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Table of Contents
REVIEW ARTICLE
Year : 2021  |  Volume : 4  |  Issue : 4  |  Page : 150-153

Thyroid nodule location and the risk of thyroid cancer: What do we know?


1 Department of Internal Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, Saint Louis, MO, USA
2 Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

Date of Submission30-Oct-2021
Date of Decision30-Oct-2021
Date of Acceptance30-Oct-2021
Date of Web Publication30-Dec-2021

Correspondence Address:
Dr. Hossein Gharib
Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic College of Medicine, Rochester, MN, 200 First Street SW, Rochester, Minnesota 55905
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jdep.jdep_51_21

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  Abstract 


Thyroid nodules are common in clinical practice and are routinely evaluated with neck ultrasound. Multiple guidelines rely on sonographic features to assist physicians when deciding if nodules require observation or fine-needle aspiration (FNA). Existing classification systems for risk stratification of thyroid nodules are different but equally accurate. The purpose of this article is to review the significance of thyroid nodule location as an important factor in assessing the risk of malignancy. Several topical issues are addressed. (1) Thyroid nodule location and risk of differentiated thyroid cancer, (2) Thyroid nodule location and risk of nodal metastasis, (3) Thyroid nodule location and surgical approach, (4) Thyroid nodule location and stratifications systems (5) Conclusions and future direction. In conclusion, it is advisable not to reply solely on ultrasound-derived risk levels when evaluating thyroid nodules to determine optimal management including nodule FNA, follow-up or no additional intervention. This is likely because other clinically important features might not be accounted for when using those risk stratification algorithms. There are now reasonable data to suggest thyroid nodule location may be an additional prognostic predictor. In the lack of clear radiologic guidance, clinical judgment remains the main driving factor.

Keywords: Differentiated thyroid cancer, fine-needle aspiration, neck ultrasound, risk stratification systems, thyroid nodule location, thyroid nodules


How to cite this article:
Jasim S, Gharib H. Thyroid nodule location and the risk of thyroid cancer: What do we know?. J Diabetes Endocr Pract 2021;4:150-3

How to cite this URL:
Jasim S, Gharib H. Thyroid nodule location and the risk of thyroid cancer: What do we know?. J Diabetes Endocr Pract [serial online] 2021 [cited 2022 Jan 17];4:150-3. Available from: https://www.jdeponline.com/text.asp?2021/4/4/150/334346




  Introduction Top


Thyroid nodules are common in clinical practice and are routinely evaluated with neck ultrasound. Multiple guidelines rely on sonographic features to assist physicians when deciding if nodules require observation or fine-needle aspiration (FNA). The American College of Radiology (ACR) developed a Thyroid Imaging Reporting and Data System (TI-RADS),[1] which uses a point-based classification system for risk stratification of thyroid nodules based on well-established US features[2] similar to those used in the American Thyroid Association[3] and, the American Association of Clinical Endocrinology[4] guidelines which offer a rather simple, but equally accurate, classification of US-based risk analysis of thyroid nodules.

The purpose of this article is to review the significance of thyroid nodule location as an important factor in assessing the risk of malignancy.


  Thyroid Nodule Location and Risk of Differentiated Thyroid Cancer Top


While multiple studies correlated above sonographic features of thyroid nodules and their risk of malignancy, there are limited studies correlating the location of the nodule and the risk of thyroid cancer. Few studies suggested that thyroid nodule location might be an independent risk factor for malignancy even after adjusting for other predictors of thyroid cancer and have proposed the use of thyroid nodule location in stratifying the risk of thyroid cancer.[5],[6],[7],[8],[9] Initial reports in small cohorts of patients with thyroid nodules showed that the risk of malignancy was lowest for lower lobe nodules and higher for upper and middle lobe nodules.[7],[9] Furthermore, additional look at the transverse, in addition to longitudinal, planes on neck ultrasound suggested that lateral, anterior-lateral, and upper pole nodules carried the highest risk versus posterior nodules and inferior nodules.[10]

Those findings were confirmed in a larger scale study where the odds ratios of thyroid cancer compared to the lower lobe were 1.9 for the upper lobe (statistically significant) and 1.3 for the middle lobe (not statistically significant).[5] More importantly, the latter study showed that thyroid nodules located in the isthmus had the highest risk of being malignant (odds ratio 2.4) despite being the least frequent (6%) and smallest in size.[5] This risk remained significant after adjusting for multiple risk factors including patient age, sex, family history of thyroid cancer, radiation exposure, maximum nodule size, and ACR TI-RADS score.[5] In this study, 1% of malignant nodules were seen in the isthmus (17.4% of all isthmic nodules were malignant), which is comparable with previous reports. While the number of thyroid cancers located in the isthmus is relatively small, the isthmic location was at higher risk of differentiated thyroid cancer (DTC) despite smaller sample size, smaller nodule size, and adjusting for all other demographic and sonographic features, suggesting a likely true effect.[5]

Those rates were also validated in a larger cohort study, which reported a significantly higher risk of malignancy in isthmic thyroid nodules based on a large, retrospective, multicenter data set of nearly 10,000 cytology samples. The malignant diagnosis was more than twice as common in the isthmus compared with the lateral lobes (no longitudinal locations specified) based on cytology as well as pathology results for those who underwent a subsequent surgical resection.[6] The authors attributed some of that difference in malignancy risk to the different embryologic nature of the isthmus and the lobes, thus, reflecting a different cellular composition and higher associated risk of malignancy.[6],[11]


