Inflammatory Myofibroblastic Tumour of the Sinonasal Tract with Orbital and Intracranial Extensions Simulating a Malignancy: A Case Report and Review of Literature

Abstract

Inflammatory Myofibroblastic Tumour (IMT) is a rare pathology of unknown etiology. It is pathologically benign, but clinically locally invasive. We are herewith reporting a unique case of rapidly growing sinonasal IMT with orbital and intracranial extensions in a middle aged female patient masquerading as a malignancy. The lesion was excised endoscopically with margins and the patient is presently under close follow up. The report also reviews the common sites of involvement and management options available, based on a literature review.

Introduction

IMT, also called as inflammatory pseudotumour and plasma cell granuloma is a benign lesion mimicking malignancy clinically and radiologically [1]. It is a rare neoplasm that occurs preferentially in children and young adults [2]. Head and neck sites are the least common with around 23 cases reported so far, out of which 18 cases involved maxillary sinus and 5 affected the nasal cavity [3]. This case had a rare involvement of ethmoid sinus as the primary site of origin with intra orbital (extra conal) and intra-cranial (extra dural) involvement. Due to sparse availability of literature, the management of this rare tumour is not standardized. This report discusses the presentation, management options and anticipated outcomes based on literature review.

Case Report

A 40-year-old female patient presented to our otolaryngology department with 1 year history of left nasal obstruction associated with a mass and a gradually progressive swelling of the left cheek. Patient gradually developed hyposmia in left nasal cavity. She also complained of lacrimation and swelling of left eye since 6 months. There was no history of epistaxis, headache, vomiting, fever, decreased vision, diplopia or neck mass. General physical and systemic examinations were normal with notable absence of lymphadenopathy. All cranial nerves were intact except that hyposmia was noted. On examination, there was distorted external appearance of dorsum of the nose on the left side with swelling extending to left cheek and obliteration of left nasolabial fold (Fig. 1a) Sensation over the area was preserved. Anterior rhinoscopic examination revealed a fleshy smooth mass protruding out of the left nasal cavity which could be probed all around anteriorly and bled on touch (Fig. 1b). A deviated nasal septum (DNS) to the right was seen. On 0⁰ nasal endoscopy, the scope could not be passed into the left nasal cavity. Gross DNS to right was seen due to the mass. Right choanae and nasopharynx were mass-free. Mild proptosis with downward and lateral displacement of left eyeball along with elevation deficit was seen (Fig. 1c). Both pupils were round, regular and reacting to light, visual acuity being normal with no signs of papilledema on fundoscopy. Mouth opening was adequate and no palatal bulge was seen in the oral cavity.

Fig. 1.

a Distorted external appearance of dorsum of the nose on the left side with swelling extending to left cheek and obliteration of left nasolabial fold. b A fleshy smooth mass protruding out of the left nasal cavity. c Mild proptosis seen in left eye

Lab investigations revealed a normal ESR and CBC. Cytoplasmic antineutrophil cytoplasmic antibody (cANCA), perinuclear antineutrophil cytoplasmic antibody (pANCA), Treponema pallidum particle agglutination test and the Mantoux test were negative.

CECT (face and brain) showed a heterogenous and expansile soft tissue mass occluding the left nasal cavity, filling it and extending into left ethmoid sinuses, frontal sinus region, left orbit and left frontal lobe. The nasal septum (posteriorly), medial wall of left maxillary antrum and lamina papyracea of left orbit had been eroded by the mass (Fig. 2a).

Fig. 2.

a CECT(Brain and face) A heterogenous and expansile soft tissue mass occluding the left nasal cavity, filling it and extending into left ethmoid sinuses, frontal sinus region, left orbit and left frontal lobe. Left lamina papyracea seen eroded. b CEMRI (Brain and face) A lobulated moderately enhancing T1 hypointense, T2/TIRM heterogenous lesion centred over left nasal cavity causing its expansion and extending posteriorly till choanae involving left ethmoid sinuses, left frontal sinus and bulging into left maxillary sinus. The lesion shows extraconal extension into left orbit abutting superior and medial recti muscles. The lesion erodes frontal bone and cribriform plate showing intracranial extradural extension into left frontal lobe

