Paranasal sinus fungus ball: diagnosis and management

Original article Paranasal sinus fungus ball: diagnosis and management Fabio Pagella,1 Elina Matti,1 Francesca De Bernardi,2 Lucia Semino,1 Caterina Cavanna,3 Piero Marone,3 Claudio Farina4 and Paolo Castelnuovo2 1 Department of Otorhinolaryngology, IRCCS Policlinico San Matteo, University of Pavia, Pavia, 2Department of Otorhinolayngology, Fondazione Macchi, University of Insubria, Varese, 3Laboratory of Bacteriology and Mycology, Laboratori Sperimentali di Ricerca, IRCCS Policlinico San Matteo, University of Pavia, Pavia and 4Microbiology Institute, AO ÔOspedale San Carlo BorromeoÕ, Milan, Italy Summary Paranasal sinus fungus ball is an extramucosal mycosis, usually occurring in immunocompetent people as a monolateral lesion. To review the literature data and to report the Policlinico S. Matteo, University of Pavia experience, 81 patients presenting paranasal fungus ball have been treated (January 1994 to May 2005). Twenty-seven men and 54 women (19–91 years old; mean 49.4 years) were considered. Seventy-three patients had a single sinus affected, but eight presented multiple localisations. Maxillary was the most involved sinus followed by sphenoidal and ethmoidal. Moulds have been isolated in 28/81 cases. Histology showed fungal colonisation but not invasion in all cases. Tomography showed bone erosion in 33.3% of patients. All have been treated only by functional endoscopic sinus surgery. Seventyseven of 81 patients have been cured. Four of 81 patients needed another surgical treatment. Follow up was between 6 and 132 months (average: 63 months). Fungus ball is a sinusal pathology caused by mycetes like Aspergillus spp. Histology confirms the fungal aethiology excluding tissue invasion. Mycological culture consented to identify the pathogenic mould in 34.5% of cases. Actually functional endoscopic sinus surgery is the gold standard for treatment of this pathology, and antifungal therapy is unnecessary. Key words: endoscopic sinus surgery, fungus ball, paranasal sinuses. Introduction Paranasal fungal sinusitis are classified in two categories: invasive and non-invasive pathologies. Invasive forms include acute fulminant fungal sinusitis, granulomatous and chronic invasive mycosis.1,2 Non-invasive forms include eosinophilic localisations (allergic fungal sinusitis and eosinophilic fungal sinusitis) and fungus ball.1,3,4 The presence of hyphae within mucosa, submucosa, vessels and bone at histopathological examinations identifies invasive forms. Some authors classified fungal sinusitis with bone erosion and without tissue invasion as Ôdistructive non-invasiveÕ forms.5–8 Invasive paranasal fungal sinusitis may be observed in Correspondence: Claudio Farina MD, Microbiology Institute, Azienda Ospedaliera ÔOspedale San Carlo BorromeoÕ, via Pio II, 3, Milan 20153, Italy. Tel.: +39 02 4022 2456. Fax: +39 02 4022 2829. E-mail: [email protected] Accepted for publication 21 May 2007 hosts with immunodeficiency, on the contrary non-invasive form may be observed in immunocompetent patients.9,10 Paranasal sinus fungus ball is an extramucosal fungal proliferation which completely fills one or more paranasal sinuses.1 Colonisation is mostly caused by Aspergillus spp. and usually involves maxillary or sphenoid sinus. Ethmoidal, frontal or multiple localisations are rarer.9–12 In this report, we review the English literature about fungus ball with particular regard for clinical, cultural, histological features and treatment. We report 81 cases of paranasal fungus ball, treated with endoscopic approach. Materials and methods Literature review Computed-based literature search (Medline) was used to identify available English language report about  2007 The Authors Journal Compilation  2007 Blackwell Publishing Ltd • Mycoses (2007), 50, 451–456 doi:10.1111/j.1439-0507.2007.01416.x F. Pagella et al. non-invasive fungal sinusitis. Only those cases meeting criteria reported in Table 1 were included. Case reports were not included. The latest literature review about fungus ball was performed by de Shazo et al., [13] so we included only reports published after that date. Milanese (Milano), Italia) for fungi isolation. Plates were incubated at 25 and 30 C for 3 weeks respectively. Subcultures were done on 2% Malt Agar (MA) and on Czapek Dox Agar (CDA) (Difco Laboratories, Detroit, MI, USA). A slide culture performed by the Riddell technique on Sab + C Agar, on MA and on CDA, and stained by lactophenol