1 SUBMITTED 20 JUN 22 1 REVISION REQ. 1 AUG 22; REVISION RECD. 16 AUG 22 2 ACCEPTED 7 SEP 22 3 ONLINE-FIRST: DECEMBER 2022 4 DOI: https://doi.org/10.18295/squmj.12.2022.063 5 6 Unilateral Retroorbital Pain Secondary to Isolated Sphenoid Sinus 7 Aspergillosis 8 *Toshimasa Yamaguchi, Rie Oyama, Katsushu Shimizu 9 10 Primary Care and Advanced Triage Section, Osaka City General Hospital, Osaka, Japan. 11 *Corresponding Author’s e-mail: dtoryamaguchi@gmail.com 12 13 A 75-year-old man with type 2 diabetes mellitus presented with a one-day history of general 14 fatigue, vomiting, and headache. He noted severe pain in the left retroorbital region, not 15 increasing on eye movement. He was awake and alert, and febrile (38.6 °C). No meningeal 16 signs, diplopia, or visual disturbance were noted. Laboratory examination revealed a white 17 blood cell count of 7.23 × 103 cells/μL (normal range, 3.58 × 103 to 8.15 × 103 cells/μL) with 18 90.1% neutrophils (normal range, 39.6% to 67.0%) and C-reactive protein level of 27.1 mg/L 19 (normal value < 2.6 mg/L). His nasal endoscopic examination findings were unremarkable. 20 Plain cranial computed tomography revealed a soft tissue density with high-density 21 calcifications on the left sphenoid sinus (Figures 1A and B; blue arrowheads), suggestive of 22 fungal sinusitis. Bone destruction and other sinus lesions were not noted. 23 24 The patient underwent trans-nasal endoscopic sphenoidotomy. Examination of the resected 25 tissue revealed mycetoma with longitudinal septate hyphae. These branched at acute angles 26 and stained black on Grocott’s methenamine silver stain under bright-field microscopy 27 (Figure 2). These findings were indicative of aspergillosis. The resected tissue culture was 28 positive for Aspergillus fumigatus. The patient was prescribed 400 mg oral voriconazole twice 29 daily on the first day, followed by 200 mg twice daily for eight weeks. His headache 30 eventually subsided, and the postoperative course was uneventful. He was discharged three 31 weeks after admission. No recurrence was found on computed tomography performed at the 32 12-week follow-up visit. 33 34 2 Patient consent for publication has been obtained. 35 36 Comment 37 Isolated sphenoid sinus aspergillosis is rare due to the preferential seeding of fungal spores in 38 the ethmoid and maxillary sinuses.1,2 The incidence of sphenoid sinus aspergillosis is low, 39 between 0.5 and 1.2% per year.1 The most common symptom is retroorbital and occipital 40 headaches, followed by nasal blockage or discharge and recurrent mild epistaxis.1 However, 41 the diagnosis of aspergillosis in an isolated sphenoid sinus is challenging because of its non-42 specific symptoms. Therefore, this condition is often diagnosed at the time of operation or 43 postoperatively and perhaps is even underdiagnosed. 44 45 Fortunately, chronic non-invasive sphenoid sinus aspergillosis is a benign disease. However, 46 the sphenoid sinus is adjacent to vital structures, such as the cranial nerves, including the 47 optic nerve, internal carotid artery, and cavernous sinus. Therefore, a prompt diagnosis is 48 essential for patients with sphenoid sinus aspergillosis because its delayed diagnosis may lead 49 to serious complications such as cerebral nerve involvement and cavernous sinus thrombosis 50 due to bone destruction and invasion to adjacent organs. 51 52 Imaging modalities are essential in the diagnosis of sphenoid sinus aspergillosis. With the 53 prevalent use of computed tomography for the evaluation of headaches, the identification rate 54 of sphenoid sinus aspergillosis has increased considerably. The central high density in 55 sphenoid sinus lesions on computed tomography, caused by the accumulation of calcium salts 56 towards the necrotic area of central mycetoma, is considered characteristic of aspergillosis 57 and is useful in the diagnosis of this condition.3 It has been reported that the sensitivity of 58 computed tomography for the diagnosis of this disease is 53%1 based on the presence of 59 calcification in