NIFTP Cytologic Aspects

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NIFTP Cytologic Aspects William C. Faquin, MD PhD Director, Head and Neck Pathology Massachusetts General Hospital & Massachusetts Eye and Ear Infirmary Boston, MA USA

So, what is the story about FVPTC and NIFTP in cytology???

FNA of the Follicular Variant of Papillary Thyroid Carcinoma Easily recognized as PTC More difficult to recognize as PTC

FNA of the Follicular Variant of Papillary Thyroid Carcinoma Problematic Variant for FNA: 30-40% have subtle nuclear features Microarchitecture mimics a follicular neoplasm or adenomatous nodule FNA shows variable accuracy: 30-40% diagnosed as MALIGNANT 25-30% diagnosed as SUSPICIOUS FOR MALIGNANCY 25-30% diagnosed as SUSPICIOUS FOR FOLLICULAR NEOPLASM 10-20% diagnosed as AUS/FLUS

Follicular Variant of PTC: Common Cause of False Negative FNA Diagnosis With NIFTP, this could become a cause of a False Positive FNA diagnosis of cancer

FVPTC vs NIFTP: Cannot be accurately distinguished by FNA Invasive FVPTC NIFTP

Follicular-patterned Nuclear: Enlargement Pallor Grooves Overlap Rare: Pseudoinclusions Absent: Papillae Psammoma bodies FNA of NIFTP: Cytologic Features

NIFTP: Solves a major problem but creates others 8

Regardless of the thyroid FNA reporting system that you use, NIFTP will create some issues for cytology!

Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) The prospects of NIFTP for thyroid cytology: The ROM for indeterminate diagnostic categories of TBSRTC will change The PPV/NPV for molecular testing panels will change Management issues for FVPTC Medicolegal issues for FP diagnosis of PTC Future modifications in our approach to the indeterminate thyroid FNA will be needed

Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) Cancer Cytopathology, 2015.

Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) Malignant Surgical Follow-Up (877) 756 were PTC 173 PTC cases were NIFTP (23% of PTC) Distribution of NIFTP Cases: Non-Diagnostic 0.6% Benign 8.7% AUS/FLUS 31.2% Foll Neoplasm 26.6% Susp Mal 24.3% Malignant 8.7%

Effect of NIFTP reclassification on ROM for different Bethesda categories

Thyroid, 2015 Brigham and Women s Hospital, Boston, MA USA Consecutive Thyroid FNAs with corresponding resection over 22 months 655 thyroid FNAs Assess the ROM +/- NIFTP for each Bethesda diagnostic category

NIFTP Study: ROM +/- NIFTP MGH BWH Non-Diagnostic 4.4-25.3% 18.9% 4.1-23.9% 17.0% Benign 0.9-9.3% 13.2% 0.5-5.8% 5.4% AUS/FLUS 12-31.2% 39.2% 6.8-17.6% 21.6% Foll Neoplasm 21.8-33.2% 45.5% 11.8-18% 37.5% Susp Mal 62.1-82.6% 87.2% 44.5-59.2% 45.7% Malignant 75.9-99.1% 98.7% 73.4-95.7% 93.6%

Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) NIFTP classified as AUS/FLUS (15%), FN (56%), SM (27%), Malignant (2%) Nuclear features are indistinguishable from invasive EFVPTC Nuclear enlargement, pallor, grooves Lack papillary architecture and infrequent intranuclear inclusions Cannot be reproducibly diagnosed preoperatively Human Pathology 2016

How should FNA classification & clinical management change based upon expected impacts on the ROM for thyroid FNA reporting categories? Modify the cytologic criteria for classifying follicular patterned FNAs: FN with atypia vs Susp Malignancy Avoid diagnosing follicular patterned PTC as malignant Put a disclaimer statement about possible NIFTP on Susp for PTC cases Rely more on pre-op molecular testing (BRAF vs RAS) Use frozen section to guide the surgery Increase clinical threshold for performing TT

An option is to add a NIFTP disclaimer note on the cytology report for SM and Malignant categories SUSPICIOUS MAL NOTE (BWH): The overall cytomorphologic features are suggestive of a follicular variant of papillary carcinoma or its recently described indolent counterpart, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Definitive distinction among these entities is not possible on cytologic material.

A Final GOOD Word about FNA of NIFTP Most NIFTP are detected by FNA +/- molecular testing Most NIFTP are triaged for surgery NIFTP is considered a potential precursor to carcinoma Lobectomy is an appropriate treatment for NIFTP Most FP diagnoses of NIFTP can be avoided

Thank You!