blue method showed the fungal morphological characteristics. Serological testing to detect Aspergillus antigen (Platelia Aspergillus, Biorad; cut off: 1.5 lg ml)1) and antibodies (Aspergillose Fumouze Laboratories Division Diagnostics, Clichy, France) have been done. Patients and clinical materials After a review of the clinical records of all patients who underwent endoscopic sinus surgery at Policlinico S. Matteo, University of Pavia, between January 1994 and May 2005, 81 patients were selected according to de Shazo diagnostic criteria (Table 1).13 Detailed history, clinical examination (nasal endoscopy), imaging studies [computerised tomography (CT)/magnetic resonance (MR)], operative reports and videotapes, mycological and histopathological findings from these cases were retrospectively reviewed. Follow up and clinical results were also evaluated. Results Clinical data Twenty-seven men and 54 women ranging between from 19 to 91 years old (mean 49.4 years) were considered. Symptoms were different according to the paranasal sinus involved (Table 2). The most frequent maxillary fungus ball clinical manifestation was facial ache, followed by rhinorrea, nasal obstruction and cacosmia. Sphenoidal localisation was characterised by recurrent retro-orbital ache, associated (four cases) to visual disturbances (Table 3). Headache and nasal obstruction are the commonest clinical presentations in the ethmoidal fungus balls. All patients were immunocompetent and none of them had a previous or concomitant history of pulmonary aspergillosis, asthma or atopia. Sixty per cent of patients (49/81) had a previous history of endodontic care and 40 of them (81%) had a maxillary localisation. Preoperative endoscopic aspect was similar Mycological and histopathological evaluation Mucosal biopsies were collected for all patients and sent to the Bacteriology/Mycology Laboratory and the Histo pathology Laboratory (IRCCS, Policlinico S. Matteo, Pavia, Italy) for fungal cultures and histological examinations. Biopsy was homogenised in 0.9% sterile saline, and it was stained by Periodic Acid-Schiff, Chromotroph-aniline blue and haematoxylin–eosine for microscopic examination. The remaining part of the specimen was streaked onto two petri plates of Sabouraud Dextrose Agar plus Chloramphenicol, Sab + C, (Oxoid SpA, Garbagnate Table 1 deShazo’s et al. [13] clinicopathological criteria for diagnosis of fungus ball 1 2 3 4 Radiological evidence of sinus opacification with or without associated flocculent calcifications Mucopurulent, cheesy or clay-like material within a sinus A matted, dense conglomeration of hyphae separate from but adjacent to sinus respiratory mucosa A chronic inflammatory response of variable intensity in the mucosa adjacent to fungal elements. This response includes lymphocytes, plasma cells, mat cells and eosinophils without an eosinophil predominance or a granuloma response. Allergic mucine is absent on haematoxylin–eosin stained material 5 No histological evidence of fungal invasion of mucosa, associated blood vessels, or underlying bone visualised microscopically on Gomori methenamine silver or other special stains for fungus Maxillary sinus Sphenoid sinus Ethmoid sinus Multiple sites 452 Facial-ache Headache Nasal obstruction 26 0 0 3 3 12 2 4 6 0 1 0 Rhinorrea Cacosmia Visual disturbances 10 4 0 0 5 0 0 1 0 4 0 0 Table 2 Main symptoms distributed for each sites  2007 The Authors Journal Compilation  2007 Blackwell Publishing Ltd • Mycoses (2007), 50, 451–456 Paranasal sinus fungus ball Table 3 Ocular findings in patients with sphenoidal fungus ball Patients Symptoms Postoperative SU Unilateral blindness III nerve palsy III, IV, VI nerve palsy Blurred vision III, VI nerve palsy Not recovered Recovered Recovered Recovered Recovered UM CM CE Figure 1 Axial computerised tomography reveals typical appearance of fungus ball in left maxillary sinus. to a bacterial rhinosinusitis with oedema and purulent secretions in all cases. All patients performed a CT scan of the face and eleven also a MR (Fig. 1 and Fig. 2). Seventy-three (90.1%) patients had a single sinus affected, but eight (9.9%) presented multiple localisations. Maxillary was the most involved sinus (50/81, 61.7%), followed by sphenoidal (20/81, 24.7%) and ethmoidal (3/81, 3.7%) localisations (Fig. 3). Eight patients presented multiple localisations, three of them were bilateral maxillary sited. CT scan evaluation showed a bone erosion in 27/81 cases (33.3%). All patients underwent