Salivary gland lesions present a significant diagnostic challenge due to their diverse histopathological spectrum. Fine-needle aspiration cytology (FNAC) is a widely used, minimally invasive technique that aids in the preoperative assessment of these lesions. However, the absence of standardized reporting criteria has historically led to variability in diagnosis and management. To address this, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was introduced, providing a structured, risk-stratified classification system that enhances diagnostic accuracy and clinical decision-making.^1,2,3

The Milan system categorizes salivary gland FNAC findings into six distinct groups, each associated with a defined risk of malignancy (ROM) and corresponding clinical recommendations. This standardized approach improves communication between cytopathologists and clinicians, ensuring appropriate surgical or conservative management strategies.^4,5

Epidemiology and Burden of Salivary Gland Lesions

Salivary gland neoplasms account for approximately 3-6% of all head and neck tumors worldwide. The incidence rate of salivary gland tumors varies between 0.4 to 2.6 cases per 100,000 population annually, with the parotid gland being the most commonly affected site (~80% of cases). Submandibular and minor salivary gland tumors account for a smaller proportion.

Among these lesions, benign neoplasms (e.g., pleomorphic adenomas and Warthin’s tumor) constitute 60-80% of cases, whereas malignant tumors (e.g., mucoepidermoid carcinoma, adenoid cystic carcinoma) comprise approximately 15-30%. Malignant salivary gland tumors often exhibit slow-growing but locally invasive behavior, making early and accurate diagnosis crucial for optimal patient management.^6,7,8

FNAC plays a critical role in distinguishing between benign and malignant lesions, allowing clinicians to stratify patients based on risk assessment and surgical necessity. Despite its high accuracy, FNAC results can sometimes be inconclusive or misleading, emphasizing the importance of a standardized classification system like MSRSGC.

Classification of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC)

The Milan System classifies salivary gland FNAC into six diagnostic categories, each with a corresponding risk of malignancy (ROM) and recommended clinical action:

Aims of the Study

To classify salivary gland FNAC cases according to the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and correlate them with histopathological findings.

To determine the risk of malignancy (ROM) for each category in the Milan system and assess its diagnostic accuracy in differentiating benign and malignant salivary gland lesions.

Study Design: This is a retrospective observational study conducted over a two-year period at a tertiary care centre. The study involved the review and analysis of fine-needle aspiration cytology (FNAC) samples from patients presenting with salivary gland lesions.

Study Population:All patients who underwent FNAC of salivary gland lesions over the study period were included. Cases with available histopathological follow-up were analyzed for cytohistological correlation. Exclusion Criteria: Cases with inadequate FNAC samples or lost follow-up were excluded from the final analysis.

Cytological Evaluation and Classification

• FNAC was performed under aseptic precautions using a 22-25G needle, and smears were stained with Hematoxylin & Eosin (H&E), Papanicolaou, and May-Grünwald Giemsa (MGG) stains.
• The cytological findings were classified according to the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) into six diagnostic categories:
• Category I: Nondiagnostic
• Category II: Nonneoplastic
• Category III: Atypia of undetermined significance (AUS)
• Category IVa: Benign neoplasm
• Category IVb: Salivary gland neoplasm of uncertain malignant potential (SUMP)
• Category V: Suspicious for malignancy
• Category VI: Malignant

Histopathological Correlation: Histopathological follow-up was obtained for all surgically resected cases, and cytohistological concordance was evaluated.Cases were compared based on cytological and histopathological features, and discrepancies were analyzed.

Statistical Analysis:Diagnostic performance metrics such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated. The risk of malignancy (ROM) was determined for each category and compared with existing literature.

This methodology ensures a structured and standardized approach in evaluating the role of FNAC and MSRSGC in salivary gland lesion diagnosis.

Table 1: Milan System Distribution of Salivary Gland Cytopathology

This table categorizes the 150 cases based on the Milan System classification. The majority of cases fall under the Nonneoplastic category (64 cases, 42.7%). The Benign Neoplasms category accounts for 48 cases (32%), while Malignant cases comprise 24 cases (16%). The Atypia of undetermined significance category has no cases.

Table 2: Age Group Distribution of Cases

This table represents the age-wise distribution of cases. The 21-40 years age group has the highest number of cases (61 cases, 40.7%), followed by the 41-60 years group (52 cases, 34.7%). The 0-20 years and 61+ years groups contribute to 10% and 14.7%, respectively.

Table 3: Gender Distribution of Cases

This table presents the gender-wise distribution of cases. The majority of cases (54.7%) were male (82 cases), while 45.3% were female (68 cases).

Table 4: Diagnostic Performance Metrics

The diagnostic performance metrics indicate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of cytological diagnoses. Sensitivity and PPV values are notably high, reflecting strong diagnostic accuracy.

