Professional Documents
Culture Documents
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
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 CT scan 10 months post-excision showed no evidence
two weeks of Amoxicillin/clavulanic acid followed by of disease (Figure 4).
an additional 10 days of clindamycin. CT scan showed
a left level 1B multilobulated neck mass between
Case 3
the parotid tail and submandibular gland that
extended supercially to the platysma muscle A 32-year-old female with no signicant past medical
(Figure 3(a) and (b)). Fine-needle aspiration (FNA) history presented with left otalgia, jaw pain, and tris-
and core needle biopsy illustrated acute and chronic mus. She received several courses of antibiotics for
inammation with histiocytes, granulation tissue, and treatment of left otitis media. CT and magnetic reson-
fragments of skeletal muscle, but malignant cells were ance imaging (MRI) revealed a 3 cm left parapharyn-
absent. Excisional biopsy showed spindle cell prolifer- geal space mass extending to the adjacent nasopharynx
ation with chronic lymphoplasmacytic inltration and and skull base with left neck level Ib lymphadenopathy
acute inammation, favoring an infectious or inam- (Figures 5 and 6). CT-guided biopsy of the mass sug-
matory myobroblastic process. Flow cytometry and gested bromuscular connective tissue with no evidence
immunohistochemical stains showed a polytypic of malignancy. FNA and core needle biopsies of
plasma and B-cell population without evidence of enlarged left neck lymphadenopathy revealed poly-
lymphoma or IgG4 disease. Tissue cultures were morphous lymphoid population consistent with
positive for Aggregatibacter actinomycetemcomitans. 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.
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- similar histopathologic features include IMT-like
upon she had signicant improvement in pain and de-dierentiated liposarcoma and EpsteinBarr virus
trismus. (EBV)-associated IP-like follicular dendritic cell
tumor. Numerous studies have attempted to character-
ize and prognosticate these IP subsets. Con et al.
Discussion showed that half of IMTs express cytoplasmic anaplas-
IP is rare, and is often considered a diagnosis of exclu- tic lymphoma kinase (ALK), a receptor tyrosine
sion related to idiopathic inammation. Since patients kinase.6 All patients with metastatic IMTs were ALK
with IP generally present with clinical and radiological negative. Furthermore, nuclear expression of p53
features concerning for malignancy, the rst priority occurred in 80% of IMTs, but only in 25% of the meta-
is to establish a diagnosis. In Cases 1 and 3, incisional static subset. As a result, ALK and p53 expression may
biopsy was required for diagnostic purposes. Complete predict a favorable prognosis. On the other hand, pres-
excision would have resulted in signicant morbidity, ence of ganglion-like cells, aneuploidy, and perinuclear
including resection of cranial nerves, major blood ves- ALK expression portend a more aggressive course.7,8
sels, and adjacent muscles. Diagnostic incisional biopsy Infection, trauma, and foreign bodies are among the
was followed by corticosteroids, which resulted in a numerous etiologies that may be involved in the patho-
signicant clinical and radiographic response (Case 1). genesis of IP. Organisms such as mycobacteria,
In Case 2, the tumor was excised completely with min- Rhodococcus equi and Klebsiella rhinoscleromatis have
imal morbidity. been shown to cause IPs.9,10 The tissue culture in Case 2
Within the spectrum of IP, there are a variety of grew A. actinomycetemcomitans, an organism found in
disease entities. IgG4 sclerosing disease is one such sub- periodontal disease. Case reports have demonstrated
type that involves lymphocytes, IgG4-positive plasma this bacteria to occur in association with a mediastinal
cells, and brosis. This has been reported in several sites mass imitating malignancy.11 Actinomyces, a closely
in the head and neck and has a favorable response to related species, has been implicated in submandibular
corticosteroids if diagnosed early.4 Centers for Disease IP mimicking scrofula.12 These microbes incite inam-
Control (CDC) criteria for IgG4 disease requires: a mation, resulting in the characteristic pathology seen in
clinical exam showing localized swelling, blood studies Case 2: spindle cell proliferation with chronic lympho-
showing elevated serum IgG4, and histology showing cytoplasmic inltration along with atypical epithelioid
lymphocyte and plasmacyte inltration with IgG4 / histiocytes (Figure 4(d) and (e)).
