Section 1 -

Introduction to Salivary Gland Cytology William C. Faquin, M.D., Ph.D. Celeste N. Powers, M.D., Ph.D.

Challenging Areas of Salivary Gland Cytology Salivary gland cytology represents one of the most challenging areas of all of cytopathology owing to the wide range of lesions that can be encountered and the significant degree of overlap between some benign and malignant tumors. The following is a list of some of the more challenging diagnostic problems that you will encounter in salivary gland cytology: Challenging Diagnostic Issues in Salivary Gland Cytology : Matrix-containing lesions: e.g. pleomorphic adenoma versus adenoid cystic carcinoma Basaloid neoplasms: e.g. basal cell adenoma versus basal cell adenocarcinoma versus solid variant of adenoid cystic carcinoma Oncocytic lesions: e.g. Warthin's tumor versus oncocytoma versus acinic cell carcinoma Mucinous cysts: e.g. low-grade mucoepidermoid carcinoma versus mucocele High-grade carcinomas: e.g. mucoepidermoid carcinoma versus salivary duct carcinoma versus carcinoma ex pleomorphic adenoma Lymphoid lesions: LESA vs lymphoma Clear cell tumors: e.g. epithelial-myoepithelial carcinoma vs metastasis vs myoepithelioma Mesenchymal lesions vs myoepithelial Rationale and Indications for Salivary Gland FNAB: FNAB is widely used at many institutions for the evaluation of salivary gland lesions. Overall, FNAB is safe, cost-effective, and accurate. Most often, FNAB acts as a guide for the clinician in assessing the need for surgical or other clinical intervention for any unexplained salivary gland mass. When surgery is indicated, results from the FNAB can assist in the pre-operative strategy: Non-neoplastic lesions (e.g. chronic sialadenitis) may not require surgical intervention Benign tumors (e.g. pleomorphic adenoma) treated with limited surgical resection Low-grade malignancies are usually treated with limited surgical resection High-grade carcinomas are usually treated with radical surgical resection Facial nerve sacrifice may be necessary Lymph node neck dissection and neo-adjuvant therapy are often indicated Accuracy Overall, FNAB is fairly accurate in the assessment of salivary gland lesions. In recent studies, sensitivity and specificity for neoplasia is >90%. The distinction between benign and malignant neoplasms has a sensitivity of 80-90% and a specificity of >90%. Diagnostic accuracy is lower for rendering a specific diagnosis. High diagnostic accuracy for neoplastic versus non-neoplastic lesions High accuracy for low-grade versus high-grade lesions Variable accuracy depending upon the specific entity (e.g. high accuracy for pleomorphic adenoma, lower for basal cell adenocarcinoma) Important!!! Sample Preparation: Both Romanowsky-type (Diff-Quik, Giemsa, MGG) and Papanicolaou stains are essentialin the evaluation of most salivary gland lesions by FNAB, especially those with matrix material. Air-dried Romanowsky-stained smears highlight diagnostically useful features of the matrix component that are poorly visualized in alcohol-fixed preparations of lesions such as pleomorphic adenoma, basal cell tumors, and adenoid cystic carcinoma. Romanowsky stains also aid in the evaluation of lymphoid lesions. Papanicolaou-stained smears are especially useful for evaluating nuclear features and cytoplasmic differentiation. The Normal Salivary Gland Aspirate: Aspirates of normal salivary gland are hypocellular, comprised of groups of acinar cells, occasional ductal cells, and admixed adipose tissue. Acinar cells are usually present as cohesive polarized grape-like clusters with associated small inconspicuous tubules and honeycomb sheets of cohesive ductal cells. Naked nuclei from crushed acinar cells may be present in the background. The presence of normal salivary gland as the only cytologic finding warrants careful clinical correlation to exclude the possibility of a sampling error. Other explanations for normal-appearing salivary gland elements include a prominent but normal salivary gland, sialadenosis, and lipoma. Pitfall: A pitfall for the diagnosis of normal salivary gland tissue is mistaking it for acinic cell carcinoma (and vice versa). Cytologic Features of the Normal Salivary Gland Aspirate: Serous and mucinous acinar cells in grapelike clusters + background naked nuclei Admixed small tubules and/or sheets of ductal epithelium Adipose tissue Section 1 - Figure 1 Normal salivary gland showing ductal cells and acinar cells Histologic Features of Normal Salivary Gland: The normal salivary gland appears histologically as numerous lobules of acinar cells with a surrounding capsule and fibroadipose connective tissue septa. The lobules of acinar cells are connected by an arborizing network of ducts with the larger bilayered ducts being the excretory ducts, these are connected to smaller striated ducts, and the smallest cuboidal lined ducts which feed into the lobules are the intercalated ducts. The acinar cells within the lobules may be serous, mucinous, or a mixture of both depending upon the type of salivary gland tissue (parotid is entirely serous, submandibular is mixed, and minor salivary glands are mucinous). The parotid gland is unique in that it has lymph nodes associated near and within its structure. Section 1 - Figure 2 Normal salivary gland showing serous-type acinar cells, striated ducts, and fibroadipose stroma.