Incomplete ablation of thyroid cancer: Achilles’ Heel?

Abstract

Background

In recent years, the incidence of thyroid nodules has increased significantly. There are various ways to treat thyroid nodules, and ablation therapy is one of the important ways to treat thyroid nodules. However, there are many complications and deficiencies in the current ablation treatment of thyroid nodules, especially the incomplete ablation of thyroid cancer nodules, which limits the further application of ablation technology.

Case Summary

In this paper, we report two cases of incomplete ablation of thyroid nodules, one of which underwent surgical treatment due to anxiety after ablation, and the postoperative pathology confirmed that there was still residual papillary thyroid carcinoma, and the other patient underwent an operation after ablation, but visited our medical institution again due to cervical lymph node metastasis in a short period of time, and after radical cervical lymph node dissection, pathology confirmed multiple cervical lymph node metastasis. Radionuclide therapy was performed after surgery, and two patients are currently receiving endocrine suppression therapy, and their condition is stable with no signs of recurrence.

Conclusion

The incomplete ablation of thyroid cancer nodules limits the development of ablation therapy, making ablation treatment a double-edged sword. Guidelines and expert consensus can guide their development, but they need to evolve with the times, and a multidisciplinary diagnostic team can help screen the most suitable patients. Only by using this technology more standardly, using the most appropriate technology, and treating the most suitable patients, can benefit more and more patients.

Core Tip

Ablation is one of the important methods for the treatment of thyroid nodules, but there are still many problems in the treatment of thyroid malignant nodules, especially the incomplete ablation of thyroid cancer. We reported two patients with incomplete ablation who were stable after surgery and endocrine therapy. In view of this, we reviewed the literature on thyroid nodule ablation, in order to provide some reference for future medical practitioners in the treatment of thyroid nodule ablation.

Introduction

Thyroid nodules are one of the most common diseases of the endocrine system, with studies showing that 68% of the population suffers from thyroid nodules [1]. Exposure to ionizing radiation in childhood, bad mood, irregular work and rest, abnormal hormone secretion, and heredity are associated with the onset of thyroid nodules [2]. Some thyroid nodules are presented with a neck mass, but most patients with nodules have no obvious symptoms and are mostly found during physical examination. The treatment methods for thyroid nodules include drug treatment, dynamic observation (including dynamic monitoring of cancer nodules), surgery, ablation therapy, etc., and the current treatment strategies for thyroid cancer nodules are mainly the latter three strategies [3].

The development of thyroid ablation technology has been rapid in the last 20 years since the beginning of the 21st century. The efficacy of ablation in the treatment of benign thyroid nodules, especially cystic solid nodules, has been affirmed by many studies and has been recognized and recommended by many medical experts [4, 5]. Its treatment of malignant thyroid nodules is still under clinical research, and some existing studies have affirmed its efficacy [6,7,8], but some studies and case reports also question and worry about its application in the treatment of malignant nodules, especially the incomplete ablation discourages many medical workers and patients [9].

This article reported two cases of incomplete ablation, summarized the application status of ablation in the treatment of thyroid nodules by reviewing the relevant literature, and put forward some thoughts on the future ablation in the treatment of thyroid nodules. Hopefully, our article can provide some reference for medical professionals who perform thyroid malignant nodule ablation in the future.

Case presentation 1

Chief complaints

The patient Song, female, 34 years old, farmer, was admitted to the hospital because of “After ablation of thyroid carcinoma, anxiety persisted for 1 month.“.

History of present illness

The patient was admitted to the local hospital for neck discomfort 1 month before admission, and thyroid B ultrasound showed hypoechoic nodules (size, 4 × 3 mm) in the right lobe of the thyroid gland (TI-RAIDS IV class), papillary thyroid carcinoma was considered after FNA, and microwave ablation of the right lobe nodule of the thyroid gland under ultrasound guidance was performed in the local hospital. After ablation, the surface skin was not red, swollen or ulcerated, there was no hoarseness, no cough when drinking water, no chest tightness, shortness of breath, no dizziness, headache, no emotional irritability, no trembling hands, sweating. But the patient was now undergoing persist anxiety. She was admitted to our hospital and admitted to the outpatient clinic with “thyroid malignancy”. During the period of the disease, the patient was in anxiety spirits, ate and slept well, and had no other symptoms, and there is no significant change in recent body weight.

