Chronic rhinosinusitis (CRS) is defined as persistent inflammation of the nasal and paranasal sinus mucosa lasting more than 12 weeks and is associated with symptoms such as nasal obstruction, discharge, facial pain, and olfactory dysfunction [1]. It represents a major global health burden, affecting approximately 5–12% of the population and significantly impairing quality of life [2].

CRS is broadly categorized into two phenotypes:

• CRS with nasal polyps (CRSwNP)
• CRS without nasal polyps (CRSsNP)

These phenotypes differ significantly in their immunopathology, inflammatory mediators, and tissue remodeling patterns [3]. CRSwNP is typically associated with eosinophilic inflammation and Th2-mediated responses, whereas CRSsNP often demonstrates neutrophilic inflammation and fibrosis [4].

Computed tomography (CT) remains the imaging modality of choice for CRS due to its superior ability to delineate sinonasal anatomy and disease extent [5]. The Lund–Mackay scoring system is widely used to quantify radiological severity, assigning scores based on sinus opacification and ostiomeatal complex obstruction [6]. However, CT findings primarily reflect anatomical and mucosal thickening rather than cellular-level inflammation.

Histopathological examination provides direct insight into mucosal changes, including:

• Eosinophilic and neutrophilic infiltration
• Basement membrane thickening
• Subepithelial fibrosis
• Goblet cell hyperplasia and glandular hypertrophy [7]

Despite the widespread use of both modalities, the correlation between radiological findings and histopathological severity remains inconsistent across studies. Some studies report poor correlation between CT scores and inflammatory severity [8], while others demonstrate moderate to strong associations, particularly in CRSwNP [9].

Understanding this relationship is crucial for clinical decision-making, especially in guiding surgical interventions and targeted therapies. Therefore, this systematic review and meta-analysis aims to comprehensively evaluate the correlation between radiological findings and histopathological changes in CRS.

METHODS

Study Design

This systematic review and meta-analysis was conducted following PRISMA 2020 guidelines and Cochrane recommendations [10].

Search Strategy

A comprehensive literature search was performed in:

• PubMed
• Scopus
• Web of Science
• Google Scholar

Search terms included: “chronic rhinosinusitis,” “CT scan,” “radiological findings,” “histopathology,” “Lund-Mackay score,” and “correlation” [11].

Eligibility Criteria

Inclusion Criteria:

• Studies involving adult CRS patients
• Reporting both radiological and histopathological findings
• Providing correlation data or extractable statistics
• Observational, cross-sectional, or cohort studies

Exclusion Criteria:

• Case reports, reviews, editorials
• Studies without histopathological confirmation
• Pediatric-only populations
• Non-English publications

Data Extraction

Two independent reviewers extracted:

• Study characteristics (year, country, design)
• Sample size
• Imaging modality and scoring system
• Histopathological parameters
• Correlation coefficients

Discrepancies were resolved by consensus [12].

Quality Assessment

Study quality was assessed using the Newcastle–Ottawa Scale (NOS) for observational studies [13].

Statistical Analysis

• Random-effects meta-analysis model
• Pooled correlation coefficient (r)
• Heterogeneity assessed using I² statistics
• Subgroup analysis based on CRS phenotype

RESULTS

Study Selection

A total of 1,243 studies were identified. After screening and eligibility assessment, 18 studies were included in the final analysis.

Figure 1: PRISMA 2020 flow diagram illustrating the study selection process. A total of 1,243 records were identified through database searching. After removal of duplicates and screening, 110 full-text articles were assessed for eligibility. Eighteen studies met the inclusion criteria and were included in the qualitative and quantitative synthesis.

Study Characteristics

Radiological–Histopathological Correlation

Subgroup Analysis

CRSwNP demonstrated a stronger correlation, likely due to prominent eosinophilic inflammation and polyp formation visible on CT imaging [14].

Heterogeneity

Heterogeneity may be attributed to:

• Variability in histopathological scoring systems
• Differences in patient populations
• Study design heterogeneity

Figure 2: Forest plot showing the correlation between radiological findings and histopathological changes in chronic rhinosinusitis across included studies. Each point represents the correlation coefficient (r) for an individual study, with horizontal lines indicating 95% confidence intervals. The vertical line represents the pooled correlation estimate (r = 0.46), demonstrating a moderate overall association.

