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

In response to the confusion, a multidisciplinary panel, the Endocrine Pathology Society (EPS) Working Group including thyroid pathologists, endocrinologists, and an endocrine surgeon, was established to address the impor- tant controversies surrounding the diagnosis of encapsulat- ed and noninvasive FVPTC. The panel deliberations were based on the clinical outcomes and tumor molecular analy- ses of a case cohort of noninvasive EFVPTC patients for whom there was diagnostic consensus among the patholo- gy experts in the group. All noninvasive EFVPTC patients, followed for 10 to 26 years after diagnosis, were alive with- out evidence of disease. Importantly, none of these patients received radioiodine ablation, and >50% were treated by lobectomy only. In addition, molecular alterations typically seen in classic PTC ( BRAF V600E mutations or RET gene fusions) were not seen in noninvasive EFVPTC cases. The molecular profiles of these cases included RAS gene muta- tions (30% cases) and PPARG or THADA gene fusions (44% cases). Based on the benign clinical outcomes and characteristic molecular analysis data in these patients, the

EPS Working Group recommended that truly noninvasive EFVPTC tumors be redesignated as nonmalignant entity termed “noninvasive follicular thyroid neoplasms with papillary-like nuclear features” (NIFTP). This reclassifica- tion will have a significant effect on a large population of patients worldwide, hopefully resulting in a diminution of overaggressive treatment with a concomitant reduction in clinical consequences and psychologic sequelae related to the diagnosis of “cancer” (18). Although the case cohort long-term outcome data supporting the nomenclature change is strong, in the absence of prospective study confir- mation, it is essential that endocrine physicians prospec- tively follow patients with NIFTP pathology to verify that these patients’ postoperative courses are truly indolent. NIFTP – DIAGNOSTIC CRITERIA For optimal clinical management, it is important that NIFTP is a surgical disease and this diagnosis cannot be rendered on pre-operative fine-needle aspiration (FNA).

Table 1 Diagnostic Histopathologic Criteria for NIFTP

Diagnostic criteria

Comments

Inclusion criteria (Fig. 2 A - C ) 1. Well demarcated/encapsulated follicular patterned tumor

2. Nuclear cytology of PTC 3. Noninvasive characteristics

It is of utmost importance that a thorough sampling of tumor and its interface with either tumor capsule or surrounding uninvolved thyroid parenchyma is carried out to exclude invasive characteristics

a. No tumor capsule invasion or invasion into the surrounding thyroid parenchyma b. No lymphovascular invasion

Exclusion criteria

• Invasion beyond the periphery of tumor excludes the diagnosis of NIFTP • This includes invasion by the tumor cells into the tumor capsule, extension into the surrounding thyroid parenchyma, and/or vascular invasion into vessels within the tumor capsule or beyond • NIFTP predominantly shows a follicular growth pattern. However, the presence of <1% papillary structures a and ≤30% of solid growth pattern (by area) is allowed (papillary structures are hallmark features of conventional carcinoma) • Presence of any other growth patterns indicative of aggressive variants of PTC such as tall cell, columnar cell, and hobnail variant exclude the diagnosis of NIFT • Psammoma bodies represent “dead” papillary structures and can be seen in tumor as well as within the lymphatics away from tumor • Any form of “true” tumor necrosis (excludes necrosis associated with preoperative fine-needle aspiration) and or mitoses can be associated with high-grade transformation and/or aggressive clinical behavior • Three or more mitotic figures in 10 consecutive high-power fields exclude the diagnosis of NIFTP (this criterion requires future clinicopathologic validation)

Invasion

Tumor growth pattern

Lymphovascular invasion and/or lymph node metastases Psammoma bodies

Tumor necrosis and or mitoses

Abbreviation: NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclei. a Based on a study by Cho et al (19), 3% lymph node metastases were noted in cases with a 1% cutoff value for papillary structures. These authors have suggested not to render a diagnosis of NIFTP even in the presence of a single papillary structure.

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