CEMRI (face and brain) showed a lobulated moderately enhancing T1 hypointense, T2/TIRM heterogenous lesion centred over left nasal cavity causing its expansion and extending posteriorly till choanae involving left ethmoid sinuses, left frontal sinus and bulging into left maxillary sinus with blockage of osteomeatal complex (OMC). T2W hyperintense mucoasal thickening and mucous retention was seen in left maxillary, frontal and sphenoid sinuses. The lesion showed extraconal extension into left orbit abutting superior and medial recti muscles. The lesion eroded frontal bone and cribriform plate showing intracranial extradural extension into left frontal lobe. No parenchymal invasion was seen in frontal bone. Bilateral optic nerves were normal. No extension into sphenoid sinuses, sellar, suprasellar or cavernous sinus was noted (Fig. 2b).

Biopsy was taken under local anaesthesia and sent for histopatholological examination (HPE) which showed mild dysplasia of squamous epithelium. Lymphoid follicles (plasma cells mixed with lymphocytes) with scattered eosinophils and myofibroblasts were seen. No mitotic activity or cellular atypia was present (Fig. 3a, b, c). On immunohistochemistry (IHC), tumour cells showed positivity for Smooth Muscle Actin (SMA) and vimentin and were negative for ALK-1, S-100, MyoD1, EMA, PAN-CK and desmin—suggestive of IMT.

Fig. 3.

a Myofibroblasts (black circle), Scattered Eosinophils (yellow circle). b Underlying fibrocollagenous stroma with dense lymphocytic infiltration (arrows). c Lymphoid follicle (circle) showing lymphocytes mixed with plasma cells

The patient’s case was discussed in a multidisciplinary team meeting involving E.N.T, Radiology, Pathology and Neurosurgery services.

The patient underwent surgical debridement endoscopically under general anaesthesia. A solid gritty mass found in left nasal cavity was removed with debrider. Choanae and nasopharynx were tumour free. Maxillary antrum was visualised after widening and was found to be tumour free. Posterior part of nasal septum was found to be eroded. Tumour mass that was adherent to left periorbita was removed with periorbital margin. Orbital fat prolapsed into left nasal cavity and was tumour free (Fig. 4a). Frontal beak drilling was done, posterior table of frontal sinus and cribriform area were found to be eroded (Fig. 4b). Right frontal sinus, bilateral maxillary sinuses and bilateral sphenoid sinuses were tumour free. DRAF 2b frontal sinusotomy was done and trans septal (inter-sinus septum) entry to opposite frontal sinus was performed. The posterior table of frontal sinus was eroded, which was drilled and rendered tumor free and repaired with a multilayered technique using fascia lata graft, fat, surgicel and fibrin glue (Fig. 4c).

Fig. 4.

a Orbital fat prolapsed into left nasal cavity (arrow). b Posterior table of frontal sinus eroded with exposed intact dura seen (arrow). c Posterior table of frontal sinus (dural plate defects) repaired with fascia lata graft (green arrow), fat (blue arrow), surgicel (black arrow) and prolapsed orbital fat repaired with surgicel (yellow arrow)

CEMRI (Brain and Face) was done on post operative day 7. Left OMC appeared widened with a post operative cavity. Upper part of nasal septum was not visualized. Left inferior and medial recti appeared hyperintense on T2W. Mild fat strands were seen in left orbit likely to be post operative changes. Bilateral optic nerves were normal. No residual mass was seen (Fig. 5).

Fig. 5.

CEMRI (post op): Left OMC appeared widened with a post operative cavity. Upper part of nasal septum not visualized. Left inferior and medial recti appeared hyperintense on T2W. Mild fat strands seen in left orbit likely to be post operative changes. Bilateral optic nerves normal. No residual mass seen

The patient had an uneventful postoperative period and has been followed up without any recurrence till date.

Discussion

According to World Health Organisation (WHO) classification, IMT is an intermediate tumour that primarily occurs in children and young adults [4] but in our case it was a middle aged female patient. The overall prevalence of IMT is 0.04–0.7% [5]. IMT arising from the nasal cavity with orbital and intracranial extensions is exceedingly rare. Although imaging and endoscopic examinations play an important role in the diagnosis of IMT, histolopathogy is the gold standard [6, 7]. Variable degree of spindle cell proliferation with a background of myxoid/collagenous stroma and significant inflammatory infiltrate composed of lymphocytes, histiocytes, plasma cells, neutrophils and eosinophils is descriptive of such lesions [8]. Apparently, as with any unregulated cell growth resulting in tumor formation, chromosomal aberrations leading to cellular atypia, nuclear pleomorphism, abnormal mitotic rate, DNA aneuploidy, and tumor suppressor inactivation have been shown to be beneficial in predicting IMTs as reported by Hussong et al. in their study [9]. This heightened neoplastic capability gives IMTs potential for particularly aggressive clinical behaviour with local recurrence or malignant transformation.

