Salivary gland lesions encompass a wide morphological spectrum ranging from non-neoplastic inflammatory conditions to benign and malignant neoplasms, often presenting as cystic or solid swellings of the parotid, submandibular, sublingual, or minor salivary glands. Their clinical presentation frequently overlaps, making accurate preoperative diagnosis crucial for patient management. Fine-Needle Aspiration Cytology (FNAC) has emerged as the first-line, minimally invasive, cost-effective diagnostic modality, offering rapid tissue assessment and playing a decisive role in differentiating benign from malignant salivary gland lesions. FNAC is particularly valuable because salivary gland neoplasms exhibit significant heterogeneity, variable stromal components, and overlapping cytomorphological features, often complicating diagnosis if cytology is used in isolation.[1] Radiological imaging, especially ultrasonography (USG), serves as an essential adjunct to FNAC. USG offers real-time evaluation, precisely localizes the lesion, distinguishes cystic from solid components, guides aspiration, and identifies calcifications, vascularity, and deep-lobe extension. Its non-invasive nature, accessibility, and superior spatial resolution make it an indispensable tool in initial evaluation. However, operator dependency and limited ability to characterize complex lesions necessitate complementary diagnostic methods.[2] Cross-sectional imaging modalities-CT and MRI-add value in lesions with heterogeneous appearance, infiltration, suspected malignancy, or deep parotid involvement by demonstrating extension patterns, margin characteristics, perineural spread, and nodal involvement.[3] The diagnostic synergy between radiology and cytology has gained prominence in recent years, especially with the introduction of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), which provides standardized reporting, risk stratification, and management guidance. MSRSGC categorizes lesions into six diagnostic tiers with associated Risk of Malignancy (ROM), thereby optimizing communication between cytopathologists and clinicians and improving clinical decision pathways.[4] Cystic salivary gland lesions pose unique diagnostic challenges. Aspirates may be hypocellular, obscured by mucin or debris, or fail to capture representative epithelial elements, leading to atypical or non-diagnostic reports. Cystic variants of neoplasms-such as Warthin tumor, low-grade mucoepidermoid carcinoma, and cystic pleomorphic adenoma-often mimic benign retention cysts radiologically and cytologically.[5] Aim To integrate radiological and cytological findings for accurate classification of cystic and solid salivary gland lesions using the Milan System for Reporting Salivary Gland Cytopathology. Objectives 1. To evaluate ultrasonographic characteristics of cystic and solid salivary gland lesions. 2. To correlate FNAC findings of salivary gland lesions with Milan System-based diagnostic categories. 3. To assess radiocytological concordance and final diagnostic accuracy in available histopathology cases.

Source of Data Data were collected from patients presenting with salivary gland swellings to the Departments of Pathology and Radiology at a tertiary care hospital. USG reports, FNAC smears, and histopathology slides (where applicable) were included. Data extraction was conducted from institutional records and prospective case evaluation. Study Design A prospective observational cross-sectional study was conducted. Study Location Department of Pathology and Department of Radiology, at tertiary care hospital. Study Duration 18 months. Sample Size 50 cases of salivary gland lesions (cystic and solid). Inclusion Criteria • Patients aged ≥18 years with clinically or radiologically detectable salivary gland lesions. • Patients who underwent both ultrasonography and FNAC. • Cases with adequate cytological material for interpretation as per MSRSGC criteria. Exclusion Criteria • Patients with recurrent salivary gland malignancies. • Cases with incomplete