Radiological diagnostic dilemma in a child with small aggressive facial mass, time to increase the differentials: an inflammatory myofibroblastic tumour

Abstract

A 5-year-old girl with left facial swelling in the medial maxillary region close to the nasal ala was brought by her parents to our head and neck clinic. They have visited other doctors for similar presentation in the last 6 months, which started as redness and swelling, with occasional epiphora. The redness resolved after medical treatment, with slight regression of swelling, although it did not disappear. CT and MRI showed a locally aggressive, small enhancing soft tissue mass involving the left anteromedial maxillary wall, the nasal bone and the orbital floor. The mass involved the bony course of the nasolacrimal duct, which was the aetiology of the epiphora. The head and neck team performed an incisional biopsy through a sublabial approach. Concurrently, a nasolacrimal duct stent was inserted by an ophthalmologist. Histopathology was consistent with inflammatory myofibroblastic tumour with positive stains for CD68, CD163 and anaplastic lymphoma kinase-1. The tumour was excised and presently the patient is on periodic follow-up with head and neck and ophthalmology clinics.

Background

Aggressive behaviour of an intermediary tumour has always been a diagnostic dilemma. Here multidisciplinary opinion plays a vital role, as clinical, radiological as well as pathological findings complement each other, not only in the diagnosis but also in the decision of a management plan with the least morbidity. We encountered a similar case of an inflammatory myofibroblastic tumour (IMT) in a child which is peculiar due to its location and unusual presenting feature of epiphora.

IMT is an intermediate mesenchymal neoplasm with a rare incidence and variable age and gender predominance.^1–3 Its occurrence in the head and neck is even rarer and accounts for 8%–18% of extrapulmonary sites, of which 2.17% are seen in the maxillary sinus and 1.09% in the orbital region; however, no body region is spared.^{1 4–6} To the best of our knowledge, maxillary bone involvement is usually secondary to maxillary sinus involvement. Only two cases of isolated anteromedial maxillary IMT have been reported to date, ours being the third.^{7 8}

A patient usually presents with a short history of mass; however, signs and symptoms vary according to location and invasion. Clinically non-resolving mass or recurrence of symptoms raises suspicion for sinister aetiology.^{1 2} Its radiological imaging traits are inconsistent and depend on tissue dominance and cellularity. If there is more cellular content, it appears bright on CT images, while more fibrotic content makes its appearance hypointense on T2. The tumour’s destructive behaviour but non-specific imaging features raises a radiological opinion of malignancy, and differentials are made according to the age and site of the mass.^9–12

Histopathology is paramount for definitive diagnosis. The appearance of myofibroblasts and chronic inflammatory cells backed by positive anaplastic lymphoma kinase-1 (ALK-1) on immunohistochemistry is diagnostic.^{1 8} The most accepted management is complete surgical excision due to its local deleterious behaviour. Radiotherapy, chemotherapy, immunosuppressants and immunomodulators have also been proven to be successful in some patients and are preferred for palliation or downsizing of the tumour.^{8 13}

The uncommon presentation of our patient can assist radiologists and clinicians in considering IMT in the differential list of small, locally adverse-looking mass, which can later help them make an early decision for histopathological analysis and better treatment plan. Additionally, the application and usefulness of three-dimensional (3D) volume-rendered images for cases with ambiguous involvement of airspaces, as in our patient, can be intriguing for a radiologist. Various radiological findings of IMT and its distinguishing features from other imaging differentials are discussed in this report.

Case presentation

A 5-year-old girl was brought to our head and neck clinic with 6-month history of left facial swelling in the medial maxillary region close to the orbit and the nose. The parents noticed that it started as an acute periocular swelling and redness, which reduced after medical treatment from some local hospital. However, the swelling on the left medial maxillary region persisted, which gradually increased in size over these 6 months with a periodic complaint of epiphora. During the 6-month period, she had been receiving anti-inflammatory medications, antibiotics and eye-drops periodically, but the swelling and symptoms never resolved completely.

The family denied a history of associated pain, fever, weight loss, nasal symptoms, trauma, surgery, radiation exposure and other constitutional symptoms.

On local examination, the mass was hard but not tender. Nasal endoscopic evaluation manifested a mass pushing the left nasal wall medially. To assess the aetiology of epiphora, the patient was also sent to the ophthalmology clinic for evaluation. The dye disappearance test of her left eye revealed that the mass had involved left-sided nasolacrimal drainage system, which had led to its obstruction. The symptoms of epiphora and initial presentation of swelling with inflammatory signs were actually the sequelae of an occluded lacrimal drainage system. Extraocular muscles and other eye examination were found to be unremarkable.

