Old patients with subclinical low-risk PTMC may be the best candidates for observation. Although PTMC in young patients may be more progressive than in older patients, it might not be too late to perform surgery after subclinical PTMC has progressed to clinical disease, regardless of patient age.

Background The recent development and spread of ultrasonography and ultrasonography-guided fine needle aspiration biopsy (FNAB) has facilitated the detection of small papillary microcarcinomas of the thyroid measuring 1 cm or less (PMC). The marked difference in prevalence between clinical thyroid carcinoma and PMC detected on mass screening prompted us to observe PMC unless the lesion shows unfavorable features, such as location adjacent to the trachea or on the dorsal surface of the thyroid possibly invading the recurrent laryngeal nerve, clinically apparent nodal metastasis, or high-grade malignancy on FNAB findings. In the present study we report comparison of the outcomes of 340 patients with PMC who underwent observation and the prognosis of 1,055 patients who underwent immediate surgery without observation. Methods Between 1993 and 2004, 340 patients underwent observation and 1,055 underwent surgical treatment without observation. These 1,395 patients were enrolled in the present study. Observation periods ranged from 18 to 187 months (average 74 months). Results The proportions of patients whose PMC showed enlargement by 3 mm or more were 6.4 and 15.9% on 5-year and 10-year follow-up, respectively. Novel nodal metastasis was detected in 1.4% at 5 years and 3.4% at 10 years. There were no factors related to patient background or clinical features linked to either tumor enlargement or the novel appearance of nodal metastasis. After observation 109 of the 340 patients underwent surgical treatment for various reasons, and none of those patients showed carcinoma recurrence. In patients who underwent immediate surgical treatment, clinically apparent lateral node metastasis (N1b) and male gender were recognized as independent prognostic factors of disease-free survival. Conclusions Papillary microcarcinomas that are not associated with unfavorable features can be candidates for observation regardless of patient background and clinical features. If there are subsequent signs of progression, such as tumor enlargement and novel nodal metastasis, it would not be too late to perform surgical treatment. Even though the primary tumor is small, careful surgical treatment including therapeutic modified neck dissection is necessary for N1b PMC patients.

Background: The incidence of papillary microcarcinoma (PMC) of the thyroid is rapidly increasing globally, making the management of PMC an important clinical issue. Excellent oncological outcomes of active surveillance for low-risk PMC have been reported previously. Here, unfavorable events following active surveillance and surgical treatment for PMC were studied.Methods: From February 2005 to August 2013, 2153 patients were diagnosed with low-risk PMC. Of these, 1179 patients chose active surveillance and 974 patients chose immediate surgery. The oncological outcomes and the incidences of unfavorable events of these groups were analyzed.Results: In the active surveillance group, 94 patients underwent surgery for various reasons; tumor enlargement and the appearance of novel lymph node metastases were the reasons in 27 (2.3%) and six patients (0.5%), respectively. One of the patients with conversion to surgery had nodal recurrence, and five patients in the immediate surgery group had a recurrence in a cervical node or unresected thyroid lobe. All of these recurrences were successfully treated. None of the patients had distant metastases, and none died of the disease. The immediate surgery group had significantly higher incidences of transient vocal cord paralysis (VCP), transient hypoparathyroidism, and permanent hypoparathyroidism than the active-surveillance group did (4.1% vs. 0.6%, p < 0.0001; 16.7% vs. 2.8%, p < 0.0001; and 1.6% vs. 0.08%, p < 0.0001, respectively). Permanent VCP occurred only in two patients (0.2%) in the immediate surgery group. The proportion of patients on L-thyroxine for supplemental or thyrotropin (TSH)-suppressive purposes was significantly larger in the immediate surgery group than in the active surveillance group (66.1% vs. 20.7%, p < 0.0001). The immediate surgery group had significantly higher incidences of postsurgical hematoma and surgical scar in the neck compared with the active surveillance group (0.5% vs. 0%, p < 0.05; and 8.0% vs. 100%, p < 0.0001, respectively).Conclusions: The oncological outcomes of the immediate surgery and active surveillance groups were similarly excellent, but the incidences of unfavorable events were definitely higher in the immediate surgery group. Thus, active surveillance is now recommended as the best choice for patients with low-risk PMC.

