abnormal growth of the maxillary sinus and orbit

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J Oral Maxillofac Surg69:2167-2172, 2011

Abnormal Growth of the Maxillary Sinusand Orbit

Virendra Singh, MDS,* Bindu Sharma, MDS,† Rajeev Sen, MD,‡

Shalini Agrawal, MD,§ and Rahul Dhingra, MDS�

Case Presentation

A 48-year-old man was referred to our departmentfrom the ear, nose, and throat service with a chiefcomplaint of pain and swelling in the right maxillaryregion. Mild to moderate pain radiating toward theright eye was associated with diminished and blurredvision in the same eye for a few days. Firm and tenderswelling with indefinite margins was palpated occu-pying the entire right cheek region. Hypoesthesia wasobserved in the distributing area of the infraorbitalnerve. The patient’s medical history was not signifi-cant for any underlying medical ailment. On generalphysical examination, he was found to be normallybuilt and well oriented to time, place, and person. Hewas afebrile, and his vital signs were stable. His ad-mission laboratory findings were within normal range.The total and differential cell counts were within normallimits, and biochemical analysis showed no abnormality.No documented evidence of compromised immunitywas observed. Diffuse swelling involving the entireright palate and vestibule was observed intraorally.The overlying mucosa was normal in color and out-line, with no evidence of necrosis. The maxilla wasintact, and no mobility was observed. The nasal mu-cosal lining was found to be intact and normal. Thepatient’s social history showed a village backgroundand association with farming and cattle rearing.

Received from Pt. B.D. Sharma University of Medical Sciences,

Rohtak, India.

*Professor and Head, Department of Oral and Maxillofacial Sur-

gery, Government Dental College.

†Junior Resident, Department of Oral and Maxillofacial Surgery,

Government Dental College.

‡Professor and Head, Department of Pathology.

§Associate professor, Department of Radiology.

�Junior Resident, Department of Oral and Maxillofacial Surgery,

Government Dental College.

Address correspondence and reprint requests to Dr Singh: De-

partment of Oral and Maxillofacial Surgery, Government Dental

College, Pt. B.D. Sharma University of Medical Sciences, Room 12,

Rohtak, Haryana 124001, India; e-mail: drvirendrasingh1@yahoo.

co.in

© 2011 American Association of Oral and Maxillofacial Surgeons

278-2391/11/6908-0022$36.00/0

oi:10.1016/j.joms.2010.10.036

2167

The conventional radiographs showed opacifica-tion of the sinus and was noncontributory towardconfirmation of diagnosis. The computed tomography(CT) scan showed a diffuse soft tissue mass withpatchy hyperdensity involving the right maxillary si-nus and extending into the right orbit inferomediallyand ethmoid sinus. There was involvement of theright inferior rectus and inferior oblique muscle aswell (Fig 1). The patient was discharged 10 days afterinitial treatment. Three months later, the patient againpresented to us, with a complaint of further decreasein the vision of the right eye along with increasedintensity of pain on the right side of the face. This wasassociated with a persistent headache and occasionalgiddiness. Other clinical manifestations included prop-tosis in the right eye, ophthalmoplegia, and restric-tion of eyeball movements in all gazes, along withcompressive ophthalmopathy. The vision was 6/60 inthe right eye and 6/6 in the left eye. The patient againunderwent CT scan examination, which showedproptosis of the right eye caused by a diffusely en-hancing lesion with ill-defined borders involving theretromolar fat, optic nerve, and medial and lateralrectus with intracranial extension involving the righttemporal lobe. There was also erosion of the greaterwing of the sphenoid (Fig 2).

Differential Diagnosis

Combined sinus and orbital involvement can beseen in various conditions. The initial clinical andradiographic findings support a chronic sinusitis–likecondition. However, aggressive recurrence alongwith ocular symptoms and features showing intracra-nial involvement give us suspicion of some fatal un-derlying condition that needs to be diagnosed earlyand treated aggressively. Some conditions that resem-ble this case in terms of clinical and radiographicappearance are described.

SINUSITIS

Sinusitis is an inflammation of the nasal sinuses. It isusually caused by infection (bacterial or viral), but itcan also be caused by allergic reactions or otherresponses to environmental agents. In its initial
stages, the present condition of the patient resembled
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2168 ABNORMAL GROWTH OF MAXILLARY SINUS AND ORBIT

sinusitis. However, the recurrence in aggressive formis not usually expected, and ocular involvement is notusually seen in these cases. The diagnosis was con-firmed by CT scan, nasal endoscopy, or tissue samplefor histology and culture. The imaging studies showopacification and air fluid levels in the sinuses.