Table 5: Malignancy Risk by Category

This table highlights the malignancy risk percentages for different categories. Category 6 (Malignant) has the highest malignancy risk (117.6%), while Category 2 (Benign) has a much lower risk (8.3%).

Nondiagnostic Cases

Currently, no standardized adequacy criteria exist for fine-needle aspiration (FNA) of salivary glands. However, studies suggest that low cellularity can lead to increased discrepancies in diagnosis. In this study, 4 cases were classified as nondiagnostic. These cases exhibited smears with minimal cellular content and necrotic debris in the background. Some samples contained only cystic aspirate, making it impossible to establish a cytological diagnosis.

Nonneoplastic Cases

The majority of cases (82 cases, 54.7%) fell under the nonneoplastic category. These cases included conditions such as sialadenitis, chronic sialadenitis, acute-on-chronic sialadenitis, lymphoepithelial sialadenitis, granulomatous sialadenitis, and cystic lesions of the salivary gland. Cytological smears in this group lacked any features suggestive of malignancy, showing only acinar or ductal epithelial cells within an inflammatory background.

Atypia of Undetermined Significance

No cases were categorized under atypia of undetermined significance (AUS) in this study.

Benign Neoplasms

A total of 38 cases were classified as benign neoplasms. The most common benign tumors included pleomorphic salivary adenoma (PSA) and Warthin’s tumor, both of which have well-defined cytological features. Other benign neoplasms, which displayed minimal to mild cytological atypia, were characterized by a fibrillary or myxoid stroma and were grouped into basaloid or oncocytic neoplasms. Cases with high cellularity (>75%) and moderate atypia were categorized under salivary gland neoplasm of uncertain malignant potential (SUMP), accounting for 3 cases.

Suspicious for Malignancy

A total of 4 cases were classified as suspicious for malignancy. These smears exhibited cytological features that were qualitatively or quantitatively insufficient to confirm a diagnosis of carcinoma or other malignant salivary gland neoplasms.

Malignant Cases

A total of 19 cases were identified as malignant, with mucoepidermoid carcinoma (MEC) being the most frequently diagnosed malignancy (8 of 19 cases). Other confirmed malignant cases included adenoid cystic carcinoma, as well as rarer tumors such as squamous cell carcinoma and acinic cell carcinoma. Some cases could not be definitively classified beyond the general term “malignant tumor” based on cytological findings alone.

Diagnostic Performance & Malignancy Risk

Cytohistological correlation was performed for 150 cases, and the diagnostic accuracy metrics were as follows:

• Sensitivity: 97.64%, Specificity: 80.95%
• Positive Predictive Value (PPV): 96.35%,  Negative Predictive Value (NPV): 84%

The malignancy risk was calculated for each category, with the highest risk observed in Category 6 (malignant) at 94.3%, while the lowest malignancy risk (7.2%) was seen in Category 2 (benign cases).

Fine-needle aspiration cytology (FNAC) remains a key preoperative diagnostic tool for salivary gland lesions, helping differentiate benign from malignant neoplasms. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was developed to standardize cytopathology reporting and provide risk stratification for improved clinical decision-making.

Our study demonstrates a high sensitivity (97.64%) and diagnostic accuracy (93%), which aligns with the findings of previous studies. However, the specificity (80.95%) in our study was relatively lower than in some reports, suggesting a potential for false positives in malignancy detection. The risk of malignancy (ROM) for the malignant category (94.3%) was consistent with earlier studies, reinforcing the reliability of MSRSGC in predicting malignancy. Additionally, the lowest ROM (7.2%) in the benign category highlights its strong negative predictive value.

Compared to previous studies, our study had complete histopathological follow-up for all cases (150/150), strengthening the validity of our diagnostic performance metrics. Notably, our results reaffirm the role of FNAC as a highly accurate diagnostic tool, with the Milan system serving as an effective framework for categorization and risk stratification. However, the variability in ROM across different categories suggests a need for further refinement, particularly in cases classified as suspicious for malignancy (SFM) or SUMP (salivary gland neoplasm of uncertain malignant potential).

The findings from this study support the continued application of MSRSGC as a valuable classification system in salivary gland cytopathology. With high sensitivity and diagnostic accuracy, it enhances communication between cytopathologists and clinicians, ultimately improving patient management. However, variations in specificity and ROM across different studies highlight the need for continuous validation and refinement of the classification criteria. Future research should focus on integrating clinical, radiological, and molecular markers to further enhance diagnostic precision and minimize false positives or negatives.

Summary Table: Comparison of Studies on Milan System for Salivary Gland Cytopathology

Conflict of Interest:         None

Funding Support: Nil.

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