Molecular characterisation and clinical correlation of papillary thyroid microcarcinoma

Abstract

Purpose Papillary thyroid microcarcinoma (mPTC) is defined as a papillary thyroid cancer sized 10 mm or less. Despite their generally indolent clinical course and good prognosis, a subset of mPTCs shows potentially aggressive behaviour. Methods To search for predictors of clinical outcome of mPTCs, we retrospectively evaluated the genetic tumour profile of 100 patients (23 M/77 F, mean age ± SD 53.8 ± 13.4 years) with histologically confirmed mPTCs through analysis of BRAF, NRAS and TERT promoter mutations as well as RET/PTC translocations. Results Mean follow-up period was 8.4 ± 3.6 years. In 55 cases, mPTC were detected incidentally after surgery. Capsular invasion, bilateralism and multifocality were found in 11/100, 17/100 and 24/100 cases, respectively, while lymph-nodes metastases were present at diagnosis in 9/100 cases. After 3.5 ± 2.0 years, tumour relapse occurred in 6/100 cases and was locoregional in five (two in the thyroid bed, three in laterocervical lymph-nodes), while lung metastasis occurred in one case. Biochemical persistence of disease was seen in 1/100 case. Mutations occurred in 55/100 cases; BRAF V600E was the most frequently detected (49/100) and was associated with higher tumour size, bilateralism and follicular variant but not with capsular invasion. RET/PTC rearrangements were found in 2/100 cases, NRAS Q61R in 4/100, while no mutations of TERT promoter gene were detected. Despite the observed association between BRAF V600E mutation and unfavourable histopathological features, we found no direct association with tumour recurrence, distant metastases and mortality. Conclusion In our study, the search for the most frequent genetic alterations as prognostic markers in mPTCs would not have changed the therapeutic strategy.

TERT Promoter Mutations Are an Independent Predictor of Distant Metastasis in Middle Eastern Papillary Thyroid Microcarcinoma

“…Interestingly, incidence of DM in this cohort was 6% among PTMC patients (3.3% patients developed DM after a median of 3.2 years of initial diagnosis while 2.7% presented with DM at diagnosis). This relatively high incidence rate among Middle Eastern PTMC patients is in contrast to previous reports from other ethnicities, where DM from PTMC was very rare ( 10 , 12 , 45 – 48 ). We were intrigued by the occurrence of distance metastasis at this relatively high rate.…”

“…( 36 ) have reported the prevalence of TERT promoter mutations in 4.7% (19/404) PTMC from Italy, whereas Sama et al. ( 45 ) found the prevalence to be 2% (2/100) in PTMC from the same population. Three other studies from Asian population reported a frequency of 3.2% (16/504) from Korea ( 39 ), 1.2% (1/86) from China ( 37 ) and 0% (0/26) from Japan ( 38 ).…”

Molecular Pathology of Non-familial Follicular Epithelial–Derived Thyroid Cancer in Adults: From RAS/BRAF-like Tumor Designations to Molecular Risk Stratification

“…In another study, TERTp mutations were found in 4.7% of the 431 miPTCs analyzed, but no association between TERTp mutations and aggressive features or clinical outcome was found [53]. Consistent with all these data and the excellent prognosis of PMCs, no [57][58][59][60][61] or very low percentage [52,62] of TERTp mutations have been detected in PMCs, indicating no [52,53,58] or a limited role in risk stratification in PMCs [62]. It remains unknown if the coexistence of BRAF and TERTp mutations could be associated with PMCs with a poor clinical outcome [63].…”

BRAFV600E mutation test on fine‐needle aspiration specimens of thyroid nodules: Clinical correlations for 4600 patients

“…Third, the ratio of PTC to other thyroid cancers may also affect the sensitivity of BRAF V600E mutation evaluation since BRAF V600E mutation is absent in follicular thyroid carcinomas and occurs at a lower rate in follicular variants of PTC. 53 Although the BRAF V600E test would allow clinicians to optimize management to avoid surgery for benign nodules, thereby decreasing health costs and postsurgical complications, 54 nearly 20% of PTC cases could not be properly distinguished preoperatively by BRAF V600E mutation detection, even when combined with FNA. This is likely related to the complexity of the carcinogenesis of PTC.…”