History of past illness

The patient underwent thyroid cancer ablation treatment 1 month, In addition, there had no history of other specific medical conditions.

Personal and family history

The patient had no family history.

Physical examination

The neck was soft, there was no resistance, the jugular veins were not distended, the carotid artery was not abnormal, the trachea was centered, the left thyroid gland was not palpated, and the right thyroid gland was locally hard.

Laboratory examinations

The patient had normal CEA, PTH, and calcitonin, thyroid-stimulating hormone 0.120 mIU/L, total thyroxine 18.28 ug/dL, free thyroxine 1.92 ng/dL, and thyroglobulin 66.04 ng/mL. The rest of the test results were not abnormal.

Imaging examinations

Thyroid ultrasound showed: Mixed echogenic nodule in the right lobe of the thyroid gland (TI-RADS category III) (Fig. 1). CT examination of neck showed: The right lobe of the thyroid gland was round and mixed with dense shadows (Fig. 2). Pathological section consultation: (right thyroid nodules) consider papillary carcinoma (Fig. 3).

Fig. 1

Ultrasound (US) showed changes in the right lobe of the thyroid gland after ablation

Fig. 2

Computerized Tomography (CT) imaging showed hypoechoic lesions in the right lobe of the patient’s thyroid gland

Fig. 3

Pathological consultation on needle cell smear suggested that papillary thyroid carcinoma should be considered

Final diagnosis

According to the patient’s medical history, clinical characteristics, and test results, the patient was diagnosed with after ablation of thyroid cancer.

Treatment

Due to the patient’s severe anxiety after thyroid ablation, we then performed the total thyroidectomy with right central node dissection for right-sided thyroid cancer and lymph node dissection in the right central area, and the postoperative pathology showed that papillary thyroid carcinoma (right and isthmus thyroid), no lymph node metastasis in the central area and anterior laryngeal tissue (0/6), AJCC-p TNM stage: T1aN0Mx (Fig. 4).

Fig. 4

Immunohistochemistry (IHC) showed papillary carcinoma of the right lobe of the thyroid gland

Outcome and follow-up

The patient underwent regular endocrine suppression therapy after surgery, and at present, 75ug levothyroxine sodium tablets were taken orally every day, and thyroid function and thyroid ultrasound were monitored dynamically, and there was no sign of recurrence.

Case presentation 2

Chief complaints

The patient An, male, 47 years old, employee, was admitted to the hospital because of " Six months after thyroid ablation, cervical lymphadenopathy was found to be swollen for one month.“.

History of present illness

The patient complained of thyroid radiofrequency ablation + thyroid tumor needle biopsy in a local hospital for “thyroid nodules” 6 months before admission, and the postoperative pathology showed papillary carcinoma of the left lobe of the thyroid gland, and then endoscopic left lobe and isthmus resection of the thyroid gland under general anesthesia on 2023-02-10. The operation went smoothly, and the patient was regularly taken levothyroxine sodium tablets after surgery. The patient’s cervical lymphadenopathy was found to be abnormally swollen in the re-examination 1 month ago, and now the patient is admitted to our hospital for further treatment, and is admitted to the outpatient clinic with “thyroid malignant tumor”. During the period of the disease, the patient was in anxiety spirits, ate and slept well, and had no other symptoms, and there is no significant change in recent body weight.

History of past illness

The patient underwent thyroid cancer ablation and surgery 6 month ago. In addition, there was no history of other specific medical conditions.

Personal and family history

The patient had no family history.

Physical examination

The neck was soft, there was no resistance, the jugular veins were not distended, the carotid artery was not abnormal, the trachea was centered, the thyroid gland was not palpated.

Laboratory examinations

The test results were not abnormal.