Abstract. Recent studies have demonstrated that BRAF V600E mutation is a common event in papillary thyroid carcinoma and a majority of these lesions have shown a direct relationship between BRAF V600E mutation and aggressive characteristics, including a worse patient prognosis. However, there are no studies from Japan regarding this issue in a large series with adequate postoperative follow-up periods. We investigated BRAF V600E mutation in 631 patients with papillary carcinoma having median follow-up periods of 83 months. The prevalence of BRAF V600E mutation was 38.4%, and the rate was higher in carcinoma larger than 1.0 cm but did not successively increase with tumor size. Furthermore, the prevalence did not significantly increase in cases demonstrating high-risk biological features such as clinically apparent lymph node metastasis, massive extrathyroid extension, advanced age, distant metastasis at surgery, and advanced Stage. The disease-free survival of patients with BRAF V600E mutation did not differ from that of those without BRAF V600E mutation. These findings indicate that, although BRAF V600E mutation may play some roles in local carcinoma development, there is no evidence that BRAF V600E mutation significantly reflects the aggressive characteristics and poor prognosis of patients with papillary carcinoma in Japan.Key words: BRAF mutation, Papillary carcinoma, Thyroid, Prognosis (Endocrine Journal 56: 89-97, 2009) PAPILLARY carcinoma of the thyroid is the most common malignancy arising from thyroid follicular cells. Although papillary carcinoma frequently metastasizes to the regional lymph node, it generally shows an indolent character and grows slowly. However, cases displaying certain characteristics are progressive, show a dire prognosis and are considered highrisk. There are several classification systems evaluating the progression of thyroid carcinoma and among these, the UICC/AJCC TNM staging system is the most widely adopted [1]. It consists of three components; T factor, tumor size and extrathyroid extension; N factor, lymph node metastasis; M factor, distant metastasis. Then, each case is staged based on the TNM classification and patient age. This system is evaluated on preoperative imaging studies (TNM and Stage) and also on postoperative pathological examination (pTNM and pStage). We previously demon-

Tg-DT (all data or first four data) is a very strong prognostic predictor superior to the classical prognostic factors in patients with PTC.

Prophylactic MND is recommended for cases of papillary carcinoma demonstrating two or more of the following four characteristics; male gender, age 55 years or older, maximal tumor diameter larger than 3 cm, and massive extrathyroid extension.

IntroductionPapillary thyroid carcinoma (PTC) generally shows an excellent prognosis except in cases with aggressive backgrounds or clinicopathological features. Although the cause-specific survival (CSS) of PTC patients has been extensively investigated, the overall survival (OS) of these patients is unclear. We herein investigated both the OS and CSS of a large PTC patient series.Materials and methodsWe enrolled 5897 PTC patients who underwent initial surgery between 1987 and 2005 (658 males and 5339 females; median age 51 years). Their median postoperative follow-up period was 177 months. Univariate and multivariate analyses for OS and CSS assessed the effects of gender, older age (≥55 years), distant metastasis at diagnosis (M1), significant extrathyroid extension, tumor size (cutoffs 2 and 4 cm), large node metastasis (N ≥ 3 cm), and extranodal tumor extension.ResultsTo date, 387 patients (7%) in this series have died from various causes, including 117 (2%) due to PTC. The 10-, 15-, and 20-year OS rates are 97, 95, and 90%, respectively. Older age and M1 were important prognostic factors for OS and CSS. Older age was a more significant factor than M1 for OS and vice versa for CSS. In the older patients, M1 was a prominent prognostic factor for both OS and CSS. In the young patients, M1 had less prognostic impact than in the older patients, and the prognostic values of M1 and N ≥ 3 cm for OS and CSS were identical and similar, respectively.ConclusionsThe most important prognostic value for OS was patient age, indicating that PTC is generally indolent. However, the control of distant metastasis in older patients remains a future challenge in order to further improve their OS and CSS. PTC of ≥3 cm in young patients should be carefully followed, even in the absence of metastases, and these patients should undergo aggressive therapies for recurrent lesions and metastases.

Central node metastasis independently predicts a worse DFS for patients with papillary carcinoma larger than 1 cm.