functional endoscopic sinus surgery. Patients with ethmoidal and maxillary localisations underwent ethmoidectomy and meatotomy, and in 33/50 maxillary cases (66%) a sinusoscopy via fossa canina was associated. Out of 20 patients with a sphenoidal fungus ball, 10 underwent a trans-nasal sphenoidotomy and 10 had a transethmoidal approach. To obtain a complete cleaning of the sinuses, physiological water washings were used. In all cases, the sinus was then explored with an angled endoscope to detect any remaining fungal material. No patient was treated with local sinusal anti-mycotic therapy or with systemic anti-fungal therapy. Follow up ranges from 6 to 132 months, mean 63 months. Four patients (4.9%) had a recurrence by Figure 2 Magnetic resonance imaging (T1-weighted sequence with gadolinium) shows typical appearance of fungus ball in left maxillary sinus. Figure 3 Fungus ball localisations. the first year from the surgery with a restenosis of the sinusal ostium, and in all cases the natural ostium was reopened with an endoscopic technique. Recurrences were in two cases in maxillary localisations, in one case in sphenoidal localisation and in an additional one in  2007 The Authors Journal Compilation  2007 Blackwell Publishing Ltd • Mycoses (2007), 50, 451–456 453 F. Pagella et al. multiple sited localisations. Three out four patients with ocular symptoms were cured, but one had a complete recovery of only the ocular motility and not of the eye’s capacity (Table 3). Up to now, all patients are without symptoms and free of disease. Mycological and histopathological evaluation Microscopic examination of histological preparations revealed the presence of a high number of hyphae. Mycotic colonisation has been confirmed by culture in 28/81 (34.5%) cases. Aspergillus fumigatus was the most common mould (75%). Other species (Aspergillus flavus, Chrysosporium and Penicillium) were only sporadically described (Table 4). Aspergillus galactomannan serology confirmed histological data only when A. fumigatus and A. flavus yielded in culture. On the contrary, in case of cultural biopsy positivity for Penicillium spp. and Chrysosporium spp., Aspergillus (antigen and antibodies) serology was negative. When erosion was present, culture was positive in 37% (10 out of 27) cases. Aspergillus fumigatus was the most frequent pathogen (nine out 10 cases) and only in one patient the aethiological mould was Penicillium spp. Histology confirmed in all cases the presence of hyphae in biopsies without tissue invasion. Discussion Paranasal sinus fungus ball is an extramucosal, intrasinusal mycosis, usually occurring in immunocompetent people as a monolateral lesion mainly caused by Aspergillus spp.1,9,11–13 They occur in adult patients and show a female predominance. No paediatric cases have been reported. Plaignaud [14] described the first case report in the French literature, Schubert in 1885 the first A. fumigatus infection in the German literature and Mackenzie [15] the first one in the English literature. A review of the literature on fungus ball is summarised in Table 5. Twenty-four articles were considered reporting 983 cases. Only 13 authors (54.1%) described Table 4 Culture findings (28/81 positive results) No. patients Species 21 3 2 2 Aspergillus fumigatus Penicillium spp. Aspergillus flavus Crysosporium 454 cultural findings. Except for Panda et al. [7] who reports a positive culture in 100%, other authors had positive culture only in 10.5–72.7% of the cases. Aspergillus fumigatus was the commonest isolated mould, followed by A. flavus. At imaging testing, bone erosion was reported by 12 authors (50%) and ranged through 2.2– 63%. Every case underwent surgery. Sixteen authors (66.6%) treated patients by endoscopic sinus surgery. Dhong et al. [16] and Ferreiro et al. [17] used traditional approaches such as Caldwell–Luc procedure, whilst Panda utilised exclusively external approaches like lateral rhinotomy or Linch incision. Four reports do not describe the surgical approach. Only 14 authors (58.3%) reported long-term results with a 5.2% of revision surgery (29/549). de Shazo et al. [13] defined the clinical diagnostic criteria and reviewed the English literature data till 1996. Twenty fungus ball cases were found in eleven papers, and five personal case reports were described.13 Here, we complete the literature review till 2005 (Table 5) to evaluate the aethiological and clinical characteristics of fungus ball, and the surgical results. A nasal Ôfungus