Paranasal sinus fungus balls (FBs) are a noninvasive type of fungal rhinosinusitis, characterized by the presence of fungal hyphae without microscopic tissue invasion in the sinus [1]. Although FBs were once thought to be rare, their prevalence has significantly increased over the last four decades. This increase is likely attributable to the more frequent use of radiological evaluations, such as computed tomography (CT) scans, along with improvements in fungal culture techniques and surgical treatments [2].

Galactomannan (GM), a component of the cell wall in Aspergillus species, is measured using an enzyme-linked immunosorbent assay (ELISA) test. The serum GM test can be used to detect acute invasive fungal rhinosinusitis early [3]. The (1,3)-β-D-glucan (G test) detects wall polysaccharides present in most fungi and can assist in diagnosing invasive fungal infections, including invasive fungal rhinosinusitis [4].

Studies have been conducted on the effectiveness of the G test in analyzing sinus mucus from patients with FBs and chronic rhinosinusitis (CRS) with nasal polyps [5], as well as in FB specimens collected during surgery [6]. However, to our knowledge, studies have examined the sera of patients with FBs and CRS using both the GM and G tests. Therefore, this study aimed to evaluate the utility of the serum GM and G tests in diagnosing FBs.

The study included 42 patients with FBs (10 men and 32 women) and 63 with CRS (27 men and 36 women). There were no significant differences in the incidence of hypertension, diabetes mellitus, asthma, or allergic rhinitis between the two groups. However, the CRS group exhibited significantly higher SNOT-22 scores, averaging 26.0±20.2, compared to 17.3±15.9 in the FB group (p=0.023). In contrast, the FB group demonstrated a significantly higher olfactory function score, averaging 22.0±4.4, versus 18.9±6.7 in the CRS group (p=0.005). Additionally, the incidence of anosmia was greater in the CRS group at 23.8%, compared to 4.8% in the FB group (p=0.031).

However, there were no significant differences in the positivity rate between the two groups for either the serum GM test (7.1% for the FB group vs. 3.2% for the CRS group, respectively; p=0.640), or the G test (9.5% for the FB group vs. 11.1% for the CRS group, respectively; p=0.482) (Table 1). The serum GM test showed low sensitivity (7.1%) but high specificity (96.8%). The PPV was 60.0%, and the NPV was 61.0%. The serum G test results were similar, with a sensitivity of 9.5%, specificity of 88.9%, PPV of 36.3%, and NPV of 59.6% (Fig. 1).

Our study revealed no significant differences in serum GM and G test results between FB and CRS patients. Additionally, these tests exhibited low sensitivity and PPV, underscoring their unsuitability for diagnosing FBs. In line with the findings of Kostamo et al. [5] regarding GM tests in FB patient mucus, our data also indicate that GM is unreliable for diagnosing FBs.

Paranasal sinus FBs are the most prevalent form of noninvasive fungal rhinosinusitis and are responsible for recurrent sinusitis in approximately 3.7% of CRS patients [1]. Its incidence has been on the rise worldwide, including in Korea [7]. The exact mechanisms behind FB formation are not well understood, but potential contributing factors include environmental influences, changes in sinus airflow resistance, and variations in nasal cavity anatomy [8]. The maxillary sinus, which is often affected by FBs, is commonly associated with dental procedures such as implant surgery. One study indicated that between 65% and 86.7% of FB patients had undergone previous dental treatments [9]. This link underscores the importance of meticulous implant placement in the maxillary sinus floor, as dental implants may pose a risk factor for FB development, a finding corroborated by other recent studies [10].

The GM test serves as a valuable initial screening tool for diagnosing acute invasive fungal sinusitis, which is characterized by elevated serum GM levels and high clinical suspicion [11]. In the study conducted by Melancon et al. [11], the GM test demonstrated a sensitivity of 44.8%, a specificity of 100%, a PPV of 100%, and an NPV of 36% for diagnosing acute invasive fungal sinusitis. Despite its relatively low sensitivity, the presence of acute invasive fungal sinusitis is confirmed when the GM test is positive and clinical suspicion is high. Conversely, the serum GM test is deemed ineffective for diagnosing FBs, as evidenced by the low sensitivity (7.1%) and PPV (60.0%) observed in our study. Invasive fungal sinusitis is characterized by the infiltration of surrounding tissues. In contrast, FBs involve the formation of dense clusters of fungal hyphae that do not invade the mucosa, blood vessels, or bones [2]. Therefore, unless there is an invasion into surrounding blood vessels, it is improbable that cell wall components of Aspergillus species will be detected in the serum. Consistent with this understanding, our study reported a low positivity rate for both GM and G tests in patients with FBs. Similarly, a study on pulmonary FBs indicated that the sensitivity of the GM test increased with the presence of hemoptysis [12], further underscoring the association between the test and blood vessel involvement.

The GM test sometimes shows false-positive results, which seem to be linked to the use of beta-lactam antibiotics. Components of these beta-lactam antibiotics, being semisynthetic drugs derived from fungi or higher bacteria, may exhibit cross-reactivity with Aspergillus GM molecules [13]. Consequently, varying concentrations of these cross-reactive GM molecules in different moieties of beta-lactam antibiotics can lead to positive results in the GM test

A limitation of our study is that we did not investigate dental treatment in CRS patients, which is a potential risk factor for FBs. However, our histopathological approach to distinguishing between FBs and CRS reduces the likelihood of overlooking FBs in the CRS group. Beta-lactam antibiotics can influence GM levels, which may lead to false positives [13]. Nonetheless, this is unlikely to significantly affect the overall sensitivity of the GM test in our study. Another limitation is that when the GM test yielded positive results in patients with FBs, we could not confirm the presence of infections in other areas. We plan to address this by conducting additional tests on the patient.

Despite these limitations, this is the first study to evaluate the diagnostic utility of the serum GM and G tests for FBs. Our findings confirm that the GM and G tests are not useful for diagnosing FBs, as indicated by their sensitivity, specificity, PPV, and NPV. Additionally, we observed a low probability of fungal invasion into the blood vessels of paranasal sinus FBs. This observation is further supported by the higher presence of fungal components in pulmonary FBs with hemoptysis, which may be attributed to anatomical differences between the paranasal sinuses and the lungs.

In conclusion, the serum GM and G tests for FBs demonstrate limited clinical diagnostic value. Although these tests exhibit high specificity, their low NPV indicates that a negative result does not exclude the presence of FBs. Consequently, clinicians should base their diagnosis of FBs on a comprehensive assessment that includes clinical symptoms, imaging studies such as CT scans, and, ultimately, histopathological examination during surgery.