Encapsulated Papillary Thyroid Tumor with Delicate Nuclear Changes and a <i>KRAS</i> Mutation as a Possible Novel Subtype of Borderline Tumor

Abstract

Although papillary thyroid carcinoma (PTC)-type nuclear changes are the most reliable morphological feature in the diagnosis of PTC, the nuclear assessment used to identify these changes is highly subjective. Here, we report a noninvasive encapsulated thyroid tumor with a papillary growth pattern measuring 23 mm at its largest diameter with a nuclear score of 2 in a 26-year-old man. After undergoing left lobectomy, the patient was diagnosed with an encapsulated PTC. However, a second opinion consultation suggested an alternative diagnosis of follicular adenoma with papillary hyperplasia. When providing a third opinion, we identified a low MIB-1 labeling index and a heterozygous point mutation in the KRAS gene but not the BRAF gene. We speculated that this case is an example of a novel borderline tumor with a papillary structure. Introduction of the new terminology "noninvasive encapsulated papillary RAS-like thyroid tumor (NEPRAS)" without the word "cancer" might relieve the psychological burden of patients in a way similar to the phrase "noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)."

Updates in the Pathologic Classification of Thyroid Neoplasms: A Review of the World Health Organization Classification

“…There should be borderline/precursor thyroid tumors with a papillary growth pattern that was not clearly defined in the current WHO classification ( Fig. 3 ) [ 27 ]. Ohba et al [ 27 ] recently proposed a new borderline thyroid tumor with a papillary growth pattern and named it noninvasive encapsulated papillary RAS-like thyroid tumor (NEPRAS) ( Fig.…”

“…3 ) [ 27 ]. Ohba et al [ 27 ] recently proposed a new borderline thyroid tumor with a papillary growth pattern and named it noninvasive encapsulated papillary RAS-like thyroid tumor (NEPRAS) ( Fig. 4 ).…”

“…Noninvasive encapsulated papillary patterned thyroid tumors with papillary thyroid carcinoma (PTC)-like nuclear features were not defined in the fourth edition World Health Organization classification of tumors of endocrine organs [ 2 ]. Ohba et al [ 27 ] proposed to name it noninvasive encapsulated papillary RAS-like thyroid tumor (NEPRAS). FT-UMP, follicular tumor of uncertain malignant potential; WDT-UMP, well-differentiated tumor of uncertain malignant potential; WDC-NOS, well-differentiated carcinoma not otherwise specified.…”

“…(B) Higher magnification reveals mild nuclear enlargement and nuclear membrane irregularity which correspond to a nuclear score of 2 (H&E stain, ×400). Ohba et al [ 27 ] proposed to name this tumor NEPRAS.…”

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: From Echography to Genetic Profile

“…The main differential diagnoses of NIFTP include: follicular adenoma, from which NIFTP differs because of the presence of PTC-like nuclei; encapsulated follicular variant of PTC, which shows focal or extensive capsular and/or vascular invasion; infiltrative follicular variant of PTC which has no capsule or demarcation, but rather shows an infiltrative pattern of growth into the surrounding thyroid parenchyma; other borderline capsulated and follicular-pattern tumors such as WDT-UMP, FT-UMP (follicular tumor of uncertain malignant potential), WDT-UB (well-differentiated tumor with uncertain behavior); and the recently introduced borderline tumor with papillary structure "NEPRAS," mentioned above (Ohba et al 2019).…”