Synchronous occurrence of papillary thyroid carcinoma and medullary thyroid carcinoma in the setting of Hashimoto’s thyroiditis: a case report with literature review

Introduction

According to the Global Malignant Tumor Statistical Report 2022 (1), the incidence rate of thyroid cancer is ranked seventh worldwide, with women accounting for approximately 75% of cases. Histopathologically, thyroid cancer can be classified into three distinct types: (I) differentiated thyroid cancer (DTC): comprising papillary thyroid cancer and follicular thyroid cancer; (II) medullary thyroid carcinoma (MTC); (III) undifferentiated thyroid carcinoma: a highly aggressive tumor with a high mortality rate.

Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer. Currently, surgical resection is the primary clinical treatment, supplemented by I¹³¹, thyroid stimulating hormone (TSH) inhibition therapy, and targeted therapy following surgery. The necessity for prophylactic central and lateral cervical lymph node dissection remains a subject of debate. Accordingly, the Guidelines for the Diagnosis and Treatment of Thyroid Nodules and Differentiated Thyroid Cancer (second edition) strongly advocate that, in cases of DTC where parathyroid glands and recurrent laryngeal nerves are successfully preserved, at least ipsilateral central lymph node dissection should be performed (2).

MTC which accounts for 5–10% of thyroid cancers originates from the parafollicular cells (C cells) of the thyroid gland. Serum calcitonin (Ctn) is a peptide hormone secreted by thyroid C-cells-the most sensitive indicator for monitoring the prognosis and recurrence of MTC patients. Due to the insensitivity of MTC to radiotherapy, I¹³¹ treatment, and endocrine therapy, MTC is still predominantly resected surgically in clinical practice.

The occurrence of PTC complicating MTC is an uncommon phenomenon in clinical settings, and its classification can be categorized into two distinct categories based on the divergent histological origins: (I) mixed medullary and follicular cell carcinoma (MMFCC): a thyroid malignancy characterized by the presence of follicular and parafollicular cell elements within a singular lesion, predominantly manifesting as MTC mixed PTC (MMPTC); (II) MTC combined with PTC (MTC-PTC): existing in one and/or both glands with their independent foci (3). The pathological features of MMPTC are analogous to those of MTC alone, i.e., the cells are arranged in solid sheets, nests, papillae, or follicular structures with amyloid deposits. Conversely, MTC-PTC exhibited the distinct pathological characteristics of both MTC and PTC, featuring complex branching papillae with fibrovascular axons, as observed in PTC (4,5). The pathological findings are important for the early diagnosis of PTC complicating MTC and for improving the prognosis.

Hashimoto’s thyroiditis (HT) is an autoimmune disease. The mechanisms of HT with PTC are as follows (6): (I) gene variant (RET; p63; BRAF); (II) inflammatory response [interleukin-4 (IL-4)/10; reactive oxygen species (ROS)]; (III) immune function [abnormal expression of immunomodulatory factors, such as programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1)]; (IV) hormone metabolism (TSH; oestrogen; aberrant protein expression); (V) cell cycle disorder (PI3K/AKT/mTOR-signaling; COX-2). Similarly, autoimmune inflammation is triggered during the anti-tumor immune response. However, HT combined with MTC is rare, and no study has confirmed whether there is a correlation between the two. The reason for the co-occurrence of HT, PTC, and MTC may be attributable to the rearrangement of certain genes (4).

To date, there is a paucity of clinical reports of HT patients with concomitant PTC and MTC. The present case report and literature review may, however, contribute to the study and treatment of subsequent similar cases. We present this article in accordance with the CARE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-141/rc).

Case presentation

Patient information

The female, 59 years old, was admitted to the hospital with the main cause of “right neck pain for 6 months and right thyroid nodule for 20 days”. The patient exhibited no skin redness or swelling, no fear of cold or fever, no hyperphagia, no irritability, no fear of heat or excessive sweating, no palpitation or hand trembling, and no emaciation. The patient is in good physical condition and has no history of chronic or infectious diseases, nor any family history of thyroid cancer, parathyroid, adrenal, or renal stones.

