2018-19 Section 7-Neoplastic and Inflammatory Diseases of the Head and Neck eBook

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Managing Thyroid Tumors Diagnosed as NIFTP, Endocr Pract. 2017;23(No. 9)

the diagnosis of NIFTP in large-sized tumors should only be entertained, when the entire tumor capsule has been evaluated by histopathologic evaluation to exclude invasive characteristics. Impact of Preoperative FNA Diagnosis The most important issue that has surfaced with the newly created diagnosis of NIFTP is the inevitable increase in the “false-positive” rates for cases diagnosed as suspi- cious or consistent with PTC by preoperative FNA cytol- ogy and molecular assessment (23-25). Recent studies have shown that noninvasive EFVPTC have previously comprised a significant proportion of malignant diag- noses associated with the indeterminate diagnostic cate- gories of The Bethesda System for Reporting Thyroid Cytology (TBSRTC) (26-29): atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), follicular neoplasm/suspicious for follicu- lar neoplasm (FN/SFN), and suspicious for malignancy (14). However, one would predict no appreciable change in the risk of malignancy for FNA cases diagnosed as benign (Bethesda 2) and malignant (Bethesda 6) based on the NIFTP nomenclature change. The initial studies have shown an appreciable decrease in the rate of malignancy for indeterminate categories of TBSRTC. The reported ranges for changes in the rate of malignancy are AUS/ FLUS 19 to 45% to 15-30%, FN/SFN –22 to 45% to 10 to 37%, and SM 72 to 87% to 46 to 68% (24,25,29,30) (Table 2) . Such alterations in the rate of malignancy for the indeterminate diagnostic categories (Bethesda III-V) may lead to changes in the thyroid nodule pre- and postsurgi- cal management paradigms, especially for those classified as SM, as recommended by the American Association of Clinical Endocrinologists (AACE) and American Thyroid Association for low-risk thyroid neoplasms (31-33). It is hoped that with the emergence of this new nonmalignant category, physicians may tend to recommend lobectomy with greater assurance in patients with Bethesda III-IV cytology, especially in those with RAS mutations and PPARG or THADA gene fusions (18). Recent retrospective studies have shown that NIFTP comprises approximately 5% of thyroid FNA speci-

mens diagnosed as malignant (25,28,30,36). Though this percentage may not appear significant, even a small decrease in risk of malignancy for the “malignant” FNA category could raise concerns about potential medicolegal implications in the pathology community. As a result, some pathologists have suggested that the diagnosis of PTC in FNA specimens be limited to cases that demonstrate diag- nostic features of the classic or tall cell variants of PTC: papillary architecture, psammomatous calcifications, and well-formed pseudo-inclusions. Based on these potential future concerns, some pathologists are now including an explanatory note regarding the possibility that NIFTP tumors are part of the differential diagnosis list for Bethesda III-VI cytology results and that this new noncancerous diagnostic category may change Bethesda III-V category- based performance characteristics (25). It is also crucial to understand and explain to patients that NIFTP is not a “benign tumor” but a “low-risk neoplasm” that requires surgical excision for diagnosis followed by comprehen- sive pathologic evaluation of the tumor contents and its capsule. Moreover, it is reasonable to suggest that in thyroid nodules demonstrating indeterminate or low-risk ultrasound features, FNAs in the Bethesda III-V categories and/or with NIFTP-suggestive molecular profiles (only RAS -mutations and/or PPARG and THADA gene fusions, without BRAF or TERT promoter mutations), conservative management with hemithyroidectomy for diagnosis may be the best surgical approach (18,23,25). What to advise patients whose tumors have been reclassi- fied as NIFTP? (37) (1) “I was told that I had a follicular variant of papillary carcinoma. Did I have cancer ?” (a) In order to confirm that a tumor originally clas- sified as a follicular variant of papillary cancer is a NIFTP, it needs to be reread by a patholo- gist familiar with the new criteria. Some patients will have invasive tumors, some may have classic papillary cancer, and some may be NIFTP. The diagnosis cannot be based on the original pathol- ogy report. Within a few years of diagnosis, the original pathology tissue specimen blocks may still be available for resectioning and re-evalua-

Table 2 Change in the Risk of Malignancy of TBSRTC Diagnostic Categories due to NIFTP Diagnosis TBSRTC Cancer risk based on TBSRTC 2007 (34) Cancer risk based on post-2007 studies (24,27,28,35) NIFTP effect on lowest to highest cancer risk (24,28,30) AUS/FLUS (TBSRTC Cat-3) 5-15% 19-45% 15-30% FN/SFN (TBSRTC Cat-4) 15-30% 22-45% 10-37% SM (TBSRTC Cat-5) 60-75% 72-87% 46-68% Abbreviations: AUS/FLUS = atypia/follicular lesion of undetermined significance; Cat = category; FN/SFN = follicu- lar neoplasm/suspicious for follicular neoplasm; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclei; SM = suspicious for malignancy; TBSRTC = The Bethesda System for Reporting Thyroid Cytology.

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