Salivary gland tumor cytologic and histologic correlation: Algorithmic and risk stratification based approaches

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1 Salivary gland tumor cytologic and histologic correlation: Algorithmic and risk stratification based approaches Christopher C. Griffith, MD, PhD Raja R. Seethala, MD 1. Salivary gland tumor cytology: A pattern based approach and risk stratification scheme a. Salivary gland aspiration cytology i. Salivary gland tumor FNA 1. Pre-operative triage of salivary tumors a. High specificity in differentiation of 1 : i. Benign versus malignant (97%) ii. Neoplastic versus non-neoplastic (98%) b. Limit unnecessary surgical excision in cases of non-neoplastic disease 2 c. Guide extent of surgical excision, especially when combined with frozen section at time of excision 3,4 2. However, ability of FNA cytology to provide specific diagnosis is limited, particularly for malignant tumors 5,6 a. Wide range of aggressiveness within lesions having extensive morphologic overlap. For example basaloid neoplasms show extensive morphologic overlap but range from benign to highly malignant neoplasms: i. Pleomorphic adenoma ii. Basal cell adenoma/adenocarcinoma iii. Adenoid cystic carcinoma b. Some malignant diagnoses have low grade or subtle cytologic features or require identification of invasion i. Basal cell adenoma versus adenocarcinoma ii. Acinic cell carcinoma iii. Low grade mucoepidermoid carcinoma iv. Polymorphous low grade adenocarcinoma 3. Potential approaches to overcome limitations in salivary gland tumor FNA a. Improve morphologic criteria to make more accurate distinctions between mimickers i. Literature often points to very subtle features, some requiring highly specialized techniques ii. Most salivary gland tumors are so rare that it is challenging for anyone to gain sufficient experience b. Accept current morphologic limitations and devise a pattern based risk stratification scheme b. Design of a pattern based risk stratification scheme for salivary gland FNA 7 i. Common, morphologically characteristic tumors can often be identified and diagnosed on FNA and therefore are placed into named categories 1. Pleomorphic adenoma 1

2 2. Warthin tumor ii. Basaloid neoplasms have significant morphologic overlap and many produce stroma which is used to subclassify these neoplasms: 1. Quantity of stroma versus cellularity 2. Stromal character fibrillary versus hyaline a. For example, in many texts and articles, the presence of hyaline stromal spheres is stated to be a characteristic feature of adenoid cystic carcinoma. However, in our experience this is not the case with many tumors showing hyaline stroma being basal cell neoplasms on excision. Aspirates of adenoid cystic carcinoma often show stroma which is more challenging to clearly characterize on aspiration smears iii. Oncocytoid neoplasms can also show morphologic overlap and range from benign to malignant lesions. Mucoepidermoid carcinoma is a prototypical oncocytoid neoplasm which frequently shows mucus production and therefore background material, particularly mucus, is used to subclassify oncocytoid neoplasms iv. Acinic cell carcinoma is a special case of oncocytoid neoplasm in that the cytoplasmic coarse granularity is highly characteristic on cytology. Therefore a special oncocytoid category is used to capture acinic cell carcinoma. Mammary analogue secretory carcinoma shows similar features to acinic cell carcinoma on cytology and is grouped in this category of oncocytoid neoplasm with granular/vacuolated cytoplasm v. Some tumor types are clearly malignant on cytologic grounds due to high nuclear grade. These neoplasms often show pleomorphic nuclei with other high grade features. Division into basaloid and oncocytoid pleomorphic groups is also helpful as pleomorphic oncocytoid neoplasm is a common pattern for salivary duct carcinoma and pleomorphic basaloid neoplasm is predicted to capture salivary gland tumors with high grade transformation as well as a variety of other malignant basaloid neoplasms. vi. This scheme is designed for primary salivary gland epithelial tumors and therefore, an attempt should be made to exclude metastasis. lymphoproliferative and mesenchymal lesions when possible by morphology and/or immunostains. c. Definition of salivary gland aspiration cytology patterns 7 i. The common named patterns: 1. Pleomorphic adenoma features should be highly characteristic for the diagnosis of pleomorphic adenoma a. Fibrillary stroma is characteristic and should comprise at least 25% of lesional material ( troll-doll hair ) b. Bland myoepithelial cells embedded in stroma may show spindle, stellate, or plasmacytoid morphology c. Bland ductal cells may also be seen but are less prominent 2. Warthin tumor features should be highly characteristic for Warthin tumor; clinical history is also helpful as younger, non-smoker patients are unlikely to develop Warthin tumors and other possible diagnoses should be considered 2