ALLERGIC FUNGAL SINUSITIS

Allergic fungal sinusitis is caused by phaeohypho-mycosis in individuals with allergic rhinitis. This con-dition is slow growing, and proptosis can occur be-cause of a large mass that has developed over themonths and years. It does not invade the tissues andmeninges.1 It occurs in atopic immunocompetent pa-ients. It begins with colonization of fungus in para-asal sinuses, which elicits an intense immune re-ponse. There is an elevated immunoglobulin E level.his leads to chronic sinusitis and polyposis with

requent postsurgical recurrences.2 Confirmation ofhis condition can be done histopathologically.

ASPERGILLOSIS

Aspergillosis has been reported to occur in bothhealthy and compromised individuals. Aspergillosismay take a noninvasive or invasive course. In the headand neck region, both forms of aspergillosis havebeen seen. It may present with destructive lesions ofthe central nervous system, maxillary sinus, and orbitand has a poor prognosis. The diagnosis is confirmed

FIGURE 1. Coronal non-contrast CT scan image showing diffusesoft tissue mass with patchy hyperdensity involving right maxillarysinus and extending into orbit and ethmoid sinus.

Singh et al. Abnormal Growth of Maxillary Sinus and Orbit.J Oral Maxillofac Surg 2011.

by biopsy specimen, which shows comparatively

thinner but septate hyphae, which branch at acuteangles, compared with mucormycosis, with branch-ing at right angles.3

ORBITAL CELLULITIS

Orbital cellulitis is purulent inflammation of cellulartissues of the orbit. It is most frequently due to ex-tension of inflammation from neighboring parts, es-pecially the nasal sinuses. There is great swelling oflids with chemosis, proptosis, and diplopia, and eye-ball movements are hampered. Pain is severe andcerebral symptoms may arise, but the patient is alsofebrile, which was not a feature in our patient.4

CAVERNOUS SINUS THROMBOSIS

Cavernous sinus thrombosis can be the sequela ofsome abnormal growth in the orbit itself as the infec-tion spreads posteriorly from either the orbit or thesinuses to the central nervous system. The symptomscan be confused with primary involvement of thecavernous sinus, which is accompanied by rigor, vom-iting, and severe cerebral symptoms. The diagnosiscan be confirmed by blood counts and culture show-ing the primary infectious source. Contrast-enhancedCT scan may show underlying sinusitis, thickening ofthe superior ophthalmic vein, and irregular fillingdefects within the cavernous sinus; however, the find-ings may be normal early in the disease course.

FIGURE 2. Axial contrast-enhanced CT scan showing proptosis ofright eye caused by diffusely enhancing mass involving retro-orbitalfat, optic nerve, and medial and lateral rectus with intracranialextension to right the temporal lobe.

Singh et al. Abnormal Growth of Maxillary Sinus and Orbit.
J Oral Maxillofac Surg 2011.

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SINGH ET AL 2169

MALIGNANCY

Rapidly progressing malignant orbital tumors canlead to the same clinical picture. They can be unilat-eral or bilateral. There may be considerable proptosis,and restriction of movements is common. Again, thehigh index of suspicion and early surgical explorationcan lead us to the target. Moreover, on CT scanexamination, malignant lesions are more infiltrativeand larger areas of bone destruction are evident. Inmalignancy clear spaces between the tissues are notvisible.5

WEGENER GRANULOMATOSIS

Orbital inflammation in Wegener granulomatosisoccurs as a result of either a primary granulomatousvasculitic process or a contiguous spread from theparanasal sinuses. Ophthalmic involvement is a com-mon feature and is potentially life-threatening. Prop-tosis is the most common clinical finding. This can beassociated with paralysis of the extraocular muscles,necrotizing sclerokeratitis, and orbital inflammatorydisease. Serum classical anti-neutrophil sytoplasmicantibodies has been proven invaluable in the diagno-sis of both ocular disease and a systemic form of thisdisease. Prompt administration of immunosuppres-sive agents is the mainstay of treatment.6

MUCORMYCOSIS

Rhinocerebral mucormycosis, also known as zygo-mycosis or phycomycosis, is an acute fungal diseaseplagued by agonizing complications and a very highmortality rate. Rhinocerebral mucormycosis is themost common form of mucormycosis and typicallyinvolves the nose and sinuses.7 The patient generally

resents with involvement of the head and neck re-ion. The fungi of order Mucorales are the causes ofife-threatening fungal infection largely affecting im-

unocompromised hosts, although rare cases haveeen reported in immunocompetent hosts also.8,9

The lesion is best diagnosed by biopsy. The fungus isusually identified in necrotic tissue on hematoxylin-eosin–stained sections, appearing as large, non-sep-tate hyphae that tend to branch at right angles.

