Thyroid microcarcinomas are most often papillary (65–99 %) and only rarely follicular (0.3–23.6 %) tumours (Baudin et al. 1998; Lee et al. 2006). The wide range in prevalence of the follicular microcarcinoma may at least in part be due to its substantial similarity with the follicular variant of PTMC. However, both patients with follicular and those with papillary microcarcinoma have an excellent prognosis (Rahbar et al. 2008). At the Department of Nuclear Medicine of the University of Münster, a tertiary referral centre for differentiated thyroid cancer, thyroid microcarcinoma showed excellent event-free survival rates irrespective of their histology (Fig. 2). Accordingly, the European guidelines recommend common therapeutic algorithms for both types of differentiated microcarcinomas (Pacini et al. 2006). The PTMC is often non-encapsulated and sclerosing, although encapsulated variants exist. The tumour is commonly located near the thyroid capsule. Small PTMC <1 mm frequently present with a follicular architecture and lack stromal sclerosis (DeLellis et al. 2004). In contrast, PTMC with a mean diameter of about 2 mm often show a prominent desmoplastic stroma. Larger tumours with an average size of 5 mm are less common and often characterised by a papillary pattern. The more virulent variants of PTMC such as tall cell, columnar cell, oncocytic and diffuse sclerosing subtypes are rare. The prevalence of oncocytic and tall cell variants in PTMC is only 0.8 % (Pelizzo et al. 2004). However, the corresponding value for the sclerosing subtype amounts to 5.0 % (Pelizzo et al. 2004). Until 2009, the American and European guidelines concordantly recommended radioiodine ablation after total or near-total thyroidectomy in these more aggressive subtypes of PTMC (Cooper et al. 2006; Luster et al. 2008). In contrast, the current American guidelines have confined the use of radioiodine ablation to PTMC patients with extrathyroidal extension and lymph node or distant metastasis, respectively (Cooper et al. 2009). However, this highly restrictive approach is not shared by European stakeholders who still suggest radioiodine ablation in selected PTMC patients with T1 N0 M0 (Table 1).

From a nuclear medicine perspective, the deeper insights into the molecular characteristics of PTMC will have a growing impact on the therapeutic management of these patients. Several genetic alterations have been described in PTMC which are associated with distinct biological features. Most common mutations in papillary carcinoma are point mutations of the BRAF and RAS genes and receptor tyrosine kinase (RET) rearrangements, all of which encode proteins that act along the same intracellular signalling pathway leading to the activation of the mitogen-activated protein kinase (MAPK) cascade (Nikiforov 2008). Chromosomal rearrangements of the RET gene represent the most common structural genetic alterations in papillary carcinoma. These rearrangements have been found in up to 52 % of PTMC and represent an early event in the process of thyroid cell transformation (Adeniran et al. 2006; Viglietto et al. 1995). More aggressive PTMCs which present with cervical lymph node metastases often show loss of the p27 gene (Khoo et al. 2002). In addition, cyclin D1 showed significantly higher median expression in PTMC with metastases compared to those without, indicating a correlation to tumour aggressiveness (Londero et al. 2008). Lim et al. (2007) have shown that the absence of epidermal growth factor receptor expression is closely correlated with lymph node metastasis and extrathyroidal growth. Furthermore, they have demonstrated that the absence of cyclooxygenase-2 expression is associated with multiplicity and bilaterality.

The guidelines of the ATA, ETA and the Therapy Committee of the EANM agree on a risk-adapted therapeutic management of patients with PTMC as outlined below (Pacini et al. 2006; Cooper et al. 2006a, b; Luster et al. 2008).