IMTs stain positive for vimentin, desmin, SMA, muscle specific actin, and keratin [10]. As per Cook et al., ALK-1 gene has been implicated in the pathogenesis of IMT supporting neoplastic origin [11]. Approximately 50% of all IMTs are ALK positive. Adequate evidence exists to demonstrate the role of ALK-1 in conveying metastatic and invasive potential to IMTs. In fact, several recent retrospective studies have shown a marked increase in metastasis and recurrence in IMTs that are ALK-1 negative when compared to ALK-1 positive lesions [12–14]. In light of such information, ALK-1 negativity, as seen in the case presented above, demands an aggressive therapeutic approach and increased vigilance for distant metastases or local recurrence.

The described case was also vimentin positive. IMTs stain negative for myogenin (Myf4) and MyoD1 which are positive in embryonal rhamdomyosarcoma, that shares similar histologic features with IMT [10]. Due to ambiguous presentation, IMT needs to be differentiated from other infectious, granulomatous, autoimmune and malignant lesions by histopathology and immunohistochemistry. This case emphasizes the difficulty in presurgical differentiation of IMT from sinonasal malignancies, even with multimodal investigations. At one extreme, advanced disease is misdiagnosed as malignant tumor because of extensive infiltration and bone destruction [15]. At the other extreme, it simulates benign lesions in its earliest stage when confined to mucosa [16].

Management of IMT can be challenging as there are no established treatment protocols [17].

Surgery is considered first line for resectable lesions and may be combined with alternate regimens such as corticosteroids, radiotherapy or chemotherapy [16]. Radical surgical excision has shown to be curative in 90% of the cases [18]. However, the anatomical location and proximity to vital structures may preclude surgical excision [19]. Mortality is well documented despite optimal multimodal therapy [20, 21]. After complete resection, the prognosis of IMT is good with low risk of distant metastasis [8, 22, 23].

Glucocorticoids are considered more effective in children than in adults as stated by Hammas et al. in their study [24]. Variable response to long term use of steroids as well as complete remission following weaning of steroids has been noted [25]. Steroid dependence to maintain remission is a therapeutic problem often encountered in the treatment of IMT [12]. Steroid refractory IMT requiring alternate agents is well documented [26]. The definitive role of glucocorticoid therapy in IMT is not clearly understood but a therapeutic trial should be considered in appropriate cases and continued into remission if clinical and radiological response is apparent.

Chemotherapy is recommended when IMT is multifocal, invasive or shows local recurrence [24]. It is often a combination of agents including methotrexate, cisplatin, vinorelbine, adriamycin, carboplatin and paclitaxel given with a view of achieving complete remission [26–30]. Immunomodulation with intravenous immunoglobulin therapy has been tried with success for post-surgical residual tumour with successful long term remission [31]. Another novel therapy under evaluation is the ALK inhibitor crizotinib, which showed long term partial response in those who were ALK positive as reported by Tothova et al. [32]. Radiotherapy is usually considered ineffective at standard doses. Response with high doses is purported, however the side effects and complications may be a limiting factor [33].

Conclusion

We performed a literature search for IMTs and a total of 34 studies were reviewed and 25 cases were studied. Out of those only 11 involved head and neck sites. Maxillary sinus was found to be the most common site involved and the optimal first line treatment was found to be surgery. Inability to diagnose this lesion may lead to unnecessary aggressive surgery or radiotherapy causing functional disability. On account of vague biological behaviour, it is considered beneficial to keep such patients under observation after treatment to rule out local recurrence and malignant transformations. Concluding, description of this exclusive sinonasal IMT with orbital and intracranial extensions adds to the previously reported clinical spectrum of this rare and poorly understood entity.

Funding

No funding was received for conducting this study.

Declarations

Conflict of Interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Availability of Data and Material

Available in the hospital records.

Informed Consent

Informed consent for participation and publication was obtained from the patient.