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Diagnostic challenge in Inflammatory Myofibroblastic Tumor: Case Report
T. Tefera
Department of Oral and maxillofacial surgery, Yekatit 12 Hospital Medical college,
Corespondence to: Dr. Tewodros Tefera, Email: [email protected]
Inflammatory myofibroblastic tumor (IMT) is a rarely described tumor of unknown etiology and
pathogenesis. It occurs primarily in the lungs, but has occurred in other extra-pulmonary sites.
Histologically these lesions appear as an inflammatory infiltrate within a variably myofibrotic background.
Current evidence shows that inflammatory myofibroblastic tumors are neoplastic processes resulting from
chromosomal translocations that often cause an overexpression of ALK kinase, which is often assessed
using immunohistochemical studies. Currently, the biological behavior of oral inflammatory
myofibroblastic tumor is still uncertain. This article describes the clinical, histological, and operative
features of a case of IMT of the Mandible. I report such a case of inflammatory myofibroblastic tumor of
the mandible in a 16-year-old girl. The patient presented with a large aggressive ulcerative soft tissue
mass of 3 year duration in the rigth mandibular molar gingiva. Histologically, section show; loosely
arranged myofibroblasts in an edematous and myxoid background with plasma cells, lymphocytes,
eosinophils, and blood vessels and overlined by ulcerative skin, no necrosis or mitosis.
Immunohistochemically, the fibroblastic or myofibroblastic spindle cells were positive for vimentin, smooth muscle actin, and Ki-67 (MIB-1) but negative for desmin, pan-cytokeratin, S-100 protein, CD34,
CD68, CD99, bcl-2, -catenin, estrogen receptor, progesterone receptor. These spindle cells were focally
and weakly Ki-67- (MIB-1-) positive. A pathological diagnosis of inflammatory myofibroblastic tumor was
made. The postoperative course was uneventful, and the patient has had no recurrence in the 1 year
follow-up period. Although no evidence of oral inflammatory myofibroblastic tumor recurrence or
malignant transformation has been reported, it has been observed that in inflammatory myofibroblastic
tumors of other regions, a prolonged follow-up is necessary after surgical resection.
Introduction
Inflammatory myofibroblastic tumor (IMT) is a rare entity included in a heterogeneous group of spindle cell
proliferations, which encompasses a broad phenotypic and biologic spectrum of diseases ranging from
reactive lesions to benign neoplasms1. It was first observed in the lung and described by Brunn in 1939 and
was so named by Umiker in 1954 because of its clinical and radiological behavior that mimics a malignant
process2. The most common sites of involvement include the lung, liver and orbit, but it has been reported
to occur in nearly every site of the body, including the major salivary glands and the oral cavity2, 3. It was
called inflammatory pseudotumor (IPT) until 1998 when the term inflammatory myofibroblastic tumor (IMT)
was proposed as being a more descriptive name1. The terms inflammatory pseudotumor and
inflammatory myofibroblastic tumor were used synonymously in most publications, all 22 cases diagnosed
in the English literature as IPT or IMT (Based on criteria followed by Brooks et al. 2004). The most common
intraoral site observed was the buccal mucosa, with lesions occurring over a wide age range 2 to 82 years
with a mean of 32 years and showing a 1.6:1 female predilection. The lesion typically presents as a firm,
indurated swelling and does not produce significant systemic symptoms, unlike its counterpart in visceral
organs4.5. Intrabony presentation of IMT is rare. Only three cases have been reported[6-8] .
The purpose of this study is primarily to present a case of IMT in the mandible, describing its clinical aspect,
immunophenotype and management, showing for the first time myofibroblastic fibronectin expression
contributing to the knowledge and characterization of this entity. Treatment of IMT should entail complete
surgical resection4,12 and since IMT may present a low-grade malignancy, longer follow-up is needed13.
Extrapulmonary IMTs seem to exhibit a more favorable clinical course and treatment outcome, evolving with
lower rates of recurrence, malignant transformation, metastasis, and mortality.
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Case report
A 16-year-old woman presented for evaluation of a painless swelling with a three-year history of progressive
growing on the right side of the mandible (Figure 1). Her medical and surgical histories were unremarkable,
and she denied any previous lesions or local trauma. Intraoral examination revealed a 10 cm reddish
exophytic mass extending to the oropharynx pushing the tongue laterally, with a rubbery consistency,
attached to the mucosa (Figure 2). The overlying mucosa presented ulcerated areas with no discharge. On
the basis of the clinical findings, glandular neoplasm, non-neoplastic proliferative process or malignant
tumour were considered as differential diagnosis. Imaging studies were performed Plain film radiography of
the postero-anterior view of mandible revealed destruction of the right mandible and one impacted molar
tooth on the right proximal part of the ascending ramus (Figure 3).
An incisional biopsy was performed and, microscopic examination revealed an ulcerated nodular mass
composed of proliferating spindle cells in a predominantly myxoid stroma admixed with a variable amount of
acute and chronic inflammatory cells along with a rich vascular network (Figure 5). Towards the periphery,
the lesion was more cellular with a focal fascicular arrangement of the spindle cells. In all fields, an
inflammatory component was prominent and was formed mainly by neutrophil and lymphocytes with a few
plasma cells, histiocytes and eosinophils. The spindle cells exhibited plump tapering vesicular nuclei and
were haphazardly arranged. Non-cohesive larger stellate or polygonal cells with ovoid vesicular nuclei and
prominent nucleoli were scattered. Nuclear atypia and mitosis were not evident.
In addition, immunohistochemistry was performed with proliferating spindle cells showing intense and
diffuse positivity for vimentin (M0725, DakoCytomation, Carpinteria, CA, USA), smooth muscle actin
(SMA;M0851, DakoCytomation) and muscle specific actin (HHF-35; M0635, DakoCytomation) . The
immunostaining for desmin, however, was negative as were also negative reactions to AE1/AE3 (M3515,
DakoCytomation), S-100 (Z311, DakoCytomation), CD68 (M0814, DakoCytomation), MyoD1 (M3512,
DakoCytomation), and caldesmon (M3557, DakoCytomation). In an attempt to delineate the potential
neoplastic nature of this lesion, we assessed the immunohistochemical expression of ALK protein (M7195,
DakoCytomation), although none reactivity was found. A diagnosis of IMT was established. Furthermore,
fibronectin (A0245, DakoCytomation) immunostaining was performed, showing strong positivity in spindle
cells, corroborating with a myofibroblastic phenotype.
On surgical procedure Prophylactic tracheotomy done for intubation as well as for post operative air way
management and all aseptic precautions, tumor mass was exposed externally. After extraction of left lower
first premolar, osteotomy cut was placed and completed lingually and buccally and right side
hemimandibuloectomy with disarticulation done.
The tumor mass was removed along with bone margin of 1.5 cm (Figures 4 and 6). Hemostasis was achieved,
vacuum drain was secured and closure was done in layers. Antibiotics, analgesics and anti-inflammatory
drugs were given postoperatively
The wounds healed unevenly and sutures were removed on 7th postoperative day. Patient has been kept
under periodic follow up since then. No recurrence had been reported by the time of presenting this article.
The patient was satisfied with her quality of life and remained disease free the time of her last follow-up,
1 year after surgery (Figure 7).

