F: female, M: male, (m): months, NA: non available, NED: no evidence of disease.

Indolent Mucormycosis of the Paranasal Sinus: An Emerging Entity

Erika Celis-Aguilar, MD1, Alan Burgos-Páez 1, Nadia Villanueva-Ramos 1, José Solórzano-Barrón 1, Juan Manjarrez-Velázquez, MD2, Lucero Escobar-Aispuro 1, Alma de la Mora-Fernández, MD 1

1Department of Otolaryngology, Hospital Civil de Culiacán, México2 Department of Otolaryngology, Hospital General de Culiacán, México

INTRODUCTION DISCUSSION

RESULTS

ABSTRACT

METHODS AND MATERIALS

CONCLUSIONS

REFERENCES

CONTACT

Outcome Objectives: 1. Describe theclinical characteristics and managementof indolent mucormycosis of thenasal/paranasal sinus 2. Describe theoutcomes and follow up of patientswith indolent mucormycosis.Methods: Study design: Multicenterclinical chart review, setting: secondarycare centers. From November 2012 toJanuary 2015. Subjects included werepatients with indolent mucormycosis,defined by pathological confirmation ofmucormycosis and evidence ofsymptoms of paranasal sinus diseaselonger than 1 month. All patientsunderwent imaging, laboratory workup& surgical treatment.Results: Six cases were included withindolent mucormycosis, 2 female and 4male patients, mean age was 54.3years. Three patients wereimmunosuppressed and three patientsimmunocompetent. Symptoms werenonspecific, facial pain, mucoiddischarge and cacosmia were the mostfrequently reported. Maxillary sinusinvolvement was present in all casesand it was the only paranasal sinusinvolved in the immunocompetentcases. Mainly, the surgical procedureperformed consisted in anteriormaxillary approach and endoscopicethmoidectomy and antrostomy. Onlyone immunosuppressed patientunderwent orbital exenteration. Twoimmunosuppressed subjects receivedamphotericin. Posaconazol was the onlytreatment in one immunosuppressedpatient. Immunocompetent casesunderwent only surgical treatment. Inthe follow up, patients have noevidence of disease.Conclusion: Indolent mucormycosis ofthe paranasal sinus is an emergingentity of immunosuppressed andimmunocompetent patients. Singleparanasal sinus disease is a frequentpresentation and should not beoverlooked as a differential diagnosis inthese patients. Immunocompetentpatients should only be treatedsurgically. More studies are needed toconfirm our results.

Results: We included 6 patients, 2 female and 4 malesubjects. Mean age was 54.33 years. Three patientswere immunosuppressed and 3 immunocompetent.Maxillary sinus involvement was present in allpatients. Among the immunosuppressed patients allhad diabetes. Symptoms were nonspecific. Facialpain, mucoid discharge and cacosmia were thesymptoms most frequently reported. Two patientshad asymptomatic mucormycosis, found incidentallyon CT scan.

Chronic or indolent mucormycosis of the paranasalsinuses has been described as early as 1964 byVignale with over 30 cases in the literature1.Interestingly; it can affect immunocompetent andimmunosuppressed individuals. Immunocompetentcases are associated with a less severe disease; therecould be predisposing factors such as chronicrhinosinusitis or penetrating trauma or have noidentifiable risk factors. Signs and symptoms aresimilar to those of chronic rhinosinusitis with gradualonset through years2. The definition of chronicmucormycosis has been controversial, with thepresence of mucormycosis for at least one month 3,4.All the patients of our series had one month or moreof suggestive mucormycosis infection.One common clinical feature we could find in most ofour patients is the presence of facial pain orheadache, this could be a hallmark symptom in apatient with chronic paranasal sinus disease withevident CT scan sinus occupation. The most commonpresentation in our series was unilateral maxilar sinusoccupation (two right, three left), only one patientalso had orbital apex syndrome (Case 1). Necrosis wasseen in most of our patients during Caldwell Lucprocedure in maxillary mucosa, but no evidence ofnecrosis was seen on rhinoscopy or nasal endoscopy,a common finding in acute invasive mucormycosis(80% of patients 5).There is controversy on the best treatment availablefor this pathology. Some authors advocate towards asurgical and amphotericin B treatment, while otherssupport only the surgical or medical treatment asmonotherapy; it has been reported the successfultreatment of chronic paranasal mucormycosis withonly surgical treatment; three cases of the studyreceived only surgical procedure without recurrence 6.In contrast to acute fulminant invasive sinusitis,chronic mucormycosis, could have better survival. Allcases reported in this study had a 100% survival rate.

Methods and materials: Study design: Multicenterclinical chart review, setting: secondary care centers.Patients were recruited from November 2012 toJanuary 2015. Indolent mucormycosis was definedby pathological confirmation of mucormycosis andevidence of symptoms of paranasal sinus diseaselonger than 1 month. All patients underwentimaging, laboratory workup & surgical treatment.Surgical procedures consisted in external maxillaryapproach and endoscopic ethmoidectomy andantrostomy. All surgical specimens were evaluatedby a certified pathologist

Indolent mucormycosis of the paranasal sinus is anemerging entity of immunosuppressed andimmunocompetent patients. Single paranasal sinusdisease is a frequent presentation and should not beoverlooked as a differential diagnosis in thesepatients. Immunocompetent patients should only betreated surgically. More studies are needed to confirmour results.