Clinical examination

Upon thorough inspection, the patient’s neck exhibited a symmetrical appearance, devoid of any notable skin elevations in the anterior neck region. A meticulous examination revealed no significant swelling in the thyroid gland bilaterally, and no vascular murmur was audible. Additionally, no palpable lymph nodes were identified on either side of the neck.

Diagnostic assessment

Ultrasound grading of thyroid nodules revealed the presence of multiple hypoechoic nodules in the right lobe, the largest of which was located centrally (19.2 mm × 11.5 mm × 14.9 mm), exhibiting clear borders, peripheral ring blood flow signals, and hardness comparable to that of the surrounding glandular tissues, classified as Thyroid Imaging-Reporting and Data System (TI-RADS) grade 3. A hypoechoic nodule measuring 12.1 mm × 6.7 mm × 11.0 mm was identified in the right lobe, near the isthmus, with poorly defined borders, visible blood flow signals, and a hardness slightly higher than that of the surrounding glandular tissues, TI-RADS grade 4a. The remainder of the nodules were TI-RADS grade 3. No enlarged lymph nodes were observed in the anterior neck. Stage 2 enhanced CT of the neck showed multiple hypodense nodular shadows in the right lobe of the thyroid gland with clear borders, enhancement that was not significantly increased, adenoma was considered, and the density of the left lobe of the thyroid gland was uneven, which needed to be combined with the clinic. Hematology: free T3 (FT3) and free T4 (FT4) levels were normal, high-sensitivity thyrotropin (TSH) 4.75 mIU/L (normal range, 0.27–4.2 mIU/L), thyroid peroxidase antibody (anti-TPO) 9.40 IU/mL (normal range, 0.00–34.00 IU/mL), anti-thyroglobulin antibody (anti-Tg) 23.80 IU/mL (normal range, 0–115 IU/mL), thyroglobulin (Tg) 1.26 ng/mL (normal range, 3.5–77 ng/mL), Ctn 614.9 pg/mL (normal range, 0.00–6.40 pg/mL), carcinoembryonic antigen (CEA) 4.98 ng/mL (normal range, 0–5.0 ng/mL).

Therapeutic intervention

In the course of the operation, the right thyroid lobectomy was initiated first, and the resulting resection specimen was transferred to the pathology department. The intraoperative frozen section pathology suggested a diagnosis of papillary thyroid carcinoma, and the other nodule required further investigation using paraffin and immunohistochemistry. The possibility of medullary carcinoma could not be excluded. The procedure was continued with the left thyroid lobectomy and bilateral central zone lymph node dissection. Postoperative histopathological findings were returned (shown in Figures 1-6): papillary carcinoma of the right thyroid gland (maximum diameter 1 cm), invading the peritoneum of the thyroid gland, immunohistochemical staining showed cytokeratin 19 (CK19) (+), Galectin3 (+), neural cell adhesion molecule 1 (CD56) (−), TPO (−), BRAF (weakly +), and Ki-67 (index of about 5%); a more diffusely growing medium-sized heterogeneous cell nodules (maximum diameters of 2 and 0.4 cm) with well-defined borders and immunohistochemical staining showed chromogranin A (CgA) (+), synaptophysin (Syn) (+), CD56 (+), calcitonin (CT) (+), CK (+), and Ki-67 (index about 5%), which were consistent with medullary carcinoma of the thyroid gland; suggestive of a background of HT. The presence of metastatic cancer was observed in the right central zone lymph nodes (2/4), with a metastatic component of PTC, while no metastatic cancer was detected in the right VI b zone, left central zone, and laryngeal lymph nodes.

Figure 1 Papillary thyroid carcinoma. (A) Papillary appearance and psammoma bodies (black arrow) (×40, H&E). (B) Intranuclear pseudoinclusion (black star) (×400, H&E). H&E, hematoxylin and eosin.