IgG cells > 40%.5 The patient in Case 1 displayed The most critical feature of IP on pathologic exam is
localized tissue swelling and histopathologic exam the presence of spindle cells, plasma cells, and lympho-
with lymphocytic inltrate, but an IgG4/IgG cell ratio cytes.10 Fibroblasts, myobroblasts, histiocytes, and
of only 20%. Although these ndings are not consistent inammatory inltrate may also be present.13 In a lit-
with the diagnosis of IgG4 disease, the patient did erature review of 84 cases of IPs, three basic patterns
respond to multiple courses of corticosteroids, which were recognized: (a) myxoid, vascular, and inamma-
is characteristic of IgG4 disease. tory; (b) spindle cells with lymphocytes and plasma
Other disease subtypes within the umbrella of IP cells; and (c) dense collagenous type resembling scar
include benign tumors such as calcifying brous tissue. However, as opposed to hematologic malig-
tumors as well as inammatory myobroblastic tumor nancy, mitotic gures and necrosis are usually
(IMT). More aggressive and malignant tumors with absent.10 Pathology in Cases 1 and 3 showed densely
6 The Neuroradiology Journal 0(00)
sclerotic/brous tissue, whereas pathology in Case 2 IP treatment includes corticosteroids, surgical resec-
showed the classic spindle cell proliferation with tion, or both. Approximately 80% of IPs respond to
chronic lymphoplasmacytic inltration and acute corticosteroid treatment but there is a 50 to 60%
inammation. Lymphocytic inltration, the seminal chance of disease recurrence. Maintenance-dose cortico-
feature of IP, was present in all of the cases. steroids are recommended for at least six months to pre-
Immunohistochemical exam of IP often reveals posi- vent recurrence of disease.17 Patients unresponsive to
tive stains for cytokeratins, smooth muscle actin, ALK, systemic corticosteroids may benet from intralesional
CD20, and an increased population of IgG4-positive steroids.18 A favorable response with corticosteroids is
plasma cells.10 Immunostaining of Case 1 revealed seen especially in IPs that are predominated by lympho-
CD3, CD20, CD138, and IgG4, indicating cytes and plasma cells. In Case 1, the lymphoplasmocytic
mixed populations of polytypic B- and T-cells without predominant mass responded to corticosteroids.
evidence for malignancy. Similar to Case 1, ow cyto- Resection should be considered when alternative nonin-
metry and staining of tissue obtained in Case 2 revealed vasive treatments have failed; if the diagnosis cannot by
a polytypic plasma and B-cell population without evi- established by FNA and core biopsy alone; or if the mass
dence of lymphoma or increased plasmacytic dendritic can be resected with minimal morbidity. In Case 2, sur-
cells. Immunohistochemical studies of the mass in gical resection was necessary because of lack of denitive
Case 3 showed negative CD20, CD3, CD30, CD68, diagnosis. Recurrence of head and neck IPs after
lysozyme, k, and stains, excluding hematological attempts at surgical excision approaches 10 to 20%.10
neoplasm. The absence of CD3 and CD20 staining in Alternative treatments include radiotherapy, small-
Case 3 underlines the scarcity of B- and T-cell popula- molecule inhibitors, and Igs. In a clinical trial involving
tions within the mass, which was composed mostly of orbital pseudotumors, 75% of patients responded to
brous stroma and collagenous material (Figure 5(c) radiotherapy treatment.19 It is not known if the same
and (d)). response would be seen in extraorbital IP cases. Small-
IP is nonspecic on imaging and presents as an inl- molecule inhibitors have shown results in small subsets
trative soft tissue mass, which can be mistaken for a of patients. For example, rituximab is a chimeric anti-
variety of disease processes. Plain radiographs can dis- CD20 antibody that provoked a sustained response in a
play regional changes including hyperostosis or bony recurrent IP of the mandible.20 Crizotinib, an ALK
erosion, suggesting a destructive process. The lesions inhibitor, induced a partial response in a patient with
on ultrasound are variable and may display decreased ALK-translocated inammatory myobroblastic
echogenicity (as in this case), or even increased echo- tumor.21
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-
Conclusion
geneous (Figure 3(a)) or heterogeneous (Figure 2(a)), as In conclusion, three cases of extraorbital IPs in the
well as variable densities compared to the surrounding head and neck are described. IPs of the head and
skeletal muscle. The lesions are typically seen as T1 neck mimic malignancy in clinical and radiographic
and T2 hypointense on MR imaging (Figure 6). presentation and must be distinguished from malig-
T1-weighted imaging following gadolinium contrast nancy by comprehensive histopathologic evaluation.
typically reveals marked enhancement. Incisional or excisional biopsy is often required to
Orbital IPs present with fat inltration, edema, and establish the diagnosis and rule out malignancy.
bone remodeling.14 Sinonasal IPs can be more aggres- Tumors that can be completely excised without long-
sive; bony erosion and subsequent remodeling and term morbidity may be treated with complete surgical
hyperostosis are often present. Temporal bone IPs pre- excision. Tumors for which complete resection would
sent with destruction of the mastoid but sparing of the result in morbidity may be treated more conservatively
inner ear and ossicles, which helps to rule out a malig- with corticosteroids and close follow-up.
nant process. Dural thickening, enhancement, or calci-
cation may be visualized.15 Neck soft tissue and Acknowledgment
parapharyngeal IPs (as seen in Case 1 and 3, respect- Informed consent was obtained from each of the three indi-
ively) are exceedingly rare and have not been well viduals in this case series.
described. Pathologic lymph nodes, when they occur
(see Case 1), present with homogeneous attenuation Funding
and enhancement on CT. T2-weighted MRI can show This research received no specic grant from any funding
hypointense lymph node involvement.16 Alternative agency in the public, commercial, or not-for-prot sectors.
modalities such as FDG-PET have been implemented
with some success. Fujita et al. conrm that increased Conflict of interest
FDG uptake is demonstrated during active disease, The authors declared no potential conicts of interest with
with remission following corticosteroid therapy (see respect to the research, authorship, and/or publication of this
Case 1, Figure 1(e)).16 article.
Kansara et al. 7