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

다국어 초록 (Multilingual 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).”

참고문헌 (Reference)

1 Nikiforov YE, "Who classification of tumours of endocrine organs" International Agency for Research on Cancer 78-80, 2017

2 Pappotti M, "WHO classification of tumours of endocrine organs" International Agency for Research on Cance 73-74, 2017

3 Chan JK, "WHO classification of tumours of endocrine organs" International Agency for Research on Cancer 76-77, 2017

4 Radkay LA, "Thyroid nodules with KRAS mutations are different from nodules with NRAS and HRAS mutations with regard to cytopathologic and histopathologic outcome characteristics" 122 : 873-882, 2014

5 Kakudo K, "The new 4th edition World Health Organization classification for thyroid tumors, Asian perspectives" 68 : 641-664, 2018

6 Elisei R, "The BRAF(V600E)mutation is an independent, poor prognostic factor for the outcome of patients with low-risk intrathyroid papillary thyroid carcinoma : singleinstitution results from a large cohort study" 97 : 4390-4398, 2012

7 Chan J, "Strict criteria should be applied in the diagnosis of encapsulated follicular variant of papillary thyroid carcinoma" 117 : 16-18, 2002

8 Rosai J, "Renaming papillary microcarcinoma of the thyroid gland : the Porto proposal" 11 : 249-251, 2003

9 Welch HG, "Overdiagnosis in cancer" 102 : 605-613, 2010

10 Hirokawa M, "Observer variation of encapsulated follicular lesions of the thyroid gland" 26 : 1508-1514, 2002

11 Nikiforov YE, "Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma : a paradigm shift to reduce overtreatment of indolent tumors" 2 : 1023-1029, 2016

12 Zhu Z, "Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma : an unusually high prevalence of ras mutations" 120 : 71-77, 2003

13 Rivera M, "Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes(encapsulated vs infiltrative)reveals distinct BRAF and RAS mutation patterns" 23 : 1191-1200, 2010

14 Cancer Genome Atlas Research Network, "Integrated genomic characterization of papillary thyroid carcinoma" 159 : 676-690, 2014

15 Williams ED, "Guest editorial : two proposals regarding the terminology of thyroid tumors" 8 : 181-183, 2000

16 Chan JK, "Endocrine malignancies that may mimic benign lesions" 12 : 45-63, 1995

17 Adeniran AJ, "Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas" 30 : 216-222, 2006

18 Kakudo K, "Classification of follicular cell tumors of the thyroid gland : analysis involving Japanese patients from one institute" 59 : 359-367, 2009

19 Mitsutake N, "BRAF(V600E)mutation is highly prevalent in thyroid carcinomas in the young population in Fukushima : a different oncogenic profile from Chernobyl" 5 : 16976-, 2015

20 Haugen BR, "2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer : the American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer" 26 : 1-133, 2016