DISCUSSION

The present systematic review and meta-analysis demonstrate a moderate positive correlation (r = 0.46) between radiological findings and histopathological changes in chronic rhinosinusitis (CRS), suggesting that while imaging provides valuable structural information, it does not fully capture the underlying inflammatory pathology. This finding aligns with earlier studies that have reported partial agreement between computed tomography (CT) severity scores and mucosal inflammatory changes, reinforcing the concept that CRS is a complex and heterogeneous disease entity with multifactorial pathophysiology [8,15]. The Lund–Mackay scoring system, although widely used due to its simplicity and reproducibility, primarily reflects the degree of sinus opacification and ostiomeatal obstruction rather than cellular or molecular inflammatory activity, thereby limiting its ability to predict histopathological severity [6,17].

The stronger correlation observed in CRS with nasal polyps (CRSwNP) compared to CRS without nasal polyps (CRSsNP) is particularly noteworthy and can be explained by the distinct immunopathological mechanisms underlying these subtypes. CRSwNP is typically characterized by eosinophilic inflammation, edematous stroma, and polypoidal mucosal changes, which are more readily visualized on CT imaging as diffuse opacification and polyp formation [14,18]. In contrast, CRSsNP often exhibits a predominance of neutrophilic inflammation, fibrosis, and less conspicuous mucosal thickening, which may not be adequately reflected in radiological findings, thereby contributing to the relatively weaker correlation [3,4]. This discrepancy highlights the importance of considering CRS endotypes rather than relying solely on phenotypic or radiological classification.

Another important consideration is the inherent difference in what each modality measures. Radiological imaging assesses macroscopic anatomical changes such as mucosal thickening, sinus opacification, and obstruction of drainage pathways, whereas histopathology evaluates microscopic features including inflammatory cell infiltrates, epithelial damage, basement membrane thickening, and tissue remodeling [7,16]. These differences in measurement domains contribute significantly to the observed moderate correlation, as structural abnormalities on CT do not always correspond to the intensity or type of inflammation at the cellular level. Additionally, temporal variation between imaging and biopsy sampling may further weaken the correlation, as inflammatory activity in CRS can fluctuate over time depending on disease stage and treatment status [19].

Sampling variability in histopathological analysis also plays a role in the discordance between radiological and pathological findings. Biopsy specimens are typically obtained from limited areas of the sinonasal mucosa and may not represent the overall disease burden visualized on CT imaging. Furthermore, the lack of standardized histopathological scoring systems across studies introduces additional variability, making direct comparisons challenging and contributing to heterogeneity in pooled estimates [13]. The moderate heterogeneity (I² = 58%) observed in this meta-analysis likely reflects these methodological differences, as well as variations in study design, patient populations, and inclusion criteria.

From a clinical perspective, the findings of this study underscore the complementary roles of radiology and histopathology in the evaluation of CRS. While CT imaging remains indispensable for diagnosis, assessment of disease extent, and preoperative planning, it should not be considered a surrogate for histopathological evaluation, particularly in cases where precise characterization of inflammation is required for targeted therapy [5,16]. This is especially relevant in the current era of precision medicine, where treatment decisions increasingly depend on identifying specific inflammatory endotypes and biomarkers [18]. For instance, the use of biologic agents targeting eosinophilic inflammation necessitates accurate histopathological or molecular characterization, which cannot be reliably inferred from imaging alone.

The moderate correlation observed in this study also has implications for clinical decision-making, particularly in determining the need for surgical intervention. While higher CT scores are often associated with more extensive disease, they do not necessarily indicate greater inflammatory severity or predict response to medical therapy [8]. Therefore, reliance solely on radiological findings may lead to overestimation or underestimation of disease activity. Integrating clinical symptoms, endoscopic findings, radiological assessment, and histopathological evaluation provides a more comprehensive understanding of disease status and enables individualized treatment planning.

Overall, the findings of this meta-analysis highlight the need for a multimodal approach in the assessment of CRS, combining structural imaging with functional and pathological evaluation. Future research should focus on developing standardized histopathological grading systems and exploring advanced imaging techniques, such as functional imaging and artificial intelligence-based analysis, to improve the correlation between radiological findings and underlying inflammatory processes.

CONCLUSION

Radiological findings demonstrate a moderate correlation with histopathological severity in chronic rhinosinusitis. While CT imaging remains essential for diagnosis and surgical planning, it cannot fully substitute histopathological evaluation. A multimodal approach combining clinical, radiological, and pathological assessment is necessary for optimal patient management.

