Modern diagnosis and treatment of papillary thyroid cancer

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Introduction
According to the data obtained during the GLOBOCAN study of morbidity and mortality from malignant neoplasms, in 2020, in the structure of oncological diseases, malignant neoplasms of the thyroid gland (TG) are in ninth place and occupy8.6% of the total number (Pizzato M, Vaccarella S, 2022;Sung H, Bray F, 2020).Thyroid cancer (TC) is the most common malignant tumor of the endocrine glands, which accounts for 1% of all cases of malignant neoplasms (Megwalu UC, Moon PK, 2022).Diagnosis of TC remains a difficult problem.The standard method of preoperative diagnosis of TC after ultrasound examination (ultrasound) is fineneedle aspiration puncture biopsy (FNA) with a cytological examination (Smith T, Kaufman CS, 2021).FNA allows to assess the risk of malignant potential and determines clear indications for operative treatment.However, the result depends on the accuracy of getting into the focus and has certain limitations, in particular, in the differential diagnosis of follicular tumors of the TG, assigned to the diagnostic category III-V according to the Bethesda classification (Kiernan CM, Solórzano CC, 2017).Similar cytological findings occur in about 10-40% of cases and require surgical interventions for diagnostic purposes, although only in 10-15% of cases a malignant process is confirmed during a histological examination.(Mon SY, Hodak SP, 2018).
In Ukraine, up to 3,000 cases of TChave registeredannually, and the mortality rate reaches 10-12 people per 1 million population, which is twice as high as the averagestatistical indicators in the world.According to the National Cancer Registry, in Ukraine for the period from 2014 to 2021, 24,626 patients with TC were identified, of which 4,556 were men (18.5%) and 20,070 were women (81.5%).On average, 3078.25 ± 136.15 people were diagnosed per year.The incidence rate among women is 3.8 times higher than among men.The average incidence rate in Ukraine for 2014-2021 was 6.5 per 100,000 population (Kurochkin A, Moskalenko Yu, 2022).
The study of histological types of malignant neoplasms of the TG showed that the papillary variant of the TC is the most often observed (70.5-81.9%).The share of follicular TC ranges from 12.8 to 19.2%.Medullar cancer occurs much less often -in 1.5-4.6% of cases, while undifferentiated and squamous cell carcinoma is extremely rare (0.2-3.3% of cases) (Kurochkin A, Moskalenko Yu, 2022;Tovkai, O. A.,YI Komisarenko, 2022).The prognosis of TC is generally favorable, and the relapse rate is in the range of 5 to 20% (Ulisse S, Ferent IC, 2021).
The results of researchesin recent years indicate that the increase in the incidence of papillary TC is partially related to the increase in the number of preventive examinations (Olson E,Silberstein PT, 2019).
Treatment of papillary TC combines three methods: surgery, the use of radioiodine therapy, and hormone replacement therapy with levothyroxine drugs (Nguyen QT, Plodkowski RA, 2015).
Therefore, it is important to use modern diagnostic methodsaimed at establishing and confirming the diagnosis in order to identify thyroid neoplasms to choose the right treatment tactics and the fastest recovery of the patient.

Aim
The purpose of this work, based on the example of a clinical case, was to analyze the patient's route, methods of diagnosis, and treatment of a thyroid neoplasm according tocurrent instructionsand recommendations.