Figure 2 Medullary thyroid carcinoma. (A) Tumour tissue separated by vascular-rich mesenchyme, hyaline collagen and amyloid (×40, H&E). (B) Cytoplasm is eosinophilic or biphilic (×400, H&E). H&E, hematoxylin and eosin.

Figure 3 Hashimoto’s thyroiditis. (A) Atrophy of thyroid follicles, reduction of colloid in the follicular lumen and formation of lymphoid follicles with germinal centres (×40, H&E). (B) Extensive lymphocytic infiltration of the mesenchyme (×400, H&E). H&E, hematoxylin and eosin.

Figure 4 Tumour markers. (A) CK19 expression in papillary thyroid carcinoma (IHC, ×200). (B) Galectin3 expression in papillary thyroid carcinoma (IHC, ×200). IHC, immunohistochemistry.

Figure 5 Tumour markers. (A) CgA expression in medullary thyroid carcinoma (IHC, ×200). (B) CT expression in medullary thyroid carcinoma (IHC, ×200). (C) Syn expression in medullary thyroid carcinoma (IHC, ×200). CgA, chromogranin A; IHC, immunohistochemistry; Syn, synaptophysin.

Figure 6 Right central neck lymph node metastasis (papillary carcinoma) (×200, H&E). H&E, hematoxylin and eosin.

Follow-up

The surgical procedure was completed, and the patient has prescribed oral levothyroxine sodium tablets and calcium carbonate D3 tablets on the first day post-surgery. The patient demonstrated a positive recovery trajectory and was discharged from the medical facility for scheduled follow-up appointments to monitor thyroid function, Ctn, CEA, and parathyroid hormone levels. The following results were obtained: FT3 4.54 pmol/L (normal range, 3.1–6.8 pmol/L), FT4 19.40 pmol/L (normal range, 12.0–22.0 pmol/L), TSH 0.565 mIU/L, anti-Tg 20.10 IU/mL, CEA 1.30 mIU/L. Tg <0.040 ng/mL, Ctn 4.68 pg/mL. A recent review of lymph node ultrasound showed no significant abnormalities.

The patient is satisfied with the treatment outcome. She believes that we have taken the correct treatment measures.

All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This study protocol was reviewed and approved by Tianjin First Central Hospital (approval number BL202501). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

PTC represents the most prevalent form of thyroid cancer, however, the combination of PTC and MTC is rare. The following theories have been postulated with regard to the mechanism of concurrence of the two tumors: (I) Hijacking theory: MTC-coated follicular cells are subject to the influence of the tumor microenvironment, resulting in overproliferation and gene mutation. (II) Local effect theory: certain physicochemical factors have been demonstrated to exert influence on both tumor cells, inducing mutations and proliferation. (III) Stem cell theory: given the common origins and proto-oncogene of follicular and parafollicular cells, MTC is predominantly associated with RET mutations. However, PTCs also exhibit aberrant expression of RET. (IV) Common pathway theory: both types of cells activate the same oncogenic pathway. Nonetheless, the most widely accepted clinical theory is the collision theory which posits that the coincidental simultaneity of the two tumours is merely coincidental. A particular study demonstrated that the incidence of PTC with MTC was analogous to the incidence of PTC in patients with follicular thyroid cancer or Graves’ disease (GD), thereby further substantiating the collision theory (7).

Thyroid TI-RADS classification is currently the most common clinical classification system for assessing the risk of benign and malignant thyroid nodules, however, its results are susceptible to subjective judgment by doctors. Typically, fine-needle aspiration biopsy (FNAB) is considered to be performed on all nodes that meet the criteria. However, in this case, the operation was not performed. On the one hand, the operation is considered to be invasive, and the family refuses to perform it. On the other hand, in patients with PTC complicated by MTC, FNAB may lead to a missed diagnosis, which may result in a delay in diagnosis and treatment of the disease. Furthermore, synchronous detection of serum Ctn and CEA levels is imperative for a comprehensive assessment. In recent years, there has been an increasing application of advanced technologies in the diagnosis and treatment of thyroid cancer. The emerging imaging histology can accurately quantify the phenotypic and microenvironmental information of images with the help of big data and artificial intelligence (AI), and use machine learning to construct prediction models applicable to clinical diagnosis and prognosis judgment (8). The establishment of the radio mics-TI-RADS model (RTM) by one team involved the combination of imaging, histology scores, tumor margins, and TI-RADS levels. The resultant model was found to enhance the performance of predicting lateral cervical lymph node metastasis (LLNM) in MTC patients (9). AI system has also been designed and developed by a team to preoperatively predict neck lymph node metastasis (LNM) in both PTC and MTC patients based on CT images, with a higher prediction accuracy than that of radiomics and clinical models (10,11). In the subsequent clinical work, the application of AI to the diagnosis and treatment process of thyroid cancer is also a potential avenue for exploration.