Although many diagnostic possibilities exist in thiscase, the clinical and radiographic presentation ismost consistent with aspergillosis and mucormycosis.Incisional biopsy is indicated to confirm the finaldiagnosis and establish a treatment plan.

Subsequent Course

After clinical and radiologic assessment, the histopatho-logic examination of the tissue was performed. Biopsy ex-amination confirmed the diagnosis of mucormycosis, afterwhich aggressive surgical intervention was planned in the
form of hemimaxillectomy along with orbital floor recon-
struction (Fig 3). A Weber-Fergusson approach was under-taken to expose the maxilla, and firm fibrous tissue wasobserved occupying the right maxillary region extendinginto the orbit. All pathologic tissue along with the maxillawas resected. This was followed by intravenous administra-tion of amphotericin B at a dosage of 0.5 mg/kg of bodyweight per day. The patient was discharged after 10 days.Three months later, the patient again presented, with ag-gressive recurrence of signs and symptoms. He was againhospitalized, and intravenous amphotericin B was started,which was given over a period of 15 days. However, thesymptoms did not subside, and there was no improvementin the condition of the patient. Because of a lack of availableclinical trials and limited retrospective reviews, we reliedon our observation with successful use of oral voriconazolein this patient. The results were dramatically positive. Thepatient was given an initial dose of 400 mg twice a day (BD)for the first day, followed by a maintenance dose of 200 mgBD daily. The patient’s compliance was good, and there wasdrastic improvement in clinical as well as radiologic features(Fig 4). Then, after 2 months, reconstructive surgery wasaccomplished successfully. Temporalis myofascial flap wasused to reconstruct the defect that remained after the pre-vious surgery (Fig 5). There was no significant alteration inclinical or radiographic findings at regular follow-up of 12months.

Discussion

Rhinocerebral mucormycosis is a rare fungal infec-tion with a fatal outcome. It involves the sinuses andbrain and is caused by saprophytic fungi. It commonlyaffects individuals with diabetes and those in an im-

FIGURE 3. Weber-Fergusson approach undertaken for hemimax-illectomy and orbital floor reconstruction.


munocompromised state, but the fungus can even

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become pathogenic in a normal host.8-10 The fungusis ubiquitous in nature, grows rapidly, and releases alarge number of airborne spores. The fungus belongsto the class Phycomycetes, and Rhizopus is the pre-dominant genus isolated as a pathogen accounting for90% of the cases of rhinocerebral mucormycosis.11 In

ost cases the route of transmission is aerogenic, andungi gain entry through the nose via inhalation ofirborne spores and are frequently found colonizinghe nose, oral mucosa, paranasal sinuses, and throat.he hallmark of mucormycosis infection is the pres-nce of extensive angio-invasion with resultant vesselhrombosis leading to tissue necrosis.12

Rhinocerebral mucormycosis is the most commonform of disease, accounting for between one-thirdand one-half of all cases of mucormycosis.7 The liter-ature also reports that about 70% of cases are associ-ated with diabetes.13

The initial symptoms of rhinocerebral mucormyco-sis are consistent with either sinusitis or periorbitalcellulites and include eye or facial pain followed bythe onset of soft tissue swelling and diminished vi-sion. If untreated, it usually spreads to the ethmoidsinuses and then to the orbit, resulting in loss ofextraocular muscle function and proptosis. This caneven lead to ophthalmoplegia, cavernous sinus throm-bosis, and complete vision loss. It can also spread tothe oral cavity from the sinuses and produce painfululcers, leading to necrosis in the hard palate. Our

FIGURE 4. Axial T2-weighted image of the patient shown inFigures 1-3 showing reduced proptosis in right eye and residualgliosis in temporal lobe. However, the hypointensity still persists inthe retro-orbital fat pad.


patient’s findings were consistent with most of these

findings, but instead of necrosis of the bone, therewas reactive fibrosis of the soft tissues, which is apeculiar finding in an immunocompetent host.

