Cholesterol Granuloma of the Frontal Sinus Complicated by Mycetoma: A Rare Case Report

Abstract

Cholesterol granuloma is an uncommon inflammatory lesion whose etiology is still unclear. It is thought to originate from blood accumulation in a pneumatized space, probably after bleeding. The most frequent site is the petrous apex of the temporal bone, whilst it is very uncommon in the paranasal sinuses. We present a clinical case of an 80-year-old female patient with intense frontal headache and diplopia who underwent a neuro-navigated endoscopic sinus surgery. The histological diagnosis was a cholesterol granuloma of the frontal sinus, contaminated by Aspergillus Fumigatus hyphae. Cholesterol granuloma of the frontal sinus is a rare finding in clinical practice, but it should be taken into account in the diagnostic path in presence of rapidly increasing sight alterations and headache, even without rhinological symptoms.

1. Introduction

Cholesterol granuloma is a benign lesion characterized by the progressive accumulation of blood-derived products within a pneumatized structure, leading to gradual expansion [1]. It is hypothesized that the lesion arises from blood extravasation into a pneumatized cavity, potentially facilitated by a bony dehiscence between the bone marrow and the cavity itself, which could account for a non-traumatic source of hemorrhage [1,2]. Subsequent anaerobic degradation of blood components, including cholesterol crystals, triggers a foreign-body granulomatous reaction that progressively enlarges over time.

Cholesterol granulomas are uncommon lesions, most frequently occurring in the petrous apex, with an incidence of approximately 0.6 cases per million for this specific location [1,3]. Involvement of the paranasal sinuses is uncommon and predominantly affects males over 40 years of age, often following trauma-related hemorrhage. Other proposed etiologies include bone malformations and impaired nasosinusal ventilation [4].

We report the case of a female patient who presented to the Emergency Department with severe headache, progressive diplopia, and left-sided exophthalmos. Endoscopic sinus surgery (ESS) revealed a cholesterol granuloma associated with a concurrent mycetoma in the left frontal sinus.

2. Case Report

In April 2023, an 80-year-old woman presented to our Emergency Department with a debilitating frontal headache and left-sided diplopia. Headache had been persistent for the previous six months, with progressive worsening, while ocular symptoms had appeared over the preceding three weeks. The patient had been referred to the Emergency Department by the ophthalmologist she had consulted for diplopia, who had excluded primary ocular disease.

The patient’s medical history was notable for gastroesophageal reflux disease and hypertension. No drug allergies, nasal obstruction, or recent craniofacial trauma were reported.

Endoscopic examination of the nasal cavities revealed no mucosal inflammation or nasal discharge.

Contrast-enhanced computed tomography (CT) demonstrated inflammatory tissue involving the left frontal sinus and multiple ipsilateral ethmoidal air cells. With erosion of both the anterior and posterior frontal sinus walls as well as the lamina papyracea, with proximity to the left orbital cavity. Also, rectus medialis and inferior rectus muscles seemed displaced from their normal anatomical position (Figure 1).

Magnetic resonance imaging (MRI) revealed T2-weighted hyperintensity and mixed hyper-/hypointensity on T1-weighted sequences involving the left ethmoidal–orbital region, with extension to the frontal sinuses. The lesion, resembling two adjacent mucoceles, demonstrated extraconal spread, with displacement of the medial rectus muscle and, to a lesser extent, the superior oblique muscle (Figure 2).

The patient underwent bilateral endoscopic sinus surgery (ESS) and endoscopic frontal sinusotomy via a Draf IIb approach. Neuronavigation was used to facilitate access to the left ethmoid and frontal sinuses, where a double mucocelic sac filled with thick, clay-like material occupying the entire sinus and extending close to orbital lamina papyracea (Figure 3). No intraoperative complications occurred. Histopathological analysis on specimens confirmed the presence of a cholesterol granuloma in the left frontal sinus. In addition, fungal material was identified, excised, and submitted for histological and bacteriological examination. The findings were consistent with a mycetoma (hyphae compatible with Aspergillus fumigatus) without evidence of invasion into the frontal sinus mucosa, thereby ruling out the invasive form.

