Abstract
We read with interest the Letter to the Editor by Marcy et al. recently published in Thyroid (1). It described bilateral breast metastases of medullary thyroid carcinoma (MTC) in a 43-year-old woman who had been operated about 15 years ago for a stage III MTC. Initial surgical treatment consisted of partial thyroid resection. This was followed by loco-regional relapses that required further surgery as well as radiation therapy. She had metastases to bone, lungs, and lymph nodes when breast involvement was diagnosed. She died shortly afterward. The authors suggested a possible retrograde lymphatic metastatic spread of MTC from the supraclavicular nodes to the subclavicular axillary ones, and then to the breast, caused by the blockage of the lymphatic pathway secondary to radiation therapy or lymph node dissection, but they did not exclude the possibility of a hematogenous spread. They also questioned the utility of an aggressive neck dissection in patients with advanced stage disease (1), based on their speculation on how the tumor disseminated.
We recently observed a 54-year-old woman who underwent total thyroidectomy for MTC in 1994. Due to persistently high serum calcitonin and carcinoembryonic antigen (CEA) levels and evidence of lateral neck node metastases, she underwent bilateral modified radical neck dissection. Shortly after, computed tomography (CT) scan showed small diffuse pulmonary lesions. She started treatment with somatostatin analogues. Two years after neck dissection CT scan showed liver and lung metastases. With ongoing somatostatin analogs therapy, calcitonin and CEA levels were constantly elevated, but imaging findings and disease activity were stable. Five years later there was evidence of mediastinal lymph node involvement and rib metastasis by CT and bone scan. She was stable for the next 6 years at which point she underwent routine screening mammography, which revealed multiple bilateral calcifications. Further investigation by breast ultrasonography showed a 7-mm nodule in the external upper quadrant of the left breast. Fine-needle aspiration cytology on the left breast nodule was suggestive of carcinoma. Therefore, a wide local excision of breast lump was performed. Final histology confirmed the diagnosis of multiple metastatic foci of MTC.
On the basis of this experience and a review of the literature, which includes 13 other patients with breast metastases from MTC, we partially disagree with the conclusions of Marcy et al. (1). Breast metastases represent a very rare and late manifestation of widely metastatic MTCs. Nonetheless, patients with breast metastases from MTC seem to have a longer survival compared to patients with breast metastases from other solid tumors, and often undergo metastasectomy for local disease control (2). Metastases to breast due to MTC usually occur in the presence of widespread metastases (1,2). Most patients did not have signs of axillary lymph node involvement. Moreover, in more than one half multiple and/or bilateral breast metastases were found. In all patients there was widespread metastatic MTC. This is not consistent with aberrant lymphatic retrograde dissemination via the axillary lymph nodes as a typical pathway for MTC breast metastasis, caused by radiation therapy or lymph node dissection. Rather, they support a hematogenous spread that was considered the alternative route by Marcy et al. (1).
For these reasons, we believe that the cases here described point toward the importance of an early diagnosis and an adequate surgical treatment in patients with MTC, both sporadic and familial.
In an evidence-based approach to the disease, thorough surgical eradication of the primary tumor and node metastases by a compartment-oriented resection has been demonstrated to be the mainstay of the treatment of MTC (3). Moreover, the American Thyroid Association Guidelines Task Force has recently published the MTC management guidelines, confirming the utility of total thyroidectomy and compartment-oriented neck dissection, to prevent local recurrence, even in the presence of limited distant metastases (4). On the other hand, a less aggressive neck approach is advocated only in case of largely infiltrating tumors or extensive distant metastases (4).
In conclusion, MTC is a malignant disease for which proper management depends on an early diagnosis and a complete surgical resection, which should include total thyroidectomy and appropriate neck dissection (3,4). Breast metastases seem to be a late manifestation of widely disseminated disease caused by hematogenous diffusion rather than retrograde lymphatic diffusion consequent to lymph node dissection.