Fungal rhinosinusitis (FRS) has emerged as a clinically significant entity within the spectrum of paranasal sinus infections, particularly in immunocompromised individuals. While bacterial rhinosinusitis remains more common, fungal etiologies have gained increased attention due to their association with higher morbidity, diagnostic challenges, and the need for aggressive medical and surgical interventions [1]. Among vulnerable populations, individuals with diabetes mellitus represent a distinct subgroup at elevated risk due to impaired neutrophil function, ketoacidosis, and hyperglycemia, all of which promote fungal proliferation and invasion [2].

FRS is broadly categorized into invasive and non-invasive forms. The invasive type is most concerning in diabetics and is characterized by tissue necrosis, vascular invasion, and rapid progression, often requiring urgent surgical debridement and antifungal therapy [3]. The non-invasive type, although indolent, may still contribute to significant symptom burden and complications if left untreated. The most frequently implicated organisms include Aspergillus and Mucor species, although regional variations exist depending on climatic and environmental factors [4].

Traditional diagnosis of FRS has relied on clinical features, radiological imaging, and intraoperative findings. However, definitive diagnosis is based on laboratory methods, including histopathological identification of fungal elements in tissue sections and microbiological isolation via culture or potassium hydroxide (KOH) mount. Despite advancements, discrepancies between these modalities are not uncommon and may influence treatment strategies and prognostication [5]. Furthermore, the relationship between specific histological findings—such as angioinvasion, necrosis, and granulomatous inflammation—and clinical outcomes remains underexplored in diabetic cohorts.

The literature reveals limited studies specifically addressing the concordance between histopathological and microbiological findings in fungal rhinosinusitis among diabetic patients. Given the often subtle clinical presentation and the high risk of progression to life-threatening complications in this population, timely and accurate diagnosis is essential [6]. Invasive FRS, particularly mucormycosis, has been associated with poor outcomes and high mortality if not identified early. Moreover, a lack of correlation between diagnostic modalities may lead to misdiagnosis or delayed treatment initiation [7, 8].

This study aims to address the existing gap by investigating the histopathological and microbiological features of FRS in diabetic patients and correlating these findings with clinical outcomes. By comparing the diagnostic yield of each modality and analyzing their relationship with disease severity and recovery trajectory, this research seeks to enhance the understanding of fungal rhinosinusitis in a high-risk cohort.

This prospective observational study was conducted in the Department of Pathology at the Society for Tripura Medical College and Dr. B. R. Ambedkar Memorial Teaching Hospital, Agartala, over a 12-month period from October 2009 to September 2010. The study population comprised diabetic patients presenting with clinical and radiological suspicion of rhinosinusitis, referred for functional endoscopic sinus surgery (FESS).

Inclusion and Exclusion Criteria

Inclusion criteria consisted of adult patients (aged ≥18 years) with known Type 1 or Type 2 diabetes mellitus, radiologically confirmed sinus involvement, and intraoperative tissue samples available for both histopathological and microbiological evaluation. Patients with prior antifungal therapy, known immunodeficiencies apart from diabetes, or incomplete clinical records were excluded from the study.

Sample Collection and Processing

Intraoperative specimens from affected sinuses were divided into two portions. One portion was fixed in 10% formalin for histopathological examination using Hematoxylin & Eosin (H&E) staining. Special stains including Periodic Acid-Schiff (PAS) and Gomori Methenamine Silver (GMS) were employed where necessary to enhance fungal visualization.

The second portion was transported in sterile saline to the microbiology laboratory for direct microscopy using 10% KOH mount and fungal culture. Cultures were performed on Sabouraud Dextrose Agar (SDA) and incubated at 25°C and 37°C for up to 3 weeks. Identification of fungal isolates was done based on colony morphology and lactophenol cotton blue staining.

Clinical Evaluation and Outcome Assessment

Patient demographics, glycemic control (as measured by HbA1c), clinical presentation, comorbidities, and radiological findings were recorded. Postoperative clinical outcomes were assessed at 1-month and 3-month intervals using a standardized scoring system incorporating symptom resolution, recurrence, and need for repeat intervention. Outcomes were categorized as favorable (complete recovery or significant symptom relief) or unfavorable (persistent symptoms, recurrence, or complications).