Imaging techniques are rarely diagnostic of rhino-cerebral mucormycosis, and there are no serologictests to allow rapid diagnosis. Thus many cases arereported to be diagnosed post mortem.14,15 Patientswith early disease may have normal CT or magneticresonance imaging findings. The main contribution ofCT to the diagnosis of mucormycosis is its clear dem-onstration of the relationship between sinus and or-bital disease that should be considered when com-bined sinus and orbital disease is present. There isinvasion of the medial wall of the orbit causing lateraldisplacement of the medial rectus muscle. There canbe enlargement of the muscle due to direct invasionby fungal hyphae.5 With the limitations of imagingstudies, diagnosing mucormycosis always requireshistopathologic evidence of fungus invading the tis-sues. Fungus culture from the infected site is notsufficient to establish the diagnosis because tissueprocessing may destroy the organism and the fungusmay colonize in normal persons as well.12 The diag-

osis should be confirmed by biopsy of infected tis-ue. In our patient, the culture sensitivity report forhe fungus came out to be sterile. The biopsy speci-en showed ribbon-like aseptate hyphae, which is a

haracteristic feature of mucormycosis. These hyphaeere surrounded by necrotic tissue along with reac-

ive giant cells (Fig 6); the same was also confirmedn a section specially stained with periodic acid–chiff (Fig 7).

Internal carotid angiography can be helpful in eval-ating the extension of the disease.5 Occlusion or

narrowing of the cavernous carotid artery or ophthal-mic artery can be looked for. Venography can some-

FIGURE 5. Picture after 2 months when reconstructive surgery wasundertaken with help of temporalis myofascial flap.


SINGH ET AL 2171

times help in differentiating the signs of acute orbitalinvolvement due to pathologic involvement in theorbital apex or acute cavernous sinus thrombosis.16

Mucormycosis is a medical emergency, and thefactors that are critical for its management includerapidity of diagnosis and early initiation of vigoroussurgical and medical therapy. The radiographic ap-pearance of the tissue may lag behind the clinicalprogression of this disease. The delay in diagnosis canlead to a worse outcome, so if the clinical suspicion ishigh, one should aggressively pursue the diagnosticbiopsy.12 Timing is the key in the management ofmucormycosis. Antifungal therapy alone is often in-adequate to control the infection, so the workup doesnot include the antifungal therapy alone: urgent sur-gery is definitely the key addition to treatment. Surgi-cal involvement includes debridement of all infectedtissues. In some cases radical resection may be re-quired, which can include partial or total maxillec-tomy, mandibulectomy, and orbital exenteration.Combined surgical and medical treatment can in-crease the survival rate, although some functional oresthetic deficits can remain.17

In our case, the aggressive surgical interventionwas done in the form of hemimaxillectomy on anurgent basis. Amphotericin B was started intrave-nously at a dosage of 0.5 to 0.7 mg/kg per day undercontinuous monitoring for renal toxicity. The patientdid not respond to the treatment later on. The choiceof other currently available antifungal agents was dif-ficult because clinical trials are lacking. Consideringthe close resemblance clinically and radiographicallywith aspergillosis, the role of the antifungal agentvoriconazole needed to be observed, which yieldedradically positive results. The availability of both par-enteral and oral formulations and almost complete

FIGURE 6. Hematoxylin-eosin–stained section (original magnifica-tion �200) showing mucor hyphae with giant cell reaction.

absorption of the drug after oral administration pro-vide for ease of use and potential cost savings. Thepatient was switched to medical therapy with oralvoriconazole at a dose of 400 mg BD for the first dayas a loading dose, followed by 200 mg BD as a main-tenance dose.18

Our patient was histopathologically confirmed ashaving mucormycosis with no underlying compro-mised medical state. The role of voriconazole as anantifungal therapeutic agent in an immunocompetenthost was positively concluded in our case with rela-tion to noncompromised medical status, but this factdefinitely needs to be investigated further for confir-mation of this inference, despite limited activity ofthis agent in mucormycosis as reported in the litera-ture.

A high index of suspicion is required to establishthe diagnosis of rhinocerebral mucormycosis, espe-cially in cases of immunocompetent hosts with com-bined sinus and orbital involvement. The involvementof several sinuses with unilateral predilection is alsoan important factor. The clinician should be vigilantabout the relationship between sinus and orbital dis-ease on CT imaging. Early biopsy in an immunocom-petent host is a key factor because of the absence oftypical clinical features and predisposing causes. Forthe eradication of mucormycosis, rapidity of diagno-sis, appropriate surgical debridement of infected tis-sue, and appropriate antifungal therapy must governthe treatment. Because mucormycosis is less commonthan aspergillosis, with a rapidly progressing course,the effectiveness of antifungal chemotherapy in smallcase studies is difficult to evaluate and needs further

FIGURE 7. Special section stained with periodic acid–Schiff show-ing mucor hyphae with giant cell reaction (original magnification,�200).


exploration.


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abnormal growth of the maxillary sinus and orbit

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