Comprehensive Evaluation of Medullary Thyroid Carcinoma Before Surgery

Medullary thyroid carcinoma (MTC) is a rare but aggressive form of thyroid cancer, accounting for approximately 2% to 5% of all thyroid malignancies globally. Despite its rarity, MTC is responsible for a significant proportion of thyroid cancer-related deaths due to its aggressive behavior, including lymph node metastasis and recurrence. Accurate preoperative diagnosis is crucial for guiding surgical decisions and improving patient outcomes. This study aimed to enhance the diagnostic accuracy of MTC before surgery by analyzing clinical and ultrasonic data from patients with histopathologically confirmed MTC.

The study included 71 patients (96 lesions) diagnosed with MTC between April 2011 and September 2016 at the Cancer Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College. The patients were divided into two groups based on the accuracy of their preoperative ultrasound diagnoses: the ultrasonic correct diagnosis group and the ultrasonic misdiagnosed group. The clinical characteristics and sonographic findings were retrospectively reviewed and compared between the two groups using statistical tests appropriate for quantitative and qualitative parameters.

The results revealed significant differences in the sonographic features between the two groups. In the ultrasonic misdiagnosed group, the proportion of cystic changes was higher (25.0% vs. 4.2%), while the proportions of uncircumscribed margins and irregular shapes were lower (20.8% and 58.3% vs. 74.7% and 87.3%, respectively). Calcifications were relatively rare in the misdiagnosed group (20.8% vs. 56.3%), and rich vascularity was also less common (25.0% vs. 78.9%). These findings suggest that atypical MTC lesions, characterized by cystic changes, circumscribed margins, regular shapes, absence of calcifications, and lack of rich vascularity, are more likely to be misdiagnosed as benign by ultrasound.

Clinical Characteristics

The study included 71 patients (34 males and 37 females) with an average age of 47.0±13.4 years. Among these patients, 55 had sporadic medullary thyroid carcinoma (SMTC), six had hereditary medullary thyroid carcinoma (HMTC), and ten had a family history of other malignant tumors. The majority of patients (73.2%) had single lesions, while 25.4% had multiple lesions, and one patient had a missed diagnosis.

The clinical characteristics were compared between the ultrasonic correct diagnosis group and the ultrasonic misdiagnosed group. There were no significant differences in mean age or sex between the two groups. However, the reasons for patients’ visits differed, with a higher proportion of patients in the ultrasonic correct diagnosis group presenting with palpable cervical masses (35.8% vs. 11.1%). Additionally, patients in the correct diagnosis group were more likely to exhibit symptoms such as diarrhea, hoarseness, suffocation, pain, dysphagia, and cough, while the misdiagnosed group had no such symptoms.

Serum calcitonin levels were elevated in 98.5% of the patients, with higher levels observed in the ultrasonic correct diagnosis group (median: 932.0 ng/mL) compared to the misdiagnosed group (median: 86.0 ng/mL). This difference may be related to the size of the nodules, the secretory activity of the lesion subtype, or RET mutations. One patient with a normal serum calcitonin level had a small lesion (0.3 cm), which may have been due to the nodule size or a dedifferentiated state of the lesion.

Sonographic Characteristics

Ultrasound is a critical tool for evaluating thyroid nodules, with features such as irregular margins, microcalcifications, an aspect ratio greater than one, hypoechoic echogenicity, and invasion of the thyroid membrane being indicative of malignancy. However, these features are more commonly associated with papillary thyroid carcinoma (PTC) than with MTC.

In this study, the majority of MTC lesions were hypoechoic with an aspect ratio less than one, and only 6.3% of lesions had an aspect ratio greater than one. Hyperechoic lesions were rare, with only one case observed in the misdiagnosed group. The presence of cystic changes was more common in the misdiagnosed group (25.0% vs. 4.2%), suggesting that larger cystic solid nodules should be considered for further evaluation, including serum calcitonin measurement and fine-needle aspiration (FNA).

The margins and shapes of the lesions also differed between the two groups. Lesions with circumscribed margins or regular shapes were more likely to be misdiagnosed. Calcifications were present in 56.3% of lesions in the correct diagnosis group, with no significant difference between microcalcifications and coarse calcifications. In contrast, only 20.8% of lesions in the misdiagnosed group had calcifications. The vascularity of the lesions was another distinguishing feature, with internal rich vascularity being more common in the correct diagnosis group (78.9% vs. 25.0%) and absent vascularity being more common in the misdiagnosed group (41.7% vs. 5.6%).

Cavernous nodules were detected by preoperative ultrasonography in 29 patients, with a higher proportion in the misdiagnosed group (72.2% vs. 30.2%). This difference may be related to imprecise observations during the ultrasound examination.

Cervical Lymph Node Metastasis

MTC has a high propensity for lymph node metastasis, with studies reporting an incidence of 75% to 80%. In this study, 69% of patients (49/71) were diagnosed with lymph node metastases after surgery, and 49.3% (35/71) were found to have abnormal lymph nodes before surgery. This discrepancy highlights the limitations of preoperative ultrasound in detecting cervical lymph node metastasis.

Fine-Needle Aspiration Cytology

FNA cytological examination is a common preoperative diagnostic method for thyroid nodules. In this study, 37 patients underwent FNA before surgery, with an accuracy of 67.6% in diagnosing MTC. This rate is lower than that for PTC, indicating that FNA has limitations in diagnosing MTC. However, the diagnostic accuracy of FNA can be improved by immunohistochemical analysis of the FNA specimen and measuring calcitonin levels in the FNA washout fluid.

Discussion

The findings of this study underscore the challenges in diagnosing MTC preoperatively, particularly in cases with atypical sonographic features. Lesions with cystic changes, circumscribed margins, regular shapes, absence of calcifications, and lack of rich vascularity are more likely to be misdiagnosed as benign. Therefore, a comprehensive evaluation that includes ultrasound, serum calcitonin measurement, and FNA cytology is essential for accurate preoperative diagnosis.

Serum calcitonin is a valuable marker for MTC, with elevated levels observed in the majority of patients. However, serum calcitonin is not routinely measured in patients with thyroid nodules, partly due to its low incidence and the fact that other conditions can also cause elevated calcitonin levels. This study suggests that routine measurement of serum calcitonin in patients with thyroid nodules may be beneficial for early detection of MTC.

Ultrasound remains a critical tool for evaluating thyroid nodules, but its diagnostic accuracy for MTC is influenced by the sonographic features of the lesions. Atypical MTC lesions, such as those with cystic changes or circumscribed margins, are more likely to be misdiagnosed. Therefore, clinicians should be aware of these limitations and consider additional diagnostic methods, such as serum calcitonin measurement and FNA, when evaluating thyroid nodules.

FNA cytology has limitations in diagnosing MTC, but its accuracy can be improved by immunohistochemical analysis and measurement of calcitonin levels in the FNA washout fluid. These methods can provide additional diagnostic information and help distinguish MTC from other types of thyroid cancer.

In conclusion, accurate preoperative diagnosis of MTC requires a comprehensive evaluation that includes ultrasound, serum calcitonin measurement, and FNA cytology. Clinicians should be aware of the limitations of each diagnostic method and consider atypical sonographic features when evaluating thyroid nodules. By improving the diagnostic accuracy of MTC before surgery, clinicians can make more informed decisions regarding surgical treatment and improve patient outcomes.

doi.org/10.1097/CM9.0000000000000160

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