BACKGROUND: Recent discussions have focused on redefining noninvasive follicular variant of papillary thyroid carcinoma (NI-FVPTC) as a neoplasm rather than a carcinoma. This study assesses the potential impact of such a reclassification on the implied risk of malignancy (ROM) for the diagnostic categories of The Bethesda System for Reporting Thyroid The FNAB cohort consisted of 6943 thyroid nodules representing 5179 women and 1409 men with an average age of 54 years (range, 9-94 years). The combined average ROM and OROM for the diagnostic categories of TBSRTC were as follows: nondiagnostic, 4.4% to 25.3%; benign, 0.9% to 9.3%; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 12.1% to 31.2%; follicular neoplasm (FN), 21.8% to 33.2%; suspicious for malignancy (SM), 62.1% to 82.6%; and malignant, 75.9% to 99.1%. The impact of reclassifying NI-FVPTC on the ROM and OROM was most pronounced and statistically significant in the 3 indeterminate categories: the AUS/FLUS category had a decrease of 5.2% to 13.6%, the FN category had a decrease of 9.9% to 15.1%, and the SM category had a decrease of 17.6% to 23.4% (P < .05), whereas the benign and malignant categories had decreases of 0.3% to 3.5% and 2.5% to 3.3%, respectfully. The trend of the effect on the ROM and OROM was similar for all 5 institutions. CONCLUSIONS: The results from this multiinstitutional cohort indicate that the reclassification of NI-FVPTC will have a significant impact on the ROM for the 3 indeterminate categories of TBSRTC.

BACKGROUND: Fine-needle aspiration cytology (FNAC) has proven its value as an essential step in the diagnosis of salivary gland lesions. Although the majority of salivary gland lesions, especially those that are common and benign, can be diagnosed with ease on FNAC, limited cellularity and morphologic lesion heterogeneity can pose diagnostic challenges and lead to false-positive and false-negative diagnoses. This study presents the institutional experience of FNAC of salivary gland lesions from 2 academic centers. METHODS: A retrospective analysis was conducted on 1729 salivary gland FNAC specimens that were diagnosed over an 8-year period from January 2008 to March 2015. All samples were processed either with liquid-based cytology alone or in combination with air-dried, Diff-Quik-stained or alcohol-fixed, Papanicolaou-stained smears. RESULTS: Surgical excision was performed in 709 of 1749 FNACs (41%) that were diagnosed as nondiagnostic/inadequate (n 5 29), benign (n 5 111), neoplasm (n 5 453), atypical (n 5 15), suspicious for malignancy (n 5 28), and malignant (n 5 73). The overall concordance between cytologic and histologic diagnoses was 92.2%, with 91.8% concordance in the benign category and 89.5% concordance in cases diagnosed as suspicious for malignancy and malignant. The most frequent benign and malignant lesions were pleomorphic adenoma and squamous cell carcinoma, respectively. There were 46 false-negative and 13 false-positive results, leading to an overall specificity of 97.6% and diagnostic accuracy of 91.3%. CONCLUSIONS: FNAC is a reliable diagnostic modality for the diagnosis and management of salivary gland lesions based on its high specificity and diagnostic accuracy. Cancer Cytopathol 2016;124:388-96. V C 2016 American Cancer Society.

Objective: To perform a retrospective investigation of our institutional experience with salivary gland fine needle aspirations (FNA) through the framework of The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and assess the risks of neoplasm and malignancy for each diagnostic category.were retrospectively categorised according to the MSRSGC. When available, preoperative cytological results were correlated with subsequent histological follow-up. Results: In total, 893 FNAs were reviewed. The specimens were retrospectively classified as nondiagnostic (ND: 13.5%), non-neoplastic (NN: 16.1%), atypia of undetermined significance (AUS: 10.8%), benign neoplasm (BN: 34.9%), salivary gland neoplasm of uncertain malignant potential (SUMP: 8.2%), suspicious for malignancy (SM: 2.7%) and malignant (M: 13.8%). Histological follow-up was available for 429 cases (48%); the majority (68.1%) were benign. The risks of neoplasm and malignancy for each category were as follows: ND: 64.5%, 16.1%; NN: 42.9%, 17.9%; AUS: 79.6%, 30.6%; BN: 100%, 2.2%; SUMP: 100%, 46.6%; SM: 94.7%, 78.9%; and M: 100%, 98.5%. Conclusions: The MSRSGC is a useful classification scheme for stratifying salivary gland lesions according to their associated risk of malignancy and guiding clinicians toward appropriate management. Diagnostic pitfalls are seen in a small proportion of cases and a multidisciplinary approach for assessing salivary gland pathology is essential in their evaluation. K E Y W O R D S cytology, fine needle aspiration, Milan system, risk of malignancy, salivary gland 1 | INTRODUCTION Fine needle aspiration (FNA) is a well established, cost-effective, and minimally invasive diagnostic tool for sampling salivary gland lesions. 1,2FNA cytology can be useful for distinguishing between non-neoplastic and neoplastic entities. 3 However, due to intratumoral heterogeneity and frequent overlapping cytomorphological features between many tumours, precise subtyping of neoplasms can be challenging. 4-7 This distinction is important as the treatment options vary across the spectrum of salivary gland pathologies. Non-neoplastic lesions can be managed conservatively, whereas a neoplastic diagnosis warrants surgical excision-in most cases with extensive surgery for high-grade malignancies, lymph node dissection for metastases and a haematology-oncology referral for haematological malignancies. Hence, cytological diagnoses that are descriptive without proper categorisation can be confusing for clinicians who need more definitive diagnoses to guide their management decisions. 8Until recently, there has been a lack of a uniform reporting scheme for cataloguing salivary gland lesions. It is in this setting that an international panel of experts under the joint efforts of the American

The GEC showed improved performance characteristics when coupled with a repeat FNA. It continues to be of low specificity and positive predictive value in oncocytic follicular lesions. Diagn. Cytopathol. 2016;44:867-873. © 2016 Wiley Periodicals, Inc.