To date, no guidelines have been established for the treatment of MTC in combination with PTC. However, guidelines from Chinese Society of Clinical Oncology (CSCO) (12), American Thyroid Association (ATA) (13), and European Society for Medical Oncology (ESMO) (14) advocate total (or near-total) thyroidectomy as the primary treatment modality for both hereditary and sporadic MTC cases. The aggressive nature of MTC, coupled with the tendency for early LNM, resulted in central LNM in more than half of the patients, irrespective of tumor size. Consequently, the implementation of bilateral prophylactic central nodal dissection (PCND) has been demonstrated to enhance the prognosis. In conclusion, the CSCO guideline (12) has designated central lymph node dissection in patients with cN0 or cN1a as a class I recommendation. Consequently, the surgical approach for MTC in conjunction with PTC typically involves a total thyroidectomy accompanied by bilateral central lymph node dissection.

There is ongoing clinical controversy regarding the necessity of prophylactic lateral cervical lymph node dissection (PLND) for MTC patients with stage cN0. The guidelines established by the CSCO (12), ATA (13), Japan Association of Endocrine Surgeons (JAES) (15), and ESMO (14), state that it should be determined based on the serum Ctn level to an extent. In this particular case, the preoperative serum Ctn level was recorded at 614.9 pg/mL, which exceeded the reference threshold stipulated by the aforementioned guidelines recommending PLND. However, the decision was taken against performing PLND in this particular patient, based on the following considerations: firstly, the 2022 CSCO guidelines (12) explicitly stipulate that only therapeutic lateral cervical lymph node dissection should be performed for MTC, and the patient’s preoperative ultrasound and enhanced CT did not indicate the presence of lymph node abnormality; secondly, the Chinese Anti-Cancer Association (CACA) Guidelines for Holistic Integrative Management of Cancer 2024 guidelines (16) state that MTC with negative lateral cervical lymph nodes on clinical assessment generally does not work PLND; thirdly, complications have been observed in association with PLND. The ATA guidelines (13) stipulate that surgery should only be considered if the patient is assessed to have a high likelihood of LLNM and the benefits of PLND outweigh the risks of surgery; fourthly, many retrospective clinical studies have shown that PLND exerts no impact on the overall survival of patients diagnosed with MTC who are deemed to have no cervical LNM before surgery (17-19); finally, preoperative refusal of the patient’s family to perform PLND. Subsequent postoperative pathology revealed no evidence of metastasis from medullary carcinoma in the central region lymph nodes.

As reported in the literature, in patients without distant metastases or disease progression, 19% of N0 cases had a Ctn higher than 500 pmol/L, while 17% of N1b cases had a Ctn lower than 500 pmol/L (20). The role of preoperative serum Ctn in predicting LLNM should not be utilized as an independent predictor. As this article deals with only one case, the above conclusions are still inappropriate. However, a combination of central area lymph node status and Ctn level is also recommended in various guidelines. It has also been highlighted that the concentrations of Ctn, CEA, and neuron-specific enolase (NSE) are all closely associated with LLNM in MTC patients (21). Furthermore, the presence of circulating tumor cells (CTC), cell-free DNA (cfDNA), and microRNAs (miRNAs) may serve as potential biomarkers for MTC (22). Furthermore, this approach may facilitate the development of personalized and targeted therapies for MTC patients (23). In addition to the presence of biomarkers, a meta-analysis has indicated that risk factors related to gender, T category of the main component (including the tumor size and shape, multiplicity, bilaterality, cystic invasion, extra-thyroidal extension, tumor margins), and metastatic status of lymph nodes in the central region also have an impact on LLNM (24).