Investigations

One month before reporting to our hospital, only plain CT and MRI paranasal sinuses (PNS) were done in a local hospital; however, due to unavailability of further facilities, the parents were instructed to seek further management in a tertiary care centre and so the patient was brought to our hospital. After all examination findings, we planned to do contrast-enhanced CT (CECT) of the head and neck in our hospital for further characterisation of the mass.

Radiological investigation

Findings of consolidated radiological investigations, including previous plain CT examination, new CECT scan and MRI, are described in the following sections:

Plain and contrast-enhanced CT of head and neck

This revealed an enhancing, solitary, irregular but well-defined soft tissue mass in the medial part of the left upper maxillary bone at its bony junction with the nasal bone. No focus of calcification or necrosis was seen. The mass was locally aggressive to its neighbouring structures (figure 1A–C). The dimensions of the mass were 2.1 (anteroposterior) × 1.5 (transverse) × 2.3 (craniocaudal) cm.

Figure 1.

Axial contrast-enhanced CT soft tissue window at the level of the maxillary sinus. (A, B) Enhancing, well-defined soft tissue mass at the bony junction of the upper left anteromedial maxilla and the nasal bone (yellow arrows) showing destruction of the nasal bone (short open arrow, A) and the anteromedial corner of the maxilla (long open arrow, B). (C) The lower extent of the mass (asterisk).

Anteromedially the mass was occupying the site of the intraosseous lacrimal duct throughout its length (figures 2 and 3). It was also causing destruction of the ipsilateral nasal bone and dehiscence of the basal attachment of the inferior turbinate (figures 1–4). No obvious dilatation of the proximal lacrimal drainage system was observed.

Figure 2.

(A) Axial and (B) coronal sections of plain CT paranasal sinuses (bone windows) showing involvement of the intraosseous left nasolacrimal duct (long arrow, solid oval) compared with the normal contralateral side (short arrow, dotted oval). Note the destruction of the anteromedial corner of the left maxilla (asterisk), nasal bone (open arrow) and left orbital floor (arrowhead).

Figure 3.

Plain CT paranasal sinuses (A) axial, (B) coronal and (C) sagittal soft tissue windows showing involvement of the intraosseous left nasolacrimal duct (shown with locator Φ corresponding to each plane) and destruction of the left orbital floor (asterisk) and the nasal bone (open arrow).

Figure 4.

Plain CT paranasal sinuses axial section bone window. (A) Destruction of the left nasal bone (open arrow) and the anterior maxillary sinus wall corner (asterisk). (B) Dehiscence of the base of the left inferior nasal turbinate (small yellow arrow) and wall of the infraorbital nerve (arrowhead). (C) Magnifier on the left anterior maxillary sinus corner showing corner destruction and early involvement of the maxillary sinus cavity (arrow).

Posteriorly, the anteromedial bony corner of the maxillary sinus wall was partially destroyed (figures 1B, 2A and 4). The anterior wall of the infraorbital foramen was missing, raising the suspicion for its involvement, but the foramen was not enlarged (figure 4B). Superiorly, it was causing inferomedial orbital wall destruction but not extending into the extraocular muscles (figures 2B and 3B). Inferiorly, the upper bony arch of the unerupted tooth was eroded, but the tooth itself as well as the erupted teeth were spared (figure 5A–D).

Figure 5.

Plain CT paranasal sinuses (bone window) coronal (A, B) and sagittal (C, D) images showing erosion of the roof of the unerupted tooth on unmagnified images (dotted circles in A and C) and images with magnifier (arrows in B and D). The normal erupted tooth is also shown (open arrow in C).

3D volume-rendered CT

3D volume-rendered images of the skin

We could very well see the location of left facial swelling at the time of presentation to our department (figure 6A, B).

Figure 6.

(A, B) Three-dimensional volume-rendered images of the skin showing left facial swelling (arrows).

3D volume-rendered images of the bone

We did volumetric 3D CT reconstruction to determine the extent of facial bone involvement for future reference during surgical planning. It manifested distinctly the extent of nasal bone, orbital floor and maxillary bone destruction (figure 7A, B).

Figure 7.

(A, B) Three-dimensional volume-rendered images of the bone showing the extent of bone damage caused by the mass (open arrows).

3D volume-rendered images of airspaces

On cross-sectional, two-dimensional routine CT images, the involvement of left maxillary sinus and membranous part of the lacrimal duct were uncertain, so we did airspace volumetric 3D reconstruction.

