Thyroid ultrasound
A doctor and medical students perform an ultrasound on the thyroid. Credit: Getty Images

Medullary thyroid carcinoma (MTC) represents only 1% to 2% of thyroid carcinomas, making it an exceedingly rare disease. We know it is a malignancy arising from parafollicular thyroid C cells. A key diagnostic tool, aside from fine-needle aspiration, is ultrasound. Ultrasound is the most important preoperative diagnostic tool and can be used by skilled physicians to approximate the cancer stage and its corresponding prognosis. 

What makes ultrasound so useful? Mainly, it allows for the identification of key features of the tumor, such as its shape, margin, composition, echogenicity, and vascularity, as well as the presence or absence of calcification. These features largely correspond to its biological features, meaning that physicians can infer a lot about the disease even before surgical exploration. 

However, misdiagnoses from ultrasound can occur. The difficulty arises when malignant features are not readily observed in an ultrasound scan, causing physicians to misdiagnose the thyroid tumor or only arrive at a correct diagnosis at a later follow-up scan. 

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Read more about MTC epidemiology

Researchers from Tianjin Medical University Cancer Institute and Hospital in China recently investigated the ultrasound and clinical features of MTC and published their findings in Endocrine. They recruited 189 patients treated at their institution between 2010 to 2015 and used ultrasound to categorize their MTC as either “indeterminate” (i-MTC) or “malignant” (m-MTC). The categorization was made according to the Thyroid Imaging, Reporting and Data System (TI-RADS) published by America College of Radiology, a widely used scoring system based on ultrasound features that is helpful at predicting the probability of thyroid malignancy. 


A total of 29 patients were categorized as i-MTC and 160 as m-MTC. Researchers then compared the ultrasound findings and clinical features between the 2 groups. It is their findings in these areas that we will explore in detail. 

Preoperative Findings 

There were some differences between ultrasound features in i-MTC and m-MTC. In i-MTC, the tumor tended to have a round to oval shape (69.0%) with a smooth margin (86.2%); in m-MTC, the tumor tended to be irregular in shape (81.2%) with an ill-defined margin (65.6%). In terms of echogenicity, both i-MTC and m-MTC tended to be hypoechoic (86.2% and 75.6% respectively), but m-MTC had a greater tendency to be markedly hypoechoic (24.4%). Calcifications were observed more often in m-MTC (88.7%) than in i-MTC (10.3%). 

However, there were also similarities in the ultrasound findings between i-MTC and m-MTC. The composition tended to be solid in both i-MTC (86.2%) and m-MTC (96.2%). In terms of vascularity, both i-MTC and m-MTC were observed to have a greater frequency of I-type (34.5% and 49.4% respectively) and III-type (41.4% and 37.5% respectively) vascularity when compared to II-type (13.8% and 10.6% respectively) and IV-type (10.3% and 2.5% respectively). 

Clinicopathological Findings  

The mean age of diagnosis was 49.8 years and 48.6 years in i-MTC and m-MTC patients respectively. In both cancers, the frequency was slightly higher in females than in males. 

There were some significant differences between i-MTC and m-MTC. In terms of lymph node dissection, the most frequent surgery type observed in i-MTC was bilateral central neck dissection (58.6%), followed by ipsilateral lateral neck dissection (24.1%); in m-MTC, the most frequent type was ipsilateral lateral neck dissection (40.0%), followed by bilateral central neck dissection (31.9%). 

In terms of the extent of the tumor, in i-MTC it tended to be intrathyroidal (75.9%) rather than extrathyroidal (24.1%); in m-MTC, the percentage of intrathyroidal to extrathyroidal extension was 55.0% to 45.0%. In terms of lymph node metastasis, the most common grade in i-MTC was N0 (75.9%), followed by N1a (13.8%) and N1b (10.3%); in m-MTC, the most common grade was N1b (47.5%), followed closely by N0 (41.3%), then N1a (11.2%).

Read more about MTC prognosis

In terms of TNM staging, stage II was most commonly observed in i-MTC (44.8%), followed by stages I (31.0%), III (13.8%), and IV (10.3%); in m-MTC, the most common TNM staging was stage IV (47.5%), followed by stages I (25.6%), II (16.9%), and III (10.0%). 

Close similarities were also observed between the two tumor types. Total thyroidectomy was more commonly performed in both i-MTC and m-MTC, compared to unilateral lobectomy. When complete thyroid tumor excision was needed, both i-MTC and m-MTC patients tended to have complete surgery performed. The mean tumor size in i-MTC was 1.93 and 2.04 in m-MTC. i-MTC and m-MTC also shared similar tumor multifocality. Distant metastasis tended to be absent in both groups. 

Follow-up Findings 

The mean follow-up time in this study was 60.5 months in i-MTC and 64.8 months in m-MTC. The vast majority (79.3%) of i-MTC patients were found to be biochemically cured; in m-MTC, 48.8% were found to be biochemically cured, with 26.2% experiencing biochemical recurrence, and 25.0% experiencing structural persistence/recurrence. 

The vast majority (96.6%) of i-MTC patients had no cervical persistence/recurrence; in m-MTC, the percentage was 80.0%, with 20% experiencing cervical persistence/recurrence. In both i-MTC and m-MTC, distant metastasis was mostly absent. 


First of all, the wealth of information that ultrasound scans can provide should not be underestimated, and physicians should not see them as merely a triage tool for a preliminary diagnosis to be made. Instead, a close study of the various features that can be revealed through an ultrasound scan should encourage physicians to leave no stone unturned when performing the procedure. 

With regards to this specific study, researchers confirmed what we knew about MTC, in that it typically has a late presentation, with more than half of MTC cases only diagnosed at advanced stages of the disease. 

At present, an ultrasound scan combined with fine-needle aspiration represents the best combination of preoperative diagnostic tools at our disposal. It would be wise for physicians to utilize both tools with the greatest care and skill to approach the operating room with as much information as possible. 


Zhao J, Yang F, Wei X, et al. Ultrasound features value in the diagnosis and prognosis of medullary thyroid carcinoma. Endocrine. 2021;72(3):727-734. doi:10.1007/s12020-020-02510-2. 

Kebebew E, Ituarte PHG, Siperstein AE, Duh Q-Y, Clark OH. Medullary thyroid carcinoma. Cancer. Published online November 20, 2020. doi:10.1002/(SICI)1097-0142(20000301)88:5<1139::AID-CNCR26>3.0.CO;2-Z