radiological or FNAC data. • Lesions not amenable to FNAC (deep inaccessible lesions). • Patients unwilling to participate or undergo procedures. Procedure and Methodology Clinical Evaluation: All patients underwent clinical examination including lesion duration, site, tenderness, mobility, and consistency. Radiological Assessment: High-resolution ultrasonography (7.5-10 MHz) was performed. Each lesion was assessed for: Size, shape, echogenicity. Cystic vs solid nature. Septations, margins, calcifications. Vascularity on Doppler. Deep-lobe extension. CT/MRI was performed in selected heterogeneous or suspicious lesions. Fine-Needle Aspiration Cytology: FNAC was performed using a 22-24G needle. Smears were prepared-both air-dried and alcohol-fixed. Air-dried smears were stained with MGG. Alcohol-fixed smears were stained with H&E and Papanicolaou stains. Cytological interpretation was categorized using Milan System 2018 into six tiers. Histopathology Correlation: Where surgical specimens were available, histopathology was considered the gold standard. H&E-stained tissue sections were evaluated for tumor type and grade. Sample Processing Smears were screened for cellularity, epithelial cell type, stromal matrix, cyst macrophages, necrosis, mucin, lymphoid population, and malignant features. Radiological findings were compared with cytological categories for concordance. Cases with cystic smears and low cellularity were re-evaluated for repeat aspiration. Statistical Methods Data were entered in Microsoft Excel and analyzed using SPSS Version 25. Descriptive statistics: means, percentages, standard deviations. Inferential statistics: Chi-square test for categorical correlations. Sensitivity, specificity, PPV, NPV for FNAC and USG. Cohen’s kappa coefficient for radiocytological concordance. p < 0.05 was considered statistically significant. Data Collection Structured proforma included: Demographics (age, sex). Clinical features (pain, duration, site). USG findings. FNAC category (Milan I-VI). Histopathology (where available). Radiocytological concordance outcome

Table 1: Baseline Characteristics and Integrated Radiocytological Classification (N = 50) Variable Total (N = 50) Cystic Lesions (n=20) Solid Lesions (n=30) Test Statistic 95% CI of Difference p-value Age (years), Mean ± SD 44.8 ± 13.2 41.2 ± 12.8 46.9 ± 13.1 t = 1.54 -2.2 to 12.8 0.129 Male, n (%) 28 (56%) 10 (50%) 18 (60%) χ² = 0.54 - 0.462 Female, n (%) 22 (44%) 10 (50%) 12 (40%) - - - Parotid gland, n (%) 34 (68%) 12 (60%) 22 (73.3%) χ² = 1.04 - 0.307 Submandibular gland, n (%) 12 (24%) 6 (30%) 6 (20%) - - - Minor glands, n (%) 4 (8%) 2 (10%) 2 (6.7%) - - - Final Cytology (MSRSGC) Benign (II), n (%) 30 (60%) 14 (70%) 16 (53.3%) χ² = 1.58 - 0.208 Suspicious/Malignant (IV-VI), n (%) 12 (24%) 2 (10%) 10 (33.3%) χ² = 3.76 - 0.052 Non-diagnostic, n (%) 8 (16%) 4 (20%) 4 (13.3%) χ² = 0.43 - 0.514 In the present study (N = 50), the mean age of patients with salivary gland lesions was 44.8 ± 13.2 years, with cystic lesions showing a slightly younger mean age (41.2 ± 12.8 years) compared to solid lesions (46.9 ± 13.1 years), though the difference was not statistically significant (t = 1.54, p = 0.129). The gender distribution showed a mild male predominance (56%), which was comparable between cystic (50%) and solid lesions (60%) (p = 0.462). The parotid gland was the most commonly involved site (68%), especially among solid lesions (73.3%), whereas cystic lesions comprised 60% of parotid swellings; however, the distribution did not reach statistical significance (p = 0.307). Submandibular (24%) and minor salivary glands (8%) constituted the remainder of cases. Cytological evaluation revealed that Benign (Milan Category II) diagnoses accounted for 60% of all cases, with a higher proportion among cystic lesions (70%) than solid lesions (53.3%) (p = 0.208). In contrast, Milan Categories IV-VI (Suspicious/Malignant) were more frequent in solid lesions (33.3%) compared to cystic ones (10%), approaching borderline statistical significance (χ² = 