MTC is characteristically known to metastasize from the central region to the lateral cervical lymph nodes. However, a retrospective correlation analysis encompassing 640 patients with unilateral MTC revealed that jumping cervical LNM, characterized by the presence of metastatic lymph nodes in the lateral cervical region while no metastatic lymph nodes were detected in the central region, occurred in 11.3–14.1% of patients. Furthermore, the probability of skip metastasis in MTC was found to be 1.5–2 times higher than that of PTC (25). This finding indicates that central regional lymph node involvement alone is not a highly accurate predictor of LLNM. Consequently, it emphasizes the necessity of integrating multiple biomarkers, imaging characteristics, and clinical risk factors when determining the appropriateness of performing PLND treatment.

HT has been identified as a risk factor for the development of PTC including the increased risk of having multifocal tumors (26). However, recent studies have suggested that, in patients with PTC, the rate of central lymph node metastasis (CLNM) is lower in those with autoimmune diseases compared to those without (6,27,28). This finding indicates that HT may act as a protective factor in terms of recurrence, LNM, BRAF^V600E mutation, and the prognosis of PTC. Microscopically, the primary foci of PTC are observed to be surrounded by a fibroblastic layer, thus limiting their progression. However, the presence of HT does not affect the results of ultrasound, FNAB, and enhanced CT. Different expression levels of factors such as E-cadherin and vascular endothelial growth factor (VEGF), the presence of specific antibodies, and the Fas-mediated apoptotic pathway are associated with this phenomenon (29). Furthermore, a retrospective cross-sectional study was conducted to explore the relationship between HT and MTC. The results did not show a statistically significant relationship between the two, which may be related to their different cellular origins (30). There are few case reports and related studies on the co-occurrence of PTC, MTC, and HT. The prevailing view is that the co-existence is related to the rearrangement of certain genes. However, there remains a paucity of high-quality evidence-based medicine and fundamental theoretical support. It is anticipated that future studies will be conducted, to provide standardized treatments for this patient group.

Elevated postoperative Ctn levels and their shortened doubling time are associated with a poor prognosis in patients with MTC. Biochemical cure in patients with MTC is defined as a postoperative period in which there are no abnormalities on imaging tests and the serum Ctn level is reduced to normal. However, after radical surgery, more than half of the patients still did not achieve a biochemical cure, and even the possibility of structural recurrence existed. Therefore, timely monitoring of Ctn levels after surgery is important. A clinical retrospective study demonstrated that Ctn levels were an independent predictor of disease-free survival (DFS) as well (31). A retrospective observational study proposed that in biochemically cured MTC patients, the recurrence rate was reduced in patients with undetectable postoperative serum Ctn/CEA concentrations compared to those within the normal range but detectable (32). In the present case, the patient’s serum Ctn was 5.78 pg/mL at 1-month postoperative follow-up, which was consistent with a biochemical cure. There are no guidelines on whether postoperative serum Ctn concentrations need to be reduced to unmeasurable levels, so a larger and better-matched study should be conducted.

Conclusions

The synchronous concurrence of PTC, MTC and HT is a rare pathology of the thyroid gland. This paper provides a review of the relevant literature, discusses the possible causes of the condition, and makes suggestions about the need for certain medical procedures and the best ways to monitor patients after surgery. In the future, we can make full use of the advantages of AI in the process of disease diagnosis and treatment. This will involve combining intelligent diagnostic systems with traditional diagnostic and treatment modes and applying innovative technologies to clinical practice.

