Clinicopathological Evaluation of Papillary Thyroid Microcarcinoma

Abstract

Background and aims: Clinicians sometimes encounter papillary thyroid microcarcinoma (PMC) that is less than 10 mm, associated with lymph node metastasis. In this study, we assessed PMC clinicopathologically to clarify risk factors for poor prognosis.

Patients and methods: Fifty-one patients who underwent thyroid surgery at Aichi Medical University from September 2009 to October 2016 were included. Patients were divided into two groups, pEX-positive (23 patients) and pEX-negative (28 patients), based on the pathological finding of thyroid capsule invasion. The former indicates that the tumor infiltrated the thyroid capsule and spread to the neighboring tissue, and the latter indicates no capsule invasion. We analyzed factors such as patient characteristics, pathological findings, and serum levels of thyroid hormones in the two groups.

Results: No statistical differences were observed between the two groups in gender distribution or age at surgery. Preoperative cancer diagnoses were established for more patients in the pEX-positive group than in the pEX-negative group (n = 21 and 14, respectively; P = 0.004). The mean (±SD) pathological tumor diameter was 5.42 ± 2.77 in the pEX-negative group and 8.32 ± 1.61 in the pEX-positive group (P < 0.001). No significant differences in preoperative serum levels of free T3, free T4, thyroid-stimulating hormone, or thyroglobulin were observed between the two groups. The odds ratio for node positivity in tumors invading thyroid capsules (pEX-positive) compared to those with no capsule invasion (pEX-negative) was 13.20 (95% confidence interval, 3.45-50.42). Immunohistological staining for phosphatase and tensin homolog deleted from chromosome 10 (PTEN) and Akt (protein kinase B) revealed the facilitation of PTEN and suppression of Akt, which might indicate downregulation of the phosphoinositide 3-kinase-Akt (PI3K-Akt) cascade.

Discussion: In general, the prognosis of PMC is favorable. However, the prognosis is less favorable in patients with nodal metastasis or extrathyroidal invasion. It is controversial whether resection is required for proven PMCs. For PMCs associated with extrathyroidal invasion, regional lymph node resection with lobectomy should be performed due to the high risk for lymphatic spread. There might be a possibility that the natural progression of PMC seems to be controlled by the facilitation of PTEN. However, a tumor in the lateral peripheral region of the thyroid parenchyma might be associated with capsule invasion followed by lymphatic spread.

Keywords: extrathyroidal invasion; lymph node metastasis; papillary thyroid microcarcinoma; pten; thyroid capsule invasion.

Figure 1. Microscopic findings

Microscopic findings in a patient who was in the pEX-positive group. Hematoxylin–eosin (HE) and immunohistochemical staining results are presented in semi-serial sections. The list includes the name of the antibody and the reaction. Magnification, ×20. The assessments of the staining are listed as follows: (A) HE; (B) phospho-Akt, negative; (C) PTEN, positive; (D) CXCR4, positive; (E) VEGF, negative; (F) E-cadherin, positive; (G) MMP-2, positive; (H) p38 MAPK, positive. Those staining results can be referred to in Table 6. HE: hematoxylin and eosin; MAPK: mitogen-activated protein kinase; PTEN: phosphatase and tensin homolog deleted from chromosome 10; VEGF: vascular endothelial growth factor; CXCR4: CXC chemokine receptor type 4; MMP-2: matrix metalloproteinase 2.