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Figure 1. Clinical View of the Mandible Showing

Right side laterally Expanded Round Mass.

Figure 3. PA View of Mandible Showing Gross

Destruction of Right Body and Ramus of the
Mandible with Flecks of Bone within the Lesion
and One Impacted Molar Tooth at the Proximal
Part of Ascending Ramus (Arrow).

Figure 2. Shows the Intra Oral view with the

Tongue Pushed Laterally by the Mass

Figure 4. Trans-operative Aspect of the

Inflammatory Myofibroblastic Tumor during
Surgical Excision

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A

Figure 5. Photomicrographs of Inflammatory myofibroblastic tumor. A: Spindle Tumor Cells Scattered in a

Loosely and Myxoid Background with Inflammatory Proliferation; in detail, myofibroblasts and eosinophils
(hematoxylin and eosin stain). B: Immunohistochemical Staining of SMA in Spindled Myofibroblasts.

Figure 6. Excised Tumor with Size of 14 cm

Anteriopostherioly and 16 cm Superioinferiorly

Figure 7. Postoperative Appearance with Minimal

Facial Disfigurement

Discussion
Oral IMT is a very rare lesion which along with its nonspecific clinical appearance may pose difficulties to
diagnosis and management. Its rapid growth rate may simulate a malignant disorder and therefore warrants
a comprehensive histopathological assessment12. Originally reported in the lung, extra-pulmonary IMTs have
been described1, including head and neck region4 mainly in the aerodigestive tract, major salivary glands and
soft tissues of the neck1,14,15. A limited number of patients with oral IMT have been reported12, thus
contributing with the unspecified pattern of clinical aspects and clues to diagnosis. In the oral mucosa, the
most reported sites of occurrence are submandibular region16, parotid duct14, retromolar area17, alveolar
mucosa of the molar region12, tongue13, maxilla14 and the hard palate4. Typically, oral IMTs have been
described as a well circumscribed, solitary nodule or mass, frequently pedunculated, and rubbery
consistency, as the present one, have been reported14. The etiology of most oral IMTs remains controversial.
Some authors widely consider it a benign neoplastic lesion4, and others support a reactive etiology17, since
the rapid growth and subsequent indolent behavior of most oral IMT are similar to that of many common
reactive oral lesions12.