The patient was discharged two days postoperatively without complications and was prescribed a seven-day course of oral antibiotics (Cefditoren 400 mg). Additionally, the patient performed multiple daily nasal irrigations with saline solution at home. Scheduled outpatient follow-up visits included crust removal under endoscopic guidance. Throughout the follow-up period, there were no signs of cerebrospinal fluid leakage, infection, or epistaxis. A computed tomography scan conducted six months postoperatively demonstrated favorable surgical outcomes, with satisfactory pneumatization of the frontal sinuses and no evidence of disease recurrence (Figure 4).

3. Discussion

Our patient presented with two distinct conditions: cholesterol granuloma and isolated mycetoma of the frontal sinus. Cholesterol granuloma results from a foreign body reaction to the deposition of cholesterol crystals and membrane phospholipids following hemorrhage. Several hypotheses have been proposed to explain the origin of this hemorrhage, including prior trauma, bone malformations, and impaired ventilation in the setting of nasal polyposis [4].

In a review by Durgam et al. [5], 135 cases were reported between 1970 and 2010. The frontal sinus was the most frequently involved site (60%), followed by the maxillary sinus (34.1%) and the ethmoid sinus (3.7%). A more recent study by Wershoven et al. [6], which updated and extended Durgam’s dataset to include the period from 2011 to 2021, reported similar findings, with an additional 18 cases involving the frontal sinus alone.

Reports of cholesterol granuloma in other anatomical locations are also found in the literature (

Table 1. Cases of cholesterol granuloma reported in other anatomical sites. Both case reports and cases series studies are reported in this table.

Authors	Site	No. Cases
Lin J. I. et al. [7] (1979)	Testis	1
Grignon D. J. et al. [8] (1985)	Lymph nodes	1
Amer A. F. et al. [9] (1990)	Peritoneum	1
Mafee M. F. et al. [10] (1994)	Brain	7
Nativ O. et al. [11] (1995)	Testis	1
Fariña Pérez L. A. et al. [12] (1998)	Testis	1
Schultz R. et al. [13] (2001)	Lung	1
Mendonça R. et al. [14] (2007)	Brain	1
Paluzzi A. et al. [15] (2012)	Petrous apex	17
Krishnan T. R. et al. [16] (2013)	Mediastinum	1
Young Sa Y. J. et al. [17] (2013)	Bone (rib)	1
Unal D. et al. [18] (2015)	Testis	1
Raghavan D. et al. [19] (2015)	Petrous apex	18
Zhang M. et al. [20] (2016)	Lung	1
Nam G. et al. [21] (2019)	Breast	79
Eba S. et al. [22] (2021)	Mediastinum	1
Hassen S. S. et al. [23] (2022)	Lung	1
Vinciguerra A. et al. [24] (2022)	Petrous apex	29

).

The clinical and radiological presentation of our patient could resemble that of an orbitofrontal cholesterol granuloma, a benign lesion involving the diploe of the frontal bone, typically located in the superolateral quadrant. This condition predominantly affects males over 40 years of age [25] and may present with proptosis, periorbital pain, reduced ocular motility, diplopia, and decreased visual acuity [26]. Radiologically, it demonstrates a characteristic pattern, appearing hyperintense on both T1- and T2-weighted MRI sequences and hypodense on CT [1,26,27]. Histologically, it is composed of aggregates of cholesterol crystals and phospholipids, without epithelial lining [28].