3 a. Epithelial component composed of truly oncocytic epithelium which are highly cohesive, well organized, and of low to moderate nuclear grade b. A lymphoid component is represented by lymphocytes in the background or by lymphoid tangles c. Small amounts of mucin in the background are acceptable but should not be prominent ii. Monomorphic cellular basaloid neoplasms aspirate smears show a neoplasm composed of low to moderate nuclear grade basaloid cells. Basaloid cells have scant cytoplasm as would be expected in basal or myoepithelial cells. Stroma usually comprises less than 25% of lesional material. Subclassify as follows: 1. With fibrillary stroma fibrillary stroma is present similar to that seen in pleomorphic adenoma but the aspirate is more cellular with stroma comprising less than 25% of lesional material 2. With hyaline stroma stroma has a hyaline character which is more dense and smooth than fibrillary stroma. Hyaline stroma often forms spheres but may also have a membranous pattern. Cellular components are usually excluded from hyaline stroma 3. With mixed/other stroma stroma is absent or difficult to characterize as either fibrillary or hyaline. Reasons for difficulty in characterizing the stroma include 1) stroma too scant to characterize, 2) stroma is fibrillary in some areas but hyaline in other areas, or 3) stroma shows features indeterminate between fibrillary and hyaline stroma iii. Monomorphic oncocytoid neoplasms neoplastic cells have more cytoplasm than basaloid cells and are reminiscent of oncocytic cells although they may not be true oncocytes. Nuclear grade is low to moderate but smears are not sufficiently characteristic of Warthin tumor. Fine dense granularity of on oncocyte is included but coarse foamy/vacuolated cytoplasm is excluded. Subclassify as follows: 1. With cystic background mostly histiocytes and granular debris make up the background material 2. With mucinous background mucinous strands are present in the background. Cells having large single cytoplasmic vacuoles are often present but are not required 3. With other background Background features are not classifiable as cyst contents or mucin. A clean background is common in this category iv. Oncocytoid neoplasm with granular/vacuolated cytoplasm neoplastic cells have prominent foamy and coarsely granular cytoplasm or multiple small vacuoles in the cytoplasm. Cells are more dyshesive and have fragile cytoplasm resulting in naked nuclei v. Pleomorphic neoplasms 1. Pleomorphic basaloid neoplasms Smears show a predominantly basaloid neoplasm with high grade nuclear features including pleomorphism, increased mitotic activity, apoptosis, and nuclear membrane irregularity 2. Pleomorphic oncocytoid neoplasms Neoplastic cells have fairly abundant cytoplasm but also show high grade nuclear features including pleomorphism, mitoses, apoptosis, and nuclear membrane irregularities 3

4 d. Pattern based risk stratification and differential diagnoses i. Relative risk of malignancy based on cytomorphologic pattern (data based on selected cohort with surgical excision within 6 months of aspiration) 7 4

5 ii. Primary considerations in the differential diagnosis for patterns in salivary gland cytology References: 1. Schmidt RL, Hall BJ, Wilson AR, et al. A systematic review and meta-analysis of the diagnostic accuracy of fine-needle aspiration cytology for parotid gland lesions. Am J Clin Pathol. 2011;136: Layfield LJ, Gopez E, Hirschowitz S. Cost efficiency analysis for fine-needle aspiration in the workup of parotid and submandibular gland nodules. Diagn Cytopathol. 2006;34: Schmidt RL, Hunt JP, Hall BJ, et al. A systematic review and meta-analysis of the diagnostic accuracy of frozen section for parotid gland lesions. Am J Clin Pathol. 2011;136: Seethala RR, LiVolsi VA, Baloch ZW. Relative accuracy of fine-needle aspiration and frozen section in the diagnosis of lesions of the parotid gland. Head Neck. 2005;27: Colella G, Cannavale R, Flamminio F, et al. Fine-needle aspiration cytology of salivary gland lesions: a systematic review. J Oral Maxillofac Surg. 2010;68: Hughes JH, Volk EE, Wilbur DC. Pitfalls in salivary gland fine-needle aspiration cytology: lessons from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology. Arch Pathol Lab Med. 2005;129: Griffith CC, Pai RK, Schneider F, Duvvuri U, Ferris RL, Johnson JT, Seethala RR. Salivary gland tumor fine-needle aspiration cytology: a proposal for a risk stratification classification. Am J Clin Pathol Jun;143(6):