• papillary thyroid cancer
• TSH

Papillary carcinoma is the most common thyroid cancer and its incidence has been increasing in recent years, largely due to increased detection of small lesions. TSH is an important growth factor for thyroid follicular cells. In literature it is well known that there is a relationship between serum TSH and papillary thyroid carcinoma (PTC): higher TSH levels are associated with a higher frequency of papillary carcinoma (even when serum TSH is in the normal range) and with a more advanced cancer stage. Aim of this project was to understand the role of serum TSH in PTC, and in particular if serum TSH can be a progression factor for the tumor. For this purpose, in the present work, we focused on papillary thyroid microcarcinoma. Papillary microcarcinoma, defined as a tumor with size equal to or less than one centimeter in its larger diameter, is today frequently found and its clinical behavior is generally non-aggressive. Increase in number of diagnoses, together with low morbidity and mortality of microcarcinoma raises the problem of its management. Microcarcinoma may be diagnosed as two forms not yet well studied: 1) an “incidental” or “subclinical” microcarcinoma defined as an occult microcarcinoma diagnosed “post-surgery” (occasionally identified on histology in patients submitted to thyroidectomy for other reasons i.e. benign thyroid disease) and 2) “non incidental” or “clinical” microcarcinoma, detected “pre-surgery” because clinically suspected during neck ultrasound or on cytology. Objective of the study is to clarify if these two categories of microcarcinoma reflect the same tumor or are two distinct clinical entities and eventually if serum TSH play a role in their different clinical manifestations .

Patients and Methods: 665 consecutive patients underwent thyroidectomy for benign thyroid disease or for PTC indicative/suspected cytology were recruited. We evaluated preoperative clinical features (thyroid function tests, neck ultrasound, cytology on fine needle aspiration) and histology.
Results: 259 patients presented with a single thyroid nodule and 406 patients with multiple nodules. At histology 92 “incidental” microcarcinomas, 67 “non incidental” microcarcinomas, 215 carcinomas larger than 1 cm and 291 benign nodules were diagnosed.
“Incidental” microcarcinoma was significantly more frequent in patients with a multinodular thyroid compared to patients with a single nodule (66/406, 16.2% compared to 26/259, 10%; p=0.02), while in patients with single nodule, “non incidental” microcarcinoma was the most frequent (33/259, 12.7%, compared to 34/406, 8.4%, with multiple nodules, p=0.04). Patients with “incidental” microcarcinoma vs patients with “non incidental” microcarcinoma, were on average older (mean age±standard deviation 53.3±13.2 years compared to 44.9±14.8 in the case of “non incidental” forms; p=0.0002), had a smaller neoplasia (median 4 mm, IQR 2-7 mm, against 9 mm, IQR 7-10 mm of “non incidental” form; Mann-Whitney p<0.0001), more frequently had multiple neoplastic foci (70/92, 76.1 % compared to 35/67, 52.2%; p=0.001) and had lower levels of TSH (median 0.6 mIU /L, IQR: 0.4-1.0 mIU/L, compared to 1.1 mIU/L, IQR: 0.6-1.4 mIU/L; p=0.0001). More aggressive variants were detected more frequently in “non incidental” microcarcinoma (18/67, 26.9% compared to “incidental” microcarcinoma 11/92, 11.9% , χ2 p 0.016), as well as the presence of lymph node metastasis that have been identified in 17/67, 25.4% of patients with “non incidental” form and in any patient with an “incidental” microcarcinoma (χ2 p<0.0001).
Conclusion: “incidental” differs from “non incidental” microcarcinoma in size, clinical diagnosis, multifocality, aggressiveness on histology and in TSH levels: in the presence of lower levels of serum TSH, microcarcinoma is more frequently "subclinical", multifocal, associated with multinodular goiter and has a less aggressive variant on histology. In the presence of higher levels of serum TSH, microcarcinoma is more frequently "clinically” detectable, associated with lymph node metastasis, with a single nodule, less frequently multifocal and has a more aggressive variant. These data indicate that “incidental” and “non incidental” microcarcinomas are two distinct clinical entities with different growth, aggressiveness and eventually prognosis. These features are related to different levels of serum TSH, suggesting a possible effects of this hormone on clinical course of these two cancer presentations.