3.76, p = 0.052). Non-diagnostic aspirates constituted 16% of the study population without significant group differences. Table 2: Ultrasonographic Characteristics of Cystic vs. Solid Salivary Gland Lesions (N = 50) USG Feature Cystic (n=20) Solid (n=30) Test Statistic 95% CI p-value Lesion Size (cm), Mean ± SD 2.8 ± 0.9 3.4 ± 1.1 t = 2.05 0.01 to 1.13 0.046 Well-defined margins, n (%) 14 (70%) 20 (66.7%) χ² = 0.06 - 0.808 Ill-defined margins, n (%) 6 (30%) 10 (33.3%) - - - Hypoechoic pattern, n (%) 6 (30%) 22 (73.3%) χ² = 10.06 - 0.002 Complex cystic pattern, n (%) 12 (60%) 4 (13.3%) χ² = 14.08 - <0.001 Increased Doppler vascularity, n (%) 4 (20%) 16 (53.3%) χ² = 5.77 - 0.016 Ultrasonographic evaluation showed distinct differences between cystic and solid salivary gland lesions. The mean lesion size was significantly larger in solid lesions (3.4 ± 1.1 cm) compared to cystic lesions (2.8 ± 0.9 cm), with statistical significance (t = 2.05, p = 0.046). Well-defined margins were commonly seen in both groups (70% in cystic vs 66.7% in solid), indicating that margin definition alone was not discriminatory (p = 0.808). However, echotexture patterns differed markedly: hypoechoic echogenicity was observed in 73.3% of solid lesions compared to only 30% of cystic lesions (p = 0.002). Conversely, complex cystic patterns, including septations or internal echoes, were significantly more common in cystic lesions (60%) versus solid lesions (13.3%), demonstrating a highly significant association (χ² = 14.08, p < 0.001). Doppler assessment further differentiated lesion types, with increased vascularity present in 53.3% of solid lesions but only 20% of cystic ones (p = 0.016). These sonographic parameters collectively highlight that hypoechogenicity and vascularity strongly favor solid lesions, whereas complex cystic morphology is characteristic of cystic lesions. Table 3: FNAC Findings vs. Milan System Categories (N = 50) Milan Category n (%) Cystic (n=20) Solid (n=30) Test Statistic p-value Category I - Non-diagnostic 8 (16%) 4 (20%) 4 (13.3%) χ² = 0.43 0.514 Category II - Non-neoplastic 10 (20%) 6 (30%) 4 (13.3%) χ² = 2.16 0.141 Category III - Atypia of Undetermined Significance (AUS) 6 (12%) 4 (20%) 2 (6.7%) χ² = 2.22 0.136 Category IVA - Benign neoplasm 20 (40%) 6 (30%) 14 (46.7%) χ² = 1.55 0.212 Category IVB - Salivary gland neoplasm NOS 2 (4%) 0 2 (6.7%) χ² = 1.38 0.240 Category V - Suspicious for malignancy 2 (4%) 0 2 (6.7%) χ² = 1.38 0.240 Category VI - Malignant 2 (4%) 0 2 (6.7%) χ² = 1.38 0.240 FNAC categorization using the Milan System demonstrated variable distribution across cystic and solid lesions. Non-diagnostic aspirates (Category I) accounted for 16% of cases and were slightly more common among cystic lesions (20%) than solid lesions (13.3%), though not statistically significant (p = 0.514). Non-neoplastic lesions (Category II) comprised 20% overall, with higher proportions in cystic lesions (30%) compared to solid lesions (13.3%), suggesting that cystic lesions frequently yield benign or inflammatory cytology, though this difference did not reach statistical significance (p = 0.141). AUS (Category III) was identified in 12% of cases, again more common in cystic lesions (20% vs 6.7%), reflecting cellular sparsity or obscuring cystic fluid as typical diagnostic challenges. Benign neoplasms (Category IVA) formed the largest category (40%), seen more frequently in solid lesions (46.7%) than cystic ones (30%). Malignant-associated categories (IVB, V, VI) were exclusively observed in solid lesions, accounting for a combined 15% of solid lesions, whereas no cystic lesion fell into these categories. Table 4: Radiocytological Concordance and Diagnostic Accuracy (Histopathology n = 30) Parameter Value Test Statistic 95% CI p-value Histopathology available, n (%) 30 (60%) - - - Benign on Histopathology, n (%) 22 (73.3%) - - - Malignant on Histopathology, n (%) 8 (26.7%) - - - Radiological diagnosis accuracy (%) 76.7% χ² = 12.45 - 0.001 Cytology diagnosis accuracy (%) 83.3% χ² = 19.88 - <0.001 