CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Dana Razzano, MD
He Wang, MD, PhD
August 2021—Salivary gland neoplasms (SGN) are a special group of tumors due to the high variation in histologic subtypes that are further complicated by frequent overlapping morphological features. Fine-needle aspiration is a safe, cost-effective, first-line modality for diagnosing SGNs, an integral part of SGN preoperational workup. In 2018, Faquin and Rossi led the effort to standardize the reporting system of salivary gland lesions.1 Their final product, Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), has had a huge impact on salivary gland FNA practice in the United States and worldwide. The system has promoted improved communication between clinical practices by fostering consistency and transferability of diagnoses, resulting in improved patient care.
The system put forth a uniform tiered framework for classifying and reporting SGNs, an evidence-based scale for estimating the risk of malignancy (ROM), and clear-cut management recommendations. The MSRSGC also provides metrics for ongoing quality assurance and improvement. The six tiers of the MSRSGC and respective ROMs are as follows: 1) nondiagnostic (ND), 25 percent; 2) non-neoplastic, 10 percent; 3) atypia of undetermined significance (AUS), 20 percent; 4a) neoplasm, benign, less than five percent; 4b) neoplasm, salivary gland of uncertain malignant potential, 36 percent; 5) suspicious for malignancy, 60 percent; 6) malignant, 90 percent.
As of now, more than 100 articles have been published related to the MSRSGC, many of which are international collaborations. These studies have examined the applicability of the system in various clinical scenarios: retrospective versus prospective; interobserver reproducibility2; salivary gland cystic lesions3; submandibular lesions4; and lesions in pediatric patients.5 Some studies even retrospectively evaluated the FNA diagnosis of resected specific entities such as pleomorphic adenoma or Warthin tumor.6 The studies confirm that FNA has excellent diagnostic performance in differentiating between benign and malignant salivary gland lesions and effectively distinguishes low- from high-grade neoplasms. The MSRSGC is a valuable tool for preoperative risk stratification.
Like all good classification systems, widespread application has prompted new questions and suggestions for improvement and opportunities for clarification. A few recent advancements in salivary gland cytopathology deserve particular attention and could potentially be included in future discussion of updated guidelines:
● Questions related to the nondiagnostic category. Although the cytologic criteria of the ND category are tentatively defined by the MSRSGC as “<60 lesional cells or normal salivary gland tissue only within the clinical setting of an evident mass,” the criteria have not been validated or established in the literature. Not everyone agrees that the criteria are adequate to address all potentially nondiagnostic scenarios. For instance, aspirates that consist of abundant matrix material without a cellular component should not be classified as nondiagnostic according to the current MSRSGC. This has impelled debate among pathologists. Further study is necessary to address the questions that have arisen surrounding this category.
A related question in the ND category of the MSRSGC is the relatively high risk of malignancy. Results from meta-analyses have demonstrated variation: Hollyfield, et al., reported a ROM of 38 percent, and Wei, et al., reported a ROM of 25 percent.7 In more recent studies, the ROMs for the ND category are much lower than the 25 percent reported in the MSRSGC. As some authors have pointed out, the variability between ROM in different studies may be due to multiple factors such as sample size variation, nonrepresentative sampling, and/or the low surgical resection rates of ND specimens.7 Ultimately, accumulated literature after the widespread application of the MSRSGC is likely to modify the ROM for the ND category.
● Subclassification of current MSRSGC categories. Suggestions have been proposed in the literature to subclassify certain categories of the MSRSGC. Because of differences in clinical management, it has been proposed that category six be divided into two subdivisions and one additional unique category (creation of category seven), as follows8: 6a) low-grade malignancy that requires complete surgical excision without concurrent neck dissection; 6b) high-grade malignant neoplasms that require more radical surgical excision with concurrent neck dissection. High-grade primary salivary gland neoplasms and metastatic lesions to the parotid gland lymph nodes (squamous cell carcinoma, metastatic melanoma, and Merkel cell carcinoma) were grouped together because both require treatment of draining the lymph node basin; 7) hematological malignancies, to ensure the clinician obtains appropriate hematological consultation and the specimen is sent fresh for flow cytometry.
Another study analyzed the risk stratification and clinical outcome of lesions in MSRSGC category three (AUS) when they were further subdivided. The risk of malignancy was found to be highest in the category of specimens with obscuring preparation artifacts and lowest in the cases categorized as indefinite for neoplasm with reactive and reparative atypia present. The authors therefore suggest it is important to subgroup AUS.9