  Thyroid Nodule Location and Risk of Nodal Metastasis Top


The isthmus is the small central part of the thyroid gland that connects the thyroid lobes. It lies directly anterior to the trachea, overlying the second to fourth tracheal rings and is covered by the strap muscles, fascia, and skin in the middle of the neck.[12] The reported rates of DTC located in the isthmus range from 1% to 9.2%.[12],[13],[14],[15],[16],[17],[18]

Papillary thyroid carcinoma (PTC) in the isthmus has been reported to be associated with more frequent lymph nodes metastases,[19] multifocality,[13],[14] and extrathyroidal extension,[20] all of which are independent of tumor size.[14] In fact, a tumor size of more than 1 cm might be associated with contralateral nodal metastasis.[21] In addition, isthmic thyroid location was found to be an additional risk factor for distant metastatic disease in low-risk DTC, regardless of the presence or absence of other risk factors.[22] A recent study suggested a high likelihood of lateral lymph node metastases in T1a PTC when tumors were located in the upper lobe of the thyroid gland (compared to middle and lower poles), especially the tumor >5 mm in size, however, it is worth noting the isthmus tumors were included in the middle lobe in this study.[23]

The tendency of isthmic thyroid cancer for local and regional metastasis is likely related to the smaller size and the thin shape of the isthmus, which may facilitate direct invasion of adjacent tissues, including the strap muscles and trachea. In addition, lymphatic drainage from the isthmus travels more frequently to the prelaryngeal and pretracheal nodes and then spreads to the paratracheal nodes.[24],[25],[26]


  Thyroid Nodule Location and Surgical Approach Top


While thyroid nodules are extremely common in clinical practice, thyroid cancer is only diagnosed 10%–15% of the time,[27] most of which is likely low-risk thyroid cancer; therefore, the clinical practice guidelines call for more conservative surgical approach in those cases.[3]

Given the unique location and lymphatic drainage of the isthmus, surgical protocols for isthmic PTCs can differ from those for PTCs located in the lobes. To our knowledge, the extent of surgical resection for PTCs located in the isthmus has remained a matter of considerable debate as there are no specific guidelines for the management of patients with PTC located predominantly in the isthmus.[3],[28],[29] However, the greater risk for extrathyroidal extension and lymph node metastasis has led some authors to advocate total thyroidectomy as the first treatment choice for these patients.[13],[14],[25],[30]


  Thyroid Nodule Location and Stratifications Systems Top


The ACR TI-RADS uses a point-based system for risk stratification. Higher point assignments indicate a greater risk of malignancy and lead to recommendations for FNA or follow-up at lower size thresholds. Based on the aforementioned facts, a study sought to determine if the performance of the ACR TI-RADS could be improved by adding location as a 6th feature category (in addition to composition, echogenicity, margins, shape, and echogenic foci).[31] In particular, the study was interested in determining if adding points for thyroid location would improve the detection of malignant nodules in higher-risk locations without an unacceptable increase in FNA of benign nodules.

In addition to isthmus nodules increased risk of malignancy, the sonographic appearance of those lesions is limited suggesting isthmic nodules are less likely to have a taller-than wide shape than nodules in the lobes.[20] This fact minimizes this feature as a mean of detecting malignant nodules in the isthmus and is likely due to their location in a portion of the neck where expansion in the anterior direction is limited.

More importantly, there are reasonable data suggesting that DTCs originating from the thyroid isthmus were more likely to have extrathyroidal extension,[20] tendency for loco-regional spread and possibly a worse prognosis compared to those originating in the thyroid lobes.[29] This, in addition to some reports suggesting lateral nodal metastasis with upper lobe DTC lead the authors to believe isthmic and upper pole are likely higher risk locations compared with lower lobe.[31]

In a recent study, suggested revised scoring algorithms that added 1 or 2 points to higher-risk locations were associated with lowered accuracy due to lower specificity. However, an algorithm that added 1 point to isthmic nodules did not differ significantly from ACR TI-RADS in accuracy; one additional isthmic cancer was diagnosed for each 10.3 additional benign nodules recommended for biopsy.[31]

The ACR TI-RADS was designed to emphasize specificity over sensitivity.[32] This was largely in response to the growing recognition of thyroid cancer overdiagnosis. Given the largely innocuous nature of differentiated thyroid cancer, particularly papillary microcarcinoma, this was reasonable. However, placing a greater emphasis on sensitivity may be reasonable for isthmus nodules given the data suggesting that cancers in the isthmus may be less innocuous than in other locations and that they may be underscored sonographically due to the low chance of having a taller-than-wide shape and the increasing evidence that isthmic nodules are more likely to be malignant to begin with.[5],[6] It is worth pointing out that upper lobe nodules are also more likely to be malignant, and possibly related to higher risk of lymph node metastasis, however, sonographically they will not be missed.


  Conclusion and Future Direction Top


In thyroid clinical practice, it is advisable not to reply solely on ultrasound-derived risk levels when evaluating thyroid nodules to determine optimal management including nodule FNA, follow up or no additional intervention. This is likely because other clinically important features might not be accounted for when using those risk stratification algorithms. Those features may include patient sex, age, and history of radiation exposure, family history of thyroid cancer, autoimmune thyroid disease or other diseases that may influence diagnostic and therapeutic decision-making. In the aging population, for instance, balancing potential harm from thyroid cancer overdiagnosis against properly detecting potentially aggressive thyroid cancer that may occur more frequently in older adults is important to reduce patient harm and improve quality of life.[33] There is now reasonable data to suggest thyroid nodule location may be an additional prognostic predictor that should be included when risk stratification algorithm is employed and may potentially lead to modification to ACR TI-RADS as more data emerge.[32] In the lack of clear radiologic guidance, clinical judgment remains the main driving factor.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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