One possible hypothesis in our case is that the lesion initially developed as an orbitofrontal cholesterol granuloma and progressively extended into the frontal sinus cavity, as suggested by the areas of bone erosion evident on CT and similarly reported by Shrirao et al. [29]. Alternatively, obstruction of the frontal sinus ostium by coagulation products—secondary to mucosal bleeding—may have impaired ventilation, leading to the accumulation of cholesterol crystals. This mechanism was also proposed by Ochiai et al. [4], who described a 59-year-old patient with a post-traumatic left frontal sinus cholesterol granuloma exhibiting a radiological appearance similar to that of a mucocele, given that the sinus mucosa may produce mucus-like secretions in response to non-specific inflammatory stimuli. This presentation closely resembles the cases reported by Li et al. [30] and our own, both of which exhibited a mucocele-like appearance on CT imaging.

Beyond mucoceles, the differential diagnosis of orbitofrontal cholesterol granuloma includes cholesteatoma, dermoid and epidermoid cysts, and lacrimal gland tumors [31].

The treatment of cholesterol granuloma is surgical [32,33], with the approach varying according to lesion characteristics, ranging from simple cyst drainage to frontal craniotomy or lateral orbitotomy [4]. Endoscopic sinus surgery (ESS) is preferred in cases with intracranial extension [34,35], as was the case for our patient. The most common complication associated with this procedure is cerebrospinal fluid (CSF) leakage [36], which was successfully avoided in our case.

Similarly, an isolated fungus ball (FB), or mycetoma, of the frontal sinus is an uncommon fungal infection that rarely invades the mucosa, except under predisposing conditions such as immunosuppression [37,38]. It is believed to result from the inhalation of fungal spores—most commonly Aspergillus fumigatus—which subsequently colonize the frontal sinus. Involvement of the frontal sinus is rare (approximately 2% of all FB cases) due to its poor accessibility to inhaled spores [39]. According to the diagnostic criteria proposed by deShazo et al. [40], radiological evaluation is fundamental and highly pathognomonic. Fadda et al. [41] reported that CT scans typically demonstrate near-complete opacification of the affected sinus, with multiple hyperdense foci representing microcalcifications from matted fungal hyphae and metabolic deposits. Bony wall alterations—such as sclerosis or thickening from chronic reactive osteitis, or focal thinning, dehiscence, and sinus expansion—may also be present. On gadolinium-enhanced MRI, FB usually appears iso- or hypointense on T1-weighted images and hypointense on T2-weighted images, reflecting high iron and manganese content as well as calcium in the form of microcalcifications.

In the case presented, radiological findings were more suggestive of a cholesterol granuloma, with no clear evidence of FB. CT scans revealed homogeneous isodense inflammatory tissue without microcalcifications, while MRI demonstrated T2-weighted hyperintensity and mixed hyper-/hypointensity on T1-weighted sequences. These MRI patterns, together with possible bone erosion, may occur in both FB and cholesterol granuloma. Therefore, in addition to imaging, intraoperative identification of the characteristic cheesy, clay-like material and subsequent histopathological confirmation were essential for diagnosis.

Regarding the unusual coexistence of fungal colonization within a cholesterol granuloma, we hypothesize that FB development may have been facilitated by obstruction and impaired ventilation of the sinus caused by the granuloma itself. Furthermore, both cholesterol granuloma and FB may mimic mycetoma [39], underscoring the need for an accurate differential diagnosis, particularly in the presence of bone erosion and sinus involvement. If left untreated, both conditions tend to enlarge, causing bone erosion and subsequent extension to adjacent structures, which may result in complications such as debilitating headache, proptosis, visual impairment, and displacement of the ocular globe, as observed in the present case.

4. Conclusions

Cholesterol granuloma of the frontal sinus is an uncommon lesion that should be considered during the diagnostic workup when a frontal or supraorbital mass associated with ocular symptoms is encountered. It is important to differentiate it from the more common frontal mucocele, as well as from other less frequent lesions. An accurate clinical and radiological assessment is crucial as well as a rapid treatment, which is always surgical with an endoscopic approach if possible. Histological and bacteriological examination of the samples is essential for a definitive diagnosis.

Our findings suggest that in challenging cases, neuronavigation, in addition to adequate instrumentation, can assist the surgeon during ESS and reduce the risk of complications.