Radiocytological concordance, n (%) 24/30 (80%) Cohen’s κ = 0.62 0.38-0.86 <0.001 Sensitivity (malignant) 75% - - - Specificity (benign) 90% - - - PPV 75% - - - NPV 90% - - - Histopathological confirmation was available in 30 cases (60%), of which 73.3% were benign and 26.7% were malignant. Radiological evaluation demonstrated a diagnostic accuracy of 76.7% with statistically significant reliability (χ² = 12.45, p = 0.001), while cytology showed a higher diagnostic accuracy of 83.3%, which was highly significant (χ² = 19.88, p < 0.001). The radiocytological concordance rate (agreement between USG impression and FNAC category) was 80%, corresponding to a Cohen’s kappa value of 0.62, indicating substantial agreement (p < 0.001). Diagnostic performance indices revealed high specificity for benign lesions (90%) and a strong negative predictive value (90%), indicating that benign cytological diagnoses were reliably confirmed on histopathology. The sensitivity for detecting malignant cases was 75%, with a positive predictive value of 75%. Figure 1 Figure 2 Figure 1: FNAC of Acute Sialadenitis showing acinar cells in a tiny cluster interspersed with neutrophils and histiocytes against the background of cellular debris. 40x, H&E Figure 2: USG of Parotid gland - Gland is enlarged, hypoechoic and hyperaemic, suggestive of an inflammatory lesion. FNAC diagnosis was acute sialadenitis Figure 3 Figure 4 Figure 3: FNAC of Benign Lymphoepithelial Lesion of right parotid gland showing tiny epithelial clusters with lymphocyte. 40x, MGG Figure 4: USG: Heterogenous echotexture with multiple tiny, well defined hypoechoic/anechoic cystic lesion diffusely distributed within right parotid gland. FNAC diagnosis was Benign Lymphoepithelial Lesion Figure 5 Figure 6 Figure 5: FNAC of Pleomorphic Adenoma having the classic fibrillary chondromyxoid Figure 6: Pleomorphic Adenoma - USG showing a well-defined, lobulated, hypoechoic lesion with posterior acoustic enhancement in the right parotid gland. Figure 7 Figure 8 Figure 7: FNAC of Warthin’s Tumor showing oncocytic cells in a background of lymphocytes.40 x, H&E Figure 8: Warthin’s tumor – USG showing an ovoid lesion with well-defined margins and having multiple small irregular anechoic areas in the right parotid gland

The baseline characteristics presented in Table 1 demonstrate that salivary gland lesions affected individuals primarily in the fourth to fifth decade of life, with a mean age of 44.8 years. This aligns with the findings of Hafez NH et al. (2020)[6], who reported a mean age of 45.3 years for mixed salivary gland pathologies, indicating that both cystic and solid lesions tend to occur in middle-aged adults. The slight male predominance (56%) observed in this study parallels the results of Rossi ED.et al. (2021)[7], who described a similar demographic distribution. As in prior research, the parotid gland emerged as the most frequently involved site (68%), consistent with the classic epidemiological distribution described by Romanò R et al. (2024)[8], who reported the parotid as the location for 70-80% of salivary neoplasms. Cytologically, a greater proportion of cystic lesions were classified as Milan II (benign/non-neoplastic) compared to solid lesions (70% vs. 53.3%), reflecting the known challenges in aspirating representative epithelial cells from cystic lesions-a finding similar to Sakr M. (2025)[9], who emphasized that cystic changes often lead to benign or non-diagnostic categories. Conversely, solid lesions demonstrated a higher proportion of Milan IV-VI diagnoses (33.3%), approximating the malignant yield reported by Mezi S et al. (2020)[10] in their Milan-based stratification studies. Although differences were not statistically significant, the trend is clinically relevant and mirrors established pathology patterns. Table 2 highlights significant ultrasonographic differences between cystic and solid lesions. Solid lesions were significantly larger (p = 0.046), more frequently hypoechoic (73.3%), and exhibited increased vascularity (53.3%). These