the sphenoid sinus, as seen in this case. Moreover, magnetic resonance 60 imaging is useful due to its high sensitivity and specificity, especially in differentiating 61 sphenoid sinus tumours.1 Therefore, if computed tomography findings are suggestive of a 62 tumour, magnetic resonance imaging may be useful to more clearly delineate the lesion.4 63 Histological examination using Grocott's methenamine silver stain is sufficient to confirm the 64 diagnosis of sinus aspergillosis. However, because the fungal ball is composed of dead spores, 65 it is estimated that culture identifies the pathogen in only 30% of the cases.1 Moreover, 66 invasive aspergillosis requires prompt diagnosis and treatment, and the presence of invasion 67 of the mucosa by the pathogen should be confirmed. 68 3 69 The sphenoid sinus aspergillosis in this case was of a non-invasive type and was considered to 70 be aspergilloma of the sphenoid sinus.5 Since this condition has a chronic course, an acute 71 course of fever and elevated C-reactive protein, an inflammatory marker, as observed in this 72 case were findings suggestive of a bacterial infection. Therefore, although culture of the 73 resected tissue and pus were negative for bacteria, it cannot to be ruled out that complications 74 from an acute bacterial sinusitis with aspergilloma increased the pressure in the sphenoid 75 sinus, leading to retroorbital pain. Although no antibiotics were prescribed in this case, 76 drainage, a basic surgical principle for abscesses, may have been sufficiently effective for 77 bacterial sinusitis. Medical therapy alone is insufficient for aspergilloma, and a surgical 78 intervention is always recommended. 79 80 Isolated sphenoid sinus aspergillosis is a rare but crucial disease that should be considered as 81 a cause of sphenoid sinusitis. Moreover, surgical resection of the aspergilloma may prevent 82 further complications, such as acute bacterial sinusitis, and more invasive sinus involvement, , 83 especially in patients with diabetes and other immunocompromised conditions. 84 85 Authors’ Contribution 86 All authors had access to the patient's data and played a role in writing the manuscript. All 87 authors approved the final version of the manuscript. 88 89 Acknowledgements 90 We would like to thank Dr. Keiji Konishi for the useful discussion. We are grateful to Editage 91 (www.editage.com) for English language editing. 92 93 4 References 94 1. Thery A, Espitalier F, Cassagnau E, Durand N, Malard O. Clinical features and outcome of 95 sphenoid sinus aspergillosis: A retrospective series of 15 cases. Eur Ann Otorhinolaryngol 96 Head Neck Dis 2012;129:179-184. https://doi.org/10.1016/j.anorl.2011.06.005. 97 2. Deutsch PG, Whittaker J, Prasad S. Invasive and non-invasive fungal rhinosinusitis-a 98 review and update of the evidence. Medicina (Kaunas) 2019;55:319. 99 https://doi.org/10.3390/medicina55070319. 100 3. Lee DH, Yoon TM, Lee JK, Joo YE, Park KH, Lim SC. Invasive fungal sinusitis of the 101 sphenoid sinus. Clin Exp Otorhinolaryngol 2014;7:181-187. 102 https://doi.org/10.3342/ceo.2014.7.3.181. 103 4. Kumar D, Nepal P, Singh S, Ramanathan S, Khanna M, Sheoran R, et al. CNS 104 aspergilloma mimicking tumors: Review of CNS aspergillus infection imaging 105 characteristics in the immunocompetent population. J Neuroradiol 2018;45:169-176. 106 https://doi.org/10.1016/j.neurad.2017.11.001. 107 5. Charakorn N, Snidvongs K. Chronic sphenoid rhinosinusitis: management challenge. J 108 Asthma Allergy 2016;9:199-205. https://doi.org/10.2147/JAA.S93023. 109 110 https://doi.org/10.3390/medicina55070319 5 111 Figure 1: Axial (A) and coronal (B) planes of plain cranial computed tomography 112 demonstrating a soft tissue mass with abnormal high-density calcifications in the left 113 sphenoid sinus (blue arrowheads). 114 6 115 Figure 2: Bright-field microscopy of the resected tissue showing septate hyphae branching at 116 acute angles and producing the characteristic black stain on Grocott’s methenamine silver 117 staining, indicative of aspergillosis. 118