The involvement of the membranous part of the left nasolacrimal duct was suspected due to partial filling of the inferior meatus by the soft tissue which is the site of the distal opening of the duct (figure 4). However, 3D volumetric airspace imaging explicitly demonstrated that it was just slightly irregularly narrowed rather than being obliterated, which probably ruled out the involvement of the distal duct opening (figure 8A, B).

Figure 8.

Three-dimensional volume-rendered images of airspaces showing air in the paranasal sinuses, nasal meati, mastoids and airway. (A) Note the irregularity of the left inferior meatus (arrow). (B) Magnified image of the meati clearly showing irregularity of the left inferior meatus compared with the contralateral side (arrows). (C) Submentovertical view showing the irregularity of the anterior corner of the left maxillary sinus compared with the contralateral side (arrows).

It also clearly depicted the early involvement of the left maxillary sinus, where it was seen that its anteromedial corner was blunted, compared with the contralateral side (figure 8C).

Plain MRI of PNS

The mass seen on plain MRI confirmed well-defined margins with a size of about 2.3 (anteroposterior) × 1.5 (transverse) × 2.5 (craniocaudal) cm. It was of intermediate signal intensity on T1 and fluid attenuation recovery, but slightly hypointense on T2. Other findings seen on CT scan were confirmed on MRI. Additionally, MRI revealed the involvement of regional facial muscles (figure 9A–C).

Figure 9.

Axial plain MRI paranasal sinuses (A) T1-weighted, (B) T2-weighted and (C) fluid attenuation recovery (FLAIR) sequences showing well-defined soft tissue mass at the junction of the left medial maxilla and the nasal bone (asterisks). The facial muscle involvement is prominent on FLAIR image (arrow).

Excluding the better soft tissue characterisation of MRI, the size of the mass compared with the new CT remained unchanged in 1 month. We did not perform contrast-enhanced MRI further as it was not considered to be helpful in other radiological differentials or management choices.

Pathology

After a multidisciplinary meeting among head and neck specialists, ophthalmologists and radiologists, incisional biopsy was planned and opening the lacrimal drainage system was considered. The patient underwent an incisional biopsy through a sublabial approach under general anaesthesia with the head and neck team. They found it to be a whitish hard mass adherent to the subcutaneous tissue. Two specimens were taken and sent for histopathology.

Histopathology

Both specimens showed florid fibrohistiocytic proliferation with foci of storiform fibroblastic arrangements and heavy lymphoplasmacytic infiltration. The proliferating cells appeared to be infiltrating the adjacent bone marrow spaces. Specimens were negative for necrosis, marked pleomorphism and increased mitosis.

Immunohistochemical analysis

The stains were strongly positive for histiocytic markers (CD68 and CD163) and ALK-1. All the above pathology findings were consistent with the diagnosis of IMT.

The surgically excised specimen also concluded the same histological diagnosis. Additionally, it was found that neoplastic cells were negative for desmin. Apart from ALK-1, immunohistochemistry showed positivity for caldesmon and smooth muscle actin (focal).

Blood investigation

Complete blood examination, coagulation profile and routine chemistry were within normal range.

Differential diagnosis

Rhabdomyosarcoma (RMS) is the leading imaging differential in this patient, but histological features of nuclear atypia and increased mitosis differentiate it from IMT. Lymphoma is another differential. Lack of lymphadenopathy and constitutional symptoms in our patient are against it. Another possibility could be granulomatous lesion, but the absence of systemic and chest symptoms makes it unlikely.

Treatment

After an incisional biopsy, an oculoplastic consultant joined the head and neck surgeons in the operation theatre and inserted a nasolacrimal drainage stent to relieve the obstruction.

The patient remained admitted for 1 day post biopsy and lacrimal drainage procedure. She was given an intravenous antibiotic during her hospital stay and was discharged on oral antibiotics, topical tobramycin and dexamethasone eye-drops for 1 week. She was instructed to practise good oral hygiene due to the sublabial wound. Regular follow-up with head and neck and ophthalmology clinics was done to monitor the incisional and stent sites until the postintervention inflammation resolved. After obtaining histopathology results, the stent was removed by the head and neck surgeon through an external lateral nasal and transnasal endoscopic approach to prevent recurrent symptoms and to ensure the least morbidity.

Outcome and follow-up

At 2-week postbiopsy ENT (ear, nose and throat) follow-up, the patient’s wound was found to be healthy-looking with no signs of infection or bleeding. The facial swelling and epiphora improved. She was then instructed to visit ENT and eye clinics bimonthly, during which she received erythromycin tablet for 7 days due to scanty left conjunctival discharge, along with respiratory infection, and she eventually became asymptomatic.

