J Pathol Transl Med.  2019 Mar;53(2):136-141. 10.4132/jptm.2018.12.07.

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

• Ohba K
• Mitsutake
• Matsuse M
• Rogounovitch T
• Nishino N
• Oki Y
• Goto Y
• Kakudo K

• KMID: 2465454
• DOI: http://doi.org/10.4132/jptm.2018.12.07

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)."

Keyword

Borderline/precursor tumor; Observer variation; RAS-like tumor

MeSH Terms

Adenoma
Adult
Diagnosis
Humans
Hyperplasia
Observer Variation
Point Mutation
Referral and Consultation
Thyroid Gland*
Thyroid Neoplasms

Figure

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  Fig. 1. Encapsulated papillary growth-patterned tumor with equivocal papillary thyroid carcinoma (PTC)-type nuclear features in a 26-year-old man (nuclear score 2 according to Nikiforov et al[4].) (A) B-mode ultrasonography showing a hypoechoic, heterogeneous nodule with a largest diameter of 23 mm and a slightly jagged border. (B) Fine-needle aspiration cytology revealing a number of crowded groups of follicular cells with slight nuclear enlargement and mild nuclear overlapping (Papanicolaou stain). (C, D) The resected solid tumor showing a capsule (arrow) and two types of papillary lesions: one covered with follicular cells containing small hyperchromatic nuclei (adenomatous nodule-like lesion, AN) and the other covered with larger follicular cells having nonhyperchromatic nuclei (P). (E, F) High-power views of the second type of papillary lesion showing nuclear elongation and overlapping as well as a one- to two-fold enlargement of nuclei size with granular chromatin. Nuclear grooves are not abundant, and pseudoinclusions are absent. Chromatin characteristics of PTC-type nuclear features are insufficient.

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  Fig. 2. Immunohistochemical and mutational analyses. (A, B) Immunohistochemical staining with cytokeratin 19 and BRAFV600E led to negative results in the cytoplasm of the tumor cells. (C) The MIB-1 labeling index was approximately 1%–2%. (D) Sequence analysis revealed a heterozygous point mutation of the KRAS gene in exon 2 (GGT to GCT) resulting in the substitution of alanine for glycine at codon 12 (G12A) in the tissue sample from the papillary lesion with a nuclear score of two and an adenomatous nodule-like lesion (D).

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