.14 Sinonasal IPs can be more aggres-
sive; bony erosion and subsequent remodeling and
hyperostosis are often present. Temporal bone IPs pre-
sent with destruction of the mastoid but sparing of the
inner ear and ossicles, which helps to rule out a malig-
nant process. Dural thickening, enhancement, or calci-
cation may be visualized.15 Neck soft tissue and
parapharyngeal IPs (as seen in Case 1 and 3, respect-
ively) are exceedingly rare and have not been well
described. Pathologic lymph nodes, when they occur
(see Case 1), present with homogeneous attenuation
and enhancement on CT. T2-weighted MRI can show
hypointense lymph node involvement.16 Alternative
modalities such as FDG-PET have been implemented
with some success. Fujita et al. conrm that increased
FDG uptake is demonstrated during active disease,
with remission following corticosteroid therapy (see
Case 1, Figure 1(e)).16
IP treatment includes corticosteroids, surgical resec-
tion, or both. Approximately 80% of IPs respond to
corticosteroid treatment but there is a 50 to 60%
chance of disease recurrence. Maintenance-dose cortico-
steroids are recommended for at least six months to pre-
vent recurrence of disease.17 Patients unresponsive to
systemic corticosteroids may benet from intralesional
steroids.18 A favorable response with corticosteroids is
seen especially in IPs that are predominated by lympho-
predominant mass responded to corticosteroids.
Resection should be considered when alternative nonin-
vasive treatments have failed; if the diagnosis cannot by
established by FNA and core biopsy alone; or if the mass
can be resected with minimal morbidity. In Case 2, sur-
gical resection was necessary because of lack of denitive
diagnosis. Recurrence of head and neck IPs after
attempts at surgical excision approaches 10 to 20%.10
Alternative treatments include radiotherapy, small-
molecule inhibitors, and Igs. In a clinical trial involving
orbital pseudotumors, 75% of patients responded to
radiotherapy treatment.19 It is not known if the same
response would be seen in extraorbital IP cases. Small-
molecule inhibitors have shown results in small subsets
of patients. For example, rituximab is a chimeric anti-
CD20 antibody that provoked a sustained response in a
recurrent IP of the mandible.20 Crizotinib, an ALK
inhibitor, induced a partial response in a patient with
ALK-translocated inammatory myobroblastic
tumor.21
Conclusion
In conclusion, three cases of extraorbital IPs in the
head and neck are described. IPs of the head and
neck mimic malignancy in clinical and radiographic
presentation and must be distinguished from malig-
nancy by comprehensive histopathologic evaluation.
Incisional or excisional biopsy is often required to
establish the diagnosis and rule out malignancy.
Tumors that can be completely excised without long-
term morbidity may be treated with complete surgical
excision. Tumors for which complete resection would
result in morbidity may be treated more conservatively
with corticosteroids and close follow-up.
Acknowledgment
Informed consent was obtained from each of the three indi-
viduals in this case series.
Funding
This research received no specic grant from any funding
agency in the public, commercial, or not-for-prot sectors.
Conflict of interest
The authors declared no potential conicts of interest with
respect to the research, authorship, and/or publication of this
article.
Kansara et al.
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