characteristics correlate with the malignancy-associated sonographic features described by Hafez NH et al. (2020)[6], who noted that hypoechogenicity and hypervascularity strongly predicted neoplastic or malignant pathology. Conversely, cystic lesions displayed complex internal echoes in 60% of cases, comparable to the findings of Rossi ED. (2021)[7], who observed complex cystic patterns in benign cystadenomas, Warthin tumors, and cystic variants of pleomorphic adenoma. The FNAC-Milan System correlation in Table 3 reveals diagnostic patterns consistent with previous validation studies. The proportion of Milan I (non-diagnostic) cases (16%) closely matches the 10-20% range reported by Mezi S et al. (2020)[10], who attributed inadequacy primarily to cystic fluid aspirates-a trend reflected in our data since cystic lesions showed a higher proportion of AUS and non-diagnostic samples. The dominance of Category IVA (benign neoplasm) is also expected, as pleomorphic adenoma and Warthin tumor comprise the majority of salivary gland neoplasms. Malignant categories (IVB-VI) were exclusively seen in solid lesions in this study, which is consistent with the typical morphology of malignancies being solid rather than cystic, as reaffirmed by Pusztaszeri M et al. (2024)[3]. Table 4 demonstrates strong radiocytological performance. The accuracy of radiology (76.7%) and cytology (83.3%) closely mirrors published literature, such as the study by Kumar M et al. (2024)[11], who noted FNAC accuracy between 80-90% for salivary neoplasms. The radiocytological concordance rate of 80% with a Cohen’s κ of 0.62 signifies substantial agreement, again consistent with the findings of Rondi P et al. (2024)[12], who reported kappa values between 0.55-0.70 when correlating imaging with Milan System categories. The sensitivity and specificity values (75% and 90%) demonstrate high reliability of cytology for distinguishing malignant from benign lesions, supporting the diagnostic utility of the Milan System.

The present study demonstrates that the integrated use of ultrasonography, fine-needle aspiration cytology, and the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) enhances diagnostic accuracy for both cystic and solid salivary gland lesions. FNAC proved to be highly reliable in distinguishing benign from malignant lesions, particularly when supported by characteristic radiological features. Ultrasonography effectively differentiated cystic vs. solid architecture and suggested benignity in well-defined, homogeneous lesions, whereas FNAC contributed essential cellular details that resolved diagnostic ambiguities-especially in cystic lesions where hypocellularity and overlapping cytomorphology often limit interpretation. The combined radiocytological approach showed high concordance with final histopathology wherever tissue diagnosis was available, validating its role as a robust, minimally invasive diagnostic pathway. The study reinforces that FNAC, interpreted through the MSRSGC framework, remains the cornerstone investigation, and its integration with radiology optimizes early diagnosis, clinical decision-making, and treatment planning for salivary gland lesions. LIMITATIONS 1. Small sample size (n = 50) limits generalizability of diagnostic accuracy estimates. 2. Histopathological confirmation was available only for surgically managed cases, restricting the ability to measure true sensitivity and specificity across all MSRSGC categories. 3. Ultrasonography interpretations varied with operator experience, introducing subjective variation. 4. Cystic lesions had hypocellular aspirates, reducing FNAC yield and potentially causing under-classification in Milan categories II-III. 5. Advanced imaging (CT/MRI) was not performed uniformly for all complex or deep-lobe lesions, limiting radiological correlation in selected cases. 6. The study was conducted in a single tertiary-care center, which may not reflect diagnostic practices or lesion patterns in other settings.

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