Introduction: Mucormycosis refers to any fungalinfection by members of the order Mucorales, in theclass of Zygomycetes. Rhizopus, Mucor, Rhizomucorand species of Aspergillus are the most commonetiologic agents in the sinonasal cavity.Mucormycosis of the nasal cavity and paranasalsinuses is an uncommon infection with a rapidaggressive, life threatening course, often inimmunosuppressed patients, potentially fatal.Microscopically, these fungi demonstrate broad non-septate hyphae, thick walled with branching at rightangles. In contrast with this fulminant entity, there´sother form of mucormycosis known as chronic orindolent among immunosuppressed andimmunocompetent patients. Is limited, chronic (> 1month), less aggressive and frequently withinvolvement of single paranasal sinus disease withnon-specific nasal symptoms. This study describes 6cases of indolent mucormycosis.

1. Waizel-Haiat, Salomón, et al. "Mucormicosis rinocerebral invasoracrónica."Cirugía y Cirujanos . 2003; 71.2: 145-149.

2. Jung H, Park SK. Indolent mucormycosis of the paranasal sinus inimmunocompetent patients: are antifungal drugs needed?. JLaryngol Otol. 2013;127(09):872-5.

3. Manuel, Marín-Méndez Héctor, et al. "Síndrome de ápex orbitariocausado por mucormicosis orbitocerebral crónica e indolente:reporte de dos casos." An Orl Mex. 2005; Vol. 50. No. 1: 64-68.

4. Dooley, David P., et al. "Indolent orbital apex syndrome caused byoccult mucormycosis." J Neuroophthalmol. 1992; 12: 245-249.

5. Busaba, Nicolas Y., et al. "Chronic invasive fungal sinusitis: a report oftwo atypical cases.(Original Article)." Ear Nose Throat J. 2002; 81:462-467.

6. Ketenci, Ibrahim, et al. "Indolent mucormycosis of the sphenoidsinus." Am J Otolaryngol Head Neck Med Surg. 2005; 132: 341-342.

Erika Celis-Aguilar MDHospital Civil de CuliacanEmail: erikacelis@hotmail.com

CASES

Fig 1A, 1B: Coronal and sagittal CT scan shows involvement of left maxillarysinus, left nasal cavity and left orbitary apex. 1C: pathology result confirmedmucormycosis with broad non-septate hyphae

Case

1C

ase

2

Fig 2A: Coronal CT scan showed findings compatible with fungus ball in leftmaxillary sinus pathology. 2B: PAS staining revealed mucormycosis, withright angle hyphae. 2C: Coronal CT scan of 2 years follow up

Fig. 3A: pathology report of mucormycosiswith broad non-septate hyphae

Case

3Fig 4A: Axial CT scan demonstrate occupation of left maxillary sinus andosteitis of the sinus walls. 4B: PAS staining; positive suggestive of sporesand hyphae that support Zygomycetes

Case

4

Fig 5A: Axial CT scan reported occupation of right nasal cavity, no erosion,no bone involvement, with occupation of left maxillary sinus. The mass ofright nasal cavity was reported as a polyp and the occupation of leftmaxillary sinus revealed mucormycosis. 5B: Histopathologic image ofGrocott-Gomori stain with abundant broad hyphae and positive staining.Coronal CT scan 1 year follow up (Fig 5C)

Case

5

Fig 6A: Coronal CT scan reported occupation of right maxillary sinus withenlargement of maxillary ostium and osteitis of lateral wall. 6B: Pathologyreported abundant hyphae compatible with mucormycosis at PAS staining.6C: Axial CT scan at one year follow up, which shows thickening of the rightmucosal of the maxillary sinus.

Case

6

TABLE 1. Clinical features, treatment and follow up.

Patient

numberSex Age

Immunocompetent

status

Anatomic

localization

Duration of

symptoms (m)Clinical features Treatment Follow up

1 F 38 Immunosuppressed

Rhino-orbital

Left maxillary

Left ethmoid

Left Orbit

1

Maxillary pain, proptosis, pupil

dilation, restriction of ocular

movements.

Acute facial pain

Left Caldwell Luc

Ethmoidectomy

Orbital exenteration

Liposomal Amphotericine 3gr

Posaconazol 45 days

Two years

follow up,

NED

2 F 61 ImmunosuppressedLeft maxillary

sinus6

Headache, facial pain, purulent

rhinorrhea, halitosis, cacosmia

Left Caldwell Luc

Amphotericin B 750 mg

2.5 years follow

up, NED

3 M 54 ImmunosuppressedRight maxillary

sinusNA Asymptomatic

Right Cadwell Luc

Posaconazol

Two years

follow up, NED

4 M 42 ImmunocompetentLeft maxillary

sinus24

Mucoid discharge, nasal

obstruction, headache.Left Caldwell Luc

One year

follow up, NED

5 M 77 ImmunocompetentLeft maxillary

sinus60

Contralateral nasal mass

(right nasal polyp) obstruction,

asymptomatic

Left Caldwell Luc

Resection of contralateral mass

One year

follow up, NED

6 M 54 ImmunocompetentRight maxillary

sinus8 Headache, cacosmia

Right Caldwell Luc (Caldwell Luc

a year after, no recurrence)

1.6 year,

asymptomatic