At postsurgical ophthalmology follow-up, she developed local cellulitis, for which she received cefuroxime for 7 days and topical fusidic acid ointment for 14 days, after which the wound remained healthy.

Discussion

IMT is an infrequent neoplasm with elusive clinical and radiological behaviours, but distinctive histopathological and molecular characteristics.⁴ It was considered to be an inflammatory pseudotumour for more than two decades due to some of the common histological features, but later classified by WHO as a distinct entity of an intermediate malignant mesenchymal tumour under a broad category of fibroblastic and myofibroblastic tumours. This label was assigned owing to its local invasiveness, recurrence, and distinct immunohistochemical and rarely metastasising features.^{4 12 14}

Accurate data regarding the epidemiology and anatomical distribution of IMT are difficult to obtain due to the rarity of the tumour and the use of both terms, that is, ‘inflammatory pseudotumor’ and ‘IMT’, correspondingly in the literature.1 2 8 15 However, it is thought to be more frequent in extrapulmonary sites, and in children and young adults. The reported age range is from 1 month to eighth decade of life.^{1 3}

It was first reported as an inflammatory pseudotumour in the lungs and is considered more prevalent in the abdominal viscera, but can arise in any region or organ of the body.^{1 4} IMT in the head and neck region is exceptionally rare, while the upper respiratory tract is the most common site (11%). The rest of the sites in the head and neck are involved in less than 5%,^{1 4–6} and the locations reported so far are the larynx, epiglottis, nasopharynx, tonsils, parapharyngeal space, buccal mucosa, gingiva, tongue, salivary gland, hard palate, maxillary sinus, mandible, maxilla, temporal bone, posterior auricle, orbit and lacrimal gland. Intraosseous IMT is very rare.6 7 15–18 To the best of our literature search, only two cases have been reported in the anterior maxillary region close to the location similar to our case: one in a 53-year-old woman where it presented as a metastatic maxillary deposit of a primary pulmonary IMT,⁷ and the other case is of a 26-year-old woman who presented with occasional epistaxis and sensitivity of the upper incisor.⁸ None of them had eye symptoms or contiguous orbital floor involvement.

Its aetiopathogenesis remains a subject of debate; however, injury, infection and autoimmunity have been ascribed to it.^{17 19}

Other than symptoms of mass, associated constitutional complaints are found only in 15%–30% of patients, usually due to release of some inflammatory mediators from the tumour. They can be fever, malaise, weight loss, anaemia, thrombocytosis, increased erythrocyte sedimentation rate and polyclonal hyperglobulinaemia, which usually resolve after excision of the mass.^{1 12 20}

The radiological diagnosis of IMT is an existing challenge as no hallmark finding has been assigned to it. Imaging is pivotal not only to see the behaviour of the tumour but also to determine the extent, biopsy decision, surgical planning and post-treatment follow-up. Only few studies or reports on its detailed radiological imaging findings are available. Ultrasound has no benefit, but cross-sectional imaging plays a promising role.^{8 15}

CT and MRI show inconsistent appearance due to variable tissue content, quantity of fibrotic tissue, cellularity and nuclear to cytoplasmic ratio. Its destructive behaviour to the surrounding bones is better seen on CT scan. On plain CT it is hypoattenuating or isoattenuating to the surrounding muscles, but can be hyperattenuating due to hypercellularity. The texture of the tumour can either be heterogeneous or homogeneous. Likewise, its contrast uptake on CT and MRI may vary from mild to severe. On delayed contrast images it shows persistent or increasing enhancement due to fibrotic component.^{9 11 12} MRI is of added value to improve diagnostic accuracy and effectiveness of surgical resection. Margins of the tumour can be lobulated with well-defined, infiltrative or ill-defined borders. On T1 and T2 sequences of MRI, it can show hypointense, isointense or intermediate to high signal intensities. If there is more fibrous content, it will be hypointense on T2, as seen in our case. Peritumoural oedema on MRI can also be seen in some cases, which may necessitate removal of the tumour with the oedema. A tumour is less likely to show calcification, haemorrhage or necrosis and may be seen if the size is large.10–12 21–24

Angiographic characteristics have been described only once in the literature, located in the nasal cavity which showed hypervascularity and slow washout in the capillary phase without intratumoural arteriovenous shunting.²²

One study mentioned slight hyperintense signals on diffusion-weighted images in more patients, which might be related to its intermediate malignant nature.¹⁰

Spectroscopy in brain IMT shows relatively elevated choline peak, reduced N-acetylaspartate and creatine peaks which mimic malignant neoplasm, thus necessitating histopathology.⁹ Fluorine 18 fluorodeoxyglucose uptake on positron emission tomography is variable and may be efficacious in determining distant metastasis and recurrence.¹²

