Noninvasive follicular thyroid neoplasm with papillary‐like nuclear features in the pediatric age group

Rossi, Esther Diana; Mehrotra, Swati; Kılıç, Ayşe; Toslak, İclal Erdem; Lim-Dunham, Jennifer E.; Martini, Maurizio; Fadda, Guido; Lombardi, Celestino Pio; Larocca, Luigi Maria; Barkan, Güliz A.

doi:10.1002/cncy.21933

Cited by 32 publications

(37 citation statements)

References 42 publications

(268 reference statements)

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“…The percentage of indeterminate diagnoses in the literature ranged from 13% to 43%. The indeterminate diagnosis rate in our study (14%) is significantly lower than some of the indeterminate rates reported by other institutions (Table ) . Specifically, the rates of AUS/FLUS (9%) and FN/SFN (3%) in the current study are significantly lower than those reported by Monaco et al (24% and 11%, respectively; P < .001 for both categories).…”

Section: Resultscontrasting

confidence: 82%

“…We compared the findings from our institution with all previously published series on pediatric thyroid cytopathology that used TBSRTC categories, and 6 met the literature selection criteria . The percentage of indeterminate diagnoses in the literature ranged from 13% to 43%.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, data from AUS/FLUS and FN/SFN categories in that investigation were excluded for the calculation of average FNA diagnoses percentages and malignancy rates regarding these 2 TBSRTC categories. In another study, all FNAs selected were followed by resection, reflecting an over‐representation or bias toward indeterminate categories for which surgery is recommended for management . Therefore, data from that study were excluded from the calculation of average FNA diagnoses percentages but were included for the calculation of malignancy rates.…”

Section: Methodsmentioning

confidence: 99%

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Incidence and malignancy rates of indeterminate pediatric thyroid nodules

Wang

Mehrad

Ely

et al. 2019

Cancer Cytopathology

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Background The American Thyroid Association guidelines task force currently recommends definitive thyroidectomy or lobectomy after an indeterminate thyroid biopsy in children. This recommendation is based on evidence of a greater incidence and a higher risk of malignancy compared with adults in earlier pediatric studies. Such management may lead to overtreatment and unnecessary surgery for many children in the United States. Methods The objective of the current study was to re‐evaluate pediatric thyroid nodules and assess the overall percentages and malignancy rates for indeterminate thyroid biopsies in children. In total, 302 pediatric thyroid fine‐needle aspirations (FNAs) were analyzed retrospectively (2001‐2018). Distribution percentages and malignancy rates were calculated for each category of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Results Two indeterminate TBSRTC groups (atypia of undetermined significance/follicular lesion of undetermined significance and follicular neoplasm/suspicious for a follicular neoplasm) had much lower distribution percentages and malignancy rates compared with earlier pediatric series and American Thyroid Association guidelines. A meta‐analysis further supported these findings and demonstrated distinctly different malignancy rates for the indeterminate groups (atypia of undetermined significance/follicular lesion of undetermined significance, follicular neoplasm/suspicious for a follicular neoplasm, and suspicious for malignancy), suggesting the need for TBSRTC category‐specific management recommendations rather than a nondiscriminatory, up‐front surgical approach. Conclusions Adult patients with indeterminate preoperative thyroid cytopathology are followed by repeat biopsy and possibly molecular testing before undergoing definitive surgery. However, in children, the guidelines are considerably more aggressive and recommend definitive surgery after the first indeterminate thyroid biopsy. Here, the largest pediatric cohort to date with meta‐analysis is presented, and the authors propose a re‐evaluation of this up‐front approach to pediatric thyroid care.