Imaging examinations

Thyroid ultrasound showed: Hypoechoic nodules in the right lobe of the thyroid gland (TI-RADS category IVa class) and multiple abnormally enlarged lymph nodes in the left side of the neck (Fig. 5). CT examination of neck showed: After thyroid surgery, lymph nodes in the left neck zones 2 and 5 enlarged and abnormally strengthened (Fig. 6).

Fig. 5

Ultrasound (US) showed hypoechoic nodular lesions in the right lobe of the thyroid gland that break through the dorsal membrane of the thyroid gland. Multiple abnormally enlarged lymph nodes may be seen in the neck

Fig. 6

Computerized Tomography (CT) imaging showed multiple swollen lymph nodes on the left side of the neck, partially enhanced during the enhancement phase

Final diagnosis

According to the patient’s medical history, clinical characteristics, and test results, the patient was diagnosed with after ablation of thyroid cancer.

Treatment

We performed cervical lymph node biopsy, frozen pathology during surgery showed: (Left cervical lymph nodes) papillary carcinoma (Fig. 7), then we performed the total thyroidectomy with right central node dissection for right-sided thyroid cancer. The postoperative pathology showed that papillary thyroid carcinoma (right and isthmus thyroid), and lymph node metastasis in the central area and anterior laryngeal tissue (4/22), AJCC-p TNM stage: T1aN1bMx (Fig. 8).

Fig. 7

Intraoperative frozen pathology showed metastatic papillary carcinoma (lymph nodes in the left neck zone 4)

Fig. 8

Immunohistochemistry (IHC) showed that the right thyroid gland was papillary carcinoma, and the left cervical lymph node had multiple metastases

Outcome and follow-up

The patient underwent one dose of iodine-131 treatment postoperatively, and then underwent regular endocrine suppression therapy, and at present, 100ug levothyroxine sodium tablets were taken orally every day, and thyroid function and thyroid ultrasound were monitored dynamically, and there was no sign of recurrence [10].

Discussion

In recent years, with the improvement of socio-economic level, people’s awareness of physical examination has also been significantly improved, which has led to a rapid increase in the incidence of thyroid nodules [1, 2, 10]. Studies have shown that the onset of thyroid nodules may be related to childhood radiation exposure, bad mood, endocrine disorders, etc. Thyroid nodules include benign thyroid nodules and malignant thyroid nodules, and benign nodules include thyroid cysts, thyroid adenomas, nodular goiters, etc. Observation, medication, and surgery are the traditional forms of routine treatment [2].

The boom in ablation technology has given the thyroid nodule treatment an option. Benign thyroid nodule ablation has been developed for more than 20 years, and its treatment effect is good, and the patient experience is good [11,12,13,14]. In view of the successful application of ablation technology in benign nodules, some researchers have begun to try to apply this technique to the treatment of malignant thyroid nodules [14]. Many studies have shown that ablation can also be effective in the treatment of malignant thyroid nodules [15, 16]. However, incomplete ablation of malignant nodules and recurrence after ablation still plague medical workers and discourage many patients [9, 17].

We reported two patients with incomplete ablation, one of whom underwent FNA during ablation treatment, and the pathology after ablation showed papillary carcinoma. Another patient also underwent FNA at the time of ablation, and the pathology showed papillary carcinoma and then underwent the total thyroidectomy with central node dissection surgery, but unfortunately, abnormal lymph nodes in the left neck and high-risk nodules on the right thyroid gland were found in the reexamination six months after surgery, and the left cervical lymph node was confirmed to be metastatic papillary carcinoma after puncture, and the postoperative pathology also showed that the right nodule was also papillary carcinoma. Such cases make us doubt the application of ablation in the treatment of thyroid cancer nodules. A proverb says: know yourself and know your enemy, and win all battles. To better understand the causes of incomplete ablation, we reviewed and analyzed literatures that is relevant to it.

