Case presentation: Mr. K.M is a 44 year old gentleman, diabetic (uncontrolled), who presented with a right cheek mass that grew progressively over a 20-day period. Patient also reports associated right otalgia, headache, blurring of vision in the right eye and weight loss. Patient had no fever, chills, or nasal discharge. On physical exam he had a 4x3 cm solid, fixed mass over the right cheek, abutting on the right lateral nasal bone, and pushing the nose laterally. He also had a small ulceration and erythema of the skin overlying the mass. His blood sugar was 465 mg/dl upon presentation. CT scan of sinuses and neck was done and showed an aggressive soft tissue lesion in the right maxillary sinus with erosion of the anterior and lateral wall of the maxillary sinus, and erosion of the orbital floor on the right side with invasion of the inferior aspect of the right orbit.

Fig 1. CT sinuses with IV contrast (axial and coronal) showing a soft tissue lesion in the right maxillary sinus with bony erosion Three days later, the patient was taken to the OR and underwent nasal endoscopy with right maxillary antrostomy and biopsy of the mass. Pathology revealed invasive fungal sinusitis consistent with mucormycosis. The patient was taken to the OR again and underwent debridement of the right maxillary sinus with exploration of the right orbital floor. Postoperatively the patient was started on liposomal amphotericin B. One week later, he developed swelling of the right eye with inability to abduct the eye, absent sensation over the 1st and 2nd branches of CN V, and decreased sensation over 3rd branch of CN V. An MRI of the brain showed inflammatory changes involving the right maxillary sinus, pterygopalatine, subtemporal fossa and inferior

aspect of the right orbital cavity, as well as inflammatory reaction in the right temporal lobe with enhancement of right CN V.

Fig 2. MRI sinuses and brain showing inflammatory changes in the right maxillary sinus, inferior aspect of right orbital cavity and right temporal lobe with enhancement of right CN V Patient continued antifungal therapy and an MRI was repeated three weeks later showing decreased edema in the right temporal lobe with a decrease in the area of enhancement within the middle cranial fossa, but persisting enhancement at the origin of the CN V. Fig 3. MRI brain showing decrease in the area of enhancement

The patient completed 36 days of liposomal amphotericin B and was discharged home on posaconazole. When an MRI was repeated two weeks later, findings were stable. However, the following week, the patient presented to the ER with high dextro, vomiting and dizziness. He was admitted and taken to the OR three days later and underwent endoscopic debridement of right maxillary sinus and infratemporal fossa. He was discharged home on posaconazole the following day. A follow up CT was done 45 days later showing abnormal enhancement in the infratemporal fossa and base of skull with extension in the right Meckel’s cave and cavernous sinus. The neurosurgery team was consulted but elected not to intervene surgically.

Fig 4. CT sinuses showing decrease in mucosal disease within the right maxillary sinus with abnormal enhancement in the infratemporal fossa Diagnosis: Mucormycosis Discussion: Mucormycosis is a rare but life-threatening fungal infection, affecting uncontrolled diabetics (ketoacidosis), immunocompromised individuals, and patients receiving deferoxamine.(1,2) It is known best for its rhinocerebral presentation but can infect any system. Mucormycosis refers to several different diseases due to fungi of the order Mucorales with Rhizopus being the predominant pathogen (90% of cases).(3) Given the ubiquitous nature of the fungi, humans are frequently exposed to these organisms .(1) Rhizopus organisms have an active ketone reductase system and thrive in high glucose, acidotic media.(4) Once the spores begin to grow, fungal hyphae invade blood vessels, producing tissue infarction, necrosis, and thrombosis.(1)

Mucormycosis has no sex or race predilection and affects a wide age range. It has a mortality rate of 50-85%.(1) Rhinocerebral disease may manifest as unilateral, retro-orbital headache, facial pain and swelling, fever, and nasal stuffiness that progress to black discharge. Late symptoms include diplopia and visual loss (indicating orbital involvement).(1,2) On physical exam we can have orbital swelling and facial cellulitis, discharge of black pus from the necrotic palatine or nasal eschars, and facial numbness (involvement of CN V and VII).(1,2) Retro-orbital extension can present as proptosis, ptosis, chemosis, and ophthalmoplegias.(6)

Differential diagnosis includes: Bacterial orbital cellulitis, Cavernous sinus thrombosis, Aspergillosis, Pseudallescheria boydii infection, and rapidly growing orbital tumor.(1) The diagnosis of mucormycosis is established by obtaining a biopsy specimen of the involved tissue. Stains of fixed tissues with hematoxylin and eosin (H&E) or specialized fungal stains (Grocott methenamine-silver or periodic acid-Schiff stains) show broad-based (10- 20 um diameter), ribbonlike, nonseptate hyphae with right-angle branching. Neutrophil infiltration, vessel invasion, and tissue infarction are often observed in advanced disease.(1,2) A culture of tissue biopsies is required to determine the species of Mucorales (needs 2-3 days).(1) A CT scan of the sinuses may show sinusitis of the ethmoid and sphenoid sinuses, as well as orbital and intracranial extension. In early disease, the CT can be normal. As the disease progresses, the bone may erode and the infection may spread into the brain or orbits.(1,5) An MRI of the facial sinuses and brain provides information superior to a CT scan for assessing the need for ongoing surgery.(1) Treatment consists of correction of the underlying abnormality, prompt institution of amphotericin B therapy and surgical resection. If the underlying abnormality cannot be reversed then other adjuncts are not effective.(1,2) Orbital exenteration was once advocated for ocular involvement but is now considered controversial.(1,6)

Acknowledgement: On the behalf of the Otolaryngology-head and neck surgery team, I would like to thank the infectious team for the great effort and help they provided to the patient. References: 1. Mucormycosis, N.F.Crum-Cianflone, e-medicine, updated October 2,2006;

(www.emedicine.com/MED/topic1513.htm) 2. Ferguson: Mucormycosis of the nose and paranasal sinuses. Otolaryngol Clin North Am. 2000

Apr;33(2):349-65.

3. Scholer HJ, Muller E, Schipper MAA: Mucorales. In Howard DH (ed): Fungi Pathogenic for

Humans and Animals. Part A. New York, Marcel Dekker, 1983, pp 9-59. 4. Blitzer A, Lawson W, Meyers BR, et al: Patient survival factors in paranasal sinus

mucormycosis. Laryngoscope 90:635-648, 1980 5. Faillo P, Sube HP, Anderson NH: Mucormycosis of the paranasal sinuses and the maxilla. Oral

Surg Oral Med Oral Pathol 12:304-309, 1959. 6. VA.Epstein: Invasive fungal sinusitis and complications of rhinosinusitis. Otolaryngol Clin

North Am. 2008 Jun;41(3):497-524, viii. Review.