Journal of Surgery

Introduction

Thyroid nodules are a common clinical finding, and while most are benign, a subset represents differentiated thyroid carcinomas, including the Follicular Variant of Papillary Thyroid Carcinoma (FVPTC). In recent years, growing evidence has demonstrated that a specific subset of encapsulated FVPTCs behaves in an indolent, non-invasive manner and carries an extremely low risk of recurrence or metastasis [1,2]. This observation led to a landmark reclassification in 2016, when an international panel of experts proposed the term Non-Invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) to replace these tumors. The goal was to reduce overtreatment and alleviate the psychological impact of a cancer diagnosis in patients with tumors that pose minimal clinical risk [3,4]. NIFTP is characterized by a completely encapsulated or well-demarcated lesion, follicular growth pattern, and nuclear features reminiscent of papillary thyroid carcinoma, but without capsular or vascular invasion. Since its redefinition, NIFTP has significantly influenced thyroid pathology and surgical decision-making. However, accurate diagnosis can be challenging, particularly on Fine Needle Aspiration Cytology (FNAC), as its features often overlap with those of other benign or malignant follicular-patterned lesions [5,6]. The diagnostic criteria for NIFTP have evolved since the original 2016 reclassification. The American Thyroid Association (ATA) and subsequent expert consensus groups have refined the histopathological criteria to improve diagnostic accuracy and ensure the indolent nature of NIFTP is preserved [5-8] (Table 1).

Table 1: Demographics and Tumor Characteristics of Patients with NIFTP.

Updated Diagnostic Criteria for NIFTP (Based on ATA and Recent Expert Guidelines)

According to the most recent guidelines and expert consensus updates endorsed by the American Thyroid Association, NonInvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) must fulfill strict histopathological criteria to ensure its low-risk biological behavior. The revised criteria are as follows [8-10]:

1.  Encapsulation or Clear Demarcation

The tumor must be completely encapsulated or clearly demarcated from surrounding thyroid parenchyma.

Absence of infiltrative growth pattern is mandatory.

2.  Follicular Growth Pattern

The tumor must show a pure follicular architecture. No true papillae are allowed. Presence of less than 1% papillae may be considered in exceptional cases by some pathologists, but current trend discourages any papillary formation.

3.  Papillary-like Nuclear Features

Nuclear features of PTC must be present, including:Enlarged nuclei,Irregular nuclear contours,Chromatin clearing,Nuclear grooves and occasional pseudoinclusions .These features should be diffuse and convincing, not focal.

4. Absence of Invasion

There must be no capsular or vascular invasion.Entire capsule must be submitted for microscopic evaluation to confidently exclude invasion.

5. Absence of High-Risk Features

No necrosis.,No high mitotic activity (should be <3 mitoses per 10 high-power fields) and No solid/trabecular/insular growth pattern involving >30% of the tumor.

6.  Optional Immunohistochemistry or Molecular Testing

While not required for diagnosis, absence of high-risk mutations such as BRAF V600E and TERT promoter mutations supports the diagnosis.RAS-like mutations are more commonly associated with NIFTP. These refined criteria emphasize complete histological evaluation, especially thorough sampling of the tumor capsule, to avoid misclassification. The aim is to maintain a highly specific definition that ensures all NIFTP cases are truly indolent, thus supporting conservative management and avoiding overtreatment [11,12]. These refined criteria emphasize complete histological evaluation, especially thorough sampling of the tumor capsule, to avoid misclassification. The aim is to maintain a highly specific definition that ensures all NIFTP cases are truly indolent, thus supporting conservative management and avoiding overtreatment [12].

Methods

Study Design and Setting

This is a retrospective case series conducted at Dubai hospital , Dubai Health, UAE.The study included patients who underwent thyroid surgery and were diagnosed with Non-Invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) on final histopathology between July 2022 till July 2024.

Inclusion Criteria

Patients were included in the study if they met the following criteria:

1. Age ≥ 18 years
2. Histopathological diagnosis of NIFTP based on updated diagnostic criteria (ATA 2016 and recent consensus refinements)
3. Availability of complete clinical, cytological, and histopathological records

Data Collection

Clinical and pathological data were retrieved from hospital medical records and pathology archives. The following variables were collected:

Demographics: age, sex

Clinical presentation: symptoms, nodule size, location

Preoperative imaging: ultrasound findings, TI-RADS category if available

Cytology: FNAC results reported according to the Bethesda System

Surgical details: type of surgery (lobectomy vs total thyroidectomy)

Histopathology: tumor size, encapsulation, nuclear features, presence of invasion, presence of papillae, mitotic activity, necrosis

Follow-up: All patients had follow up for one year or more .

