Medullary thyroid carcinoma (MTC) constitutes only 5% to 8% of thyroid cancers, making it one of the rarer types of thyroid cancer. It is known to be very aggressive and when metastasis occurs, it usually involves the lung, bone, or liver. The breast is rarely involved.

“MTC can be a very indolent disease despite its aggressiveness,” Meng et al stated in a recently published study. This means that in MTC patients with local recurrence or distant metastasis that is resectable, reoperation should be considered. 

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Because breast metastasis of MTC is exceedingly rare, Japanese researchers described the case of a patient with this diagnosis in Surgical Case Reports. In this article, we will explore the circumstances surrounding the patient’s initial MTC diagnosis and the subsequent discovery of recurrent MTC with breast metastasis.

Examining the Case  

A 54-year-old woman was being treated for recurring MTC and breast cancer at the Department of Breast and Endocrine Surgery at Tokyo Women’s Medical University in Japan. 

Three years prior, she had undergone a total thyroidectomy and neck lymph node dissection at a different hospital due to multiple endocrine neoplasia (MEN) 2A. She had a family history of MTC; both her mother and brother were diagnosed with the disease. After her surgery, positron emission tomography (PET) scans revealed that the MTC was successfully removed and that no abnormal accumulation was detected in the neck or breast.

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Two years later, her calcitonin levels began to rise and continued to rise. Half a year after this, blood tests revealed the following results: 

  • Carcinoembryonic antigen (CEA): 6.3 ng/mL (normal range: ≤5 ng/mL)
  • Calcitonin: 246 pg/mL (normal range: ≤6.4 pg/mL) 

PET was performed again to investigate the possibility of recurrent disease. Physicians found 18F-fluorodeoxyglucose (FDG) accumulation in the neck, mediastinum, and both breasts. Breast ultrasound further revealed multiple tumors bilaterally with low echogenicity and irregular margins that were 4 to 19 mm in size. No axillary lymph node involvement was detected. A breast mammogram revealed focal asymmetric density in the left breast. 

Core needle biopsy specimens were obtained from 3 tumors in different areas and showed similar histological findings: solid growth without tubular structures, diagnosed as invasive ductal carcinoma. Progesterone receptor, estrogen receptor, and human epidermal growth factor receptor 2 (HER2) were all negative. 

Following these findings, the physicians decided that further neck surgery was needed to address the recurrent MTC, followed by neoadjuvant chemotherapy for the “triple-negative” breast tumors. The neck surgery was performed, with metastatic lymph nodes in the superior mediastinum and the left lateral neck region removed. 

However, postoperative serum calcitonin levels rose to 409 pg/mL, and PET revealed FDG accumulation in the bilateral breast tumors and metastatic lymph nodes in the neck. The patient was then referred to Tokyo Women’s Medical University for further management. 

Physicians began to suspect that the breast tumors were metastatic because they were multiple, bilateral, and had similar ultrasonographic features. Before starting chemotherapy for the breast cancer as planned, fine-needle aspirations (FNAs) were performed to investigate their suspicion. The calcitonin levels of diluted specimens obtained by adding 1 mL of saline to the FNAs from the 3 breast tumors were extremely high at 17,500 pg/mL, 24,800 pg/mL, and 29,200 pg/mL, indicating that the breast tumors were metastatic lesions from MTC. 

An immunohistological examination of the core biopsy material returned the following results: 

  • Positive calcitonin staining
  • Negative gross cystic disease fluid protein 15 (GCDFP-15) staining in all 3 tumors
  • CEA was positive in one breast tumor and negative in the rest
  • GATA3 was examined in one of the CEA-negative breast tumors and was not found to be expressed

Following these findings, the patient’s treating physicians started her on daily vandetanib (300 mg). After 1 month of treatment, her serum calcitonin levels dropped from 417 pg/mL to 165 pg/mL.

Value of Diagnostics in Breast Metastasis

This study demonstrates the value of serum calcitonin in monitoring MTC progression and possible metastasis. In this case study, it was the increasing serum calcitonin levels that prompted further investigation and the subsequent discovery of metastatic breast cancer. “Serum calcitonin is an important prognostic biomarker for MTC,” according to Meng et al, and “monitoring the serum calcitonin level, particularly for those patients with an increased preoperative calcitonin level” is helpful “in the diagnosis of MTC recurrence and metastasis.” In addition, calcitonin levels of the washout fluid from FNA have a 97.9% sensitivity for MTC, regardless of cytologic findings. 

In this case study, the histological finding of solid growth without tubular formation prompted physicians to suspect MTC metastasis. In fact, diagnosing metastatic breast tumors is challenging from a histological perspective. “The presence of elastosis, carcinoma in situ, and calcification are common features of primary mammary carcinomas but rare in extramammary tumors,” the authors of the case study explained. To arrive at a correct diagnosis, it is thus important to narrow down the diagnosis morphologically, in which case hematoxylin-eosin staining is incredibly useful.

“Although breast metastasis of medullary thyroid carcinoma is rare, a correct diagnosis is indispensable for appropriate treatment,” the authors of the study concluded. Thus, physicians should be alert of the possibility of metastasis when breast tumors demonstrate atypical morphological features and the patient has a history of cancer. 

References

Omi Y, Kamio H, Yoshida Y, et al. Breast metastasis from medullary thyroid carcinoma: a report of a case. Surg Case Rep. 2021;7(1):188. doi:0.1186/s40792-021-01273-w

Meng K, Chen W, Tian W, Sun K, Chen H. Medullary thyroid carcinoma with breast metastasis: two case reports. Medicine (Baltimore). 2018;97(47):e13193. doi:10.1097/MD.0000000000013193