and Mine Onenerk
Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
The salivary glands are comprised of three major (parotid, submandibular, and sublingual) and numerous minor salivary glands which are dispersed within the upper aerodigestive tract. Combined with clinical and radiologic evaluation, fine needle aspiration (FNA) represents a useful initial procedure in the assessment of a salivary gland mass. The normal salivary gland parenchyma is composed of small exocrine units consisting of acini and a ductal system (intercalated, striated, and excretory ducts in the major glands). The serous or mucinous content of the acinar cells and length of the ducts show site-specific differences.
Salivary gland tumors constitute a heterogeneous group with more than 40 primary benign and malignant neoplasms described by the WHO. Although some exceptions exist, there is a female predominance and mean overall age of 46–47 years for patients presenting with a salivary gland tumor. Benign tumors outnumber malignant, and pleomorphic adenoma (PA) is the most common type of salivary gland neoplasm in the adult population.
Except for PA, the prevalence of benign and malignant tumors is reported to be highly variable among different populations. In most of the series, Warthin tumor is the second most common benign tumor, and it is almost exclusively seen in the parotid gland. Mucoepidermoid carcinoma (MEC), polymorphous low-grade adenocarcinoma, adenoid cystic carcinoma, and acinic cell carcinoma comprise the more common malignant tumors.
Several studies have shown that the majority of primary salivary gland tumors occur in the parotid gland (64–80 %). Tumor prevalence is relatively low in other sites – approximately 10 % for submandibular gland, 1 % for sublingual gland, and 9–23 % for minor salivary glands. The rate of malignancy is inversely proportional to the gland size: 15–32 % for the parotid gland, 41–45 % for the submandibular gland, 70–90 % for the sublingual gland, and 90 % for the minor salivary glands. Metastatic tumors comprise only 5 % of all malignant salivary gland tumors, and the majority is squamous cell carcinomas. FNA can also be performed for nonneoplastic mass-forming salivary gland lesions such as acute or chronic sialoadenitis and granulomatous sialoadenitis. Cytological diagnoses are based on cytomorphologic criteria. Ancillary tests including immunohistochemistry, histochemistry, flow cytometry, and molecular analysis (e.g., FISH, NGS, PCR) can contribute to improved cytologic accuracy. Surgery is the treatment option for almost all primary salivary gland tumors, but the extent of surgery, facial nerve conservation, and performance of a neck dissection will vary depending on the preoperative diagnosis. Thus, an accurate FNA diagnosis is useful for guiding the preoperative management strategy.
Cytological Reporting Guidelines
Currently, a uniform reporting system is lacking for salivary gland FNAs. Most laboratories use conventional cytologic categories to report results (nondiagnostic, negative for malignant cells, atypical, suspicious for malignancy, or positive for malignant cells) and a specific (pleomorphic adenoma, Warthin tumor, acinic cell carcinoma, etc.) or descriptive diagnosis (basaloid or myoepithelial neoplasm, etc.) in their reports. There have been efforts to introduce a more reproducible and risk-based classification system known as the Milan System for Reporting Salivary Gland Cytopathology.
The Milan System is a six-tiered system with the following proposed categories: Non-diagnostic, Non-neoplastic, Atypia of Undetermined Significance (AUS), Neoplastic, Suspicious for Malignancy and Malignant. It is important in the ‘Suspicious for Malignancy and the Malignant’ categories to distinguish low-grade from high-grade tumors.
Indication, Collection, and Laboratory Processing of Cytological Samples
Salivary gland FNA is an accurate and cost-effective method in the preoperative management of patients with a salivary gland mass. The overall accuracy ranges from 81 to 98 % and is higher for benign tumors when compared to malignant. An accurate assessment of salivary gland cytology depends on the adequacy/preparation quality of the specimen and the cytopathologists’ awareness of overlapping features of different tumor types and diverse cytomorphologic appearances of any given specific tumor.
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Methods of Specimen Collection
An FNA of a salivary gland mass can be performed by using a 23–27-gauge needle with or without applying negative pressure. Air-dried and alcohol-fixed smears as well as liquid-based slides can give complementary information in the characterization of cytologic features. For example, air-dried smears are especially valuable for appreciating the different stromal and matrix characteristics of various tumor types which can be a significant diagnostic clue to the correct diagnosis. Correlation of the cytologic specimen and radiologic findings is essential for an accurate diagnosis and can be integrated when the FNA is performed under ultrasound guidance.
Chronic sialadenitis of the submandibular gland. (a) Aspirations from chronic sialadenitis are generally hypocellular. In this case ductal cells form a flat sheet which resembles a tubule. Cells have evenly spaced nuclei, an important finding supporting the benign nature of the ductal cells. Ductal nuclei are slightly enlarged and uniform with fine chromatin. Acinar cells are generally rarely encountered in chronic sialadenitis. Inflammatory cells are present in the background, and they rarely infiltrate ductal cells (Pap-stained DS). (b) Inflammation is more easily recognized in this slide. Histiocytes and lymphocytes are admixed with dispersed ductal cells (SP). (c) Lymphocytes infiltrate around the intercalated ducts. Fibrosis around the ducts and acinar atrophy are also present (H&E)
Pleomorphic adenoma (PA) of the parotid gland. (a) Epithelial and myoepithelial cells are admixed with characteristic metachromatic fibrillary matrix with frayed edges (Giemsa-stained DS). Romanovsky-type stains are more valuable for the evaluation of the matrix characteristics. The fibrillary consistency of the matrix is important in the differentiation of PA from other salivary gland neoplasms such as adenoid cystic carcinoma or basal cell adenoma. (b) Myoepithelial cells are embedded within the fibrillary matrix. Neoplastic cells have moderate amounts of cytoplasm, nuclei are uniform and bland, and the chromatin is fine and evenly dispersed (SP). (c, d) A different PA case with fibrillary matrix and cells with round to oval nuclei and moderate amounts of cytoplasm (c, Pap-stained DS; d, TP). (e) The biphasic growth pattern with ducts lined by cuboidal epithelial cells and intervening cellular myxoid stromal component (H&E)
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