Acknowledgments

The authors would like to thank Caihong Wang (China-Tianjin First Central Hospital, Supervising Pathologist Technician) for her valuable help in microscopic evaluation, which significantly contributed to this study.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-141/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-141/prf

Funding: This work was supported by Natural Science Foundation of Tianjin (No. 23JCYBJC01730).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-141/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This study protocol was reviewed and approved by Tianjin First Central Hospital (approval number BL202501). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Zhang X, Yang L, Liu S, et al. Interpretation on the report of global cancer statistics 2022. Zhonghua Zhong Liu Za Zhi 2024;46:710-21. [Crossref] [PubMed]
2. Chinese Society of Endocrinology; Thyroid and Metabolism Surgery Group of the Chinese Society of Surgery; China Anti-Cancer Association, Chinese Association of Head and Neck Oncology, et al. Guidelines for the diagnosis and management of thyroid nodules and differentiated thyroid cancer(Second edition). Chinese Journal of Endocrinology and Metabolism 2023;39:181-226.
3. Baloch ZW, Asa SL, Barletta JA, et al. Overview of the 2022 WHO Classification of Thyroid Neoplasms. Endocr Pathol 2022;33:27-63. [Crossref] [PubMed]
4. Fallahi P, Patrizio A, Stoppini G, et al. Simultaneous Occurrence of Medullary Thyroid Carcinoma and Papillary Thyroid Carcinoma: A Case Series with Literature Review. Curr Oncol 2023;30:10237-48. [Crossref] [PubMed]
5. Zhang D, Yang M, Zhang X, et al. Thirty synchronous medullary and papillary thyroid carcinomas. Front Endocrinol (Lausanne) 2023;14:1153248. [Crossref] [PubMed]
6. Xu J, Ding K, Mu L, et al. Hashimoto's Thyroiditis: A "Double-Edged Sword" in Thyroid Carcinoma. Front Endocrinol (Lausanne) 2022;13:801925. [Crossref] [PubMed]
7. Kim WG, Gong G, Kim EY, et al. Concurrent occurrence of medullary thyroid carcinoma and papillary thyroid carcinoma in the same thyroid should be considered as coincidental. Clin Endocrinol (Oxf) 2010;72:256-63. [Crossref] [PubMed]
8. Wang F, Xia Y, Chai X, et al. Analysis process and clinical application of radiomics. Chinese Journal of Anatomy and Clinics 2021;26:236-41.
9. Liu Z, Zhang X, Zhao X, et al. Combining radiomics with thyroid imaging reporting and data system to predict lateral cervical lymph node metastases in medullary thyroid cancer. BMC Med Imaging 2024;24:64. [Crossref] [PubMed]
10. Luvhengo TE, Moeng MS, Sishuba NT, et al. Holomics and Artificial Intelligence-Driven Precision Oncology for Medullary Thyroid Carcinoma: Addressing Challenges of a Rare and Aggressive Disease. Cancers (Basel) 2024;16:3469. [Crossref] [PubMed]
11. Wang C, Yu P, Zhang H, et al. Artificial intelligence-based prediction of cervical lymph node metastasis in papillary thyroid cancer with CT. Eur Radiol 2023;33:6828-40. [Crossref] [PubMed]
12. Chinese Society of Clinical Oncology (CSCO) Guidelines Working Committee. Guidelines for the Diagnosis and Treatment of Medullary Thyroid Carcinoma. Beijing: People’s Medical Publishing House; 2022.
13. Wells SA Jr, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015;25:567-610. [Crossref] [PubMed]
14. Filetti S, Durante C, Hartl D, et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol 2019;30:1856-83. [Crossref] [PubMed]
15. Ito Y, Onoda N, Okamoto T. The revised clinical practice guidelines on the management of thyroid tumors by the Japan Associations of Endocrine Surgeons: Core questions and recommendations for treatments of thyroid cancer. Endocr J 2020;67:669-717. [Crossref] [PubMed]