Background:The overall malignancy rate for the thyroid fine-needle aspiration (FNA) diagnosed as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) ranges from 5% to 30%. In this study, we present our institutional experience with thyroid nodules diagnosed as AUS/FLUS and further stratified into subcategories. In addition, we also assessed the significance of various clinicopathologic factors that may influence AUS/FLUS diagnoses and their outcomes.Design:A search of our laboratory information system was performed to identify all in-house thyroid FNA cases diagnosed as AUS/FLUS from 2008 to 2012. The data were collected and characterized by patient demographic information, cytopathology diagnosis with sub-classifiers and follow-up.Results:The case cohort included 457 cases diagnosed as AUS/FLUS. These were further sub-classified into one of six subcategories depending on the cytomorphologic findings and suspicion for or against a neoplastic process. Of the 457 cases, repeat FNA and/or surgical follow-up was available in 363 cases. There were 182 (39.8%) cases with cytologic follow-up only; 18 (9.9%) remained as AUS/FLUS, while 158 (86.8%) were re-classified with the majority being benign (142 cases). Histologic follow-up was available in 181 (39.6%) cases. There were 60 malignant cases confirmed by surgical excision, with an overall malignancy rate of 33.1%. The malignancy rate was 38.8% for cases with a repeat FNA versus 25.6% for cases that went directly to surgery without a repeat FNA. Papillary thyroid carcinoma accounted for 93.3% (56 cases) of the malignant cases.Conclusion:Based on our study, even though the malignancy rate of AUS/FLUS cases is similar to those reported for cases diagnosed as follicular neoplasm/suspicious for follicular neoplasm, we are of the belief that these comparable malignancy rates are a product of better clinical management and selection of patients diagnosed as AUS/FLUS for surgery after a repeat FNA.

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The Bethesda System for Reporting Thyroid Cytopathology is a standardized reporting system for classifying thyroid fine-needle aspiration results comprising of 6 diagnostic categories with unique risks of malignancy and recommendations for clinical management. The majority of thyroid nodules are benign; however, up to 30% of fine-needle aspiration of thyroid nodule results are equivocal. Until 2007, various diagnostic terms were used to classify such cases, including "atypical," "indeterminate," and rule-out or cannot exclude malignancy. A literature review of 13 original studies was conducted to evaluate whether utilization of the Bethesda System for Reporting Thyroid Cytopathology nomenclature represent an improvement over thyroid cytopathology reporting schemes used before 2007 in diagnosing thyroid malignancy. The sensitivity and specificity of thyroid fine-needle aspiration was high in the studies that assessed the measures. However, a selection bias exists and most studies do not include indeterminate diagnosis in their calculations. Although the Bethesda System for Reporting Thyroid Cytopathology recommends a repeat fine-needle aspiration to follow-up nondiagnostic specimens, in the majority of studies, an appreciable number of cases underwent follow-up surgical biopsy or thyroidectomy. The diagnostic category of atypia/follicular lesion of undetermined significance remains heterogenous in terms of usage and clinical outcome. The majority of the studies that utilize the Bethesda System for Reporting Thyroid Cytopathology in this literature review retrospectively reclassified thyroid fine-needle aspiration into the Bethesda System for Reporting Thyroid Cytopathology nomenclature with reported malignancy rates that are similar between cases reclassified as atypia/follicular lesion of undetermined significance and follicular neoplasm/suspicious for follicular neoplasm.

The diagnostic category of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has proven to be heterogeneous in terms of usage and clinical outcome. Several factors have been noted in the literature to lead to AUS/FLUS diagnosis. In this study, we assessed the significance of various clinicopathologic factors that may influence AUS/FLUS diagnosis. A search of our laboratory information system was performed to identify all in-house thyroid fine-needle aspiration (FNA) cases performed under ultrasound (US) guidance and diagnosed as AUS/FLUS from 2008-2011. Data-points collected for this study included: patient demographic information, size of the thyroid nodule sampled, aspirator, pathologist rendering the final diagnosis, and applicable follow up. The case cohort included 348 cases diagnosed as AUS/FLUS in 87 males and 261 females (average age of 56 years). All FNAs were performed under ultrasound guidance; 171 (49%) nodules were aspirated by a team of endocrinologists and 177 (51%) by a team of radiologists. The nodule size was available in 328 cases (average size of 2.63 cm); 14 (4%) measured <1.0 cm, 217 (66%) were 1.1-3.0 cm and 97 (30%) were 3.1->4.1 cm. Five cytopathologists interpreted all thyroid FNA cases; the AUS/FLUS rate varied from 10.2% in 2009 to 8% in 2011. Of the 348 cases diagnosed as AUS/FLUS, 219 (63%) were interpreted by two and the remaining 129 (37%) by three cytopathologists. Follow-up was available in 260 (75%) cases; 187 (54%) had 1-3 repeat FNA procedures. Histologic follow-up was available in 139 (40%) cases with an overall malignancy rate of 32% (45 cases). The malignancy rate was highest (32%) in nodules measuring 2.1-3.0 cm. Based on this study cytopathologic interpretation is the most significant factor for the variable rate and follow-up of cases diagnosed as AUS/FLUS.