ballÕ describes the colonisation caused by the sinusal ostium lock because of anatomical abnormalities or mucous oedema.9,12 A bone resorption of the nasal sinus can be caused by hyphal proliferation, as shown by radiology. Some authors consider these as Ônon-invasive destructiveÕ cases, occurring in 2.2–63%, and associate medical to surgical approach.5–7,18,19 In particular, 53 erosive cases received only surgery, and 31 both surgery and systemic antifungal treatment. However, bone erosion never cause any progression and invasion nor relapse. In our experience, all cases (27/81) presenting erosion (33.3%) requested only a surgical approach, and never an antifungal therapy was done. Where a sphaenoidal localisation is present, symptomatology can be very evident (ophtalmoplegia, ptosis, frontal hypoaesthesia, postorbital pain and visus abnormalities) because of connection between sphenoidal sinus and anatomical structures like internal carotis, cavernous sinus, optic nerve, eyehole and brain.20 The involvement risk, like the orbital apex syndrome or the superior orbital fissura, suggests performing an urgency surgery. Literature reports sphaenoidal localisation in 13% considering 89 out of 683 cases where localisation is well known (86 of them have been treated only by surgery, three with an associated surgical and systemic antifungal approach). Our experience refers about a more important ratio of sphaenoidal fungus ball (20/81) (24.7%) than  2007 The Authors Journal Compilation  2007 Blackwell Publishing Ltd • Mycoses (2007), 50, 451–456 Paranasal sinus fungus ball Table 5 Literature review (1997–2005) References Dufour et al.10 Castelnuovo et al.21 Chobillon and Jankowski22 Panda and Balaji7 Granville et al.30 Kaplan and Kountakis31 Jiang and Hsu32 Willinger et al.33 Uri et al.8 Martin et al.23 Karci et al.34 Har-El and Swanson24 Cakmak et al.35 Chakrabarti and Sharma36 Dhong et al.16 Castelnuovo et al.25 Vennewald et al.12 Sethi26 Panda et al.6 Nicolai et al.18 Klossek et al.27 Ferreiro et al.17 Fang28 Yiotakis et al.19 2005 2005 2004 2004 2004 2004 2004 2003 2003 2002 2001 2001 2000 2000 2000 2000 1999 1999 1998 1998 1997 1997 1997 1997 Cases Erosion (%) Culture (%) Therapy Recurrence (%) 175 11 31 19 11 2 30 112 15 3 11 4 13 97 52 34 117 1 92 4 109 29 7 4 2.2 18 – 63 – – – – 33.3 – – – 30.7 16.4 – 38.2 – – 17.3 25 3.6 17.2 – 50 28.5 72.7 – 100 66.6 – – 51.6 36.8 – – – – – 10.5 61.8 23.5 – 100 – 30 22.7 – 0 FESS FESS FESS Surgery1 Surgery ND FESS FESS Surgery ND FESS FESS FESS FESS Surgery ND Surgery ND FESS e CL FESS FESS FESS Surgery1 FESS FESS FESS e CL FESS FESS 4 18 0 10.5 – 0 – – 0 – 0 – 15.3 – – 8.8 – – 7.6 0 3.6 6.8 – 0 FESS, functional endoscopic sinus surgery; CL, Caldwell–Luc; ND, not defined. 1 Lateral rhinotomy or lynch incision. literature reports, and all cases underwent only to surgery. The only one case where unilateral blindness has been appreciated can be attributed to a patient presenting a longtime, irreversible lesion of the optic nerve. Surgery can be considered a useful approach, and relapse ratio is only about 5%. In effect, it is important to open the ostium to allow the correct ventilation of the sinus and to completely eliminate the fungus ball.1,3,9,11 The surgeon find in the sinus mucopurulent, cheesy or clay-like material. Aethiological diagnosis was done by fungal culture (10.5–72.7%): in our experience, this ratio is about 34% and Aspergillus spp. is the more often seen (82%) fungal species (23/28). Hystological exam shows an hyphal intrasinusal mass without invasion,3,13,17 but not the fungal typing.1,9,11,13 Several surgical procedures have been described, like the traditional method proposed by Caldwell–Luc or the modern functional endoscopic surgery,16,17 even if in India an external surgical approach is used.6,7 Actually, functional endoscopic sinus surgery is the gold standard for treatment of this pathology consenting to selectively remove the fungus ball. Endoscopy allows a faster cure, and avoids cutaneous anaesthetic lesions, with an highest success ratio.10,18,21–29 References 1 De Shazo RD, Chapin K, Swain RE. Fungal sinusitis. N Engl J Med 1997; 337: 254–9. 2 Castelnuovo P, De Bernardi F, Cavanna C et al. Invasive fungal sinusitis due to Bipolaris hawaiiensis. Mycoses 2004; 47: 76–81. 3 Hora JF. Primary aspergillosis of the paranasal sinuses and associated areas. Laryngoscope 1965; 75: 768–73. 4 Katzestein AL, Sale SR, Greenberger PA. 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