Data were entered into Microsoft Excel and analyzed using SPSS version 16.0. Descriptive statistics were used to summarize demographic and clinical variables. Diagnostic yields of histopathology and microbiology were calculated as percentages. Chi-square test was employed to assess associations between diagnostic modality (histopathology, culture, or both) and clinical outcome. p-values < 0.05 were considered statistically significant. Sensitivity and specificity were calculated using composite clinical and radiological diagnosis as reference standards.

Institutional Ethical Committee approval was obtained prior to study initiation. Written informed consent was secured from all participants for sample collection and use of clinical data for research purposes. Confidentiality and anonymity were maintained throughout.

Table 1: Demographic and Clinical Characteristics of Study Participants (N = 50)

Table 2: Diagnostic Modality Outcomes (N = 50)

Table 3: Microbiological Isolates (N = 23)

Table 4: Correlation of Diagnostic Modality with Clinical Outcome

Table 5: Association of Glycemic Control (HbA1c) with Type of Fungus

Fig 1: Distribution of fungal species

In this study of 50 diabetic patients with suspected fungal rhinosinusitis, the majority belonged to the 41–60 years age group (62%), with males constituting 64% of the cohort. Poor glycemic control was common, with 38% of patients having HbA1c >9%, a parameter later shown to significantly correlate with mucormycosis.

Out of all cases, 64% (32/50) were confirmed positive for fungal rhinosinusitis by at least one diagnostic modality. Histopathological examination yielded positive results in 28 cases (56%), whereas fungal culture confirmed infection in 23 cases (46%). Direct microscopy using KOH mount was positive in 38% (19/50). Dual positivity (both histopathology and culture) was found in 19 patients, comprising 38% of the cohort.

Microbiological analysis (Table 3 and Graph) revealed that Aspergillus spp. was the most common isolate, seen in 43.5% (10/23) of culture-positive cases. Mucor spp. followed with 34.8% (8/23), while Candida spp. accounted for 13.0% (3/23). Mixed fungal growth was identified in 8.7% (2/23).

Clinical outcome analysis (Table 4) revealed a distinct pattern. Among patients with dual positivity, 13 out of 19 (68.4%) experienced unfavorable outcomes. In contrast, patients with no diagnostic confirmation had better outcomes, with 15 out of 18 (83.3%) showing favorable recovery. The association between dual positivity and poor clinical outcome was statistically significant (p < 0.05), indicating that the presence of fungal elements in both modalities likely reflects a higher fungal burden or invasiveness.

Furthermore, Table 5 highlights a notable correlation between poor glycemic control and Mucor infections: 6 of the 8 Mucor cases (75%) occurred in patients with HbA1c >9%. This suggests a significant pathogenic link between uncontrolled diabetes and mucormycosis severity.

These findings underscore the critical importance of combining diagnostic modalities and monitoring glycemic control in managing diabetic patients with fungal rhinosinusitis.

Fungal rhinosinusitis (FRS) remains a diagnostic and therapeutic challenge, particularly among diabetic individuals, who are predisposed to invasive forms due to impaired immunity and hyperglycemia [1–8]. The current study aimed to correlate histopathological and microbiological findings in FRS with clinical outcomes, thereby addressing a critical gap in diagnostic concordance in this high-risk group.

The rationale stemmed from prior reports of delayed or incomplete diagnosis when relying on a single modality [9]. In our cohort, histopathology demonstrated a higher diagnostic yield (56%) than culture (46%), aligning with observations by Panda et al. [10], who emphasized the superior sensitivity of tissue-based diagnosis in invasive fungal infections. While fungal culture remains indispensable for species identification, its sensitivity is often compromised by prior antifungal use or poor sample viability, as noted by Talbot et al. [11].

Aspergillus spp. emerged as the predominant isolate, followed by Mucor spp., reflecting regional trends observed in tropical zones. Saravanan et al. [12] similarly reported Aspergillus as the leading cause of both invasive and allergic fungal sinusitis in southern India. Importantly, mucormycosis showed a significant correlation with poor glycemic control (HbA1c >9%), reinforcing findings by Yohai et al. [13], who linked uncontrolled diabetes to mucor-related rhinocerebral infections.

Dual positivity—both histopathology and culture being positive—was significantly associated with unfavorable outcomes (68.4% of such patients). This may reflect more aggressive fungal invasion, consistent with conclusions by Rowe-Jones et al. [14], who highlighted histological angioinvasion as a predictor of poor prognosis in diabetic FRS.

