Elsevier

Surgical Oncology

Volume 17, Issue 3, September 2008, Pages 253-258
Surgical Oncology

Review
Micrometastases in thyroid cancer. An important finding?

https://doi.org/10.1016/j.suronc.2008.04.005Get rights and content

Abstract

Differentiated thyroid cancer is a cancer with a good prognosis but the presence of lymph node metastases is associated with increased rates of loco-regional recurrence and in some reports decreased survival. This has led to an increased interest in the lymph node status with guidelines calling for routine central node dissection and increased interest in lateral compartment node sampling and sentinel node biopsy.

We know from studies in regions where routine central and ipsilateral node dissection is the preferred surgical management of differentiated thyroid cancer that lymph node metastases are present in the majority of cases and that many of these are micrometastatic deposits. However, where routine node dissection is not performed recurrence rates are relatively low suggesting that not all micrometastatic disease progresses to a loco-regional recurrence or that the majority of disease is mopped up by adjuvant radioactive iodine.

This review examines the available evidence for the significance of micrometastatic disease in differentiated thyroid cancer and suggests that it is probably of little clinical significance and does not warrant further aggressive surgical intervention. We would expect a conservative surgical approach combined with adjuvant radioactive iodine to lead to durable disease control.

Introduction

Differentiated thyroid cancer is a good prognosis cancer, with adequate surgery and adjuvant treatment leading to a survival rate in excess of 90%. Lymph node metastases have traditionally been thought to have no role in defining prognosis [1], [2], [3], [4] and prognostication has relied on other variables combined in a variety of prognostic algorithms [5], [6], [7], [8], [9] (EORTC, MACIS, AMES, AGES, TNM).

However, in the last decade there has been renewed interest in the role of lymph node metastases in rates of local recurrence in differentiated thyroid cancer. Loco-regional recurrence is a significant problem for those who deal with differentiated thyroid cancer with reported rates between 20% and 59% depending on tumour characteristics [2], [3], [4]. The link between the presence of lymph node metastatic disease and increased loco-regional recurrence has been demonstrated by multiple authors [2], [10], [11]. Further investigation of patients with positive lymph nodes has led to a stratification of risk and to some authors reporting a link between extent of lymph node involvement and overall survival [2], [12], [13], [14].

This renewed interest in lymph node metastatic disease has led to a shift towards a more aggressive approach to investigating and sampling of the regional lymph nodes [15] in the hope that more aggressive initial surgery will decrease rates of loco-regional recurrence [16]. Current international guidelines advocate routine central node dissection and selective ipsilateral node dissection [17], [18] and some authors have been advocating sentinel node biopsy (SNB) [19], while predominantly in Japan routine central and ipsilateral neck dissection is advocated [13], [20], [21], [22], [23].

The result of this trend is that many more lymph nodes are being assessed (and in the case of SNB subjected to closer scrutiny), and a significant proportion of these have micrometastatic spread. Certainly in those with macroscopic metastatic disease the influence on locoregional recurrence is established and therefore the need for further intervention is relatively secure.

The purpose of this review is to examine the evidence available with regards to the prognostic and therapeutic consequences of finding micrometastases in differentiated thyroid cancer. To do this we must firstly define the nature, pattern and incidence of micrometastatic disease.

Section snippets

Definition

Micrometastatic disease was defined by our pathology service as being the presence of metastatic deposits within a lymph node of less than 2 mm in diameter (Fig. 1). This is in keeping with the commonly accepted pathological definition [24], [25].

Patterns of spread

Micrometastatic spread occurs in a predictable pattern corresponding with the known lymphatic drainage of the thyroid gland. As well as an intraglandular lymphatic network the thyroid then drains to the central and lateral compartments of the neck. The isthmus and lower poles drain predominantly to the central compartment and the rest of the gland to the ipsilateral jugular nodes.

Studies on the patterns of metastatic spread to the regional lymph nodes have shown that central and lateral nodes

Prognostic significance

Reported rates of lymph node positivity are as high as 80% from those who practice routine dissection but the reported rates of locoregional recurrence only range between 3% and 30% for low risk PTC [36], [37]. Even for high risk cases the rates are only 59% often in patients with evidence of macroscopically involved nodes. This data infers that the majority of lymph node metastases do not progress following initial treatment whether they are micrometastases or macrometastases.

However it is

Role of radioactive iodine

Radioactive iodine for the treatment of differentiated thyroid cancer became established in the 1960s when it was demonstrated that metastatic disease could be destroyed with a subsequent increase in survival for those with metastatic disease [38] Its use increased in the 1970s and evidence from this period supported its role in dealing with microscopic deposits of thyroid cancer [10], [39].

Unfortunately the published data on rates of recurrence following radioactive iodine are predominantly

Therapeutic implications

The emerging evidence on micrometastatic disease in DTC that we have, suggests that it is likely to have little impact on overall survival, especially given that the effect on survival of grossly involved node remains controversial. However, as we noted previously there has been a resurgence of interest in searching for the presence of lymphatic metastases in DTC and a trend towards a more aggressive operative approach when positive nodes are found [15]. A “side effect” of a more aggressive

Conclusion

Micrometastatic spread in differentiated thyroid cancer is a not uncommon finding with rates depending on the degree of examination of the regional lymph nodes at the time of initial surgery. It is likely that with increased interest in the presence of locoregional disease more micrometastatic disease will be found and its clinical significance called into question.

Rates of micrometastatic disease are high in patients who have routine modified radical neck dissection but recurrence rates for

Conflict of interest statement

Neither author has any conflict of interest relating to this manuscript.

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