In less than 5% of cases, IMT can metastasise to the lungs, bones, brain and liver, but 7.1% of them have been found to show sarcomatous transformation.^{12 15} The recurrence rate is up to 40% depending on the location and treatment.^{20 22 25}

RMS and lymphoma remain on top of the imaging differentials in a child. Differentiating IMT from sarcoma might be challenging due to local invasiveness and variable MRI/CT features in both pathologies. Although MRI signal intensity or CT density is dependent on tumour cellularity, tissue matrix and necrosis, RMS is a high-grade malignant tumour and can be distinguished by its ill-defined margins, more aggressive behaviour, bulky size, and relatively frequent local (10%–20%) and distant metastasis (15%). Maxillary intraosseous lymphoma, although rare, can also present as an osteolytic lesion with soft tissue mass. However, restricted diffusion on diffusion-weighted MRI (DW-MRI) and associated nodal disease are radiological clues. The rest of its imaging features are non-specific.

Other less common differentials include Langerhans cell histiocytosis (LCH), Ewing sarcoma and peripheral nerve sheath tumours. LCH can involve the craniofacial bones, but the skull is the most common location. Well-defined ‘punched out’ lytic lesions with occasional reactive sclerosis, soft tissue component and periosteal reaction are its radiological manifestations. Routine MRI sequences remain non-specific in its diagnosis, but facilitate diffusion in LCH rules out malignancy.

Ewing sarcoma is a malignant tumour and is usually seen between 10 and 20 years of age. Facial bone involvement by this tumour is seldom. Some characteristic imaging features such as poorly defined permeative margins, sunburst or onion peel periosteal reaction, restricted diffusion on DW-MRI, and metastasis lead to diagnosis.

A differential of nerve sheath tumours is usually considered in the setting of pre-existing neurofibromatosis. Despite some unique imaging features of the above differentials, biopsy analysis is required to specify the diagnosis in order to plan targeted management.1 16 20 23 26 27

Pathologically it has basic histological admixture of compact spindle cells proliferation, which are in fact myofibroblasts with variable inflammatory cells like lymphocytes, plasma cells or neutrophils, and hence the name.¹⁷ Unlike many other fibroblastic and myofibroblastic tumours, the immunohistochemistry of IMT reveals the questionable diagnosis by identification of ALK locus on chromosome 2p23, which is positive in about 50% of cases.^{1 8} There is no explicit management protocol yet approved for this tumour, but complete surgical excision has been the most accepted option. Surgical approach in the lesions of maxillary region is planned according to the extent of the disease. It can be an endoscopic technique using a transnasal approach or canine fossa trephination. The predominant subcutaneous bulk of the tumour in our patient led us to choose both lateral nasal approach and transnasal endoscopic method. Radiotherapy and chemotherapy have been reserved usually for inoperable, resistant or more aggressive cases, but not appreciated for use in children due to risk of sarcomatous stimulation.^{4 13 28} For medical management and presurgical tumour debulking, non-steroidal anti-inflammatory drugs and steroids have also shown benefits due to the presence of inflammatory cells in this tumour. Postsurgical close imaging surveillance is crucial, which is monthly in the first year, followed by quarterly in the next years, and biannual in the fourth and fifth years. It has good prognosis if completely excised with free surgical margins.^{13 15 23}

Complications related to the tumour are according to the site of the mass and can be fatal if it extends from the PNS to the neurocranium through direct invasion or via the neural foramina.^{10 29}

The prognosis of IMT is linked to the surgical margins, size of the tumour, ALK positivity and necrosis.¹⁹

Patient’s perspective.

Being the mother of a female child, it was very depressing for me when I saw swelling on my daughter’s face. We used to see local doctors but were unable to understand the cause. I got anxious after knowing about this rare tumor. The doctors have given me hope that it is not very dangerous and surgery usually cures it.

Learning points.

• A child with a small soft tissue facial mass showing aggression out of proportion to its size should be considered for a diagnosis other than just rhabdomyosarcoma and lymphoma.

• Radiological features such as small-sized soft tissue lesion with well-defined margins, osteolysis, mild contrast enhancement, slight T2 hypointensity and absent nodal disease or periosteal reaction can aid inclusion of inflammatory myofibroblastic tumour in the differential list of facial mass in a child.

• Inflammatory myofibroblastic tumour, although aggressive, has good prognosis if completely excised.

• The cause of epiphora can be other than primary lacrimal drainage apparatus pathologies.