It is important to choose the right patient. At present, there is some consensus that it is recommended to choose patients with low-risk papillary carcinoma nodules or unresectable cancer nodules and strong desire for ablation [5, 18]. However, none of the patients reported in this article had pre-ablation FNA to determine the nature of the nodule and tumor risk stratification. It seems a bit arbitrary, ablation should be carried out under the guidance of a multidisciplinary team with the participation of experts from endocrinology, thyroid surgery, ultrasound, radiology, and radiotherapy [19]. Pathology classification and patient informed information are important [20]. Genetic testing also has a good guiding effect on pathological analysis and patient treatment effect [21]. When BRAF, RAS, TERT, PIK3CA, TP53 genes mutated, the malignant possibility and aggressiveness of thyroid nodules are significantly increased, and ablation treatment should be carried out cautiously when the pathology suggests the presence of one or more of the above gene mutations after puncture. At present, there is no risk stratification model that integrates multiple genes and pathological types. In practice, it is necessary to continuously accumulate experience, and ablation technology should be used cautiously for patients with suspected multifocal cancer nodules and newly diagnosed cervical lymph node metastasis [22, 23]Machine and deep learning may play a key role in the risk stratification of thyroid nodules [24].

The commonly used techniques for thyroid cancer ablation are microwave ablation and radiofrequency ablation. The former forms a microwave electromagnetic field in the ablation area, and a high temperature is formed locally for a short time, resulting in coagulative necrosis of cells [25], and the latter sends a radiofrequency current locally, causing necrosis of the lesion [26]. Its characteristics of action determine that it can only treat local lesions, and it will affect the tissues around the lesions. Therefore, ablation therapy is limited for malignant thyroid nodules close to the back membrane of the thyroid gland, especially the dorsal membrane, adjacent to the recurrent laryngeal nerve, arteries and veins, etc [4, 17].

For high-risk nodules under ultrasound, FNA and genetic testing are recommended to assess the risk of malignancy of the nodules. For low-risk PTMC and unresectable thyroid cancer, patients should be informed in detail about the condition and the advantages and disadvantages of ablation therapy, and ablation therapy can be considered after obtaining the patient’s consent. MDT should guide the entire course of treatment (Fig. 9).

Fig. 9

Flow chart of ablation treatment of thyroid nodules. PTMC, papillary thyroid microcarcinoma; FNA, fine needle aspiration; MDT, multi-disciplinary treatment; RFA, radiofrequency ablation; MWA, microwave ablation; LA, laser ablation

There have been a lot of studies that have tried to protect the normal tissue around the nodules, and the results are encouraging [27, 28]. Preoperative localization of thyroid nodules and evaluation of possible efficacy with appropriate evaluation models [29]. After ablation, appropriate evaluation indicators are used to determine the risk of incomplete ablation and recurrence in advance, post-ablation stimulated thyroglobulin (> 20.2 ng/mL) was a valuable predictor of disease persistence/recurrence in DTC patients with biochemical incomplete response [30]. A post-ablation response evaluation system consisting of ultrasound results and post-FNA pathological results was defined in one study and validated in practical applications(Fig. 10) [31].

Fig. 10

Definitions of the response-to-ablation system at 1-year follow-up [31]. PTMC, papillary thyroid microcarcinoma; CNB, core needle biopsy; FNA, fine needle aspiration

Thermal ablation may produce sublethal thermal stress, it may increase clonogenicity, migration, and invasion of thyroid cancer cells [32],and also can promote proliferation and invasion of breast cancer cells and caused gene alterations in cancer and immune system [33]. One study suggested that the VEGR and AKT pathways and related genes may be activated after radiofrequency ablation, resulting in incomplete ablation and recurrence [34]. It is worth paying attention to in future studies.

Conclusion

Ablation of thyroid cancer nodules is currently facing many challenges, and incomplete ablation is one of the important challenges. There are many factors such as social economy, operation technology, and diagnosis and treatment standards. We need to study these factors in depth, make friends with our enemies, and use the most appropriate technology to treat the most suitable patients, so as to improve the level of diagnosis and treatment of thyroid nodules and provide patients with a better medical experience.