Milan System for Reporting Salivary Gland Cytopathology
The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a standardized, evidence-based risk stratification system that categorizes salivary gland fine-needle aspiration specimens into six diagnostic categories, each with defined risk of malignancy (ROM) to guide clinical management. 1
Six Diagnostic Categories
The MSRSGC consists of the following hierarchical categories with progressively increasing malignancy risk 1:
1. Non-Diagnostic (ND)
- ROM: 0-15% across multiple validation studies 2, 3, 4
- Includes inadequate cellularity, poor preservation, or obscuring blood 2
- Management: Repeat FNA is recommended 2
2. Non-Neoplastic (NN)
- ROM: 0-14.28% 3, 5
- Includes inflammatory conditions, cysts, and normal salivary gland tissue 2
- Management: Clinical follow-up without surgery in most cases 2
3. Atypia of Undetermined Significance (AUS)
- ROM: 33.33-75% 3, 5
- Reserved for cases with cytologic atypia that cannot be definitively classified 2
- This category shows the widest variation in ROM across studies, reflecting diagnostic uncertainty 3, 5
- Management: Repeat FNA or surgical excision depending on clinical context 2
4. Benign Neoplasm (BN)
- ROM: 2.2-9.5% 3, 4
- Includes pleomorphic adenoma, Warthin tumor, and other benign salivary gland tumors 2
- Pleomorphic adenoma is the most common diagnosis in this category 5
- Management: Conservative surgical excision 2
5. Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP)
- ROM: 13.3-66.66% 4, 5
- Used for neoplasms where cytomorphology cannot reliably distinguish benign from low-grade malignancy 1
- Shows significant ROM variability, reflecting the inherent diagnostic challenge 4, 5
- Management: Surgical excision with intraoperative consultation 2
6. Suspicious for Malignancy (SM)
- ROM: 50-100% 3, 4
- Features suggestive but not diagnostic of malignancy 2
- Management: Surgical excision with consideration for more extensive resection 2
7. Malignant (M)
- ROM: 80-100% 3, 6, 5
- Definitive cytologic features of malignancy 2
- The malignant category is subdivided into low-grade and high-grade tumors 1
- Management: Radical surgery with or without adjuvant therapy based on grade and stage 2
Clinical Performance Characteristics
The Milan System demonstrates excellent diagnostic accuracy when validated against histopathology 6:
- Sensitivity: 75-94.20% for detecting malignancy 4, 6
- Specificity: 94.6-98.4% for excluding malignancy 3, 4
- Positive Predictive Value: 82.4-98.48% 3, 6
- Negative Predictive Value: 85.71-98.2% 3, 6
- Overall diagnostic accuracy: 87.50-94.4% 3, 5
Integration with Clinical Guidelines
Pathologists should report risk of malignancy using the Milan System as the standardized risk stratification scheme for salivary gland cytopathology. 7 This recommendation is supported by ASCO guidelines that emphasize standardized reporting to guide surgical decision-making 1.
Key Clinical Applications
The Milan System enables risk-based treatment selection: 2
- Categories I-II (ND, NN): Follow-up without surgery
- Category III (AUS): Repeat FNA or selective surgery
- Category IV (BN): Conservative surgical excision
- Categories V-VII (SUMP, SM, M): Surgical excision with extent determined by malignancy risk
Surgeons may request intraoperative pathologic examination for SUMP and SM categories to guide the extent of resection, but major decisions such as facial nerve sacrifice should not be based on indeterminate diagnoses alone. 1
Important Caveats
False-negative rates can reach 20% even with the Milan System, necessitating correlation with clinical findings and imaging 1. The AUS and SUMP categories show the widest ROM variability across studies (33-75% and 13-67% respectively), reflecting inherent diagnostic challenges in these borderline lesions 3, 5.
Core needle biopsy may be necessary for deep minor salivary glands where FNA access is limited, as the Milan System was primarily validated for major salivary gland lesions 7.