Clinical case description
Patient K., 57 years old, applied for a consultation at the Ukrainian Scientific and Practical Center for Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of MoH of Ukraine with complaints of pain and swelling in the right sideof the neck, swallowing disorders, shortness of breath with minor physical exertion, dizziness.These complaints have arisen in the last three months.There is no family history of thyroid pathology and oncological pathology.Objectively: at the time of examination, the general condition of the patient is relatively satisfactory.The patient has a normosthenic physique, the skin is pale pink and moist.Blood pressure 135/80 mm Hg, heart rate 85 in 1 min.Breathing is vesicular, wheezing is absent.There is no peripheral edema.The TG is not enlarged on palpation, dense consistency.
The patient was examined by an endocrinologist, and directed to laboratory tests to clarify the function of the TG, ultrasound of the TG, and ultrasound of the vessels of the head and neck.An ultrasound of the brachiocephalic arteries revealed extravasal compression of the internal jugular vein on the right, so multispiral computed tomography (MSCT) of the mediastinal organs was recommended.
Ultrasound of the TG revealed its typical location, without sealing of the capsule.An isoechoic formation of a non-homogeneous echo structure measuring 5x12 mm is visualized in the right lobe of the TG.In the upper pole, on the dorsal surface of the right lobe, a formation measuring 7x12 mm, irregular in shape, with clear borders is localized.The echo structure of the formation is heterogeneous due to small calcifications.In general, thyroid tissue is isoechoic, the echostructure is heterogeneous due to small hydrophilic areas.Additional formations along the vascular-nerve bundle are not identified.Thyroid volume according to Brunn: right lobe 8.91 cm 3 , left lobe 3.94 cm 3 .In the lower pole of the right lobe, there is an accumulation of macrocalcifications up to 7 mm in size.In the upper third of the collector to the right to the middle of the sternocleidomastoid muscle, altered lymph nodes with microcalcifications of 24 and 28 mm in size were found.
MSCT of the neck and chest with intravenous contrast revealed signs of a neoplasm of the right lobe of the TG without extrathyroidal spread, multiple small hypovascular foci in both lobes of the TG, and lymphadenopathy of neck nodes of secondary genesis.In the mediastinum and parenchyma of both lungs, volumetric, focal, and fresh infiltrative changes were not detected.
After the studies, the patient underwent FNAB of thyroid formations, followed by immunocytochemical studies.Cytological conc lusion: node of the right lobe of the TG (12 mm) -papillary cancer, class 6, DAPIV -12.DAP(dipeptidyl-aminopeptidases IV)is a cellular enzyme actively involved in oncogenesis of the thyroid gland, and the cytochemical study of DAP IV is considered as a marker of cell malignancy (Fig. 1).In the lymph nodes of the neck of the third collector on the right, metastasis of papillary TC, 26 mm in size.Class 6. DAP 12 (Fig. 2).The patient was transferred to the surgical department of the Ukrainian Scientific and Practical Center for Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of MoH of Ukraine for planned surgical intervention.Extrafascial thyroidectomy, central and right-sided modified neck dissection, and lymphadenectomy were performed.Intraoperative histological express examination revealed metastases of papillary cancer in 2-5 lymph nodes on the right.During the surgical intervention, an invasion into the reverse laryngeal nerve on the right was detected, and rein nervation of the nerve was performed.
In the postoperative period, the patient showed signs of phonation disturbance.The postoperative wound healed by primary intention.In the postoperative period, calcium D3 was prescribed at a dose of 1500 mg/day, vitamin D 4000 IU once a day, and B vitamins (B1, B6, B12).After the treatment, there was a positive trend.
Considering the size of the tumor, extra organ invasion, and presence of metastases, the patient is referred for further treatment with radioactive iodine treatment.For a month, the patient followed a diet with a low iodine content and did not receive levothyroxine preparations.
The patient received treatment with I 131 with a total dose of 5180.0MBq for five days.Whole body scintigraphy with I 131 revealed an accumulation of a radiopharmaceutical (RP) in the projection of the thyroid bed on the left and the upper third of the neck along the midline of the neck (d.Thyreoglossus).
After combined therapy (surgery and treatment with I 131 ), the patient has prescribed a suppressive dose of levothyroxine 125 mcg/day, followed by dose adjustment after 6-8 weeks.Upon reexamination, the patient noted the presence of positive dynamics, the phonation function was restored, and there were no complaints of pain and swelling of the neck, impaired swallowing, shortness of breath, and dizziness.
The woman was prescribed lifelong replacement therapy with thyroid hormone preparations (levothyroxine) at a dose of 125 mcg/day, followed by dose adjustment.It was recommended to study the level of TSH, thyroglobulin, antibodies to thyroglobulin, parathyroid hormone, ionized calcium, and ultrasound of the thyroid bed and neck after 2 months.In the future, the patient undergoes a mandatory annual oncological examination in highly specialized centers with an examination by endocrinologists.

Discussion
This clinical case makes it possible to understand the need for prompt examination of patients.The woman was examined in full according to the recommendations of the European Thyroid Association (Lebbink CA, Krude H, 2022).
In clinical practice, there are cases of unjustified surgical treatment of thyroid nodules without verification of their structure.In this case, there are operational risks, and the need to take replacement therapy throughout the patient's life.
Ultrasound of the TG is used not only as a method for detecting and describing formations of the TG and a way to monitor the implementation of FNA of suspicious nodes but also to visualize the spread of the oncological process.Ultrasound is performed to identify cervical lymph nodes suspicious for metastatic disease.Based on the data obtained, the volume of surgical intervention is determined (Tovkai, Zemskov, 2022).As noted in the American Thyroid Association guidelines for patients with thyroid nodules and differentiated TC, ultrasound is the first-line imaging modality for individuals with suspected or proven TC (Yeh MW, Bernet VA, 2015).
The generally recognized "gold standard" for the treatment of differentiated TC is total thyroidectomy, supplemented by dissection of the lymphatic collectors, followed by radioiodine ablation of the residual thyroid tissue (Yeh MW, Bernet VA, 2015).It has been proven that this approach significantly reduces the recurrence rate,mortality rates, and also allows monitoring of patients by the level of thyroglobulin in the blood and/or antibodies to it regarding the possible occurrence of metastases, which in most cases are effectively treated with radioactive iodine (Ostafiichuk M, Tarashchenko Y, 2022).In the future, patients with TC are recommended periodic outpatient monitoring with the determination of relevant indicators.
The described clinical case testifies to the high quality of diagnostics and treatment of a patient with papillary TC in a highly specialized endocrinological center.This approach fully meets international requirements for the treatment of TC.Despite the difficult epidemiological situation in Ukraine and the state of war, the patient was timely referred to the Ukrainian Scientific and Practical Center of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues, where she received the necessary assistance in full.