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Differently, in other sites, this condition can behave in a more aggressive or even malignant way13,
constituting a true neoplastic process due to the potential for local recurrence, development of multifocal
tumors, infiltrative local growth, and even distant metastasis6. Histologically, various aspects can be seen. In
the current case one of the patterns was observed; loosely arranged myofibroblasts in an edematous and
myxoid background with plasma cells, lymphocytes, eosinophils, and blood vessels12,17. A second
configuration that can occur is distinguished by the presence of dense aggregates of spindle cells arranged in
a variable myxoid or collagenized background, admixed with a distinctive inflammatory infiltrate18. Finally, a
third pattern of IMT is characterized by prominent collagen sheets, resembling scar tissue, with scattered
plasma cells and eosinophils12. Cytological atypia with nuclear pleomorphism and increased mitotic activity
are uncommon features4,12, and may be associated with malignant transformation12. Immunoprofile is
helpful in the establishment of the diagnosis of IMT especially by the identification of myofibroblasts. The
myofibroblast is becoming recognized as a target for translational medicine, since it appears as a significant
cellular participant in granulation tissue and several other human diseases12. Previously, the characterization
of the fully differentiated myofibroblast immunophenotype included positivity to vimentin and -smoothmuscle actin, and negativity to smoothmuscle myosin and usually desmin11. However, a spindle cell positive
to SMA is an imprecise definition for the myofibroblast since a number of normal cells also express it19.
In addition, lesions first regarded as myofibroblastic are shown to vary in their level of differentiation, and
some appear to be smooth-muscle rather than myofibroblastic10. Desmin negativity rather than positivity
should be seen as a more appropriate indicator of myofibroblastic differentiation19. Finally, as recently
suggested, the main characteristics of the myofibroblast include a spindled or stellate morphology,
immunostaining for alpha-smooth-muscle actin and the extra domain A variant of cellular fibronectin, and an
ultrastructure of rough endoplasmic reticulum, peripheral contractile filaments and the cell-to-matrix
junction known as the fibronexus, being important for maximum diagnostic confidence in some
myofibroblastic lesions10.
The immunophenotype of the IMT presented herein is in accordance with the identification of a
myofibroblast 10,19 and also by other IMT reports12,18 with strong diffuse cytoplasmic reactivity to vimentin,
SMA and HHF-35 in a focal or diffuse pattern and also negativity to desmin, although the latest could be
identified in many cases, as well as focal cytokeratin immunoreactivity20. Myogenin, myoglobin, and S-100
protein are also negative1 as were in the present case. Furthermore, we believe that more investigations on
tumor behavior should take into account the fibronectin immunoprofile, since it is known that this protein
shows properties that could precipitate a cascade leading to a number of cellular activities, such as
differentiation, migration, mitosis all important to tumor progression19. Recently, this marker has been
associated to the invasive phenotype of oral carcinoma cell lines, although the authors could not establish if
the presence of its expression is an associated phenomena or a causative agent in the invasive process9.
Immunohistochemical cytoplasmic positivity for ALK (Anaplastic lymphoma kinase) is linked to neoplastic
transformation since it provides strong evidence for an oncogenic activating mechanism12. Thus, at least a
proportion of IMTs presenting ALK genetic alterations are genuine neoplasms20. However, ALK expression
has been detected in approximately 50% of IMTs, and therefore shows not to be a specific marker for this
lesion1,20. The present case did not demonstrate immunoreactivity for ALK, as shown by most of the oral
cases reported in the literature with only a few reports of oral IMT ALK-positive 12,18. Whether ALK-positive
IMTs represent distinct clinicopathological entities, with different therapeutic and prognostic implications,
warrants further investigation18 in order to clarify the contribution of ALK deregulation to the pathogenesis
of oral IMT12. In addition to the controversy regarding the biologic nature of IMT, proliferating spindle cells
may mimic a sarcoma, potentially leading to a diagnostic dilemma18.
Various benign and malignant spindle cell proliferations should be included in the differential histological
diagnosis scheme of oral IMT such as proliferative fasciitis, nodular fasciitis, infantile fibromatosis,
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myofibromatosis, Rosai-Dorfman disease, fibrous histiocytoma, solitary fibrous tumor, follicular dendritic cell
tumor, low-grade myofibroblastic sarcoma, fibrosarcoma, leiomyosarcoma, rhabdomyosarcoma, and spindle
cell carcinoma9,17. So, the knowledge of the different histological patterns of IMT, identification of a
predominant inflammatory component and immunohistochemical study allow distinction between these
entities, being helpful to the accurate diagnosis12, as emphasized by the present report, and also preventing
a more aggressive surgical procedure. Management of IMT should entail complete surgical resection4,12, and
since IMT may present a low-grade malignancy, longer follow-up is need13. Extrapulmonary IMTs seem to
exhibit a more favorable clinical course and treatment outcome, evolving with lower rates of recurrence,
malignant transformation, metastasis, and mortality12. One noteworthy feature is that oral IMT seems to
behave differently from IMT occurring elsewhere in body13, displaying variable local recurrence and not
reported metastasis4. There may be a need to recognize it as a separate entity. The diversity of IMTs
microscopic appearance and the lack of correlation between these variables and the clinical evolution of
these tumors to date, encourage further research on biomarkers, such as fibronectin, that might provide
guidelines to tumor progression, treatment and prognosis.
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