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Section: Resultscontrasting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Incidence and malignancy rates of indeterminate pediatric thyroid nodules

Wang

Mehrad

Ely

et al. 2019

Cancer Cytopathology

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“…However, while interpreting these differences, one should note possible selection or sampling bias due to the limited pediatric case cohort contained in this article. Although NIFTP has not been thoroughly investigated yet in pediatric patients, this article and that of Rossi et al, which demonstrated that NIFTP comprised only 1.9% of resected pediatric thyroid nodules, suggest that NIFTP in the pediatric population is rare.…”

Section: Discussionmentioning

confidence: 69%

Malignant risk of indeterminate pediatric thyroid nodules—An institutional experience

Heider

Arnold

Lew

et al. 2019

Diagnostic Cytopathology

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Background Few studies focus on pediatric thyroid nodules categorized under indeterminate diagnostic categories. The current study was conducted to assess the risk of malignancy of indeterminate pediatric thyroid nodules. Methods A search of the institutional electronic pathology database from 01/2011 to 09/2018 was performed to identify pediatric (<21 years old) thyroid nodules that were interpreted as follicular lesion of undetermined significance (FLUS), suspicious for follicular neoplasm (SFN), or suspicious for malignancy (SFM) and subsequently managed with surgery, repeat fine‐needle aspiration (FNA), or ≥ 6 months of clinical/imaging monitoring. Results of follow‐up (F/U) surgical resections and repeat FNA/Afirma tests, and clinical and radiologic data were collected. Results We identified 46 cases from 42 patients (11‐20 years old, 33 females and 9 males), including 30 FLUS, 10 SFN, and 6 SFM. Twenty‐five FLUS, ten SFN, and six SFM cases underwent surgery. The histology revealed carcinomas in 36% of FLUS, 20% of SFN, and 100% of SFM categories; follicular adenomas in 32% of FLUS and 80% of SFN categories; and benign nodules in 32% of FLUS category. All five nonsurgically treated FLUS cases were considered benign based on the findings of repeat FNA/Afirma tests (n = 3, 3‐22 months F/U) or clinical/radiologic exams (n = 2, 8‐12 months F/U). Conclusions Based on a limited study cohort, malignancy was identified in 36%, 20%, and 100% of surgically managed pediatric thyroid nodules categorized as FLUS, SFN, and SFM, respectively; suggesting a markedly higher malignant rate than the implied malignant risk for FLUS and SFM categories in adults.

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“…It is a challenge for pathologists to distinguish encapsulated FVPTC with lymph node metastasis and/or BRAF V600E mutation from NIFTP ( RAS ‐like tumor) morphologically. NIFTP is a morphological phenotype consistent with RAS ‐like tumor, and cases with BRAF and/or TERT promoter mutation must be excluded, as per the current concept . BRAF V600E mutation was reported in “NIFTP” that fulfilled the morphological criteria by several research groups .…”

Section: Discussionmentioning

confidence: 99%

Interobserver and intraobserver variation in the morphological evaluation of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features in Asian practice

Liu

Bychkov

Jung

et al. 2019

Pathology International

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To evaluate the current diagnostic criteria in reporting nuclear features of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP), nine Asian pathologists with expertise in thyroid reviewed virtual slides of 30 noninvasive follicular patterned thyroid lesions according to the nuclear scoring system originally proposed by an international expert and a more detailed scoring system proposed by the Asian Working Group. The interobserver agreement for nuclear grading score was generally moderate (kappa value = 0.452). The best consistency fell on the chromatin features (kappa value = 0.658–1.000). A fair to moderate interobserver agreement was demonstrated in the evaluation of nuclear elongation, nuclear overlapping, membrane irregularities and distribution of papillary thyroid carcinoma (PTC) type nuclear features. A slight agreement was rendered for the evaluation of the nuclear enlargement. Intraobserver agreement was substantial to perfect when comparing results of both scoring systems. However, both scoring systems were not able to reliably separate NIFTP from an encapsulated follicular variant PTC with minimal lymph node metastasis or BRAFV600E mutation. Although the three‐point nuclear scoring system for the diagnosis of NIFTP is widely used in Asian practice, interobserver variation was considerable. Ancillary immunohistochemical or molecular testing might be helpful in differentiating NIFTP from true PTC.

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Noninvasive follicular thyroid neoplasm with papillary‐like nuclear features in the pediatric age group

Cited by 32 publications

References 42 publications

Incidence and malignancy rates of indeterminate pediatric thyroid nodules

Incidence and malignancy rates of indeterminate pediatric thyroid nodules

Malignant risk of indeterminate pediatric thyroid nodules—An institutional experience

Interobserver and intraobserver variation in the morphological evaluation of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features in Asian practice

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