All histopathological slides were reviewed by experienced endocrine pathologists to confirm the diagnosis of NIFTP according to the most recent diagnostic criteria, including complete encapsulation, absence of invasion, follicular growth pattern, and nuclear features of PTC.

Results

A total of nine patients were diagnosed with Non-Invasive

Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP). The mean age at diagnosis was 45.3 years (range: 22–72 years). Eight patients (88.9%) were male and one patient (11.1%) was female. The most common presenting symptom was neck swelling, reported either alone or in the context of a Multinodular Goiter (MNG). One patient presented with dysphagia, and another was newly diagnosed with hypothyroidism. None of the patients had a family history of thyroid cancer. Preoperative fine needle aspiration cytology (FNAC) varied, with results ranging from benign (Bethesda II) to suspicious for papillary thyroid carcinoma (Bethesda V). Most cases fell into Bethesda categories III to V. One case was non-diagnostic (Bethesda I) on one side. Five patients underwent total thyroidectomy, while four underwent left hemithyroidectomy. Final histopathology confirmed NIFTP in all cases based on strict diagnostic criteria. There was no evidence of capsular or vascular invasion, and no coexisting thyroid malignancy was found in any patient. All patients had an uneventful postoperative course, with no reported complications. Ultrasound Characteristics

Preoperative neck Ultrasound (US) was performed for all patients and revealed thyroid nodules ranging in size from 0.9 cm to 5.8 cm. The number of nodules varied, with six patients having multinodular goiter, while three had solitary nodules. Most nodules were located in the left lobe (5/9); two were bilateral and two on the right (Table 2).

All nodules were well-defined on US. Common sonographic features included:

Table 2: Ultrasound Features of Suspicious Nodules in NIFTP Cases.

1. Solid component in all nine cases
2. Heterogeneous echotexture in 6 cases (66.7%)
3. Cystic degeneration in 6 cases (66.7% ) Perilesional vascularity was present in all cases
4. Intralesional vascularity was noted in 3 cases
5. No calcifications were seen in any patient Only one nodule showed a halo sign
6. Nodules were mostly isoechoic (7/9)
7. TIRADS 3 was the most common classification (6/9), while one nodule each was categorized as TIRADS 2 and 4 Histopathological Findings

All nine patients in the series were confirmed to have Non-Invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) on final histopathological evaluation. The tumor size ranged from 0.6 cm to 5.7 cm, with a mean size of 2.3 cm. Each tumor was well circumscribed with no ill-defined margins, and all had free surgical margins. Capsular and lymphovascular invasion were absent in all cases, consistent with the strict diagnostic criteria for NIFTP. All specimens demonstrated papillary-like nuclear features, such as nuclear enlargement, irregular contours, and chromatin clearing. Eight tumors were unifocal, while one (Case 2) was multifocal. All were of the low-risk follicular cell-derived histological subtype (Table 3).

Table 3: Histopathological Characteristics of NIFTP Tumors.

Combined Summary of Findings

A total of nine patients were diagnosed with Non-Invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) at our institution. The mean age was 45.3 years (range: 22–72), with a striking male predominance (8 males, 1 female), in contrast to previous reports suggesting a female predilection. The most common presenting complaint was neck swelling, either isolated or as part of a multinodular goiter. One patient presented with dysphagia, and another had newly diagnosed hypothyroidism. All patients underwent preoperative ultrasound, which demonstrated well-defined nodules with solid components in all cases. Most nodules were isoechoic, heterogeneous, and showed cystic degeneration. Perilesional vascularity was noted in all patients, while intralesional vascularity was present in three cases. No calcifications were observed. Nodules were mostly classified as TIRADS 3, with one case each classified as TIRADS 2 and TIRADS 4. FNAC findings were variable and fell across multiple Bethesda categories, with most falling into Bethesda III to V. Only one case had a non-diagnostic result on one side, and two cases were categorized as Bethesda II. This variation highlights the