Discussion
The main finding of the present study is that, in contrast with other
PSA, FSA exhibits a distinctive prevalence of bony wall remodeling. In
particular, it is characterized by a higher incidence of bone erosion
(47% according to our findings, versus 37.8% in maxillary sinus
[2], 13-52% in sphenoid sinus [3] and incidence not established
for ethmoid sinus due to the rarity of the location), suggesting a
potentially higher number of complications in this subsite. Moreover, we
provide a new element to understand the pathogenesis focusing on
temperature variations within sinuses and the impact on spore’s
proliferation, which could explain the rarity of frontal sinus
involvement in PSA. To our knowledge, this is one of the largest single
center case series reported and it’s the first paper in which a new
hypothesis has been advanced to explain the peculiarity of this entity.
The pathogenesis of PSA poses a unique challenge, with Aspergillus
fumigatus being one of the most common isolated spores and common
component of daily respiratory exposure. Despite inhaling over 100 A.
fumigatus conidia/m³ daily, not all lead to PSA, indicating a
multifactorial origin involving host factors, environmental influences,
and fungal elements. The maxillary sinus is most frequently involved,
followed by sphenoid, while frontal aspergillomas occurrences are rare
[2]. Different hypotheses attempt to explain varied PSA distribution
within sinuses. Nicolai et al. linked maxillary sinus aspergilloma to
prior endodontic treatments, suggesting that dental sealers and an
anaerobic sinus habitat promote inflammation and fungal growth [2].
Conversely, considering the other paranasal sinuses, the only hypothesis
advanced by other authors explaining the occurrence of aspergilloma is
the aerodynamics theory. The latter, especially for the frontal sinus,
conceive that the anatomical complexity and location of the sinus makes
it less accessible for the inhaled spores compared, for example with the
sphenoidal sinus [1]. However, the peculiar anatomy of the
spheno-ethmoidal recess alone do not explain the higher incidence of
aspergilloma within sphenoid sinus compared to the frontal sinus.
Indeed, attention has been put on the mucociliary drainage pathway,
which is likely to convey spores in remote areas of the sinuses,
justifying the presence of hyphae in these peculiar subsites. This
theory, together with investigations into A. fumigatus optimal growth
conditions have been enquired to justify the difference pattern of
incidence within paranasal sinuses, highlighting temperature and pH as
crucial factors [4]. It remains unclear whether these elements are
influenced by the climate conditions rather that patient’s
microenvironment within paranasal sinuses. However, the ubiquity in the
geographic distribution of the reported cases suggests that paranasal
sinus microenvironment is more reliable in explaining the differences
and the rarity of non-maxillary PSA. In this context, the higher
incidence of sphenoid fungus balls may be due to its central head
position, surrounded by internal carotid arteries and cavernous sinuses,
maintaining a higher temperature. Conversely the frontal sinus shows as
main boundaries the outer surface and the brain, leading to lower
temperatures within the sinus and creating a less favorable environment
for spore proliferation, justifying its sporadic involvement.
Due to the rarity of frontal sinus involvement in PSA, we have
investigated whether this location was not only peculiar in terms of
prevalence and pathogenesis, but mostly in terms of behaviors. General
paranasal sinus aspergilloma is a non-invasive form of paranasal fungal
sinusitis, but cases showing a more aggressive behavior causing bone
erosion without histological evidence of tissue invasion have been
reported [5]. In these cases, erosion of the sinus walls refer to
the expansion and thinning of the bony wall of the sinus because of the
pressure caused by hyphal proliferation and necrosis. The general
incidence of erosive non-invasive forms of PSA range though 2.2-63%,
with different incidences between the paranasal sinuses and the
possibility of different complications depending on the proximity of the
adjacent structures [2; 6; 7]. According to our findings, frontal
sinus walls erosion was described in 47% of the cases. Only Gupta et
al. specifically commented on the occurrence of bony destruction of the
sinus walls, which involved exclusively the posterior plate and/or the
floor of the sinus [8]. The consequence and eventual complications
of bony destruction depends on the anatomical structures adjacent to the
sinus. Nevertheless, contrarily to sphenoid sinus aspergilloma, in which
the skull base erosion has been reported to have a clear link with the
occurrence of the intracranial and intraorbital complications, a clear
relation between frontal sinus wall destruction and the occurrence of
complications has not been established [3]. Uri et al. were the only
authors to compare patients with erosive FSA with patient with
non-erosive FSA, reporting a more violent clinical course for the first
[9]. Sporadic cases of intracranial or orbital complications such as
orbital cellulitis have been described, and the high incidence of the
destructive bone pattern can explain that proptosis secondary to orbital
erosion is the initial clinical manifestation in 37.5% of the cases
[8; 10]. However, these findings were not confirmed in our cohort,
since none of our patients experienced intracranial or intraorbital
complications and the small number of cases in the literature did not
permit to compare the two groups.
When dealing with erosive FSA, differential diagnosis with invasive
forms of chronic fungal sinusitis is mandatory since the bone erosion
could be the manifestation of tissue invasion. On this purpose, biopsy
of the tissue is mandatory to exclude tissue invasion at the
histopathological examination [2]. Once diagnosis of FSA has been
advanced, surgery is the treatment regardless the presence of symptoms
to avoid potential complications, due to the high incidence of erosive
forms and the relations of the frontal sinus with orbit and the brain.
The main limitation of this study arises from its retrospective
character and the associated bias.