Cytological, molecular, and clinical features of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features versus invasive forms of follicular variant of papillary thyroid carcinoma

Abstract

BACKGROUND:The noninvasive follicular variant of papillary thyroid carcinoma (PTC) has an indolent clinical behavior in comparison with other PTCs, including the invasive follicular variant of papillary thyroid carcinoma (IFVPTC). Recently, the term noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced to emphasize the low biological potential of these tumors. This study compares clinical, cytological, and molecular features of NIFTP and IFVPTC. METHODS: The study consisted of 97 thyroid fine-needle aspiration biopsy (FNAB) cases with corresponding surgical pathology from the pathology archives of the Massachusetts General Hospital. The collected patient data included the following: age, sex, type of surgery, tumor size, and prior cytological diagnosis with The Bethesda System for Reporting Thyroid Cytopathology. A molecular analysis using anchored multiplex polymerase chain reaction was performed for all cases. Each case was reviewed and subclassified histologically as NIFTP or IFVPTC. Cytology slides were scored semiquantitatively for nuclear atypia. The statistical analysis was performed with the nonparametric Mann-Whitney test. RESULTS: The 97-case cohort consisted of 50 NIFTP cases and 47 IFVPTC cases, including 18 encapsulated IFVPTC cases and 29 nonencapsulated IFVPTC cases. Differences in the type of surgery (P 5.0399), molecular features (P 5.0141), cytological classification (P 5.0266), and nuclear scores (P 5.0141) between NIFTP and IFVPTC were observed.There was overlap in the cytological classification of NIFTP and IFVPTC; however, NIFTP was more often classified as atypia of undetermined significance/follicular lesion of undetermined significance or follicular neoplasm/suspicious for follicular neoplasm in comparison with both subsets of IFVPTC. NIFTP was primarily associated with mutations in RAS, whereas an equal number of IFVPTC cases were associated with BRAFV600E or with RAS mutations. CONCLUSIONS:Despite differences in the cytological classification and molecular profiles between NIFTP and IFVPTC, the degree of overlap makes it unlikely that most cases of NIFTP and IFVPTC can be accurately distinguished with FNAB. Cancer Cytopathol 2017;125:323-31.

AHNS Series: Do you know your guidelines? AHNS Endocrine Section Consensus Statement: State‐of‐the‐art thyroid surgical recommendations in the era of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features

“…They concluded that because of the overlapping nuclear features with invasive EFVPTC, NIFTP cannot be reliably diagnosed preoperatively 14. Similarly, Zhao et al15 believe that even though there are differences in the cytological and molecular profiles between NIFTP and infiltrative follicular varient of papillary carcinoma (IFVPTC), the overlap between the two makes it implausible to correctly differentiate between NIFTP and IFVPTC in most cases.…”

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Can Cytology Face the Challenge of Diagnosis in the Light of the New Classification?

“…Our literature review revealed variable results between studies. NIFTP cases diagnosed as category VI vary between 0 and 18% [14]. Maletta et al [7] diagnosed NIFTP as Bethesda category IV in 56% of cases, V in 27%, III in 15%, and VI in 2%.…”

“…Mainthia et al [4] classified NIFTP as Bethesda category III in 26%, IV in 20%, V in 9%, II in 18%, I in 11%, and VI in 6%. Zhao et al [14] classified 72% of NIFTP cases as Bethesda category III. Strickland et al [15] diagnosed NIFTP mainly as Bethesda categories V (45.8%), III (20%), and II (15.2%).…”

Implementing noninvasive follicular thyroid neoplasm with papillary‐like nuclear features may potentially impact the risk of malignancy for thyroid nodules categorized as AUS/FLUS and FN/SFN

“…1 Recently, the Endocrine Pathology Society working group conducted a retrospective study of noninvasive encapsulated FVPTC with the aim of assessing clinical outcomes, refining diagnostic criteria, and developing a new terminology that appropriately reflects the biological and clinical characteristics of this entity. The rate of histology-proven malignancy after implementation of TBSRTC was 3.5%, 17 2 The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has been widely accepted as a standard reporting system for assessing fine needle aspiration (FNA) of thyroid.…”