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, MD 1 , Alan Burgos-Páez 1 , Nadia Villanueva-Ramos 1 , José Solórzano-Barrón 1 , Juan Manjarrez-Velázquez, MD 2 , Lucero Escobar-Aispuro 1 , Alma de la Mora-Fernández, MD 1 1 Department of Otolaryngology, Hospital Civil de Culiacán, México 2 Department of Otolaryngology, Hospital General de Culiacán, México INTRODUCTION DISCUSSION RESULTS ABSTRACT METHODS AND MATERIALS CONCLUSIONS REFERENCES CONTACT Outcome Objectives: 1. Describe the clinical characteristics and management of indolent mucormycosis of the nasal/paranasal sinus 2. Describe the outcomes and follow up of patients with indolent mucormycosis. Methods: Study design: Multicenter clinical chart review, setting: secondary care centers. From November 2012 to January 2015. Subjects included were patients with indolent mucormycosis, defined by pathological confirmation of mucormycosis and evidence of symptoms of paranasal sinus disease longer than 1 month. All patients underwent imaging, laboratory workup & surgical treatment. Results: Six cases were included with indolent mucormycosis, 2 female and 4 male patients, mean age was 54.3 years. Three patients were immunosuppressed and three patients immunocompetent. Symptoms were nonspecific, facial pain, mucoid discharge and cacosmia were the most frequently reported. Maxillary sinus involvement was present in all cases and it was the only paranasal sinus involved in the immunocompetent cases. Mainly, the surgical procedure performed consisted in anterior maxillary approach and endoscopic ethmoidectomy and antrostomy. Only one immunosuppressed patient underwent orbital exenteration. Two immunosuppressed subjects received amphotericin. Posaconazol was the only treatment in one immunosuppressed patient. Immunocompetent cases underwent only surgical treatment. In the follow up, patients have no evidence of disease. Conclusion: Indolent mucormycosis of the paranasal sinus is an emerging entity of immunosuppressed and immunocompetent patients. Single paranasal sinus disease is a frequent presentation and should not be overlooked as a differential diagnosis in these patients. Immunocompetent patients should only be treated surgically. More studies are needed to confirm our results. Results: We included 6 patients, 2 female and 4 male subjects. Mean age was 54.33 years. Three patients were immunosuppressed and 3 immunocompetent. Maxillary sinus involvement was present in all patients. Among the immunosuppressed patients all had diabetes. Symptoms were nonspecific. Facial pain, mucoid discharge and cacosmia were the symptoms most frequently reported. Two patients had asymptomatic mucormycosis, found incidentally on CT scan. Chronic or indolent mucormycosis of the paranasal sinuses has been described as early as 1964 by Vignale with over 30 cases in the literature 1 . Interestingly; it can affect immunocompetent and immunosuppressed individuals. Immunocompetent cases are associated with a less severe disease; there could be predisposing factors such as chronic rhinosinusitis or penetrating trauma or have no identifiable risk factors. Signs and symptoms are similar to those of chronic rhinosinusitis with gradual onset through years 2 . The definition of chronic mucormycosis has been controversial, with the presence of mucormycosis for at least one month 3,4 . All the patients of our series had one month or more of suggestive mucormycosis infection. One common clinical feature we could find in most of our patients is the presence of facial pain or headache, this could be a hallmark symptom in a patient with chronic paranasal sinus disease with evident CT scan sinus occupation. The most common presentation in our series was unilateral maxilar sinus occupation (two right, three left), only one patient also had orbital apex syndrome (Case 1). Necrosis was seen in most of our patients during Caldwell Luc procedure in maxillary mucosa, but no evidence of necrosis 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 available for this pathology. Some authors advocate towards a surgical and amphotericin B treatment, while others support only the surgical or medical treatment as monotherapy; it has been reported the successful treatment of chronic paranasal mucormycosis with only surgical treatment; three cases of the study received only surgical procedure without recurrence 6 . In contrast to acute fulminant invasive sinusitis, chronic mucormycosis, could have better survival. All cases reported in this study had a 100% survival rate. Methods and materials: Study design: Multicenter clinical chart review, setting: secondary care centers. Patients were recruited from November 2012 to January 2015. Indolent mucormycosis was defined by pathological confirmation of mucormycosis and evidence of symptoms of paranasal sinus disease longer than 1 month. All patients underwent imaging, laboratory workup & surgical treatment. Surgical procedures consisted in external maxillary approach and endoscopic ethmoidectomy and antrostomy. All surgical specimens were evaluated by a certified pathologist Indolent mucormycosis of the paranasal sinus is an emerging entity of immunosuppressed and immunocompetent patients. Single paranasal sinus disease is a frequent presentation and should not be overlooked as a differential diagnosis in these patients. Immunocompetent patients should only be treated surgically. More studies are needed to confirm our results. Introduction: Mucormycosis refers to any fungal infection by members of the order Mucorales, in the class of Zygomycetes. Rhizopus, Mucor, Rhizomucor and species of Aspergillus are the most common etiologic agents in the sinonasal cavity. Mucormycosis of the nasal cavity and paranasal sinuses is an uncommon infection with a rapid aggressive, life threatening course, often in immunosuppressed patients, potentially fatal. Microscopically, these fungi demonstrate broad non- septate hyphae, thick walled with branching at right angles. In contrast with this fulminant entity, there´s other form of mucormycosis known as chronic or indolent among immunosuppressed and immunocompetent patients. Is limited, chronic (> 1 month), less aggressive and frequently with involvement of single paranasal sinus disease with non-specific nasal symptoms. This study describes 6 cases of indolent mucormycosis. 1. Waizel-Haiat, Salomón, et al. "Mucormicosis rinocerebral invasora crónica."Cirugía y Cirujanos . 2003; 71.2: 145-149. 2. Jung H, Park SK. Indolent mucormycosis of the paranasal sinus in immunocompetent patients: are antifungal drugs needed?. J Laryngol Otol. 2013;127(09):872-5. 3. Manuel, Marín-Méndez Héctor, et al. "Síndrome de ápex orbitario causado 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 by occult mucormycosis." J Neuroophthalmol. 1992; 12: 245-249. 5. Busaba, Nicolas Y., et al. "Chronic invasive fungal sinusitis: a report of two atypical cases.(Original Article)." Ear Nose Throat J. 2002; 81: 462-467. 6. Ketenci, Ibrahim, et al. "Indolent mucormycosis of the sphenoid sinus." Am J Otolaryngol Head Neck Med Surg. 2005; 132: 341-342. Erika Celis-Aguilar MD Hospital Civil de Culiacan Email: [email protected] CASES Fig 1A, 1B: Coronal and sagittal CT scan shows involvement of left maxillary sinus, left nasal cavity and left orbitary apex. 1C: pathology result confirmed mucormycosis with broad non-septate hyphae Case 1 Case 2 Fig 2A: Coronal CT scan showed findings compatible with fungus ball in left maxillary sinus pathology. 2B: PAS staining revealed mucormycosis, with right angle hyphae. 2C: Coronal CT scan of 2 years follow up Fig. 3A: pathology report of mucormycosis with broad non-septate hyphae Case 3 Fig 4A: Axial CT scan demonstrate occupation of left maxillary sinus and osteitis of the sinus walls. 4B: PAS staining; positive suggestive of spores and 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 of right nasal cavity was reported as a polyp and the occupation of left maxillary sinus revealed mucormycosis. 5B: Histopathologic image of Grocott-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 with enlargement of maxillary ostium and osteitis of lateral wall. 6B: Pathology reported abundant hyphae compatible with mucormycosis at PAS staining. 6C: Axial CT scan at one year follow up, which shows thickening of the right mucosal of the maxillary sinus. Case 6 TABLE 1. Clinical features, treatment and follow up. Patient number Sex 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 Immunosuppressed Left maxillary sinus 6 Headache, facial pain, purulent rhinorrhea, halitosis, cacosmia Left Caldwell Luc Amphotericin B 750 mg 2.5 years follow up, NED 3 M 54 Immunosuppressed Right maxillary sinus NA Asymptomatic Right Cadwell Luc Posaconazol Two years follow up, NED 4 M 42 Immunocompetent Left maxillary sinus 24 Mucoid discharge, nasal obstruction, headache. Left Caldwell Luc One year follow up, NED 5 M 77 Immunocompetent Left maxillary sinus 60 Contralateral nasal mass (right nasal polyp) obstruction, asymptomatic Left Caldwell Luc Resection of contralateral mass One year follow up, NED 6 M 54 Immunocompetent Right maxillary sinus 8 Headache, cacosmia Right Caldwell Luc (Caldwell Luc a year after, no recurrence) 1.6 year, asymptomatic