This is a case of a 60-years-old male who had diagnosed with diabetes 7 years ago, treated with metformin orally, and presented with a left anterior neck mass more than 1 year ago inadvertently. No pain, redness, fever, hoarseness, dysphagia, dyspnea, excitability, irritability and hunger was found during the period, and the patient did not go to the hospital and receive any treatment. The patient noticed an enlargement of the mass recently, and then came to our hospital for further treatment. There was no abnormal carotid pulse, venous engorgement, and hepatojugular reflux on relevant physical examination. However, a 2.5×2.5×2 cm3, smooth, hard, clear boundaries and solid nodule on the left thyroid gland was found. The patient had no familial genetic, psychosocial and exposure to radiation and toxins history. Furthermore, he was conducted in line with the care check-list. A timeline with relevant information, and follow-up process of the patient was shown in Fig. 1A. The pathological diagnosis process was shown in Fig. 1B.
Laboratory tests of the tumor biomarkers such as CA125 (17.20 U/ml) shown slightly increased, and cytokeratin 19 (CK19) fragment shown a critical value. The levels of thyroid function indexes and parathyroid hormone were normal. Thyroid function determination shown a free thyroxine (FT4) level of 112.70 nmol/L, thyroid-stimulating hormone (TSH) level of 1.83 µIU/ml, thyroglobulin (TG) level of 20.6 ng/ml and AbTg level of 15.50U/ml.
Then, he was admitted and underwent gray scale ultrasonography and color doppler flow imaging (CDFI). The gray scale ultrasonography shown a sized 2.1×2.6×2.7cm3 low echoic shadow and a few striped strong echoes (Fig. 2A). CDFI shown streaks of blood flow signal in and around the thyroid, and the pulsed wave shown the arterial spectrum with maximum speed of 21 cm/s (Fig. 2B). Hypoecho of lymph nodes in submandibular space and the lymphatic hilar blood flow signals were detected by CDFI (Fig. 2C).
The patient refused the fine needle aspiration (FNA) administration. And then, the unilateral radical resection of thyroid carcinoma was performed. After surgery, thyroid function determination shown a FT4 level of 100.20 nmol/L, TSH level of 3.19 µIU/ml, TG level of 3.76 ng/ml and AbTg level of 19.20U/ml.
The mass was about 3×2×2cm3 in size with a 0.2 cm capsule of the left thyroid. The histological characteristics were sclerosing with clear boundaries by the capsule (Fig. 3A). At low magnification, the extensive vitrification, calcification, and necrosis was in the background, and the tumor cells were squamous metaplasia, scattered, and arranged in clusters with diffuse growth pattern (Fig. 3B). Besides, some tumor cells and psammoma bodies have infiltrated to the capsule (Fig. 3C). At high magnification, the tumor cells were enlarged and shown stretched nucleus, the follicular epithelium cells of thyroid were atypical (Fig. 3D). Furthermore, the nuclear grooves (Fig. 3E) and internuclear pseudoinclusion (Fig. 3F) was detected.
Immunohistochemical staining shown strong positiveness of CK19, TTF-1, P40 and Galectin-3, partial positiveness of TG of tumor cells and negativeness of Calcitonin (Fig. 4A-F). Besides, CK-pan, Pax-8, P63, P16, P53 and TPO was strong positive, CK5/6 and CD56 was partial positive, and then Syn and CgA was negative.
First generation sequencing techniques of thyroid carcinoma test containing AKT1, GNAS, KRAS, PIK3CA, PTEN, TERT, BRAF, HRAS, NRAS, PAX8/PPARG, RET, TP53, CTNNB1, NTRK, ZNF148, SPOP, EZH1 and TSHR was used in this case. The RET gene shown Exon 11c.2071G > A p.G691S mutation, and abundance of mutation was 52.53% (S1. A). The NRAS gene revealed Exon 3c.182A > G p.Q61R mutation, and abundance of mutation was 19.80% (S1. B). The TERT gene indicated c.-124C > T (C228T) mutation, and abundance of mutation was 15.08% (S1. C). The PIK3CA gene resulted Exon 21c.3140A > G p.H1047R mutation, and abundance of mutation was 1.50% (S1. D). Finally, we made the diagnosed of typical papillary thyroid carcinoma with squamous metaplasia and RET/NRAS/TERT/PIK3CA mutations pathologically.
The patient remained under careful observation by ultrasonic examination follow-up and treated with levothyroxine sodium tablets orally. and there was no recurrence or metastasis in the 6 months follow-up. The patient got appropriate perspective including the assessment and the episode of care in every 3 months. No adverse and unanticipated events happened during the period. Finally, the patient was satisfied with the treatment plan, process and prognosis, and will continue to follow up as prescribed by the doctors.