16. Chinese Anti-Cancer Association (CACA). China Guideline for Holistic Integrative Management of Oncology: Carcinoma Section. 2024 edition. Tianjin: Tianjin Science and Technology Press; 2024.
17. Szabo Yamashita T, Rogers RT, Foster TR, et al. Medullary thyroid cancer: What is the optimal management of the lateral neck in a node negative patient at index operation? Surgery 2022;171:177-81. [Crossref] [PubMed]
18. Hao W, Zhao J, Guo F, et al. The survival outcomes of prophylactic lateral neck dissection for medullary thyroid carcinoma, a retrospective cohort study. Clin Otolaryngol 2023;48:734-9. [Crossref] [PubMed]
19. Spanheimer PM, Ganly I, Chou JF, et al. Prophylactic Lateral Neck Dissection for Medullary Thyroid Carcinoma is not Associated with Improved Survival. Ann Surg Oncol 2021;28:6572-9. [Crossref] [PubMed]
20. Opsahl EM, Akslen LA, Schlichting E, et al. The Role of Calcitonin in Predicting the Extent of Surgery in Medullary Thyroid Carcinoma: A Nationwide Population-Based Study in Norway. Eur Thyroid J 2019;8:159-66. [Crossref] [PubMed]
21. Ye L, Zhou X, Lu J, et al. Combining serum calcitonin, carcinoembryonic antigen, and neuron-specific enolase to predict lateral lymph node metastasis in medullary thyroid carcinoma. J Clin Lab Anal 2020;34:e23278. [Crossref] [PubMed]
22. De Falco N, Agresti M, De Falco M, et al. Simultaneous Medullary and Papillary Thyroid Carcinomas: Personal Experience Report and Literature Review. J Clin Med 2025;14:1382. [Crossref] [PubMed]
23. Ricci C, Salvemini A, Dalmiglio C, et al. From Circulating Tumor Cells to Mirna: New Challenges in the Diagnosis and Prognosis of Medullary Thyroid Cancer. Cancers (Basel) 2023;15:4009. [Crossref] [PubMed]
24. Lin X, Huo J, Su H, et al. Risk factors for cervical lymph node metastasis in the central or lateral cervical region in medullary thyroid carcinoma: a systematic review and meta-analysis. Eur Arch Otorhinolaryngol 2024;281:547-61. [Crossref] [PubMed]
25. Machens A, Lorenz K, Weber F, et al. Anatomical Patterns of Nodal Spread in Unilateral Papillary and Medullary Thyroid Cancer. Thyroid 2024;34:871-9. [Crossref] [PubMed]
26. Wang L, Chen J, Yuan X, et al. Lymph node metastasis of papillary thyroid carcinoma in the context of Hashimoto's thyroiditis. BMC Endocr Disord 2022;22:12. [Crossref] [PubMed]
27. Yao S, Zhang H. Papillary thyroid carcinoma with Hashimoto's thyroiditis: impact and correlation. Front Endocrinol (Lausanne) 2025;16:1512417. [Crossref] [PubMed]
28. Janicki L, Patel A, Jendrzejewski J, et al. Prevalence and Impact of BRAF mutation in patients with concomitant papillary thyroid carcinoma and Hashimoto's thyroiditis: a systematic review with meta-analysis. Front Endocrinol (Lausanne) 2023;14:1273498. [Crossref] [PubMed]
29. Song WJ, Um IC, Kwon SR, et al. Predictive factors of lymph node metastasis in papillary thyroid cancer. PLoS One 2023;18:e0294594. [Crossref] [PubMed]
30. Zayed AA, Ali MK, Jaber OI, et al. Is Hashimoto's thyroiditis a risk factor for medullary thyroid carcinoma? Our experience and a literature review. Endocrine 2015;48:629-36. [Crossref] [PubMed]
31. Guo F, Fu G, Li F, et al. Time Kinetics and prognosis roles of calcitonin after surgery for medullary thyroid carcinoma. World J Surg Oncol 2024;22:121. [Crossref] [PubMed]
32. Fanget F, Demarchi MS, Maillard L, et al. Medullary thyroid cancer outcomes in patients with undetectable versus normalized postoperative calcitonin levels. Br J Surg 2021;108:1064-71. [Crossref] [PubMed]