The clinical and radiologic features were also typical: nasal obstruction (82%) and maxillary sinus opacification (68%) were the most common findings. Karthikeyan et al. [15] similarly documented maxillary sinus predominance in diabetic fungal sinusitis cases.

One key limitation of the study is its single-center design, which may not account for geographical variations in fungal species. Additionally, the lack of antifungal susceptibility testing restricted therapeutic correlations. However, the strength lies in the prospective design and direct correlation of diagnostic modality with outcome.

Future directions should explore molecular diagnostic tools such as PCR and real-time sequencing to improve early detection, especially in culture-negative cases. Multi-center trials with long-term follow-up can provide stronger validation for dual positivity as a prognostic marker.

Fungal rhinosinusitis (FRS) in diabetic patients is a clinically significant condition requiring timely diagnosis and appropriate intervention. This study demonstrated that histopathological examination had a higher diagnostic yield than fungal culture, although both modalities play complementary roles. Dual positivity was significantly associated with poorer clinical outcomes, particularly among patients with uncontrolled diabetes mellitus and mucormycosis. The findings underscore the importance of integrated diagnostic evaluation using both tissue histology and microbiological culture in high-risk diabetic patients. Additionally, poor glycemic control emerged as a key modifiable risk factor associated with more aggressive fungal infections. These insights should prompt clinicians to maintain a high index of suspicion and initiate early, aggressive treatment in diabetic individuals presenting with sinonasal infections. Future research focusing on rapid diagnostics and multicentric outcome assessments may further enhance management protocols.

Acknowledgement

The authors would like to express their sincere gratitude to the departmental staff for their collaboration and technical support during the course of this study.

Conflicts of Interest

The authors declare no conflicts of interest related to this study.

1. Chakrabarti A, Das A, Panda NK. Controversies surrounding the categorization of fungal rhinosinusitis. Med Mycol. 2009;47(Suppl 1):S299–S308.
2. Panda NK, Sharma SC, Chakrabarti A. Paranasal sinus mycoses. Indian J Otolaryngol Head Neck Surg. 1998;50(1):33–9.
3. Chakrabarti A, Panda NK. Mucormycosis in India: unique features. Mycoses. 2009;52(6):385–90.
4. Kumar R, Bakshi J, Kansal AP. Mucormycosis presenting as orbital cellulitis: early diagnosis and management. Indian J Ophthalmol. 2004;52(4):309–12.
5. Saravanan K, Panda NK, Chakrabarti A. Allergic fungal sinusitis: an Indian perspective. Mycoses. 2006;49(3):241–5.
6. Ferguson BJ. Fungus balls of the paranasal sinuses. Otolaryngol Clin North Am. 2000;33(2):389–98.
7. Gungor A, Reiersen DA. Fungal sinusitis: current trends in diagnosis and treatment. Curr Infect Dis Rep. 2004;6(6):487–92.
8. deShazo RD, Swain RE. Diagnostic criteria for noninvasive fungal sinusitis. J Allergy Clin Immunol. 1995;96(1 Pt 1):24–35.
9. Chakrabarti A, Denning DW, Ferguson BJ. Defining and classifying fungal rhinosinusitis. Curr Fungal Infect Rep. 2006;1(1):22–8.
10. Panda NK, Sharma SC, Chakrabarti A, Mann SB. Paranasal sinus mycoses in north India. Mycoses. 1998;41(7–8):281–6.
11. Talbot GH, Huang A, Provencher M. Invasive aspergillosis: diagnostic strategies and therapeutic outcomes. Rev Infect Dis. 1990;12(Suppl 3):S325–S333.
12. Saravanan K, Panda NK, Chakrabarti A. Allergic fungal sinusitis: histological spectrum and implications. Indian J Pathol Microbiol. 2007;50(3):496–9.
13. Yohai RA, Bullock JD, Aziz AA. Survival factors in rhino-orbital-cerebral mucormycosis. Surv Ophthalmol. 1994;39(1):3–22.
14. Rowe-Jones JM, Moore-Gillon V. Diagnosis and management of fungal sinusitis. J Laryngol Otol. 1992;106(6):505–10.
15. Karthikeyan P, Kumar R, Seth R. Fungal sinusitis in diabetic patients: a clinical and CT correlation. Indian J Otolaryngol Head Neck Surg. 2005;57(4):301–4.