REFERENCES

1. Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, et al. European position paper on rhinosinusitis and nasal polyps 2020. Rhinology. 2020;58(Suppl S29):1–464.
2. Hastan D, Fokkens WJ, Bachert C, Newson RB, Bislimovska J, Bockelbrink A, et al. Chronic rhinosinusitis in Europe—an underestimated disease. Allergy. 2011;66(9):1216–1223.
3. Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Ashok Kumar K, Kramper M, et al. Clinical practice guideline (update): adult sinusitis. Otolaryngol Head Neck Surg. 2015;152(2 Suppl):S1–S39.
4. Kim DW, Cho SH. Emerging endotypes of chronic rhinosinusitis and its application to precision medicine. J Allergy Clin Immunol Pract. 2017;5(5):1284–1292.
5. Zinreich SJ. Imaging of inflammatory sinus disease. Radiology. 2000;215(3):701–708.
6. Lund VJ, Mackay IS. Staging in rhinosinusitis. Rhinology. 1993;31(4):183–184.
7. Bachert C, Zhang N. Chronic rhinosinusitis and asthma: novel understanding of the role of IgE ‘above atopy’. Allergy. 2012;67(11):1479–1487.
8. Bhattacharyya N. Radiographic stage fails to predict symptom outcomes after endoscopic sinus surgery for chronic rhinosinusitis. Laryngoscope. 2006;116(1):18–22.
9. Smith TL, Litvack JR, Hwang PH, Loehrl TA, Mace JC, James KE. Determinants of outcomes of sinus surgery: a multi-institutional prospective cohort study. Otolaryngol Head Neck Surg. 2010;142(4):551–556.
10. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
11. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses. PLoS Med. 2009;6(7):e1000097.
12. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane handbook for systematic reviews of interventions. 2nd ed. Chichester: Wiley; 2019.
13. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute; 2014.
14. Stevens WW, Schleimer RP, Kern RC. Chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol Pract. 2016;138(6):1545–1556.
15. Jones NS. CT of the paranasal sinuses: a review of the correlation with clinical, surgical and histopathological findings. Clin Otolaryngol Allied Sci. 2002;27(1):11–17.
16. Kennedy DW. Functional endoscopic sinus surgery: technique. Arch Otolaryngol. 1985;111(10):643–649.
17. Van Zele T, Gevaert P, Holtappels G, Van Cauwenberge P, Bachert C. Local immunoglobulin production in nasal polyposis is modulated by superantigens. J Allergy Clin Immunol. 2006;118(5):1134–1141.
18. Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Gevaert P, et al. Effect of subcutaneous dupilumab on nasal polyposis. N Engl J Med. 2016;374(18):1758–1769.
19. Tomassen P, Vandeplas G, Van Zele T, Cardell LO, Arebro J, Olze H, et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol. 2016;137(5):1449–1456.
20. Meltzer EO, Hamilos DL, Hadley JA, Lanza DC, Marple BF, Nicklas RA, et al. Rhinosinusitis: establishing definitions for clinical research and patient care. Otolaryngol Head Neck Surg. 2004;131(6 Suppl):S1–S62.
21. Van Crombruggen K, Zhang N, Gevaert P, Tomassen P, Bachert C. Pathogenesis of chronic rhinosinusitis: inflammation. J Allergy Clin Immunol. 2011;128(4):728–732.
22. DeConde AS, Mace JC, Bodner TE, Hwang PH, Rudmik L, Alt JA, et al. SNOT-22 quality of life domains differentially predict treatment modality selection in chronic rhinosinusitis. Int Forum Allergy Rhinol. 2014;4(12):972–979.
23. Hopkins C, Browne JP, Slack R, Lund V, Brown P. The Lund–Mackay staging system for chronic rhinosinusitis: how is it used and what does it predict? Otolaryngol Head Neck Surg. 2007;137(4):555–561.
24. Orlandi RR, Kingdom TT, Hwang PH, Smith TL, Alt JA, Baroody FM, et al. International consensus statement on allergy and rhinology: rhinosinusitis 2021. Int Forum Allergy Rhinol. 2021;11(3):213–739.
25. Snidvongs K, Lam M, Sacks R, Earls P, Kalish L, Pratt E, et al. Structured histopathology profiling of chronic rhinosinusitis in routine practice. Int Forum Allergy Rhinol. 2012;2(5):376–385.