Lymphatic versus hematogeneous metastasis

Regional lymphatic spread and hematogeneous routes to distant sites occur in medullary carcinoma, Hürthle cell carcinoma, poorly differentiated and anaplastic thyroid carcinomas as mentioned in previous chapters. Of the well-differentiated thyroid carcinomas, papillary carcinomas mainly spread via a lymphatic route (distant metastasis outside of neck occurs in only ~5–7%), while follicular carcinomas mainly spread via a hematogeneous route (regional lymph node metastasis occur in only 5% of the cases). The differences in the clinical behavior have a biological basis. In an immunohistochemical study of 35 cases of follicular patterned thyroid tumors, including follicular adenoma, follicular carcinoma, and follicular variant of papillary carcinoma, it was found that the lymphatic vessel density was significantly higher in papillary carcinoma than that of follicular adenoma/follicular carcinoma. The opposite is true, though not statistically significant, in blood vessel density.

In one study, the incidence of pulmonary metastasis is lowest in patients with papillary carcinoma (9%), compared with that in patients with follicular (13%) or Hürthle cell (25%) carcinoma. In another study, distant metastasis occurred in 7% of the 859 patients with papillary carcinoma, 19% of the 100 patients with follicular carcinoma, and 34% of the 29 patients with Hürthle cell carcinoma. Lung (53%) was the most frequent site for first metastasis, followed by bone (20%), while 16% had multiple organ involvement. The occurrence of lung metastasis worsens the prognosis slightly, whereas the development of bone metastasis carries an ominous prognostic significance, even when the metastases concentrate I131.–8 However, Schlumberger et al. reported that the site of metastases (lung or bone) was not a prognostic factor for survival after treatment of metastatic disease in a study of long-term follow-up of patients with metastasis. Patient age, tumor extent, pattern of lung involvement, radioiodine uptake of the metastases, and radioiodine treatment were significant prognostic factors by univariate analysis.